Libre Pathology - User contributions [en]

Thyroid gland

2013-06-14T13:57:21Z

Ingo: /* Microscopic */

The '''thyroid gland''' is an important little endocrine organ in the anterior [[neck]]. It is frequently afflicted by [[cancer]]... but the common cancer has such a good prognosis there is debate about how aggressively it should be treated. The [[cytopathology]] of the thyroid gland is dealt with in the ''[[thyroid cytology]]'' article.

The gland frustrates a significant number of pathologists, as the criteria for cancer are considered a bit wishy-washy.

=Thyroid specimens=
==They come in three common varieties==
*FNA (fine needle aspiration).
**Done to triage patients/rule-out malignancy - discussed in the article ''[[thyroid cytopathology]]''.
*Hemithyroid.
**Done to get a definitive diagnosis.
**May be a "completion" - removal of the other half following definitive diagnosis.
*Total thyroid.
**Done for malignancy or follicular lesion.

==Gross pathology==
*White nodules - think:
**Lymphoid tissue.
**Papillary thyroid carcinoma - may be calcified.<ref>BEC. 20 October 2009.</ref>

=Diagnoses=
==Common==
*[[Thyroid gland nodular hyperplasia|Nodular hyperplasia]] -- most common.
*[[Lymphocytic thyroiditis]].
*Papillary thyroid carcinoma (PTC) -- most common cancer.
**[[Papillary thyroid carcinoma follicular variant]].
*[[Parathyroid]] tissue.

==Pitfalls/weird stuff==
*Thyroid tissue lateral to the jugular vein (often referred to as ''lateral aberrant thyroid tissue'') is generally considered metastatic thyroid carcinoma ([[papillary thyroid carcinoma]]) even if it looks benign.<ref name=pmid14452106>{{Cite journal | last1 = JOHNSON | first1 = RW. | last2 = SAHA | first2 = NC. | title = The so-called lateral aberrant thyroid. | journal = Br Med J | volume = 1 | issue = 5293 | pages = 1668-9 | month = Jun | year = 1962 | doi = | PMID = 14452106 | PMC = 1958877 }}</ref>
**This dictum is disputed.<ref name=pmid17319317>{{Cite journal | last1 = Escofet | first1 = X. | last2 = Khan | first2 = AZ. | last3 = Mazarani | first3 = W. | last4 = Woods | first4 = WG. | title = Lessons to be learned: a case study approach. Lateral aberrant thyroid tissue: is it always malignant? | journal = J R Soc Promot Health | volume = 127 | issue = 1 | pages = 45-6 | month = Jan | year = 2007 | doi = | PMID = 17319317 }}</ref>
**The level VI and VII [[lymph nodes]] are medial to the jugular.
*[[Hashimoto's disease]] may have so many lymphocytes that it mimics a lymph node -- may lead to misdiagnosis of PTC.
*Parasitic nodule: clump of thyroid that is attached by a thin thread... but looks like a separate nodule; may lead to misdiagnosis of PTC.

Image:
*[http://images.radiopaedia.org/images/26383/ad505c78a87e71180792049299f5cd_big_gallery.jpg Neck levels (radiopaedia.org)].<ref>URL: [http://radiopaedia.org/articles/lymph-node-levels-of-the-neck http://radiopaedia.org/articles/lymph-node-levels-of-the-neck]. Accessed on: 5 November 2012.</ref>

==Diagnostic keys==
The following should prompt careful examination:<ref>SR. 17 January 2011.</ref>
*Architecture: microfollicular, trabecular, solid, insular.
*Thick capsule.
*Necrosis - rare in the thyroid.

==Thyroid IHC - general comments==
*Not really useful.
*Papers with very small sample sizes abound.

===Follicular thyroid carcinoma vs. papillary thyroid carcinoma===
*CD31 more frequently positive in follicular lesions.<ref name=pmid18795075>{{Cite journal | last1 = Rydlova | first1 = M. | last2 = Ludvikova | first2 = M. | last3 = Stankova | first3 = I. | title = Potential diagnostic markers in nodular lesions of the thyroid gland: an immunohistochemical study. | journal = Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub | volume = 152 | issue = 1 | pages = 53-9 | month = Jun | year = 2008 | doi = | PMID = 18795075 }}</ref>
**CD31 is a marker for microvessel density.
*Galectin-3 thought to be positive in papillary carcinoma.<ref name=pmid18795075/>
*HBME-1 thought to be positive in papillary lesions.<ref name=pmid15529186>{{Cite journal | last1 = Papotti | first1 = M. | last2 = Rodriguez | first2 = J. | last3 = De Pompa | first3 = R. | last4 = Bartolazzi | first4 = A. | last5 = Rosai | first5 = J. | title = Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential. | journal = Mod Pathol | volume = 18 | issue = 4 | pages = 541-6 | month = Apr | year = 2005 | doi = 10.1038/modpathol.3800321 | PMID = 15529186 }}</ref>

==Thyroid lesions per WHO==
*Adapted from the ''Washington Manual of Surgical Pathology''.<ref name=Ref_WMSP331>{{Ref WMSP|331}}</ref>
===Adenoma===
*Follicular adenoma.
*Hyalinizing trabecular tumour.

===Carcinoma===
*[[Papillary thyroid carcinoma|Papillary carcinoma]].
*[[Follicular thyroid carcinoma|Follicular carinoma]].
*[[Medullary thyroid carcinoma|Medullary carcinoma]].
*Undifferentiated (anaplastic) carcinoma.

*Poorly differentiated carcinoma.
*[[Squamous cell carcinoma]].
*[[Mucoepidermoid carcinoma]].
*Sclerosing mucoepidermoid carcinoma with eosinophilia.
*Mucinous carcinoma.

*Mixed medullary and follicular carinoma.
*Spindle cell tumour with thymus-like differentiation.
*Carcinoma showing thymus-like differentiation.

===Others===
*[[Teratoma]].
*[[Lymphoma]].
*Ectopic thymoma.
*[[Angiosarcoma]] + other [[soft tissue lesions]].
*[[Paraganglioma]].
*[[Solitary fibrous tumour]].
*[[Follicular dendritic cell tumour]].
*[[Langerhans cell histiocytosis]].
*[[Metastasis]].

=Parathyroid glands=
{{Main|Parathyroid glands}}
*May make an appearance in the context of thyroid surgery.

=Benign=
==Solid cell nest of the thyroid gland==
*[[AKA]] ''solid cell nest of thyroid''.
===General===
*Embryonic remnants endodermal origin.<ref name=pmid12527712>{{cite journal |author=Reis-Filho JS, Preto A, Soares P, Ricardo S, Cameselle-Teijeiro J, Sobrinho-Simões M |title=p63 expression in solid cell nests of the thyroid: further evidence for a stem cell origin |journal=Mod. Pathol. |volume=16 |issue=1 |pages=43–8 |year=2003 |month=January |pmid=12527712 |doi=10.1097/01.MP.0000047306.72278.39 |url=http://www.nature.com/modpathol/journal/v16/n1/full/3880708a.html}}</ref>
*Incidental finding.

Note:
*Hypothesized to have some relation to [[mucoepidermoid carcinoma]] of the thyroid gland;<ref name=pmid1413837>{{Cite journal | last1 = Ozaki | first1 = O. | last2 = Ito | first2 = K. | last3 = Sugino | first3 = K. | last4 = Yasuda | first4 = K. | last5 = Yamashita | first5 = T. | last6 = Toshima | first6 = K. | title = Solid cell nests of the thyroid gland: precursor of mucoepidermoid carcinoma? | journal = World J Surg | volume = 16 | issue = 4 | pages = 685-8; discussion 688-9 | month = | year = | doi = | PMID = 1413837 }}</ref> however, another study suspects a relationship with [[papillary thyroid carcinoma]].<ref name=pmid22224821>{{Cite journal | last1 = Prichard | first1 = RS. | last2 = Lee | first2 = JC. | last3 = Gill | first3 = AJ. | last4 = Sywak | first4 = MS. | last5 = Fingleton | first5 = L. | last6 = Robinson | first6 = BG. | last7 = Sidhu | first7 = SB. | last8 = Delbridge | first8 = LW. | title = Mucoepidermoid carcinoma of the thyroid: a report of three cases and postulated histogenesis. | journal = Thyroid | volume = 22 | issue = 2 | pages = 205-9 | month = Feb | year = 2012 | doi = 10.1089/thy.2011.0276 | PMID = 22224821 }}</ref>

===Microscopic===
Features:<ref name=pmid12527712/>
*Cellular solid ''or'' cystic cluster of variable size with:
**Cuboidal cellular morphology.
***May have columnar morphology.
**Moderate-to-scant eosinophilic cytoplasm.
**Round/ovoid nuclei with finely granular chromatin.
*+/-Goblet cells (~30% of cases).<ref name=pmid7509563>{{cite journal |author=Mizukami Y, Nonomura A, Michigishi T, ''et al.'' |title=Solid cell nests of the thyroid. A histologic and immunohistochemical study |journal=Am. J. Clin. Pathol. |volume=101 |issue=2 |pages=186–91 |year=1994 |month=February |pmid=7509563 |doi= |url=}}</ref>

Images:
*www:
**[http://farm6.static.flickr.com/5143/5685400518_c4f506d370.jpg Solid cell next (flickr.com)].
**[http://www.nature.com/modpathol/journal/v16/n1/fig_tab/3880708f1.html#figure-title Crappy B&W of solid cell nest (nature.com)].
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Solid_cell_nest_of_the_thyroid_gland_-_intermed_mag.jpg Solid cell nest of the thyroid gland - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Solid_cell_nest_of_the_thyroid_gland_-_very_high_mag.jpg Solid cell nest of the thyroid gland - very high mag. (WC)].

DDx:<ref name=pmid12527712/>
*[[C-cell hyperplasia]].
*[[Medullary thyroid carcinoma|Medullary carcinoma]].
*Squamous lesions.

===IHC===
Features:<ref name=pmid12527712/>
*p63 +ve.
**-ve in clear cells.
*CEA +ve (polyconal).<ref name=pmid7509563>{{cite journal |author=Mizukami Y, Nonomura A, Michigishi T, ''et al.'' |title=Solid cell nests of the thyroid. A histologic and immunohistochemical study |journal=Am. J. Clin. Pathol. |volume=101 |issue=2 |pages=186–91 |year=1994 |month=February |pmid=7509563 |doi= |url=}}</ref>
**+ve also in clear cells.
*Chromogranin A +ve ~45% of cases.<ref name=pmid7509563/>

===Sign out===
Solid cell nests of the thyroid gland are usually not reported.

==Thyroid gland nodular hyperplasia==
*[[AKA]] ''[[nodular hyperplasia]]''.
*[[AKA]] ''adenomatoid nodule''.

===General===
*Clinical diagnosis: ''goitre'', [[AKA]] ''sporadic goitre'', AKA ''multinodular goitre'' (MNG).
*Most common diagnosis in the thyroid.
**If you've seen a handful of thyroids you've seen this.

Notes:
*Large lesions may be clonal; however, this is clinically irrelevant.

===Gross===
Features:
*Enlarge thyroid gland.
*+/-Distinct (well-circumscribed) nodules.

===Microscopic===
Features:
*Follicles of variable size - '''key feature'''.
**Should be obvious at low power, i.e. with the 2.5x objective.
*+/-Nodules.
**Do not have a thick fibrous capsule.
**May have a high cellularity.
**Architecture: solid or microfollicular.<ref name=Ref_EP36>{{Ref EP|36}}</ref>

Negatives:
*No nuclear features suggestive of malignancy (at lower power).
**One should not look at high power.
*Not cellular.

DDx:
*[[Papillary thyroid carcinoma]] - esp. [[papillary thyroid carcinoma follicular variant]].
*[[Follicular thyroid adenoma]] - contained in a fibrous capsule.
*[[Follicular thyroid carcinoma]] - has fibrous capsule and invasion through it.

===Sign out===
<pre>
HEMITHYROID, RIGHT, HEMITHYROIDECTOMY:
- NODULAR HYPERPLASIA.
- NEGATIVE FOR MALIGNANCY.
</pre>

<pre>
HEMITHYROID, RIGHT, HEMITHYROIDECTOMY:
- CELLULAR ADENOMATOID NODULE ON A BACKGROUND OF NODULAR HYPERPLASIA.
- NEGATIVE FOR MALIGNANCY.
</pre>

==Follicular thyroid adenoma==
*[[AKA]] follicular adenoma, [[AKA]] thyroid follicular adenoma.
===General===
*Most common neoplasm of thyroid.<ref name=Ref_EP51>{{Ref EP|51}}</ref>
*Encapusled lesion (surrounded by fibrous capsule).

===Gross===
*Thick capsule.

Notes:
*The entire capsule should be submitted.<ref>SR. 17 January 2011.</ref>
**A good start for most thyroid specimens with a thick capsule is 10 blocks.

===Microsopic===
Features:
*Cellular.
*Thick capsule - '''key feature'''.

Negatives.
*No invasion of the capsule (see ''[[follicular thyroid carcinoma]]'' section).
*No nuclear features suggestive of [[papillary thyroid carcinoma]].

DDx:
*[[Thyroid gland nodular hyperplasia]] with an encapsulated nodule - not as cellular.

==Graves disease==
===General===
*Often misspelled "Grave's disease".
*Autoimmune disease leading to hyperthyroidism.
*Eye problems not resolved with thyroid removal.{{fact}}
*Higher risk of [[papillary thyroid carcinoma]].

Clinical:
*TSH-receptor antibody +ve.<ref name=pmid19576193>{{Cite journal | last1 = Massart | first1 = C. | last2 = Gibassier | first2 = J. | last3 = d'Herbomez | first3 = M. | title = Clinical value of M22-based assays for TSH-receptor antibody (TRAb) in the follow-up of antithyroid drug treated Graves' disease: comparison with the second generation human TRAb assay. | journal = Clin Chim Acta | volume = 407 | issue = 1-2 | pages = 62-6 | month = Sep | year = 2009 | doi = 10.1016/j.cca.2009.06.033 | PMID = 19576193 }}</ref>

===Gross===
Features:<ref>{{Ref EP|30}}</ref>
*Enlarged 50-150 g.
*"Beefy-red" appearance, looks like raw beef.

===Microscopic===
Features:
*Classic:
**Hypercellular
**Patchy lymphocytes.
**Little colloid.
*Scalloping of colloid; colloid has undulating border.
**Non-specific finding.
*+/-Nuclear clearing.
*+/-Papillae (may mimic papillary thyroid carcinoma in this respect).

Notes:
*Usually has an unimpressive appearance... as it is treated, i.e. history is important.
*Nuclear clearing and papillae are usu. diffuse in Graves disease - unlike in papillary thyroid carcinoma.

Image:
*[http://library.med.utah.edu/WebPath/jpeg4/ENDO022.jpg Graves disease (med.utah.edu)].<ref>URL: [http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html]. Accessed on: 4 December 2011.</ref>

==Idiopathic granulomatous thyroiditis==
*[[AKA]] ''granulomatous thyroiditis'' - non-specific term; granulomas may be due a number of causes.
*AKA ''subacute thyroiditis''.
*[[AKA]] ''de Quervain thyroiditis''.
**Should '''not''' be confused with ''[[de Quervain's disease]]'' (AKA ''gamer's thumb'') something completely unrelated to the thyroid.

===General===
*Women > men.
*Etiology: possibly viral.<ref name=llyod/>

Clinical:
*Tenderness.<ref name=pmid22538753>{{Cite journal | last1 = Szczepanek-Parulska | first1 = E. | last2 = Zybek | first2 = A. | last3 = Biczysko | first3 = M. | last4 = Majewski | first4 = P. | last5 = Ruchała | first5 = M. | title = What might cause pain in the thyroid gland? Report of a patient with subacute thyroiditis of atypical presentation. | journal = Endokrynol Pol | volume = 63 | issue = 2 | pages = 138-42 | month = | year = 2012 | doi = | PMID = 22538753 }}</ref>

===Microscopic===
Features:<ref name=Ref_Sternberg4_559>{{Ref Sternberg4|559}}</ref><ref name=llyod>{{cite book |title=Endocrine Diseases (AFIP Atlas of Nontumor Pathology) |last= Lloyd |first = Ricardo V. |authorlink= |coauthors= |year= 2002 |publisher= American Registry of Pathology |location= Toronto |isbn=978-1881041733 |page= |pages= |url=http://www.amazon.com/Endocrine-Diseases-Atlas-Nontumer-Pathology/dp/1881041735 |accessdate=}}</ref>
*[[Granulomas]] with multinucleated giant cells - usu. with engulfed colloid.
*Lymphocytes.
*Plasma cells.
*+/-Fibrosis.

DDx:
*Infectious granulomatous disease (fungal, microbacterial).
*[[Palpation thyroiditis]].
*[[Sarcoidosis]] (classically intrafollicular distribution).

Images:
*[http://commons.wikimedia.org/wiki/File:Subacute_thyroiditis_-_intermed_mag.jpg Subacute thyroiditis - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Subacute_thyroiditis_-_high_mag.jpg Subacute thyroiditis - high mag. (WC)].

===Stains===
*ZN -ve.
*GMS -ve.

==Palpation thyroiditis==
===General===
*Granulomatous inflammation due to palpation.
**Incidence of granulomas higher in surgical thyroid specimens than autopsies.<ref name=llyod/>

===Microscopic===
Features:<ref name=llyod>{{cite book |title=Endocrine Diseases (AFIP Atlas of Nontumor Pathology) |last= Lloyd |first = Ricardo V. |authorlink= |coauthors= |year= 2002 |publisher= American Registry of Pathology |location= Toronto |isbn=978-1881041733 |page= |pages= |url=http://www.amazon.com/Endocrine-Diseases-Atlas-Nontumer-Pathology/dp/1881041735 |accessdate=}}</ref>
*[[Granuloma]]s involving the follicle.
**Histiocytes within the colloid.

DDx:
*[[Idiopathic granulomatous thyroiditis]].
*[[Sarcoidosis]].
*Infectious granulomatous thyroiditis.

===Stains===
*ZN -ve.
*GMS -ve.

==Riedel thyroiditis==
*[[AKA]] ''invasive fibrous thyroiditis''.<ref name=pmid21568724>{{Cite journal | last1 = Fatourechi | first1 = MM. | last2 = Hay | first2 = ID. | last3 = McIver | first3 = B. | last4 = Sebo | first4 = TJ. | last5 = Fatourechi | first5 = V. | title = Invasive fibrous thyroiditis (Riedel thyroiditis): the Mayo Clinic experience, 1976-2008. | journal = Thyroid | volume = 21 | issue = 7 | pages = 765-72 | month = Jul | year = 2011 | doi = 10.1089/thy.2010.0453 | PMID = 21568724 }}</ref>
===General===
Clinical features:<ref name=pmid21568724/>
*Extremely rare.
*Women > men.
*Usually smokers.
*May be associated with ''[[retroperitoneal fibrosis]]''.
*May be hypothyroid.
*+/-Obstructive symptoms.

===Microscopic===
Features:
*Fibrosis.
*Specimen often fragmented as it was difficult to remove.

DDx:
*[[Anaplastic thyroid carcinoma|Anaplastic carcinoma]], spindle cell variant.

==Hashimoto thyroiditis==
===General===
*'''This is a clinical diagnosis'''.
**The histomorphologic findings, generally, are '''not''' diagnostic.

Etiology:
*Autoimmune disease leading to hypothyroidism.
**Often genetic/part of a syndrome.

====Clinical====
Serology:<ref name=pmid7813361>{{cite journal |author=Poropatich C, Marcus D, Oertel YC |title=Hashimoto's thyroiditis: fine-needle aspirations of 50 asymptomatic cases |journal=Diagn. Cytopathol. |volume=11 |issue=2 |pages=141–5 |year=1994 |pmid=7813361 |doi= |url=http://www3.interscience.wiley.com/journal/112701408/abstract?CRETRY=1&SRETRY=0}}</ref>
*Antimicrosomal (antithyroid peroxidase) +ve.
*Antithyroglobulin +ve.

Associated pathology:<ref name=pmid7813361/>
*Increased risk of B-cell lymphoma; these are classically:<ref name=pmid18018576 >{{Cite journal | last1 = Ohye | first1 = H. | last2 = Fukata | first2 = S. | last3 = Hirokawa | first3 = M. | title = [Malignant lymphoma of the thyroid]. | journal = Nihon Rinsho | volume = 65 | issue = 11 | pages = 2092-8 | month = Nov | year = 2007 | doi = | PMID = 18018576 }}</ref>
**[[MALT lymphoma]].
**[[Diffuse large B cell lymphoma]] (DLBCL).

===Microscopic===
Features:
*Lymphocytic infiltrate - '''key feature'''.
*Nuclear clearing common.
**May confuse with [[papillary thyroid carcinoma]].
*Polymorphous lymphoplasmacytic infiltrate with germinal centres.<ref name=Ref_APBR672>{{Ref APBR|672}}</ref>
*+/-Oncocytic metaplasia.

Notes:
*Histologically often '''not''' possible to separate from "non-specific" thyroiditis.<ref name=Ref_Sternberg4_560>{{Ref Sternberg4|560}}</ref>

DDx:
*[[Lymphocytic thyroiditis]].
*[[Papillary thyroid carcinoma]].
*[[MALT lymphoma]].
*[[Diffuse large B cell lymphoma]].

===IHC===
*Panel to exclude lymphoma may be required, e.g. CD3, CD20, CD10, BCL6, BCL2, kappa, lambda.

===Molecular===
*Occasionally done to exclude lymphoma - see ''[[MALT lymphoma]]'' and ''[[DLBCL]]''.

==C-cell hyperplasia==
*Abbreviated ''CCH''.
===General===
*Screening for C-cell hyperplasia/[[medullary thyroid carcinoma]] done with ''serum calcitonin level''.<ref name=pmid19726541>{{cite journal |author=Machens A, Hoffmann F, Sekulla C, Dralle H |title=Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer |journal=Endocr. Relat. Cancer |volume=16 |issue=4 |pages=1291–8 |year=2009 |month=December |pmid=19726541 |doi=10.1677/ERC-09-0136 |url=http://erc.endocrinology-journals.org/cgi/content/full/16/4/1291}}</ref>

===Gross===
*Not visible.

===Microscopic===
Features:
*Location:<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Thyroid_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Thyroid_11protocol.pdf]. Accessed on: 7 April 2012.</ref>
**Mid portion of lobe to upper third of lobe.
***Not at the poles.
***Not in the isthmus.

*Definitions vary.<ref>SR. 17 January 2011.</ref>

One definition - either of the following:<ref name=pmid19726541>{{cite journal |author=Machens A, Hoffmann F, Sekulla C, Dralle H |title=Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer |journal=Endocr. Relat. Cancer |volume=16 |issue=4 |pages=1291–8 |year=2009 |month=December |pmid=19726541 |doi=10.1677/ERC-09-0136 |url=http://erc.endocrinology-journals.org/cgi/content/full/16/4/1291}}</ref>
#>50 C-cells per low-power field (x100).
#*This part of the definition suffers from [[LPFitis]]. The paper should have been rejected.
#Confined to the thyroid gland and no larger than 10 mm in greatest dimension.

Another definition:
*Invasion of the basement membrane with stromal reaction.

A third definition:
*"Several clusters" of more than six C cells.

====Images====
*[http://www.nature.com/modpathol/journal/v16/n8/fig_tab/3880836f2.html CCH - crappy B&W image (nature.com)].<ref>{{Cite journal | last1 = Guyétant | first1 = S. | last2 = Josselin | first2 = N. | last3 = Savagner | first3 = F. | last4 = Rohmer | first4 = V. | last5 = Michalak | first5 = S. | last6 = Saint-André | first6 = JP. | title = C-cell hyperplasia and medullary thyroid carcinoma: clinicopathological and genetic correlations in 66 consecutive patients. | journal = Mod Pathol | volume = 16 | issue = 8 | pages = 756-63 | month = Aug | year = 2003 | doi = 10.1097/01.MP.0000081727.75778.0C | PMID = 12920219 }}</ref>
*[http://www.nature.com/modpathol/journal/v16/n8/fig_tab/3880836f3.htm CCH - crappy B&W image (nature.com)].
*[http://www.forpath.org/workshops/0201/photos/fullsize/cas7c.jpg CCH (forpath.org)].<ref>URL: [http://www.forpath.org/workshops/0201/html/case_7.asp http://www.forpath.org/workshops/0201/html/case_7.asp]. Accessed on: 21 May 2013.</ref>
*[http://alf3.urz.unibas.ch/pathopic/e/getpic-fra.cfm?id=4849 CCH (unibas.ch)].
*[http://alf3.urz.unibas.ch/pathopic/e/getpic-fra.cfm?id=10739 Nodular CCH (unibas.ch)].

=Malignant neoplasm=
There are a bunch of 'em. The most common, by far, is papillary.

==Papillary thyroid carcinoma==
*Abbreviated ''PTC''.
===General===
Medical school memory device P's:
*Palpable nodes.
*Popular (most common malignant neoplasm of the thyroid).
*Prognosis is good.
*Pre-Tx iodine scan.
*Post-Sx iodine scan.
*[[Psammoma bodies]].

Notes:
*PTC is associated with radiation exposure.<ref name=Ref_Sternberg4_564>{{Ref Sternberg4|564}}</ref>
*''Papillary thyroid microcarcinoma'' is defined as a tumour with a maximal dimension of 1.0 cm or less.<ref name=pmid21267823>{{Cite journal | last1 = Sethom | first1 = A. | last2 = Riahi | first2 = I. | last3 = Riahi | first3 = K. | last4 = Akkari | first4 = K. | last5 = Benzarti | first5 = S. | last6 = Miled | first6 = I. | last7 = Chebbi | first7 = MK. | title = [Management of thyroid microcarcinoma. Report of 13 cases]. | journal = Tunis Med | volume = 89 | issue = 1 | pages = 23-5 | month = Jan | year = 2011 | doi = | PMID = 21267823 }}</ref>

====Prognosis====
Prognosis can be predicted by ''MAICS'' score. It which includes:<ref name=pmid12016468>{{Cite journal | last1 = Hay | first1 = ID. | last2 = Thompson | first2 = GB. | last3 = Grant | first3 = CS. | last4 = Bergstralh | first4 = EJ. | last5 = Dvorak | first5 = CE. | last6 = Gorman | first6 = CA. | last7 = Maurer | first7 = MS. | last8 = McIver | first8 = B. | last9 = Mullan | first9 = BP. | title = Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940-1999): temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients. | journal = World J Surg | volume = 26 | issue = 8 | pages = 879-85 | month = Aug | year = 2002 | doi = 10.1007/s00268-002-6612-1 | PMID = 12016468 }}</ref>
*'''M'''etastases.
*'''A'''ge.
*'''I'''nvasion of surround tissues.
*'''C'''completeness of excision.
*'''S'''ize of tumour.

===Microscopic===
Features:
*Nuclear changes - '''key feature'''.
*#"Shrivelled nuclei"/"raisin" like nuclei, nuclei with a wavy ("textured", convoluted) nuclear membrane -- usu. easy to find.
*#[[Nuclear pseudoinclusions]] -- usu. harder to find; have high [[specificity]] (nuclear pseudoinclusions appear as a result of the very convoluted nuclear membrane wrapping around parts of the cytoplasm; true nuclear inclusions in contrast are seen only in viral infections).
*#Nuclear grooves, seen as a result of the highly "textured" nuclear membrane.
*#Nuclear clearing (only on permanent section) - also known as "Orphan Annie eyes".
*Overlap of nuclei - "cells do not respect each other's borders" (easy to see at '''key feature at low power''').
*Classically has papillae (nipple-like shape); papilla (definition): epithelium on fibrovascular core.
**Absence of papillae does not exclude diagnosis.
*[[Psammoma bodies]].
**Circular, acellular, eosinophilic whorled bodies.
**Not necessary to make diagnosis - but very specific in the context of a specimen labeled "thyroid".
**Arise from infarction & calcification of papilla tips.<ref name=Ref_Sternberg4_565>{{Ref Sternberg4|565}}</ref>

Notes:
*Psammoma bodies are awesome if you see 'em, i.e. useful for arriving at the diagnosis.
**If there are no papillae structures -- you're unlikely to see psammoma bodies.
*At low power look for cellular areas/loss of follicles.
*Nuclear clearing seen in:
**Hashimoto's and papillary thyroid carcinoma.<ref name=Ref_Sternberg4_566>{{Ref Sternberg4|566}}</ref>
**May be an artifact of [[fixation]]/processing.
*Nuclear overlapping is easy to see at lower power-- should be the tip-off to look at high power for nuclear features.
*Nuclear inclusions are quite rare and not required to make the diagnosis -- but a very convincing feature if seen.
*Papillae may be seen in Graves disease.

DDx:
*[[Lymphocytic thyroiditis]]:
**[[Graves disease]].
**[[Hashimoto thyroiditis]].
*[[Solid cell nest of thyroid]].<ref name=pmid16830963>{{Cite journal | last1 = Baloch | first1 = ZW. | last2 = LiVolsi | first2 = VA. | title = Cytologic and architectural mimics of papillary thyroid carcinoma. Diagnostic challenges in fine-needle aspiration and surgical pathology specimens. | journal = Am J Clin Pathol | volume = 125 Suppl | issue = | pages = S135-44 | month = Jun | year = 2006 | doi = | PMID = 16830963 | URL = http://ajcp.ascpjournals.org/content/supplements/125/Suppl_1/S135.full.pdf }}</ref>

====Subtypes of papillary thyroid carcinoma====
There are many.

Poor prognosis variants:
*[[Papillary thyroid carcinoma tall cell variant|Tall cell variant]].<ref name=pmid22432054>{{Cite journal | last1 = Gonzalez-Gonzalez | first1 = R. | last2 = Bologna-Molina | first2 = R. | last3 = Carreon-Burciaga | first3 = RG. | last4 = Gómezpalacio-Gastelum | first4 = M. | last5 = Molina-Frechero | first5 = N. | last6 = Salazar-Rodríguez | first6 = S. | title = Papillary thyroid carcinoma: differential diagnosis and prognostic values of its different variants: review of the literature. | journal = ISRN Oncol | volume = 2011 | issue = | pages = 915925 | month = | year = 2011 | doi = 10.5402/2011/915925 | PMID = 22432054 | PMC = 3302055 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22432054/?tool=pubmed }}</ref>
*[[Papillary thyroid carcinoma columnar cell variant|Columnar cell variant]].<ref name=pmid22432054/>
*[[Papillary thyroid carcinoma solid variant|Solid variant]].<ref name=pmid22432054/>
*[[Papillary thyroid carcinoma diffuse sclerosing variant|Diffuse sclerosing variant]].<ref>URL: [http://emedicine.medscape.com/article/849000-overview#a0104 http://emedicine.medscape.com/article/849000-overview#a0104]. Accessed on: 1 May 2012.</ref>

=====Papillary thyroid carcinoma tall cell variant=====
======General======
*~10% of PTC.<ref>{{Ref Sternberg5|505}}</ref>
*Often large > 6 cm.

======Microscopic======
Features:<ref name=pmid19373912>{{cite journal |author=Urano M, Kiriyama Y, Takakuwa Y, Kuroda M |title=Tall cell variant of papillary thyroid carcinoma: Its characteristic features demonstrated by fine-needle aspiration cytology and immunohistochemical study |journal=Diagn. Cytopathol. |volume= |issue= |pages= |year=2009 |month=April |pmid=19373912 |doi=10.1002/dc.21086 |url=}}</ref>
*50% of cells with height 2x the width.<ref name=pmid18925842>{{cite journal |author=Ghossein R, Livolsi VA |title=Papillary thyroid carcinoma tall cell variant |journal=Thyroid |volume=18 |issue=11 |pages=1179–81 |year=2008 |month=November |pmid=18925842 |doi=10.1089/thy.2008.0164 |url=}}</ref>
**There is some disagreement on these criteria;<ref name=pmid18925842/> Raphael believes the height ought to be ~3x width, for 50% of the cells.<ref>S. Raphael. 17 January 2011.</ref>
*Eosinophilic cytoplasm.
*Well-defined cell borders.
*Nucleus stratified; basal location, i.e. closer to the basement membrane.

Negative:
*Nuclei ''not'' pseudostratified, if pseudostratified consider ''columnar cell variant''.

Images:
*[http://commons.wikimedia.org/wiki/File:Papillary_thyroid_carcinoma_tall_cell_var_intermed_mag.jpg PTC tall cell variant - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Papillary_thyroid_carcinoma_tall_cell_var_high_mag.jpg PTC tall cell variant - high mag. (WC)].

=====Papillary thyroid carcinoma columnar cell variant=====
======General======
Epidemiology:
*Poor prognosis.
*Very rare.

======Microscopic======
Features:<ref name=Ref_Sternberg5_506>{{Ref Sternberg5|506}}</ref>
*Elongated nuclei (similar to colorectal adenocarcinoma) - '''key feature'''.
*+/-Pseudostratification of the nuclei (like in colorectal adenocarcinoma), differentiates from ''tall cell variant''.
*Nuclear stratification - '''key feature'''.
*"Minimal" papillary features.
*"Tall cells".
*Clear-eosinophilic cytoplasm.
*Mitoses common.

Image: [http://www3.interscience.wiley.com/cgi-bin/fulltext/75000320/nfig003a?CRETRY=1&SRETRY=0 Columnar variant PTC (wiley.com)].
=====Papillary thyroid carcinoma follicular variant=====
======General======
*May be confused with [[follicular thyroid carcinoma|follicular carcinoma]] or [[follicular thyroid adenoma|follicular adenoma]].
*Pathologists often disagree about this diagnosis.<ref name=pmid21940284>{{Cite journal | last1 = Daniels | first1 = GH. | title = What if many follicular variant papillary thyroid carcinomas are not malignant? A review of follicular variant papillary thyroid carcinoma and a proposal for a new classification. | journal = Endocr Pract | volume = 17 | issue = 5 | pages = 768-87 | month = | year = | doi = 10.4158/EP10407.RA | PMID = 21940284 }}</ref>

======Microscopic======
Features:<ref name=Ref_EP88>{{Ref EP|88}}</ref>
*Small tightly packed follicles - '''key feature'''.
*Hypereosinophilic colloid.
*Nuclear features of PTC.
**Large nuclei.
**Typically have less [[nuclear pseudoinclusion]]s than the conventional type.
*+/-Fibrous capsule (common).

