Libre Pathology - User contributions [en]

Cytopathology

2018-03-08T03:38:15Z

Kaitlin: /* Principles of FNA */

[[Image:Serous carcinoma 2c - cytology.gif | thumb| right|An animation showing two [[micrograph]]s in different planes of focus of a cytopathology specimen with [[serous carcinoma]]. (WC)]]
[[Image:Granulomatous inflammation - alt -- high mag.jpg|thumb|right|Granulomatous inflammation in the hilum of lung. [[Diff-Quik stain]].]]
'''Cytopathology''', often called ''cytology'', is the study of pathologic changes in cells.

Specimen types include exfoliated cervical cytology (Pap tests), urine, body cavity fluids (pleural, pericardial, and peritoneal), cerebrospinal fluid, and fine needle aspirations from any body site, among others. These are often collected by minimally invasive means.

Cytologic preparation methods usually include viewing single cells or small clusters of cells on slides, in contrast to surgical biopsy specimens that usually include larger pieces of tissue, with tissue architecture. In some institutions, small tissue biopsies such as core needle biopsies may also be assigned to the cytology service.

It is often divided into ''[[gynecologic cytology|gynecologic]]'' and ''non-gynecologic''. ''Gynecologic'' in this context usually refers to Pap test specimens, i.e. uterine cervix, vaginal vault; other gynecologic specimens are considered ''non-gynecologic''.

=Slide-marking conventions=
Conventions are important for facilitating communication between various team members.

Common conventions:<ref>UHN Screening process. PCY50001.08.</ref>
*The slide is placed with the label on the right hand side.
*"Marks-of-interest", e.g. dots, are place above the field of interest (when viewed through a microscope - that does not correct for image inversion).
**Microscopes used for surgical pathology, generally, do not correct for image inversion.
***The "marks-of-interest" appear below the field of interest when the slide is viewed with the naked eye.

Marks-of-interest:
*Dot - region of interest.
*Inverted "V" - transformation zone (in cervical cytology specimen).
*Inverted "Y" - benign finding.

Notes:
*Image inversion in the microscope comes about as light travels in a straight line.
*Marks should draw attention to the best examples of the highest grade lesion present.
**More than 7 marks on slide is generally considered excessive.

=Dictums of cytopathology=
*Malignant cells are malignant because they have malignant features.
*Benign cells are benign because they lack malignant features and have benign features.

Corollaries:
*Cells lacking malignant features are '''not''' malignant.
*Cells lacking benign features are '''not''' malignant.

===Cytologic features of malignancy===
Cytologic features of malignancy:
#High nuclear-to-cytoplasmic ratio.
#Nuclear membrane irregularities.
#*Notches/sharp discontinuities.
#Chromatin abnormalities.
#*Clumped chromatin, esp. differences between quadrants of a nucleus.
#*Chromatin clumping at the nuclear membrane (chromatin margination).
#Hyperchromatic nucleus (when compared to other cells).
#Nuclear pleomorphism (comparison of neighbouring cells).
#*Def'n: variable ''staining, shape, and size''.

Notes:
*Not all features of malignancy will be present in one cell.<ref>WG. 19 February 2010.</ref>

=Cell types=
WG's cell typing guide:<ref>WG. 6 January 2010.</ref>
{| class="wikitable sortable"
|-
! Cell type
! Nucleus location
! Nucleus shape
! Cytoplasm
! Chromatin
! Nucleoli
! Other
! Architecture
|-
| Squamous
| Center
| Oval/Spindle
| Solid/dense
| Coarse
| Absent
| Squamous pearls, streaming
| Streaming
|-
| Secretory/ glandular (adenocarcinoma)
| Eccentric
| Oval
| Vacuoles
| Fine
| Present
| Columnar
| Acini (glandular structures), (true) papillae
|-
| Neuroendocrine
| Center (?)
| Oval
| Fine granules (neuroendocrine granules - seen on Romanowsky type stains)
| Reticulated "stippled"
| Absent
| Perinuclear blue bodies (not seen in lymphoid cells)
| Clusters, may appear dyscohesive
|-
| Lymphoid
| Eccentric
| Oval
| Very scant, basophilic
| Coarse
| Usually absent
| Lymphoglandular bodies, dyscohesive
| Single cells
|-
| Germ cell
| Central/variable
| Oval
| Variable
| Variable
| (?), present in seminoma
| Tigroid background in seminoma (Romanowsky stains)
| Usu. in clusters
|-
| Mesenchymal
| Central
| Spindle
| (?)
| Fine (?)
| Absent
| Variable
| Clusters, streaming
|}

===The big list of hole-y cells===
#Large Golgi apparatus.
#*May be seen in melanoma.
#Phagocytic vacuole
#*Contains foreign material.
#Fat.
#*Usually small.
#Glycogen.
#Mucin.
#Hydropic.

Notes:
*The last two are the most important.

====Vacuoles====
''Hydropic vacuoles'' and ''secretory vacuoles'':<ref>SM. 5 January 2010.</ref>
{| class="wikitable"
|-
!
! Contents
! Distorts nucleus
! Significance
! Classic description
|-
| Hydropic vacuole
| empty (clear)
| less common
| dying cell
| diamond engagement ring
|-
| Secretory vacuole
| "globs" of stuff (usu. pink)
| more common
| secretory cell/consider adenocarcinoma
| signet ring
|}

Notes:
*Size the vacuole is not discriminative.<ref>SB. 27 January 2010.</ref>
*Nuclear distortion (by the vacuole) is probably the strongest indicator the vacuole is secretory.

===Subtyping adenocarcinoma===
Adenocarcinoma can be subtyped:<ref>SM. 16 May 2008.</ref>
{| class="wikitable"
|-
!
! Architecture
! Group borders
! Group cellular/nuclear pleomorphism
! Vacuoles (cytoplasmic)
! Nucleoli
! Other
|-
| Serous carcinoma
| Micropapillae
| Knobby
| '''Marked size variation''', +/-second benign pop.
| Hydropic
| '''Large, red'''
| Psammoma bodies
|-
| Gastric (signet ring) carcinoma
| Single cells, groups
| Community border (?)
| Limited, '''cells uniform''', +/-second benign pop.
| '''Mucin'''
| Usu. inconspicuous
| -
|-
| Breast ductal carcinoma
| '''Clusters (tubular)'''
| Community border
| Limited, cells uniform, +/-second benign pop.
| '''Mucin'''
| Inconspicuous/small
| -
|-
| Adenocarcinoma not otherwise specified (NOS)
| '''3-D clusters'''
| Community border
| Limited, malignant cells uniform, +/-second benign pop.
| '''Mucin'''
| Inconspicuous/small
| -
|-
| [[Malignant mesothelioma|Mesothelioma]] (see ''Note 1'')
| Clusters (usu. large), single cells
| Knobby border
| '''Usu. uniform size, one cell population'''
| Hydropic
| Often large
| Intercellular windows, cytoplasmic blebs
|}

Note 1:
*Mesothelioma is a type of ''carcinoma'',<ref>URL: [http://www.mesothelioma-peritoneum.info/ http://www.mesothelioma-peritoneum.info/]. Accessed on: March 18, 2010.</ref> yet is ''not'' an ''adenocarcinoma''; it is added to the table to make the point that it is similar to ''adenocarcinoma''.
**Mesothelioma arises from the mesothelium, a type of epithelium. Carcinomas are epithelial derived malignant tumours (by definition).

