Difference between revisions of "Lymph node pathology"

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This article deals with non-haematologic malignant 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]]''.
==Overview in a table==
==Overview in a table==
{| class="wikitable"
{| class="wikitable"
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| large spaced cortical follicles
| large spaced cortical follicles
| tingible body macrophages, normal dark/light GC pattern
| tingible body macrophages, normal dark/light GC pattern
| BCL-2 -ve
| BCL2 -ve
| infection (Toxoplasmosis, HIV/AIDS), [[Hodgkin's lymphoma]]
| infection (Toxoplasmosis, HIV/AIDS), [[Hodgkin's lymphoma]]
| image ?  
| image ?  
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| Langerhans cell histiocytosis
| Langerhans cell histiocytosis
| [http://commons.wikimedia.org/w/index.php?title=File:Emperipolesis_-_very_high_mag.jpg]  
| [http://commons.wikimedia.org/w/index.php?title=File:Emperipolesis_-_very_high_mag.jpg]  
|-
| Systemic lupus erythematosus lymphadenopathy
| (blue) hematoxylin bodies
| necrosis, no PMNs
| IHC ?
| Kikuchi disease
| image ?
|-
|-
<!-- | entity  
<!-- | entity  
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| abnormal
| abnormal
|}
|}
==Progressive transformation of germinal centers==
===General===
*Abbreviated as ''PTGC''.
*Benign.
*Classically in younger patients.
*Associated with [[Hodgkin's lymphoma]] - non-classic type (nodular lymphocyte predominant Hodgkin's lymphoma).
===Microscopic===
Features:
*'''Focally''' large germinal centers with:
**Expanded mantle zone.
**Poorly demarcated germinal centre (due to infiltration by mantle zone lymphocytes) -- '''key feature'''.
==Reactive follicular hyperplasia==
===General===
*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.
IHC:
*BCL-2 -ve.
Image: [http://pleiad.umdnj.edu/hemepath/normal_node/normal_node.html Normal lymph node (umdnj.edu)].
==Diffuse paracortical hyperplasia==
===General===
*Benign.
===Microscopic===
Features:<ref name=Ref_ILNP179>{{Ref_ILNP|179}}</ref>
*Interfollicular areas enlarged - '''key feature'''.
**T cell population increased.
**Plasma cells.
**Macrophages.
**Large Reed-Sternberg-like cells.
==Sinus histiocytosis==
===General===
*Benign.
===Microscopic===
Features:<ref name=Ref_ILNP179>{{Ref_ILNP|179}}</ref>
*Sinuses distended with histiocytes - '''key feature'''.
*Plasma cells increased.
==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> and ''Kikuchi-Fujimoto disease''.
*Rare disease that may mimic cancer, esp. lymphoma.
**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.
**Hematoxyphil bodies in necrotic foci.
***Dark blue irregular bodies on H&E.
===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 nucleolus.
Images:
*[http://commons.wikimedia.org/w/index.php?title=File:Histiocytic_necrotizing_lymphadenitis_-_intermed_mag.jpg Kikuchi disease - intermed mag (WC)].
*[http://commons.wikimedia.org/w/index.php?title=File:Histiocytic_necrotizing_lymphadenitis_-_high_mag.jpg Kikuchi disease - high mag (WC)].
*[http://commons.wikimedia.org/w/index.php?title=File:Histiocytic_necrotizing_lymphadenitis_-_very_high_mag.jpg Kikuchi disease - very high mag (WC)].
===IHC===
*CD68 +ve.
*CD8 +ve.
*CD4, CD20, CD3, and CD30 - mixed.
**Done to excluded lymphoma; should show a mixed population of lymphocytes.
==Systemic lupus erythematosus lymphadenopathy==
===General===
*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.
==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>
*Benign.
*Abbreviated '''CD'''.
===Classification===
CD is grouped by histologic appearance:<ref name=Ref_ILNP228>{{Ref ILNP|228}}</ref>
#Hyaline vascular (HV) variant (described by Castleman).
#*Usually unicentric.
#*Typically mediastinal or axial.
#*More common than plasma cell variant; represents 80-90% of CD cases.
#Plasma cell (PC) variant.
#*Usually multicentric, may be unicentric.
#*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===
Hyaline-vascular variant - 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><ref name=Ref_ILNP236>{{Ref ILNP|236}}</ref>
*Pale concentric (expanded) mantle zone lymphocytes - '''key feature'''.
**"Regressed follicles" - germinal center (pale area) is small.
*"Lollipops":
**Germinal centers fed by prominent (radially penetrating sclerotic) vessels; lollipop-like appearance.
*Two germinal centers in one follicle.
*Hyaline material (pink acellular stuff on H&E) in germinal center.
*Sinuses effaced (lost).
*Mitoses absent.
Plasma cell variant - features:<ref name=Ref_ILNP236>{{Ref ILNP|236}}</ref>
*Interfollicular sheets of plasma cells - '''key feature'''.
