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)
Error creating thumbnail:
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 S100+ve (interdigitating dendritic cells), CD1a+ve (Langerhans cells) cutaneous T-cell lymphoma
Error creating thumbnail:
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 S100+, CD1a+ Kimura disease (eosinophilia), Rosai-Dorfman disease
LCH - very high mag.
Rosai-Dorfman disease sinus histiocytosis emperipolesis (intact cell within a macrophage) S100+, 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

General

  • Determination of lymph node status is one of the most common indications for the examination of lymph nodes.
  • It is a good idea to look at the tumour (if available) ...before looking at the LNs for mets.
  • Lymph node metastasis, in the absence of other metastases, often up-stage a cancer from stage II to stage III.

Gross

  • Outside:
    • "Large" - size varies by site.
      • Neck >10 mm.[3]
    • Shape - round more suspicious than oval.
  • Sectioned:
    • White firm lesion with irregular border - classic appearance.
    • Non-fatty hilum.[3]

Microscopic

Features:

  • Foreign cell population - key feature.
    • Classic location: subcapsular sinuses.
  • +/-Cells with cytologic features of malignancy.
    • Nuclear pleomorphism (variation in size, shape and staining).
    • Nuclear atypia:
      • Nuclear enlargement.
      • Irregular nuclear membrane.
      • Irregular chromatin pattern, esp. asymmetry.
      • Large or irregular nucleolus.
    • Abundant mitotic figures.
  • +/-Cells in architectural arrangements seen in malignancy; highly variable - dependent on tumour type and differentiation.
    • +/-Gland formation.
    • +/-Single cells.
    • +/-Small clusters of cells.

Notes:

  1. Cytologic features of malignancy may not be present; some tumours, e.g. gallbladder carcinoma, do not always have overt cytologic features of malignancy.
    • The diagnosis is based on the fact that they are foreign to the lymph node and architecturally consistent with a well-differentiated malignancy.
  2. Lymph node metastases in sarcomas are uncommon; they are seen in <3% of cases.[4]
  3. Fatty lymph nodes (esp. fatty hilus[3]) are less likely to harbor metastases.[5]

DDx - mimics of metastatic disease:

Images

  • Breast carcinoma LN metastasis (WC)

  • Thyroid carcinoma LN metastasis (WC)

  • Colorectal carcinoma LN metastasis (WC)

  • Melanoma in a lymph node. (WC)

Mimics

  • Decidua in a LN - low mag. (WC)

  • Decidua in a LN - high mag. (WC)

  • Endometriosis in a LN - intermed. mag. (WC)

  • Endosalpingiosis in a LN - intermed. mag. (WC)

  • Endosalpingiosis in a LN - very high mag. (WC)

Kaposi sarcoma

Main article: Kaposi sarcoma
  • One of the few non-lymphoid primary lymph node tumours.[9]

Melanocytic nevi

Main article: Melanocytic lesions
See: Dermatopathic lymphadenopathy.
  • Benign melanocytic nevi can be found in lymph nodes.[9]

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.[10]

Microscopic

Features:[11]

  • 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:

  • CD3.
  • CD5.
  • CD10.
  • CD20.
  • CD30.
  • CD15.

Others:

  • BCL2 -ve.

Diffuse paracortical hyperplasia

General

  • Benign.

Microscopic

Features:[11]

  • 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).[12]
  • AKA Kikuchi-Fujimoto disease.
Main article: Kikuchi disease

Systemic lupus erythematosus lymphadenopathy

General

Microscopic

Features:[13]

  • Necrosis.
  • Hematoxylin bodies (in necrotic foci).
    • Dark blue irregular bodies on H&E.

DDx:

Images

  • SLE lymphadenopathy - high mag. (WC)

  • SLE lymphadenopathy - very high mag. (WC)

Castleman disease

  • AKA angiofollicular lymph node hyperplasia, giant lymph node hyperplasia.[14]
  • 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:[15]

  • 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.[16]

Microscopic

Features:

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

Subdivided into:[16]

  • 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:

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 3.2 Mack, MG.; Rieger, J.; Baghi, M.; Bisdas, S.; Vogl, TJ. (Jun 2008). "Cervical lymph nodes.". Eur J Radiol 66 (3): 493-500. doi:10.1016/j.ejrad.2008.01.019. PMID 18337039.
  4. ↑ Fong, Y.; Coit, DG.; Woodruff, JM.; Brennan, MF. (Jan 1993). "Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients.". Ann Surg 217 (1): 72-7. PMC 1242736. PMID 8424704. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1242736/.
  5. ↑ Korteweg, MA.; Veldhuis, WB.; Mali, WP.; Diepstraten, SC.; Luijten, PR.; van den Bosch, MA.; Eijkemans, RM.; van Diest, PJ. et al. (Feb 2012). "Investigation of lipid composition of dissected sentinel lymph nodes of breast cancer patients by 7T proton MR spectroscopy.". J Magn Reson Imaging 35 (2): 387-92. doi:10.1002/jmri.22820. PMID 21972135.
  6. ↑ Wu, DC.; Hirschowitz, S.; Natarajan, S. (May 2005). "Ectopic decidua of pelvic lymph nodes: a potential diagnostic pitfall.". Arch Pathol Lab Med 129 (5): e117-20. doi:10.1043/1543-2165(2005)129e117:EDOPLN2.0.CO;2. PMID 15859655.
  7. ↑ Corben, AD.; Nehhozina, T.; Garg, K.; Vallejo, CE.; Brogi, E. (Aug 2010). "Endosalpingiosis in axillary lymph nodes: a possible pitfall in the staging of patients with breast carcinoma.". Am J Surg Pathol 34 (8): 1211-6. doi:10.1097/PAS.0b013e3181e5e03e. PMID 20631604.
  8. ↑ Biddle, DA.; Evans, HL.; Kemp, BL.; El-Naggar, AK.; Harvell, JD.; White, WL.; Iskandar, SS.; Prieto, VG. (May 2003). "Intraparenchymal nevus cell aggregates in lymph nodes: a possible diagnostic pitfall with malignant melanoma and carcinoma.". Am J Surg Pathol 27 (5): 673-81. PMID 12717252.
  9. ↑ 9.0 9.1 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/.
  10. ↑ Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 174. ISBN 978-0781775960.
  11. ↑ 11.0 11.1 Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 179. ISBN 978-0781775960.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ URL: http://www.mayoclinic.com/health/castleman-disease/DS01000. Accessed on: 17 June 2010.
  15. ↑ Ioachim, Harry L; Medeiros, L. Jeffrey (2008). Ioachim's Lymph Node Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 113. ISBN 978-0781775960.
  16. ↑ 16.0 16.1 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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