=Staining=
There are two standard stains:
#Papanicolaou stain (Pap stain).
#*Is a modified H&E stain.
#*Done on alcohol-fixed material.
#Romanowsky stain.
#*Many variants exist.
#*Used on air-dried specimens; air-dried cells are much larger, it is easier to see the nuclear detail.

Processing:
*''Carnoy's solution'' (ethanol, glacial acetic acid) - used to lyze RBCs to get rid of 'em.

Further details are in the main article on [[staining]].

Notes:
*Jörundsson et al. compare the types of stains.<ref>[http://www3.interscience.wiley.com/journal/121642912/abstract?CRETRY=1&SRETRY=0 http://www3.interscience.wiley.com/journal/121642912/abstract?CRETRY=1&SRETRY=0]</ref>
*Romanowsky type staining is uncommon in the Canadian cytopathology community and ''not'' on [[FRCPC]] exams.

===Pap stain===
{{Main|Pap stain}}
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>
*Blue = nucleus, basophilic cytoplasm.
*Pink = cytoplasm.
*Orange = keratin.

DDx of orange:
#Keratin.
#Dying/dead cell.
#Center of cluster effect/diffusion effect.
#*The center of large clumps of cells are often artifactually pink/orange, as the eosin (a small molecule) get there but the azure (a large molecule) does not.

===Romanowsky stains===
Variants:
*[[Diff-Quik]].
*Field's stain.
*May-Grünwald-Giemsa.
*Wright stain.

Interpretation (Romanowsky stain):<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 - [[RBC]]s, [[eosinophil]] granules, neuroendocrine granules.<ref name=pmid9769124>{{cite journal |author=Sapino A, Papotti M, Pietribiasi F, Bussolati G |title=Diagnostic cytological features of neuroendocrine differentiated carcinoma of the breast |journal=Virchows Arch. |volume=433 |issue=3 |pages=217–22 |year=1998 |month=September |pmid= |doi= |url=}}</ref>
*Blue (basophilic) - lymphocyte cytoplasm.
*Purple - nuclear chromatin, neutrophil granules, platelets.

Notes:
*May have air-drying artifact.
**Usually on slide periphery.
**Appearance: white holes.
***Air-drying may mimic the appearance of nuclear pseudoinclusions.
*Cells tend to be larger than on Pap stain.

=Adequacy of specimens=
Standards are lacking for most types of specimens. A generally accepted standard is established only for cervical cytology specimens.
===Non-gynecologic===
Standards at one large centre for non-gyne specimens:<ref>UHN PCY50001.08 P.11.</ref>
*Breast: >= 6 cell groups (6 cells/cluster).
*Thyroid: >= 20 cell cluster (20 cells/cluster).
*Urine: >=50 urothelial cells.
*Sputum: >= 10 pulmonary macrophages.

===Gynecologic===
There is a generally accepted standard for cervical (liquid-based) cytology specimens:<ref>UHN PCY50001.08 P.10.</ref>
*>5000 squamous cells/slide, if no abnormality is present.
**If abnormal cells are present, any number of cells is acceptable.
***This works-out to approx. 4 cells/HPF.
****Where: HPF = area seen at 400X with an eye piece diameter is ~22 mm.
***10 HPFs are counted and a table is used to see whether the sample is adequate.

Note:
*The standard for conventional pap smears is: 8000-12000 squamous cells/slide.<ref>GR. 4 February 2010.</ref>

====Transformation zone (TZ)====
The presence of the TZ should be commented on:<ref>GR. 4 February 2010.</ref>
*An adequate TZ is 10 cells - endocervical cells ''or'' squamous metaplastic cells (per Bethesda).

Difficulties in obtaining a TZ may arise in the following populations:
*Pregnant (endocervical canal not sampled).
*Menopausal.
*Young nulliparous.

==Principles of FNA==
General:
*Fine needle aspiration of superficial lesions may be performed by pathologists or other clinicians
*Fine needle aspiration of deep-seated lesions may be performed by interventional radiologists under imaging guidance
*Endobronchial ultrasound may be used by pulmonologists and thoracic surgeons to access pulmonary lesions, while endoscopic ultrasound may be used by gastroenterologists to access GI tract or pancreatic lesions
*Fine needle aspiration is an oxymoron.<ref>SB. 11 January 2010.</ref>
**One does not really aspirate.

Principles:<ref>SB. 11 January 2010.</ref>
*Use a small needle - 22-25 gauge.
*Use minimal suction - aspiration per se is not the key; the sample is obtained by coring.
*Use minimal back and forth angulation - it destroys blood vessels

History:
*Popularized by the Swedes.<ref>{{cite journal |author=Diamantis A, Magiorkinis E, Koutselini H |title=Fine-needle aspiration (FNA) biopsy: historical aspects |journal=Folia Histochem. Cytobiol. |volume=47 |issue=2 |pages=191–7 |year=2009 |pmid=19995703 |doi=10.2478/v10042-009-0027-x |url=http://versita.metapress.com/content/p1p772662w5u373p/}}</ref>

=Triage of specimens=
At some large centres the specimens are triaged. This is an uncommon practise in the world of cytopathology.

Options:
*Smear.
*Fancy (automated) thin layer preparations:
**Cytospin - centrifuged onto slide.
**ThinPrep - centrifuged onto filter then onto slide.
*Smear + IHC.
*Cell block. + IHC.

Triage of cytopathology specimens:

{{familytree/start}}
{{familytree | | | | | | | | | | | A | | | | | | | | | | |A=Triage of specimens}}
{{familytree | | | | | | | | | | | |!| | | | | | | | | | | |}}
{{familytree | | | | | | | | | | | B | | | | | | | | | | |B=Morphologic analysis}}
{{familytree | | | | | |,|-|-|-|-|-|^|-|-|-|-|-|.| | | | | |}}
{{familytree | | | | | C1 | | | | | | | | | | C2 | | | | |C1=Abnormal|C2=Normal}}
{{familytree | |,|-|-|-|+|-|-|-|.| | | | | | | |!| | | | | |}}
{{familytree | D1 | | D2 | | D3 | | | | | | D4 | | | | |D1=Lymphoid|D2=Non-lymphoid|D3=Unknown|D4=Rest to morphology}}
{{familytree/end}}

Management (liquid):
*Lymphoid:
**Fresh:
***Flow cytometry (FC) ''or'' laser scanning cytometry (LSC) if sufficient.
***Additional preps (i.e. CytoSpin) not usually useful.
**Fixed:
***Minimal material: smear + immunostains.
***Abundant material: cell block + immunostains.
*Non-lymphoid:
**Cell block immunostains.
*Unknown:
**Minimal material: smear + immunostains, possibly cell block + immunostains.
**Abundant material: cell block + immunostains ''and'' [[flow cytometry]].

Management (solid/clot):
*Cell block +/- immunostains.

