Difference between revisions of "Lymph node pathology"
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==Progressive transformation of germinal centers== | ==Progressive transformation of germinal centers== | ||
*Abbreviated as ''PTGC''. | |||
===General=== | ===General=== | ||
*Benign. | *Benign. | ||
*Classically in younger patients. | *Classically in younger patients. | ||
*Associated with [[Hodgkin's lymphoma]] | *Associated with nodular lymphocyte predominant [[Hodgkin's lymphoma]] (NLPHL); NLPHL found in up to 5% in a 7 year follow-up.<ref name=pmid12145465>{{cite journal |author=Verma A, Stock W, Norohna S, Shah R, Bradlow B, Platanias LC |title=Progressive transformation of germinal centers. Report of 2 cases and review of the literature |journal=Acta Haematol. |volume=108 |issue=1 |pages=33–8 |year=2002 |pmid=12145465 |doi= |url=}}</ref> | ||
Clinical: | |||
*Asymptomatic lymphadenopathy. | |||
===Microscopic=== | ===Microscopic=== | ||
Features: | Features: | ||
*Follicular hyperplasia (many follicles). | |||
*'''Focally''' large germinal centers with: | *'''Focally''' large germinal centers with: | ||
**Poorly demarcated germinal center (GC)/mantle zone interfaces (as GCs infiltrated by mantle zone lymphocytes) -- '''key feature'''.<ref name=pmid12145465/> | |||
**Expanded mantle zone. | **Expanded mantle zone. | ||
==Reactive follicular hyperplasia== | ==Reactive follicular hyperplasia== | ||
Revision as of 19:49, 27 August 2010
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
| 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 for toxoplasma | NSRFH, HIV/AIDS, Hodgkin's lymphoma | [1], [2] |
| Kikuchi disease (histiocystic necrotizing lymphadenitis) | No PMNs | histiocytes, necrosis | IHC neg. for malignancy | SLE (has (blue) hematoxylin bodies in necrotic areas) | [3] |
| Cat-scratch disease | PMNs in necrotic area | "stellate" (or serpentine) shaped microabscesses, granulomas | B. henselae, Dieterle stain | HIV/AIDS, NSRFH | [4] |
| Dermatopathic lymphadenopathy | melanin-laden histiocytes | histiocytosis | S100+ve (interdigitating dendritic cells), CD1a+ve (Langerhans cells) | DDx ? | [5], [6] |
| Kimura disease | eosinophils | angiolymphoid proliferation (thick-walled blood vessels with hobnail endothelial cells) | IHC ? | eosinophilic granuloma | [7] |
| Langerhans cell histiocytosis | abundant histiocytes with reniform nuclei | often prominent eosinophilia | S100+, CD1a+ | Kimura disease (eosinophilia), Rosai-Dorfman disease | [8] |
| Rosai-Dorfman disease | sinus histiocytosis | emperipolesis (intact cell within a macrophage) | S100+, CD1a- | Langerhans cell histiocytosis | [9] |
| Systemic lupus erythematosus lymphadenopathy | (blue) hematoxylin bodies | necrosis, no PMNs | IHC ? | Kikuchi disease | [10] |
| 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 | [11], [12] |
| Castleman disease, plasma cell variant | thick mantle cell layer | sinus perserved, interfollicular plasma cells, mitoses in GC | HHV-8 | HIV/AIDS | image ? |
![[1]](http://commons.wikimedia.org/wiki/File:Toxoplasmosis_lymphadenopathy_-_low_mag.jpg){kind=link}
![[2]](http://commons.wikimedia.org/wiki/File:Toxoplasmosis_lymphadenopathy_-_high_mag.jpg){kind=link}
![[3]](http://commons.wikimedia.org/w/index.php?title=File:Histiocytic_necrotizing_lymphadenitis_-_very_high_mag.jpg){kind=link}
![[4]](http://commons.wikimedia.org/wiki/File:Cat_scratch_disease_-_very_low_mag.jpg){kind=link}
