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Lymph node pathology (view source)

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This article deals with '''lymph node pathology'''.  An introduction to the lymph node is in the ''[[lymph nodes]]'' article.
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.


==Progressive transformation of germinal centers==
Haematologic malignancies (in lymph nodes) are dealt with in other articles - see ''[[haematopathology]]'' and ''[[lymphoma]]''.
===General===
 
*Abbreviated as ''PTGC''.
==Overview==
*Benign.
Clinical:
*Classically in younger patients.
*Lymphadenopathy.
*Associated with Hodgkin's lymphoma - non-classic type (nodular lymphocyte predominant Hodgkin's lymphoma).
 
Differential diagnosis:<ref>URL: [http://path.upmc.edu/cases/case289.html http://path.upmc.edu/cases/case289.html]. Accessed on: 14 January 2012.</ref>
*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==
{| class="wikitable sortable"
! 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]])
| [[Image:Crc_met_to_node1.jpg|thumb|center|125px| CRC metastasis]] [[Image:Breast_carcinoma_in_a_lymph_node.jpg|thumb|center|125px | 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
| [[Image:Progressive transformation_of_germinal_centres_-1-_very_low_mag.jpg|thumb|center|150px | 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]]
| [[Image:Toxoplasmosis_lymphadenopathy_-_low_mag.jpg|thumb|center|150px | 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
| [[Image:Histiocytic_necrotizing_lymphadenitis_-_very_high_mag.jpg |thumb|center|150px| HNL - very high mag.]]
|-
| [[Cat-scratch disease]]
| PMNs in necrotic area
| "stellate" (or serpentine) shaped microabscesses, granulomas
| B. henselae, [[Dieterle stain]]
| [[HIV]]/AIDS, NSRFH
| [[Image:Cat_scratch_disease_-_very_low_mag.jpg|thumb|center|150px|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]]
| [[Image:Dermatopathic_lymphadenopathy_-_intermed_mag.jpg |thumb|center|150px| DL - intermed. mag.]]
|-
| [[Kimura disease]]
| eosinophils
| angiolymphoid proliferation (thick-walled blood vessels with [[hobnail]] endothelial cells)
| IHC ?
| [[Langerhans cell histiocytosis]], drug reaction, [[angiolymphoid hyperplasia with eosinophilia]]
| [[Image:Kimura_disease_-_very_high_mag.jpg|thumb|center|150px|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]]
| [[Image:Langerhans_cell_histiocytosis_-_very_high_mag.jpg|thumb|center|150px|LCH - very high mag.]]
|-
| [[Rosai-Dorfman disease]]
| sinus histiocytosis
| emperipolesis (intact cell within a macrophage)
| [[S-100]]+, CD1a-
| Langerhans cell histiocytosis
| [[Image:Emperipolesis_-_very_high_mag.jpg |thumb|center|150px | 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 [[lymphoma]]s
| [[Image:Systemic_lupus_erythematosus_lymphadenopathy_-_high_mag.jpg|thumb|center|150px | 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
| [[Image:Castleman_disease_-_intermed_mag.jpg|thumb|center|150px | 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]]
| [[Image:Intranodal_palisaded_myofibroblastoma_-_very_high_mag.jpg|thumb|center|150px|IPM - very high mag.]]
|-
<!-- | entity
| key feature
| other features
| IHC
| DDx
| image -->
|}


===Microscopic===
===Follicular lymphoma vs. reactive follicular hyperplasia===
Features:
Factors to consider:<ref>DB. 4 August 2010.</ref>
*Large germinal centers - focally.
{| class="wikitable"
**No mass lesions.
!
! Reactive follicular <br>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/<br>compressed to nothingness
|-
| Tingible body <br>macrophages
| common
| uncommon
|-
| Germinal center<br>light/dark pattern
| normal
| abnormal
|}


==Reactive follicular hyperplasia==
==Lymph node metastasis==
===General===
{{Main|Lymph node metastasis}}
*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===
==Kaposi sarcoma==
Features:<ref name=Ref_ILNP179>{{Ref_ILNP|179}}</ref>
{{Main|Kaposi sarcoma}}
*Enlarged follicles, follicle size variation - '''key feature''' with:
*One of the few non-lymphoid primary lymph node tumours.<ref name=pmid1918406>{{Cite journal  | last1 = Bigotti | first1 = G. | last2 = Coli | first2 = A. | last3 = Mottolese | first3 = M. | last4 = Di Filippo | first4 = F. | title = Selective location of palisaded myofibroblastoma with amianthoid fibres. | journal = J Clin Pathol | volume = 44 | issue = 9 | pages = 761-4 | month = Sep | year = 1991 | doi =  | PMID = 1918406 | PMC = 496726 }}</ref>
**Large germinal centers (pale on H&E).
***Mitoses common.
***Variable lymphocyte morphology.
***Tingible-body macrophage (large, pale cells with junk in the cytoplasm).
**Rim of small (inactive) lymphocytes.