Notes:
*It may be hard to diagnose large B cell lymphoma from LSC; thus, a cell block is useful if you have the material.<ref>WG. 16 February 2010.</ref>
*Abundant macrophages cause problems with LSC.<ref>SB. March 8, 2010.</ref>
*It is not worthwhile to do LSC if there is a scant amount of lymphoid tissue present in the specimen.<ref>SB. March 8, 2010.</ref>
*LSC is (usually) not done on CSF specimens with less than 7 mL of volume.<ref>SB. March 11, 2010.</ref>

===Number of cells for LSC - calculation===
<math>\psi_{20xo} V_{sample} = \frac {S_{needed} V_{RA} A_{20xo}}{A_{RA}} </math>

====Parameters====
<math>S_{needed} = 50,000~cells</math> -- number of cells needed. 
<math>V_{sample} = 2-10~ml</math> -- volume of sample. 
<math>V_{RA} = 0.5~ml</math> -- est. volume of rapid assessment (RA). 
<math>A_{RA} = \frac{\pi}{4} (11)^2~mm^2</math> -- est. rapid assessment (RA) area. 
<math>A_{20xo} = \frac{\pi}{4} (18/20)^2~mm^2</math> -- area with 20x obj. on microscope with 18 mm eye piece. 

====Rule====
<math>\psi_{20xo} V_{sample} = 167.36~cells~ml</math>

====Application of rule====
#Count cells in one field (on the microscope with the 18 mm eye piece) at 20x.
#Divide 167.36 cells ml by the volume of the sample.
#If the cell count in (1) is greater than the number of cells in (2) there are enough cells for a full panel.

==Prepartions==

{| class="wikitable"
|-
!
! Cost
! Cells required
! [[Fixation]]
! Disadvantages/problems
|-
| Smear
| Minimal ~$5/slide
| 1+
| Air dry/alcohol
| Layering of cells
|-
| CytoSpin
| Expensive
| 50
| ?
| Expensive
|-
| ThinPrep (liquid-based cytology)
| Expensive ~$35/slide; intermediate for several slides
| 300-400
| Always alcohol (methanol)
| Filter damage at edge of prep.
|-
| Sure-Path (liquid-based cytology) - see ''Note 1''
| Expensive (?)
| 300-400 (?)
| Always alcohol (ethanol)
| (?)
|-
| Cell block
| Expensive
| >500
| Usually [[formalin]]
| Expensive, loss of cells large, truncation artifact in [[FISH]]
|-
| Laser scanning cytometry
| Expensive
| ~50,000 for full B cell panel + minimal T cell panel - see ''Note 2''
| None
| Tissue needs to be fresh
|}

Note 1:
*''Sure-Path'' (from TriPath) is not used at many teaching centres (in Ontario) as it has some short coming for non-gyne specimens vis-a-vis ''ThinPrep'' (from Cytyc).<ref>SM. January 2010.</ref>
**It is used by the private labs in Ontario and seems to be better for Pap tests.
*A comparison between ''SurePath'' and ''ThinPrep''/experience from one lab in the USA is here: [http://www.palpath.com/MedicalTestPages/papthin1.htm http://www.palpath.com/MedicalTestPages/papthin1.htm].
Note 2 - see ''[[lymphoma]]'' article for detailed description of markers:
*The typical "full" panel is:
**B-cell markers: CD10, CD19, [[CD20]], [[CD23]], FMC7, Kappa, Lambda.
**T-Cell markers: CD3, CD5, CD4, CD8, CD7, CD2.
**NK-Cell markers: [[CD56]], CD16.
**Miscellaneous markers: CD11c, CD14.
Notes (general):
*'''C'''ytoSpin used for '''C'''SF specimens.

=Cytologic features=
===Large clusters===
*Large clusters - fibrin (junk) vs. other:
**Small (~1/10 of RBC diameter) ovoid, purple staining (on Field stain) = platelets.
***If you see platelets think ''fibrin''.

===[[Necrosis]]===
*Blobs of acellular material.
*No nucleus or pyknosis of nucleus.
*Disrupted/frayed cellular membrane.
*Orangeophilic material (orange material) - on Pap stained material.

===Granulomata===
{{Main|Granulomas}}
Cytology (six features):<ref>GS. 26 January 2010.</ref>
#Foamy/bubbly cytoplasm, abundant - '''low power'''.
#Epithelioid morphology - cell borders ''near'' indistinct - '''key feature'''.
#"Footprint" pattern nuclei/bean-shaped nuclei - '''key feature'''.
#*Macrophages usu. have an ovoid nucleus.
#+/-Nucleoli, small.
#+/-Fibrosis.
#+/-Palisading at edge.

Notes:
*Granulomas are ''not'' always nice and round, as in non-cytology specimens.

DDx:
*Infectious:
**AFB:
***[[Tuberculosis]].
***[[MAC]].
**Fungal:
***[[Histoplasmosis]].
**Bacterial:
***Bartonella (gram -ve) ([[Cat-scratch disease]]).<ref>[http://emedicine.medscape.com/article/781320-overview http://emedicine.medscape.com/article/781320-overview]</ref>

====Images====
<gallery>
Image:Granuloma_cytology.jpg | Granuloma - cytology. (WC)
</gallery>
<gallery>
Image: Granulomatous inflammation -- intermed mag.jpg | GI - intermed. mag. (WC)
Image: Granulomatous inflammation -- high mag.jpg | GI - high mag. (WC)
Image: Granulomatous inflammation - alt -- high mag.jpg | GI - high mag. (WC)
Image: Granulomatous inflammation -- very high mag.jpg | GI - very high mag. (WC)
</gallery>
*[http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CI-Image-0803/FQ-051a.gif Granuloma (ouhsc.edu)].<ref name=ouhsc_31>URL: [http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-031-M.htm http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-031-M.htm]. Accessed on: 9 April 2012.</ref>
*[http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CI-Image-0803/FQ-051b.gif Granuloma (ouhsc.edu)].<ref name=ouhsc_31>URL: [http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-031-M.htm http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-031-M.htm]. Accessed on: 9 April 2012.</ref>

=Detail articles=
Details are dealt with in separate articles.

===Gynecologic cytopathology===
{{Main|Gynecologic cytopathology}}
Gynecologic cytopathology is the origins of cytopathology and still a large part of cytopathology practise. It is deal with in separate article.

===CNS cytopathology===
{{Main|CNS cytopathology}}
The above article deals with CNS cytopathology, i.e. lumbar puncture specimens.

===Pulmonary cytopathology===
{{Main|Pulmonary cytopathology}}
The above article deals with pulmonary cytopathology, i.e. FNA specimens and sputum specimens.

===Fluid from mesothelial-lined space cytopathology===
{{Main|Mesothelial cytopathology}}
The above article deals with cytopathology specimens from spaces lined with mesothelium.

===Urine cytopathology===
{{Main|Urine cytopathology}}
The above article deals with urine cytopathology.

===Thyroid cytopathology===
{{Main|Thyroid cytopathology}}
The above article deals with thyroid cytopathology.

===Head & neck cytopathology===
{{Main|Head and neck cytopathology}}
The above article deals with head and neck cytopathology, excluding thyroid cytopathology.

===Breast cytopathology===
{{Main|Breast cytopathology}}
The above article deals with breast cytopathology.

===Gastrointestinal cytopathology===
{{Main|Gastrointestinal cytopathology}}
The above article deals with gastrointestinal cytopathology.