DDx:
*[[Follicular thyroid carcinoma]] - has a fibrous capsule and invasion though it.
*[[Follicular thyroid adenoma]] - surrounded by a fibrous capsule.
*[[Adenomatoid nodule]] - round nuclei, no nuclear features of PTC.

Images:
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=2008080217023776 PTC follicular variant (surgicalpathologyatlas.com)].
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=2008080216593186 PTC follicular variant (surgicalpathologyatlas.com)].
*[http://www.thyroidcancercanada.org/userfiles/images/Follicular_slide.jpg PTC follicular variant (thyroidcancercanada.org)].<ref>URL: [http://www.thyroidcancercanada.org/types-of-thyroid-cancer.php?lang=en http://www.thyroidcancercanada.org/types-of-thyroid-cancer.php?lang=en]. Accessed on: 9 January 2013.</ref>

=====Papillary thyroid carcinoma cribriform-morular variant=====
======General======
*Associated with [[familial adenomatous polyposis]] (FAP).<ref name=pmid18612695>{{cite journal |author=Groen EJ, Roos A, Muntinghe FL, ''et al.'' |title=Extra-intestinal manifestations of familial adenomatous polyposis |journal=Ann. Surg. Oncol. |volume=15 |issue=9 |pages=2439–50 |year=2008 |month=September |pmid=18612695 |pmc=2518080 |doi=10.1245/s10434-008-9981-3 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518080/?tool=pubmed}}</ref>

======Microscopic======
Features:
*Cribriform architectural pattern.
*Morules - balls of tissue.

=====Papillary thyroid carcinoma diffuse sclerosing variant=====
======General======
*Usually young adults, children.

======Microscopic======
Features:<ref>{{Ref PBoD8|1122}}</ref>
*Papillae - usu. prominent.
*Squamous morules - '''key features'''.<ref name=pmid15233643>{{Cite journal | last1 = Hirokawa | first1 = M. | last2 = Kuma | first2 = S. | last3 = Miyauchi | first3 = A. | last4 = Qian | first4 = ZR. | last5 = Nakasono | first5 = M. | last6 = Sano | first6 = T. | last7 = Kakudo | first7 = K. | title = Morules in cribriform-morular variant of papillary thyroid carcinoma: Immunohistochemical characteristics and distinction from squamous metaplasia. | journal = APMIS | volume = 112 | issue = 4-5 | pages = 275-82 | month = | year = | doi = 10.1111/j.1600-0463.2004.apm11204-0508.x | PMID = 15233643 }}
</ref>
*Lymphocytes - abundant.
*Fibrosis.

DDx:
*Lymphocytic thyroiditis (esp. Hashimoto's thyroiditis).

=====Papillary thyroid carcinoma warthin-like variant=====
*Resemble [[Warthin tumour]].
======Microscopic======
Features:<ref name=Ref_Sternberg5_506>{{Ref Sternberg5|506}}</ref>
*Eosinophilic cytoplasm.
*Lymphocytic thyroiditis.
*Papillae.

=====Papillary thyroid carcinoma solid variant=====
Features:<ref name=pmid22432054/>
*Some studies suggest this has a poor prognosis.
*More common in children.
*Associated with Chernobyl nuclear accident.

======Microscopic======
Features:
*Solid sheets >50% of tumour mass.<ref name=pmid22432054/>

===IHC===
Thyroid versus something else:
*Thyroglobulin +ve.
*TTF-1 (thyroid transcription factor-1) +ve.
*CD15 +ve.{{fact}}

PTC versus benign:<ref>{{Cite journal | last1 = Mataraci | first1 = EA. | last2 = Ozgüven | first2 = BY. | last3 = Kabukçuoglu | first3 = F. | title = Expression of cytokeratin 19, HBME-1 and galectin-3 in neoplastic and nonneoplastic thyroid lesions. | journal = Pol J Pathol | volume = 63 | issue = 1 | pages = 58-64 | month = Mar | year = 2012 | doi = | PMID = 22535608 }}</ref>
*HBME-1 +ve (strong, diffuse).
*CK19 +ve (strong, diffuse).
*Galectin-3 +ve (strong, diffuse).

===Molecular===
*Currently not widely used in a diagnostic context.

====Tabular summary====
Molecular changes in papillary thyroid carcinoma as per ''Adeniran et al'':<ref name=pmid16434896>{{Cite journal | last1 = Adeniran | first1 = AJ. | last2 = Zhu | first2 = Z. | last3 = Gandhi | first3 = M. | last4 = Steward | first4 = DL. | last5 = Fidler | first5 = JP. | last6 = Giordano | first6 = TJ. | last7 = Biddinger | first7 = PW. | last8 = Nikiforov | first8 = YE. | title = Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. | journal = Am J Surg Pathol | volume = 30 | issue = 2 | pages = 216-22 | month = Feb | year = 2006 | doi = | PMID = 16434896 }}</ref>
{| class="wikitable sortable"
! Molecular change
! Frequency
! Histology
! Notes
|-
|BRAF point mutations
| ~ 40%
| [[papillary thyroid carcinoma tall cell variant|tall cell variant]]
| poorer prognosis, older individuals
|-
|RET/PTC rearrangments
| ~ 20%
| papillary architecture, [[psammoma bodies]]
| younger individuals
|-
|RAS point mutations
| ~ 15%
| exclusively [[papillary thyroid carcinoma follicular variant|follicular variant]]
| -
|}

===Sign out===
<pre>
HEMITHYROID, RIGHT, COMPLETION OF TOTAL THYROIDECTOMY:
- PAPILLARY THYROID CARCINOMA, FOLLICULAR VARIANT.
-- TUMOUR SIZE: 4 MM (MAXIMAL).
-- ARCHITECTURE: FOLLICULAR.
-- CYTOMORPHOLOGY: CLASSICAL.
-- HISTOLOGIC GRADE: G1 (WELL DIFFERENTIATED).
-- NO TUMOUR CAPSULE IDENTIFIED.
-- NEGATIVE FOR LYMPHOVASCULAR INVASION.
-- NEGATIVE FOR PERINEURAL INVASION.
-- NEGATIVE FOR EXTRATHYROIDAL EXTENSION.
-- SURGICAL MARGINS NEGATIVE FOR MALIGNANCY.
</pre>

Note:
*If it is a completion thyroidectomy and the staging changes one should do a full synoptic report.

==Insular carcinoma==
===General===
Features:<ref name=pmid17665497>{{cite journal |author=Rufini V, Salvatori M, Fadda G, ''et al.'' |title=Thyroid carcinomas with a variable insular component: prognostic significance of histopathologic patterns |journal=Cancer |volume=110 |issue=6 |pages=1209–17 |year=2007 |month=September |pmid=17665497 |doi=10.1002/cncr.22913 |url=}}</ref>
*Rare - approximately 5% of all thyroid carcinomas.
*Thought to be a separate tumour from papillary thyroid carcinoma and follicular thyroid carcinoma with a focal insular pattern.
*Some lump this entity with papillary carcinoma, i.e. consider it a variant of papillary thyroid carcinoma.

===Microscopic===
Features:<ref name=pmid17665497/>
*Islands of cells - '''key feature'''.
*Scant cytoplasm.
*Nuclei monomorphic and round.

DDx:<ref>Endo. fellow. 17 September 2009.</ref>
*[[Medullary thyroid carcinoma]].
*Poorly differentiated thyroid carcinoma.

==Follicular thyroid carcinoma==
*[[AKA]] ''follicular carcinoma''.
===Clinical===
Medical school memory device ''4 Fs'':
*FNA NOT diagnosable.
*Far away mets (sometimes).
*Female predominant.
*Favourable prognosis.

Notes:
*Usu. has a hematologic spread.
**PTC usu. spread via lymphatics.

===Microscopic===
Features:
*Defined by either:
*#Invasion through the capsule:
*#*Should be all the way through.<ref>SR. 17 January 2011.</ref>
*#**1/2 does not count.
*#**Fibrous reaction does not count.
*#**"Above the contour" does not count.
*#Vascular invasion (all of the following):
*##In a small vein (not a capillary), that is outside of the tumour mass.
*##Tumour adherent to the side of the vessel.
*##Tumour must be re-endothelialized.

Notes:
*'''Impossible''' to differentiate from ''[[follicular thyroid adenoma|follicular adenoma]]'' on FNA (no cytologic differences).
*Described as "over-diagnosed" ... misdiagnoses: PTC follicular variant, follicular adenoma, multinodular goitre with a thick capsule.

Images:
*[http://path.upmc.edu/cases/case653.html Follicular thyroid carcinoma - several images (upmc.edu)].

==Medullary thyroid carcinoma==
*Abbreviated ''MTC''.
===General===
Medical school memory device - 3 M's:
*[[amyloid|aMyloid]].
*Median node dissection done.
*[[MEN IIa syndrome]]/[[MEN IIb syndrome]].
**Medullary thyroid carcinoma.
**[[Pheochromocytoma]].
**[[Parathyroid adenoma]].

Epidemiology:
*Very rare.
*Poor prognosis.
*May be genetic (MEN IIa/b syndrome).
*Arises from C cells (which produce calcitonin).

Syndromic tumours - typically:<ref name=pmid21455198>{{Cite journal | last1 = Nosé | first1 = V. | title = Familial thyroid cancer: a review. | journal = Mod Pathol | volume = 24 Suppl 2 | issue = | pages = S19-33 | month = Apr | year = 2011 | doi = 10.1038/modpathol.2010.147 | PMID = 21455198 |URL = http://www.nature.com/modpathol/journal/v24/n2s/full/modpathol2010147a.html }}</ref>
*Present in 30s or 40s.
*+/-Multifocal.
*+/-Bilateral.
*[[C-cell hyperplasia]].

===Gross===
Features:<ref name=pmid21455198/>
*Usu. well-circumscribed.
*White, gray or yellow.
*Gritty.
*Firm.

Image:
*[http://www.nature.com/modpathol/journal/v24/n2s/fig_tab/modpathol2010147f2.html MTC (nature.com)].

===Microscopic===
Features:
*Nuclei with "neuroendocrine features".
**Small, round nuclei.
**Coarse chromatin (''salt and pepper nuclei'').
*+/-[[Amyloid]] deposits - fluffy appearing acellular eosinophilic material in the cytoplasm.
*+/-[[C-cell hyperplasia]] - seen with familial forms of MTC.
**C cells (AKA ''parafollicular cell''): abundant cytoplasm - clear/pale.

Note:
*The amyloid is formed from ''calcitonin''.<ref name=pmid15459123>{{Cite journal | last1 = Khurana | first1 = R. | last2 = Agarwal | first2 = A. | last3 = Bajpai | first3 = VK. | last4 = Verma | first4 = N. | last5 = Sharma | first5 = AK. | last6 = Gupta | first6 = RP. | last7 = Madhusudan | first7 = KP. | title = Unraveling the amyloid associated with human medullary thyroid carcinoma. | journal = Endocrinology | volume = 145 | issue = 12 | pages = 5465-70 | month = Dec | year = 2004 | doi = 10.1210/en.2004-0780 | PMID = 15459123 }}</ref>

Images:
*www:
**[http://jcp.bmj.com/content/vol57/issue3/images/large/cp8474.f16.jpeg Medullary thyroid carcinoma (bmj.com)].
**[http://www.nature.com/ki/journal/v70/n11/fig_tab/5001888f2.html C cell hyperplasia (nature.com)].
**[http://lifesci.rutgers.edu/~babiarz/Review3/Lp6/scope8.htm C cell (rutgers.edu)].
**[http://www.anatomyatlases.org/MicroscopicAnatomy/Images/Plate287.jpg Parafollicular cells (anatomyatlases.org)].
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_low_mag.jpg MTC - low mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_high_mag.jpg MTC - high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_2_-_high_mag.jpg MTC and amyloid - high mag. (WC)].

===IHC===
Features:<ref>URL: [http://pathologyoutlines.com/thyroid.html#medullary http://pathologyoutlines.com/thyroid.html#medullary]. Accessed on: 17 January 2011.</ref>
*[[Calcitonin]] +ve - it arises from C cells (which produce calcitonin).
*Congo-red +ve (amyloid present) - mnemonic: ''CRAP'' -- congo red amyloid protein.
*Neuroendocrine markers.
**[[Chromogranin A]].
**[[Synaptophysin]].
*CEA +ve (often better staining than calcitonin).<ref>SB. 7 January 2010.</ref>
*Thyroglobulin usu. -ve.<ref name=pmid8454270>{{Cite journal | last1 = de Micco | first1 = C. | last2 = Chapel | first2 = F. | last3 = Dor | first3 = AM. | last4 = Garcia | first4 = S. | last5 = Ruf | first5 = J. | last6 = Carayon | first6 = P. | last7 = Henry | first7 = JF. | last8 = Lebreuil | first8 = G. | title = Thyroglobulin in medullary thyroid carcinoma: immunohistochemical study with polyclonal and monoclonal antibodies. | journal = Hum Pathol | volume = 24 | issue = 3 | pages = 256-62 | month = Mar | year = 1993 | doi = | PMID = 8454270 }}</ref>

===EM===
*Neurosecretory granules.
**Feature seen in neuroendocrine tumours.

Images: [http://pathhsw5m54.ucsf.edu/case7/image77.html Neurosecretory granules (ucsf.edu)].

==Anaplastic thyroid carcinoma==
===Epidemiology===
*Very rare.
*Horrible prognosis.
*Often presents with obstruction.
*Typically there is a history of a thyroid mass.

===Microscopic===
Features:
*Cytologically malignant:
**Huge [[NC ratio]].
**Mitoses.
*+/-[[Necrosis]].

Notes:
*May have features of other thyroid carcinomas, e.g. psammoma bodies, papillae, nuclear changes of PTC.

Image: [http://commons.wikimedia.org/wiki/File:Anaplastic_thyroid_carcinoma_low_mag.jpg Anaplastic thyroid carcinoma with a component of papillary thyroid carcinoma (WC)].

DDx:
*[[Poorly differentiated carcinoma of the thyroid|Poorly differentiated carcinoma]].
*[[Squamous cell carcinoma]].
*[[Medullary thyroid carcinoma]].
*Sarcoma.

===IHC===
*Keratin (AE1/AE3) +ve.
*Vimentin +ve, >90%.<ref name=pmid1712540>{{cite journal |author=Ordóñez NG, El-Naggar AK, Hickey RC, Samaan NA |title=Anaplastic thyroid carcinoma. Immunocytochemical study of 32 cases |journal=Am. J. Clin. Pathol. |volume=96 |issue=1 |pages=15–24 |year=1991 |month=July |pmid=1712540 |doi= |url=}}</ref>
*Thyroglobulin - rarely +ve (~15%).<ref name=pmid1712540/>
*CEA -ve, calcitonin -ve; to r/o medullary.
*p53 +ve.
*TTF-1 +ve.

==Lymphomas of the thyroid==
{{Main|Lymphoma}}
===General===
*Rare.
*Increased risk with chronic inflammatory conditions.
*Fit in the the greater category of ''[[MALT lymphoma]]''.

===Microscopic===
Features:
*Lymphoepithelial lesion - '''key feature'''.
*Plasma cells.
*"Overgrowth" - thyroid parenchyma displaced by lymphocytes.

=Weird stuff=
==Hyalinizing trabecular tumour==
*[[AKA]] ''hyalinizing trabecular adenoma''.
*Abbreviated ''HTT''.
===General===
*Considered by some (e.g. Silvia Asa) to be a variant of [[papillary thyroid carcinoma]].<ref name=pmid11117782>{{cite journal |author=Cheung CC, Boerner SL, MacMillan CM, Ramyar L, Asa SL |title=Hyalinizing trabecular tumor of the thyroid: a variant of papillary carcinoma proved by molecular genetics |journal=Am. J. Surg. Pathol. |volume=24 |issue=12 |pages=1622–6 |year=2000 |month=December |pmid=11117782 |doi= |url=}}</ref>
*Behaviour similar to papillary thyroid carcinoma - indolent.

===Microscopic===
Features:
*Trabecular arrangement of cells.
**May have "curved" trabeculae.
*Extracellular space has hyaline material - '''key feature'''.
*Cytoplasm mimics hyaline material in the extracellular space.

Images:
*[http://archive.biomedcentral.com/1742-6413/3/17/figure/F2?highres=y HTT (biomedcentral.com)].<ref name=pmid16867191>{{Cite journal | last1 = Baloch | first1 = ZW. | last2 = Puttaswamy | first2 = K. | last3 = Brose | first3 = M. | last4 = LiVolsi | first4 = VA. | title = Lack of BRAF mutations in hyalinizing trabecular neoplasm. | journal = Cytojournal | volume = 3 | issue = | pages = 17 | month = | year = 2006 | doi = 10.1186/1742-6413-3-17 | PMID = 16867191 }}</ref>
*[http://www.ispub.com/journal/the-internet-journal-of-endocrinology/volume-2-number-1/hyalinizing-trabecular-neoplasm-of-the-thyroid-controversies-in-management.article-g01.fs.jpg HTT (ispub.com)].<ref>URL: [http://www.ispub.com/journal/the-internet-journal-of-endocrinology/volume-2-number-1/hyalinizing-trabecular-neoplasm-of-the-thyroid-controversies-in-management.html http://www.ispub.com/journal/the-internet-journal-of-endocrinology/volume-2-number-1/hyalinizing-trabecular-neoplasm-of-the-thyroid-controversies-in-management.html]. Accessed on: 1 January 2012.</ref>

DDx:
*[[Papillary thyroid carcinoma]] (if one believes this is a separate entity).
*[[Medullary thyroid carcinoma]] - not trabecular, nuclei not [[PTC]]-like.
*[[Paraganglioma]].<ref>URL: [http://path.upmc.edu/cases/case465/dx.html http://path.upmc.edu/cases/case465/dx.html]. Accessed on: 17 January 2011.</ref>

===IHC===
*Thyroglobulin +ve.
*NSE +ve.

==Hürthle cell neoplasm==
*[[AKA]] ''oncocytic neoplasm''.
*Also spelled ''Hurthle cell neoplasm''.

===General===
*Incidence: uncommon.
*This is a general category - includes:
**Hürthle cell adenoma.
**Hürthle cell carcinoma.

*Some advocate ''total thyroidectomy'' for all Hürthle cell neoplasms, as it is difficult to reliably differentiate adenomas and carcinomas.<ref name=pmid9697901>{{Cite journal | last1 = Wasvary | first1 = H. | last2 = Czako | first2 = P. | last3 = Poulik | first3 = J. | last4 = Lucas | first4 = R. | title = Unilateral lobectomy for Hurthle cell adenoma. | journal = Am Surg | volume = 64 | issue = 8 | pages = 729-32; discussion 732-3 | month = Aug | year = 1998 | doi = | PMID = 9697901 }}</ref>
*It can be understood as a special type of ''follicular neoplasm'' (including ''[[follicular thyroid adenoma]]'' and ''[[follicular thyroid carcinoma]]'').<ref name=Ref_EP104>{{Ref EP|104}}</ref>

====Adenoma vs. carcinoma====
Suggestive for carcinoma:<ref name=pmid9697901/>
*Male.
*>4 cm
**Adenomas usu. <3 cm.
Definite for carcinoma:<ref name=pmid9697901/>
*Lymphovascular invasion.
*Capsular invasion.

===Gross===
*Yellow.
*Encapsulated.

===Microscopic===
Features:<ref name=Ref_EP104>{{Ref EP|104}}</ref>
*Oncocytes >= 75% of cells:
**Abundant granular, eosinophilic cytoplasm.
**Round regular nucleus +/- prominent nucleolus.
*+/-Degenerative changes.

Negatives:
*Lack nuclear features of [[papillary thyroid carcinoma]].
*Lack features of [[medullary thyroid carcinoma]].

DDx:<ref name=pmid18684023>{{cite journal |author=Montone KT, Baloch ZW, LiVolsi VA |title=The thyroid Hürthle (oncocytic) cell and its associated pathologic conditions: a surgical pathology and cytopathology review |journal=Arch. Pathol. Lab. Med. |volume=132 |issue=8 |pages=1241–50 |year=2008 |month=August |pmid=18684023 |doi= |url=}}</ref>
*Papillary thyroid carcinoma oncocytic variant.
*Medullary thyroid carcinoma oncocytic variant.
*Others.

==Minocycline associated thyroid pigmentation==
*[[AKA]] ''minocycline thyroid''.

===General===
*Benign pigmentation of the thyroid due to ''minocycline'', an antibiotic.
**Reported at other sites, e.g. [[heart valves]],<ref name=pmid10615019/> coronary arteries.

===Gross===
*Black thyroid.<ref name=pmid2780449>{{Cite journal | last1 = Noble | first1 = JG. | last2 = Christmas | first2 = TJ. | last3 = Chapple | first3 = C. | last4 = Katz | first4 = D. | last5 = Milroy | first5 = EJ. | title = The black thyroid: an unusual finding during neck exploration. | journal = Postgrad Med J | volume = 65 | issue = 759 | pages = 34-5 | month = Jan | year = 1989 | doi = | PMID = 2780449 | PMC = 2429157 }}</ref>

Images:
*[http://images.rheumatology.org/viewphoto.php?albumId=89099&imageId=5231272 Pigmented thyroid gland (rheumatology.org)].
*[http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2004)128%3C355:PQCTIP%3E2.0.CO;2 Minocycline thyroid - gross and microscopic (archivesofpathology.org)].<ref name=pmid14987144>{{Cite journal | last1 = Raghavan | first1 = R. | last2 = Snyder | first2 = WH. | last3 = Sharma | first3 = S. | title = Pathologic quiz case: tumor in pigmented thyroid gland in a young man. Papillary thyroid carcinoma in a minocycline-induced, diffusely pigmented thyroid gland. | journal = Arch Pathol Lab Med | volume = 128 | issue = 3 | pages = 355-6 | month = Mar | year = 2004 | doi = 10.1043/1543-2165(2004)128355:PQCTIP2.0.CO;2 | PMID = 14987144 }}</ref>

===Microscopic===
Features:
*Granular yellow blobs:
**Location:
***Intracytoplasmic in the follicule-lining cells, i.e. follicular cells.
***Intrafollicular.
**Variable size ~0.5-4 micrometers.

Notes:
*Pigment described as ''lipofuscin-like''.<ref name=pmid6435454>{{Cite journal | last1 = Gordon | first1 = G. | last2 = Sparano | first2 = BM. | last3 = Kramer | first3 = AW. | last4 = Kelly | first4 = RG. | last5 = Iatropoulos | first5 = MJ. | title = Thyroid gland pigmentation and minocycline therapy. | journal = Am J Pathol | volume = 117 | issue = 1 | pages = 98-109 | month = Oct | year = 1984 | doi = | PMID = 6435454 | PMC = 1900569 }}</ref>

Images:
*[http://flylib.com/books/2/953/1/html/2/44%20-%20Thyroid_files/DA11C44FF7.png Pigmentation due to minocycline (flylib.com)].<ref>URL: [http://flylib.com/books/en/2.953.1.50/1/ http://flylib.com/books/en/2.953.1.50/1/]. Accessed on: 11 March 2012.</ref>
*[http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2004)128%3C355:PQCTIP%3E2.0.CO;2 Minocycline thyroid - gross and microscopic (archivesofpathology.org)].<ref name=pmid14987144>{{Cite journal | last1 = Raghavan | first1 = R. | last2 = Snyder | first2 = WH. | last3 = Sharma | first3 = S. | title = Pathologic quiz case: tumor in pigmented thyroid gland in a young man. Papillary thyroid carcinoma in a minocycline-induced, diffusely pigmented thyroid gland. | journal = Arch Pathol Lab Med | volume = 128 | issue = 3 | pages = 355-6 | month = Mar | year = 2004 | doi = 10.1043/1543-2165(2004)128355:PQCTIP2.0.CO;2 | PMID = 14987144 }}</ref>

===Stains===
*Fontana-Masson stain +ve.<ref name=pmid10615019>{{Cite journal | last1 = Sant'Ambrogio | first1 = S. | last2 = Connelly | first2 = J. | last3 = DiMaio | first3 = D. | title = Minocycline pigmentation of heart valves. | journal = Cardiovasc Pathol | volume = 8 | issue = 6 | pages = 329-32 | month = | year = | doi = | PMID = 10615019 }}</ref>

=See also=
*[[Thyroid cytopathology]].
*[[Head and neck cytopathology]].
*[[Salivary gland]].
*[[Cytopathology]].

=References=
{{reflist|2}}

[[Category:Endocrine pathology]]

Thyroid gland

2013-06-13T18:46:51Z

Ingo: /* Microscopic */

The '''thyroid gland''' is an important little endocrine organ in the anterior [[neck]]. It is frequently afflicted by [[cancer]]... but the common cancer has such a good prognosis there is debate about how aggressively it should be treated. The [[cytopathology]] of the thyroid gland is dealt with in the ''[[thyroid cytology]]'' article.

The gland frustrates a significant number of pathologists, as the criteria for cancer are considered a bit wishy-washy.

=Thyroid specimens=
==They come in three common varieties==
*FNA (fine needle aspiration).
**Done to triage patients/rule-out malignancy - discussed in the article ''[[thyroid cytopathology]]''.
*Hemithyroid.
**Done to get a definitive diagnosis.
**May be a "completion" - removal of the other half following definitive diagnosis.
*Total thyroid.
**Done for malignancy or follicular lesion.

==Gross pathology==
*White nodules - think:
**Lymphoid tissue.
**Papillary thyroid carcinoma - may be calcified.<ref>BEC. 20 October 2009.</ref>

=Diagnoses=
==Common==
*[[Thyroid gland nodular hyperplasia|Nodular hyperplasia]] -- most common.
*[[Lymphocytic thyroiditis]].
*Papillary thyroid carcinoma (PTC) -- most common cancer.
**[[Papillary thyroid carcinoma follicular variant]].
*[[Parathyroid]] tissue.

==Pitfalls/weird stuff==
*Thyroid tissue lateral to the jugular vein (often referred to as ''lateral aberrant thyroid tissue'') is generally considered metastatic thyroid carcinoma ([[papillary thyroid carcinoma]]) even if it looks benign.<ref name=pmid14452106>{{Cite journal | last1 = JOHNSON | first1 = RW. | last2 = SAHA | first2 = NC. | title = The so-called lateral aberrant thyroid. | journal = Br Med J | volume = 1 | issue = 5293 | pages = 1668-9 | month = Jun | year = 1962 | doi = | PMID = 14452106 | PMC = 1958877 }}</ref>
**This dictum is disputed.<ref name=pmid17319317>{{Cite journal | last1 = Escofet | first1 = X. | last2 = Khan | first2 = AZ. | last3 = Mazarani | first3 = W. | last4 = Woods | first4 = WG. | title = Lessons to be learned: a case study approach. Lateral aberrant thyroid tissue: is it always malignant? | journal = J R Soc Promot Health | volume = 127 | issue = 1 | pages = 45-6 | month = Jan | year = 2007 | doi = | PMID = 17319317 }}</ref>
**The level VI and VII [[lymph nodes]] are medial to the jugular.
*[[Hashimoto's disease]] may have so many lymphocytes that it mimics a lymph node -- may lead to misdiagnosis of PTC.
*Parasitic nodule: clump of thyroid that is attached by a thin thread... but looks like a separate nodule; may lead to misdiagnosis of PTC.

Image:
*[http://images.radiopaedia.org/images/26383/ad505c78a87e71180792049299f5cd_big_gallery.jpg Neck levels (radiopaedia.org)].<ref>URL: [http://radiopaedia.org/articles/lymph-node-levels-of-the-neck http://radiopaedia.org/articles/lymph-node-levels-of-the-neck]. Accessed on: 5 November 2012.</ref>

==Diagnostic keys==
The following should prompt careful examination:<ref>SR. 17 January 2011.</ref>
*Architecture: microfollicular, trabecular, solid, insular.
*Thick capsule.
*Necrosis - rare in the thyroid.

==Thyroid IHC - general comments==
*Not really useful.
*Papers with very small sample sizes abound.

===Follicular thyroid carcinoma vs. papillary thyroid carcinoma===
*CD31 more frequently positive in follicular lesions.<ref name=pmid18795075>{{Cite journal | last1 = Rydlova | first1 = M. | last2 = Ludvikova | first2 = M. | last3 = Stankova | first3 = I. | title = Potential diagnostic markers in nodular lesions of the thyroid gland: an immunohistochemical study. | journal = Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub | volume = 152 | issue = 1 | pages = 53-9 | month = Jun | year = 2008 | doi = | PMID = 18795075 }}</ref>
**CD31 is a marker for microvessel density.
*Galectin-3 thought to be positive in papillary carcinoma.<ref name=pmid18795075/>
*HBME-1 thought to be positive in papillary lesions.<ref name=pmid15529186>{{Cite journal | last1 = Papotti | first1 = M. | last2 = Rodriguez | first2 = J. | last3 = De Pompa | first3 = R. | last4 = Bartolazzi | first4 = A. | last5 = Rosai | first5 = J. | title = Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential. | journal = Mod Pathol | volume = 18 | issue = 4 | pages = 541-6 | month = Apr | year = 2005 | doi = 10.1038/modpathol.3800321 | PMID = 15529186 }}</ref>

==Thyroid lesions per WHO==
*Adapted from the ''Washington Manual of Surgical Pathology''.<ref name=Ref_WMSP331>{{Ref WMSP|331}}</ref>
===Adenoma===
*Follicular adenoma.
*Hyalinizing trabecular tumour.

===Carcinoma===
*[[Papillary thyroid carcinoma|Papillary carcinoma]].
*[[Follicular thyroid carcinoma|Follicular carinoma]].
*[[Medullary thyroid carcinoma|Medullary carcinoma]].
*Undifferentiated (anaplastic) carcinoma.

*Poorly differentiated carcinoma.
*[[Squamous cell carcinoma]].
*[[Mucoepidermoid carcinoma]].
*Sclerosing mucoepidermoid carcinoma with eosinophilia.
*Mucinous carcinoma.

*Mixed medullary and follicular carinoma.
*Spindle cell tumour with thymus-like differentiation.
*Carcinoma showing thymus-like differentiation.

===Others===
*[[Teratoma]].
*[[Lymphoma]].
*Ectopic thymoma.
*[[Angiosarcoma]] + other [[soft tissue lesions]].
*[[Paraganglioma]].
*[[Solitary fibrous tumour]].
*[[Follicular dendritic cell tumour]].
*[[Langerhans cell histiocytosis]].
*[[Metastasis]].

=Parathyroid glands=
{{Main|Parathyroid glands}}
*May make an appearance in the context of thyroid surgery.

=Benign=
==Solid cell nest of the thyroid gland==
*[[AKA]] ''solid cell nest of thyroid''.
===General===
*Embryonic remnants endodermal origin.<ref name=pmid12527712>{{cite journal |author=Reis-Filho JS, Preto A, Soares P, Ricardo S, Cameselle-Teijeiro J, Sobrinho-Simões M |title=p63 expression in solid cell nests of the thyroid: further evidence for a stem cell origin |journal=Mod. Pathol. |volume=16 |issue=1 |pages=43–8 |year=2003 |month=January |pmid=12527712 |doi=10.1097/01.MP.0000047306.72278.39 |url=http://www.nature.com/modpathol/journal/v16/n1/full/3880708a.html}}</ref>
*Incidental finding.

Note:
*Hypothesized to have some relation to [[mucoepidermoid carcinoma]] of the thyroid gland;<ref name=pmid1413837>{{Cite journal | last1 = Ozaki | first1 = O. | last2 = Ito | first2 = K. | last3 = Sugino | first3 = K. | last4 = Yasuda | first4 = K. | last5 = Yamashita | first5 = T. | last6 = Toshima | first6 = K. | title = Solid cell nests of the thyroid gland: precursor of mucoepidermoid carcinoma? | journal = World J Surg | volume = 16 | issue = 4 | pages = 685-8; discussion 688-9 | month = | year = | doi = | PMID = 1413837 }}</ref> however, another study suspects a relationship with [[papillary thyroid carcinoma]].<ref name=pmid22224821>{{Cite journal | last1 = Prichard | first1 = RS. | last2 = Lee | first2 = JC. | last3 = Gill | first3 = AJ. | last4 = Sywak | first4 = MS. | last5 = Fingleton | first5 = L. | last6 = Robinson | first6 = BG. | last7 = Sidhu | first7 = SB. | last8 = Delbridge | first8 = LW. | title = Mucoepidermoid carcinoma of the thyroid: a report of three cases and postulated histogenesis. | journal = Thyroid | volume = 22 | issue = 2 | pages = 205-9 | month = Feb | year = 2012 | doi = 10.1089/thy.2011.0276 | PMID = 22224821 }}</ref>

===Microscopic===
Features:<ref name=pmid12527712/>
*Cellular solid ''or'' cystic cluster of variable size with:
**Cuboidal cellular morphology.
***May have columnar morphology.
**Moderate-to-scant eosinophilic cytoplasm.
**Round/ovoid nuclei with finely granular chromatin.
*+/-Goblet cells (~30% of cases).<ref name=pmid7509563>{{cite journal |author=Mizukami Y, Nonomura A, Michigishi T, ''et al.'' |title=Solid cell nests of the thyroid. A histologic and immunohistochemical study |journal=Am. J. Clin. Pathol. |volume=101 |issue=2 |pages=186–91 |year=1994 |month=February |pmid=7509563 |doi= |url=}}</ref>

Images:
*www:
**[http://farm6.static.flickr.com/5143/5685400518_c4f506d370.jpg Solid cell next (flickr.com)].
**[http://www.nature.com/modpathol/journal/v16/n1/fig_tab/3880708f1.html#figure-title Crappy B&W of solid cell nest (nature.com)].
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Solid_cell_nest_of_the_thyroid_gland_-_intermed_mag.jpg Solid cell nest of the thyroid gland - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Solid_cell_nest_of_the_thyroid_gland_-_very_high_mag.jpg Solid cell nest of the thyroid gland - very high mag. (WC)].

DDx:<ref name=pmid12527712/>
*[[C-cell hyperplasia]].
*[[Medullary thyroid carcinoma|Medullary carcinoma]].
*Squamous lesions.

