Difference between revisions of "Lymph node pathology"

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*Neoplastic - lymphoma, carcinoma.
*Neoplastic - lymphoma, carcinoma.
*Endocrine - [[hyperthyroidism]].
*Endocrine - [[hyperthyroidism]].
*Trauma.
*Trauma.  
*Autoimmune - [[SLE]], [[RA]], [[dermatomyositis]].
*Autoimmune - [[SLE]], [[RA]], [[dermatomyositis]].
*Inflammatory - drugs (phenytoin).
*Inflammatory - drugs (phenytoin).
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| melanin-laden histiocytes
| melanin-laden histiocytes
| [[histiocytosis]]
| [[histiocytosis]]
| S100+ve (interdigitating dendritic cells), CD1a+ve (Langerhans cells)
| [[S-100]]+ve (interdigitating dendritic cells), CD1a+ve (Langerhans cells)
| [[cutaneous T-cell lymphoma]]
| [[cutaneous T-cell lymphoma]]
| [[Image:Dermatopathic_lymphadenopathy_-_intermed_mag.jpg |thumb|center|150px| DL - intermed. mag.]]  
| [[Image:Dermatopathic_lymphadenopathy_-_intermed_mag.jpg |thumb|center|150px| DL - intermed. mag.]]  
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| [[Kimura disease]]
| [[Kimura disease]]
| eosinophils
| eosinophils
| angiolymphoid proliferation (thick-walled blood vessels with hobnail endothelial cells)
| angiolymphoid proliferation (thick-walled blood vessels with [[hobnail]] endothelial cells)
| IHC ?
| IHC ?
| [[Langerhans cell histiocytosis]], drug reaction, [[angiolymphoid hyperplasia with eosinophilia]]
| [[Langerhans cell histiocytosis]], drug reaction, [[angiolymphoid hyperplasia with eosinophilia]]
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| abundant histiocytes with reniform nuclei
| abundant histiocytes with reniform nuclei
| often prominent eosinophilia
| often prominent eosinophilia
| S100+, CD1a+
| [[S-100]]+, CD1a+
| [[Kimura disease]] (eosinophilia), [[Rosai-Dorfman disease]]
| [[Kimura disease]] (eosinophilia), [[Rosai-Dorfman disease]]
| [[Image:Langerhans_cell_histiocytosis_-_very_high_mag.jpg|thumb|center|150px|LCH - very high mag.]]
| [[Image:Langerhans_cell_histiocytosis_-_very_high_mag.jpg|thumb|center|150px|LCH - very high mag.]]
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| sinus histiocytosis
| sinus histiocytosis
| emperipolesis (intact cell within a macrophage)
| emperipolesis (intact cell within a macrophage)
| S100+, CD1a-
| [[S-100]]+, CD1a-
| Langerhans cell histiocytosis
| Langerhans cell histiocytosis
| [[Image:Emperipolesis_-_very_high_mag.jpg |thumb|center|150px | RDD - very high mag.]]  
| [[Image:Emperipolesis_-_very_high_mag.jpg |thumb|center|150px | RDD - very high mag.]]  
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==Lymph node metastasis==
==Lymph node metastasis==
===General===
{{Main|Lymph node metastasis}}
*Determination of ''lymph node status'' is one of the most common indications for the examination of lymph nodes.
*It is a good idea to look at the tumour (if available) ...before looking at the LNs for mets.
*Lymph node metastasis, in the absence of other metastases, often up-stage a cancer from [[cancer staging|stage]] II to stage III.
 
===Gross===
*Outside:
**"Large" - size varies by site.
***Neck >10 mm.<ref name=pmid18337039>{{Cite journal  | last1 = Mack | first1 = MG. | last2 = Rieger | first2 = J. | last3 = Baghi | first3 = M. | last4 = Bisdas | first4 = S. | last5 = Vogl | first5 = TJ. | title = Cervical lymph nodes. | journal = Eur J Radiol | volume = 66 | issue = 3 | pages = 493-500 | month = Jun | year = 2008 | doi = 10.1016/j.ejrad.2008.01.019 | PMID = 18337039 }}</ref>
**Shape - round more suspicious than oval.
*Sectioned:
**White firm lesion with irregular border - classic appearance.
**Non-fatty hilum.<ref name=pmid18337039/>
 
===Microscopic===
Features:
*Foreign cell population - '''key feature'''.
**Classic location: subcapsular sinuses.
*+/-Cells with cytologic features of malignancy.
**Nuclear pleomorphism (variation in size, shape and staining).
**Nuclear atypia:
***Nuclear enlargement.
***Irregular nuclear membrane.
***Irregular chromatin pattern, esp. asymmetry.
***Large or irregular nucleolus.
**Abundant mitotic figures.
*+/-Cells in architectural arrangements seen in malignancy; highly variable - dependent on tumour type and differentiation.
**+/-Gland formation.
**+/-Single cells.
**+/-Small clusters of cells.
 