===Kidney cytopathology===
{{Main|Kidney cytopathology}}

=Grab bag of stuff=
The following is a grab bag of stuff that is:
*Not covered in the above articles.
*Something that applies to multiple sites (e.g. melanoma).

=Mediastinum=
{{Main|Mediastinum}}
DDx:
*[[Teratoma]] and other [[germ cell tumour]]s (GCTs).
**Seminoma/dysgerminoma is the most common.
*Terrible [[lymphoma]].
*[[Thymoma]].
**Mix of epithelial cells and small lymphoid cells.
*[[Thyroid gland]].
*[[Metastasis]].

==Thymoma==
{{Main|Thymoma}}
===Cytopathology===
Features:<ref>FNAC PP.203-4.</ref>
*Mixed population of cells:
**Epithelial cells.
***Circular nuclei with well seen micro[[nucleoli]] (seen at ~10X objective).
***+/-Nuclear membrane invaginations.
**Mature Lymphocytes.

DDx (pitfalls):
*Lymphoproliferative disorder (when epithelial component sparse).
*Carcinoma (when lymphoid population small).
**Should not have nuclear features of malignancy.
***Adenocarcinoma: marked size variation, larger [[nucleoli]].
***[[Squamous carcinoma]]: often no nucleoli. (???)

Notes:
*May have necrosis.
*Should not mistake for granuloma... as nuclei of epithelial cells round ''not'' oval.

====Image====
<gallery>
Image:Thymoma_-_cytology_high_mag.jpg | Thymoma - Field stain. (WC)
</gallery>

==Benign ovarian cyst==
====General====
*Common - typically ''[[serous cystadenoma of the ovary|serous cystadenoma]]''.

====Cytology====
Features:
*Benign epithelial cells - often ciliated.
*Macrophages.
*+/-Rare squamous cells.

DDx:
*[[Serous carcinoma]].
*[[Adenocarcinoma]].

====Sign out====
<pre>
Ovarian Cyst, Left, Fine Needle Aspiration:
- Compatible with cyst contents; consisting of macrophages, small groups of ciliated cells and rare squamous cells.
- Low cellularity.
- NEGATIVE for atypia and NEGATIVE for malignancy.
</pre>

==Germ cell tumours==
{{Main|Germ cell tumours}}
===Seminoma===
{{Main|Seminoma}}
====General====
Classic scenario:
*Retroperitoneal lymph node enlargement and testicular mass.

====Cytology====
Features:
*+/-"Corners" in the nuclear membrane.
*Cells cohesive.
*Central nucleus.
*Clear cytoplasm - may be stripped.
*Background with "viscous" or "tigroid" appearance on (air dried) Romanowsky type stains - '''key feature'''.
**Tigroid = striped or spotted appearance.<ref>URL: [http://www.merriam-webster.com/medical/tigroid http://www.merriam-webster.com/medical/tigroid]. Accessed on: January 4, 2010.</ref>
***Related to the presence of ''glycogen''.
**Tigroid pattern ''not'' seen on Pap stain.
**Not always seen.
*+/-Small mature lymphocytes (common).
*+/-Granulomas.

Images:
*[http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040-Ans/CI-Image-0803/FQ-060a.gif Seminoma - Diff-Quik - low mag. (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-040-M.htm http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-040-M.htm]. Accessed on: 10 April 2012.</ref>
*[http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040-Ans/CI-Image-0803/FQ-060b.gif Seminoma - Diff-Quik - high mag. (ouhsc.edu)].
*[http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040-Ans/CI-Image-0803/FQ-060d.gif Seminoma - Pap stain - high mag. (ouhsc.edu)].

=Crystals in fluids=
{{main|Crystals in fluids}}

The above article covers gout, pseudogout and urine crystals.

=Skin=
==Malignant melanoma==
{{Main|Malignant melanoma}}
Classic features:
#Loosely cohesive cells and single cells.
#Mixure of epithelioid cells and spindle cells.
#Malignant cells have:
#*Prominent [[red nucleolus]].
#*Pigmented cytoplasm - '''key feature''' (often not pigmented).
#*Pigment may only be present in macrophages
#*Occasional large binucleated cells (bug-eyed monster cell).
#**Nuclei are often at opposite poles of the cell, i.e. the nuclei are as far apart as possible ("divorce cells").<ref>GS. 24 February 2010.</ref>
#*Intranuclear inclusions.
#Pigmented macrophages (useful feature - but less specific for melanoma than pigment in malignant looking cells).

Notes:
#[[Large nucleolus]] - may vaguely resemble adenocarcinoma.
#*Prominent red nucleolus common in: serous carcinoma.
#The classic appearance of melanoma without pigment is closest to adenocarcinoma (which may have red nucleoli, large cells, abundant cytoplasm, occasional binucleation).
#*Differentiating morphologic features: adenocarcinoma - 3-D clusters of cells, no spindle-shaped cells.
#Bug-eyed monster cells - may vaguely resemble Reed-Sternberg cells (RSCs) which are diagnostic of [[Hodgkin's lymphoma]] (HL).
#*RSCs do not have the granular cytoplasm typical of melanoma.
#*Nuclei usually adjacent, i.e. not at opposite poles of the cell.
#*Background of melanoma different than HL.

===Images===
<gallery>
Image:Melanoma_-_cytology_field_stain.jpg | Bug-eyed monster cell in melanoma - Field stain. (WC)
Image:Pigmented_melanoma_-_cytology.jpg | Pigmented melanoma - Pap stain. (WC)
</gallery>

=Bone marrow/vertebrae=
{{Main|Haematopoiesis}}
Components:<ref>SB. 25 January 2010.</ref>
#One should see three lineages:
#*Megakaryocytes.
#**Large cells ~ 5-10X RBC.
#**Eccentric nuclei.
#*Erythrocyte precursor.
#**Central nucleus.
#**Chromatin - granular.
#**One should see ejected nuclei of the same size.
#*Granulocytes.
#Fat.
#*May be seen in a lymph node.

Notes:
*Megakaryocytes - reduced post-bone marrow transplant.

Short DDx:
*Plasma cell lesion, e.g. [[plasmacytoma]].
*Carcinoma (metastatic).
*[[Lymphoma]].

=Soft tissue lesions=
==Nodular fasciitis==
{{Main|Nodular fasciitis}}
===General===
*Rapid growth - need clinical.

===Cytology===
Features:
*Tissue culture-like appearance - '''key feature'''.
*Myxoid background.
*Moderate nuclear pleomorphism.

==Schwannoma==
{{Main|Schwannoma}}
===Cytology===
Features:
*Bent fish hook-like nuclei - '''key feature'''.
*Variable cellularity (Antoni A = cellular, Antoni B = paucicellular).

==Solitary fibrous tumour==
{{Main|Solitary fibrous tumour}}
===Cytology===
Features:
*Spindle cells with oval nuclei.
*Wire-like lamellar collagen.
===IHC===
*CD34 +ve.
*BCL2 +ve.
*CD99 +ve.

=See also=
*[[Basics]].

=References=
{{reflist|2}}

=External links=
*[http://www.uniklinik-duesseldorf.de/deutsch/Unternehmen/Institute/InstitutfrCytopathologie/page.html Cytopathology Institute Duesseldorf].
*[http://pathology2.jhu.edu/cytopath/posttest.html Cytopathology test (jhu.edu)].
*[http://www.bccancer.bc.ca/HPI/CE/cytotechnology/cytosleuthquiz/nongyne/ngcase01.htm BC cancer agency quiz (bccancer.bc.ca)].

