Lymphoma & related disorders

Hodgkin lymphoma

Nodular lymphocyte predominant

Last author update: 11 October 2019
Last staff update: 23 August 2022 (update in progress)

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PubMed Search: Nodular lymphocyte predominant Hodgkin lymphoma

Jayalakshmi Balakrishna, M.D.
Elaine S. Jaffe, M.D.
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Cite this page: Balakrishna J, Jaffe ES. Nodular lymphocyte predominant. website. Accessed December 9th, 2022.
Definition / general
Essential features
  • LP cells initially arise within altered follicles
  • Background small B cells are numerous in early phases and decrease with time
  • LP cells rosetted by CD4+, PD-1+ T cells
  • Number of background T cells increases over time, along with the loss of the nodular pattern
  • Diffuse pattern resembles T cell / histiocyte rich large B cell lymphoma
  • LP cells display a germinal center B cell phenotype: CD20, PAX5, OCT2 and BCL6 are positive, negative for CD10
  • CD30 is variably positive and if positive, usually weak
  • Most cases negative for CD15
  • Hodgkin paragranuloma (obsolete)
ICD coding
  • ICD-10: C81.0 - nodular lymphocyte predominant Hodgkin lymphoma
  • ICD-10: C81.00 - nodular lymphocyte predominant Hodgkin lymphoma, unspecified site
  • ICD-10: C81.01 - nodular lymphocyte predominant Hodgkin lymphoma, lymph nodes of head, face and neck
  • ICD-10: C81.02 - nodular lymphocyte predominant Hodgkin lymphoma, intrathoracic lymph nodes
  • ICD-10: C81.03 - nodular lymphocyte predominant Hodgkin lymphoma, intra-abdominal lymph nodes
  • ICD-10: C81.04 - nodular lymphocyte predominant Hodgkin lymphoma, lymph nodes of axilla and upper limb
  • ICD-10: C81.05 - nodular lymphocyte predominant Hodgkin lymphoma, lymph nodes of inguinal region and lower limb
  • ICD-10: C81.06 - nodular lymphocyte predominant Hodgkin lymphoma, intrapelvic lymph nodes
  • ICD-10: C81.07 - nodular lymphocyte predominant Hodgkin lymphoma, spleen
  • ICD-10: C81.08 - nodular lymphocyte predominant Hodgkin lymphoma, lymph nodes of multiple sites
  • ICD-10: C81.09 - nodular lymphocyte predominant Hodgkin lymphoma, extranodal and solid organ sites
  • ICD-10: C81 - Hodgkin lymphoma
Clinical features
  • Usually presents as localized disease; usually stage I / II (70 - 80%); 20% may present with advanced stage disease (Oncologist 2009;14:739)
  • Advanced stage disease treated as an aggressive B cell lymphoma (Blood 2017;130:472)
  • Presents with peripheral lymphadenopathy; rarely mediastinal or bone marrow involvement; often long history of localized disease (Am J Surg Pathol 2004;28:489)
  • M > F
  • Wide age range; may present in children
  • B symptoms are uncommon (5 - 10%)
  • Late recurrences more common than in classic Hodgkin lymphoma (Cancer 2010;116:631)
  • Biopsy of the involved lymph node with immunohistochemistry
  • LP cells in a background of small lymphocytes admixed with histiocytes
  • LP cells: CD45+, CD20+, PAX5+ OCT+, BCL6+, CD15-, CD30 variable; Subset positive for IgD, mainly in young males
  • Background: small B cells and T cells positive for CD4, PD-1 and partial CD57
  • Variant histological patterns have prognostic relevance (Am J Surg Pathol 2003;27:1346)
  • Expanded follicular dendritic cell meshwork within nodular areas; follicular dendritic cell meshwork lost with diffuse growth
  • With progression to diffuse growth pattern, histology resembles T cell / histiocyte rich large B cell lymphoma
Prognostic factors
Case reports
Gross description
  • Involved lymph node is enlarged
  • Firm, fleshy mass
Microscopic (histologic) description
  • Usually total replacement of nodal architecture by expansive vague nodules of small lymphocytes with sparse, relatively large tumor cells with multilobulated or round nucleus, thin nuclear membrane, finely granular chromatin and variable small nucleoli (popcorn cells) (Semin Hematol 2016;53:190, Clin Lymphoma Myeloma 2009;9:206)
  • May have rim of normal lymph node
  • Large cells are called LP cells; previously known as lymphocytic and histiocytic cells
  • LP cells are admixed with numerous small B lymphocytes, epithelioid histiocytes and CD21+ follicular dendritic cells
  • Often PD-1+, T cell rosettes surrounding LP cells (Am J Surg Pathol 2008;32:1252, Blood 2017;129:802)
  • Scant eosinophils, plasma cells or fibrosis
  • Prominent sclerosis is unusual but may occur in older lesions
  • Small germinal centers are rare between the nodules and usually present only at the compressed edge of normal lymph node tissue
  • No / rare classic Reed-Sternberg (RS) cells, although LP cells may occasionally resemble Reed-Sternberg cells / variants
  • No well formed granulomas, although epithelioid histiocytes may be prominent
  • Diffuse patterns has background of reactive T cells
  • 6 immunoarchitectural patterns have been described (Am J Surg Pathol 2003;27:1346):
    • Typical - B cell rich nodular
    • Serpiginous interconnected B cell rich
    • Variant - extranodular LP cells
    • T cell rich nodular
    • Diffuse T cell rich
    • Diffuse B cell rich
  • Variant patterns are associated with disease recurrence and transformation (Br J Haematol 2018;181:403, Br J Haematol 2014;167:238)
  • Nodular lymphocyte predominant Hodgkin lymphoma and T cell histiocyte rich large B cell lymphoma are considered to be parts of the same disease spectrum (PLoS One 2013;8:e78812, Br J Haematol 2015;169:415)
  • Syncytial variant is rarely reported (Am J Surg Pathol 2009;33:1725)
  • Bone marrow involvement: 3% of cases; involvement by large B cells (< 10% of all cases) in background of T cells and histiocytes
Microscopic (histologic) images

