Triple-hit blastoid mantle cell lymphoma presenting like acute leukemia

Jie Xu and Shaoying Li

A 67-year-old woman presented with leukocytosis (white blood cells, 65.5×109/L) and 82% circulating “blasts.” The “blasts” were large with irregular nuclei and some had “flower-like” nuclei (panels A-B; original magnification ×500, Wright-Giemsa stain). Bone marrow biopsy revealed diffuse medium-large blastoid neoplastic cells and frequent mitosis and apoptosis (panel C; original magnification ×400, hematoxylin and eosin stain). They were positive for PAX5, CD20, MYC, BCL6, cyclin D1 (panels D [original magnification ×400, CD20 stain], E [original magnification ×400, MYC stain], F [original magnification ×400, BCL6 stain], and G [original magnification ×400, cyclin D1 stain]), and negative for CD5. Ki67 proliferation index was >95% (panel H; original magnification ×400, Ki67 stain). Chromosome analysis showed a complex karyotype: t(2;8)(p11.2;q24.3),der(3)t(3;?)(q27;?),+5,+5,der(5)t(1;5)(q12;q11.2),+6,del(6)(q13),+7,+8,der(8)t(2;8),+12,der(14)t(11;14)(q13;q32),add(16)(q22),+17,+2mar[2]/55,sl,-11[2]/55,sdl1,add(13)(q32)[2]/46,XX[14]. Fluorescence in situ hybridization confirmed IGH/CCND1 translocation, MYC rearrangement, and BCL6 rearrangement. She was diagnosed with de novo blastoid mantle cell lymphoma (MCL), stage IV, with high-risk Mantle Cell Lymphoma International Prognostic Index. Despite treatment with rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, her disease progressed rapidly, and she went to hospice care 6 months after initial diagnosis.

Blastoid MCL is associated with circulating lymphoma cells, particularly in the presence of MYC rearrangement. Concurrent rearrangements of CCND1, MYC, and BCL6 (triple-hit) are extremely rare. With an initial presentation of marked leukocytosis and circulating “blasts” in a patient without lymphoma history, it may be misdiagnosed as acute leukemia, especially when the tumor is negative for CD5 as seen in this case. A thorough workup is critical in reaching the correct diagnosis.


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