[[Category:Cytopathology|Cytopathology]]

Cytopathology

2018-03-05T00:18:20Z

Kaitlin:

[[Image:Serous carcinoma 2c - cytology.gif | thumb| right|An animation showing two [[micrograph]]s in different planes of focus of a cytopathology specimen with [[serous carcinoma]]. (WC)]]
[[Image:Granulomatous inflammation - alt -- high mag.jpg|thumb|right|Granulomatous inflammation in the hilum of lung. [[Diff-Quik stain]].]]
'''Cytopathology''', often called ''cytology'', is the study of pathologic changes in cells.

Specimen types include exfoliated cervical cytology (Pap tests), urine, body cavity fluids (pleural, pericardial, and peritoneal), cerebrospinal fluid, and fine needle aspirations from any body site, among others. These are often collected by minimally invasive means.

Cytologic preparation methods usually include viewing single cells or small clusters of cells on slides, in contrast to surgical biopsy specimens that usually include larger pieces of tissue, with tissue architecture. In some institutions, small tissue biopsies such as core needle biopsies may also be assigned to the cytology service.

It is often divided into ''[[gynecologic cytology|gynecologic]]'' and ''non-gynecologic''. ''Gynecologic'' in this context usually refers to Pap test specimens, i.e. uterine cervix, vaginal vault; other gynecologic specimens are considered ''non-gynecologic''.

=Slide-marking conventions=
Conventions are important for facilitating communication between various team members.

Common conventions:<ref>UHN Screening process. PCY50001.08.</ref>
*The slide is placed with the label on the right hand side.
*"Marks-of-interest", e.g. dots, are place above the field of interest (when viewed through a microscope - that does not correct for image inversion).
**Microscopes used for surgical pathology, generally, do not correct for image inversion.
***The "marks-of-interest" appear below the field of interest when the slide is viewed with the naked eye.

Marks-of-interest:
*Dot - region of interest.
*Inverted "V" - transformation zone (in cervical cytology specimen).
*Inverted "Y" - benign finding.

Notes:
*Image inversion in the microscope comes about as light travels in a straight line.
*Marks should draw attention to the best examples of the highest grade lesion present.
**More than 7 marks on slide is generally considered excessive.

=Dictums of cytopathology=
*Malignant cells are malignant because they have malignant features.
*Benign cells are benign because they lack malignant features and have benign features.

Corollaries:
*Cells lacking malignant features are '''not''' malignant.
*Cells lacking benign features are '''not''' malignant.

===Cytologic features of malignancy===
Cytologic features of malignancy:
#High nuclear-to-cytoplasmic ratio.
#Nuclear membrane irregularities.
#*Notches/sharp discontinuities.
#Chromatin abnormalities.
#*Clumped chromatin, esp. differences between quadrants of a nucleus.
#*Chromatin clumping at the nuclear membrane (chromatin margination).
#Hyperchromatic nucleus (when compared to other cells).
#Nuclear pleomorphism (comparison of neighbouring cells).
#*Def'n: variable ''staining, shape, and size''.

Notes:
*Not all features of malignancy will be present in one cell.<ref>WG. 19 February 2010.</ref>

=Cell types=
WG's cell typing guide:<ref>WG. 6 January 2010.</ref>
{| class="wikitable sortable"
|-
! Cell type
! Nucleus location
! Nucleus shape
! Cytoplasm
! Chromatin
! Nucleoli
! Other
! Architecture
|-
| Squamous
| Center
| Oval/Spindle
| Solid/dense
| Coarse
| Absent
| Squamous pearls, streaming
| Streaming
|-
| Secretory/ glandular (adenocarcinoma)
| Eccentric
| Oval
| Vacuoles
| Fine
| Present
| Columnar
| Acini (glandular structures), (true) papillae
|-
| Neuroendocrine
| Center (?)
| Oval
| Fine granules (neuroendocrine granules - seen on Romanowsky type stains)
| Reticulated "stippled"
| Absent
| Perinuclear blue bodies (not seen in lymphoid cells)
| Clusters, may appear dyscohesive
|-
| Lymphoid
| Eccentric
| Oval
| Very scant, basophilic
| Coarse
| Usually absent
| Lymphoglandular bodies, dyscohesive
| Single cells
|-
| Germ cell
| Central/variable
| Oval
| Variable
| Variable
| (?), present in seminoma
| Tigroid background in seminoma (Romanowsky stains)
| Usu. in clusters
|-
| Mesenchymal
| Central
| Spindle
| (?)
| Fine (?)
| Absent
| Variable
| Clusters, streaming
|}

===The big list of hole-y cells===
#Large Golgi apparatus.
#*May be seen in melanoma.
#Phagocytic vacuole
#*Contains foreign material.
#Fat.
#*Usually small.
#Glycogen.
#Mucin.
#Hydropic.

Notes:
*The last two are the most important.

====Vacuoles====
''Hydropic vacuoles'' and ''secretory vacuoles'':<ref>SM. 5 January 2010.</ref>
{| class="wikitable"
|-
!
! Contents
! Distorts nucleus
! Significance
! Classic description
|-
| Hydropic vacuole
| empty (clear)
| less common
| dying cell
| diamond engagement ring
|-
| Secretory vacuole
| "globs" of stuff (usu. pink)
| more common
| secretory cell/consider adenocarcinoma
| signet ring
|}

Notes:
*Size the vacuole is not discriminative.<ref>SB. 27 January 2010.</ref>
*Nuclear distortion (by the vacuole) is probably the strongest indicator the vacuole is secretory.

===Subtyping adenocarcinoma===
Adenocarcinoma can be subtyped:<ref>SM. 16 May 2008.</ref>
{| class="wikitable"
|-
!
! Architecture
! Group borders
! Group cellular/nuclear pleomorphism
! Vacuoles (cytoplasmic)
! Nucleoli
! Other
|-
| Serous carcinoma
| Micropapillae
| Knobby
| '''Marked size variation''', +/-second benign pop.
| Hydropic
| '''Large, red'''
| Psammoma bodies
|-
| Gastric (signet ring) carcinoma
| Single cells, groups
| Community border (?)
| Limited, '''cells uniform''', +/-second benign pop.
| '''Mucin'''
| Usu. inconspicuous
| -
|-
| Breast ductal carcinoma
| '''Clusters (tubular)'''
| Community border
| Limited, cells uniform, +/-second benign pop.
| '''Mucin'''
| Inconspicuous/small
| -
|-
| Adenocarcinoma not otherwise specified (NOS)
| '''3-D clusters'''
| Community border
| Limited, malignant cells uniform, +/-second benign pop.
| '''Mucin'''
| Inconspicuous/small
| -
|-
| [[Malignant mesothelioma|Mesothelioma]] (see ''Note 1'')
| Clusters (usu. large), single cells
| Knobby border
| '''Usu. uniform size, one cell population'''
| Hydropic
| Often large
| Intercellular windows, cytoplasmic blebs
|}

Note 1:
*Mesothelioma is a type of ''carcinoma'',<ref>URL: [http://www.mesothelioma-peritoneum.info/ http://www.mesothelioma-peritoneum.info/]. Accessed on: March 18, 2010.</ref> yet is ''not'' an ''adenocarcinoma''; it is added to the table to make the point that it is similar to ''adenocarcinoma''.
**Mesothelioma arises from the mesothelium, a type of epithelium. Carcinomas are epithelial derived malignant tumours (by definition).