===IHC===
Features:<ref name=pmid12527712/>
*p63 +ve.
**-ve in clear cells.
*CEA +ve (polyconal).<ref name=pmid7509563>{{cite journal |author=Mizukami Y, Nonomura A, Michigishi T, ''et al.'' |title=Solid cell nests of the thyroid. A histologic and immunohistochemical study |journal=Am. J. Clin. Pathol. |volume=101 |issue=2 |pages=186–91 |year=1994 |month=February |pmid=7509563 |doi= |url=}}</ref>
**+ve also in clear cells.
*Chromogranin A +ve ~45% of cases.<ref name=pmid7509563/>

===Sign out===
Solid cell nests of the thyroid gland are usually not reported.

==Thyroid gland nodular hyperplasia==
*[[AKA]] ''[[nodular hyperplasia]]''.
*[[AKA]] ''adenomatoid nodule''.

===General===
*Clinical diagnosis: ''goitre'', [[AKA]] ''sporadic goitre'', AKA ''multinodular goitre'' (MNG).
*Most common diagnosis in the thyroid.
**If you've seen a handful of thyroids you've seen this.

Notes:
*Large lesions may be clonal; however, this is clinically irrelevant.

===Gross===
Features:
*Enlarge thyroid gland.
*+/-Distinct (well-circumscribed) nodules.

===Microscopic===
Features:
*Follicles of variable size - '''key feature'''.
**Should be obvious at low power, i.e. with the 2.5x objective.
*+/-Nodules.
**Do not have a thick fibrous capsule.
**May have a high cellularity.
**Architecture: solid or microfollicular.<ref name=Ref_EP36>{{Ref EP|36}}</ref>

Negatives:
*No nuclear features suggestive of malignancy (at lower power).
**One should not look at high power.
*Not cellular.

DDx:
*[[Papillary thyroid carcinoma]] - esp. [[papillary thyroid carcinoma follicular variant]].
*[[Follicular thyroid adenoma]] - contained in a fibrous capsule.
*[[Follicular thyroid carcinoma]] - has fibrous capsule and invasion through it.

===Sign out===
<pre>
HEMITHYROID, RIGHT, HEMITHYROIDECTOMY:
- NODULAR HYPERPLASIA.
- NEGATIVE FOR MALIGNANCY.
</pre>

<pre>
HEMITHYROID, RIGHT, HEMITHYROIDECTOMY:
- CELLULAR ADENOMATOID NODULE ON A BACKGROUND OF NODULAR HYPERPLASIA.
- NEGATIVE FOR MALIGNANCY.
</pre>

==Follicular thyroid adenoma==
*[[AKA]] follicular adenoma, [[AKA]] thyroid follicular adenoma.
===General===
*Most common neoplasm of thyroid.<ref name=Ref_EP51>{{Ref EP|51}}</ref>
*Encapusled lesion (surrounded by fibrous capsule).

===Gross===
*Thick capsule.

Notes:
*The entire capsule should be submitted.<ref>SR. 17 January 2011.</ref>
**A good start for most thyroid specimens with a thick capsule is 10 blocks.

===Microsopic===
Features:
*Cellular.
*Thick capsule - '''key feature'''.

Negatives.
*No invasion of the capsule (see ''[[follicular thyroid carcinoma]]'' section).
*No nuclear features suggestive of [[papillary thyroid carcinoma]].

DDx:
*[[Thyroid gland nodular hyperplasia]] with an encapsulated nodule - not as cellular.

==Graves disease==
===General===
*Often misspelled "Grave's disease".
*Autoimmune disease leading to hyperthyroidism.
*Eye problems not resolved with thyroid removal.{{fact}}
*Higher risk of [[papillary thyroid carcinoma]].

Clinical:
*TSH-receptor antibody +ve.<ref name=pmid19576193>{{Cite journal | last1 = Massart | first1 = C. | last2 = Gibassier | first2 = J. | last3 = d'Herbomez | first3 = M. | title = Clinical value of M22-based assays for TSH-receptor antibody (TRAb) in the follow-up of antithyroid drug treated Graves' disease: comparison with the second generation human TRAb assay. | journal = Clin Chim Acta | volume = 407 | issue = 1-2 | pages = 62-6 | month = Sep | year = 2009 | doi = 10.1016/j.cca.2009.06.033 | PMID = 19576193 }}</ref>

===Gross===
Features:<ref>{{Ref EP|30}}</ref>
*Enlarged 50-150 g.
*"Beefy-red" appearance, looks like raw beef.

===Microscopic===
Features:
*Classic:
**Hypercellular
**Patchy lymphocytes.
**Little colloid.
*Scalloping of colloid; colloid has undulating border.
**Non-specific finding.
*+/-Nuclear clearing.
*+/-Papillae (may mimic papillary thyroid carcinoma in this respect).

Notes:
*Usually has an unimpressive appearance... as it is treated, i.e. history is important.
*Nuclear clearing and papillae are usu. diffuse in Graves disease - unlike in papillary thyroid carcinoma.

Image:
*[http://library.med.utah.edu/WebPath/jpeg4/ENDO022.jpg Graves disease (med.utah.edu)].<ref>URL: [http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html]. Accessed on: 4 December 2011.</ref>

==Idiopathic granulomatous thyroiditis==
*[[AKA]] ''granulomatous thyroiditis'' - non-specific term; granulomas may be due a number of causes.
*AKA ''subacute thyroiditis''.
*[[AKA]] ''de Quervain thyroiditis''.
**Should '''not''' be confused with ''[[de Quervain's disease]]'' (AKA ''gamer's thumb'') something completely unrelated to the thyroid.

===General===
*Women > men.
*Etiology: possibly viral.<ref name=llyod/>

Clinical:
*Tenderness.<ref name=pmid22538753>{{Cite journal | last1 = Szczepanek-Parulska | first1 = E. | last2 = Zybek | first2 = A. | last3 = Biczysko | first3 = M. | last4 = Majewski | first4 = P. | last5 = Ruchała | first5 = M. | title = What might cause pain in the thyroid gland? Report of a patient with subacute thyroiditis of atypical presentation. | journal = Endokrynol Pol | volume = 63 | issue = 2 | pages = 138-42 | month = | year = 2012 | doi = | PMID = 22538753 }}</ref>

===Microscopic===
Features:<ref name=Ref_Sternberg4_559>{{Ref Sternberg4|559}}</ref><ref name=llyod>{{cite book |title=Endocrine Diseases (AFIP Atlas of Nontumor Pathology) |last= Lloyd |first = Ricardo V. |authorlink= |coauthors= |year= 2002 |publisher= American Registry of Pathology |location= Toronto |isbn=978-1881041733 |page= |pages= |url=http://www.amazon.com/Endocrine-Diseases-Atlas-Nontumer-Pathology/dp/1881041735 |accessdate=}}</ref>
*[[Granulomas]] with multinucleated giant cells - usu. with engulfed colloid.
*Lymphocytes.
*Plasma cells.
*+/-Fibrosis.

DDx:
*Infectious granulomatous disease (fungal, microbacterial).
*[[Palpation thyroiditis]].
*[[Sarcoidosis]] (classically intrafollicular distribution).

Images:
*[http://commons.wikimedia.org/wiki/File:Subacute_thyroiditis_-_intermed_mag.jpg Subacute thyroiditis - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Subacute_thyroiditis_-_high_mag.jpg Subacute thyroiditis - high mag. (WC)].

===Stains===
*ZN -ve.
*GMS -ve.

==Palpation thyroiditis==
===General===
*Granulomatous inflammation due to palpation.
**Incidence of granulomas higher in surgical thyroid specimens than autopsies.<ref name=llyod/>

===Microscopic===
Features:<ref name=llyod>{{cite book |title=Endocrine Diseases (AFIP Atlas of Nontumor Pathology) |last= Lloyd |first = Ricardo V. |authorlink= |coauthors= |year= 2002 |publisher= American Registry of Pathology |location= Toronto |isbn=978-1881041733 |page= |pages= |url=http://www.amazon.com/Endocrine-Diseases-Atlas-Nontumer-Pathology/dp/1881041735 |accessdate=}}</ref>
*[[Granuloma]]s involving the follicle.
**Histiocytes within the colloid.

DDx:
*[[Idiopathic granulomatous thyroiditis]].
*[[Sarcoidosis]].
*Infectious granulomatous thyroiditis.

===Stains===
*ZN -ve.
*GMS -ve.

==Riedel thyroiditis==
*[[AKA]] ''invasive fibrous thyroiditis''.<ref name=pmid21568724>{{Cite journal | last1 = Fatourechi | first1 = MM. | last2 = Hay | first2 = ID. | last3 = McIver | first3 = B. | last4 = Sebo | first4 = TJ. | last5 = Fatourechi | first5 = V. | title = Invasive fibrous thyroiditis (Riedel thyroiditis): the Mayo Clinic experience, 1976-2008. | journal = Thyroid | volume = 21 | issue = 7 | pages = 765-72 | month = Jul | year = 2011 | doi = 10.1089/thy.2010.0453 | PMID = 21568724 }}</ref>
===General===
Clinical features:<ref name=pmid21568724/>
*Extremely rare.
*Women > men.
*Usually smokers.
*May be associated with ''[[retroperitoneal fibrosis]]''.
*May be hypothyroid.
*+/-Obstructive symptoms.

===Microscopic===
Features:
*Fibrosis.
*Specimen often fragmented as it was difficult to remove.

DDx:
*[[Anaplastic thyroid carcinoma|Anaplastic carcinoma]], spindle cell variant.

==Hashimoto thyroiditis==
===General===
*'''This is a clinical diagnosis'''.
**The histomorphologic findings, generally, are '''not''' diagnostic.

Etiology:
*Autoimmune disease leading to hypothyroidism.
**Often genetic/part of a syndrome.

====Clinical====
Serology:<ref name=pmid7813361>{{cite journal |author=Poropatich C, Marcus D, Oertel YC |title=Hashimoto's thyroiditis: fine-needle aspirations of 50 asymptomatic cases |journal=Diagn. Cytopathol. |volume=11 |issue=2 |pages=141–5 |year=1994 |pmid=7813361 |doi= |url=http://www3.interscience.wiley.com/journal/112701408/abstract?CRETRY=1&SRETRY=0}}</ref>
*Antimicrosomal (antithyroid peroxidase) +ve.
*Antithyroglobulin +ve.

Associated pathology:<ref name=pmid7813361/>
*Increased risk of B-cell lymphoma; these are classically:<ref name=pmid18018576 >{{Cite journal | last1 = Ohye | first1 = H. | last2 = Fukata | first2 = S. | last3 = Hirokawa | first3 = M. | title = [Malignant lymphoma of the thyroid]. | journal = Nihon Rinsho | volume = 65 | issue = 11 | pages = 2092-8 | month = Nov | year = 2007 | doi = | PMID = 18018576 }}</ref>
**[[MALT lymphoma]].
**[[Diffuse large B cell lymphoma]] (DLBCL).

===Microscopic===
Features:
*Lymphocytic infiltrate - '''key feature'''.
*Nuclear clearing common.
**May confuse with [[papillary thyroid carcinoma]].
*Polymorphous lymphoplasmacytic infiltrate with germinal centres.<ref name=Ref_APBR672>{{Ref APBR|672}}</ref>
*+/-Oncocytic metaplasia.

Notes:
*Histologically often '''not''' possible to separate from "non-specific" thyroiditis.<ref name=Ref_Sternberg4_560>{{Ref Sternberg4|560}}</ref>

DDx:
*[[Lymphocytic thyroiditis]].
*[[Papillary thyroid carcinoma]].
*[[MALT lymphoma]].
*[[Diffuse large B cell lymphoma]].

===IHC===
*Panel to exclude lymphoma may be required, e.g. CD3, CD20, CD10, BCL6, BCL2, kappa, lambda.

===Molecular===
*Occasionally done to exclude lymphoma - see ''[[MALT lymphoma]]'' and ''[[DLBCL]]''.

==C-cell hyperplasia==
*Abbreviated ''CCH''.
===General===
*Screening for C-cell hyperplasia/[[medullary thyroid carcinoma]] done with ''serum calcitonin level''.<ref name=pmid19726541>{{cite journal |author=Machens A, Hoffmann F, Sekulla C, Dralle H |title=Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer |journal=Endocr. Relat. Cancer |volume=16 |issue=4 |pages=1291–8 |year=2009 |month=December |pmid=19726541 |doi=10.1677/ERC-09-0136 |url=http://erc.endocrinology-journals.org/cgi/content/full/16/4/1291}}</ref>

===Gross===
*Not visible.

===Microscopic===
Features:
*Location:<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Thyroid_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Thyroid_11protocol.pdf]. Accessed on: 7 April 2012.</ref>
**Mid portion of lobe to upper third of lobe.
***Not at the poles.
***Not in the isthmus.

*Definitions vary.<ref>SR. 17 January 2011.</ref>

One definition - either of the following:<ref name=pmid19726541>{{cite journal |author=Machens A, Hoffmann F, Sekulla C, Dralle H |title=Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer |journal=Endocr. Relat. Cancer |volume=16 |issue=4 |pages=1291–8 |year=2009 |month=December |pmid=19726541 |doi=10.1677/ERC-09-0136 |url=http://erc.endocrinology-journals.org/cgi/content/full/16/4/1291}}</ref>
#>50 C-cells per low-power field (x100).
#*This part of the definition suffers from [[LPFitis]]. The paper should have been rejected.
#Confined to the thyroid gland and no larger than 10 mm in greatest dimension.

Another definition:
*Invasion of the basement membrane with stromal reaction.

A third definition:
*"Several clusters" of more than six C cells.

====Images====
*[http://www.nature.com/modpathol/journal/v16/n8/fig_tab/3880836f2.html CCH - crappy B&W image (nature.com)].<ref>{{Cite journal | last1 = Guyétant | first1 = S. | last2 = Josselin | first2 = N. | last3 = Savagner | first3 = F. | last4 = Rohmer | first4 = V. | last5 = Michalak | first5 = S. | last6 = Saint-André | first6 = JP. | title = C-cell hyperplasia and medullary thyroid carcinoma: clinicopathological and genetic correlations in 66 consecutive patients. | journal = Mod Pathol | volume = 16 | issue = 8 | pages = 756-63 | month = Aug | year = 2003 | doi = 10.1097/01.MP.0000081727.75778.0C | PMID = 12920219 }}</ref>
*[http://www.nature.com/modpathol/journal/v16/n8/fig_tab/3880836f3.htm CCH - crappy B&W image (nature.com)].
*[http://www.forpath.org/workshops/0201/photos/fullsize/cas7c.jpg CCH (forpath.org)].<ref>URL: [http://www.forpath.org/workshops/0201/html/case_7.asp http://www.forpath.org/workshops/0201/html/case_7.asp]. Accessed on: 21 May 2013.</ref>
*[http://alf3.urz.unibas.ch/pathopic/e/getpic-fra.cfm?id=4849 CCH (unibas.ch)].
*[http://alf3.urz.unibas.ch/pathopic/e/getpic-fra.cfm?id=10739 Nodular CCH (unibas.ch)].

=Malignant neoplasm=
There are a bunch of 'em. The most common, by far, is papillary.

==Papillary thyroid carcinoma==
*Abbreviated ''PTC''.
===General===
Medical school memory device P's:
*Palpable nodes.
*Popular (most common malignant neoplasm of the thyroid).
*Prognosis is good.
*Pre-Tx iodine scan.
*Post-Sx iodine scan.
*[[Psammoma bodies]].

Notes:
*PTC is associated with radiation exposure.<ref name=Ref_Sternberg4_564>{{Ref Sternberg4|564}}</ref>
*''Papillary thyroid microcarcinoma'' is defined as a tumour with a maximal dimension of 1.0 cm or less.<ref name=pmid21267823>{{Cite journal | last1 = Sethom | first1 = A. | last2 = Riahi | first2 = I. | last3 = Riahi | first3 = K. | last4 = Akkari | first4 = K. | last5 = Benzarti | first5 = S. | last6 = Miled | first6 = I. | last7 = Chebbi | first7 = MK. | title = [Management of thyroid microcarcinoma. Report of 13 cases]. | journal = Tunis Med | volume = 89 | issue = 1 | pages = 23-5 | month = Jan | year = 2011 | doi = | PMID = 21267823 }}</ref>

====Prognosis====
Prognosis can be predicted by ''MAICS'' score. It which includes:<ref name=pmid12016468>{{Cite journal | last1 = Hay | first1 = ID. | last2 = Thompson | first2 = GB. | last3 = Grant | first3 = CS. | last4 = Bergstralh | first4 = EJ. | last5 = Dvorak | first5 = CE. | last6 = Gorman | first6 = CA. | last7 = Maurer | first7 = MS. | last8 = McIver | first8 = B. | last9 = Mullan | first9 = BP. | title = Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940-1999): temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients. | journal = World J Surg | volume = 26 | issue = 8 | pages = 879-85 | month = Aug | year = 2002 | doi = 10.1007/s00268-002-6612-1 | PMID = 12016468 }}</ref>
*'''M'''etastases.
*'''A'''ge.
*'''I'''nvasion of surround tissues.
*'''C'''completeness of excision.
*'''S'''ize of tumour.

===Microscopic===
Features:
*Nuclear changes - '''key feature'''.
*#"Shrivelled nuclei"/"raisin" like nuclei, nuclei with a wavy ("textured") nuclear membrane -- usu. easy to find.
*#[[Nuclear pseudoinclusions]] -- usu. harder to find; have high [[specificity]] (nuclear pseudoinclusions appear as a result of the "textured" nuclear membrane wrapping around parts of the cytoplasm; true nuclear inclusions in contrast are seen only in viral infections).
*#Nuclear grooves, seen as a result of the highly "textured" nuclear membrane.
*#Nuclear clearing (only on permanent section) - also known as "Orphan Annie eyes".
*Overlap of nuclei - "cells do not respect each other's borders" (easy to see at '''key feature at low power''').
*Classically has papillae (nipple-like shape); papilla (definition): epithelium on fibrovascular core.
**Absence of papillae does not exclude diagnosis.
*[[Psammoma bodies]].
**Circular, acellular, eosinophilic whorled bodies.
**Not necessary to make diagnosis - but very specific in the context of a specimen labeled "thyroid".
**Arise from infarction & calcification of papilla tips.<ref name=Ref_Sternberg4_565>{{Ref Sternberg4|565}}</ref>

Notes:
*Psammoma bodies are awesome if you see 'em, i.e. useful for arriving at the diagnosis.
**If there are no papillae structures -- you're unlikely to see psammoma bodies.
*At low power look for cellular areas/loss of follicles.
*Nuclear clearing seen in:
**Hashimoto's and papillary thyroid carcinoma.<ref name=Ref_Sternberg4_566>{{Ref Sternberg4|566}}</ref>
**May be an artifact of [[fixation]]/processing.
*Nuclear overlapping is easy to see at lower power-- should be the tip-off to look at high power for nuclear features.
*Nuclear inclusions are quite rare and not required to make the diagnosis -- but a very convincing feature if seen.
*Papillae may be seen in Graves disease.

DDx:
*[[Lymphocytic thyroiditis]]:
**[[Graves disease]].
**[[Hashimoto thyroiditis]].
*[[Solid cell nest of thyroid]].<ref name=pmid16830963>{{Cite journal | last1 = Baloch | first1 = ZW. | last2 = LiVolsi | first2 = VA. | title = Cytologic and architectural mimics of papillary thyroid carcinoma. Diagnostic challenges in fine-needle aspiration and surgical pathology specimens. | journal = Am J Clin Pathol | volume = 125 Suppl | issue = | pages = S135-44 | month = Jun | year = 2006 | doi = | PMID = 16830963 | URL = http://ajcp.ascpjournals.org/content/supplements/125/Suppl_1/S135.full.pdf }}</ref>

====Subtypes of papillary thyroid carcinoma====
There are many.

Poor prognosis variants:
*[[Papillary thyroid carcinoma tall cell variant|Tall cell variant]].<ref name=pmid22432054>{{Cite journal | last1 = Gonzalez-Gonzalez | first1 = R. | last2 = Bologna-Molina | first2 = R. | last3 = Carreon-Burciaga | first3 = RG. | last4 = Gómezpalacio-Gastelum | first4 = M. | last5 = Molina-Frechero | first5 = N. | last6 = Salazar-Rodríguez | first6 = S. | title = Papillary thyroid carcinoma: differential diagnosis and prognostic values of its different variants: review of the literature. | journal = ISRN Oncol | volume = 2011 | issue = | pages = 915925 | month = | year = 2011 | doi = 10.5402/2011/915925 | PMID = 22432054 | PMC = 3302055 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22432054/?tool=pubmed }}</ref>
*[[Papillary thyroid carcinoma columnar cell variant|Columnar cell variant]].<ref name=pmid22432054/>
*[[Papillary thyroid carcinoma solid variant|Solid variant]].<ref name=pmid22432054/>
*[[Papillary thyroid carcinoma diffuse sclerosing variant|Diffuse sclerosing variant]].<ref>URL: [http://emedicine.medscape.com/article/849000-overview#a0104 http://emedicine.medscape.com/article/849000-overview#a0104]. Accessed on: 1 May 2012.</ref>

=====Papillary thyroid carcinoma tall cell variant=====
======General======
*~10% of PTC.<ref>{{Ref Sternberg5|505}}</ref>
*Often large > 6 cm.

======Microscopic======
Features:<ref name=pmid19373912>{{cite journal |author=Urano M, Kiriyama Y, Takakuwa Y, Kuroda M |title=Tall cell variant of papillary thyroid carcinoma: Its characteristic features demonstrated by fine-needle aspiration cytology and immunohistochemical study |journal=Diagn. Cytopathol. |volume= |issue= |pages= |year=2009 |month=April |pmid=19373912 |doi=10.1002/dc.21086 |url=}}</ref>
*50% of cells with height 2x the width.<ref name=pmid18925842>{{cite journal |author=Ghossein R, Livolsi VA |title=Papillary thyroid carcinoma tall cell variant |journal=Thyroid |volume=18 |issue=11 |pages=1179–81 |year=2008 |month=November |pmid=18925842 |doi=10.1089/thy.2008.0164 |url=}}</ref>
**There is some disagreement on these criteria;<ref name=pmid18925842/> Raphael believes the height ought to be ~3x width, for 50% of the cells.<ref>S. Raphael. 17 January 2011.</ref>
*Eosinophilic cytoplasm.
*Well-defined cell borders.
*Nucleus stratified; basal location, i.e. closer to the basement membrane.

Negative:
*Nuclei ''not'' pseudostratified, if pseudostratified consider ''columnar cell variant''.

Images:
*[http://commons.wikimedia.org/wiki/File:Papillary_thyroid_carcinoma_tall_cell_var_intermed_mag.jpg PTC tall cell variant - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Papillary_thyroid_carcinoma_tall_cell_var_high_mag.jpg PTC tall cell variant - high mag. (WC)].

=====Papillary thyroid carcinoma columnar cell variant=====
======General======
Epidemiology:
*Poor prognosis.
*Very rare.

======Microscopic======
Features:<ref name=Ref_Sternberg5_506>{{Ref Sternberg5|506}}</ref>
*Elongated nuclei (similar to colorectal adenocarcinoma) - '''key feature'''.
*+/-Pseudostratification of the nuclei (like in colorectal adenocarcinoma), differentiates from ''tall cell variant''.
*Nuclear stratification - '''key feature'''.
*"Minimal" papillary features.
*"Tall cells".
*Clear-eosinophilic cytoplasm.
*Mitoses common.

Image: [http://www3.interscience.wiley.com/cgi-bin/fulltext/75000320/nfig003a?CRETRY=1&SRETRY=0 Columnar variant PTC (wiley.com)].
=====Papillary thyroid carcinoma follicular variant=====
======General======
*May be confused with [[follicular thyroid carcinoma|follicular carcinoma]] or [[follicular thyroid adenoma|follicular adenoma]].
*Pathologists often disagree about this diagnosis.<ref name=pmid21940284>{{Cite journal | last1 = Daniels | first1 = GH. | title = What if many follicular variant papillary thyroid carcinomas are not malignant? A review of follicular variant papillary thyroid carcinoma and a proposal for a new classification. | journal = Endocr Pract | volume = 17 | issue = 5 | pages = 768-87 | month = | year = | doi = 10.4158/EP10407.RA | PMID = 21940284 }}</ref>

======Microscopic======
Features:<ref name=Ref_EP88>{{Ref EP|88}}</ref>
*Small tightly packed follicles - '''key feature'''.
*Hypereosinophilic colloid.
*Nuclear features of PTC.
**Large nuclei.
**Typically have less [[nuclear pseudoinclusion]]s than the conventional type.
*+/-Fibrous capsule (common).

DDx:
*[[Follicular thyroid carcinoma]] - has a fibrous capsule and invasion though it.
*[[Follicular thyroid adenoma]] - surrounded by a fibrous capsule.
*[[Adenomatoid nodule]] - round nuclei, no nuclear features of PTC.

Images:
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=2008080217023776 PTC follicular variant (surgicalpathologyatlas.com)].
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=2008080216593186 PTC follicular variant (surgicalpathologyatlas.com)].
*[http://www.thyroidcancercanada.org/userfiles/images/Follicular_slide.jpg PTC follicular variant (thyroidcancercanada.org)].<ref>URL: [http://www.thyroidcancercanada.org/types-of-thyroid-cancer.php?lang=en http://www.thyroidcancercanada.org/types-of-thyroid-cancer.php?lang=en]. Accessed on: 9 January 2013.</ref>

=====Papillary thyroid carcinoma cribriform-morular variant=====
======General======
*Associated with [[familial adenomatous polyposis]] (FAP).<ref name=pmid18612695>{{cite journal |author=Groen EJ, Roos A, Muntinghe FL, ''et al.'' |title=Extra-intestinal manifestations of familial adenomatous polyposis |journal=Ann. Surg. Oncol. |volume=15 |issue=9 |pages=2439–50 |year=2008 |month=September |pmid=18612695 |pmc=2518080 |doi=10.1245/s10434-008-9981-3 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518080/?tool=pubmed}}</ref>

======Microscopic======
Features:
*Cribriform architectural pattern.
*Morules - balls of tissue.

=====Papillary thyroid carcinoma diffuse sclerosing variant=====
======General======
*Usually young adults, children.

======Microscopic======
Features:<ref>{{Ref PBoD8|1122}}</ref>
*Papillae - usu. prominent.
*Squamous morules - '''key features'''.<ref name=pmid15233643>{{Cite journal | last1 = Hirokawa | first1 = M. | last2 = Kuma | first2 = S. | last3 = Miyauchi | first3 = A. | last4 = Qian | first4 = ZR. | last5 = Nakasono | first5 = M. | last6 = Sano | first6 = T. | last7 = Kakudo | first7 = K. | title = Morules in cribriform-morular variant of papillary thyroid carcinoma: Immunohistochemical characteristics and distinction from squamous metaplasia. | journal = APMIS | volume = 112 | issue = 4-5 | pages = 275-82 | month = | year = | doi = 10.1111/j.1600-0463.2004.apm11204-0508.x | PMID = 15233643 }}
</ref>
*Lymphocytes - abundant.
*Fibrosis.

DDx:
*Lymphocytic thyroiditis (esp. Hashimoto's thyroiditis).

=====Papillary thyroid carcinoma warthin-like variant=====
*Resemble [[Warthin tumour]].
======Microscopic======
Features:<ref name=Ref_Sternberg5_506>{{Ref Sternberg5|506}}</ref>
*Eosinophilic cytoplasm.
*Lymphocytic thyroiditis.
*Papillae.

=====Papillary thyroid carcinoma solid variant=====
Features:<ref name=pmid22432054/>
*Some studies suggest this has a poor prognosis.
*More common in children.
*Associated with Chernobyl nuclear accident.

======Microscopic======
Features:
*Solid sheets >50% of tumour mass.<ref name=pmid22432054/>

===IHC===
Thyroid versus something else:
*Thyroglobulin +ve.
*TTF-1 (thyroid transcription factor-1) +ve.
*CD15 +ve.{{fact}}

PTC versus benign:<ref>{{Cite journal | last1 = Mataraci | first1 = EA. | last2 = Ozgüven | first2 = BY. | last3 = Kabukçuoglu | first3 = F. | title = Expression of cytokeratin 19, HBME-1 and galectin-3 in neoplastic and nonneoplastic thyroid lesions. | journal = Pol J Pathol | volume = 63 | issue = 1 | pages = 58-64 | month = Mar | year = 2012 | doi = | PMID = 22535608 }}</ref>
*HBME-1 +ve (strong, diffuse).
*CK19 +ve (strong, diffuse).
*Galectin-3 +ve (strong, diffuse).

===Molecular===
*Currently not widely used in a diagnostic context.

====Tabular summary====
Molecular changes in papillary thyroid carcinoma as per ''Adeniran et al'':<ref name=pmid16434896>{{Cite journal | last1 = Adeniran | first1 = AJ. | last2 = Zhu | first2 = Z. | last3 = Gandhi | first3 = M. | last4 = Steward | first4 = DL. | last5 = Fidler | first5 = JP. | last6 = Giordano | first6 = TJ. | last7 = Biddinger | first7 = PW. | last8 = Nikiforov | first8 = YE. | title = Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. | journal = Am J Surg Pathol | volume = 30 | issue = 2 | pages = 216-22 | month = Feb | year = 2006 | doi = | PMID = 16434896 }}</ref>
{| class="wikitable sortable"
! Molecular change
! Frequency
! Histology
! Notes
|-
|BRAF point mutations
| ~ 40%
| [[papillary thyroid carcinoma tall cell variant|tall cell variant]]
| poorer prognosis, older individuals
|-
|RET/PTC rearrangments
| ~ 20%
| papillary architecture, [[psammoma bodies]]
| younger individuals
|-
|RAS point mutations
| ~ 15%
| exclusively [[papillary thyroid carcinoma follicular variant|follicular variant]]
| -
|}

===Sign out===
<pre>
HEMITHYROID, RIGHT, COMPLETION OF TOTAL THYROIDECTOMY:
- PAPILLARY THYROID CARCINOMA, FOLLICULAR VARIANT.
-- TUMOUR SIZE: 4 MM (MAXIMAL).
-- ARCHITECTURE: FOLLICULAR.
-- CYTOMORPHOLOGY: CLASSICAL.
-- HISTOLOGIC GRADE: G1 (WELL DIFFERENTIATED).
-- NO TUMOUR CAPSULE IDENTIFIED.
-- NEGATIVE FOR LYMPHOVASCULAR INVASION.
-- NEGATIVE FOR PERINEURAL INVASION.
-- NEGATIVE FOR EXTRATHYROIDAL EXTENSION.
-- SURGICAL MARGINS NEGATIVE FOR MALIGNANCY.
</pre>

Note:
*If it is a completion thyroidectomy and the staging changes one should do a full synoptic report.

==Insular carcinoma==
===General===
Features:<ref name=pmid17665497>{{cite journal |author=Rufini V, Salvatori M, Fadda G, ''et al.'' |title=Thyroid carcinomas with a variable insular component: prognostic significance of histopathologic patterns |journal=Cancer |volume=110 |issue=6 |pages=1209–17 |year=2007 |month=September |pmid=17665497 |doi=10.1002/cncr.22913 |url=}}</ref>
*Rare - approximately 5% of all thyroid carcinomas.
*Thought to be a separate tumour from papillary thyroid carcinoma and follicular thyroid carcinoma with a focal insular pattern.
*Some lump this entity with papillary carcinoma, i.e. consider it a variant of papillary thyroid carcinoma.

===Microscopic===
Features:<ref name=pmid17665497/>
*Islands of cells - '''key feature'''.
*Scant cytoplasm.
*Nuclei monomorphic and round.

DDx:<ref>Endo. fellow. 17 September 2009.</ref>
*[[Medullary thyroid carcinoma]].
*Poorly differentiated thyroid carcinoma.

==Follicular thyroid carcinoma==
*[[AKA]] ''follicular carcinoma''.
===Clinical===
Medical school memory device ''4 Fs'':
*FNA NOT diagnosable.
*Far away mets (sometimes).
*Female predominant.
*Favourable prognosis.

Notes:
*Usu. has a hematologic spread.
**PTC usu. spread via lymphatics.

===Microscopic===
Features:
*Defined by either:
*#Invasion through the capsule:
*#*Should be all the way through.<ref>SR. 17 January 2011.</ref>
*#**1/2 does not count.
*#**Fibrous reaction does not count.
*#**"Above the contour" does not count.
*#Vascular invasion (all of the following):
*##In a small vein (not a capillary), that is outside of the tumour mass.
*##Tumour adherent to the side of the vessel.
*##Tumour must be re-endothelialized.

Notes:
*'''Impossible''' to differentiate from ''[[follicular thyroid adenoma|follicular adenoma]]'' on FNA (no cytologic differences).
*Described as "over-diagnosed" ... misdiagnoses: PTC follicular variant, follicular adenoma, multinodular goitre with a thick capsule.

Images:
*[http://path.upmc.edu/cases/case653.html Follicular thyroid carcinoma - several images (upmc.edu)].

==Medullary thyroid carcinoma==
*Abbreviated ''MTC''.
===General===
Medical school memory device - 3 M's:
*[[amyloid|aMyloid]].
*Median node dissection done.
*[[MEN IIa syndrome]]/[[MEN IIb syndrome]].
**Medullary thyroid carcinoma.
**[[Pheochromocytoma]].
**[[Parathyroid adenoma]].

Epidemiology:
*Very rare.
*Poor prognosis.
*May be genetic (MEN IIa/b syndrome).
*Arises from C cells (which produce calcitonin).

Syndromic tumours - typically:<ref name=pmid21455198>{{Cite journal | last1 = Nosé | first1 = V. | title = Familial thyroid cancer: a review. | journal = Mod Pathol | volume = 24 Suppl 2 | issue = | pages = S19-33 | month = Apr | year = 2011 | doi = 10.1038/modpathol.2010.147 | PMID = 21455198 |URL = http://www.nature.com/modpathol/journal/v24/n2s/full/modpathol2010147a.html }}</ref>
*Present in 30s or 40s.
*+/-Multifocal.
*+/-Bilateral.
*[[C-cell hyperplasia]].

===Gross===
Features:<ref name=pmid21455198/>
*Usu. well-circumscribed.
*White, gray or yellow.
*Gritty.
*Firm.

Image:
*[http://www.nature.com/modpathol/journal/v24/n2s/fig_tab/modpathol2010147f2.html MTC (nature.com)].