IHC:
==Melanocytic nevi==
*BCL-2 -ve.
{{Main|Melanocytic lesions}}
:See: ''[[Dermatopathic lymphadenopathy]]''.
*Benign melanocytic nevi can be found in lymph nodes.<ref name=pmid1918406>{{Cite journal  | last1 = Bigotti | first1 = G. | last2 = Coli | first2 = A. | last3 = Mottolese | first3 = M. | last4 = Di Filippo | first4 = F. | title = Selective location of palisaded myofibroblastoma with amianthoid fibres. | journal = J Clin Pathol | volume = 44 | issue = 9 | pages = 761-4 | month = Sep | year = 1991 | doi =  | PMID = 1918406 | PMC = 496726 }}</ref>


Image: [http://pleiad.umdnj.edu/hemepath/normal_node/normal_node.html Normal lymph node (umdnj.edu)].
==Progressive transformation of germinal centers==
{{Main|Progressive transformation of germinal centers}}
*Abbreviated as ''PTGC''.
 
==Reactive follicular hyperplasia==
{{Main|Reactive follicular hyperplasia}}


==Diffuse paracortical hyperplasia==
==Diffuse paracortical hyperplasia==
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==Sinus histiocytosis==
==Sinus histiocytosis==
===General===
:Should '''not''' be confused with ''[[sinus histiocytosis with massive lymphadenopathy]]'', also known as Rosai-Dorfman disease.
*Benign.
{{Main|Sinus histiocytosis}}
 
===Microscopic===
Features:<ref name=Ref_ILNP179>{{Ref_ILNP|179}}</ref>
*Sinuses distended with histiocytes - '''key feature'''.
*Plasma cells increased.


==Kikuchi disease==
==Kikuchi disease==
===General===
*[[AKA]] ''histiocytic necrotising lymphadenitis'' (HNL).<ref name="pmid15570824">{{cite journal |author=Kaushik V, Malik TH, Bishop PW, Jones PH |title=Histiocytic necrotising lymphadenitis (Kikuchi's disease): a rare cause of cervical lymphadenopathy |journal=Surgeon |volume=2 |issue=3 |pages=179–82 |year=2004 |month=June |pmid=15570824 |doi= |url=}}</ref>
*AKA ''histiocytic necrotising lymphadenitis'' (HNL),<ref name="pmid15570824">{{cite journal |author=Kaushik V, Malik TH, Bishop PW, Jones PH |title=Histiocytic necrotising lymphadenitis (Kikuchi's disease): a rare cause of cervical lymphadenopathy |journal=Surgeon |volume=2 |issue=3 |pages=179–82 |year=2004 |month=June |pmid=15570824 |doi= |url=}}</ref> and ''Kikuchi-Fujimoto disease''.
*[[AKA]] ''Kikuchi-Fujimoto disease''.
*Rare disease that may mimic cancer, esp. lymphoma.
{{Main|Kikuchi disease}}
**May cause fever & systemic symptoms.<ref name=pmid20121621>{{cite journal |author=Hutchinson CB, Wang E |title=Kikuchi-Fujimoto disease |journal=Arch. Pathol. Lab. Med. |volume=134 |issue=2 |pages=289–93 |year=2010 |month=February |pmid=20121621 |doi= |url=}}</ref>
 
Epidemiology:<ref name=pmid20121621/>
*Usually <40 years old.
*Asian.
*Female:Male = 3:1.<ref>URL: [http://emedicine.medscape.com/article/210752-overview http://emedicine.medscape.com/article/210752-overview]. Accessed on: 3 June 2010.</ref>
 
Treatment:
*Usually self-limited.<ref name=pmid20121621/>
*Oral corticosteroids.
 
DDx:
*Non-Hodgkin lymphoma.
*Systemic lupus erythematosus.
 