=Staining=
There are two standard stains:
#Papanicolaou stain (Pap stain).
#*Is a modified H&E stain.
#*Done on alcohol-fixed material.
#Romanowsky stain.
#*Many variants exist.
#*Used on air-dried specimens; air-dried cells are much larger, it is easier to see the nuclear detail.

Processing:
*''Carnoy's solution'' (ethanol, glacial acetic acid) - used to lyze RBCs to get rid of 'em.

Further details are in the main article on [[staining]].

Notes:
*Jörundsson et al. compare the types of stains.<ref>[http://www3.interscience.wiley.com/journal/121642912/abstract?CRETRY=1&SRETRY=0 http://www3.interscience.wiley.com/journal/121642912/abstract?CRETRY=1&SRETRY=0]</ref>
*Romanowsky type staining is uncommon in the Canadian cytopathology community and ''not'' on [[FRCPC]] exams.

===Pap stain===
{{Main|Pap stain}}
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>
*Blue = nucleus, basophilic cytoplasm.
*Pink = cytoplasm.
*Orange = keratin.

DDx of orange:
#Keratin.
#Dying/dead cell.
#Center of cluster effect/diffusion effect.
#*The center of large clumps of cells are often artifactually pink/orange, as the eosin (a small molecule) get there but the azure (a large molecule) does not.

===Romanowsky stains===
Variants:
*[[Diff-Quik]].
*Field's stain.
*May-Grünwald-Giemsa.
*Wright stain.

Interpretation (Romanowsky stain):<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 - [[RBC]]s, [[eosinophil]] granules, neuroendocrine granules.<ref name=pmid9769124>{{cite journal |author=Sapino A, Papotti M, Pietribiasi F, Bussolati G |title=Diagnostic cytological features of neuroendocrine differentiated carcinoma of the breast |journal=Virchows Arch. |volume=433 |issue=3 |pages=217–22 |year=1998 |month=September |pmid= |doi= |url=}}</ref>
*Blue (basophilic) - lymphocyte cytoplasm.
*Purple - nuclear chromatin, neutrophil granules, platelets.

Notes:
*May have air-drying artifact.
**Usually on slide periphery.
**Appearance: white holes.
***Air-drying may mimic the appearance of nuclear pseudoinclusions.
*Cells tend to be larger than on Pap stain.

=Adequacy of specimens=
Standards are lacking for most types of specimens. A generally accepted standard is established only for cervical cytology specimens.
===Non-gynecologic===
Standards at one large centre for non-gyne specimens:<ref>UHN PCY50001.08 P.11.</ref>
*Breast: >= 6 cell groups (6 cells/cluster).
*Thyroid: >= 20 cell cluster (20 cells/cluster).
*Urine: >=50 urothelial cells.
*Sputum: >= 10 pulmonary macrophages.

===Gynecologic===
There is a generally accepted standard for cervical (liquid-based) cytology specimens:<ref>UHN PCY50001.08 P.10.</ref>
*>5000 squamous cells/slide, if no abnormality is present.
**If abnormal cells are present, any number of cells is acceptable.
***This works-out to approx. 4 cells/HPF.
****Where: HPF = area seen at 400X with an eye piece diameter is ~22 mm.
***10 HPFs are counted and a table is used to see whether the sample is adequate.

Note:
*The standard for conventional pap smears is: 8000-12000 squamous cells/slide.<ref>GR. 4 February 2010.</ref>

====Transformation zone (TZ)====
The presence of the TZ should be commented on:<ref>GR. 4 February 2010.</ref>
*An adequate TZ is 10 cells - endocervical cells ''or'' squamous metaplastic cells (per Bethesda).

Difficulties in obtaining a TZ may arise in the following populations:
*Pregnant (endocervical canal not sampled).
*Menopausal.
*Young nulliparous.

==Principles of FNA==
General:
*Fine needle aspiration is an oxymoron.<ref>SB. 11 January 2010.</ref>
**One does not really aspirate.

Principles:<ref>SB. 11 January 2010.</ref>
*Use a small needle - 22 gauge.
*Use minimal suction - aspiration per se is not the key; the sample is obtained by coring.
*Use minimal back and forth angulation - it destroys blood vessels

History:
*Popularized by the Swedes.<ref>{{cite journal |author=Diamantis A, Magiorkinis E, Koutselini H |title=Fine-needle aspiration (FNA) biopsy: historical aspects |journal=Folia Histochem. Cytobiol. |volume=47 |issue=2 |pages=191–7 |year=2009 |pmid=19995703 |doi=10.2478/v10042-009-0027-x |url=http://versita.metapress.com/content/p1p772662w5u373p/}}</ref>

=Triage of specimens=
At some large centres the specimens are triaged. This is an uncommon practise in the world of cytopathology.

Options:
*Smear.
*Fancy (automated) thin layer preparations:
**Cytospin - centrifuged onto slide.
**ThinPrep - centrifuged onto filter then onto slide.
*Smear + IHC.
*Cell block. + IHC.

Triage of cytopathology specimens:

{{familytree/start}}
{{familytree | | | | | | | | | | | A | | | | | | | | | | |A=Triage of specimens}}
{{familytree | | | | | | | | | | | |!| | | | | | | | | | | |}}
{{familytree | | | | | | | | | | | B | | | | | | | | | | |B=Morphologic analysis}}
{{familytree | | | | | |,|-|-|-|-|-|^|-|-|-|-|-|.| | | | | |}}
{{familytree | | | | | C1 | | | | | | | | | | C2 | | | | |C1=Abnormal|C2=Normal}}
{{familytree | |,|-|-|-|+|-|-|-|.| | | | | | | |!| | | | | |}}
{{familytree | D1 | | D2 | | D3 | | | | | | D4 | | | | |D1=Lymphoid|D2=Non-lymphoid|D3=Unknown|D4=Rest to morphology}}
{{familytree/end}}

Management (liquid):
*Lymphoid:
**Fresh:
***Flow cytometry (FC) ''or'' laser scanning cytometry (LSC) if sufficient.
***Additional preps (i.e. CytoSpin) not usually useful.
**Fixed:
***Minimal material: smear + immunostains.
***Abundant material: cell block + immunostains.
*Non-lymphoid:
**Cell block immunostains.
*Unknown:
**Minimal material: smear + immunostains, possibly cell block + immunostains.
**Abundant material: cell block + immunostains ''and'' [[flow cytometry]].

Management (solid/clot):
*Cell block +/- immunostains.