===Microscopic===
Features:
*Nuclei with "neuroendocrine features".
**Small, round nuclei.
**Coarse chromatin (''salt and pepper nuclei'').
*+/-[[Amyloid]] deposits - fluffy appearing acellular eosinophilic material in the cytoplasm.
*+/-[[C-cell hyperplasia]] - seen with familial forms of MTC.
**C cells (AKA ''parafollicular cell''): abundant cytoplasm - clear/pale.

Note:
*The amyloid is formed from ''calcitonin''.<ref name=pmid15459123>{{Cite journal | last1 = Khurana | first1 = R. | last2 = Agarwal | first2 = A. | last3 = Bajpai | first3 = VK. | last4 = Verma | first4 = N. | last5 = Sharma | first5 = AK. | last6 = Gupta | first6 = RP. | last7 = Madhusudan | first7 = KP. | title = Unraveling the amyloid associated with human medullary thyroid carcinoma. | journal = Endocrinology | volume = 145 | issue = 12 | pages = 5465-70 | month = Dec | year = 2004 | doi = 10.1210/en.2004-0780 | PMID = 15459123 }}</ref>

Images:
*www:
**[http://jcp.bmj.com/content/vol57/issue3/images/large/cp8474.f16.jpeg Medullary thyroid carcinoma (bmj.com)].
**[http://www.nature.com/ki/journal/v70/n11/fig_tab/5001888f2.html C cell hyperplasia (nature.com)].
**[http://lifesci.rutgers.edu/~babiarz/Review3/Lp6/scope8.htm C cell (rutgers.edu)].
**[http://www.anatomyatlases.org/MicroscopicAnatomy/Images/Plate287.jpg Parafollicular cells (anatomyatlases.org)].
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_low_mag.jpg MTC - low mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_high_mag.jpg MTC - high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_2_-_high_mag.jpg MTC and amyloid - high mag. (WC)].

===IHC===
Features:<ref>URL: [http://pathologyoutlines.com/thyroid.html#medullary http://pathologyoutlines.com/thyroid.html#medullary]. Accessed on: 17 January 2011.</ref>
*[[Calcitonin]] +ve - it arises from C cells (which produce calcitonin).
*Congo-red +ve (amyloid present) - mnemonic: ''CRAP'' -- congo red amyloid protein.
*Neuroendocrine markers.
**[[Chromogranin A]].
**[[Synaptophysin]].
*CEA +ve (often better staining than calcitonin).<ref>SB. 7 January 2010.</ref>
*Thyroglobulin usu. -ve.<ref name=pmid8454270>{{Cite journal | last1 = de Micco | first1 = C. | last2 = Chapel | first2 = F. | last3 = Dor | first3 = AM. | last4 = Garcia | first4 = S. | last5 = Ruf | first5 = J. | last6 = Carayon | first6 = P. | last7 = Henry | first7 = JF. | last8 = Lebreuil | first8 = G. | title = Thyroglobulin in medullary thyroid carcinoma: immunohistochemical study with polyclonal and monoclonal antibodies. | journal = Hum Pathol | volume = 24 | issue = 3 | pages = 256-62 | month = Mar | year = 1993 | doi = | PMID = 8454270 }}</ref>

===EM===
*Neurosecretory granules.
**Feature seen in neuroendocrine tumours.

Images: [http://pathhsw5m54.ucsf.edu/case7/image77.html Neurosecretory granules (ucsf.edu)].

==Anaplastic thyroid carcinoma==
===Epidemiology===
*Very rare.
*Horrible prognosis.
*Often presents with obstruction.
*Typically there is a history of a thyroid mass.

===Microscopic===
Features:
*Cytologically malignant:
**Huge [[NC ratio]].
**Mitoses.
*+/-[[Necrosis]].

Notes:
*May have features of other thyroid carcinomas, e.g. psammoma bodies, papillae, nuclear changes of PTC.

Image: [http://commons.wikimedia.org/wiki/File:Anaplastic_thyroid_carcinoma_low_mag.jpg Anaplastic thyroid carcinoma with a component of papillary thyroid carcinoma (WC)].

DDx:
*[[Poorly differentiated carcinoma of the thyroid|Poorly differentiated carcinoma]].
*[[Squamous cell carcinoma]].
*[[Medullary thyroid carcinoma]].
*Sarcoma.

===IHC===
*Keratin (AE1/AE3) +ve.
*Vimentin +ve, >90%.<ref name=pmid1712540>{{cite journal |author=Ordóñez NG, El-Naggar AK, Hickey RC, Samaan NA |title=Anaplastic thyroid carcinoma. Immunocytochemical study of 32 cases |journal=Am. J. Clin. Pathol. |volume=96 |issue=1 |pages=15–24 |year=1991 |month=July |pmid=1712540 |doi= |url=}}</ref>
*Thyroglobulin - rarely +ve (~15%).<ref name=pmid1712540/>
*CEA -ve, calcitonin -ve; to r/o medullary.
*p53 +ve.
*TTF-1 +ve.

==Lymphomas of the thyroid==
{{Main|Lymphoma}}
===General===
*Rare.
*Increased risk with chronic inflammatory conditions.
*Fit in the the greater category of ''[[MALT lymphoma]]''.

===Microscopic===
Features:
*Lymphoepithelial lesion - '''key feature'''.
*Plasma cells.
*"Overgrowth" - thyroid parenchyma displaced by lymphocytes.

=Weird stuff=
==Hyalinizing trabecular tumour==
*[[AKA]] ''hyalinizing trabecular adenoma''.
*Abbreviated ''HTT''.
===General===
*Considered by some (e.g. Silvia Asa) to be a variant of [[papillary thyroid carcinoma]].<ref name=pmid11117782>{{cite journal |author=Cheung CC, Boerner SL, MacMillan CM, Ramyar L, Asa SL |title=Hyalinizing trabecular tumor of the thyroid: a variant of papillary carcinoma proved by molecular genetics |journal=Am. J. Surg. Pathol. |volume=24 |issue=12 |pages=1622–6 |year=2000 |month=December |pmid=11117782 |doi= |url=}}</ref>
*Behaviour similar to papillary thyroid carcinoma - indolent.

===Microscopic===
Features:
*Trabecular arrangement of cells.
**May have "curved" trabeculae.
*Extracellular space has hyaline material - '''key feature'''.
*Cytoplasm mimics hyaline material in the extracellular space.

Images:
*[http://archive.biomedcentral.com/1742-6413/3/17/figure/F2?highres=y HTT (biomedcentral.com)].<ref name=pmid16867191>{{Cite journal | last1 = Baloch | first1 = ZW. | last2 = Puttaswamy | first2 = K. | last3 = Brose | first3 = M. | last4 = LiVolsi | first4 = VA. | title = Lack of BRAF mutations in hyalinizing trabecular neoplasm. | journal = Cytojournal | volume = 3 | issue = | pages = 17 | month = | year = 2006 | doi = 10.1186/1742-6413-3-17 | PMID = 16867191 }}</ref>
*[http://www.ispub.com/journal/the-internet-journal-of-endocrinology/volume-2-number-1/hyalinizing-trabecular-neoplasm-of-the-thyroid-controversies-in-management.article-g01.fs.jpg HTT (ispub.com)].<ref>URL: [http://www.ispub.com/journal/the-internet-journal-of-endocrinology/volume-2-number-1/hyalinizing-trabecular-neoplasm-of-the-thyroid-controversies-in-management.html http://www.ispub.com/journal/the-internet-journal-of-endocrinology/volume-2-number-1/hyalinizing-trabecular-neoplasm-of-the-thyroid-controversies-in-management.html]. Accessed on: 1 January 2012.</ref>

DDx:
*[[Papillary thyroid carcinoma]] (if one believes this is a separate entity).
*[[Medullary thyroid carcinoma]] - not trabecular, nuclei not [[PTC]]-like.
*[[Paraganglioma]].<ref>URL: [http://path.upmc.edu/cases/case465/dx.html http://path.upmc.edu/cases/case465/dx.html]. Accessed on: 17 January 2011.</ref>

===IHC===
*Thyroglobulin +ve.
*NSE +ve.

==Hürthle cell neoplasm==
*[[AKA]] ''oncocytic neoplasm''.
*Also spelled ''Hurthle cell neoplasm''.

===General===
*Incidence: uncommon.
*This is a general category - includes:
**Hürthle cell adenoma.
**Hürthle cell carcinoma.

*Some advocate ''total thyroidectomy'' for all Hürthle cell neoplasms, as it is difficult to reliably differentiate adenomas and carcinomas.<ref name=pmid9697901>{{Cite journal | last1 = Wasvary | first1 = H. | last2 = Czako | first2 = P. | last3 = Poulik | first3 = J. | last4 = Lucas | first4 = R. | title = Unilateral lobectomy for Hurthle cell adenoma. | journal = Am Surg | volume = 64 | issue = 8 | pages = 729-32; discussion 732-3 | month = Aug | year = 1998 | doi = | PMID = 9697901 }}</ref>
*It can be understood as a special type of ''follicular neoplasm'' (including ''[[follicular thyroid adenoma]]'' and ''[[follicular thyroid carcinoma]]'').<ref name=Ref_EP104>{{Ref EP|104}}</ref>

====Adenoma vs. carcinoma====
Suggestive for carcinoma:<ref name=pmid9697901/>
*Male.
*>4 cm
**Adenomas usu. <3 cm.
Definite for carcinoma:<ref name=pmid9697901/>
*Lymphovascular invasion.
*Capsular invasion.

===Gross===
*Yellow.
*Encapsulated.

===Microscopic===
Features:<ref name=Ref_EP104>{{Ref EP|104}}</ref>
*Oncocytes >= 75% of cells:
**Abundant granular, eosinophilic cytoplasm.
**Round regular nucleus +/- prominent nucleolus.
*+/-Degenerative changes.

Negatives:
*Lack nuclear features of [[papillary thyroid carcinoma]].
*Lack features of [[medullary thyroid carcinoma]].

DDx:<ref name=pmid18684023>{{cite journal |author=Montone KT, Baloch ZW, LiVolsi VA |title=The thyroid Hürthle (oncocytic) cell and its associated pathologic conditions: a surgical pathology and cytopathology review |journal=Arch. Pathol. Lab. Med. |volume=132 |issue=8 |pages=1241–50 |year=2008 |month=August |pmid=18684023 |doi= |url=}}</ref>
*Papillary thyroid carcinoma oncocytic variant.
*Medullary thyroid carcinoma oncocytic variant.
*Others.

==Minocycline associated thyroid pigmentation==
*[[AKA]] ''minocycline thyroid''.

===General===
*Benign pigmentation of the thyroid due to ''minocycline'', an antibiotic.
**Reported at other sites, e.g. [[heart valves]],<ref name=pmid10615019/> coronary arteries.

===Gross===
*Black thyroid.<ref name=pmid2780449>{{Cite journal | last1 = Noble | first1 = JG. | last2 = Christmas | first2 = TJ. | last3 = Chapple | first3 = C. | last4 = Katz | first4 = D. | last5 = Milroy | first5 = EJ. | title = The black thyroid: an unusual finding during neck exploration. | journal = Postgrad Med J | volume = 65 | issue = 759 | pages = 34-5 | month = Jan | year = 1989 | doi = | PMID = 2780449 | PMC = 2429157 }}</ref>

Images:
*[http://images.rheumatology.org/viewphoto.php?albumId=89099&imageId=5231272 Pigmented thyroid gland (rheumatology.org)].
*[http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2004)128%3C355:PQCTIP%3E2.0.CO;2 Minocycline thyroid - gross and microscopic (archivesofpathology.org)].<ref name=pmid14987144>{{Cite journal | last1 = Raghavan | first1 = R. | last2 = Snyder | first2 = WH. | last3 = Sharma | first3 = S. | title = Pathologic quiz case: tumor in pigmented thyroid gland in a young man. Papillary thyroid carcinoma in a minocycline-induced, diffusely pigmented thyroid gland. | journal = Arch Pathol Lab Med | volume = 128 | issue = 3 | pages = 355-6 | month = Mar | year = 2004 | doi = 10.1043/1543-2165(2004)128355:PQCTIP2.0.CO;2 | PMID = 14987144 }}</ref>

===Microscopic===
Features:
*Granular yellow blobs:
**Location:
***Intracytoplasmic in the follicule-lining cells, i.e. follicular cells.
***Intrafollicular.
**Variable size ~0.5-4 micrometers.

Notes:
*Pigment described as ''lipofuscin-like''.<ref name=pmid6435454>{{Cite journal | last1 = Gordon | first1 = G. | last2 = Sparano | first2 = BM. | last3 = Kramer | first3 = AW. | last4 = Kelly | first4 = RG. | last5 = Iatropoulos | first5 = MJ. | title = Thyroid gland pigmentation and minocycline therapy. | journal = Am J Pathol | volume = 117 | issue = 1 | pages = 98-109 | month = Oct | year = 1984 | doi = | PMID = 6435454 | PMC = 1900569 }}</ref>

Images:
*[http://flylib.com/books/2/953/1/html/2/44%20-%20Thyroid_files/DA11C44FF7.png Pigmentation due to minocycline (flylib.com)].<ref>URL: [http://flylib.com/books/en/2.953.1.50/1/ http://flylib.com/books/en/2.953.1.50/1/]. Accessed on: 11 March 2012.</ref>
*[http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2004)128%3C355:PQCTIP%3E2.0.CO;2 Minocycline thyroid - gross and microscopic (archivesofpathology.org)].<ref name=pmid14987144>{{Cite journal | last1 = Raghavan | first1 = R. | last2 = Snyder | first2 = WH. | last3 = Sharma | first3 = S. | title = Pathologic quiz case: tumor in pigmented thyroid gland in a young man. Papillary thyroid carcinoma in a minocycline-induced, diffusely pigmented thyroid gland. | journal = Arch Pathol Lab Med | volume = 128 | issue = 3 | pages = 355-6 | month = Mar | year = 2004 | doi = 10.1043/1543-2165(2004)128355:PQCTIP2.0.CO;2 | PMID = 14987144 }}</ref>

===Stains===
*Fontana-Masson stain +ve.<ref name=pmid10615019>{{Cite journal | last1 = Sant'Ambrogio | first1 = S. | last2 = Connelly | first2 = J. | last3 = DiMaio | first3 = D. | title = Minocycline pigmentation of heart valves. | journal = Cardiovasc Pathol | volume = 8 | issue = 6 | pages = 329-32 | month = | year = | doi = | PMID = 10615019 }}</ref>

=See also=
*[[Thyroid cytopathology]].
*[[Head and neck cytopathology]].
*[[Salivary gland]].
*[[Cytopathology]].

=References=
{{reflist|2}}

[[Category:Endocrine pathology]]

Thyroid gland

2013-06-13T18:41:08Z

Ingo: /* Microscopic */

The '''thyroid gland''' is an important little endocrine organ in the anterior [[neck]]. It is frequently afflicted by [[cancer]]... but the common cancer has such a good prognosis there is debate about how aggressively it should be treated. The [[cytopathology]] of the thyroid gland is dealt with in the ''[[thyroid cytology]]'' article.

The gland frustrates a significant number of pathologists, as the criteria for cancer are considered a bit wishy-washy.

=Thyroid specimens=
==They come in three common varieties==
*FNA (fine needle aspiration).
**Done to triage patients/rule-out malignancy - discussed in the article ''[[thyroid cytopathology]]''.
*Hemithyroid.
**Done to get a definitive diagnosis.
**May be a "completion" - removal of the other half following definitive diagnosis.
*Total thyroid.
**Done for malignancy or follicular lesion.

==Gross pathology==
*White nodules - think:
**Lymphoid tissue.
**Papillary thyroid carcinoma - may be calcified.<ref>BEC. 20 October 2009.</ref>

=Diagnoses=
==Common==
*[[Thyroid gland nodular hyperplasia|Nodular hyperplasia]] -- most common.
*[[Lymphocytic thyroiditis]].
*Papillary thyroid carcinoma (PTC) -- most common cancer.
**[[Papillary thyroid carcinoma follicular variant]].
*[[Parathyroid]] tissue.

==Pitfalls/weird stuff==
*Thyroid tissue lateral to the jugular vein (often referred to as ''lateral aberrant thyroid tissue'') is generally considered metastatic thyroid carcinoma ([[papillary thyroid carcinoma]]) even if it looks benign.<ref name=pmid14452106>{{Cite journal | last1 = JOHNSON | first1 = RW. | last2 = SAHA | first2 = NC. | title = The so-called lateral aberrant thyroid. | journal = Br Med J | volume = 1 | issue = 5293 | pages = 1668-9 | month = Jun | year = 1962 | doi = | PMID = 14452106 | PMC = 1958877 }}</ref>
**This dictum is disputed.<ref name=pmid17319317>{{Cite journal | last1 = Escofet | first1 = X. | last2 = Khan | first2 = AZ. | last3 = Mazarani | first3 = W. | last4 = Woods | first4 = WG. | title = Lessons to be learned: a case study approach. Lateral aberrant thyroid tissue: is it always malignant? | journal = J R Soc Promot Health | volume = 127 | issue = 1 | pages = 45-6 | month = Jan | year = 2007 | doi = | PMID = 17319317 }}</ref>
**The level VI and VII [[lymph nodes]] are medial to the jugular.
*[[Hashimoto's disease]] may have so many lymphocytes that it mimics a lymph node -- may lead to misdiagnosis of PTC.
*Parasitic nodule: clump of thyroid that is attached by a thin thread... but looks like a separate nodule; may lead to misdiagnosis of PTC.

Image:
*[http://images.radiopaedia.org/images/26383/ad505c78a87e71180792049299f5cd_big_gallery.jpg Neck levels (radiopaedia.org)].<ref>URL: [http://radiopaedia.org/articles/lymph-node-levels-of-the-neck http://radiopaedia.org/articles/lymph-node-levels-of-the-neck]. Accessed on: 5 November 2012.</ref>

==Diagnostic keys==
The following should prompt careful examination:<ref>SR. 17 January 2011.</ref>
*Architecture: microfollicular, trabecular, solid, insular.
*Thick capsule.
*Necrosis - rare in the thyroid.

==Thyroid IHC - general comments==
*Not really useful.
*Papers with very small sample sizes abound.

===Follicular thyroid carcinoma vs. papillary thyroid carcinoma===
*CD31 more frequently positive in follicular lesions.<ref name=pmid18795075>{{Cite journal | last1 = Rydlova | first1 = M. | last2 = Ludvikova | first2 = M. | last3 = Stankova | first3 = I. | title = Potential diagnostic markers in nodular lesions of the thyroid gland: an immunohistochemical study. | journal = Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub | volume = 152 | issue = 1 | pages = 53-9 | month = Jun | year = 2008 | doi = | PMID = 18795075 }}</ref>
**CD31 is a marker for microvessel density.
*Galectin-3 thought to be positive in papillary carcinoma.<ref name=pmid18795075/>
*HBME-1 thought to be positive in papillary lesions.<ref name=pmid15529186>{{Cite journal | last1 = Papotti | first1 = M. | last2 = Rodriguez | first2 = J. | last3 = De Pompa | first3 = R. | last4 = Bartolazzi | first4 = A. | last5 = Rosai | first5 = J. | title = Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential. | journal = Mod Pathol | volume = 18 | issue = 4 | pages = 541-6 | month = Apr | year = 2005 | doi = 10.1038/modpathol.3800321 | PMID = 15529186 }}</ref>

==Thyroid lesions per WHO==
*Adapted from the ''Washington Manual of Surgical Pathology''.<ref name=Ref_WMSP331>{{Ref WMSP|331}}</ref>
===Adenoma===
*Follicular adenoma.
*Hyalinizing trabecular tumour.

===Carcinoma===
*[[Papillary thyroid carcinoma|Papillary carcinoma]].
*[[Follicular thyroid carcinoma|Follicular carinoma]].
*[[Medullary thyroid carcinoma|Medullary carcinoma]].
*Undifferentiated (anaplastic) carcinoma.

*Poorly differentiated carcinoma.
*[[Squamous cell carcinoma]].
*[[Mucoepidermoid carcinoma]].
*Sclerosing mucoepidermoid carcinoma with eosinophilia.
*Mucinous carcinoma.

*Mixed medullary and follicular carinoma.
*Spindle cell tumour with thymus-like differentiation.
*Carcinoma showing thymus-like differentiation.

===Others===
*[[Teratoma]].
*[[Lymphoma]].
*Ectopic thymoma.
*[[Angiosarcoma]] + other [[soft tissue lesions]].
*[[Paraganglioma]].
*[[Solitary fibrous tumour]].
*[[Follicular dendritic cell tumour]].
*[[Langerhans cell histiocytosis]].
*[[Metastasis]].

=Parathyroid glands=
{{Main|Parathyroid glands}}
*May make an appearance in the context of thyroid surgery.

=Benign=
==Solid cell nest of the thyroid gland==
*[[AKA]] ''solid cell nest of thyroid''.
===General===
*Embryonic remnants endodermal origin.<ref name=pmid12527712>{{cite journal |author=Reis-Filho JS, Preto A, Soares P, Ricardo S, Cameselle-Teijeiro J, Sobrinho-Simões M |title=p63 expression in solid cell nests of the thyroid: further evidence for a stem cell origin |journal=Mod. Pathol. |volume=16 |issue=1 |pages=43–8 |year=2003 |month=January |pmid=12527712 |doi=10.1097/01.MP.0000047306.72278.39 |url=http://www.nature.com/modpathol/journal/v16/n1/full/3880708a.html}}</ref>
*Incidental finding.

Note:
*Hypothesized to have some relation to [[mucoepidermoid carcinoma]] of the thyroid gland;<ref name=pmid1413837>{{Cite journal | last1 = Ozaki | first1 = O. | last2 = Ito | first2 = K. | last3 = Sugino | first3 = K. | last4 = Yasuda | first4 = K. | last5 = Yamashita | first5 = T. | last6 = Toshima | first6 = K. | title = Solid cell nests of the thyroid gland: precursor of mucoepidermoid carcinoma? | journal = World J Surg | volume = 16 | issue = 4 | pages = 685-8; discussion 688-9 | month = | year = | doi = | PMID = 1413837 }}</ref> however, another study suspects a relationship with [[papillary thyroid carcinoma]].<ref name=pmid22224821>{{Cite journal | last1 = Prichard | first1 = RS. | last2 = Lee | first2 = JC. | last3 = Gill | first3 = AJ. | last4 = Sywak | first4 = MS. | last5 = Fingleton | first5 = L. | last6 = Robinson | first6 = BG. | last7 = Sidhu | first7 = SB. | last8 = Delbridge | first8 = LW. | title = Mucoepidermoid carcinoma of the thyroid: a report of three cases and postulated histogenesis. | journal = Thyroid | volume = 22 | issue = 2 | pages = 205-9 | month = Feb | year = 2012 | doi = 10.1089/thy.2011.0276 | PMID = 22224821 }}</ref>

===Microscopic===
Features:<ref name=pmid12527712/>
*Cellular solid ''or'' cystic cluster of variable size with:
**Cuboidal cellular morphology.
***May have columnar morphology.
**Moderate-to-scant eosinophilic cytoplasm.
**Round/ovoid nuclei with finely granular chromatin.
*+/-Goblet cells (~30% of cases).<ref name=pmid7509563>{{cite journal |author=Mizukami Y, Nonomura A, Michigishi T, ''et al.'' |title=Solid cell nests of the thyroid. A histologic and immunohistochemical study |journal=Am. J. Clin. Pathol. |volume=101 |issue=2 |pages=186–91 |year=1994 |month=February |pmid=7509563 |doi= |url=}}</ref>

Images:
*www:
**[http://farm6.static.flickr.com/5143/5685400518_c4f506d370.jpg Solid cell next (flickr.com)].
**[http://www.nature.com/modpathol/journal/v16/n1/fig_tab/3880708f1.html#figure-title Crappy B&W of solid cell nest (nature.com)].
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Solid_cell_nest_of_the_thyroid_gland_-_intermed_mag.jpg Solid cell nest of the thyroid gland - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Solid_cell_nest_of_the_thyroid_gland_-_very_high_mag.jpg Solid cell nest of the thyroid gland - very high mag. (WC)].

DDx:<ref name=pmid12527712/>
*[[C-cell hyperplasia]].
*[[Medullary thyroid carcinoma|Medullary carcinoma]].
*Squamous lesions.

===IHC===
Features:<ref name=pmid12527712/>
*p63 +ve.
**-ve in clear cells.
*CEA +ve (polyconal).<ref name=pmid7509563>{{cite journal |author=Mizukami Y, Nonomura A, Michigishi T, ''et al.'' |title=Solid cell nests of the thyroid. A histologic and immunohistochemical study |journal=Am. J. Clin. Pathol. |volume=101 |issue=2 |pages=186–91 |year=1994 |month=February |pmid=7509563 |doi= |url=}}</ref>
**+ve also in clear cells.
*Chromogranin A +ve ~45% of cases.<ref name=pmid7509563/>

===Sign out===
Solid cell nests of the thyroid gland are usually not reported.

==Thyroid gland nodular hyperplasia==
*[[AKA]] ''[[nodular hyperplasia]]''.
*[[AKA]] ''adenomatoid nodule''.

===General===
*Clinical diagnosis: ''goitre'', [[AKA]] ''sporadic goitre'', AKA ''multinodular goitre'' (MNG).
*Most common diagnosis in the thyroid.
**If you've seen a handful of thyroids you've seen this.

Notes:
*Large lesions may be clonal; however, this is clinically irrelevant.

===Gross===
Features:
*Enlarge thyroid gland.
*+/-Distinct (well-circumscribed) nodules.

===Microscopic===
Features:
*Follicles of variable size - '''key feature'''.
**Should be obvious at low power, i.e. with the 2.5x objective.
*+/-Nodules.
**Do not have a thick fibrous capsule.
**May have a high cellularity.
**Architecture: solid or microfollicular.<ref name=Ref_EP36>{{Ref EP|36}}</ref>

Negatives:
*No nuclear features suggestive of malignancy (at lower power).
**One should not look at high power.
*Not cellular.

DDx:
*[[Papillary thyroid carcinoma]] - esp. [[papillary thyroid carcinoma follicular variant]].
*[[Follicular thyroid adenoma]] - contained in a fibrous capsule.
*[[Follicular thyroid carcinoma]] - has fibrous capsule and invasion through it.

===Sign out===
<pre>
HEMITHYROID, RIGHT, HEMITHYROIDECTOMY:
- NODULAR HYPERPLASIA.
- NEGATIVE FOR MALIGNANCY.
</pre>

<pre>
HEMITHYROID, RIGHT, HEMITHYROIDECTOMY:
- CELLULAR ADENOMATOID NODULE ON A BACKGROUND OF NODULAR HYPERPLASIA.
- NEGATIVE FOR MALIGNANCY.
</pre>

==Follicular thyroid adenoma==
*[[AKA]] follicular adenoma, [[AKA]] thyroid follicular adenoma.
===General===
*Most common neoplasm of thyroid.<ref name=Ref_EP51>{{Ref EP|51}}</ref>
*Encapusled lesion (surrounded by fibrous capsule).

===Gross===
*Thick capsule.

Notes:
*The entire capsule should be submitted.<ref>SR. 17 January 2011.</ref>
**A good start for most thyroid specimens with a thick capsule is 10 blocks.

===Microsopic===
Features:
*Cellular.
*Thick capsule - '''key feature'''.

Negatives.
*No invasion of the capsule (see ''[[follicular thyroid carcinoma]]'' section).
*No nuclear features suggestive of [[papillary thyroid carcinoma]].

DDx:
*[[Thyroid gland nodular hyperplasia]] with an encapsulated nodule - not as cellular.

==Graves disease==
===General===
*Often misspelled "Grave's disease".
*Autoimmune disease leading to hyperthyroidism.
*Eye problems not resolved with thyroid removal.{{fact}}
*Higher risk of [[papillary thyroid carcinoma]].

Clinical:
*TSH-receptor antibody +ve.<ref name=pmid19576193>{{Cite journal | last1 = Massart | first1 = C. | last2 = Gibassier | first2 = J. | last3 = d'Herbomez | first3 = M. | title = Clinical value of M22-based assays for TSH-receptor antibody (TRAb) in the follow-up of antithyroid drug treated Graves' disease: comparison with the second generation human TRAb assay. | journal = Clin Chim Acta | volume = 407 | issue = 1-2 | pages = 62-6 | month = Sep | year = 2009 | doi = 10.1016/j.cca.2009.06.033 | PMID = 19576193 }}</ref>

===Gross===
Features:<ref>{{Ref EP|30}}</ref>
*Enlarged 50-150 g.
*"Beefy-red" appearance, looks like raw beef.

===Microscopic===
Features:
*Classic:
**Hypercellular
**Patchy lymphocytes.
**Little colloid.
*Scalloping of colloid; colloid has undulating border.
**Non-specific finding.
*+/-Nuclear clearing.
*+/-Papillae (may mimic papillary thyroid carcinoma in this respect).

Notes:
*Usually has an unimpressive appearance... as it is treated, i.e. history is important.
*Nuclear clearing and papillae are usu. diffuse in Graves disease - unlike in papillary thyroid carcinoma.

Image:
*[http://library.med.utah.edu/WebPath/jpeg4/ENDO022.jpg Graves disease (med.utah.edu)].<ref>URL: [http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html]. Accessed on: 4 December 2011.</ref>

==Idiopathic granulomatous thyroiditis==
*[[AKA]] ''granulomatous thyroiditis'' - non-specific term; granulomas may be due a number of causes.
*AKA ''subacute thyroiditis''.
*[[AKA]] ''de Quervain thyroiditis''.
**Should '''not''' be confused with ''[[de Quervain's disease]]'' (AKA ''gamer's thumb'') something completely unrelated to the thyroid.

===General===
*Women > men.
*Etiology: possibly viral.<ref name=llyod/>

Clinical:
*Tenderness.<ref name=pmid22538753>{{Cite journal | last1 = Szczepanek-Parulska | first1 = E. | last2 = Zybek | first2 = A. | last3 = Biczysko | first3 = M. | last4 = Majewski | first4 = P. | last5 = Ruchała | first5 = M. | title = What might cause pain in the thyroid gland? Report of a patient with subacute thyroiditis of atypical presentation. | journal = Endokrynol Pol | volume = 63 | issue = 2 | pages = 138-42 | month = | year = 2012 | doi = | PMID = 22538753 }}</ref>

===Microscopic===
Features:<ref name=Ref_Sternberg4_559>{{Ref Sternberg4|559}}</ref><ref name=llyod>{{cite book |title=Endocrine Diseases (AFIP Atlas of Nontumor Pathology) |last= Lloyd |first = Ricardo V. |authorlink= |coauthors= |year= 2002 |publisher= American Registry of Pathology |location= Toronto |isbn=978-1881041733 |page= |pages= |url=http://www.amazon.com/Endocrine-Diseases-Atlas-Nontumer-Pathology/dp/1881041735 |accessdate=}}</ref>
*[[Granulomas]] with multinucleated giant cells - usu. with engulfed colloid.
*Lymphocytes.
*Plasma cells.
*+/-Fibrosis.

DDx:
*Infectious granulomatous disease (fungal, microbacterial).
*[[Palpation thyroiditis]].
*[[Sarcoidosis]] (classically intrafollicular distribution).

Images:
*[http://commons.wikimedia.org/wiki/File:Subacute_thyroiditis_-_intermed_mag.jpg Subacute thyroiditis - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Subacute_thyroiditis_-_high_mag.jpg Subacute thyroiditis - high mag. (WC)].

===Stains===
*ZN -ve.
*GMS -ve.

==Palpation thyroiditis==
===General===
*Granulomatous inflammation due to palpation.
**Incidence of granulomas higher in surgical thyroid specimens than autopsies.<ref name=llyod/>

===Microscopic===
Features:<ref name=llyod>{{cite book |title=Endocrine Diseases (AFIP Atlas of Nontumor Pathology) |last= Lloyd |first = Ricardo V. |authorlink= |coauthors= |year= 2002 |publisher= American Registry of Pathology |location= Toronto |isbn=978-1881041733 |page= |pages= |url=http://www.amazon.com/Endocrine-Diseases-Atlas-Nontumer-Pathology/dp/1881041735 |accessdate=}}</ref>
*[[Granuloma]]s involving the follicle.
**Histiocytes within the colloid.

DDx:
*[[Idiopathic granulomatous thyroiditis]].
*[[Sarcoidosis]].
*Infectious granulomatous thyroiditis.

===Stains===
*ZN -ve.
*GMS -ve.

==Riedel thyroiditis==
*[[AKA]] ''invasive fibrous thyroiditis''.<ref name=pmid21568724>{{Cite journal | last1 = Fatourechi | first1 = MM. | last2 = Hay | first2 = ID. | last3 = McIver | first3 = B. | last4 = Sebo | first4 = TJ. | last5 = Fatourechi | first5 = V. | title = Invasive fibrous thyroiditis (Riedel thyroiditis): the Mayo Clinic experience, 1976-2008. | journal = Thyroid | volume = 21 | issue = 7 | pages = 765-72 | month = Jul | year = 2011 | doi = 10.1089/thy.2010.0453 | PMID = 21568724 }}</ref>
===General===
Clinical features:<ref name=pmid21568724/>
*Extremely rare.
*Women > men.
*Usually smokers.
*May be associated with ''[[retroperitoneal fibrosis]]''.
*May be hypothyroid.
*+/-Obstructive symptoms.

===Microscopic===
Features:
*Fibrosis.
*Specimen often fragmented as it was difficult to remove.

DDx:
*[[Anaplastic thyroid carcinoma|Anaplastic carcinoma]], spindle cell variant.

==Hashimoto thyroiditis==
===General===
*'''This is a clinical diagnosis'''.
**The histomorphologic findings, generally, are '''not''' diagnostic.

Etiology:
*Autoimmune disease leading to hypothyroidism.
**Often genetic/part of a syndrome.

====Clinical====
Serology:<ref name=pmid7813361>{{cite journal |author=Poropatich C, Marcus D, Oertel YC |title=Hashimoto's thyroiditis: fine-needle aspirations of 50 asymptomatic cases |journal=Diagn. Cytopathol. |volume=11 |issue=2 |pages=141–5 |year=1994 |pmid=7813361 |doi= |url=http://www3.interscience.wiley.com/journal/112701408/abstract?CRETRY=1&SRETRY=0}}</ref>
*Antimicrosomal (antithyroid peroxidase) +ve.
*Antithyroglobulin +ve.