![[5]](http://commons.wikimedia.org/wiki/File:Dermatopathic_lymphadenopathy_-_low_mag.jpg){kind=link}
![[6]](http://commons.wikimedia.org/wiki/File:Dermatopathic_lymphadenopathy_-_intermed_mag.jpg){kind=link}
![[7]](http://commons.wikimedia.org/wiki/File:Kimura_disease_-_very_high_mag.jpg){kind=link}
![[8]](http://commons.wikimedia.org/w/index.php?title=File:Langerhans_cell_histiocytosis_-_very_high_mag.jpg){kind=link}
![[9]](http://commons.wikimedia.org/w/index.php?title=File:Emperipolesis_-_very_high_mag.jpg){kind=link}
![[10]](http://commons.wikimedia.org/wiki/File:Systemic_lupus_erythematosus_lymphadenopathy_-_high_mag.jpg){kind=link}
![[11]](http://commons.wikimedia.org/wiki/File:Castleman_disease_-_intermed_mag.jpg){kind=link}
![[12]](http://commons.wikimedia.org/wiki/File:Castleman_disease_-_high_mag.jpg){kind=link}
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, sinuses open | crowded, sinuses effaced/ compressed to nothingness |
| Tingible body macrophages |
common | uncommon |
| Germinal center light/dark pattern |
normal | abnormal |
Progressive transformation of germinal centers
- Abbreviated as PTGC.
General
- Benign.
- Classically in younger patients.
- Associated with nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL); NLPHL found in up to 5% in a 7 year follow-up.[2]
Clinical:
- Asymptomatic lymphadenopathy.
Microscopic
Features:
- Follicular hyperplasia (many follicles).
- Focally large germinal centers with:
- Poorly demarcated germinal center (GC)/mantle zone interfaces (as GCs infiltrated by mantle zone lymphocytes) -- key feature.[2]
- Expanded mantle zone.
Reactive follicular hyperplasia
General
- Many causes - including: bacteria, viruses, chemicals, drugs, allergens.
- In only approximately 10% can definitive cause be identified.[3]
Microscopic
Features:[4]
- 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.
- Large germinal centers (pale on H&E).
IHC:
- BCL2 -ve.
Image: Normal lymph node (umdnj.edu).
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
General
- Benign.
Microscopic
Features:[4]
- Sinuses distended with histiocytes - key feature.
- Plasma cells increased.
Kikuchi disease
General
- AKA histiocytic necrotising lymphadenitis (HNL),[5] and Kikuchi-Fujimoto disease.
- Rare disease that may mimic cancer, esp. lymphoma.
- May cause fever & systemic symptoms.[6]
Epidemiology:[6]
- Usually <40 years old.
- Asian.
- Female:Male = 3:1.[7]
Treatment:
- Usually self-limited.[6]
- Oral corticosteroids.
DDx:
- Non-Hodgkin lymphoma.
- Systemic lupus erythematosus.
- Hematoxyphil bodies in necrotic foci.
- Dark blue irregular bodies on H&E.
- Hematoxyphil bodies in necrotic foci.
Micrograph
Features (the three main features - just as the name suggests):[8]
- Histiocytes.
- May be crescentic.
- Necrosis (due to apoptosis) - paracortical areas.[6]
- Necrosis without neutrophils - key feature.
- Lymphocytes (CD8 +ve).
- Plasmacytoid dendritic cells.
Notes:
- Dendritic cell - vaguely resembles a macrophage:[9]
- Long membrane projections - key feature.
- Abundant blue-grey cytoplasm, +/- ground-glass appearance.
- Nucleus: small, ovoid, usu. single nucleolus.
Images:
- Kikuchi disease - intermed mag (WC).
- Kikuchi disease - high mag (WC).
- 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:[10]
- Necrosis.
- Hematoxylin bodies (in necrotic foci).
- Dark blue irregular bodies on H&E.
Images:
DDx:
- Kikuchi disease.