===Micrograph===
Features (the three main features - just as the name suggests):<ref>URL: [http://www.ispub.com/journal/the_internet_journal_of_head_and_neck_surgery/volume_1_number_1_30/article_printable/kikuchi_s_lymphadenitis_in_a_young_male.html http://www.ispub.com/journal/the_internet_journal_of_head_and_neck_surgery/volume_1_number_1_30/article_printable/kikuchi_s_lymphadenitis_in_a_young_male.html]. Accessed on: 1 June 2010.</ref>
*Histiocytes.
**May be crescentic.
*Necrosis (due to apoptosis) - paracortical areas.<ref name=pmid20121621/>
**Necrosis without neutrophils - '''key feature'''.
*Lymphocytes (CD8 +ve).
*Plasmacytoid dendritic cells.
 
 
Notes:
*Dendritic cell - vaguely resembles a macrophage:<ref>URL: [http://www.healthsystem.virginia.edu/internet/hematology/hessedd/benignhematologicdisorders/normal-hematopoietic-cells/dendritic-cell.cfm?drid=214 http://www.healthsystem.virginia.edu/internet/hematology/hessedd/benignhematologicdisorders/normal-hematopoietic-cells/dendritic-cell.cfm?drid=214]. Accessed on: 3 June 2010.</ref>
**Long membrane projections - '''key feature'''.
**Abundant blue-grey cytoplasm, +/- ground-glass appearance.
**Nucleus: small, ovoid, usu. single nucleolous.
 
Images:
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?s=20080802171644281 Kikuchi disease (surgicalpathologyatlas.com)].
*[http://www.healthsystem.virginia.edu/internet/hematology/hessedd/benignhematologicdisorders/normal-hematopoietic-cells/dendritic-cell.cfm?drid=214 Dendritic cell (virginia.edu)].


===IHC===
==Systemic lupus erythematosus lymphadenopathy==
*CD68 +ve.
{{Main|Systemic lupus erythematosus lymphadenopathy}}
*CD8 +ve.
*CD4, CD20, CD3, and CD30 - mixed.
**Done to excluded lymphoma; should show a mixed population of lymphocytes.


==Castleman disease==
==Castleman disease==
===General===
*[[AKA]] ''angiofollicular lymph node hyperplasia'', ''giant lymph node hyperplasia''.<ref>URL: [http://www.mayoclinic.com/health/castleman-disease/DS01000 http://www.mayoclinic.com/health/castleman-disease/DS01000]. Accessed on: 17 June 2010.</ref>
*[[AKA]] ''angiofollicular lymph node hyperplasia'', ''giant lymph node hyperplasia''.<ref>URL: [http://www.mayoclinic.com/health/castleman-disease/DS01000 http://www.mayoclinic.com/health/castleman-disease/DS01000]. Accessed on: 17 June 2010.</ref>
*Benign.
*Abbreviated '''CD'''.
*Abbreviated '''CD'''.
 
{{Main|Castleman disease}}
===Classification===
CD is grouped by location/involvment:
*Hyaline vascular variant.
**Usually unicentric.
**Typically mediastinal or axial.
*Plasma cell variant.
**Usually multicentric.
**Abundant plasma cells.
**Associated with HHV-8 infection (the same virus implicated in ''Kaposi's sarcoma'').
 
Discussed here: <ref name=pmid19546611>PMID 19546611</ref>
 
===Microscopic===
Features:<ref>URL: [http://www.ispub.com/journal/the_internet_journal_of_otorhinolaryngology/volume_9_number_2_11/article/a_rare_case_of_castleman_s_disease_presenting_as_cervical_neck_mass.html http://www.ispub.com/journal/the_internet_journal_of_otorhinolaryngology/volume_9_number_2_11/article/a_rare_case_of_castleman_s_disease_presenting_as_cervical_neck_mass.html]. Accessed on: 15 June 2010.</ref>
*Pale concentric (expanded) mantle zone lymphocytes.
**"Regressed follicle". (???)
*"Lollipops" - germinal centers fed by prominent vessels; lollipop-like appearance.
*Two germinal centers in one follicle.


==Cat-scratch disease==
==Cat-scratch disease==
===General===
*[[AKA]] ''cat scratch fever''.
*[[AKA]] ''Cat-scratch fever''.
{{Main|Cat scratch disease}}
*Infection caused ''Bartonella henselae'',<ref name=pmid19332922>{{Cite journal  | last1 = Jerris | first1 = RC. | last2 = Regnery | first2 = RL. | title = Will the real agent of cat-scratch disease please stand up? | journal = Annu Rev Microbiol | volume = 50 | issue =  | pages = 707-25 | month =  | year = 1996 | doi = 10.1146/annurev.micro.50.1.707 | PMID = 8905096 }}</ref> a gram-negative bacilla (0.3-1.0 x 0.6-3.0 micrometers) in chains, clumps, or singular.<ref name=Ref_ILNP110>{{Ref ILNP|110}}</ref>
*Treatment: antibiotics.
 
