Lymphocyte-depleted Hodgkin Lymphoma

Lymphocyte-depleted Hodgkin Lymphoma

C. Cameron Yin, MD, PhD

Lymphocyte-depleted Hodgkin lymphoma (LDHL) involving lymph node. Hodgkin and Reed-Sternberg (HRS) cells are numerous and highly pleomorphic, and small lymphocytes are depleted.

LDHL involving lymph node. Immunohistochemical analysis for CD30 highlights numerous HRS cells. Numerous HRS cells are a feature of the reticular morphologic variant of LDHL.



  • Lymphocyte-depleted Hodgkin lymphoma (LDHL)


  • Lymphocyte-depleted classical Hodgkin lymphoma

  • Lymphocyte-depleted (depletion) Hodgkin disease


  • Classical Hodgkin lymphoma (CHL) is lymphoid neoplasm composed of Hodgkin and Reed-Sternberg (HRS) cells in variable inflammatory background

  • Lymphocyte depletion is a type of CHL characterized by depletion of small lymphocytes

    • Subset of cases has numerous &/or anaplastic HRS cells


Infectious Agents

  • Epstein-Barr virus (EBV) probably has a pathogenic role in a subset of cases that are EBV(+)

  • HIV infection is associated with higher frequency of LDHL type


  • HRS cells arise from late germinal center or early post germinal center B cells that

    • Have undergone immunoglobulin (Ig) gene rearrangements with somatic mutations

    • Undergo crippling Ig gene mutations in subset of cases

    • Do not express B-cell antigen receptors

  • HRS cells lose much of normal B-cell immunophenotype due to

    • Severe impairment of transcription factor network regulating B-cell gene expression

    • Low or undetectable levels of transcription factors: OCT2, BOB1, PU.1, and early B-cell factor (EBF)

      • Leads to low level of Ig transcripts in HRS cells

      • Made worse by epigenetic silencing (promoter hypermethylation) of Ig transcription

    • Impaired function of early B cell development transcription factors: pax-5, E2A, and EBF

      • pax-5 dimly expressed or rarely absent in HRS cells

      • Aberrant overexpression of NOTCH1, ABF, and ID2 inhibit B-cell differentiation

      • Absent or dim expression of B-cell antigens: e.g., CD20

    • Overall these abnormalities physiologically should lead to apoptosis

      • However HRS are rescued from undergoing apoptosis

  • Development of antiapoptotic mechanisms to achieve survival

    • Inhibition of executors of apoptosis

    • Dysregulation of signaling pathways

    • Microenvironment is protective of HRS cells

  • LDHL most likely represents progression from other types of CHL

    • Suggested by older patient age at onset



  • Incidence

    • < 1% of cases of CHL

  • Age

    • Median: 4th decade (or older in some studies)

  • Gender

    • M:F = 2-3:1


  • Lymph nodes: Retroperitoneal or abdominal > peripheral

  • Abdominal organs, bone marrow


  • B symptoms are frequent

  • Lymphadenopathy

  • Clinical stage III-IV disease

  • LDHL can spread contiguously (like other types of CHL) or by noncontiguous/vascular spread


  • Chemotherapy ± radiation

    • Chemotherapy ABVD: Adriamycin (doxorubicin), bleomycin, vinblastine, and dacarbazine

  • Current chemotherapy and radiation can cure disease in many patients


  • Factors relevant to prognosis and to determination of mode of therapy

    • Male sex, B symptoms, high clinical stage

    • Elevated levels of serum LDH and β2-microglobulin

  • With therapy, prognosis of LDHL patients is similar to patients with other CHL types of similar stage

  • Recurrent disease with multiple adverse factors results in ˜ 60% overall survival at 5 years


Histologic Features

  • Lymph node architecture is usually diffusely effaced

  • Generalized depletion of small lymphocytes

  • Eosinophils, neutrophils, and plasma cells are usually scant or absent

  • ± coagulative necrosis; ± sinusoidal invasion

  • ± disordered nonbirefringent fibrillary fibrosis

  • 3 morphologic variants

    • Diffuse fibrosis

      • Scant HRS cells admixed with few or abundant fibroblasts, fibrillary stroma, and scant lymphocytes

    • Reticular or sarcoma-like

      • Abundant HRS cells, including pleomorphic, bizarre (sarcomatous) cells

      • Capsular and perinodal infiltration are common

    • Mixed cellularity-like with numerous HRS cells

      • HRS cells include typical Reed-Sternberg cells and mononuclear variants

Cytologic Features

  • LDHL is difficult to diagnose in fine needle aspiration smears

    • Numerous HRS cells and depleted inflammatory background lead one away from diagnosis of CHL



  • CD30(+) in > 95%; CD15(+) in ˜ 70-80% of cases

    • Characteristic membranous pattern with accentuation in Golgi area

  • pax-5(dim +) ˜ 90%, CD20(variably +) ˜ 20%, CD79a(+) ˜ 10-20%

  • Ki-67(+), p53(+), MUM1(+)

  • CCL17(TARC)(+), fascin(+/-), Bcl-2(+/-)

  • CD45/LCA(-), EMA(-), Ig(-)

  • EBV(+) with latency type II pattern in ˜ 50% of cases

    • EBV-LMP(+), LMP2a(+), EBNA1(+), EBNA2(-)

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

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