Lymph node pathology
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 | BCL-2 -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] |
![[1]](http://commons.wikimedia.org/w/index.php?title=File:Histiocytic_necrotizing_lymphadenitis_-_very_high_mag.jpg){kind=link}
![[2]](http://commons.wikimedia.org/wiki/File:Cat_scratch_disease_-_very_low_mag.jpg){kind=link}
![[3]](http://commons.wikimedia.org/wiki/File:Kimura_disease_-_very_high_mag.jpg){kind=link}
![[4]](http://commons.wikimedia.org/w/index.php?title=File:Langerhans_cell_histiocytosis_-_very_high_mag.jpg){kind=link}
![[5]](http://commons.wikimedia.org/w/index.php?title=File:Emperipolesis_-_very_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 | crowded |
| Tingible body macrophages |
common | uncommon |
| Germinal center light/dark pattern |
normal | 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.[2]
Microscopic
Features:[3]
- 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:
- BCL-2 -ve.
Image: Normal lymph node (umdnj.edu).
Diffuse paracortical hyperplasia
General
- Benign.
Microscopic
Features:[3]
- Interfollicular areas enlarged - key feature.
- T cell population increased.
- Plasma cells.
- Macrophages.
- Large Reed-Sternberg-like cells.
Sinus histiocytosis
General
- Benign.
Microscopic
Features:[3]
- Sinuses distended with histiocytes - key feature.
- Plasma cells increased.
Kikuchi disease
General
- AKA histiocytic necrotising lymphadenitis (HNL),[4] and Kikuchi-Fujimoto disease.
- Rare disease that may mimic cancer, esp. lymphoma.
- May cause fever & systemic symptoms.[5]
Epidemiology:[5]
- Usually <40 years old.
- Asian.
- Female:Male = 3:1.[6]
Treatment:
- Usually self-limited.[5]
- 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):[7]
- Histiocytes.
- May be crescentic.
- Necrosis (due to apoptosis) - paracortical areas.[5]
- Necrosis without neutrophils - key feature.
- Lymphocytes (CD8 +ve).
- Plasmacytoid dendritic cells.
Notes:
- Dendritic cell - vaguely resembles a macrophage:[8]
- 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:[9]
- 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.[10]
- Benign.
- Abbreviated CD.
Classification
CD is grouped by histologic appearance:[11]
- 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: [12]
Microscopic
Hyaline-vascular variant - features:[13][14]
- 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:[14]
- 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,[15] a gram-negative bacilla (0.3-1.0 x 0.6-3.0 micrometers) in chains, clumps, or singular.[16]
- Treatment: antibiotics.
Clinical
Features:[17]
- Usually unilateral.
- May be disseminated in individuals with immune dysfunction.
- Contact with cats.
Micrograph
Features:[17]
- 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:[17]
- 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.
- Large cells in islands/sheets key feature with:
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:[18]
- 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:[19]
- Angiolymphoid proliferation.
- Thick walled blood vessels with (plump) hobnail endothelial cells.[20]
- Eosinophils - abundant - key feature.
Notes:
- Abundant eosinophils: consider Langerhans 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.[21]
- Super rare.
- Prognosis - good.
Microscopic
Features:
- Sinus histiocytosis:
- Histiocytes - abundant.
- Small round nuclei.
- Abundant cytoplasm.
- Histiocytes - abundant.
- 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:
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.
- ↑ Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 174. ISBN 978-0781775960.
- ↑ 3.0 3.1 3.2 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.
- ↑ 5.0 5.1 5.2 5.3 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.
- ↑ 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.
- ↑ 14.0 14.1 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.
- ↑ 17.0 17.1 17.2 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.