Castleman disease
General
- AKA angiofollicular lymph node hyperplasia, giant lymph node hyperplasia.[11]
- Benign.
- Abbreviated CD.
Classification
CD is grouped by histologic appearance:[12]
- 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).
Notes:
- The subclassification of CD is in some flux. Some authors advocate splitting-out HHV-8 and multicentric as separate subtypes.[13]
Microscopic
Hyaline-vascular variant (HVV)
- 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.
Images:
- CD HVV - "lollipop" sign - high mag. (WC).
- CD HVV - showing expanded mantle zone - intermed. mag. (WC).
Plasma cell variant
Features:[15]
- 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,[16] a gram-negative bacilla (0.3-1.0 x 0.6-3.0 micrometers) in chains, clumps, or singular.[17]
- Treatment: antibiotics.
Clinical
Features:[18]
- Usually unilateral.
- May be disseminated in individuals with immune dysfunction.
- Contact with cats.
Micrograph
Features:[18]
- Necrotizing granulomas with:
- Neutrophils present in microabscess (necrotic debris) - key feature.
- Microabscesses often described as "stellate" (star-shaped).
- Neutrophils present in microabscess (necrotic debris) - key feature.
- +/-Multinucleated giant cells.
Notes:
- May involve capsule or perinodal tissue.
Stains:
- Warthin-Starry stain +ve.
- B. henselae IHC stain +ve.
Images:
- Cat-scratch disease (webpathology.com).
- Cat-scratch disease - high mag. (webpathology.com)
- CSD - very low mag. - showing serpentine shaped microabscesses (WC).
- CSD - high mag. - showing neutrophilic abscesses (WC).
Toxoplasma lymphadenitis
General
- Caused by protozoan Toxoplasma gondii.
Microscopic
Features:[18]
- 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.
- Loose aggregates of histiocytes (do not form round granulomas):
- 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.
- Large cells in islands/sheets key feature with:
Images:
Notes:
- Monocytoid cells CD68 -ve.
IHC
- IHC for toxoplasmosis.
Dermatopathic lymphadenopathy
General
- Lymphadenopathy associated with a skin lesion - key feature.
- May be benign or malignant (e.g. T-cell lymphoma).
Microscopic
Features:[19]
- Abundant histiocytes & special histiocytes - in loose irregular clusters key feature:
- Do not form granuloma; may be similar to toxoplasma.
- Plasma cells (medulla).
- Eosinophils.
Images:
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:[20]
- Angiolymphoid proliferation.
- Thick walled blood vessels with (plump) hobnail endothelial cells.[21]
- Eosinophils - abundant - key feature.
Notes:
- Abundant eosinophils: consider Langerhans cell histiocytosis.
Images:
- Kimura disease - very high mag. (WC).
- Kimura disease - high mag. (WC).
- 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.[22]
- Super rare.
- Prognosis - good.
Microscopic
Features:
- Sinus histiocytosis:
- Histiocytes - abundant.
- Singular large round nuclei[23] ~2x the size of resting lymphocyte.
- Prominent nucleolus - visible with 10x objective.
- Abundant cytoplasm.
- Singular large round nuclei[23] ~2x the size of resting lymphocyte.
- Histiocytes - abundant.
- Emperipolesis (from Greek: em = inside, peri = around, polemai = wander about[24]):
Images:
- Emperipolesis in SHML (WC).
- Rosai-Dorfman disease (WC).
- Rosai-Dorfman disease - S100 showing emperipolesis (WC).
DDx:
- Other histiocytosis:
- Langerhans cell histiocytosis.
- Erdheim-Chester disease.
- Infection, e.g. Rhinoscleroma (nasopharynx), xanthomatous pyelonephritis.
- Xanthomatous change.
IHC
- CD68 +ve.
- S100 +ve.
- Useful for seeing emperipolesis.
- CD1a -ve.
- CD1a positive in Langerhans cell histiocytosis.
Langerhans cell histiocytosis
General
- Abbreviated LCH.