Notes:
#Cytologic features of malignancy may not be present; some tumours, e.g. gallbladder carcinoma, do not always have overt cytologic features of malignancy.
#*The diagnosis is based on the fact that they are foreign to the lymph node ''and'' architecturally consistent with a well-differentiated malignancy.
#[[Soft_tissue_lesions#Lymph_node_metastases_in_sarcomas|Lymph node metastases in sarcomas]] are uncommon; they are seen in <3% of cases.<ref name=pmid8424704>{{Cite journal  | last1 = Fong | first1 = Y. | last2 = Coit | first2 = DG. | last3 = Woodruff | first3 = JM. | last4 = Brennan | first4 = MF. | title = Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients. | journal = Ann Surg | volume = 217 | issue = 1 | pages = 72-7 | month = Jan | year = 1993 | doi =  | PMID = 8424704 | PMC = 1242736}}</ref>
#Fatty lymph nodes (esp. fatty hilus<ref name=pmid18337039>{{Cite journal  | last1 = Mack | first1 = MG. | last2 = Rieger | first2 = J. | last3 = Baghi | first3 = M. | last4 = Bisdas | first4 = S. | last5 = Vogl | first5 = TJ. | title = Cervical lymph nodes. | journal = Eur J Radiol | volume = 66 | issue = 3 | pages = 493-500 | month = Jun | year = 2008 | doi = 10.1016/j.ejrad.2008.01.019 | PMID = 18337039 }}</ref>) are less likely to harbor metastases.<ref name=pmid21972135>{{Cite journal  | last1 = Korteweg | first1 = MA. | last2 = Veldhuis | first2 = WB. | last3 = Mali | first3 = WP. | last4 = Diepstraten | first4 = SC. | last5 = Luijten | first5 = PR. | last6 = van den Bosch | first6 = MA. | last7 = Eijkemans | first7 = RM. | last8 = van Diest | first8 = PJ. | last9 = Klomp | first9 = DW. | title = Investigation of lipid composition of dissected sentinel lymph nodes of breast cancer patients by 7T proton MR spectroscopy. | journal = J Magn Reson Imaging | volume = 35 | issue = 2 | pages = 387-92 | month = Feb | year = 2012 | doi = 10.1002/jmri.22820 | PMID = 21972135 }}</ref>
 
DDx - mimics of metastatic disease:
*[[Endometriosis]].
*Ectopic [[decidua]].<ref name=pmid15859655>{{Cite journal  | last1 = Wu | first1 = DC. | last2 = Hirschowitz | first2 = S. | last3 = Natarajan | first3 = S. | title = Ectopic decidua of pelvic lymph nodes: a potential diagnostic pitfall. | journal = Arch Pathol Lab Med | volume = 129 | issue = 5 | pages = e117-20 | month = May | year = 2005 | doi = 10.1043/1543-2165(2005)129e117:EDOPLN2.0.CO;2 | PMID = 15859655 }}</ref>
*[[Endosalpingiosis]].<ref name=pmid20631604>{{Cite journal  | last1 = Corben | first1 = AD. | last2 = Nehhozina | first2 = T. | last3 = Garg | first3 = K. | last4 = Vallejo | first4 = CE. | last5 = Brogi | first5 = E. | title = Endosalpingiosis in axillary lymph nodes: a possible pitfall in the staging of patients with breast carcinoma. | journal = Am J Surg Pathol | volume = 34 | issue = 8 | pages = 1211-6 | month = Aug | year = 2010 | doi = 10.1097/PAS.0b013e3181e5e03e | PMID = 20631604 }}</ref>
*Melanocytic nevus - intracapsular or within the trabeculae.<ref name=pmid12717252>{{Cite journal  | last1 = Biddle | first1 = DA. | last2 = Evans | first2 = HL. | last3 = Kemp | first3 = BL. | last4 = El-Naggar | first4 = AK. | last5 = Harvell | first5 = JD. | last6 = White | first6 = WL. | last7 = Iskandar | first7 = SS. | last8 = Prieto | first8 = VG. | title = Intraparenchymal nevus cell aggregates in lymph nodes: a possible diagnostic pitfall with malignant melanoma and carcinoma. | journal = Am J Surg Pathol | volume = 27 | issue = 5 | pages = 673-81 | month = May | year = 2003 | doi =  | PMID = 12717252 }}</ref>
*[[Dermatopathic lymphadenopathy]].{{fact}}
*[[Sinus histiocytosis]] - especially for the junior resident.
*[[Tumour deposit]] (discoutinuous extramural extension) - definition dependent on primary tumour (e.g. in the head & neck they are tumour replaced lymph nodes, in the colon they are considered separate and not counted as lymph nodes).
 