Contributed by Elaine S. Jaffe, M.D., Jayalakshmi Balakrishna, M.D. and Lauren B. Smith, M.D.

Vaguely nodular architecture

Rare large neoplastic cells

LP cells or popcorn cells

Neoplastic cells positive for CD20

T cell rich variant with rare small B cells in the background

Neoplastic cells positive for CD20

OCT2 stain is helpful in highlighting the neoplastic cells

Neoplastic cells positive for PAX5

Neoplastic cells positive for BCL6

IgD expressing LP cells

T cell rosettes around LP cells

CD4 T cells predominate in the background

T cells express PD-1

PD-1 positive T cells form rosettes around LP cells

Expanded follicular dendritic cell meshwork

Effaced lymph node architecture

Lymphocyte predominant cell (LP cell / popcorn cell)

LP cells express CD20

Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Diagnosis: Lymph node, right cervical; excision: Nodular lymphocyte predominant Hodgkin lymphoma. See comment and synoptic report.
Differential diagnosis
Board review style question #1

A 20 year old man presents with an enlarged painless cervical lymph node he has had for the past 6 months. An excisional biopsy is shown in the image. The neoplastic cells are positive for CD45 and CD20 and are negative for CD15 and CD30. Which of the following is true about this entity?

  1. Background is rich in cytotoxic T cells
  2. Background lacks small B cells
  3. Neoplastic cells are OCT2 positive
  4. Neoplastic cells are PAX5 negative
Board review style answer #1
C. The neoplastic cells are OCT2 positive

Comment here

Reference: Nodular lymphocyte predominant Hodgkin lymphoma
Board review style question #2
What is the immunophenotype of T cells in the microenvironment of nodular lymphocyte predominant Hodgkin lymphoma?

  1. CD3+ / CD4+ / PD-1+
  2. CD3+ / CD8+ / CD57+
  3. CD3+ / CD8+ / CD57-
  4. CD3+ / CD8+ / PD-1+
Board review style answer #2
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