===Clinical===
Features:<ref name=Ref_ILNP113>{{Ref ILNP|113}}</ref>
*Usually unilateral.
**May be desseminated in individuals with immune dysfunction.
*Contact with cats.
 
===Micrograph===
Features:<ref name=Ref_ILNP113>{{Ref ILNP|113}}</ref>
*Necrotizing granulomas with:
**Neutrophils present in microabscess (necrotic debris) - '''key feature'''.
***Microabscesses often described as "stellate" (star-shaped).
*+/-Multinucleated giant cells.
 
Notes:
*May involve capsule or perinodal tissue.
 
Stains:
*Warthin-Starry stain +ve.
*B. henselae IHC stain +ve.
 
Image(s):
*[http://www.webpathology.com/image.asp?case=386&n=1 Cat-scratch disease (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=2&Case=386 Cat-scratch disease - high mag. (webpathology.com)]


==Toxoplasma lymphadenitis==
==Toxoplasma lymphadenitis==
{{Main|Toxoplasma}}
===General===
===General===
*Caused by protozoan ''Toxoplasma gondii''.
*Caused by protozoan ''Toxoplasma gondii''.
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***Well-defined cell border - '''important'''.
***Well-defined cell border - '''important'''.
***Singular nucleus.  
***Singular nucleus.  
**Cell clusters usually have interspersed neutrophils.
Images:
*[http://commons.wikimedia.org/wiki/File:Toxoplasmosis_lymphadenopathy_-_low_mag.jpg Toxoplasmosis - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Toxoplasmosis_lymphadenopathy_-_high_mag.jpg Toxoplasmosis - high mag. (WC)].


Notes:  
Notes:  
*Monocytoid cells CD68 -ve.
*Monocytoid cells CD68 -ve.
===IHC===
*IHC for toxoplasmosis.


==Dermatopathic lymphadenopathy==
==Dermatopathic lymphadenopathy==
{{Main|Dermatopathic lymphadenopathy}}
==Kimura lymphadenopathy==
{{Main|Kimura disease}}
==Rosai-Dorfman disease==
*Abbreviated ''RDD''.
*[[AKA]] ''sinus histiocytosis with massive lymphadenopathy'', abbreviated ''SHML''.
{{Main|Rosai-Dorfman disease}}
==Langerhans cell histiocytosis==
{{Main|Langerhans cell histiocytosis}}
==Lymph node hyalinization==
*[[AKA]] ''hyalinized lymph node''.
===General===
===General===
*Lymphadenopathy associated with a skin lesion. (???)
*Benign.
*May be benign of malignant (e.g. T-cell lymphoma).
*Associated with aging.<ref name=pmid12973685>{{Cite journal  | last1 = Taniguchi | first1 = I. | last2 = Murakami | first2 = G. | last3 = Sato | first3 = A. | last4 = Fujiwara | first4 = D. | last5 = Ichikawa | first5 = H. | last6 = Yajima | first6 = T. | last7 = Kohama | first7 = G. | title = Lymph node hyalinization in elderly Japanese. | journal = Histol Histopathol | volume = 18 | issue = 4 | pages = 1169-80 | month = Oct | year = 2003 | doi =  | PMID = 12973685 }}</ref>


===Microscopic===
===Microscopic===
*May see melanin pigment. (???)
Features:
*Hyaline material (acellular pink stuff on H&E) within a [[lymph node]].
 
Subdivided into:<ref name=pmid12973685/>
*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====
<gallery>
Image: Hyalinized lymph node -- intermed mag.jpg | Hyalinized LN - intermed. mag.
Image: Hyalinized lymph node - alt -- intermed mag.jpg | Hyalinized LN - intermed. mag.
Image: Hyalinized lymph node -- high mag.jpg | Hyalinized LN - high mag.
Image: Hyalinized lymph node -- very high mag.jpg | Hyalinized LN - very high mag.
</gallery>
www:
*[http://www.flickriver.com/photos/euthman/sets/72157594513987154/ Lymph node with amyloidosis - several images (flickriver.com)].
 
===Sign out===
*Not reported.


==See also==
==See also==
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[[Category:Haematopathology]]
[[Category:Haematopathology]]
[[Category:Lymph node pathology|Lymph node pathology]]
Michael
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