*Active germinal centers - mitoses present.
*Sinus perserved.
==Cat-scratch disease==
===General===
*[[AKA]] ''Cat-scratch fever''.
*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 disseminated 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.
Images:
*[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)]
*[http://commons.wikimedia.org/wiki/File:Cat_scratch_disease_-_very_low_mag.jpg CSD - very low mag. - showing serpentine shaped microabscesses (WC)].
*[http://commons.wikimedia.org/wiki/File:Cat_scratch_disease_-b-_high_mag.jpg CSD - high mag. - showing neutrophilic abscesses (WC)].
==Toxoplasma lymphadenitis==
===General===
*Caused by protozoan ''Toxoplasma gondii''.
===Microscopic===
Features:<ref name=Ref_ILNP113>{{Ref ILNP|113}}</ref>
*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.
Notes:
*Monocytoid cells CD68 -ve.
==Dermatopathic lymphadenopathy==
===General===
*Lymphadenopathy associated with a skin lesion - '''key feature'''.
*May be benign or malignant (e.g. T-cell lymphoma).
===Microscopic===
Features:<ref name=ILNP226>{{Ref ILNP|226}}</ref>
*Abundant histiocytes & special histiocytes - in loose irregular clusters '''key feature''':
**Do ''not'' form granuloma; may be similar to ''toxoplasma''.
*Plasma cells (medulla).
*Eosinophils.
Histiocytes & special histiocytes:
*Histiocytes:
**+/-Melanin pigment '''key feature''' (if present).
**Lipid-laden macrophages.
*Interdigitating dendritic cells:
**Need IHC to identify definitively.
*Langerhans cells:
**Classically have a kidney bean nuclei.
**Need IHC to identify definitively.
IHC:
*Interdigitating dendritic cells: S100 +ve, CD1a -ve.
*Langerhans cells: S100 +ve, CD1a +ve.
==Kimura lymphadenopathy==
===General===
*[[AKA]] ''eosinophilic lymphogranuloma'', ''Kimura disease''.
*Chronic inflammatory disorder - suspected to be infectious.
Clinical:
*Usually neck, periauricular.
*Peripheral blood eosinophilia.
*Increased blood IgE.
===Epidemiology===
*Males > females.
*Young.
*Asian.
===Microscopic===
Features:<ref name=Ref_ILNP190>{{Ref ILNP|190}}</ref>
*Angiolymphoid proliferation.
**Thick walled blood vessels with (plump) hobnail endothelial cells.<ref>URL: [http://emedicine.medscape.com/article/1098777-diagnosis http://emedicine.medscape.com/article/1098777-diagnosis]. Accessed on: 8 August 2010.</ref>
*Eosinophils - abundant - '''key feature'''.
Notes:
*Abundant eosinophils: consider Langerhans histiocytosis.
Images:
*[http://commons.wikimedia.org/wiki/File:Kimura_disease_-_very_high_mag.jpg Kimura disease - very high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Kimura_disease_-_high_mag.jpg Kimura disease - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Kimura_disease_-_intermed_mag.jpg Kimura disease - intermed. mag. (WC)].
===IHC===
*Used to rule-out a clonal population.
==Rosai-Dorfman disease==
===General===
*[[AKA]] ''sinus histiocytosis with massive lymphadenopathy'', abbreviated ''SHML''.<ref name=pmid17183839>{{cite journal |author=Agarwal A, Pathak S, Gujral S |title=Sinus histiocytosis with massive lymphadenopathy--a review of seven cases |journal=Indian J Pathol Microbiol |volume=49 |issue=4 |pages=509–15 |year=2006 |month=October |pmid=17183839 |doi= |url=}}</ref>
*Super rare.
*Prognosis - good.
===Microscopic===
Features:
*Sinus histiocytosis:
**Histiocytes - abundant.
***Small round nuclei.
***Abundant cytoplasm.
*Emperipolesis.
**Histiocytes "eat" other cells: neutrophils, lymphocytes, plasma cells.
IHC:
*CD68 +ve.
*S100 +ve.
**Useful for seeing emperipolesis.
*CD1a -ve.
**CD1a positive in Langerhans cell histiocytosis.
Images:
*[http://commons.wikimedia.org/wiki/File:Emperipolesis_-_very_high_mag.jpg Emperipolesis in SHML (WC)].
*[http://commons.wikimedia.org/wiki/File:Rosai-Dorfman_disease_-_very_high_mag.jpg Rosai-Dorfman disease (WC)].
==Langerhans cell histiocytosis==
===General===
*Abbreviated ''LCH''.
*Genetic thingy.
*Looks like eosinophilic granuloma of the lung - see ''[[Medical_lung_diseases#Pulmonary_Langerhans_cell_histiocytosis|medical lung diseases]]''.
===Microscopic===
Features:
*Langerhans cells histiocytes:
**Clusters of cells (histiocytes) with a reniform (kidney-shaped) nucleus and abundant foamy cytoplasm.
**+/-Eosinophils - often prominent.
Images:
*[http://commons.wikimedia.org/wiki/File:Langerhans_cell_histiocytosis_-_very_high_mag.jpg LCH - lymph node - very high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Langerhans_cell_histiocytosis_-_high_mag.jpg LCH - lymph node - high mag. (WC)].
===IHC===
*CD1a +ve.
*S100 +ve.
==See also==
*[[Haematopathology]].
==References==
{{reflist|2}}
[[Category:Haematopathology]]

