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

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) image ?
Cat-scratch disease PMNs in necrotic area "stellate" (or serpentine) shaped microabscesses, granulomas B. henselae, Dieterle stain HIV/AIDS, NSRFH image ?
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 image ?
entity key feature other features IHC DDx 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

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.

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.

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 nucleolous.

Images:

IHC

  • CD68 +ve.
  • CD8 +ve.
  • CD4, CD20, CD3, and CD30 - mixed.
    • Done to excluded lymphoma; should show a mixed population of lymphocytes.

Castleman disease

General

  • AKA angiofollicular lymph node hyperplasia, giant lymph node hyperplasia.[9]
  • Benign.
  • Abbreviated CD.

Classification

CD is grouped by histologic appearance:[10]

  1. 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.
  2. 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: [11]

Microscopic

Hyaline-vascular variant - features:[12][13]

  • 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:[13]

  • 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,[14] a gram-negative bacilla (0.3-1.0 x 0.6-3.0 micrometers) in chains, clumps, or singular.[15]
  • Treatment: antibiotics.

Clinical

Features:[16]

  • Usually unilateral.
    • May be disseminated in individuals with immune dysfunction.
  • Contact with cats.

Micrograph

Features:[16]

  • 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):

Toxoplasma lymphadenitis

General

  • Caused by protozoan Toxoplasma gondii.

Microscopic

Features:[16]

  • 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:[17]

  • 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:[18]

  • Angiolymphoid proliferation.
  • Eosinophils - abundant - key feature.

Notes:

  • Abundant eosinophils: consider Langerhans histiocytosis.

Rosai-Dorfman disease

General

  • AKA sinus histiocytosis with massive lymphadenopathy, abbreviated SHML.[19]
  • 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:

See also

References

  1. ↑ DB. 4 August 2010.
  2. ↑ Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 174. ISBN 978-0781775960.
  3. ↑ 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.
  4. ↑ 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. ↑ 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.
  6. ↑ URL: http://emedicine.medscape.com/article/210752-overview. Accessed on: 3 June 2010.
  7. ↑ 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.
  8. ↑ URL: http://www.healthsystem.virginia.edu/internet/hematology/hessedd/benignhematologicdisorders/normal-hematopoietic-cells/dendritic-cell.cfm?drid=214. Accessed on: 3 June 2010.
  9. ↑ URL: http://www.mayoclinic.com/health/castleman-disease/DS01000. Accessed on: 17 June 2010.
  10. ↑ Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 228. ISBN 978-0781775960.
  11. ↑ PMID 19546611
  12. ↑ 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.
  13. ↑ 13.0 13.1 Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 236. ISBN 978-0781775960.
  14. ↑ 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.
  15. ↑ Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 110. ISBN 978-0781775960.
  16. ↑ 16.0 16.1 16.2 Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 113. ISBN 978-0781775960.
  17. ↑ Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 226. ISBN 978-0781775960.
  18. ↑ Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 190. ISBN 978-0781775960.
  19. ↑ 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.
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