====Images====
<gallery>
Image:Breast_carcinoma_in_a_lymph_node.jpg | Breast carcinoma LN metastasis (WC)
Image:Lymph_node_with_papillary_thyroid_carcinoma.jpg | Thyroid carcinoma LN metastasis (WC)
Image:Crc_met_to_node1.jpg | Colorectal carcinoma LN metastasis (WC)
Image:Lymph_node_with_metastatic_melanoma_-_by_Gabriel_Caponetti,_MD.jpg | Melanoma in a lymph node. (WC)
</gallery>
=====Mimics=====
<gallery>
Image:Decidua_in_a_lymph_node_-_low_mag.jpg | Decidua in a LN - low mag. (WC)
Image:Decidua_in_a_lymph_node_-_high_mag.jpg | Decidua in a LN - high mag. (WC)
Image:Endometriosis_lymph_node_-_2_-_intermed_mag.jpg | Endometriosis in a LN - intermed. mag. (WC)
Image:Endosalpingiosis_in_lymph_node_-_intermed_mag.jpg | Endosalpingiosis in a LN - intermed. mag. (WC)
Image:Endosalpingiosis_in_lymph_node_-_very_high_mag.jpg | Endosalpingiosis in a LN - very high mag. (WC)
</gallery>


==Kaposi sarcoma==
==Kaposi sarcoma==
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==Reactive follicular hyperplasia==
==Reactive follicular hyperplasia==
===General===
{{Main|Reactive follicular hyperplasia}}
*Many causes - including: bacteria, viruses, chemicals, drugs, allergens.
**In only approximately 10% can definitive cause be identified.<ref name=Ref_ILNP174>{{Ref_ILNP|174}}</ref>
 
===Microscopic===
Features:<ref name=Ref_ILNP179>{{Ref_ILNP|179}}</ref>
*Enlarged follicles, follicle size variation - '''key feature''' with:
**Large germinal centers (pale on H&E).
***Mitoses common.
***Variable lymphocyte morphology.
***Tingible-body macrophage (large, pale cells with junk in the cytoplasm).
***Germinal centers (GCs) have a crisp/sharp edge.
***Normal dark/light variation of GCs; superficial aspect light, deeper aspect darker.
**Rim of small (inactive) lymphocytes.
 
DDx:
*[[Hodgkin lymphoma]] - with rare Reed-Sternberg cells.
*Non-Hodgkin [[lymphoma]].
**T-cell/histiocyte-rich large B cell lymphoma.
 
Image: [http://pleiad.umdnj.edu/hemepath/normal_node/normal_node.html Normal lymph node (umdnj.edu)].
 
===IHC===
Screening panel:
*CD3.
*CD5.
*CD10.
*CD20.
*CD30.
*CD15.
 
Others:
*BCL2 -ve.


==Diffuse paracortical hyperplasia==
==Diffuse paracortical hyperplasia==
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==Systemic lupus erythematosus lymphadenopathy==
==Systemic lupus erythematosus lymphadenopathy==
===General===
{{Main|Systemic lupus erythematosus lymphadenopathy}}
*Lymphadenopathy associated with [[systemic lupus erythematosus]] (SLE).
 
===Microscopic===
Features:<ref name=pmid9406250>{{Cite journal  | last1 = Kojima | first1 = M. | last2 = Nakamura | first2 = S. | last3 = Itoh | first3 = H. | last4 = Yoshida | first4 = K. | last5 = Asano | first5 = S. | last6 = Yamane | first6 = N. | last7 = Komatsumoto | first7 = S. | last8 = Ban | first8 = S. | last9 = Joshita | first9 = T. | title = Systemic lupus erythematosus (SLE) lymphadenopathy presenting with histopathologic features of Castleman' disease: a clinicopathologic study of five cases. | journal = Pathol Res Pract | volume = 193 | issue = 8 | pages = 565-71 | month =  | year = 1997 | doi =  | PMID = 9406250 }}</ref>
*Necrosis.
*Hematoxylin bodies (in necrotic foci).
**Dark blue irregular bodies on H&E.
 
DDx:
*[[Kikuchi disease]].
 
