Lymphoma & related disorders

Hodgkin lymphoma

CHL lymphocyte rich



Last author update: 19 October 2023
Last staff update: 19 October 2023

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PubMed Search: Lymphocyte rich classic Hodgkin lymphoma

Carmen Bárcena, M.D.
Laurence de Leval, M.D., Ph.D.
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Cite this page: Bárcena C, de Leval L. CHL lymphocyte rich. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomanonBLRHL.html. Accessed May 19th, 2024.
Definition / general
  • Subtype of classic Hodgkin lymphoma (CHL) with Hodgkin / Reed-Sternberg (HRS) cells in a nodular or less commonly diffuse background of small lymphocytes (Blood 2022;140:1229, Leukemia 2022;36:1720)
Essential features
  • B cell lymphoma derived from germinal center B cells
  • Scattered HRS cells in a nodular or diffuse background of small lymphocytes without eosinophils and neutrophils
  • Immunophenotype of HRS cells: PAX5+ (dim), CD30+, CD15 variable, CD20 variable
ICD coding
  • ICD-O: 9651/3 - classic Hodgkin lymphoma, lymphocytic rich
  • ICD-10: C81.4 - lymphocyte rich Hodgkin lymphoma
  • ICD-11: 2B30.11 - lymphocyte rich, classical Hodgkin lymphoma
Epidemiology
  • Rare subtype of CHL that accounts for 5.8% of classic Hodgkin lymphoma (Cancer Med 2018;7:953)
  • Most patients are adults (30 - 50 years)
  • Male predominance (70%)
  • EBV infection in 30 - 50% of cases; the virus is within the HRS cells and usually shows a type II latency pattern of infection
Sites
  • Peripheral lymph nodes (most often cervical) are typically affected (Leuk Lymphoma 2019;60:3426)
  • Mediastinal involvement (15%) and bulky disease are rare
Pathophysiology
  • Pathophysiology is incompletely understood
  • HRS cells derived from preapoptotic germinal center B cells with a disrupted B cell program (Leukemia 2021;35:968)
  • HRS cells harbor monoclonal IGH rearrangements with somatic mutations of their Ig variable region genes and lack the capacity of Ig expression (Leukemia 2021;35:968)
  • Genetic lesions that promote HRS cell proliferation, survival, immune evasion and interaction with their microenvironment, including alterations in NFκB and JAK / STAT signaling pathways (Leukemia 2021;35:968)
  • EBV could play a crucial role by infecting HRS cells with crippled germinal center B cell receptor (BCR), rescuing them from apoptosis and thus inducing lymphomagenesis (Blood 2005;106:4339)
  • EBV infection activates the NFκB pathway promoting survival and growth (Histopathology 2021;79:451)
Etiology
  • Remains unknown
Clinical features
  • Similar to those of nodular lymphocyte predominant Hodgkin lymphoma (WHO 5) / nodular lymphocyte predominant B cell lymphoma (ICC), except that relapses are less frequent in lymphocyte rich CHL (LRCHL) (J Clin Oncol 1999;17:776)
  • B symptoms are rare
  • Most patients are diagnosed at stage I / II (J Clin Oncol 2005;23:5739)
Diagnosis
  • Histopathological analysis of an excisional lymph node biopsy or tissue biopsy supplemented with ancillary techniques (immunohistochemistry, EBER ISH)
Laboratory
Prognostic factors
  • Approximately 90 - 95% of patients with early stage CHL and 80 - 85% with advanced stage CHL are cured (Am J Hematol 2020;95:978)
  • Prognosis is slightly better than other CHL subtypes and similar to nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), unless for the relapses, that are more common in NLPHL
  • Treatment is individualized according to defined risk groups based on following prognostic factors
Case reports
Treatment
Gross description
Gross images

Contributed by Laurence de Leval, M.D., Ph.D. and Carmen Bárcena, M.D.
Macroscopy