- Genetic thingy.
- Looks like eosinophilic granuloma of the lung - see 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:
IHC
- CD1a +ve.
- S100 +ve.
See also
References
- ↑ DB. 4 August 2010.
- ↑ 2.0 2.1 Verma A, Stock W, Norohna S, Shah R, Bradlow B, Platanias LC (2002). "Progressive transformation of germinal centers. Report of 2 cases and review of the literature". Acta Haematol. 108 (1): 33–8. PMID 12145465.
- ↑ Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 174. ISBN 978-0781775960.
- ↑ 4.0 4.1 4.2 Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 179. ISBN 978-0781775960.
- ↑ 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.
- ↑ 6.0 6.1 6.2 6.3 Hutchinson CB, Wang E (February 2010). "Kikuchi-Fujimoto disease". Arch. Pathol. Lab. Med. 134 (2): 289–93. PMID 20121621.
- ↑ URL: http://emedicine.medscape.com/article/210752-overview. Accessed on: 3 June 2010.
- ↑ 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. Accessed on: 1 June 2010.
- ↑ URL: http://www.healthsystem.virginia.edu/internet/hematology/hessedd/benignhematologicdisorders/normal-hematopoietic-cells/dendritic-cell.cfm?drid=214. Accessed on: 3 June 2010.
- ↑ Kojima, M.; Nakamura, S.; Itoh, H.; Yoshida, K.; Asano, S.; Yamane, N.; Komatsumoto, S.; Ban, S. et al. (1997). "Systemic lupus erythematosus (SLE) lymphadenopathy presenting with histopathologic features of Castleman' disease: a clinicopathologic study of five cases.". Pathol Res Pract 193 (8): 565-71. PMID 9406250.
- ↑ URL: http://www.mayoclinic.com/health/castleman-disease/DS01000. Accessed on: 17 June 2010.
- ↑ Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 228. ISBN 978-0781775960.
- ↑ Cronin, DM.; Warnke, RA. (Jul 2009). "Castleman disease: an update on classification and the spectrum of associated lesions.". Adv Anat Pathol 16 (4): 236-46. doi:10.1097/PAP.0b013e3181a9d4d3. PMID 19546611.
- ↑ 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. Accessed on: 15 June 2010.
- ↑ 15.0 15.1 Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 236. ISBN 978-0781775960.
- ↑ Jerris, RC.; Regnery, RL. (1996). "Will the real agent of cat-scratch disease please stand up?". Annu Rev Microbiol 50: 707-25. doi:10.1146/annurev.micro.50.1.707. PMID 8905096.
- ↑ Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 110. ISBN 978-0781775960.
- ↑ 18.0 18.1 18.2 Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 113. ISBN 978-0781775960.
- ↑ Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 226. ISBN 978-0781775960.
- ↑ Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 190. ISBN 978-0781775960.
- ↑ URL: http://emedicine.medscape.com/article/1098777-diagnosis. Accessed on: 8 August 2010.
- ↑ Agarwal A, Pathak S, Gujral S (October 2006). "Sinus histiocytosis with massive lymphadenopathy--a review of seven cases". Indian J Pathol Microbiol 49 (4): 509–15. PMID 17183839.
- ↑ DB. 24 August 2010.
- ↑ Stedman's Medical Dictionary. 27th Ed.
- ↑ Viswanathan P, Raghunathan K, Majhi U, Pandit RV, Shanthi R, Rajkumar T (1997). Emperipolesis : an electron microscopic characteristic in RDD (Rosai-Dorfaman disease) : a case report. pp. 14-6. http://www.ijmpo.org/article.asp?issn=0971-5851;year=1997;volume=18;issue=1;spage=14;epage=16;aulast=Viswanathan;type=0.
- ↑ Lyons DJ, Gautam A, Clark J, et al. (January 1992). "Lymphocyte macrophage interactions: peripolesis of human alveolar macrophages". Eur. Respir. J. 5 (1): 59–66. PMID 1577151.