====Images====
<gallery>
Image:Systemic_lupus_erythematosus_lymphadenopathy_-_high_mag.jpg | SLE lymphadenopathy - high mag. (WC)
Image:Systemic_lupus_erythematosus_lymphadenopathy_-_very_high_mag.jpg | SLE lymphadenopathy - very high mag. (WC)
</gallery>


==Castleman disease==
==Castleman disease==

Latest revision as of 15:16, 16 February 2021

This article deals with non-haematologic malignant, i.e. metastases, and non-malignant lymph node pathology. An introduction to the lymph node is in the lymph nodes article.

Haematologic malignancies (in lymph nodes) are dealt with in other articles - see haematopathology and lymphoma.

Overview

Clinical:

  • Lymphadenopathy.

Differential diagnosis:[1]

  • Infectious - fungal, mycobacterial, viral, protozoal (Toxoplasma), bacterial (Chlamydia, Rickettsia, Bartonella)).
  • Neoplastic - lymphoma, carcinoma.
  • Endocrine - hyperthyroidism.
  • Trauma.
  • Autoimmune - SLE, RA, dermatomyositis.
  • Inflammatory - drugs (phenytoin).
  • Idiopathic - sarcoidosis.

Overview in a table

Entity Key feature Other findings IHC DDx Image
Non-specific reactive follicular hyperplasia (NSRFH) large spaced cortical follicles tingible body macrophages, normal dark/light GC pattern BCL2 -ve infection (Toxoplasmosis, HIV/AIDS), Hodgkin's lymphoma image ?
Lymph node metastasis foreign cell population, usu. in subcapsular sinuses +/-nuclear atypia, +/-malignant architecture dependent on tumour type (see IHC) dependent on morphology, endometriosis (mimics adenocarcinoma), ectopic decidua (mimics SCC)
Error creating thumbnail:
CRC metastasis
Breast metastasis
Progressive transformation of germinal centers large (atypical) germinal centers poorly demarcated germinal center (GC)/mantle zone interfaces, expanded mantle zone IHC to r/o nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) NLPHL, follicular hyperplasia
Error creating thumbnail:
PTGC - very low mag.
Toxoplasmosis large follicles; epithelioid cells perifollicular & intrafollicular reactive GCs, monocytoid cell clusters, epithelioid cells IHC for toxoplasma NSRFH, HIV/AIDS, Hodgkin's lymphoma
Error creating thumbnail:
TL - low mag.
Kikuchi disease (histiocystic necrotizing lymphadenitis) No PMNs histiocytes, necrosis IHC for large cell lymphoma (CD30 + others) SLE (has (blue) hematoxylin bodies in necrotic areas), large cell lymphomas
HNL - very high mag.
Cat-scratch disease PMNs in necrotic area "stellate" (or serpentine) shaped microabscesses, granulomas B. henselae, Dieterle stain HIV/AIDS, NSRFH
Cat scratch - very low mag.
Dermatopathic lymphadenopathy melanin-laden histiocytes histiocytosis S-100+ve (interdigitating dendritic cells), CD1a+ve (Langerhans cells) cutaneous T-cell lymphoma
Kimura disease eosinophils angiolymphoid proliferation (thick-walled blood vessels with hobnail endothelial cells) IHC ? Langerhans cell histiocytosis, drug reaction, angiolymphoid hyperplasia with eosinophilia
File:Kimura disease - very high mag.jpg
Kimura disease - very high mag.
Langerhans cell histiocytosis abundant histiocytes with reniform nuclei often prominent eosinophilia S-100+, CD1a+ Kimura disease (eosinophilia), Rosai-Dorfman disease
Rosai-Dorfman disease sinus histiocytosis emperipolesis (intact cell within a macrophage) S-100+, CD1a- Langerhans cell histiocytosis
Error creating thumbnail:
RDD - very high mag.
Systemic lupus erythematosus lymphadenopathy (blue) hematoxylin bodies necrosis, no PMNs IHC for large cell lymphoma (CD30 + others) Kikuchi disease, large cell lymphomas
SLEL - high mag.
Castleman disease, hyaline vascular variant thick mantle cell layer with laminar appearance ("onion skin" layering) hyaline (pink crap), lollipops (large vessels into GC), no mitoses in GC IHC - to r/o mantle cell lymphoma mantle cell lymphoma, HIV/AIDS
CD - intermed. mag.
Castleman disease, plasma cell variant thick mantle cell layer sinus perserved, interfollicular plasma cells, mitoses in GC HHV-8 HIV/AIDS image ?
Intranodal palisaded myofibroblastoma spindle cells with nuclear palisading RBC extravasation, fibrillary bodies with a central vessel "amianthoid fibers" SMA+, cyclin D1+ schwannoma
IPM - very high mag.