Associated pathology:<ref name=pmid7813361/>
*Increased risk of B-cell lymphoma; these are classically:<ref name=pmid18018576 >{{Cite journal | last1 = Ohye | first1 = H. | last2 = Fukata | first2 = S. | last3 = Hirokawa | first3 = M. | title = [Malignant lymphoma of the thyroid]. | journal = Nihon Rinsho | volume = 65 | issue = 11 | pages = 2092-8 | month = Nov | year = 2007 | doi = | PMID = 18018576 }}</ref>
**[[MALT lymphoma]].
**[[Diffuse large B cell lymphoma]] (DLBCL).

===Microscopic===
Features:
*Lymphocytic infiltrate - '''key feature'''.
*Nuclear clearing common.
**May confuse with [[papillary thyroid carcinoma]].
*Polymorphous lymphoplasmacytic infiltrate with germinal centres.<ref name=Ref_APBR672>{{Ref APBR|672}}</ref>
*+/-Oncocytic metaplasia.

Notes:
*Histologically often '''not''' possible to separate from "non-specific" thyroiditis.<ref name=Ref_Sternberg4_560>{{Ref Sternberg4|560}}</ref>

DDx:
*[[Lymphocytic thyroiditis]].
*[[Papillary thyroid carcinoma]].
*[[MALT lymphoma]].
*[[Diffuse large B cell lymphoma]].

===IHC===
*Panel to exclude lymphoma may be required, e.g. CD3, CD20, CD10, BCL6, BCL2, kappa, lambda.

===Molecular===
*Occasionally done to exclude lymphoma - see ''[[MALT lymphoma]]'' and ''[[DLBCL]]''.

==C-cell hyperplasia==
*Abbreviated ''CCH''.
===General===
*Screening for C-cell hyperplasia/[[medullary thyroid carcinoma]] done with ''serum calcitonin level''.<ref name=pmid19726541>{{cite journal |author=Machens A, Hoffmann F, Sekulla C, Dralle H |title=Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer |journal=Endocr. Relat. Cancer |volume=16 |issue=4 |pages=1291–8 |year=2009 |month=December |pmid=19726541 |doi=10.1677/ERC-09-0136 |url=http://erc.endocrinology-journals.org/cgi/content/full/16/4/1291}}</ref>

===Gross===
*Not visible.

===Microscopic===
Features:
*Location:<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Thyroid_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Thyroid_11protocol.pdf]. Accessed on: 7 April 2012.</ref>
**Mid portion of lobe to upper third of lobe.
***Not at the poles.
***Not in the isthmus.

*Definitions vary.<ref>SR. 17 January 2011.</ref>

One definition - either of the following:<ref name=pmid19726541>{{cite journal |author=Machens A, Hoffmann F, Sekulla C, Dralle H |title=Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer |journal=Endocr. Relat. Cancer |volume=16 |issue=4 |pages=1291–8 |year=2009 |month=December |pmid=19726541 |doi=10.1677/ERC-09-0136 |url=http://erc.endocrinology-journals.org/cgi/content/full/16/4/1291}}</ref>
#>50 C-cells per low-power field (x100).
#*This part of the definition suffers from [[LPFitis]]. The paper should have been rejected.
#Confined to the thyroid gland and no larger than 10 mm in greatest dimension.

Another definition:
*Invasion of the basement membrane with stromal reaction.

A third definition:
*"Several clusters" of more than six C cells.

====Images====
*[http://www.nature.com/modpathol/journal/v16/n8/fig_tab/3880836f2.html CCH - crappy B&W image (nature.com)].<ref>{{Cite journal | last1 = Guyétant | first1 = S. | last2 = Josselin | first2 = N. | last3 = Savagner | first3 = F. | last4 = Rohmer | first4 = V. | last5 = Michalak | first5 = S. | last6 = Saint-André | first6 = JP. | title = C-cell hyperplasia and medullary thyroid carcinoma: clinicopathological and genetic correlations in 66 consecutive patients. | journal = Mod Pathol | volume = 16 | issue = 8 | pages = 756-63 | month = Aug | year = 2003 | doi = 10.1097/01.MP.0000081727.75778.0C | PMID = 12920219 }}</ref>
*[http://www.nature.com/modpathol/journal/v16/n8/fig_tab/3880836f3.htm CCH - crappy B&W image (nature.com)].
*[http://www.forpath.org/workshops/0201/photos/fullsize/cas7c.jpg CCH (forpath.org)].<ref>URL: [http://www.forpath.org/workshops/0201/html/case_7.asp http://www.forpath.org/workshops/0201/html/case_7.asp]. Accessed on: 21 May 2013.</ref>
*[http://alf3.urz.unibas.ch/pathopic/e/getpic-fra.cfm?id=4849 CCH (unibas.ch)].
*[http://alf3.urz.unibas.ch/pathopic/e/getpic-fra.cfm?id=10739 Nodular CCH (unibas.ch)].

=Malignant neoplasm=
There are a bunch of 'em. The most common, by far, is papillary.

==Papillary thyroid carcinoma==
*Abbreviated ''PTC''.
===General===
Medical school memory device P's:
*Palpable nodes.
*Popular (most common malignant neoplasm of the thyroid).
*Prognosis is good.
*Pre-Tx iodine scan.
*Post-Sx iodine scan.
*[[Psammoma bodies]].

Notes:
*PTC is associated with radiation exposure.<ref name=Ref_Sternberg4_564>{{Ref Sternberg4|564}}</ref>
*''Papillary thyroid microcarcinoma'' is defined as a tumour with a maximal dimension of 1.0 cm or less.<ref name=pmid21267823>{{Cite journal | last1 = Sethom | first1 = A. | last2 = Riahi | first2 = I. | last3 = Riahi | first3 = K. | last4 = Akkari | first4 = K. | last5 = Benzarti | first5 = S. | last6 = Miled | first6 = I. | last7 = Chebbi | first7 = MK. | title = [Management of thyroid microcarcinoma. Report of 13 cases]. | journal = Tunis Med | volume = 89 | issue = 1 | pages = 23-5 | month = Jan | year = 2011 | doi = | PMID = 21267823 }}</ref>

====Prognosis====
Prognosis can be predicted by ''MAICS'' score. It which includes:<ref name=pmid12016468>{{Cite journal | last1 = Hay | first1 = ID. | last2 = Thompson | first2 = GB. | last3 = Grant | first3 = CS. | last4 = Bergstralh | first4 = EJ. | last5 = Dvorak | first5 = CE. | last6 = Gorman | first6 = CA. | last7 = Maurer | first7 = MS. | last8 = McIver | first8 = B. | last9 = Mullan | first9 = BP. | title = Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940-1999): temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients. | journal = World J Surg | volume = 26 | issue = 8 | pages = 879-85 | month = Aug | year = 2002 | doi = 10.1007/s00268-002-6612-1 | PMID = 12016468 }}</ref>
*'''M'''etastases.
*'''A'''ge.
*'''I'''nvasion of surround tissues.
*'''C'''completeness of excision.
*'''S'''ize of tumour.

===Microscopic===
Features:
*Nuclear changes - '''key feature'''.
*#"Shrivelled nuclei"/"raisin" like nuclei, nuclei with a wavy ("textured") nuclear membrane -- usu. easy to find.
*#[[Nuclear pseudoinclusions]] -- usu. harder to find; have high [[specificity]].
*#Nuclear grooves, seen as a result of the highly "textured" nuclear membrane.
*#Nuclear clearing (only on permanent section) - also known as "Orphan Annie eyes".
*Overlap of nuclei - "cells do not respect each other's borders" (easy to see at '''key feature at low power''').
*Classically has papillae (nipple-like shape); papilla (definition): epithelium on fibrovascular core.
**Absence of papillae does not exclude diagnosis.
*[[Psammoma bodies]].
**Circular, acellular, eosinophilic whorled bodies.
**Not necessary to make diagnosis - but very specific in the context of a specimen labeled "thyroid".
**Arise from infarction & calcification of papilla tips.<ref name=Ref_Sternberg4_565>{{Ref Sternberg4|565}}</ref>

Notes:
*Psammoma bodies are awesome if you see 'em, i.e. useful for arriving at the diagnosis.
**If there are no papillae structures -- you're unlikely to see psammoma bodies.
*At low power look for cellular areas/loss of follicles.
*Nuclear clearing seen in:
**Hashimoto's and papillary thyroid carcinoma.<ref name=Ref_Sternberg4_566>{{Ref Sternberg4|566}}</ref>
**May be an artifact of [[fixation]]/processing.
*Nuclear overlapping is easy to see at lower power-- should be the tip-off to look at high power for nuclear features.
*Nuclear inclusions are quite rare and not required to make the diagnosis -- but a very convincing feature if seen.
*Papillae may be seen in Graves disease.

DDx:
*[[Lymphocytic thyroiditis]]:
**[[Graves disease]].
**[[Hashimoto thyroiditis]].
*[[Solid cell nest of thyroid]].<ref name=pmid16830963>{{Cite journal | last1 = Baloch | first1 = ZW. | last2 = LiVolsi | first2 = VA. | title = Cytologic and architectural mimics of papillary thyroid carcinoma. Diagnostic challenges in fine-needle aspiration and surgical pathology specimens. | journal = Am J Clin Pathol | volume = 125 Suppl | issue = | pages = S135-44 | month = Jun | year = 2006 | doi = | PMID = 16830963 | URL = http://ajcp.ascpjournals.org/content/supplements/125/Suppl_1/S135.full.pdf }}</ref>

====Subtypes of papillary thyroid carcinoma====
There are many.

Poor prognosis variants:
*[[Papillary thyroid carcinoma tall cell variant|Tall cell variant]].<ref name=pmid22432054>{{Cite journal | last1 = Gonzalez-Gonzalez | first1 = R. | last2 = Bologna-Molina | first2 = R. | last3 = Carreon-Burciaga | first3 = RG. | last4 = Gómezpalacio-Gastelum | first4 = M. | last5 = Molina-Frechero | first5 = N. | last6 = Salazar-Rodríguez | first6 = S. | title = Papillary thyroid carcinoma: differential diagnosis and prognostic values of its different variants: review of the literature. | journal = ISRN Oncol | volume = 2011 | issue = | pages = 915925 | month = | year = 2011 | doi = 10.5402/2011/915925 | PMID = 22432054 | PMC = 3302055 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22432054/?tool=pubmed }}</ref>
*[[Papillary thyroid carcinoma columnar cell variant|Columnar cell variant]].<ref name=pmid22432054/>
*[[Papillary thyroid carcinoma solid variant|Solid variant]].<ref name=pmid22432054/>
*[[Papillary thyroid carcinoma diffuse sclerosing variant|Diffuse sclerosing variant]].<ref>URL: [http://emedicine.medscape.com/article/849000-overview#a0104 http://emedicine.medscape.com/article/849000-overview#a0104]. Accessed on: 1 May 2012.</ref>

=====Papillary thyroid carcinoma tall cell variant=====
======General======
*~10% of PTC.<ref>{{Ref Sternberg5|505}}</ref>
*Often large > 6 cm.

======Microscopic======
Features:<ref name=pmid19373912>{{cite journal |author=Urano M, Kiriyama Y, Takakuwa Y, Kuroda M |title=Tall cell variant of papillary thyroid carcinoma: Its characteristic features demonstrated by fine-needle aspiration cytology and immunohistochemical study |journal=Diagn. Cytopathol. |volume= |issue= |pages= |year=2009 |month=April |pmid=19373912 |doi=10.1002/dc.21086 |url=}}</ref>
*50% of cells with height 2x the width.<ref name=pmid18925842>{{cite journal |author=Ghossein R, Livolsi VA |title=Papillary thyroid carcinoma tall cell variant |journal=Thyroid |volume=18 |issue=11 |pages=1179–81 |year=2008 |month=November |pmid=18925842 |doi=10.1089/thy.2008.0164 |url=}}</ref>
**There is some disagreement on these criteria;<ref name=pmid18925842/> Raphael believes the height ought to be ~3x width, for 50% of the cells.<ref>S. Raphael. 17 January 2011.</ref>
*Eosinophilic cytoplasm.
*Well-defined cell borders.
*Nucleus stratified; basal location, i.e. closer to the basement membrane.

Negative:
*Nuclei ''not'' pseudostratified, if pseudostratified consider ''columnar cell variant''.

Images:
*[http://commons.wikimedia.org/wiki/File:Papillary_thyroid_carcinoma_tall_cell_var_intermed_mag.jpg PTC tall cell variant - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Papillary_thyroid_carcinoma_tall_cell_var_high_mag.jpg PTC tall cell variant - high mag. (WC)].

=====Papillary thyroid carcinoma columnar cell variant=====
======General======
Epidemiology:
*Poor prognosis.
*Very rare.

======Microscopic======
Features:<ref name=Ref_Sternberg5_506>{{Ref Sternberg5|506}}</ref>
*Elongated nuclei (similar to colorectal adenocarcinoma) - '''key feature'''.
*+/-Pseudostratification of the nuclei (like in colorectal adenocarcinoma), differentiates from ''tall cell variant''.
*Nuclear stratification - '''key feature'''.
*"Minimal" papillary features.
*"Tall cells".
*Clear-eosinophilic cytoplasm.
*Mitoses common.

Image: [http://www3.interscience.wiley.com/cgi-bin/fulltext/75000320/nfig003a?CRETRY=1&SRETRY=0 Columnar variant PTC (wiley.com)].
=====Papillary thyroid carcinoma follicular variant=====
======General======
*May be confused with [[follicular thyroid carcinoma|follicular carcinoma]] or [[follicular thyroid adenoma|follicular adenoma]].
*Pathologists often disagree about this diagnosis.<ref name=pmid21940284>{{Cite journal | last1 = Daniels | first1 = GH. | title = What if many follicular variant papillary thyroid carcinomas are not malignant? A review of follicular variant papillary thyroid carcinoma and a proposal for a new classification. | journal = Endocr Pract | volume = 17 | issue = 5 | pages = 768-87 | month = | year = | doi = 10.4158/EP10407.RA | PMID = 21940284 }}</ref>

======Microscopic======
Features:<ref name=Ref_EP88>{{Ref EP|88}}</ref>
*Small tightly packed follicles - '''key feature'''.
*Hypereosinophilic colloid.
*Nuclear features of PTC.
**Large nuclei.
**Typically have less [[nuclear pseudoinclusion]]s than the conventional type.
*+/-Fibrous capsule (common).

DDx:
*[[Follicular thyroid carcinoma]] - has a fibrous capsule and invasion though it.
*[[Follicular thyroid adenoma]] - surrounded by a fibrous capsule.
*[[Adenomatoid nodule]] - round nuclei, no nuclear features of PTC.

Images:
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=2008080217023776 PTC follicular variant (surgicalpathologyatlas.com)].
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=2008080216593186 PTC follicular variant (surgicalpathologyatlas.com)].
*[http://www.thyroidcancercanada.org/userfiles/images/Follicular_slide.jpg PTC follicular variant (thyroidcancercanada.org)].<ref>URL: [http://www.thyroidcancercanada.org/types-of-thyroid-cancer.php?lang=en http://www.thyroidcancercanada.org/types-of-thyroid-cancer.php?lang=en]. Accessed on: 9 January 2013.</ref>

=====Papillary thyroid carcinoma cribriform-morular variant=====
======General======
*Associated with [[familial adenomatous polyposis]] (FAP).<ref name=pmid18612695>{{cite journal |author=Groen EJ, Roos A, Muntinghe FL, ''et al.'' |title=Extra-intestinal manifestations of familial adenomatous polyposis |journal=Ann. Surg. Oncol. |volume=15 |issue=9 |pages=2439–50 |year=2008 |month=September |pmid=18612695 |pmc=2518080 |doi=10.1245/s10434-008-9981-3 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518080/?tool=pubmed}}</ref>

======Microscopic======
Features:
*Cribriform architectural pattern.
*Morules - balls of tissue.

=====Papillary thyroid carcinoma diffuse sclerosing variant=====
======General======
*Usually young adults, children.

======Microscopic======
Features:<ref>{{Ref PBoD8|1122}}</ref>
*Papillae - usu. prominent.
*Squamous morules - '''key features'''.<ref name=pmid15233643>{{Cite journal | last1 = Hirokawa | first1 = M. | last2 = Kuma | first2 = S. | last3 = Miyauchi | first3 = A. | last4 = Qian | first4 = ZR. | last5 = Nakasono | first5 = M. | last6 = Sano | first6 = T. | last7 = Kakudo | first7 = K. | title = Morules in cribriform-morular variant of papillary thyroid carcinoma: Immunohistochemical characteristics and distinction from squamous metaplasia. | journal = APMIS | volume = 112 | issue = 4-5 | pages = 275-82 | month = | year = | doi = 10.1111/j.1600-0463.2004.apm11204-0508.x | PMID = 15233643 }}
</ref>
*Lymphocytes - abundant.
*Fibrosis.

DDx:
*Lymphocytic thyroiditis (esp. Hashimoto's thyroiditis).

=====Papillary thyroid carcinoma warthin-like variant=====
*Resemble [[Warthin tumour]].
======Microscopic======
Features:<ref name=Ref_Sternberg5_506>{{Ref Sternberg5|506}}</ref>
*Eosinophilic cytoplasm.
*Lymphocytic thyroiditis.
*Papillae.

=====Papillary thyroid carcinoma solid variant=====
Features:<ref name=pmid22432054/>
*Some studies suggest this has a poor prognosis.
*More common in children.
*Associated with Chernobyl nuclear accident.

======Microscopic======
Features:
*Solid sheets >50% of tumour mass.<ref name=pmid22432054/>

===IHC===
Thyroid versus something else:
*Thyroglobulin +ve.
*TTF-1 (thyroid transcription factor-1) +ve.
*CD15 +ve.{{fact}}

PTC versus benign:<ref>{{Cite journal | last1 = Mataraci | first1 = EA. | last2 = Ozgüven | first2 = BY. | last3 = Kabukçuoglu | first3 = F. | title = Expression of cytokeratin 19, HBME-1 and galectin-3 in neoplastic and nonneoplastic thyroid lesions. | journal = Pol J Pathol | volume = 63 | issue = 1 | pages = 58-64 | month = Mar | year = 2012 | doi = | PMID = 22535608 }}</ref>
*HBME-1 +ve (strong, diffuse).
*CK19 +ve (strong, diffuse).
*Galectin-3 +ve (strong, diffuse).

===Molecular===
*Currently not widely used in a diagnostic context.

====Tabular summary====
Molecular changes in papillary thyroid carcinoma as per ''Adeniran et al'':<ref name=pmid16434896>{{Cite journal | last1 = Adeniran | first1 = AJ. | last2 = Zhu | first2 = Z. | last3 = Gandhi | first3 = M. | last4 = Steward | first4 = DL. | last5 = Fidler | first5 = JP. | last6 = Giordano | first6 = TJ. | last7 = Biddinger | first7 = PW. | last8 = Nikiforov | first8 = YE. | title = Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. | journal = Am J Surg Pathol | volume = 30 | issue = 2 | pages = 216-22 | month = Feb | year = 2006 | doi = | PMID = 16434896 }}</ref>
{| class="wikitable sortable"
! Molecular change
! Frequency
! Histology
! Notes
|-
|BRAF point mutations
| ~ 40%
| [[papillary thyroid carcinoma tall cell variant|tall cell variant]]
| poorer prognosis, older individuals
|-
|RET/PTC rearrangments
| ~ 20%
| papillary architecture, [[psammoma bodies]]
| younger individuals
|-
|RAS point mutations
| ~ 15%
| exclusively [[papillary thyroid carcinoma follicular variant|follicular variant]]
| -
|}

===Sign out===
<pre>
HEMITHYROID, RIGHT, COMPLETION OF TOTAL THYROIDECTOMY:
- PAPILLARY THYROID CARCINOMA, FOLLICULAR VARIANT.
-- TUMOUR SIZE: 4 MM (MAXIMAL).
-- ARCHITECTURE: FOLLICULAR.
-- CYTOMORPHOLOGY: CLASSICAL.
-- HISTOLOGIC GRADE: G1 (WELL DIFFERENTIATED).
-- NO TUMOUR CAPSULE IDENTIFIED.
-- NEGATIVE FOR LYMPHOVASCULAR INVASION.
-- NEGATIVE FOR PERINEURAL INVASION.
-- NEGATIVE FOR EXTRATHYROIDAL EXTENSION.
-- SURGICAL MARGINS NEGATIVE FOR MALIGNANCY.
</pre>

Note:
*If it is a completion thyroidectomy and the staging changes one should do a full synoptic report.

==Insular carcinoma==
===General===
Features:<ref name=pmid17665497>{{cite journal |author=Rufini V, Salvatori M, Fadda G, ''et al.'' |title=Thyroid carcinomas with a variable insular component: prognostic significance of histopathologic patterns |journal=Cancer |volume=110 |issue=6 |pages=1209–17 |year=2007 |month=September |pmid=17665497 |doi=10.1002/cncr.22913 |url=}}</ref>
*Rare - approximately 5% of all thyroid carcinomas.
*Thought to be a separate tumour from papillary thyroid carcinoma and follicular thyroid carcinoma with a focal insular pattern.
*Some lump this entity with papillary carcinoma, i.e. consider it a variant of papillary thyroid carcinoma.

===Microscopic===
Features:<ref name=pmid17665497/>
*Islands of cells - '''key feature'''.
*Scant cytoplasm.
*Nuclei monomorphic and round.

DDx:<ref>Endo. fellow. 17 September 2009.</ref>
*[[Medullary thyroid carcinoma]].
*Poorly differentiated thyroid carcinoma.

==Follicular thyroid carcinoma==
*[[AKA]] ''follicular carcinoma''.
===Clinical===
Medical school memory device ''4 Fs'':
*FNA NOT diagnosable.
*Far away mets (sometimes).
*Female predominant.
*Favourable prognosis.

Notes:
*Usu. has a hematologic spread.
**PTC usu. spread via lymphatics.

===Microscopic===
Features:
*Defined by either:
*#Invasion through the capsule:
*#*Should be all the way through.<ref>SR. 17 January 2011.</ref>
*#**1/2 does not count.
*#**Fibrous reaction does not count.
*#**"Above the contour" does not count.
*#Vascular invasion (all of the following):
*##In a small vein (not a capillary), that is outside of the tumour mass.
*##Tumour adherent to the side of the vessel.
*##Tumour must be re-endothelialized.

Notes:
*'''Impossible''' to differentiate from ''[[follicular thyroid adenoma|follicular adenoma]]'' on FNA (no cytologic differences).
*Described as "over-diagnosed" ... misdiagnoses: PTC follicular variant, follicular adenoma, multinodular goitre with a thick capsule.

Images:
*[http://path.upmc.edu/cases/case653.html Follicular thyroid carcinoma - several images (upmc.edu)].

==Medullary thyroid carcinoma==
*Abbreviated ''MTC''.
===General===
Medical school memory device - 3 M's:
*[[amyloid|aMyloid]].
*Median node dissection done.
*[[MEN IIa syndrome]]/[[MEN IIb syndrome]].
**Medullary thyroid carcinoma.
**[[Pheochromocytoma]].
**[[Parathyroid adenoma]].

Epidemiology:
*Very rare.
*Poor prognosis.
*May be genetic (MEN IIa/b syndrome).
*Arises from C cells (which produce calcitonin).

Syndromic tumours - typically:<ref name=pmid21455198>{{Cite journal | last1 = Nosé | first1 = V. | title = Familial thyroid cancer: a review. | journal = Mod Pathol | volume = 24 Suppl 2 | issue = | pages = S19-33 | month = Apr | year = 2011 | doi = 10.1038/modpathol.2010.147 | PMID = 21455198 |URL = http://www.nature.com/modpathol/journal/v24/n2s/full/modpathol2010147a.html }}</ref>
*Present in 30s or 40s.
*+/-Multifocal.
*+/-Bilateral.
*[[C-cell hyperplasia]].

===Gross===
Features:<ref name=pmid21455198/>
*Usu. well-circumscribed.
*White, gray or yellow.
*Gritty.
*Firm.

Image:
*[http://www.nature.com/modpathol/journal/v24/n2s/fig_tab/modpathol2010147f2.html MTC (nature.com)].

===Microscopic===
Features:
*Nuclei with "neuroendocrine features".
**Small, round nuclei.
**Coarse chromatin (''salt and pepper nuclei'').
*+/-[[Amyloid]] deposits - fluffy appearing acellular eosinophilic material in the cytoplasm.
*+/-[[C-cell hyperplasia]] - seen with familial forms of MTC.
**C cells (AKA ''parafollicular cell''): abundant cytoplasm - clear/pale.

Note:
*The amyloid is formed from ''calcitonin''.<ref name=pmid15459123>{{Cite journal | last1 = Khurana | first1 = R. | last2 = Agarwal | first2 = A. | last3 = Bajpai | first3 = VK. | last4 = Verma | first4 = N. | last5 = Sharma | first5 = AK. | last6 = Gupta | first6 = RP. | last7 = Madhusudan | first7 = KP. | title = Unraveling the amyloid associated with human medullary thyroid carcinoma. | journal = Endocrinology | volume = 145 | issue = 12 | pages = 5465-70 | month = Dec | year = 2004 | doi = 10.1210/en.2004-0780 | PMID = 15459123 }}</ref>

Images:
*www:
**[http://jcp.bmj.com/content/vol57/issue3/images/large/cp8474.f16.jpeg Medullary thyroid carcinoma (bmj.com)].
**[http://www.nature.com/ki/journal/v70/n11/fig_tab/5001888f2.html C cell hyperplasia (nature.com)].
**[http://lifesci.rutgers.edu/~babiarz/Review3/Lp6/scope8.htm C cell (rutgers.edu)].
**[http://www.anatomyatlases.org/MicroscopicAnatomy/Images/Plate287.jpg Parafollicular cells (anatomyatlases.org)].
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_low_mag.jpg MTC - low mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_high_mag.jpg MTC - high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_2_-_high_mag.jpg MTC and amyloid - high mag. (WC)].

===IHC===
Features:<ref>URL: [http://pathologyoutlines.com/thyroid.html#medullary http://pathologyoutlines.com/thyroid.html#medullary]. Accessed on: 17 January 2011.</ref>
*[[Calcitonin]] +ve - it arises from C cells (which produce calcitonin).
*Congo-red +ve (amyloid present) - mnemonic: ''CRAP'' -- congo red amyloid protein.
*Neuroendocrine markers.
**[[Chromogranin A]].
**[[Synaptophysin]].
*CEA +ve (often better staining than calcitonin).<ref>SB. 7 January 2010.</ref>
*Thyroglobulin usu. -ve.<ref name=pmid8454270>{{Cite journal | last1 = de Micco | first1 = C. | last2 = Chapel | first2 = F. | last3 = Dor | first3 = AM. | last4 = Garcia | first4 = S. | last5 = Ruf | first5 = J. | last6 = Carayon | first6 = P. | last7 = Henry | first7 = JF. | last8 = Lebreuil | first8 = G. | title = Thyroglobulin in medullary thyroid carcinoma: immunohistochemical study with polyclonal and monoclonal antibodies. | journal = Hum Pathol | volume = 24 | issue = 3 | pages = 256-62 | month = Mar | year = 1993 | doi = | PMID = 8454270 }}</ref>

===EM===
*Neurosecretory granules.
**Feature seen in neuroendocrine tumours.

Images: [http://pathhsw5m54.ucsf.edu/case7/image77.html Neurosecretory granules (ucsf.edu)].

==Anaplastic thyroid carcinoma==
===Epidemiology===
*Very rare.
*Horrible prognosis.
*Often presents with obstruction.
*Typically there is a history of a thyroid mass.

===Microscopic===
Features:
*Cytologically malignant:
**Huge [[NC ratio]].
**Mitoses.
*+/-[[Necrosis]].

Notes:
*May have features of other thyroid carcinomas, e.g. psammoma bodies, papillae, nuclear changes of PTC.

Image: [http://commons.wikimedia.org/wiki/File:Anaplastic_thyroid_carcinoma_low_mag.jpg Anaplastic thyroid carcinoma with a component of papillary thyroid carcinoma (WC)].

DDx:
*[[Poorly differentiated carcinoma of the thyroid|Poorly differentiated carcinoma]].
*[[Squamous cell carcinoma]].
*[[Medullary thyroid carcinoma]].
*Sarcoma.

===IHC===
*Keratin (AE1/AE3) +ve.
*Vimentin +ve, >90%.<ref name=pmid1712540>{{cite journal |author=Ordóñez NG, El-Naggar AK, Hickey RC, Samaan NA |title=Anaplastic thyroid carcinoma. Immunocytochemical study of 32 cases |journal=Am. J. Clin. Pathol. |volume=96 |issue=1 |pages=15–24 |year=1991 |month=July |pmid=1712540 |doi= |url=}}</ref>
*Thyroglobulin - rarely +ve (~15%).<ref name=pmid1712540/>
*CEA -ve, calcitonin -ve; to r/o medullary.
*p53 +ve.
*TTF-1 +ve.

==Lymphomas of the thyroid==
{{Main|Lymphoma}}
===General===
*Rare.
*Increased risk with chronic inflammatory conditions.
*Fit in the the greater category of ''[[MALT lymphoma]]''.

===Microscopic===
Features:
*Lymphoepithelial lesion - '''key feature'''.
*Plasma cells.
*"Overgrowth" - thyroid parenchyma displaced by lymphocytes.

=Weird stuff=
==Hyalinizing trabecular tumour==
*[[AKA]] ''hyalinizing trabecular adenoma''.
*Abbreviated ''HTT''.
===General===
*Considered by some (e.g. Silvia Asa) to be a variant of [[papillary thyroid carcinoma]].<ref name=pmid11117782>{{cite journal |author=Cheung CC, Boerner SL, MacMillan CM, Ramyar L, Asa SL |title=Hyalinizing trabecular tumor of the thyroid: a variant of papillary carcinoma proved by molecular genetics |journal=Am. J. Surg. Pathol. |volume=24 |issue=12 |pages=1622–6 |year=2000 |month=December |pmid=11117782 |doi= |url=}}</ref>
*Behaviour similar to papillary thyroid carcinoma - indolent.

===Microscopic===
Features:
*Trabecular arrangement of cells.
**May have "curved" trabeculae.
*Extracellular space has hyaline material - '''key feature'''.
*Cytoplasm mimics hyaline material in the extracellular space.

Images:
*[http://archive.biomedcentral.com/1742-6413/3/17/figure/F2?highres=y HTT (biomedcentral.com)].<ref name=pmid16867191>{{Cite journal | last1 = Baloch | first1 = ZW. | last2 = Puttaswamy | first2 = K. | last3 = Brose | first3 = M. | last4 = LiVolsi | first4 = VA. | title = Lack of BRAF mutations in hyalinizing trabecular neoplasm. | journal = Cytojournal | volume = 3 | issue = | pages = 17 | month = | year = 2006 | doi = 10.1186/1742-6413-3-17 | PMID = 16867191 }}</ref>
*[http://www.ispub.com/journal/the-internet-journal-of-endocrinology/volume-2-number-1/hyalinizing-trabecular-neoplasm-of-the-thyroid-controversies-in-management.article-g01.fs.jpg HTT (ispub.com)].<ref>URL: [http://www.ispub.com/journal/the-internet-journal-of-endocrinology/volume-2-number-1/hyalinizing-trabecular-neoplasm-of-the-thyroid-controversies-in-management.html http://www.ispub.com/journal/the-internet-journal-of-endocrinology/volume-2-number-1/hyalinizing-trabecular-neoplasm-of-the-thyroid-controversies-in-management.html]. Accessed on: 1 January 2012.</ref>

DDx:
*[[Papillary thyroid carcinoma]] (if one believes this is a separate entity).
*[[Medullary thyroid carcinoma]] - not trabecular, nuclei not [[PTC]]-like.
*[[Paraganglioma]].<ref>URL: [http://path.upmc.edu/cases/case465/dx.html http://path.upmc.edu/cases/case465/dx.html]. Accessed on: 17 January 2011.</ref>

===IHC===
*Thyroglobulin +ve.
*NSE +ve.

==Hürthle cell neoplasm==
*[[AKA]] ''oncocytic neoplasm''.
*Also spelled ''Hurthle cell neoplasm''.

===General===
*Incidence: uncommon.
*This is a general category - includes:
**Hürthle cell adenoma.
**Hürthle cell carcinoma.

*Some advocate ''total thyroidectomy'' for all Hürthle cell neoplasms, as it is difficult to reliably differentiate adenomas and carcinomas.<ref name=pmid9697901>{{Cite journal | last1 = Wasvary | first1 = H. | last2 = Czako | first2 = P. | last3 = Poulik | first3 = J. | last4 = Lucas | first4 = R. | title = Unilateral lobectomy for Hurthle cell adenoma. | journal = Am Surg | volume = 64 | issue = 8 | pages = 729-32; discussion 732-3 | month = Aug | year = 1998 | doi = | PMID = 9697901 }}</ref>
*It can be understood as a special type of ''follicular neoplasm'' (including ''[[follicular thyroid adenoma]]'' and ''[[follicular thyroid carcinoma]]'').<ref name=Ref_EP104>{{Ref EP|104}}</ref>

====Adenoma vs. carcinoma====
Suggestive for carcinoma:<ref name=pmid9697901/>
*Male.
*>4 cm
**Adenomas usu. <3 cm.
Definite for carcinoma:<ref name=pmid9697901/>
*Lymphovascular invasion.
*Capsular invasion.

===Gross===
*Yellow.
*Encapsulated.

===Microscopic===
Features:<ref name=Ref_EP104>{{Ref EP|104}}</ref>
*Oncocytes >= 75% of cells:
**Abundant granular, eosinophilic cytoplasm.
**Round regular nucleus +/- prominent nucleolus.
*+/-Degenerative changes.

Negatives:
*Lack nuclear features of [[papillary thyroid carcinoma]].
*Lack features of [[medullary thyroid carcinoma]].