Revision as of 02:33, 13 August 2010

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 ?
Toxoplasmosis large follicles; epithelioid cells perifollicular & intrafollicular reactive GCs, monocytoid cell clusters, epithelioid cells IHC ? NSRFH, HIV/AIDS, Hodgkin's lymphoma image ?
Kikuchi disease (histiocystic necrotizing lymphadenitis) No PMNs histiocytes, necrosis IHC neg. for malignancy SLE (has (blue) hematoxylin bodies in necrotic areas) [1]
Cat-scratch disease PMNs in necrotic area "stellate" (or serpentine) shaped microabscesses, granulomas B. henselae, Dieterle stain HIV/AIDS, NSRFH [2]
Dermatopathic lymphadenopathy melanin-laden histiocytes histiocytosis S100+ve (interdigitating dendritic cells), CD1a+ve (Langerhans cells) DDx ? image ?
Kimura disease eosinophils angiolymphoid proliferation IHC ? eosinophilic granuloma [3]
Langerhans cell histiocytosis abundant histiocytes with reniform nuclei often prominent eosinophilia S100+, CD1a+ Kimura disease (eosinophilia), Rosai-Dorfman disease [4]
Rosai-Dorfman disease sinus histiocytosis emperipolesis S100+, CD1a- Langerhans cell histiocytosis [5]
Systemic lupus erythematosus lymphadenopathy (blue) hematoxylin bodies necrosis, no PMNs IHC ? Kikuchi disease image ?

Follicular lymphoma vs. reactive follicular hyperplasia

Factors to consider:[1]

Reactive follicular
hyperplasia 		Follicular lymphoma
Follicle location cortex cortex and medulla
Germinal center edge sharp/well-demarcated poorly demarcated
Germinal center density well spaced crowded
Tingible body
macrophages 		common uncommon
Germinal center
light/dark pattern 		normal abnormal
  1. ↑ DB. 4 August 2010.
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