Follicular lymphoma vs. reactive follicular hyperplasia

Factors to consider:[2]

Reactive follicular
hyperplasia
Follicular lymphoma
Follicle location cortex cortex and medulla
Germinal center edge sharp/well-demarcated poorly demarcated
Germinal center density well spaced, sinuses open crowded, sinuses effaced/
compressed to nothingness
Tingible body
macrophages
common uncommon
Germinal center
light/dark pattern
normal abnormal

Lymph node metastasis

Kaposi sarcoma

  • One of the few non-lymphoid primary lymph node tumours.[3]

Melanocytic nevi

See: Dermatopathic lymphadenopathy.
  • Benign melanocytic nevi can be found in lymph nodes.[3]

Progressive transformation of germinal centers

  • Abbreviated as PTGC.

Reactive follicular hyperplasia

Diffuse paracortical hyperplasia

General

  • Benign.

Microscopic

Features:[4]

  • Interfollicular areas enlarged - key feature.
    • T cell population increased.
    • Plasma cells.
    • Macrophages.
    • Large Reed-Sternberg-like cells.

Sinus histiocytosis

Should not be confused with sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease.

Kikuchi disease

  • AKA histiocytic necrotising lymphadenitis (HNL).[5]
  • AKA Kikuchi-Fujimoto disease.

Systemic lupus erythematosus lymphadenopathy

Castleman disease

  • AKA angiofollicular lymph node hyperplasia, giant lymph node hyperplasia.[6]
  • Abbreviated CD.

Cat-scratch disease

  • AKA cat scratch fever.

Toxoplasma lymphadenitis

General

  • Caused by protozoan Toxoplasma gondii.

Microscopic

Features:[7]

  • Reactive germinal centers (pale areas - larger than usual).
    • Often poorly demarcated - due to loose epithelioid cell clusters at germinal center edge - key feature.
  • Epithelioid cells - perifollicular & intrafollicular.
    • Loose aggregates of histiocytes (do not form round granulomas):
      • Abundant pale cytoplasm.
      • Nucleoli.
  • Monocytoid cells (monocyte-like cells) - in cortex & paracortex.
    • Large cells in islands/sheets key feature with:
      • Abundant pale cytoplasm - important.
      • Well-defined cell border - important.
      • Singular nucleus.
    • Cell clusters usually have interspersed neutrophils.

Images:

Notes:

  • Monocytoid cells CD68 -ve.

IHC

  • IHC for toxoplasmosis.

Dermatopathic lymphadenopathy

Kimura lymphadenopathy

Rosai-Dorfman disease

  • Abbreviated RDD.
  • AKA sinus histiocytosis with massive lymphadenopathy, abbreviated SHML.

Langerhans cell histiocytosis

Lymph node hyalinization

  • AKA hyalinized lymph node.

General

  • Benign.
  • Associated with aging.[8]

Microscopic

Features:

  • Hyaline material (acellular pink stuff on H&E) within a lymph node.

Subdivided into:[8]

  • Mediastinal-type.
    • Usually in medullary sinus.
    • Onion peel-like appearance.
  • Pelvic-type hyalinization.
    • Discrete round, eosinophilic, glassy appearance at low power, whirled/fibrous at high power.
    • +/-Calcification.

DDx:

  • Amyloidosis - cotton candy-like appearance, usu. no calcifications.

Images

www:

Sign out

  • Not reported.

See also

References

  1. URL: http://path.upmc.edu/cases/case289.html. Accessed on: 14 January 2012.
  2. DB. 4 August 2010.
  3. 3.0 3.1 Bigotti, G.; Coli, A.; Mottolese, M.; Di Filippo, F. (Sep 1991). "Selective location of palisaded myofibroblastoma with amianthoid fibres.". J Clin Pathol 44 (9): 761-4. PMC 496726. PMID 1918406. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC496726/.
  4. Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 179. ISBN 978-0781775960.
  5. Kaushik V, Malik TH, Bishop PW, Jones PH (June 2004). "Histiocytic necrotising lymphadenitis (Kikuchi's disease): a rare cause of cervical lymphadenopathy". Surgeon 2 (3): 179–82. PMID 15570824.
  6. URL: http://www.mayoclinic.com/health/castleman-disease/DS01000. Accessed on: 17 June 2010.
  7. Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 113. ISBN 978-0781775960.
  8. 8.0 8.1 Taniguchi, I.; Murakami, G.; Sato, A.; Fujiwara, D.; Ichikawa, H.; Yajima, T.; Kohama, G. (Oct 2003). "Lymph node hyalinization in elderly Japanese.". Histol Histopathol 18 (4): 1169-80. PMID 12973685.