DDx:<ref name=pmid18684023>{{cite journal |author=Montone KT, Baloch ZW, LiVolsi VA |title=The thyroid Hürthle (oncocytic) cell and its associated pathologic conditions: a surgical pathology and cytopathology review |journal=Arch. Pathol. Lab. Med. |volume=132 |issue=8 |pages=1241–50 |year=2008 |month=August |pmid=18684023 |doi= |url=}}</ref>
*Papillary thyroid carcinoma oncocytic variant.
*Medullary thyroid carcinoma oncocytic variant.
*Others.

==Minocycline associated thyroid pigmentation==
*[[AKA]] ''minocycline thyroid''.

===General===
*Benign pigmentation of the thyroid due to ''minocycline'', an antibiotic.
**Reported at other sites, e.g. [[heart valves]],<ref name=pmid10615019/> coronary arteries.

===Gross===
*Black thyroid.<ref name=pmid2780449>{{Cite journal | last1 = Noble | first1 = JG. | last2 = Christmas | first2 = TJ. | last3 = Chapple | first3 = C. | last4 = Katz | first4 = D. | last5 = Milroy | first5 = EJ. | title = The black thyroid: an unusual finding during neck exploration. | journal = Postgrad Med J | volume = 65 | issue = 759 | pages = 34-5 | month = Jan | year = 1989 | doi = | PMID = 2780449 | PMC = 2429157 }}</ref>

Images:
*[http://images.rheumatology.org/viewphoto.php?albumId=89099&imageId=5231272 Pigmented thyroid gland (rheumatology.org)].
*[http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2004)128%3C355:PQCTIP%3E2.0.CO;2 Minocycline thyroid - gross and microscopic (archivesofpathology.org)].<ref name=pmid14987144>{{Cite journal | last1 = Raghavan | first1 = R. | last2 = Snyder | first2 = WH. | last3 = Sharma | first3 = S. | title = Pathologic quiz case: tumor in pigmented thyroid gland in a young man. Papillary thyroid carcinoma in a minocycline-induced, diffusely pigmented thyroid gland. | journal = Arch Pathol Lab Med | volume = 128 | issue = 3 | pages = 355-6 | month = Mar | year = 2004 | doi = 10.1043/1543-2165(2004)128355:PQCTIP2.0.CO;2 | PMID = 14987144 }}</ref>

===Microscopic===
Features:
*Granular yellow blobs:
**Location:
***Intracytoplasmic in the follicule-lining cells, i.e. follicular cells.
***Intrafollicular.
**Variable size ~0.5-4 micrometers.

Notes:
*Pigment described as ''lipofuscin-like''.<ref name=pmid6435454>{{Cite journal | last1 = Gordon | first1 = G. | last2 = Sparano | first2 = BM. | last3 = Kramer | first3 = AW. | last4 = Kelly | first4 = RG. | last5 = Iatropoulos | first5 = MJ. | title = Thyroid gland pigmentation and minocycline therapy. | journal = Am J Pathol | volume = 117 | issue = 1 | pages = 98-109 | month = Oct | year = 1984 | doi = | PMID = 6435454 | PMC = 1900569 }}</ref>

Images:
*[http://flylib.com/books/2/953/1/html/2/44%20-%20Thyroid_files/DA11C44FF7.png Pigmentation due to minocycline (flylib.com)].<ref>URL: [http://flylib.com/books/en/2.953.1.50/1/ http://flylib.com/books/en/2.953.1.50/1/]. Accessed on: 11 March 2012.</ref>
*[http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2004)128%3C355:PQCTIP%3E2.0.CO;2 Minocycline thyroid - gross and microscopic (archivesofpathology.org)].<ref name=pmid14987144>{{Cite journal | last1 = Raghavan | first1 = R. | last2 = Snyder | first2 = WH. | last3 = Sharma | first3 = S. | title = Pathologic quiz case: tumor in pigmented thyroid gland in a young man. Papillary thyroid carcinoma in a minocycline-induced, diffusely pigmented thyroid gland. | journal = Arch Pathol Lab Med | volume = 128 | issue = 3 | pages = 355-6 | month = Mar | year = 2004 | doi = 10.1043/1543-2165(2004)128355:PQCTIP2.0.CO;2 | PMID = 14987144 }}</ref>

===Stains===
*Fontana-Masson stain +ve.<ref name=pmid10615019>{{Cite journal | last1 = Sant'Ambrogio | first1 = S. | last2 = Connelly | first2 = J. | last3 = DiMaio | first3 = D. | title = Minocycline pigmentation of heart valves. | journal = Cardiovasc Pathol | volume = 8 | issue = 6 | pages = 329-32 | month = | year = | doi = | PMID = 10615019 }}</ref>

=See also=
*[[Thyroid cytopathology]].
*[[Head and neck cytopathology]].
*[[Salivary gland]].
*[[Cytopathology]].

=References=
{{reflist|2}}

[[Category:Endocrine pathology]]

Thyroid gland

2013-06-13T18:34:17Z

Ingo: /* Microscopic */

The '''thyroid gland''' is an important little endocrine organ in the anterior [[neck]]. It is frequently afflicted by [[cancer]]... but the common cancer has such a good prognosis there is debate about how aggressively it should be treated. The [[cytopathology]] of the thyroid gland is dealt with in the ''[[thyroid cytology]]'' article.

The gland frustrates a significant number of pathologists, as the criteria for cancer are considered a bit wishy-washy.

=Thyroid specimens=
==They come in three common varieties==
*FNA (fine needle aspiration).
**Done to triage patients/rule-out malignancy - discussed in the article ''[[thyroid cytopathology]]''.
*Hemithyroid.
**Done to get a definitive diagnosis.
**May be a "completion" - removal of the other half following definitive diagnosis.
*Total thyroid.
**Done for malignancy or follicular lesion.

==Gross pathology==
*White nodules - think:
**Lymphoid tissue.
**Papillary thyroid carcinoma - may be calcified.<ref>BEC. 20 October 2009.</ref>

=Diagnoses=
==Common==
*[[Thyroid gland nodular hyperplasia|Nodular hyperplasia]] -- most common.
*[[Lymphocytic thyroiditis]].
*Papillary thyroid carcinoma (PTC) -- most common cancer.
**[[Papillary thyroid carcinoma follicular variant]].
*[[Parathyroid]] tissue.

==Pitfalls/weird stuff==
*Thyroid tissue lateral to the jugular vein (often referred to as ''lateral aberrant thyroid tissue'') is generally considered metastatic thyroid carcinoma ([[papillary thyroid carcinoma]]) even if it looks benign.<ref name=pmid14452106>{{Cite journal | last1 = JOHNSON | first1 = RW. | last2 = SAHA | first2 = NC. | title = The so-called lateral aberrant thyroid. | journal = Br Med J | volume = 1 | issue = 5293 | pages = 1668-9 | month = Jun | year = 1962 | doi = | PMID = 14452106 | PMC = 1958877 }}</ref>
**This dictum is disputed.<ref name=pmid17319317>{{Cite journal | last1 = Escofet | first1 = X. | last2 = Khan | first2 = AZ. | last3 = Mazarani | first3 = W. | last4 = Woods | first4 = WG. | title = Lessons to be learned: a case study approach. Lateral aberrant thyroid tissue: is it always malignant? | journal = J R Soc Promot Health | volume = 127 | issue = 1 | pages = 45-6 | month = Jan | year = 2007 | doi = | PMID = 17319317 }}</ref>
**The level VI and VII [[lymph nodes]] are medial to the jugular.
*[[Hashimoto's disease]] may have so many lymphocytes that it mimics a lymph node -- may lead to misdiagnosis of PTC.
*Parasitic nodule: clump of thyroid that is attached by a thin thread... but looks like a separate nodule; may lead to misdiagnosis of PTC.

Image:
*[http://images.radiopaedia.org/images/26383/ad505c78a87e71180792049299f5cd_big_gallery.jpg Neck levels (radiopaedia.org)].<ref>URL: [http://radiopaedia.org/articles/lymph-node-levels-of-the-neck http://radiopaedia.org/articles/lymph-node-levels-of-the-neck]. Accessed on: 5 November 2012.</ref>

==Diagnostic keys==
The following should prompt careful examination:<ref>SR. 17 January 2011.</ref>
*Architecture: microfollicular, trabecular, solid, insular.
*Thick capsule.
*Necrosis - rare in the thyroid.

==Thyroid IHC - general comments==
*Not really useful.
*Papers with very small sample sizes abound.

===Follicular thyroid carcinoma vs. papillary thyroid carcinoma===
*CD31 more frequently positive in follicular lesions.<ref name=pmid18795075>{{Cite journal | last1 = Rydlova | first1 = M. | last2 = Ludvikova | first2 = M. | last3 = Stankova | first3 = I. | title = Potential diagnostic markers in nodular lesions of the thyroid gland: an immunohistochemical study. | journal = Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub | volume = 152 | issue = 1 | pages = 53-9 | month = Jun | year = 2008 | doi = | PMID = 18795075 }}</ref>
**CD31 is a marker for microvessel density.
*Galectin-3 thought to be positive in papillary carcinoma.<ref name=pmid18795075/>
*HBME-1 thought to be positive in papillary lesions.<ref name=pmid15529186>{{Cite journal | last1 = Papotti | first1 = M. | last2 = Rodriguez | first2 = J. | last3 = De Pompa | first3 = R. | last4 = Bartolazzi | first4 = A. | last5 = Rosai | first5 = J. | title = Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential. | journal = Mod Pathol | volume = 18 | issue = 4 | pages = 541-6 | month = Apr | year = 2005 | doi = 10.1038/modpathol.3800321 | PMID = 15529186 }}</ref>

==Thyroid lesions per WHO==
*Adapted from the ''Washington Manual of Surgical Pathology''.<ref name=Ref_WMSP331>{{Ref WMSP|331}}</ref>
===Adenoma===
*Follicular adenoma.
*Hyalinizing trabecular tumour.

===Carcinoma===
*[[Papillary thyroid carcinoma|Papillary carcinoma]].
*[[Follicular thyroid carcinoma|Follicular carinoma]].
*[[Medullary thyroid carcinoma|Medullary carcinoma]].
*Undifferentiated (anaplastic) carcinoma.

*Poorly differentiated carcinoma.
*[[Squamous cell carcinoma]].
*[[Mucoepidermoid carcinoma]].
*Sclerosing mucoepidermoid carcinoma with eosinophilia.
*Mucinous carcinoma.

*Mixed medullary and follicular carinoma.
*Spindle cell tumour with thymus-like differentiation.
*Carcinoma showing thymus-like differentiation.

===Others===
*[[Teratoma]].
*[[Lymphoma]].
*Ectopic thymoma.
*[[Angiosarcoma]] + other [[soft tissue lesions]].
*[[Paraganglioma]].
*[[Solitary fibrous tumour]].
*[[Follicular dendritic cell tumour]].
*[[Langerhans cell histiocytosis]].
*[[Metastasis]].

=Parathyroid glands=
{{Main|Parathyroid glands}}
*May make an appearance in the context of thyroid surgery.

=Benign=
==Solid cell nest of the thyroid gland==
*[[AKA]] ''solid cell nest of thyroid''.
===General===
*Embryonic remnants endodermal origin.<ref name=pmid12527712>{{cite journal |author=Reis-Filho JS, Preto A, Soares P, Ricardo S, Cameselle-Teijeiro J, Sobrinho-Simões M |title=p63 expression in solid cell nests of the thyroid: further evidence for a stem cell origin |journal=Mod. Pathol. |volume=16 |issue=1 |pages=43–8 |year=2003 |month=January |pmid=12527712 |doi=10.1097/01.MP.0000047306.72278.39 |url=http://www.nature.com/modpathol/journal/v16/n1/full/3880708a.html}}</ref>
*Incidental finding.

Note:
*Hypothesized to have some relation to [[mucoepidermoid carcinoma]] of the thyroid gland;<ref name=pmid1413837>{{Cite journal | last1 = Ozaki | first1 = O. | last2 = Ito | first2 = K. | last3 = Sugino | first3 = K. | last4 = Yasuda | first4 = K. | last5 = Yamashita | first5 = T. | last6 = Toshima | first6 = K. | title = Solid cell nests of the thyroid gland: precursor of mucoepidermoid carcinoma? | journal = World J Surg | volume = 16 | issue = 4 | pages = 685-8; discussion 688-9 | month = | year = | doi = | PMID = 1413837 }}</ref> however, another study suspects a relationship with [[papillary thyroid carcinoma]].<ref name=pmid22224821>{{Cite journal | last1 = Prichard | first1 = RS. | last2 = Lee | first2 = JC. | last3 = Gill | first3 = AJ. | last4 = Sywak | first4 = MS. | last5 = Fingleton | first5 = L. | last6 = Robinson | first6 = BG. | last7 = Sidhu | first7 = SB. | last8 = Delbridge | first8 = LW. | title = Mucoepidermoid carcinoma of the thyroid: a report of three cases and postulated histogenesis. | journal = Thyroid | volume = 22 | issue = 2 | pages = 205-9 | month = Feb | year = 2012 | doi = 10.1089/thy.2011.0276 | PMID = 22224821 }}</ref>

===Microscopic===
Features:<ref name=pmid12527712/>
*Cellular solid ''or'' cystic cluster of variable size with:
**Cuboidal cellular morphology.
***May have columnar morphology.
**Moderate-to-scant eosinophilic cytoplasm.
**Round/ovoid nuclei with finely granular chromatin.
*+/-Goblet cells (~30% of cases).<ref name=pmid7509563>{{cite journal |author=Mizukami Y, Nonomura A, Michigishi T, ''et al.'' |title=Solid cell nests of the thyroid. A histologic and immunohistochemical study |journal=Am. J. Clin. Pathol. |volume=101 |issue=2 |pages=186–91 |year=1994 |month=February |pmid=7509563 |doi= |url=}}</ref>

Images:
*www:
**[http://farm6.static.flickr.com/5143/5685400518_c4f506d370.jpg Solid cell next (flickr.com)].
**[http://www.nature.com/modpathol/journal/v16/n1/fig_tab/3880708f1.html#figure-title Crappy B&W of solid cell nest (nature.com)].
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Solid_cell_nest_of_the_thyroid_gland_-_intermed_mag.jpg Solid cell nest of the thyroid gland - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Solid_cell_nest_of_the_thyroid_gland_-_very_high_mag.jpg Solid cell nest of the thyroid gland - very high mag. (WC)].

DDx:<ref name=pmid12527712/>
*[[C-cell hyperplasia]].
*[[Medullary thyroid carcinoma|Medullary carcinoma]].
*Squamous lesions.

===IHC===
Features:<ref name=pmid12527712/>
*p63 +ve.
**-ve in clear cells.
*CEA +ve (polyconal).<ref name=pmid7509563>{{cite journal |author=Mizukami Y, Nonomura A, Michigishi T, ''et al.'' |title=Solid cell nests of the thyroid. A histologic and immunohistochemical study |journal=Am. J. Clin. Pathol. |volume=101 |issue=2 |pages=186–91 |year=1994 |month=February |pmid=7509563 |doi= |url=}}</ref>
**+ve also in clear cells.
*Chromogranin A +ve ~45% of cases.<ref name=pmid7509563/>

===Sign out===
Solid cell nests of the thyroid gland are usually not reported.

==Thyroid gland nodular hyperplasia==
*[[AKA]] ''[[nodular hyperplasia]]''.
*[[AKA]] ''adenomatoid nodule''.

===General===
*Clinical diagnosis: ''goitre'', [[AKA]] ''sporadic goitre'', AKA ''multinodular goitre'' (MNG).
*Most common diagnosis in the thyroid.
**If you've seen a handful of thyroids you've seen this.

Notes:
*Large lesions may be clonal; however, this is clinically irrelevant.

===Gross===
Features:
*Enlarge thyroid gland.
*+/-Distinct (well-circumscribed) nodules.

===Microscopic===
Features:
*Follicles of variable size - '''key feature'''.
**Should be obvious at low power, i.e. with the 2.5x objective.
*+/-Nodules.
**Do not have a thick fibrous capsule.
**May have a high cellularity.
**Architecture: solid or microfollicular.<ref name=Ref_EP36>{{Ref EP|36}}</ref>

Negatives:
*No nuclear features suggestive of malignancy (at lower power).
**One should not look at high power.
*Not cellular.

DDx:
*[[Papillary thyroid carcinoma]] - esp. [[papillary thyroid carcinoma follicular variant]].
*[[Follicular thyroid adenoma]] - contained in a fibrous capsule.
*[[Follicular thyroid carcinoma]] - has fibrous capsule and invasion through it.

===Sign out===
<pre>
HEMITHYROID, RIGHT, HEMITHYROIDECTOMY:
- NODULAR HYPERPLASIA.
- NEGATIVE FOR MALIGNANCY.
</pre>

<pre>
HEMITHYROID, RIGHT, HEMITHYROIDECTOMY:
- CELLULAR ADENOMATOID NODULE ON A BACKGROUND OF NODULAR HYPERPLASIA.
- NEGATIVE FOR MALIGNANCY.
</pre>

==Follicular thyroid adenoma==
*[[AKA]] follicular adenoma, [[AKA]] thyroid follicular adenoma.
===General===
*Most common neoplasm of thyroid.<ref name=Ref_EP51>{{Ref EP|51}}</ref>
*Encapusled lesion (surrounded by fibrous capsule).

===Gross===
*Thick capsule.

Notes:
*The entire capsule should be submitted.<ref>SR. 17 January 2011.</ref>
**A good start for most thyroid specimens with a thick capsule is 10 blocks.

===Microsopic===
Features:
*Cellular.
*Thick capsule - '''key feature'''.

Negatives.
*No invasion of the capsule (see ''[[follicular thyroid carcinoma]]'' section).
*No nuclear features suggestive of [[papillary thyroid carcinoma]].

DDx:
*[[Thyroid gland nodular hyperplasia]] with an encapsulated nodule - not as cellular.

==Graves disease==
===General===
*Often misspelled "Grave's disease".
*Autoimmune disease leading to hyperthyroidism.
*Eye problems not resolved with thyroid removal.{{fact}}
*Higher risk of [[papillary thyroid carcinoma]].

Clinical:
*TSH-receptor antibody +ve.<ref name=pmid19576193>{{Cite journal | last1 = Massart | first1 = C. | last2 = Gibassier | first2 = J. | last3 = d'Herbomez | first3 = M. | title = Clinical value of M22-based assays for TSH-receptor antibody (TRAb) in the follow-up of antithyroid drug treated Graves' disease: comparison with the second generation human TRAb assay. | journal = Clin Chim Acta | volume = 407 | issue = 1-2 | pages = 62-6 | month = Sep | year = 2009 | doi = 10.1016/j.cca.2009.06.033 | PMID = 19576193 }}</ref>

===Gross===
Features:<ref>{{Ref EP|30}}</ref>
*Enlarged 50-150 g.
*"Beefy-red" appearance, looks like raw beef.

===Microscopic===
Features:
*Classic:
**Hypercellular
**Patchy lymphocytes.
**Little colloid.
*Scalloping of colloid; colloid has undulating border.
**Non-specific finding.
*+/-Nuclear clearing.
*+/-Papillae (may mimic papillary thyroid carcinoma in this respect).

Notes:
*Usually has an unimpressive appearance... as it is treated, i.e. history is important.
*Nuclear clearing and papillae are usu. diffuse in Graves disease - unlike in papillary thyroid carcinoma.

Image:
*[http://library.med.utah.edu/WebPath/jpeg4/ENDO022.jpg Graves disease (med.utah.edu)].<ref>URL: [http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html]. Accessed on: 4 December 2011.</ref>

==Idiopathic granulomatous thyroiditis==
*[[AKA]] ''granulomatous thyroiditis'' - non-specific term; granulomas may be due a number of causes.
*AKA ''subacute thyroiditis''.
*[[AKA]] ''de Quervain thyroiditis''.
**Should '''not''' be confused with ''[[de Quervain's disease]]'' (AKA ''gamer's thumb'') something completely unrelated to the thyroid.

===General===
*Women > men.
*Etiology: possibly viral.<ref name=llyod/>

Clinical:
*Tenderness.<ref name=pmid22538753>{{Cite journal | last1 = Szczepanek-Parulska | first1 = E. | last2 = Zybek | first2 = A. | last3 = Biczysko | first3 = M. | last4 = Majewski | first4 = P. | last5 = Ruchała | first5 = M. | title = What might cause pain in the thyroid gland? Report of a patient with subacute thyroiditis of atypical presentation. | journal = Endokrynol Pol | volume = 63 | issue = 2 | pages = 138-42 | month = | year = 2012 | doi = | PMID = 22538753 }}</ref>

===Microscopic===
Features:<ref name=Ref_Sternberg4_559>{{Ref Sternberg4|559}}</ref><ref name=llyod>{{cite book |title=Endocrine Diseases (AFIP Atlas of Nontumor Pathology) |last= Lloyd |first = Ricardo V. |authorlink= |coauthors= |year= 2002 |publisher= American Registry of Pathology |location= Toronto |isbn=978-1881041733 |page= |pages= |url=http://www.amazon.com/Endocrine-Diseases-Atlas-Nontumer-Pathology/dp/1881041735 |accessdate=}}</ref>
*[[Granulomas]] with multinucleated giant cells - usu. with engulfed colloid.
*Lymphocytes.
*Plasma cells.
*+/-Fibrosis.

DDx:
*Infectious granulomatous disease (fungal, microbacterial).
*[[Palpation thyroiditis]].
*[[Sarcoidosis]] (classically intrafollicular distribution).

Images:
*[http://commons.wikimedia.org/wiki/File:Subacute_thyroiditis_-_intermed_mag.jpg Subacute thyroiditis - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Subacute_thyroiditis_-_high_mag.jpg Subacute thyroiditis - high mag. (WC)].

===Stains===
*ZN -ve.
*GMS -ve.

==Palpation thyroiditis==
===General===
*Granulomatous inflammation due to palpation.
**Incidence of granulomas higher in surgical thyroid specimens than autopsies.<ref name=llyod/>

===Microscopic===
Features:<ref name=llyod>{{cite book |title=Endocrine Diseases (AFIP Atlas of Nontumor Pathology) |last= Lloyd |first = Ricardo V. |authorlink= |coauthors= |year= 2002 |publisher= American Registry of Pathology |location= Toronto |isbn=978-1881041733 |page= |pages= |url=http://www.amazon.com/Endocrine-Diseases-Atlas-Nontumer-Pathology/dp/1881041735 |accessdate=}}</ref>
*[[Granuloma]]s involving the follicle.
**Histiocytes within the colloid.

DDx:
*[[Idiopathic granulomatous thyroiditis]].
*[[Sarcoidosis]].
*Infectious granulomatous thyroiditis.

===Stains===
*ZN -ve.
*GMS -ve.

==Riedel thyroiditis==
*[[AKA]] ''invasive fibrous thyroiditis''.<ref name=pmid21568724>{{Cite journal | last1 = Fatourechi | first1 = MM. | last2 = Hay | first2 = ID. | last3 = McIver | first3 = B. | last4 = Sebo | first4 = TJ. | last5 = Fatourechi | first5 = V. | title = Invasive fibrous thyroiditis (Riedel thyroiditis): the Mayo Clinic experience, 1976-2008. | journal = Thyroid | volume = 21 | issue = 7 | pages = 765-72 | month = Jul | year = 2011 | doi = 10.1089/thy.2010.0453 | PMID = 21568724 }}</ref>
===General===
Clinical features:<ref name=pmid21568724/>
*Extremely rare.
*Women > men.
*Usually smokers.
*May be associated with ''[[retroperitoneal fibrosis]]''.
*May be hypothyroid.
*+/-Obstructive symptoms.

===Microscopic===
Features:
*Fibrosis.
*Specimen often fragmented as it was difficult to remove.

DDx:
*[[Anaplastic thyroid carcinoma|Anaplastic carcinoma]], spindle cell variant.

==Hashimoto thyroiditis==
===General===
*'''This is a clinical diagnosis'''.
**The histomorphologic findings, generally, are '''not''' diagnostic.

Etiology:
*Autoimmune disease leading to hypothyroidism.
**Often genetic/part of a syndrome.

====Clinical====
Serology:<ref name=pmid7813361>{{cite journal |author=Poropatich C, Marcus D, Oertel YC |title=Hashimoto's thyroiditis: fine-needle aspirations of 50 asymptomatic cases |journal=Diagn. Cytopathol. |volume=11 |issue=2 |pages=141–5 |year=1994 |pmid=7813361 |doi= |url=http://www3.interscience.wiley.com/journal/112701408/abstract?CRETRY=1&SRETRY=0}}</ref>
*Antimicrosomal (antithyroid peroxidase) +ve.
*Antithyroglobulin +ve.

Associated pathology:<ref name=pmid7813361/>
*Increased risk of B-cell lymphoma; these are classically:<ref name=pmid18018576 >{{Cite journal | last1 = Ohye | first1 = H. | last2 = Fukata | first2 = S. | last3 = Hirokawa | first3 = M. | title = [Malignant lymphoma of the thyroid]. | journal = Nihon Rinsho | volume = 65 | issue = 11 | pages = 2092-8 | month = Nov | year = 2007 | doi = | PMID = 18018576 }}</ref>
**[[MALT lymphoma]].
**[[Diffuse large B cell lymphoma]] (DLBCL).

===Microscopic===
Features:
*Lymphocytic infiltrate - '''key feature'''.
*Nuclear clearing common.
**May confuse with [[papillary thyroid carcinoma]].
*Polymorphous lymphoplasmacytic infiltrate with germinal centres.<ref name=Ref_APBR672>{{Ref APBR|672}}</ref>
*+/-Oncocytic metaplasia.

Notes:
*Histologically often '''not''' possible to separate from "non-specific" thyroiditis.<ref name=Ref_Sternberg4_560>{{Ref Sternberg4|560}}</ref>

DDx:
*[[Lymphocytic thyroiditis]].
*[[Papillary thyroid carcinoma]].
*[[MALT lymphoma]].
*[[Diffuse large B cell lymphoma]].

===IHC===
*Panel to exclude lymphoma may be required, e.g. CD3, CD20, CD10, BCL6, BCL2, kappa, lambda.

===Molecular===
*Occasionally done to exclude lymphoma - see ''[[MALT lymphoma]]'' and ''[[DLBCL]]''.

==C-cell hyperplasia==
*Abbreviated ''CCH''.
===General===
*Screening for C-cell hyperplasia/[[medullary thyroid carcinoma]] done with ''serum calcitonin level''.<ref name=pmid19726541>{{cite journal |author=Machens A, Hoffmann F, Sekulla C, Dralle H |title=Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer |journal=Endocr. Relat. Cancer |volume=16 |issue=4 |pages=1291–8 |year=2009 |month=December |pmid=19726541 |doi=10.1677/ERC-09-0136 |url=http://erc.endocrinology-journals.org/cgi/content/full/16/4/1291}}</ref>

===Gross===
*Not visible.

===Microscopic===
Features:
*Location:<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Thyroid_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Thyroid_11protocol.pdf]. Accessed on: 7 April 2012.</ref>
**Mid portion of lobe to upper third of lobe.
***Not at the poles.
***Not in the isthmus.

*Definitions vary.<ref>SR. 17 January 2011.</ref>

One definition - either of the following:<ref name=pmid19726541>{{cite journal |author=Machens A, Hoffmann F, Sekulla C, Dralle H |title=Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer |journal=Endocr. Relat. Cancer |volume=16 |issue=4 |pages=1291–8 |year=2009 |month=December |pmid=19726541 |doi=10.1677/ERC-09-0136 |url=http://erc.endocrinology-journals.org/cgi/content/full/16/4/1291}}</ref>
#>50 C-cells per low-power field (x100).
#*This part of the definition suffers from [[LPFitis]]. The paper should have been rejected.
#Confined to the thyroid gland and no larger than 10 mm in greatest dimension.

Another definition:
*Invasion of the basement membrane with stromal reaction.

A third definition:
*"Several clusters" of more than six C cells.

====Images====
*[http://www.nature.com/modpathol/journal/v16/n8/fig_tab/3880836f2.html CCH - crappy B&W image (nature.com)].<ref>{{Cite journal | last1 = Guyétant | first1 = S. | last2 = Josselin | first2 = N. | last3 = Savagner | first3 = F. | last4 = Rohmer | first4 = V. | last5 = Michalak | first5 = S. | last6 = Saint-André | first6 = JP. | title = C-cell hyperplasia and medullary thyroid carcinoma: clinicopathological and genetic correlations in 66 consecutive patients. | journal = Mod Pathol | volume = 16 | issue = 8 | pages = 756-63 | month = Aug | year = 2003 | doi = 10.1097/01.MP.0000081727.75778.0C | PMID = 12920219 }}</ref>
*[http://www.nature.com/modpathol/journal/v16/n8/fig_tab/3880836f3.htm CCH - crappy B&W image (nature.com)].
*[http://www.forpath.org/workshops/0201/photos/fullsize/cas7c.jpg CCH (forpath.org)].<ref>URL: [http://www.forpath.org/workshops/0201/html/case_7.asp http://www.forpath.org/workshops/0201/html/case_7.asp]. Accessed on: 21 May 2013.</ref>
*[http://alf3.urz.unibas.ch/pathopic/e/getpic-fra.cfm?id=4849 CCH (unibas.ch)].
*[http://alf3.urz.unibas.ch/pathopic/e/getpic-fra.cfm?id=10739 Nodular CCH (unibas.ch)].

=Malignant neoplasm=
There are a bunch of 'em. The most common, by far, is papillary.

==Papillary thyroid carcinoma==
*Abbreviated ''PTC''.
===General===
Medical school memory device P's:
*Palpable nodes.
*Popular (most common malignant neoplasm of the thyroid).
*Prognosis is good.
*Pre-Tx iodine scan.
*Post-Sx iodine scan.
*[[Psammoma bodies]].

Notes:
*PTC is associated with radiation exposure.<ref name=Ref_Sternberg4_564>{{Ref Sternberg4|564}}</ref>
*''Papillary thyroid microcarcinoma'' is defined as a tumour with a maximal dimension of 1.0 cm or less.<ref name=pmid21267823>{{Cite journal | last1 = Sethom | first1 = A. | last2 = Riahi | first2 = I. | last3 = Riahi | first3 = K. | last4 = Akkari | first4 = K. | last5 = Benzarti | first5 = S. | last6 = Miled | first6 = I. | last7 = Chebbi | first7 = MK. | title = [Management of thyroid microcarcinoma. Report of 13 cases]. | journal = Tunis Med | volume = 89 | issue = 1 | pages = 23-5 | month = Jan | year = 2011 | doi = | PMID = 21267823 }}</ref>

====Prognosis====
Prognosis can be predicted by ''MAICS'' score. It which includes:<ref name=pmid12016468>{{Cite journal | last1 = Hay | first1 = ID. | last2 = Thompson | first2 = GB. | last3 = Grant | first3 = CS. | last4 = Bergstralh | first4 = EJ. | last5 = Dvorak | first5 = CE. | last6 = Gorman | first6 = CA. | last7 = Maurer | first7 = MS. | last8 = McIver | first8 = B. | last9 = Mullan | first9 = BP. | title = Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940-1999): temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients. | journal = World J Surg | volume = 26 | issue = 8 | pages = 879-85 | month = Aug | year = 2002 | doi = 10.1007/s00268-002-6612-1 | PMID = 12016468 }}</ref>
*'''M'''etastases.
*'''A'''ge.
*'''I'''nvasion of surround tissues.
*'''C'''completeness of excision.
*'''S'''ize of tumour.

===Microscopic===
Features:
*Nuclear changes - '''key feature'''.
*#"Shrivelled nuclei"/"raisin" like nuclei, nuclei with a wavy ("textured") nuclear membrane -- usu. easy to find.
*#[[Nuclear inclusions]] - usu. harder to find; have high [[specificity]].
*#Nuclear grooves.
*#Nuclear clearing (only on permanent section) - also known as "Orphan Annie eyes".
*Overlap of nuclei - "cells do not respect each other's borders" (easy to see at '''key feature at low power''').
*Classically has papillae (nipple-like shape); papilla (definition): epithelium on fibrovascular core.
**Absence of papillae does not exclude diagnosis.
*[[Psammoma bodies]].
**Circular, acellular, eosinophilic whorled bodies.
**Not necessary to make diagnosis - but very specific in the context of a specimen labeled "thyroid".
**Arise from infarction & calcification of papilla tips.<ref name=Ref_Sternberg4_565>{{Ref Sternberg4|565}}</ref>

Notes:
*Psammoma bodies are awesome if you see 'em, i.e. useful for arriving at the diagnosis.
**If there are no papillae structures -- you're unlikely to see psammoma bodies.
*At low power look for cellular areas/loss of follicles.
*Nuclear clearing seen in:
**Hashimoto's and papillary thyroid carcinoma.<ref name=Ref_Sternberg4_566>{{Ref Sternberg4|566}}</ref>
**May be an artifact of [[fixation]]/processing.
*Nuclear overlapping is easy to see at lower power-- should be the tip-off to look at high power for nuclear features.
*Nuclear inclusions are quite rare and not required to make the diagnosis -- but a very convincing feature if seen.
*Papillae may be seen in Graves disease.

DDx:
*[[Lymphocytic thyroiditis]]:
**[[Graves disease]].
**[[Hashimoto thyroiditis]].
*[[Solid cell nest of thyroid]].<ref name=pmid16830963>{{Cite journal | last1 = Baloch | first1 = ZW. | last2 = LiVolsi | first2 = VA. | title = Cytologic and architectural mimics of papillary thyroid carcinoma. Diagnostic challenges in fine-needle aspiration and surgical pathology specimens. | journal = Am J Clin Pathol | volume = 125 Suppl | issue = | pages = S135-44 | month = Jun | year = 2006 | doi = | PMID = 16830963 | URL = http://ajcp.ascpjournals.org/content/supplements/125/Suppl_1/S135.full.pdf }}</ref>

====Subtypes of papillary thyroid carcinoma====
There are many.

