Lymphocyte-rich Classical Hodgkin Lymphoma

Lymphocyte-rich Classical Hodgkin Lymphoma

Sa A. Wang, MD

Lymphocyte-rich classical Hodgkin lymphoma (LRCHL), nodular variant, involving lymph node. The nodules are composed of many small lymphocytes and scattered Hodgkin and Reed-Sternberg (HRS) cells.

LRCHL, nodular variant, involving lymph node. High-power magnification shows HRS cells image in a background of numerous small lymphocytes.



  • Lymphocyte-rich classical Hodgkin lymphoma (LRCHL)


  • Follicular Hodgkin lymphoma

  • Follicular Hodgkin disease


  • LRCHL is type of classic Hodgkin lymphoma (CHL) in which small reactive lymphocytes associated with Hodgkin and Reed-Sternberg (HRS) cells predominate

    • Neutrophils and eosinophils are rare or absent in background

    • 2 variants: Nodular and diffuse


Postulated Normal Counterpart

  • LRCHL may be derived from B cells in outer zone of reactive germinal centers

    • Large cells in outer zone of reactive germinal centers have immunophenotype similar to HRS cells

      • CD30(+), OCT2(+), BOB1(+), Bcl-6(+/-)

  • Large cells surrounded by T-cell rosettes, as can occur in nodular lymphocyte predominant (NLP) HL

    • T cells are PD-1(+), CD57(+)


  • HRS cells are derived from defective germinal center B cells with abnormal B-cell transcriptional program

    • HRS cells show no immunoglobulin expression

      • Epigenetic silencing of immunoglobulin heavy chain gene (IgH) promoters

      • Impaired activation of Ig promoters & enhancers

    • In LRCHL, B-cell transcription of HRS cells is less abnormal than in other types of CHL

      • Intermediate between NLPHL and CHL

  • NF-κB is activated in HRS cells of many cases of CHL including LRCHL

    • c-Rel nuclear accumulation may be responsible for malignant transformation of B cells

  • HRS cells regulate host response

    • Through expression &/or secretion of chemokines and surface ligands

    • Interplay of HRS cells and reactive cells determines tumor growth and local and systemic symptoms



  • Incidence

    • 4-5% of all cases of Hodgkin lymphoma

  • Age

    • Most common in middle-aged persons (median age: 43 years)

  • Gender

    • Male to female ratio ˜ 2:1


  • Presentation of patients with LRCHL is similar to patients with NLPHL

    • B symptoms in ˜ 10% of patents with LRCHL

      • Less frequent compared with other types of CHL

    • Stage I or II disease in ˜ 70% of patients

    • Peripheral lymph node involvement is typical

      • Especially supradiaphragmatic lymph nodes

    • Mediastinal involvement is uncommon

      • In ˜ 15% of patients; typically not bulky

    • Visceral organ involvement is relatively rare

      • Extranodal sites include: Lungs (4%), skeleton (3%), bone marrow (2%), and liver (2%)

  • Although CHL is uncommon in Waldeyer ring, LRCHL is a common type in this location

Natural History

  • Survival curves of patients with LRCHL similar to patients with CHL

    • Early relapses followed by plateau

    • Unlike patients with NLPHL who have early and late relapses without plateau


  • Drugs

    • Various chemotherapy regimens have been used for patients with LRCHL; most common are

      • Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or rituximab + ABVD

      • Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP)

  • Radiation

    • Patients with early and intermediate-stage disease

      • Extended-field or involved-field radiotherapy plus chemotherapy

      • Radiation alone for rare early localized disease

    • Patients with advanced-stage disease

      • Local radiotherapy to debulk tumor and for residual disease, in addition to chemotherapy


  • Good to excellent with current treatment regimens

    • 95% complete remission rate; 17% relapse rate

    • However, not significantly better than other types of CHL that are stage-comparable

  • Small subset of patients with LRCHL do poorly; fatalities due to

    • Relapsed/progressive disease ˜ 9%; 2nd malignancies ˜ 4%


Radiographic Findings

  • Peripheral lymphadenopathy

  • PET/CT scan useful for staging and helpful to assess therapeutic response


Histologic Features

  • Nodular variant

    • Lymph node is replaced by large, often vague nodules

    • Nodules are composed of expanded mantle zone small lymphocytes

      • Small, compact, often eccentric germinal centers present in subset of cases

      • Histiocytes are present; relatively infrequent compared with lymphocytes

      • Plasma cells uncommon or absent within nodules

      • No eosinophils or neutrophils within nodules

    • Loose follicular dendritic cell (FDC) meshworks underlying nodules

      • Highlighted by FDC markers, such as CD21, CD23, and CD35

    • HRS cells are scattered among small lymphocytes

      • Predominantly found within expanded mantle zones

      • Most HRS cells have classical cytologic features

      • Subset of HRS cells can resemble lymphocyte-predominant (LP) cells seen in NLPHL

    • Eosinophils and neutrophils can be present around nodules; usually infrequent

  • Diffuse variant

    • Uncommon compared with nodular variant

    • Diffuse replacement of lymph node architecture

    • Cytologic composition is similar to that seen in nodules of nodular variant

Cytologic Features

  • Fine needle aspiration smears show small lymphocytes and HRS cells

    • Diagnosis of CHL can be established

    • Difficult to establish specific type of LRCHL by smear examination

  • Possible to diagnose specific type of LRCHL if clot specimen contains tissue fragments of adequate size



  • HRS cells have immunophenotype that supports CHL

    • CD15(+/-), CD30(+), CD45/LCA(-)

  • Small lymphocytes in background have immunophenotype of mantle zone B cells

    • CD19(+), CD20(+), pax-5(+), IgD(+), IgM(+)

  • LRCHL has some features intermediate between CHL and NLPHL

    • Features of HRS cells closer to LP cells of NLPHL

      • ˜ 50-60% (+) for OCT1, OCT2, and BOB1

      • Bright pax-5(+/-); CD20(+) in ˜ 30% of cases

      • Bcl-6(+) in 30% of cases

    • Features of HRS cells closer to typical cells of CHL

      • CD15(+/-), CD30(+), MUM1(+), CD45/LCA(-)

      • Expression of nuclear Rel, Rel-B, p-50, and TRAF1 consistent with NF-κB activation

      • EBV-LMP1(+) in ˜ 40% of cases; EMA usually (-)

    • Microenvironment of LRCHL is similar to NLPHL

      • Numerous small B cells in background

      • FDC networks in tumor nodules

      • T cells form rosettes around HRS cells: Often PD-1(+), CD57(+), &/or CD3(+)

Flow Cytometry

  • Numerous polytypic B cells

  • Mature T cells with normal immunophenotype

In Situ Hybridization

  • EBER(+) in HRS cells in ˜ 40% of cases


  • Monoclonal Ig gene rearrangements shown by singlecell PCR of HRS cells

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Lymphocyte-rich Classical Hodgkin Lymphoma

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