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.


TERMINOLOGY


Abbreviations



  • Lymphocyte-rich classical Hodgkin lymphoma (LRCHL)


Synonyms



  • Follicular Hodgkin lymphoma


  • Follicular Hodgkin disease


Definitions



  • 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


ETIOLOGY/PATHOGENESIS


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(+)


Tumorigenesis



  • 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


CLINICAL ISSUES


Epidemiology



  • 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



  • 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


Treatment



  • 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


Prognosis



  • 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%


IMAGE FINDINGS


Radiographic Findings



  • Peripheral lymphadenopathy


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


MICROSCOPIC PATHOLOGY


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



ANCILLARY TESTS


Immunohistochemistry



  • 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


PCR



  • 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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