Poor prognosis variants:
*[[Papillary thyroid carcinoma tall cell variant|Tall cell variant]].<ref name=pmid22432054>{{Cite journal | last1 = Gonzalez-Gonzalez | first1 = R. | last2 = Bologna-Molina | first2 = R. | last3 = Carreon-Burciaga | first3 = RG. | last4 = Gómezpalacio-Gastelum | first4 = M. | last5 = Molina-Frechero | first5 = N. | last6 = Salazar-Rodríguez | first6 = S. | title = Papillary thyroid carcinoma: differential diagnosis and prognostic values of its different variants: review of the literature. | journal = ISRN Oncol | volume = 2011 | issue = | pages = 915925 | month = | year = 2011 | doi = 10.5402/2011/915925 | PMID = 22432054 | PMC = 3302055 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22432054/?tool=pubmed }}</ref>
*[[Papillary thyroid carcinoma columnar cell variant|Columnar cell variant]].<ref name=pmid22432054/>
*[[Papillary thyroid carcinoma solid variant|Solid variant]].<ref name=pmid22432054/>
*[[Papillary thyroid carcinoma diffuse sclerosing variant|Diffuse sclerosing variant]].<ref>URL: [http://emedicine.medscape.com/article/849000-overview#a0104 http://emedicine.medscape.com/article/849000-overview#a0104]. Accessed on: 1 May 2012.</ref>

=====Papillary thyroid carcinoma tall cell variant=====
======General======
*~10% of PTC.<ref>{{Ref Sternberg5|505}}</ref>
*Often large > 6 cm.

======Microscopic======
Features:<ref name=pmid19373912>{{cite journal |author=Urano M, Kiriyama Y, Takakuwa Y, Kuroda M |title=Tall cell variant of papillary thyroid carcinoma: Its characteristic features demonstrated by fine-needle aspiration cytology and immunohistochemical study |journal=Diagn. Cytopathol. |volume= |issue= |pages= |year=2009 |month=April |pmid=19373912 |doi=10.1002/dc.21086 |url=}}</ref>
*50% of cells with height 2x the width.<ref name=pmid18925842>{{cite journal |author=Ghossein R, Livolsi VA |title=Papillary thyroid carcinoma tall cell variant |journal=Thyroid |volume=18 |issue=11 |pages=1179–81 |year=2008 |month=November |pmid=18925842 |doi=10.1089/thy.2008.0164 |url=}}</ref>
**There is some disagreement on these criteria;<ref name=pmid18925842/> Raphael believes the height ought to be ~3x width, for 50% of the cells.<ref>S. Raphael. 17 January 2011.</ref>
*Eosinophilic cytoplasm.
*Well-defined cell borders.
*Nucleus stratified; basal location, i.e. closer to the basement membrane.

Negative:
*Nuclei ''not'' pseudostratified, if pseudostratified consider ''columnar cell variant''.

Images:
*[http://commons.wikimedia.org/wiki/File:Papillary_thyroid_carcinoma_tall_cell_var_intermed_mag.jpg PTC tall cell variant - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Papillary_thyroid_carcinoma_tall_cell_var_high_mag.jpg PTC tall cell variant - high mag. (WC)].

=====Papillary thyroid carcinoma columnar cell variant=====
======General======
Epidemiology:
*Poor prognosis.
*Very rare.

======Microscopic======
Features:<ref name=Ref_Sternberg5_506>{{Ref Sternberg5|506}}</ref>
*Elongated nuclei (similar to colorectal adenocarcinoma) - '''key feature'''.
*+/-Pseudostratification of the nuclei (like in colorectal adenocarcinoma), differentiates from ''tall cell variant''.
*Nuclear stratification - '''key feature'''.
*"Minimal" papillary features.
*"Tall cells".
*Clear-eosinophilic cytoplasm.
*Mitoses common.

Image: [http://www3.interscience.wiley.com/cgi-bin/fulltext/75000320/nfig003a?CRETRY=1&SRETRY=0 Columnar variant PTC (wiley.com)].
=====Papillary thyroid carcinoma follicular variant=====
======General======
*May be confused with [[follicular thyroid carcinoma|follicular carcinoma]] or [[follicular thyroid adenoma|follicular adenoma]].
*Pathologists often disagree about this diagnosis.<ref name=pmid21940284>{{Cite journal | last1 = Daniels | first1 = GH. | title = What if many follicular variant papillary thyroid carcinomas are not malignant? A review of follicular variant papillary thyroid carcinoma and a proposal for a new classification. | journal = Endocr Pract | volume = 17 | issue = 5 | pages = 768-87 | month = | year = | doi = 10.4158/EP10407.RA | PMID = 21940284 }}</ref>

======Microscopic======
Features:<ref name=Ref_EP88>{{Ref EP|88}}</ref>
*Small tightly packed follicles - '''key feature'''.
*Hypereosinophilic colloid.
*Nuclear features of PTC.
**Large nuclei.
**Typically have less [[nuclear pseudoinclusion]]s than the conventional type.
*+/-Fibrous capsule (common).

DDx:
*[[Follicular thyroid carcinoma]] - has a fibrous capsule and invasion though it.
*[[Follicular thyroid adenoma]] - surrounded by a fibrous capsule.
*[[Adenomatoid nodule]] - round nuclei, no nuclear features of PTC.

Images:
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=2008080217023776 PTC follicular variant (surgicalpathologyatlas.com)].
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=2008080216593186 PTC follicular variant (surgicalpathologyatlas.com)].
*[http://www.thyroidcancercanada.org/userfiles/images/Follicular_slide.jpg PTC follicular variant (thyroidcancercanada.org)].<ref>URL: [http://www.thyroidcancercanada.org/types-of-thyroid-cancer.php?lang=en http://www.thyroidcancercanada.org/types-of-thyroid-cancer.php?lang=en]. Accessed on: 9 January 2013.</ref>

=====Papillary thyroid carcinoma cribriform-morular variant=====
======General======
*Associated with [[familial adenomatous polyposis]] (FAP).<ref name=pmid18612695>{{cite journal |author=Groen EJ, Roos A, Muntinghe FL, ''et al.'' |title=Extra-intestinal manifestations of familial adenomatous polyposis |journal=Ann. Surg. Oncol. |volume=15 |issue=9 |pages=2439–50 |year=2008 |month=September |pmid=18612695 |pmc=2518080 |doi=10.1245/s10434-008-9981-3 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518080/?tool=pubmed}}</ref>

======Microscopic======
Features:
*Cribriform architectural pattern.
*Morules - balls of tissue.

=====Papillary thyroid carcinoma diffuse sclerosing variant=====
======General======
*Usually young adults, children.

======Microscopic======
Features:<ref>{{Ref PBoD8|1122}}</ref>
*Papillae - usu. prominent.
*Squamous morules - '''key features'''.<ref name=pmid15233643>{{Cite journal | last1 = Hirokawa | first1 = M. | last2 = Kuma | first2 = S. | last3 = Miyauchi | first3 = A. | last4 = Qian | first4 = ZR. | last5 = Nakasono | first5 = M. | last6 = Sano | first6 = T. | last7 = Kakudo | first7 = K. | title = Morules in cribriform-morular variant of papillary thyroid carcinoma: Immunohistochemical characteristics and distinction from squamous metaplasia. | journal = APMIS | volume = 112 | issue = 4-5 | pages = 275-82 | month = | year = | doi = 10.1111/j.1600-0463.2004.apm11204-0508.x | PMID = 15233643 }}
</ref>
*Lymphocytes - abundant.
*Fibrosis.

DDx:
*Lymphocytic thyroiditis (esp. Hashimoto's thyroiditis).

=====Papillary thyroid carcinoma warthin-like variant=====
*Resemble [[Warthin tumour]].
======Microscopic======
Features:<ref name=Ref_Sternberg5_506>{{Ref Sternberg5|506}}</ref>
*Eosinophilic cytoplasm.
*Lymphocytic thyroiditis.
*Papillae.

=====Papillary thyroid carcinoma solid variant=====
Features:<ref name=pmid22432054/>
*Some studies suggest this has a poor prognosis.
*More common in children.
*Associated with Chernobyl nuclear accident.

======Microscopic======
Features:
*Solid sheets >50% of tumour mass.<ref name=pmid22432054/>

===IHC===
Thyroid versus something else:
*Thyroglobulin +ve.
*TTF-1 (thyroid transcription factor-1) +ve.
*CD15 +ve.{{fact}}

PTC versus benign:<ref>{{Cite journal | last1 = Mataraci | first1 = EA. | last2 = Ozgüven | first2 = BY. | last3 = Kabukçuoglu | first3 = F. | title = Expression of cytokeratin 19, HBME-1 and galectin-3 in neoplastic and nonneoplastic thyroid lesions. | journal = Pol J Pathol | volume = 63 | issue = 1 | pages = 58-64 | month = Mar | year = 2012 | doi = | PMID = 22535608 }}</ref>
*HBME-1 +ve (strong, diffuse).
*CK19 +ve (strong, diffuse).
*Galectin-3 +ve (strong, diffuse).

===Molecular===
*Currently not widely used in a diagnostic context.

====Tabular summary====
Molecular changes in papillary thyroid carcinoma as per ''Adeniran et al'':<ref name=pmid16434896>{{Cite journal | last1 = Adeniran | first1 = AJ. | last2 = Zhu | first2 = Z. | last3 = Gandhi | first3 = M. | last4 = Steward | first4 = DL. | last5 = Fidler | first5 = JP. | last6 = Giordano | first6 = TJ. | last7 = Biddinger | first7 = PW. | last8 = Nikiforov | first8 = YE. | title = Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. | journal = Am J Surg Pathol | volume = 30 | issue = 2 | pages = 216-22 | month = Feb | year = 2006 | doi = | PMID = 16434896 }}</ref>
{| class="wikitable sortable"
! Molecular change
! Frequency
! Histology
! Notes
|-
|BRAF point mutations
| ~ 40%
| [[papillary thyroid carcinoma tall cell variant|tall cell variant]]
| poorer prognosis, older individuals
|-
|RET/PTC rearrangments
| ~ 20%
| papillary architecture, [[psammoma bodies]]
| younger individuals
|-
|RAS point mutations
| ~ 15%
| exclusively [[papillary thyroid carcinoma follicular variant|follicular variant]]
| -
|}

===Sign out===
<pre>
HEMITHYROID, RIGHT, COMPLETION OF TOTAL THYROIDECTOMY:
- PAPILLARY THYROID CARCINOMA, FOLLICULAR VARIANT.
-- TUMOUR SIZE: 4 MM (MAXIMAL).
-- ARCHITECTURE: FOLLICULAR.
-- CYTOMORPHOLOGY: CLASSICAL.
-- HISTOLOGIC GRADE: G1 (WELL DIFFERENTIATED).
-- NO TUMOUR CAPSULE IDENTIFIED.
-- NEGATIVE FOR LYMPHOVASCULAR INVASION.
-- NEGATIVE FOR PERINEURAL INVASION.
-- NEGATIVE FOR EXTRATHYROIDAL EXTENSION.
-- SURGICAL MARGINS NEGATIVE FOR MALIGNANCY.
</pre>

Note:
*If it is a completion thyroidectomy and the staging changes one should do a full synoptic report.

==Insular carcinoma==
===General===
Features:<ref name=pmid17665497>{{cite journal |author=Rufini V, Salvatori M, Fadda G, ''et al.'' |title=Thyroid carcinomas with a variable insular component: prognostic significance of histopathologic patterns |journal=Cancer |volume=110 |issue=6 |pages=1209–17 |year=2007 |month=September |pmid=17665497 |doi=10.1002/cncr.22913 |url=}}</ref>
*Rare - approximately 5% of all thyroid carcinomas.
*Thought to be a separate tumour from papillary thyroid carcinoma and follicular thyroid carcinoma with a focal insular pattern.
*Some lump this entity with papillary carcinoma, i.e. consider it a variant of papillary thyroid carcinoma.

===Microscopic===
Features:<ref name=pmid17665497/>
*Islands of cells - '''key feature'''.
*Scant cytoplasm.
*Nuclei monomorphic and round.

DDx:<ref>Endo. fellow. 17 September 2009.</ref>
*[[Medullary thyroid carcinoma]].
*Poorly differentiated thyroid carcinoma.

==Follicular thyroid carcinoma==
*[[AKA]] ''follicular carcinoma''.
===Clinical===
Medical school memory device ''4 Fs'':
*FNA NOT diagnosable.
*Far away mets (sometimes).
*Female predominant.
*Favourable prognosis.

Notes:
*Usu. has a hematologic spread.
**PTC usu. spread via lymphatics.

===Microscopic===
Features:
*Defined by either:
*#Invasion through the capsule:
*#*Should be all the way through.<ref>SR. 17 January 2011.</ref>
*#**1/2 does not count.
*#**Fibrous reaction does not count.
*#**"Above the contour" does not count.
*#Vascular invasion (all of the following):
*##In a small vein (not a capillary), that is outside of the tumour mass.
*##Tumour adherent to the side of the vessel.
*##Tumour must be re-endothelialized.

Notes:
*'''Impossible''' to differentiate from ''[[follicular thyroid adenoma|follicular adenoma]]'' on FNA (no cytologic differences).
*Described as "over-diagnosed" ... misdiagnoses: PTC follicular variant, follicular adenoma, multinodular goitre with a thick capsule.

Images:
*[http://path.upmc.edu/cases/case653.html Follicular thyroid carcinoma - several images (upmc.edu)].

==Medullary thyroid carcinoma==
*Abbreviated ''MTC''.
===General===
Medical school memory device - 3 M's:
*[[amyloid|aMyloid]].
*Median node dissection done.
*[[MEN IIa syndrome]]/[[MEN IIb syndrome]].
**Medullary thyroid carcinoma.
**[[Pheochromocytoma]].
**[[Parathyroid adenoma]].

Epidemiology:
*Very rare.
*Poor prognosis.
*May be genetic (MEN IIa/b syndrome).
*Arises from C cells (which produce calcitonin).

Syndromic tumours - typically:<ref name=pmid21455198>{{Cite journal | last1 = Nosé | first1 = V. | title = Familial thyroid cancer: a review. | journal = Mod Pathol | volume = 24 Suppl 2 | issue = | pages = S19-33 | month = Apr | year = 2011 | doi = 10.1038/modpathol.2010.147 | PMID = 21455198 |URL = http://www.nature.com/modpathol/journal/v24/n2s/full/modpathol2010147a.html }}</ref>
*Present in 30s or 40s.
*+/-Multifocal.
*+/-Bilateral.
*[[C-cell hyperplasia]].

===Gross===
Features:<ref name=pmid21455198/>
*Usu. well-circumscribed.
*White, gray or yellow.
*Gritty.
*Firm.

Image:
*[http://www.nature.com/modpathol/journal/v24/n2s/fig_tab/modpathol2010147f2.html MTC (nature.com)].

===Microscopic===
Features:
*Nuclei with "neuroendocrine features".
**Small, round nuclei.
**Coarse chromatin (''salt and pepper nuclei'').
*+/-[[Amyloid]] deposits - fluffy appearing acellular eosinophilic material in the cytoplasm.
*+/-[[C-cell hyperplasia]] - seen with familial forms of MTC.
**C cells (AKA ''parafollicular cell''): abundant cytoplasm - clear/pale.

Note:
*The amyloid is formed from ''calcitonin''.<ref name=pmid15459123>{{Cite journal | last1 = Khurana | first1 = R. | last2 = Agarwal | first2 = A. | last3 = Bajpai | first3 = VK. | last4 = Verma | first4 = N. | last5 = Sharma | first5 = AK. | last6 = Gupta | first6 = RP. | last7 = Madhusudan | first7 = KP. | title = Unraveling the amyloid associated with human medullary thyroid carcinoma. | journal = Endocrinology | volume = 145 | issue = 12 | pages = 5465-70 | month = Dec | year = 2004 | doi = 10.1210/en.2004-0780 | PMID = 15459123 }}</ref>

Images:
*www:
**[http://jcp.bmj.com/content/vol57/issue3/images/large/cp8474.f16.jpeg Medullary thyroid carcinoma (bmj.com)].
**[http://www.nature.com/ki/journal/v70/n11/fig_tab/5001888f2.html C cell hyperplasia (nature.com)].
**[http://lifesci.rutgers.edu/~babiarz/Review3/Lp6/scope8.htm C cell (rutgers.edu)].
**[http://www.anatomyatlases.org/MicroscopicAnatomy/Images/Plate287.jpg Parafollicular cells (anatomyatlases.org)].
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_low_mag.jpg MTC - low mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_high_mag.jpg MTC - high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_2_-_high_mag.jpg MTC and amyloid - high mag. (WC)].

===IHC===
Features:<ref>URL: [http://pathologyoutlines.com/thyroid.html#medullary http://pathologyoutlines.com/thyroid.html#medullary]. Accessed on: 17 January 2011.</ref>
*[[Calcitonin]] +ve - it arises from C cells (which produce calcitonin).
*Congo-red +ve (amyloid present) - mnemonic: ''CRAP'' -- congo red amyloid protein.
*Neuroendocrine markers.
**[[Chromogranin A]].
**[[Synaptophysin]].
*CEA +ve (often better staining than calcitonin).<ref>SB. 7 January 2010.</ref>
*Thyroglobulin usu. -ve.<ref name=pmid8454270>{{Cite journal | last1 = de Micco | first1 = C. | last2 = Chapel | first2 = F. | last3 = Dor | first3 = AM. | last4 = Garcia | first4 = S. | last5 = Ruf | first5 = J. | last6 = Carayon | first6 = P. | last7 = Henry | first7 = JF. | last8 = Lebreuil | first8 = G. | title = Thyroglobulin in medullary thyroid carcinoma: immunohistochemical study with polyclonal and monoclonal antibodies. | journal = Hum Pathol | volume = 24 | issue = 3 | pages = 256-62 | month = Mar | year = 1993 | doi = | PMID = 8454270 }}</ref>

===EM===
*Neurosecretory granules.
**Feature seen in neuroendocrine tumours.

Images: [http://pathhsw5m54.ucsf.edu/case7/image77.html Neurosecretory granules (ucsf.edu)].

==Anaplastic thyroid carcinoma==
===Epidemiology===
*Very rare.
*Horrible prognosis.
*Often presents with obstruction.
*Typically there is a history of a thyroid mass.

===Microscopic===
Features:
*Cytologically malignant:
**Huge [[NC ratio]].
**Mitoses.
*+/-[[Necrosis]].

Notes:
*May have features of other thyroid carcinomas, e.g. psammoma bodies, papillae, nuclear changes of PTC.

Image: [http://commons.wikimedia.org/wiki/File:Anaplastic_thyroid_carcinoma_low_mag.jpg Anaplastic thyroid carcinoma with a component of papillary thyroid carcinoma (WC)].

DDx:
*[[Poorly differentiated carcinoma of the thyroid|Poorly differentiated carcinoma]].
*[[Squamous cell carcinoma]].
*[[Medullary thyroid carcinoma]].
*Sarcoma.

===IHC===
*Keratin (AE1/AE3) +ve.
*Vimentin +ve, >90%.<ref name=pmid1712540>{{cite journal |author=Ordóñez NG, El-Naggar AK, Hickey RC, Samaan NA |title=Anaplastic thyroid carcinoma. Immunocytochemical study of 32 cases |journal=Am. J. Clin. Pathol. |volume=96 |issue=1 |pages=15–24 |year=1991 |month=July |pmid=1712540 |doi= |url=}}</ref>
*Thyroglobulin - rarely +ve (~15%).<ref name=pmid1712540/>
*CEA -ve, calcitonin -ve; to r/o medullary.
*p53 +ve.
*TTF-1 +ve.

==Lymphomas of the thyroid==
{{Main|Lymphoma}}
===General===
*Rare.
*Increased risk with chronic inflammatory conditions.
*Fit in the the greater category of ''[[MALT lymphoma]]''.

===Microscopic===
Features:
*Lymphoepithelial lesion - '''key feature'''.
*Plasma cells.
*"Overgrowth" - thyroid parenchyma displaced by lymphocytes.

=Weird stuff=
==Hyalinizing trabecular tumour==
*[[AKA]] ''hyalinizing trabecular adenoma''.
*Abbreviated ''HTT''.
===General===
*Considered by some (e.g. Silvia Asa) to be a variant of [[papillary thyroid carcinoma]].<ref name=pmid11117782>{{cite journal |author=Cheung CC, Boerner SL, MacMillan CM, Ramyar L, Asa SL |title=Hyalinizing trabecular tumor of the thyroid: a variant of papillary carcinoma proved by molecular genetics |journal=Am. J. Surg. Pathol. |volume=24 |issue=12 |pages=1622–6 |year=2000 |month=December |pmid=11117782 |doi= |url=}}</ref>
*Behaviour similar to papillary thyroid carcinoma - indolent.

===Microscopic===
Features:
*Trabecular arrangement of cells.
**May have "curved" trabeculae.
*Extracellular space has hyaline material - '''key feature'''.
*Cytoplasm mimics hyaline material in the extracellular space.

Images:
*[http://archive.biomedcentral.com/1742-6413/3/17/figure/F2?highres=y HTT (biomedcentral.com)].<ref name=pmid16867191>{{Cite journal | last1 = Baloch | first1 = ZW. | last2 = Puttaswamy | first2 = K. | last3 = Brose | first3 = M. | last4 = LiVolsi | first4 = VA. | title = Lack of BRAF mutations in hyalinizing trabecular neoplasm. | journal = Cytojournal | volume = 3 | issue = | pages = 17 | month = | year = 2006 | doi = 10.1186/1742-6413-3-17 | PMID = 16867191 }}</ref>
*[http://www.ispub.com/journal/the-internet-journal-of-endocrinology/volume-2-number-1/hyalinizing-trabecular-neoplasm-of-the-thyroid-controversies-in-management.article-g01.fs.jpg HTT (ispub.com)].<ref>URL: [http://www.ispub.com/journal/the-internet-journal-of-endocrinology/volume-2-number-1/hyalinizing-trabecular-neoplasm-of-the-thyroid-controversies-in-management.html http://www.ispub.com/journal/the-internet-journal-of-endocrinology/volume-2-number-1/hyalinizing-trabecular-neoplasm-of-the-thyroid-controversies-in-management.html]. Accessed on: 1 January 2012.</ref>

DDx:
*[[Papillary thyroid carcinoma]] (if one believes this is a separate entity).
*[[Medullary thyroid carcinoma]] - not trabecular, nuclei not [[PTC]]-like.
*[[Paraganglioma]].<ref>URL: [http://path.upmc.edu/cases/case465/dx.html http://path.upmc.edu/cases/case465/dx.html]. Accessed on: 17 January 2011.</ref>

===IHC===
*Thyroglobulin +ve.
*NSE +ve.

==Hürthle cell neoplasm==
*[[AKA]] ''oncocytic neoplasm''.
*Also spelled ''Hurthle cell neoplasm''.

===General===
*Incidence: uncommon.
*This is a general category - includes:
**Hürthle cell adenoma.
**Hürthle cell carcinoma.

*Some advocate ''total thyroidectomy'' for all Hürthle cell neoplasms, as it is difficult to reliably differentiate adenomas and carcinomas.<ref name=pmid9697901>{{Cite journal | last1 = Wasvary | first1 = H. | last2 = Czako | first2 = P. | last3 = Poulik | first3 = J. | last4 = Lucas | first4 = R. | title = Unilateral lobectomy for Hurthle cell adenoma. | journal = Am Surg | volume = 64 | issue = 8 | pages = 729-32; discussion 732-3 | month = Aug | year = 1998 | doi = | PMID = 9697901 }}</ref>
*It can be understood as a special type of ''follicular neoplasm'' (including ''[[follicular thyroid adenoma]]'' and ''[[follicular thyroid carcinoma]]'').<ref name=Ref_EP104>{{Ref EP|104}}</ref>

====Adenoma vs. carcinoma====
Suggestive for carcinoma:<ref name=pmid9697901/>
*Male.
*>4 cm
**Adenomas usu. <3 cm.
Definite for carcinoma:<ref name=pmid9697901/>
*Lymphovascular invasion.
*Capsular invasion.

===Gross===
*Yellow.
*Encapsulated.

===Microscopic===
Features:<ref name=Ref_EP104>{{Ref EP|104}}</ref>
*Oncocytes >= 75% of cells:
**Abundant granular, eosinophilic cytoplasm.
**Round regular nucleus +/- prominent nucleolus.
*+/-Degenerative changes.

Negatives:
*Lack nuclear features of [[papillary thyroid carcinoma]].
*Lack features of [[medullary thyroid carcinoma]].

DDx:<ref name=pmid18684023>{{cite journal |author=Montone KT, Baloch ZW, LiVolsi VA |title=The thyroid Hürthle (oncocytic) cell and its associated pathologic conditions: a surgical pathology and cytopathology review |journal=Arch. Pathol. Lab. Med. |volume=132 |issue=8 |pages=1241–50 |year=2008 |month=August |pmid=18684023 |doi= |url=}}</ref>
*Papillary thyroid carcinoma oncocytic variant.
*Medullary thyroid carcinoma oncocytic variant.
*Others.

==Minocycline associated thyroid pigmentation==
*[[AKA]] ''minocycline thyroid''.

===General===
*Benign pigmentation of the thyroid due to ''minocycline'', an antibiotic.
**Reported at other sites, e.g. [[heart valves]],<ref name=pmid10615019/> coronary arteries.

===Gross===
*Black thyroid.<ref name=pmid2780449>{{Cite journal | last1 = Noble | first1 = JG. | last2 = Christmas | first2 = TJ. | last3 = Chapple | first3 = C. | last4 = Katz | first4 = D. | last5 = Milroy | first5 = EJ. | title = The black thyroid: an unusual finding during neck exploration. | journal = Postgrad Med J | volume = 65 | issue = 759 | pages = 34-5 | month = Jan | year = 1989 | doi = | PMID = 2780449 | PMC = 2429157 }}</ref>

Images:
*[http://images.rheumatology.org/viewphoto.php?albumId=89099&imageId=5231272 Pigmented thyroid gland (rheumatology.org)].
*[http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2004)128%3C355:PQCTIP%3E2.0.CO;2 Minocycline thyroid - gross and microscopic (archivesofpathology.org)].<ref name=pmid14987144>{{Cite journal | last1 = Raghavan | first1 = R. | last2 = Snyder | first2 = WH. | last3 = Sharma | first3 = S. | title = Pathologic quiz case: tumor in pigmented thyroid gland in a young man. Papillary thyroid carcinoma in a minocycline-induced, diffusely pigmented thyroid gland. | journal = Arch Pathol Lab Med | volume = 128 | issue = 3 | pages = 355-6 | month = Mar | year = 2004 | doi = 10.1043/1543-2165(2004)128355:PQCTIP2.0.CO;2 | PMID = 14987144 }}</ref>

===Microscopic===
Features:
*Granular yellow blobs:
**Location:
***Intracytoplasmic in the follicule-lining cells, i.e. follicular cells.
***Intrafollicular.
**Variable size ~0.5-4 micrometers.

Notes:
*Pigment described as ''lipofuscin-like''.<ref name=pmid6435454>{{Cite journal | last1 = Gordon | first1 = G. | last2 = Sparano | first2 = BM. | last3 = Kramer | first3 = AW. | last4 = Kelly | first4 = RG. | last5 = Iatropoulos | first5 = MJ. | title = Thyroid gland pigmentation and minocycline therapy. | journal = Am J Pathol | volume = 117 | issue = 1 | pages = 98-109 | month = Oct | year = 1984 | doi = | PMID = 6435454 | PMC = 1900569 }}</ref>

Images:
*[http://flylib.com/books/2/953/1/html/2/44%20-%20Thyroid_files/DA11C44FF7.png Pigmentation due to minocycline (flylib.com)].<ref>URL: [http://flylib.com/books/en/2.953.1.50/1/ http://flylib.com/books/en/2.953.1.50/1/]. Accessed on: 11 March 2012.</ref>
*[http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2004)128%3C355:PQCTIP%3E2.0.CO;2 Minocycline thyroid - gross and microscopic (archivesofpathology.org)].<ref name=pmid14987144>{{Cite journal | last1 = Raghavan | first1 = R. | last2 = Snyder | first2 = WH. | last3 = Sharma | first3 = S. | title = Pathologic quiz case: tumor in pigmented thyroid gland in a young man. Papillary thyroid carcinoma in a minocycline-induced, diffusely pigmented thyroid gland. | journal = Arch Pathol Lab Med | volume = 128 | issue = 3 | pages = 355-6 | month = Mar | year = 2004 | doi = 10.1043/1543-2165(2004)128355:PQCTIP2.0.CO;2 | PMID = 14987144 }}</ref>

===Stains===
*Fontana-Masson stain +ve.<ref name=pmid10615019>{{Cite journal | last1 = Sant'Ambrogio | first1 = S. | last2 = Connelly | first2 = J. | last3 = DiMaio | first3 = D. | title = Minocycline pigmentation of heart valves. | journal = Cardiovasc Pathol | volume = 8 | issue = 6 | pages = 329-32 | month = | year = | doi = | PMID = 10615019 }}</ref>

=See also=
*[[Thyroid cytopathology]].
*[[Head and neck cytopathology]].
*[[Salivary gland]].
*[[Cytopathology]].

=References=
{{reflist|2}}

[[Category:Endocrine pathology]]

Stains

2013-05-31T17:08:22Z

Ingo: /* Interpretation */

This article deals with '''stains'''. H&E isn't the only stain out there...

=Where to start...=
==Principles==
When considering additional (i.e. special) stains one should (in order) do the following:<ref>LAE. 13 July 2010.</ref>
# Make sure one has exhausted the clinical history; history is considered the best special stain.
# Special stains (below).
# [[Immunohistochemistry]] (dealt with in a separate article).
# Molecular testing, electron microscopy.

==Common stains==
# [[H&E stain]].
# [[PAS stain]].
# [[PAS-D stain]].
# [[AFB stains]], e.g. [[Ziehl-Neelsen stain]].
# [[Congo red]].
# [[GMS stain]].
# [[Gram stain]].

=Immunohistochemistry=
{{main|Immunohistochemistry}}
==General==
*Abbreviated ''IHC''.

==Interpretation==
Simple version:
*Positive is (usually): ''brown''.
*Negative tissue is: ''light blue''.

Important notes:
*One has to know where the target (of the antibody) is supposed to be, i.e. cytoplasm vs. cell membrane.
*The edge of the tissue may have light staining - ''edge effect''.
*If everything is brown... suspect that it didn't work.
*In some situations you're blessed with an ''internal control'', e.g. in renal tumours CD10 will stain [[RCC]] and the ''proximal tubule'', in GISTs - CD117 the [[mast cell]]s are positive.

=Work-up of infection=
It often not possible to be definitive by staining.<ref>{{cite journal |author=Woods GL, Walker DH |title=Detection of infection or infectious agents by use of cytologic and histologic stains |journal=Clin. Microbiol. Rev. |volume=9 |issue=3 |pages=382-404 |year=1996 |month=July |pmid=8809467 |pmc=172900 |doi= |url=http://cmr.asm.org/cgi/pmidlookup?view=long&pmid=8809467}}</ref>

Basic panel:
*Gram stain - for bacteria.
*GMS stain - [[fungi|fungal]] stain.
*PAS (''or'' PAS-D) - fungal stain.

==Fungi==
{{main|Fungi}}

Fungi are a type of [[microorganisms]]. They are seen by pathologist every once in a while.

=Specific stains=
What follows is a big list... of stains.

==Haematoxylin and eosin stain==
===General===
*Abbreviated ''H&E''.
*Standard bearer in most pathology departments.

===Intepretation===
*Blue (haematoxylin) = nucleus.
*Pink (eosin) = cytoplasm.

==Haematoxylin phyloxin saffron stain==
===General===
*Abbreviated ''HPS''.
*An alternative to the ''H&E stain'' - some pathol. departments use this as their standard.

===Interpretation===
*Haematoxylin = blue -- stains nucleus.
*Phyloxin = pink -- stains muscle and cytoplasm.
*Saffron = yellow -- stains collagen.
*An alternative to H&E stain.
**Fibrosis is easier to see on HPS than H&E... as one can see the collagen.

Images:
*[http://commons.wikimedia.org/wiki/File:Perineural_invasion_prostate_high_mag.jpg Perineural invasion - prostate - HPS stain (WC)].
*[http://commons.wikimedia.org/wiki/File:Meningioma_high_mag.jpg Meningioma - HPS stain (WC)].
*[http://commons.wikimedia.org/wiki/File:Endoneurial_fibrosis_-_very_high_mag_-_cropped.jpg Endoneurial fibrosis - HPS stain (WC)].

==Periodic acid Schiff stain==
*Abbreviated ''PAS''.

===Primary application===
*Kidney biopsies, medical.
*Liver biopsies, medical.
**Positive in ''alpha-1 antitrypsin deficiency''.

===Utility===
*Stains - lipofuscin,<ref name=pmid5463681 >{{cite journal |author=Kovi J, Leifer C |title=Lipofuscin pigment accumulation in spontaneous mammary carcinoma of A/Jax mouse |journal=J Natl Med Assoc |volume=62 |issue=4 |pages=287–90 |year=1970 |month=July |pmid=5463681 |pmc=2611776 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2611776/pdf/jnma00512-0077.pdf}}</ref> basement membranes, fungi, glycogen, (neutral) mucin.

===Interpretation===
*Magenta = glycogen, mucin, fungi.
*Blue = nuclei.

Image: [http://commons.wikimedia.org/wiki/File:Metanephric_adenoma_high_mag.jpg Metanephric adenoma - PAS (WC)].

Ref.:<ref>[http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/PAS.PDF http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/PAS.PDF]</ref>

==Periodic acid Schiff with diastase==
*Abbreviated: ''PAS-D'' and ''PASD''.

===General===
*Diastase digests the glycogen.
*"PAS diastase resistant"<ref name=pmid6189389>{{Cite journal | last1 = Qizilbash | first1 = A. | last2 = Young-Pong | first2 = O. | title = Alpha 1 antitrypsin liver disease differential diagnosis of PAS-positive, diastase-resistant globules in liver cells. | journal = Am J Clin Pathol | volume = 79 | issue = 6 | pages = 697-702 | month = Jun | year = 1983 | doi = | PMID = 6189389 }}</ref> ''implies'' PASD +ve and [[PAS stain|PAS]] +ve.

===Use===
*Stains mucin.
*Used to identify glycogen (together with PAS stain).
**Glycogen = clear (digested) on PAS-D.
**Glycogen = magenta on PAS.

Notes: <Ref>[http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/PASD.PDF http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/PASD.PDF]</ref>

==Gomori methenamine-silver stain==
*Abbreviated ''GMS''.

