Mantle Cell Lymphoma, Blastoid Variant



Mantle Cell Lymphoma, Blastoid Variant


C. Cameron Yin, MD, PhD





Key Facts


Terminology



  • Highly aggressive subtype of mantle cell lymphoma composed of cells that resemble lymphoblasts (classic variant) or are large, atypical, and pleomorphic (pleomorphic variant)


  • Clinically aggressive type of MCL with high-grade cytologic features: 2 major variants


Etiology/Pathogenesis



  • t(11;14)(q13;q32) juxtaposes CCND1 with IGH and results in Cyclin-D1 overexpression and cell cycle progression


  • Other molecular genetic abnormalities



    • P53, P21, P16, MYC


Clinical Issues



  • Clinical and biological features are comparable to those of typical MCL


  • Associated with particularly short durations of response after chemotherapy and poorer overall survival


Microscopic Pathology



  • 2 variants are recognized: Classic and pleomorphic


Top Differential Diagnoses



  • Lymphoblastic lymphoma


  • Myeloid sarcoma


  • Diffuse large B-cell lymphoma


  • Burkitt lymphoma







Lymph node involved by MCL, blastoid variant. In this case, a “starry sky” pattern is present and the neoplastic cells resemble, in part, lymphoblasts. This case carried the t(11;14)(q13;q32).






Lymph node involved by MCL, pleomorphic variant. In this case, the neoplastic cells are large and resemble, in part, large B-cell lymphoma. This case carried the t(11;14)(q13;q32).


TERMINOLOGY


Abbreviations



  • Mantle cell lymphoma (MCL), blastoid variant (BV)


Synonyms



  • Mantle cell lymphoma, lymphoblastoid variant


  • Mantle cell lymphoma, large cell variant


  • Mantle cell lymphoma, blastic


Definitions



  • Clinically aggressive type of MCL with high-grade cytologic features: 2 major variants


  • 2 variants of MCL as stated in 2001 WHO classification



    • Classical and pleomorphic


  • 2 aggressive variants of MCL as stated in 2008 WHO classification



    • Blastoid and pleomorphic


ETIOLOGY/PATHOGENESIS


t(11;14)(q13;q32)



  • Virtually all cases of MCL carry t(11;14)(q13;q32)


  • Juxtaposes CCND1 at 11q13 with IgH at 14q32 and results in Cyclin-D1 overexpression, Rb phosphorylation, and release of E2F


  • Facilitates cell cycle progression from G1 to S phase


Other Cytogenetic and Molecular Genetic Abnormalities



  • P53 overexpression and mutations


  • P16/INK4a deletions and mutations


CLINICAL ISSUES


Epidemiology



  • Incidence



    • MCL represents approximately 6% of all non-Hodgkin lymphomas


    • MCL-BV represents at least 10-15% of all MCL cases



      • Frequency is probably higher in patients who are followed for long periods of time


Presentation



  • Median age: 6th to 7th decades


  • Clinical features of MCL-BV are comparable to those of typical MCL


  • Male predominance (M:F = 2-3:1)


  • B symptoms in 30-50%; may be more common in patients with MCL-BV


  • Lymphadenopathy, generalized


  • Extranodal involvement is common



    • Gastrointestinal tract is most common site


    • Unusual extranodal sites can be involved in patients with MCL-BV


  • Most patients present with Ann Arbor clinical stage III/IV


  • MCL International Prognostic Index (MIPI) often high



    • Based on: Age, ECOG performance status, serum lactate dehydrogenase (LDH), blood leukocyte count


  • Rare prolymphocytoid variant of MCL is probably a form of MCL-BV



    • Patients present with high leukocyte count (often > 100 K/uL) and poor prognostic features



      • Extensive bone marrow involvement


      • Prominent splenomegaly


      • Often short survival


Treatment



  • Aggressive chemotherapy &/or stem cell transplantation



    • R-HyperCVAD used at many institutions



      • Rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate and cytosine arabinoside


    • R-CHOP is inadequate therapy for long-term cure




      • Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone


Prognosis



  • Short durations of clinical response after chemotherapy and poorer overall survival


  • MCL-BV patients have poor overall survival



    • Reported to be 14.5 months in 1 study


IMAGE FINDINGS


Radiographic Findings



  • Widespread lymphadenopathy

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Mantle Cell Lymphoma, Blastoid Variant

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