Notes:
*It may be hard to diagnose large B cell lymphoma from LSC; thus, a cell block is useful if you have the material.<ref>WG. 16 February 2010.</ref>
*Abundant macrophages cause problems with LSC.<ref>SB. March 8, 2010.</ref>
*It is not worthwhile to do LSC if there is a scant amount of lymphoid tissue present in the specimen.<ref>SB. March 8, 2010.</ref>
*LSC is (usually) not done on CSF specimens with less than 7 mL of volume.<ref>SB. March 11, 2010.</ref>

===Number of cells for LSC - calculation===
<math>\psi_{20xo} V_{sample} = \frac {S_{needed} V_{RA} A_{20xo}}{A_{RA}} </math>

====Parameters====
<math>S_{needed} = 50,000~cells</math> -- number of cells needed. 
<math>V_{sample} = 2-10~ml</math> -- volume of sample. 
<math>V_{RA} = 0.5~ml</math> -- est. volume of rapid assessment (RA). 
<math>A_{RA} = \frac{\pi}{4} (11)^2~mm^2</math> -- est. rapid assessment (RA) area. 
<math>A_{20xo} = \frac{\pi}{4} (18/20)^2~mm^2</math> -- area with 20x obj. on microscope with 18 mm eye piece. 

====Rule====
<math>\psi_{20xo} V_{sample} = 167.36~cells~ml</math>

====Application of rule====
#Count cells in one field (on the microscope with the 18 mm eye piece) at 20x.
#Divide 167.36 cells ml by the volume of the sample.
#If the cell count in (1) is greater than the number of cells in (2) there are enough cells for a full panel.

==Prepartions==

{| class="wikitable"
|-
!
! Cost
! Cells required
! [[Fixation]]
! Disadvantages/problems
|-
| Smear
| Minimal ~$5/slide
| 1+
| Air dry/alcohol
| Layering of cells
|-
| CytoSpin
| Expensive
| 50
| ?
| Expensive
|-
| ThinPrep (liquid-based cytology)
| Expensive ~$35/slide; intermediate for several slides
| 300-400
| Always alcohol (methanol)
| Filter damage at edge of prep.
|-
| Sure-Path (liquid-based cytology) - see ''Note 1''
| Expensive (?)
| 300-400 (?)
| Always alcohol (ethanol)
| (?)
|-
| Cell block
| Expensive
| >500
| Usually [[formalin]]
| Expensive, loss of cells large, truncation artifact in [[FISH]]
|-
| Laser scanning cytometry
| Expensive
| ~50,000 for full B cell panel + minimal T cell panel - see ''Note 2''
| None
| Tissue needs to be fresh
|}

Note 1:
*''Sure-Path'' (from TriPath) is not used at many teaching centres (in Ontario) as it has some short coming for non-gyne specimens vis-a-vis ''ThinPrep'' (from Cytyc).<ref>SM. January 2010.</ref>
**It is used by the private labs in Ontario and seems to be better for Pap tests.
*A comparison between ''SurePath'' and ''ThinPrep''/experience from one lab in the USA is here: [http://www.palpath.com/MedicalTestPages/papthin1.htm http://www.palpath.com/MedicalTestPages/papthin1.htm].
Note 2 - see ''[[lymphoma]]'' article for detailed description of markers:
*The typical "full" panel is:
**B-cell markers: CD10, CD19, [[CD20]], [[CD23]], FMC7, Kappa, Lambda.
**T-Cell markers: CD3, CD5, CD4, CD8, CD7, CD2.
**NK-Cell markers: [[CD56]], CD16.
**Miscellaneous markers: CD11c, CD14.
Notes (general):
*'''C'''ytoSpin used for '''C'''SF specimens.

=Cytologic features=
===Large clusters===
*Large clusters - fibrin (junk) vs. other:
**Small (~1/10 of RBC diameter) ovoid, purple staining (on Field stain) = platelets.
***If you see platelets think ''fibrin''.

===[[Necrosis]]===
*Blobs of acellular material.
*No nucleus or pyknosis of nucleus.
*Disrupted/frayed cellular membrane.
*Orangeophilic material (orange material) - on Pap stained material.

===Granulomata===
{{Main|Granulomas}}
Cytology (six features):<ref>GS. 26 January 2010.</ref>
#Foamy/bubbly cytoplasm, abundant - '''low power'''.
#Epithelioid morphology - cell borders ''near'' indistinct - '''key feature'''.
#"Footprint" pattern nuclei/bean-shaped nuclei - '''key feature'''.
#*Macrophages usu. have an ovoid nucleus.
#+/-Nucleoli, small.
#+/-Fibrosis.
#+/-Palisading at edge.

Notes:
*Granulomas are ''not'' always nice and round, as in non-cytology specimens.

DDx:
*Infectious:
**AFB:
***[[Tuberculosis]].
***[[MAC]].
**Fungal:
***[[Histoplasmosis]].
**Bacterial:
***Bartonella (gram -ve) ([[Cat-scratch disease]]).<ref>[http://emedicine.medscape.com/article/781320-overview http://emedicine.medscape.com/article/781320-overview]</ref>

====Images====
<gallery>
Image:Granuloma_cytology.jpg | Granuloma - cytology. (WC)
</gallery>
<gallery>
Image: Granulomatous inflammation -- intermed mag.jpg | GI - intermed. mag. (WC)
Image: Granulomatous inflammation -- high mag.jpg | GI - high mag. (WC)
Image: Granulomatous inflammation - alt -- high mag.jpg | GI - high mag. (WC)
Image: Granulomatous inflammation -- very high mag.jpg | GI - very high mag. (WC)
</gallery>
*[http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CI-Image-0803/FQ-051a.gif Granuloma (ouhsc.edu)].<ref name=ouhsc_31>URL: [http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-031-M.htm http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-031-M.htm]. Accessed on: 9 April 2012.</ref>
*[http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CI-Image-0803/FQ-051b.gif Granuloma (ouhsc.edu)].<ref name=ouhsc_31>URL: [http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-031-M.htm http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-031-M.htm]. Accessed on: 9 April 2012.</ref>

=Detail articles=
Details are dealt with in separate articles.

===Gynecologic cytopathology===
{{Main|Gynecologic cytopathology}}
Gynecologic cytopathology is the origins of cytopathology and still a large part of cytopathology practise. It is deal with in separate article.

===CNS cytopathology===
{{Main|CNS cytopathology}}
The above article deals with CNS cytopathology, i.e. lumbar puncture specimens.

===Pulmonary cytopathology===
{{Main|Pulmonary cytopathology}}
The above article deals with pulmonary cytopathology, i.e. FNA specimens and sputum specimens.

===Fluid from mesothelial-lined space cytopathology===
{{Main|Mesothelial cytopathology}}
The above article deals with cytopathology specimens from spaces lined with mesothelium.

===Urine cytopathology===
{{Main|Urine cytopathology}}
The above article deals with urine cytopathology.

===Thyroid cytopathology===
{{Main|Thyroid cytopathology}}
The above article deals with thyroid cytopathology.

===Head & neck cytopathology===
{{Main|Head and neck cytopathology}}
The above article deals with head and neck cytopathology, excluding thyroid cytopathology.

===Breast cytopathology===
{{Main|Breast cytopathology}}
The above article deals with breast cytopathology.

===Gastrointestinal cytopathology===
{{Main|Gastrointestinal cytopathology}}
The above article deals with gastrointestinal cytopathology.

===Kidney cytopathology===
{{Main|Kidney cytopathology}}

=Grab bag of stuff=
The following is a grab bag of stuff that is:
*Not covered in the above articles.
*Something that applies to multiple sites (e.g. melanoma).

