Lymph node pathology

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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.

Haematologic malignancies (in lymph nodes) are dealt with in other articles - see haematopathology and lymphoma.

Overview

Clinical:

  • Lymphadenopathy.

Differential diagnosis:[1]

  • 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

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)
CRC metastasis
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
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
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
HNL - very high mag.
Cat-scratch disease PMNs in necrotic area "stellate" (or serpentine) shaped microabscesses, granulomas B. henselae, Dieterle stain HIV/AIDS, NSRFH
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
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
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
LCH - very high mag.
Rosai-Dorfman disease sinus histiocytosis emperipolesis (intact cell within a macrophage) S-100+, CD1a- Langerhans cell histiocytosis
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 lymphomas
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
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
IPM - very high mag.

Follicular lymphoma vs. reactive follicular hyperplasia

Factors to consider:[2]

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

Lymph node metastasis

Main article: Lymph node metastasis

Kaposi sarcoma

Main article: Kaposi sarcoma
  • One of the few non-lymphoid primary lymph node tumours.[3]

Melanocytic nevi

Main article: Melanocytic lesions
See: Dermatopathic lymphadenopathy.
  • Benign melanocytic nevi can be found in lymph nodes.[3]

Progressive transformation of germinal centers

Main article: Progressive transformation of germinal centers
  • Abbreviated as PTGC.

Reactive follicular hyperplasia

General

  • Many causes - including: bacteria, viruses, chemicals, drugs, allergens.
    • In only approximately 10% can definitive cause be identified.[4]

Microscopic

Features:[5]

  • 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.

DDx:

Image: Normal lymph node (umdnj.edu).

IHC

Screening panel:

Others:

  • BCL2 -ve.

Diffuse paracortical hyperplasia

General

  • Benign.

Microscopic

Features:[5]

  • Interfollicular areas enlarged - key feature.
    • T cell population increased.
    • Plasma cells.
    • Macrophages.
    • Large Reed-Sternberg-like cells.

Sinus histiocytosis

Should not be confused with sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease.
Main article: Sinus histiocytosis

Kikuchi disease

  • AKA histiocytic necrotising lymphadenitis (HNL).[6]
  • AKA Kikuchi-Fujimoto disease.
Main article: Kikuchi disease

Systemic lupus erythematosus lymphadenopathy

Main article: Systemic lupus erythematosus lymphadenopathy

Castleman disease

  • AKA angiofollicular lymph node hyperplasia, giant lymph node hyperplasia.[7]
  • Abbreviated CD.
Main article: Castleman disease

Cat-scratch disease

  • AKA cat scratch fever.
Main article: Cat scratch disease

Toxoplasma lymphadenitis

Main article: Toxoplasma

General

  • Caused by protozoan Toxoplasma gondii.

Microscopic

Features:[8]

  • 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.
    • Cell clusters usually have interspersed neutrophils.

Images:

Notes:

  • Monocytoid cells CD68 -ve.

IHC

  • IHC for toxoplasmosis.

Dermatopathic lymphadenopathy

Main article: Dermatopathic lymphadenopathy

Kimura lymphadenopathy

Main article: Kimura disease

Rosai-Dorfman disease

  • Abbreviated RDD.
  • AKA sinus histiocytosis with massive lymphadenopathy, abbreviated SHML.
Main article: Rosai-Dorfman disease

Langerhans cell histiocytosis

Main article: Langerhans cell histiocytosis

Lymph node hyalinization

  • AKA hyalinized lymph node.

General

  • Benign.
  • Associated with aging.[9]

Microscopic

Features:

  • Hyaline material (acellular pink stuff on H&E) within a lymph node.

Subdivided into:[9]

  • 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

  • Hyalinized LN - intermed. mag.

  • Hyalinized LN - intermed. mag.

  • Hyalinized LN - high mag.

  • Hyalinized LN - very high mag.

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  • Not reported.

See also

References

  1. ↑ URL: http://path.upmc.edu/cases/case289.html. Accessed on: 14 January 2012.
  2. ↑ DB. 4 August 2010.
  3. ↑ 3.0 3.1 Bigotti, G.; Coli, A.; Mottolese, M.; Di Filippo, F. (Sep 1991). "Selective location of palisaded myofibroblastoma with amianthoid fibres.". J Clin Pathol 44 (9): 761-4. PMC 496726. PMID 1918406. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC496726/.
  4. ↑ Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 174. ISBN 978-0781775960.
  5. ↑ 5.0 5.1 Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 179. ISBN 978-0781775960.
  6. ↑ 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.
  7. ↑ URL: http://www.mayoclinic.com/health/castleman-disease/DS01000. Accessed on: 17 June 2010.
  8. ↑ Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 113. ISBN 978-0781775960.
  9. ↑ 9.0 9.1 Taniguchi, I.; Murakami, G.; Sato, A.; Fujiwara, D.; Ichikawa, H.; Yajima, T.; Kohama, G. (Oct 2003). "Lymph node hyalinization in elderly Japanese.". Histol Histopathol 18 (4): 1169-80. PMID 12973685.
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