Macroscopy

Microscopic (histologic) description
  • 2 patterns of growth: nodular or less often, diffuse proliferation with numerous reactive small lymphocytes and scattered HRS cells (Leukemia 2022;36:1720)
  • Neutrophils and eosinophils are absent from the nodules
  • In lymphocyte rich classic Hodgkin lymphoma (LRCHL) nodular cases
    • Nodules are composed of small lymphocytes and may contain eccentrically located germinal centers (small or regressed)
    • Nodules contain dense meshwork of follicular dendritic cells (CD21+)
    • HRS cells are within the nodules but outside of the germinal centers
    • Some HRS cells resemble lymphocyte predominant cells (LP cells) or lacunar cells
  • In LRCHL diffuse cases
    • Small lymphocytes of the background can be intermingled with histiocytes with or without epithelioid morphology
Microscopic (histologic) images

Contributed by Laurence de Leval, M.D., Ph.D. and Carmen Bárcena, M.D.
LRCHL, nodular pattern

Nodular pattern

CD20

CD20

HRS cells

HRS cells

CD20

CD20

PAX5

PAX5

OCT2

OCT2


CD30

CD30

CD15

CD15

MUM1

MUM1

CD3

CD3

PD-1

PD-1

EBER in situ hybridization

EBER in situ hybridization

Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Lymph node, left neck, excision:
    • Lymphocyte rich classic Hodgkin lymphoma (see comment)
    • Comment: H&E stained sections display a lymph node with architectural effacement by a nodular proliferation of abundant small lymphocytes and scattered large atypical lymphoid cells. The neoplastic cells have monolobated / bilobated / multilobated nuclei, vesicular chromatin, prominent nucleoli and amphophilic cytoplasm, consistent with HRS cells.
    • Immunophenotypically, the large atypical cells are positive for PAX5 (weak), OCT2, CD30 (strong), CD15, MUM1 and GATA3 and negative for CD20 and CD45.
    • TFH markers reveal T cell rosettes around HRS cells.
Differential diagnosis
Board review style question #1

What is the characteristic immunophenotype of the large atypical cells shown in the image above?

  1. CD20+, CD30-, CD15-, BCL6+, IgD-
  2. CD20+, PAX5+, CD23+, CD30+
  3. CD45+, OCT2+, CD20+, CD30 -, CD15-, IgD+
  4. CD45-, PAX5+, CD30+, CD15+
  5. PAX5-, CD4+, CD30+, ALK-
Board review style answer #1
D. CD45-, PAX5+, CD30+, CD15+. This is the characteristic immunophenotype of Hodgkin / Reed-Sternberg cells. Answer A is incorrect because the large atypical cells of T cell / histiocytic rich large B cell lymphoma express this immunophenotype. Answer B is incorrect because this immunophenotype is characteristic of primary mediastinal B cell lymphoma. Answer C is incorrect because the LP cells in nodular lymphocyte Hodgkin lymphoma (WHO 5) / nodular lymphocyte predominant B cell lymphoma typically express this immunophenotype (ICC 2022). Answer E is incorrect because this immunophenotype is not specific. T cells could show this immunophenotype.

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Reference: CHL lymphocyte rich
Board review style question #2
What is the typical composition of the background of lymphocyte rich classic Hodgkin lymphoma (LRCHL) with nodular pattern?

  1. Small atypical B cells: CD20+, BCL2+, BCL6+, CD10+
  2. Small B cells: CD20+, CD5+, CD23+, LEF1+
  3. Small B cells IgD+ admixed with CD4+ PD-1+ T cells
  4. Small T cells, eosinophils, plasma cells and neutrophils
Board review style answer #2
C. Small B cells IgD+ admixed with CD4+ PD-1+ T cells. The background is typically composed of B cells corresponding to expanded mantle zones (IgD+) admixed with CD4+, PD-1+ T cells, rosetting Hodgkin / Reed-Sternberg (HRS) cells. Answer B is incorrect because this is the characteristic composition of small lymphocytic lymphoma. Answer D is incorrect because this background is not specific but in the present of HRS cells it is diagnostic of mixed cellularity classic Hodgkin lymphoma. Answer A is incorrect because this is the characteristic composition of follicular lymphoma.

Comment Here

Reference: CHL lymphocyte rich
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