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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