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.
TERMINOLOGY
Abbreviations
  • Mixed cellularity Hodgkin lymphoma (MCHL)
Synonyms
  • Mixed cellularity classical Hodgkin lymphoma
  • Mixed cellularity Hodgkin disease
Definitions
  • 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
ETIOLOGY/PATHOGENESIS
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
Pathogenesis
  • 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
CLINICAL ISSUES
Epidemiology
  • 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
Site
  • Cervical and supraclavicular lymph nodes
  • Mediastinal involvement is uncommon
  • Spleen (˜ 30%), bone marrow (˜ 10%), and liver (˜ 3%)
Presentation
  • 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
Treatment
  • Current chemotherapy &/or radiation can cure disease in many patients
  • Chemotherapy with or without radiation
    • ABVD: Adriamycin (doxorubicin), bleomycin, vinblastine, and dacarbazine
Prognosis
  • 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
IMAGE FINDINGS
General Features
  • Lymphadenopathy
MICROSCOPIC PATHOLOGY
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
ANCILLARY TESTS
Immunohistochemistry
Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Mixed Cellularity Hodgkin Lymphoma

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