Note:
*''GMS'' is "Grocott's methenamine Silver" according to WMSP.<ref name=Ref_WMSP682>{{Ref WMSP|682}}</ref>

===Use===
*Useful for fungi.
**Pneumocystis jirovecii - cause of [[pneumocystis pneumonia]] (PCP).
**Histoplasma - cause of [[histoplasmosis]].
***Histoplasma = black, round balls.

Image: [http://commons.wikimedia.org/wiki/File:Histoplasma_in_granuloma_gms.jpg GMS showing histoplasma (WC)].

==Acid-fast bacilli stains==
*Abbreviated: ''AFB''.

There are several AFB stains:
*Ziehl-Neelson stain - used to look for ''[[Mycobacterium tuberculosis]]''.
*Fite stain - used to look for ''[[Mycobacterium leprae]]''.<ref>URL: [http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/FITES.PDF http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/FITES.PDF]. Accessed on: 19 May 2011.</ref>
*Auramine-rhodamine stain.

===Ziehl-Neelsen stain===
*Most popular acid-fast bacilli stain.
*Stains other mycobacteria -- not specific for tuberculosis.
**Stains ''Nocardia''.<ref>URL: [http://library.med.utah.edu/WebPath/LUNGHTML/LUNG024.html http://library.med.utah.edu/WebPath/LUNGHTML/LUNG024.html]. Accessed on: 19 May 2011.</ref>

Image: [http://commons.wikimedia.org/wiki/File:Mycobacterium_tuberculosis_Ziehl-Neelsen_stain_02.jpg ZN stain (WC/CDC)].
===Fite stain===
Interpretation:
*Red = AFB.
*Blue = background.

===Auramine-rhodamine stain===
*Fluorescent stain.

Image: [http://commons.wikimedia.org/wiki/File:Cryptosporidium_parvum_auramine-rhodamine_labeled.jpg AR stain (WC/CDC)].

===Kinyoun stain===
*Another AFB stain<ref name=pmid7536216>{{Cite journal | last1 = Kehl | first1 = KS. | last2 = Cicirello | first2 = H. | last3 = Havens | first3 = PL. | title = Comparison of four different methods for detection of Cryptosporidium species. | journal = J Clin Microbiol | volume = 33 | issue = 2 | pages = 416-8 | month = Feb | year = 1995 | doi = | PMID = 7536216 }}</ref> - useful for [[cryptosporidiosis]] and [[microsporidiosis]].<ref name=pmid9003613>{{Cite journal | last1 = Ignatius | first1 = R. | last2 = Lehmann | first2 = M. | last3 = Miksits | first3 = K. | last4 = Regnath | first4 = T. | last5 = Arvand | first5 = M. | last6 = Engelmann | first6 = E. | last7 = Futh | first7 = U. | last8 = Hahn | first8 = H. | last9 = Wagner | first9 = J. | title = A new acid-fast trichrome stain for simultaneous detection of Cryptosporidium parvum and microsporidial species in stool specimens. | journal = J Clin Microbiol | volume = 35 | issue = 2 | pages = 446-9 | month = Feb | year = 1997 | doi = | PMID = 9003613 }}
</ref>

==Congo red stain==
===Use===
*Used to look for [[amyloid]].
**Mnemonic: ''CRAP'' = congo red amyloid protein.
*An alternate stain for amyloid is ''Thioflavin T''.

Note:
*Thick sections (~10 micrometers) are considered a requirement for the stain to work properly.<ref>URL: [http://www.ihcworld.com/_protocols/special_stains/congo_red_bennhold.htm http://www.ihcworld.com/_protocols/special_stains/congo_red_bennhold.htm]. Accessed on: 26 January 2012.</ref>
**If the section is too thin... it doesn't work.

===Interpretation===
*Amyloid = pink/red.
*Nuclei = blue.

Ref.:<ref>URL: [http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/CONGORED.PDF http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/CONGORED.PDF]. Accessed on: 4 December 2010.</ref>

Image:
*[http://commons.wikimedia.org/wiki/File:Cerebral_amyloid_angiopathy_-_very_high_mag.jpg Congo red stain - cerebral amyloid angiopathy (WC)].

==Thioflavin T stain==
===Use===
*Used to look for [[amyloid]].

===Interpretation===
*Amyloid = green.

Image: [http://inano.au.dk/research/annual-reports/annual-report-2004/7-cases/protein-fibrils/ Amyloid (inano.au.dk)].

==Gram stain==
===Use===
*"It is useless for finding bacteria."<ref>St. Michael's Hospital - Stains Handout.</ref>
**If they are to be seen... they'll be visible on H&E.

Note:
*Microbiology is better at finding organisms than pathology.
**They have one significant advantage -- if a small amount of bugs are present... they grows into a large (obviously visible) colony.

====DDx for common patterns====
A short list of bacteria and their characteristics:<ref>URL: [http://www.atsu.edu/faculty/chamberlain/Website/pnebact.htm http://www.atsu.edu/faculty/chamberlain/Website/pnebact.htm]. Accessed on: 7 May 2013.</ref>
{| class="wikitable sortable"
! Shape\Gram stain
! Positive
! Negative
! Variable or negative
|-
| Bacilli
| Clostridium difficile, Bacillus anthracis, Nocardia spp.
| Escherichia coli, [[Helicobacter pylori]], Yersinia pestis, Hemophilus influenzae
| [[Tuberculosis|Mycobacterium tuberulosis]], Legionella pneumophila<ref>URL: [http://meded.ucsd.edu/isp/1999/CAP/legion.html http://meded.ucsd.edu/isp/1999/CAP/legion.html]. Accessed on: 7 May 2013.</ref>
|-
| Cocci
| Streptococcus pneumoniae, Staphylococcus aureus
| Neisseria meningitidis, Moraxella catarrhalis
|}

===Interpretation===
*Purple (or blue) = Gram positive organisms.
*Red = Gram negative organisms, nuclei.<ref>URL: [http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/GRAM.PDF http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/GRAM.PDF]. Accessed on: 7 May 2013.</ref>
*Yellow = background.

Notes:
*Many of the bacteria are quite small relative to lymphocytes; ''Escherichia coli'' is 1-2 micrometers long x 0.25 micrometers in diameter.<ref>URL: [http://www.lpi.usra.edu/publications/slidesets/marslife/slide_27.html http://www.lpi.usra.edu/publications/slidesets/marslife/slide_27.html].</ref>
*Epithelial cell nuclei & stromal cell nuclei may stain red.
*Memory device: '''p'''urple = '''p'''ositive.

Images:
*[http://commons.wikimedia.org/wiki/File:Gram_stain_01.jpg Gram positive cocci (WC)].
*[http://commons.wikimedia.org/wiki/File:Gram_Stain_Anthrax.jpg Gram positive rods - anthrax (WC)].

==Luxol fast blue stain==
*Abbreviated ''LFB''.

===Use===
*Neuropathology, myelin stain.

===Intepretation===
*Blue = myelinated fibers (contain lipoproteins), lipofuscin.<ref>MUN. 26 November 2010.</ref>
**Lack of blue (where it ought to be) = demyelination.
*Purple = nerve cell (e.g. neuron).
*Neutrophils = pink.

Image: [http://en.wikipedia.org/wiki/File:Globus_pallidus_and_putamen_-_very_low_mag.jpg Globus pallidus and putamen - H&E-LFB (WC)].

Ref.:<ref>[http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/LFB.PDF http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/LFB.PDF]</ref>

==Giemsa stain==
===Use===
*Useful for finding [[mast cell]]s.
*Useful for finding ''[[Donovan bodies]]'' and ''[[Leishmania]]''.<ref>URL: [http://library.med.utah.edu/WebPath/HISTHTML/STAINS/STAINS.html http://library.med.utah.edu/WebPath/HISTHTML/STAINS/STAINS.html]. Accessed on: April 6, 2009.</ref>

===Interpretation===
*Tissue is light blue/green.

==Reticulin stain==
===Use===
*Liver biopsy, medical.
**Demonstrates the reticular fibers (in [[cirrhosis]] the fibers are disrupted).
*Before IHC, reticulin was used to differentiate ''sarcomas'' from ''carcinomas'':<ref name=pmid13536209>{{cite journal |author=MACKENZIE DH |title=Reticulin patterns in the diagnosis of carcinomas and sarcomas |journal=Br. J. Cancer |volume=12 |issue=1 |pages=14–9 |year=1958 |month=March |pmid=13536209 |pmc=2074006 |doi= |url=}}</ref>
**Sarcomas have reticulin around ''each'' cell.
**Carcinomas have reticulin around clusters of cells.

===Interpretation===
*Black = reticular fibers.
*Red = nuclei.

Notes:<ref>[http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/RETIC.PDF http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/RETIC.PDF]</ref>

==Cresyl violet stain==
===Use===
*Used at some places (e.g. SMH) to look for Helicobacter organisms.

===Interpretation===
*Everything is shades of blue.
**Helicobacter stains blue.

==Prussian blue stain==
*AKA ''Perl's iron stain''.
===Use===
*Useful for iron and hemosiderin; useful for differentiating brown pigments (melanin, lipofuscin, tattoo pigment, hemosiderin).

===Interpretation===
*Blue = iron.

Image:
*[http://education.vetmed.vt.edu/curriculum/VM8054/labs/Lab2/Examples/exprussb.htm Prussian blue stain - hemosiderin (vetmed.vt.edu)].

Notes:
*Described well by ''vetmed.vt.edu''.<ref>Prussian blue stain. URL:[http://education.vetmed.vt.edu/curriculum/VM8054/labs/Lab2/Examples/exprussb.htm [http://education.vetmed.vt.edu/curriculum/VM8054/labs/Lab2/Examples/exprussb.htm]. Accessed on: 5 May 2010.</ref>
*DDx of brown pigment: Fontana-Masson (melanin), Kluver-Barrera stain (lipofuscin).

==Kluver-Barrera stain==
Combination of:
*Luxol Fast Blue,
*Cresyl Violet,
*Special component for lipofuscin.

===Use===
*Useful for differentiating brown pigments (melanin, lipofuscin, tattoo pigment, hemosiderin).
**Stains lipofuscin.

Notes:
*[[PAS stain|PAS]] also stains lipofuscin and is more commonly available.

===Interpretation===
*Blue pigmented granules = lipofuscin.

Notes:
*Described well by ''vetmed.vt.edu''.<ref>Kluver-Barrera stain. URL:[http://education.vetmed.vt.edu/curriculum/VM8054/labs/Lab2/Examples/exkluvbarr.htm http://education.vetmed.vt.edu/curriculum/VM8054/labs/Lab2/Examples/exkluvbarr.htm]. Accessed on: 5 May 2010.</ref>
*DDx of brown pigment: Fontana-Masson (melanin), Prussian blue stain (hemosiderin).

==Oil red O stain==
===Use===
*Stain adipose tissue.

Notes:
*Must be done on fresh tissue, i.e. it cannot be fixed in [[formalin]].

==Warthin-Starry stain==
Background:
*Developed by a bunch of pathologists in Michigan to look for spirochetes.<ref>URL: [http://www.merriam-webster.com/medical/warthin http://www.merriam-webster.com/medical/warthin]. Accessed on: 17 August 2010.</ref>

===Use===
*Find spirochetes, e.g. [[syphilis]] (Treponema pallidum),<ref>URL: [http://library.med.utah.edu/WebPath/HISTHTML/STAINS/STAINS.html http://library.med.utah.edu/WebPath/HISTHTML/STAINS/STAINS.html]. Accessed on: April 6, 2009.</ref> cat-scratch disease (Bartonella henselae).
*Find Helicobacter spp., e.g. Helicobacter pylori -- Mount Sinai Hospital.<ref>[http://www.dako.co.uk/index/prod_search/prod_products.htm?productareaid=41&baseprodidver=A224462007 http://www.dako.co.uk/index/prod_search/prod_products.htm?productareaid=41&baseprodidver=A224462007]</ref>

Interpretation:<ref>[http://library.med.utah.edu/WebPath/HISTHTML/STAINS/STAIN029.html http://library.med.utah.edu/WebPath/HISTHTML/STAINS/STAIN029.html]</ref>
*Spirochetes - black.
*Background - yellow.

Image:
*[http://commons.wikimedia.org/wiki/File:Pylorigastritis.jpg Helicobacter gastritis - Warthin-Starry stain (WC)].

Notes:
*Considered a "dirty" stain - picks-up junk in the background.<ref>DB. 4 August 2010.</ref>

==Dieterle stain==
Considered a variant of the ''Steiner stain''.<ref>URL: [http://www.mayomedicallaboratories.com/test-catalog/Overview/80327 http://www.mayomedicallaboratories.com/test-catalog/Overview/80327]. Accessed on: 8 August 2010.</ref>
===Use===
*Find spirochetes, e.g. [[syphilis]] (Treponema pallidum),<ref name=Ref_WMSP455>{{Ref WMSP|455}}</ref> donovan bodies (leishmaniasis),<ref>URL: [http://www.mondofacto.com/facts/dictionary?Dieterle%27s+stain http://www.mondofacto.com/facts/dictionary?Dieterle%27s+stain]. Accessed on: 4 August 2010.</ref> Helicobacter pylori and Bartonella henselae (Cat-scratch disease).<ref>URL: [http://www.mayomedicallaboratories.com/test-catalog/Overview/80327 http://www.mayomedicallaboratories.com/test-catalog/Overview/80327]. Accessed on: 8 August 2010.</ref>

===Interpretation===
*Spirochetes - black.
*Background - yellow.

Images: [http://en.wikipedia.org/wiki/File:Treponema_pallidum_-_very_high_mag_-_extreme_crop.jpg Dieterle stain - T. pallidum (WC)], [http://pathmicro.med.sc.edu/trepo.jpg Treponema (med.sc.edu)], [http://pathmicro.med.sc.edu/fox/spiro-neisseria.htm Spirochetes - several images (med.sc.edu)].

==Bielschowsky stain==
Abbreviated: ''Biel stain''.

===Use===
*Stains glial tissue, i.e. brain.
**Demonstrates neurofibrillary tangles, senile plaques (as in Alzheimer's disease).

===Interpretation===
*Black = axons, tangles, plaques.
*Brown/dark brown = plaque, vascular amyloid.
*Yellow/brown = other.

Image: [http://commons.wikimedia.org/wiki/File:Cerebellum_-_biel_-_very_high_mag.jpg Bielschowsky stain (WC)].

Ref.: <ref>[http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/BIELSCH.PDF http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/BIELSCH.PDF]</ref>

==Mucicarmine stain==
*Stains some mucins... uses the dye ''carmine''.

===Use===
*Identify mucin.
*Malignant cells that produce mucin... carcinomas.<ref name=Ref_APBR681>{{Ref APBR|681 (Q25)}}</ref>

===Interpretation===
*Carmine with metanil yellow and Weigert's Hematoxylin:<ref name=Ref_WMSP678>{{Ref WMSP|678}}</ref>
**Blue/black = nucleus.
**Yellow = background.
**Red = mucin.<ref>[http://www.medschool.lsuhsc.edu/pathology/pathist/SURGPATH/special%20stains/assets/mucicarmine3.jpg http://www.medschool.lsuhsc.edu/pathology/pathist/SURGPATH/special%20stains/assets/mucicarmine3.jpg]</ref>

Images:
*[http://www.medschool.lsuhsc.edu/pathology/pathist/SURGPATH/special%20stains/Pages/page6.htm Mucicarmine stained bowel (medschool.lsuhsc.edu)].
*[http://www.nature.com/modpathol/journal/v14/n5/fig_tab/3880332f4.html Mucicarmine stained pancreatic adenosquamous carcinoma (nature.com)].

==Alcian blue stain==
===General===
*Stains acidic mucin (pH=2.5); '''A'''lcian blue = '''A'''cidic.
**A variant uses pH=1.0.<ref name=Ref_WMSP682>{{Ref WMSP|682}}</ref>

Note:
*''Alcian blue'' (not otherwise specified) usu. refers to the pH=2.5.<ref>URL: [http://www.pathologyoutlines.com/topic/stainsalcianblue.html http://www.pathologyoutlines.com/topic/stainsalcianblue.html]. Accessed on: 11 October 2012.</ref>

===Use===
*Identify ''intestinal metaplasia'' in the [[stomach]] -- goblets = blue.

===Interpretation===
*Blue = acidic mucins.<ref>URL: [http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/ALCIAN.PDF http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/ALCIAN.PDF]. Accessed on: 20 December 2011.</ref>

Notes:
*Mucin stains:
**[[Alcian blue stain]], [[PASD stain]], [[Mucicarmine stain]].

==Movat's stain==
===Use===
*''[[Myxomatous degeneration]]'' of cardiac valves.

===Components===
*Acid fuchsin, alcian blue, crocein scarlet, elastic hematoxylin, and saffron.<ref>[http://www.mayomedicallaboratories.com/test-catalog/Overview/9832]</ref><ref name=penn_med>Modified Movat's Pentachrome Stain. University Penn Medicine. URL: [http://www.med.upenn.edu/mcrc/histology_core/movat.shtml http://www.med.upenn.edu/mcrc/histology_core/movat.shtml]. Accessed on: January 29, 2009.</ref>

===Interpretation of Movat stain===
*Black = nuclei and elastic fibers.
*Yellow = collagen and reticular fibers.
*Blue = mucin, ground substance.
*Red (intense) = fibrin.
*Red = muscle.
Reference: <ref name=penn_med/>

How to remember? A.: Primary colours (red, blue, yellow) + black.

Images:
*[http://commons.wikimedia.org/wiki/File:Cardiac_amyloidosis_very_high_mag_movat.jpg Cardiac amyloidosis - Movat stain (WC)].
*[http://commons.wikimedia.org/wiki/File:Cystic_medial_degeneration_-_movat_-_low_mag.jpg Cystic medial degeneration - Movat stain - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Cystic_medial_degeneration_-_movat_-_intermed_mag.jpg Cystic medial degeneration - Movat stain - intermed. mag. (WC)].

==Masson's trichrome stain==
*Should '''not''' be confused with the ''[[Mallory trichrome stain]]''.
*May be referred to as ''[[trichrome stain]]''.
===General===
*Collagen vs. muscle.

===Interpretation===
*Black = nuclei.
*Red = muscle (smooth muscle actin).
*Baby blue = collagen.

Notes: <Ref>ULR: [http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/MASSONS.PDF http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/MASSONS.PDF]. Accessed on: 2 November 2011.</ref>

===Elastic trichrome stain===
General:
*"Elastic trichrome" is one important variant of ''Masson's trichrome''.

Interpretation - as above in Masson's trichrome - plus:
*Black = nuclei and '''elastin'''.

==Mallory trichome stain==
*Should '''not''' be confused with ''[[Masson trichrome stain]]''.
*May be referred to as ''[[trichrome stain]]''.

===General===
*Collagen vs. muscle.
*May be done with elastin.

===Site===
*Kidney Bx (to assess for fibrosis).
**Considered better than the [[Masson trichrome stain]].
*Liver Bx (to assess for [[cirrhosis]]).
*Cardiovascular/lung (to see differentiate the layers of the arteries, and arteries from veins).

===Interpretation===
*Black = nuclei.
*Red = muscle (smooth muscle actin).
*Green = collagen.

Image:
*[http://commons.wikimedia.org/wiki/File:Cirrhosis_high_mag.jpg Mallory trichrome (WC)].

==Haematoxylin orcein phyloxin saffron stain==
*Abbreviated ''HOPS''.<ref name=pmid1636194>{{cite journal |author=Perry JR, Bilbao JM, Gray T |title=Fatal basilar vasculopathy complicating bacterial meningitis |journal=Stroke |volume=23 |issue=8 |pages=1175–8 |year=1992 |pmid=1636194 |doi=}} [http://stroke.ahajournals.org/cgi/reprint/23/8/1175.pdf Free Full Text].</ref>
*It should ''not'' be confused with the ''[[HPS stain]]''.

===Interpretation===
*Blue (haematoxylin) = nuclei.
*Black (orcein) = elastin.
*Red (phyloxin) = muscle.
*Yellow (saffron) = collagen.

==Jones stain==
*AKA ''PAS methenamine technique''.<ref name=pmid>{{Cite journal | last1 = Jones | first1 = DB. | title = Nephrotic glomerulonephritis. | journal = Am J Pathol | volume = 33 | issue = 2 | pages = 313-29 | month = | year = | doi = | PMID = 13402889 | PMC = 1934622 }}</ref>
*[[AKA]] ''Methenamine PAS'', abbreviated ''MPAS''.

===Use===
*Visualize basement membrane in kidney biopsies.
**Especially useful for the diagnosis of [[membranous nephropathy]] (MN).

===Interpretation===
*Black = basement membrane.
*Blue = nuclei.
*Pink = other structures/background.

Notes:<ref>URL: [http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/JONES.PDF http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/JONES.PDF]. Accessed on: 19 May 2011.</ref>

Images:
*[http://commons.wikimedia.org/wiki/File:Membranous_nephropathy_-_mpas_-_very_high_mag.jpg MN demonstrated with a MPAS - very high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Membranous_nephropathy_-_cropped_-_mpas_-_very_high_mag.jpg MN demonstrated with a MPAS - very high mag. (WC)].

==Hale's colloidal iron stain==
===Use===
*[[Chromophobe renal cell carcinoma]] vs. [[renal oncocytoma]] - chromophobe [[renal cell carcinoma]] +ve.<ref name=pmid9537468>{{cite journal |author=Tickoo SK, Amin MB, Zarbo RJ |title=Colloidal iron staining in renal epithelial neoplasms, including chromophobe renal cell carcinoma: emphasis on technique and patterns of staining |journal=Am. J. Surg. Pathol. |volume=22 |issue=4 |pages=419–24 |year=1998 |month=April |pmid=9537468 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0147-5185&volume=22&issue=4&spage=419}}</ref>

Notes:

===Interpretation===
*Blue (granular cytoplasmic) staining is positive.<ref name=Ref_WMSP682>{{Ref WMSP|682}}</ref>

Images:
*[http://www.ultrapath.org/oldsite/cases99/sep99/images/figure-3.jpg ChRCC Hale's colloidal iron (ultrapath.org)].<ref>URL: [http://www.ultrapath.org/oldsite/cases99/sep99/cotm9-2.html http://www.ultrapath.org/oldsite/cases99/sep99/cotm9-2.html]. Accessed on: 9 October 2011.</ref>
*[http://www.diagnosticpathology.org/content/4/1/21/figure/f1?highres=n ChRCC Hale's colloidal iron (diagnosticpathology.org)].

Notes:
*Often described as a "fastidious" (difficult/demanding) stain.<ref>URL: [http://www.merriam-webster.com/dictionary/fastidious?show=0&t=1319550566 http://www.merriam-webster.com/dictionary/fastidious?show=0&t=1319550566]. Accessed on: 25 October 2011.</ref>
**A few staff think this is a totally useless stain.<ref>ALS. On several occasions in 2009.</ref>

==von Kossa stain==
===Use===
*Look for calcium.

===Interpretation===
*Black = calcium.<ref name=Ref_WMSP682>{{Ref WMSP|682}}</ref>

==Toluidine blue stain==
===Use===
*May be useful in kidney biopsies.<ref name=pmid16799480>{{cite journal |author=Fischer EG, Moore MJ, Lager DJ |title=Fabry disease: a morphologic study of 11 cases |journal=Mod. Pathol. |volume=19 |issue=10 |pages=1295–301 |year=2006 |month=October |pmid=16799480 |doi=10.1038/modpathol.3800634 |url=http://www.nature.com/modpathol/journal/v19/n10/abs/3800634a.html}}</ref><ref name=pmid21659728>{{Cite journal | last1 = Nicholas | first1 = SB. | last2 = Basgen | first2 = JM. | last3 = Sinha | first3 = S. | title = Using stereologic techniques for podocyte counting in the mouse: shifting the paradigm. | journal = Am J Nephrol | volume = 33 Suppl 1 | issue = | pages = 1-7 | month = | year = 2011 | doi = 10.1159/000327564 | PMID = 21659728 }}</ref>
*Stains [[mast cell]]s, [[pneumocystis jirovecii]].

===Interpretation===
*Dark blue - nuclei, mast cell granules (darker than nuclei).
*Light blue - cytoplasm.
*Red/magneta - cartilage. (???)

Refs: looks a bit sketchy<ref>URL: [http://www.molecularstation.com/protocol-links/articles/Toluidine-Blue-Stain-32.html http://www.molecularstation.com/protocol-links/articles/Toluidine-Blue-Stain-32.html]. Accessed on: 17 March 2011.</ref>, <ref>URL: [http://www.dermnetnz.org/doctors/dermatopathology/stains.html http://www.dermnetnz.org/doctors/dermatopathology/stains.html]. Accessed on: 17 March 2011.</ref>

Image:
*[http://commons.wikimedia.org/wiki/File:Smear_of_Pneumocystis_carinii._Toluidine_blue_stain_PHIL_596_lores.jpg PCP stained with toluidine blue (mediawiki.org)].
*[http://www.biomedcentral.com/1471-2407/5/121/figure/F3?highres=y Mast cells stained with toluidine blue (biomedcentral.com)].

==Romanowsky stain==
*Occasionally spelled ''Romanowski''.
*Many variants of this stain exist.
*Specimens are air-dried.

Interpretation:<ref>{{cite journal |author=Horobin RW, Walter KJ |title=Understanding Romanowsky staining. I: The Romanowsky-Giemsa effect in blood smears |journal=Histochemistry |volume=86 |issue=3 |pages=331–6 |year=1987 |pmid=2437082 |doi= |url=http://www.springerlink.com/content/r81x25451m841866/}}</ref>
*Red - RBCs, eosinophil granules.
*Blue (basophilic) - lymphocyte cytoplasm.
*Purple - nuclear chromatin, neutrophil granules, platelets.

===Field stain===
*Variant of the ''Romanowsky stain'' for rapid processing.
*Tends to "blow-up" cell, i.e. cells are larger vis-a-vis ''[[Pap stain]]''.

===Diff-Quik===
:Pronounced ''Diff-Quick''.
*Proprietary variant of ''Romanowsky stain''.<ref>URL: [http://www.ihcworld.com/_protocols/special_stains/diff_quick_ellis.htm http://www.ihcworld.com/_protocols/special_stains/diff_quick_ellis.htm]. Accessed on: 4 January 2010.</ref>

Uses:
*[[Cytopathology]].
*[[Helicobacter gastritis]] - organisms are dark blue against a light blue background.<ref>URL: [http://www.ihcworld.com/_protocols/special_stains/diff_quick_ellis.htm http://www.ihcworld.com/_protocols/special_stains/diff_quick_ellis.htm]. Accessed on: 30 August 2012.</ref>

===Wright stain===
*A variant of the ''Romanowsky stain''; popular in North American.

Use:
*Blood films.

===May-Grünwald-Giemsa stain===
*A variant of the ''Romanowsky stain''; popular in Europe.
*Abbreviated ''MGG''.

Use:
*Blood films.
*Cytopathology.

==Papanicolaou stain==
*Often abbreviated ''Pap stain''.
*Can be thought of as the H&E of cytopathology.
**It is a modified [[H&E stain]].
*Specimens are fixed in ethanol.
*Good for seeing nuclear detail.
*Out-of-focus cytoplasm is translucent; allows one to focus overlapped cells in different planes.

===Use===
*Cytopathology.

===Interpretation===
*Blue/purple = nucleus.
*Green/pink = cytoplasm.
*Orange = keratin.

Image:
*[http://commons.wikimedia.org/wiki/File:Urine_citology_urothelial_carcinoma_2.jpg Pap stain - urine cytology (wikimedia.org)].

==Fontana-Masson stain==
*[[AKA]] ''Masson-Fontana stain'',<ref name=pmid16081962>{{Cite journal | last1 = Gaitanis | first1 = G. | last2 = Chasapi | first2 = V. | last3 = Velegraki | first3 = A. | title = Novel application of the masson-fontana stain for demonstrating Malassezia species melanin-like pigment production in vitro and in clinical specimens. | journal = J Clin Microbiol | volume = 43 | issue = 8 | pages = 4147-51 | month = Aug | year = 2005 | doi = 10.1128/JCM.43.8.4147-4151.2005 | PMID = 16081962 }}</ref> ''Fontana-Masson stain for melanin'', ''melanin stain''.
*A type of silver stain.

Stains:
#Melanin.
#"Argentaffin granules" of the digestive tract.
#Pigment deposition due to minocycline treatment.<ref name=pmid15605966>{{Cite journal | last1 = Patterson | first1 = JW. | last2 = Wilson | first2 = B. | last3 = Wick | first3 = MR. | last4 = Heath | first4 = C. | title = Hyperpigmented scar due to minocycline therapy. | journal = Cutis | volume = 74 | issue = 5 | pages = 293-8 | month = Nov | year = 2004 | doi = | PMID = 15605966 }}</ref>

===Use===
*Stain for melanin.
**Used to differentiate brown pigments (lipofuscin, hemosiderin, melanin).<ref>URL: [http://education.vetmed.vt.edu/curriculum/VM8054/labs/Lab2/Examples/exfontana.htm http://education.vetmed.vt.edu/curriculum/VM8054/labs/Lab2/Examples/exfontana.htm]. Accessed on: 5 May 2010.</ref>
***Many pathologists prefer IHC, i.e. ''Melan A'' over this stain.

Image:
*[http://education.vetmed.vt.edu/curriculum/VM8054/labs/Lab2/Examples/exfontana.htm Fontana-Masson stain (vetmed.vt.edu)].

==Schmorl's stain==
*Stains melanin.
**Similar to ''Fontana-Masson stain''.

Notes:<ref>URL: [http://library.med.utah.edu/WebPath/HISTHTML/STAINS/STAINS.html http://library.med.utah.edu/WebPath/HISTHTML/STAINS/STAINS.html]. Accessed on: 5 May 2010.</ref>

==Martius scarlet blue stain==
===General===
*Stains connective tissue and fibrin.<ref>URL: [http://www.bris.ac.uk/vetpath/cpl/msb.html http://www.bris.ac.uk/vetpath/cpl/msb.html]. Accessed on: 26 November 2010.</ref>
*Abbreviated ''MSB''.

Use:
*Look for fibrinoid [[necrosis]] in [[vasculitis]].
===Interpretation===
*Muscle and fibrin - red.
*Nuclei = brown/black.
*Collagen - blue.
*Red blood cells - yellow.

Image:
*[http://www.bris.ac.uk/vetpath/cpl/msb.jpg MSB (bris.ac.uk)].

Ref.:<ref>URL: [http://www.bris.ac.uk/vetpath/cpl/msb.html http://www.bris.ac.uk/vetpath/cpl/msb.html]. Accessed on: 26 November 2010.</ref>

==Picro-Mallory stain==
===General===
*Find fibrin.

===Interpretation<ref>{{cite web |url=http://stainsfile.info/StainsFile/stain/fibrin/picro-mallory-1.htm |title=Picro-Mallory for Fibrin – Long Version |author= |date= |work= |publisher= |accessdate=17 January 2011}}</ref>===
* Fibrin = red.
* Erythrocytes = yellow.
* Connective tissue = blue.

Image:
*[http://4.bp.blogspot.com/_rlWIjG4vffU/S3FC7BNIJHI/AAAAAAAACDc/XfOz9X_bvbY/s1600-h/publicado+lengua%233.jpg Picro-Mallary (blogspot.com)].

==Verhoeff-van Gieson stain==
*[[AKA]] Elastic van Gieson stain, abbreviated ''EVG''.
===General===
*Similar to ''Masson Trichrome & Verhoeff stain''.<ref>URL: [http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab2/Examples/exvrmass.htm http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab2/Examples/exvrmass.htm]. Accessed on: 3 January 2011.</ref>

Use:
*Examine large blood vessels.<ref>URL: [http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab2/Examples/exvvg.htm http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab2/Examples/exvvg.htm]. Accessed on: 3 January 2011.</ref>

===Interpretation===
*Elastin = black.
*Collagen = bright red.
*Muscle = dull red.

==Copper stain==
===General===
*Used in liver biopsies.
*May be seen in [[Wilson's disease]].

Note:
*Copper staining is a non-specific finding seen in many liver diseases; it is associated with impaired bile secretion.<ref name=pmid2464523>{{cite journal |author=Miyamura H, Nakanuma Y, Kono N |title=Survey of copper granules in liver biopsy specimens from various liver abnormalities other than Wilson's disease and biliary diseases |journal=Gastroenterol. Jpn. |volume=23 |issue=6 |pages=633–8 |year=1988 |month=December |pmid=2464523 |doi= |url=}}</ref>

===Interpretation===
*Copper = red granules.

Images:
*[http://www.naika.or.jp/im2/42/10/figs/14/fig1.jpg Wilson's disease (naika.or.jp)].<ref>URL: [http://www.naika.or.jp/im2/42/10/14c.aspx http://www.naika.or.jp/im2/42/10/14c.aspx]. Accessed on: 24 January 2011.</ref>

==Shikata stain==
*[[AKA]] Orcein stain for copper-protein.
*[[AKA]] Shikata-Cu,<ref>[http://www.mayomedicallaboratories.com/test-catalog/Overview/9836 http://www.mayomedicallaboratories.com/test-catalog/Overview/9836]. Accessed on: 24 January 2011.</ref>
*[[AKA]] Shikata's orcein staining.<ref>URL: [http://informahealthcare.com/doi/abs/10.3109/00313027709085239?journalCode=pat http://informahealthcare.com/doi/abs/10.3109/00313027709085239?journalCode=pat]. Accessed on: 24 January 2011.</ref>

===General===
*Used in [[medical liver disease|medical liver]] biopsies - used to find copper.

===Interpretation===
Features:<ref>URL: [http://www.nottingham.ac.uk/pathology/protocols/shikata.html http://www.nottingham.ac.uk/pathology/protocols/shikata.html]. Accessed on: 24 January 2011.</ref>
*Purple/brown = elastin fibres.
*Red = nuclei.
*Light purple = background
*??? = Copper associated protein.

=See also=
*[[Immunohistochemistry]].
*[[Basics]].

=References=
{{reflist|2}}

=External links=
*[http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/MANUALS.html Procedure manuals] - med.utah.edu.
*[http://library.med.utah.edu/WebPath/HISTHTML/STAINS/STAINS.html Special stains (introduction)] - med.utah.edu.
*[http://www.histology-world.com/stains/stains.htm Stains] - histology-world.com.

[[Category:Basics]]
[[Category:Stains|Stains]]