=Mediastinum=
{{Main|Mediastinum}}
DDx:
*[[Teratoma]] and other [[germ cell tumour]]s (GCTs).
**Seminoma/dysgerminoma is the most common.
*Terrible [[lymphoma]].
*[[Thymoma]].
**Mix of epithelial cells and small lymphoid cells.
*[[Thyroid gland]].
*[[Metastasis]].

==Thymoma==
{{Main|Thymoma}}
===Cytopathology===
Features:<ref>FNAC PP.203-4.</ref>
*Mixed population of cells:
**Epithelial cells.
***Circular nuclei with well seen micro[[nucleoli]] (seen at ~10X objective).
***+/-Nuclear membrane invaginations.
**Mature Lymphocytes.

DDx (pitfalls):
*Lymphoproliferative disorder (when epithelial component sparse).
*Carcinoma (when lymphoid population small).
**Should not have nuclear features of malignancy.
***Adenocarcinoma: marked size variation, larger [[nucleoli]].
***[[Squamous carcinoma]]: often no nucleoli. (???)

Notes:
*May have necrosis.
*Should not mistake for granuloma... as nuclei of epithelial cells round ''not'' oval.

====Image====
<gallery>
Image:Thymoma_-_cytology_high_mag.jpg | Thymoma - Field stain. (WC)
</gallery>

==Benign ovarian cyst==
====General====
*Common - typically ''[[serous cystadenoma of the ovary|serous cystadenoma]]''.

====Cytology====
Features:
*Benign epithelial cells - often ciliated.
*Macrophages.
*+/-Rare squamous cells.

DDx:
*[[Serous carcinoma]].
*[[Adenocarcinoma]].

====Sign out====
<pre>
Ovarian Cyst, Left, Fine Needle Aspiration:
- Compatible with cyst contents; consisting of macrophages, small groups of ciliated cells and rare squamous cells.
- Low cellularity.
- NEGATIVE for atypia and NEGATIVE for malignancy.
</pre>

==Germ cell tumours==
{{Main|Germ cell tumours}}
===Seminoma===
{{Main|Seminoma}}
====General====
Classic scenario:
*Retroperitoneal lymph node enlargement and testicular mass.

====Cytology====
Features:
*+/-"Corners" in the nuclear membrane.
*Cells cohesive.
*Central nucleus.
*Clear cytoplasm - may be stripped.
*Background with "viscous" or "tigroid" appearance on (air dried) Romanowsky type stains - '''key feature'''.
**Tigroid = striped or spotted appearance.<ref>URL: [http://www.merriam-webster.com/medical/tigroid http://www.merriam-webster.com/medical/tigroid]. Accessed on: January 4, 2010.</ref>
***Related to the presence of ''glycogen''.
**Tigroid pattern ''not'' seen on Pap stain.
**Not always seen.
*+/-Small mature lymphocytes (common).
*+/-Granulomas.

Images:
*[http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040-Ans/CI-Image-0803/FQ-060a.gif Seminoma - Diff-Quik - low mag. (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-040-M.htm http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-040-M.htm]. Accessed on: 10 April 2012.</ref>
*[http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040-Ans/CI-Image-0803/FQ-060b.gif Seminoma - Diff-Quik - high mag. (ouhsc.edu)].
*[http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040-Ans/CI-Image-0803/FQ-060d.gif Seminoma - Pap stain - high mag. (ouhsc.edu)].

=Crystals in fluids=
{{main|Crystals in fluids}}

The above article covers gout, pseudogout and urine crystals.

=Skin=
==Malignant melanoma==
{{Main|Malignant melanoma}}
Classic features:
#Loosely cohesive cells and single cells.
#Mixure of epithelioid cells and spindle cells.
#Malignant cells have:
#*Prominent [[red nucleolus]].
#*Pigmented cytoplasm - '''key feature''' (often not pigmented).
#*Pigment may only be present in macrophages
#*Occasional large binucleated cells (bug-eyed monster cell).
#**Nuclei are often at opposite poles of the cell, i.e. the nuclei are as far apart as possible ("divorce cells").<ref>GS. 24 February 2010.</ref>
#*Intranuclear inclusions.
#Pigmented macrophages (useful feature - but less specific for melanoma than pigment in malignant looking cells).

Notes:
#[[Large nucleolus]] - may vaguely resemble adenocarcinoma.
#*Prominent red nucleolus common in: serous carcinoma.
#The classic appearance of melanoma without pigment is closest to adenocarcinoma (which may have red nucleoli, large cells, abundant cytoplasm, occasional binucleation).
#*Differentiating morphologic features: adenocarcinoma - 3-D clusters of cells, no spindle-shaped cells.
#Bug-eyed monster cells - may vaguely resemble Reed-Sternberg cells (RSCs) which are diagnostic of [[Hodgkin's lymphoma]] (HL).
#*RSCs do not have the granular cytoplasm typical of melanoma.
#*Nuclei usually adjacent, i.e. not at opposite poles of the cell.
#*Background of melanoma different than HL.

===Images===
<gallery>
Image:Melanoma_-_cytology_field_stain.jpg | Bug-eyed monster cell in melanoma - Field stain. (WC)
Image:Pigmented_melanoma_-_cytology.jpg | Pigmented melanoma - Pap stain. (WC)
</gallery>

=Bone marrow/vertebrae=
{{Main|Haematopoiesis}}
Components:<ref>SB. 25 January 2010.</ref>
#One should see three lineages:
#*Megakaryocytes.
#**Large cells ~ 5-10X RBC.
#**Eccentric nuclei.
#*Erythrocyte precursor.
#**Central nucleus.
#**Chromatin - granular.
#**One should see ejected nuclei of the same size.
#*Granulocytes.
#Fat.
#*May be seen in a lymph node.

Notes:
*Megakaryocytes - reduced post-bone marrow transplant.

Short DDx:
*Plasma cell lesion, e.g. [[plasmacytoma]].
*Carcinoma (metastatic).
*[[Lymphoma]].

=Soft tissue lesions=
==Nodular fasciitis==
{{Main|Nodular fasciitis}}
===General===
*Rapid growth - need clinical.

===Cytology===
Features:
*Tissue culture-like appearance - '''key feature'''.
*Myxoid background.
*Moderate nuclear pleomorphism.

==Schwannoma==
{{Main|Schwannoma}}
===Cytology===
Features:
*Bent fish hook-like nuclei - '''key feature'''.
*Variable cellularity (Antoni A = cellular, Antoni B = paucicellular).

==Solitary fibrous tumour==
{{Main|Solitary fibrous tumour}}
===Cytology===
Features:
*Spindle cells with oval nuclei.
*Wire-like lamellar collagen.
===IHC===
*CD34 +ve.
*BCL2 +ve.
*CD99 +ve.

=See also=
*[[Basics]].

=References=
{{reflist|2}}

=External links=
*[http://www.uniklinik-duesseldorf.de/deutsch/Unternehmen/Institute/InstitutfrCytopathologie/page.html Cytopathology Institute Duesseldorf].
*[http://pathology2.jhu.edu/cytopath/posttest.html Cytopathology test (jhu.edu)].
*[http://www.bccancer.bc.ca/HPI/CE/cytotechnology/cytosleuthquiz/nongyne/ngcase01.htm BC cancer agency quiz (bccancer.bc.ca)].

[[Category:Cytopathology|Cytopathology]]