Mixed Cellularity Hodgkin Lymphoma

Mixed Cellularity Hodgkin Lymphoma

C. Cameron Yin, MD, PhD

Mixed cellularity Hodgkin lymphoma (MCHL) involving lymph node. A low-power view shows diffuse effacement of the lymph node architecture.

MCHL shows lymph node architecture completely effaced by abundant inflammatory cells image and scattered HRS cells image.



  • Mixed cellularity Hodgkin lymphoma (MCHL)


  • Mixed cellularity classical Hodgkin lymphoma

  • Mixed cellularity Hodgkin disease


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

  • Mixed cellularity is a type of CHL composed of classic HRS cells in a heterogeneous inflammatory cell background

    • MCHL has a diffuse or interfollicular pattern without nodules or fibrosis


Infectious Agents

  • Epstein-Barr virus (EBV) is present in HRS cells in ˜ 75% of cases and has pathogenic role

  • HIV infection predisposes to development of EBV-associated CHL and often MCHL


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

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

    • Have undergone crippling Ig mutations in a subset of cases

    • Lack B-cell antigen receptors

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

    • Severe impairment of transcription factor network that regulates 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

  • Overall, these abnormalities physiologically should lead to apoptosis

  • Development of antiapoptotic mechanisms to achieve survival

    • Dysregulation of many signaling pathways

    • Expression of EBNA1 and latent membrane proteins LMP1 and LMP2a

  • Role of microenvironment

    • Reactive cellular infiltrate is induced, in part, by HRS cells

      • Protects HRS cells from apoptosis

    • HRS cells produce a variety of cytokines, chemokines, and growth factors



  • Incidence

    • Accounts for 20-25% of CHL cases in developed countries

    • Most common type of CHL in underdeveloped countries

  • Age

    • Median: 38 years

  • Gender

    • Male to female ratio is 2:1


  • Cervical and supraclavicular lymph nodes

  • Mediastinal involvement is uncommon

  • Spleen (˜ 30%), bone marrow (˜ 10%), and liver (˜ 3%)


  • B symptoms are common

  • Patients usually present with peripheral lymphadenopathy

    • Abdominal lymph nodes common; often with splenic involvement

  • Most patients present with stage II or III disease


  • Current chemotherapy &/or radiation can cure disease in many patients

  • Chemotherapy with or without radiation

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


  • Clinical and laboratory parameters are relevant to predicting prognosis and determining mode of therapy

  • Recent study suggests that number of histiocytes in background predicts prognosis


General Features

  • Lymphadenopathy


Histologic Features

  • Complete or partial effacement of lymph node architecture

    • Interfollicular pattern can occur

  • HRS cells

    • Readily identifiable with classic features

      • Reed-Sternberg cells are bilobed with large eosinophilic nucleoli and perinuclear halo

      • Hodgkin cells are mononuclear cells with large eosinophilic nucleolus and perinuclear halo

  • Background infiltrate

    • Variable mixture of small lymphocytes, plasma cells, histiocytes, eosinophils, &/or neutrophils

    • Histiocytes can be singly scattered or present as illdefined or epithelioid granulomas

  • Occasional foci of necrosis

  • Mild to moderate interstitial fibrosis may be present

    • No nodular collagen bands; no thickening of lymph node capsule

Cytologic Features

  • HRS cells in inflammatory background can be appreciated in fine needle aspiration smears

    • Immunophenotype can be assessed in cell block

    • Difficult to determine type as MCHL versus other types of CHL



Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Mixed Cellularity Hodgkin Lymphoma

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