A 60-year-old man was admitted to our Leukemia Service for a brief history of abdominal pain and progressive leukocytosis. At admission, a complete blood count showed marked leukocytosis (191.3 × 109/L) with 91% of circulating “blasts” (panel A). Flow cytometric analysis demonstrated a large population of monotypic B cells positive for CD10, CD19, CD20 (moderate), CD38, FMC-7, and λ (bright), and negative for CD5, CD23, CD43, CD44, and CD200. Computed tomography scan revealed extensive systemic lymphadenopathy. Bone marrow was nearly entirely replaced by sheets of intermediate blastoid cells (panel B). The karyotype was: 46∼50,XY,+3,add(3)(p12),add(3)(q11.2),−4,−6,add(6)(p21),del(7)(q22q24),+8,inv(8)(p11.2q24)x2,+9,add(9)(p22),−12,t(14;18)(q32;q21.3),+15,−17,+21,+3∼6mar[cp8]/46,XY[12] (panel B, left inset). Fluorescence in situ hybridization studies revealed an IgH-BCL2 fusion signal in 95.5% of interphase nuclei, and double MYC rearrangements plus an extra MYC signal in 92.5% of interphase nuclei (panel B, right and center insets, respectively). The patient was diagnosed with double-hit high-grade B-cell lymphoma/leukemia. He was treated with hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) plus rituximab followed by ofatumumab, and achieved complete remission. Due to disease relapse and progression, he was then treated with ofatumumab EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) and autologous stem cell transplantation. He died 18 months after the initial diagnosis.

MYC/BCL2 double-hit lymphoma is a rare but aggressive lymphoma. With marked leukocytosis as the initial presentation without a previous history of lymphoma, the disease may be misdiagnosed as acute leukemia.

A 60-year-old man was admitted to our Leukemia Service for a brief history of abdominal pain and progressive leukocytosis. At admission, a complete blood count showed marked leukocytosis (191.3 × 109/L) with 91% of circulating “blasts” (panel A). Flow cytometric analysis demonstrated a large population of monotypic B cells positive for CD10, CD19, CD20 (moderate), CD38, FMC-7, and λ (bright), and negative for CD5, CD23, CD43, CD44, and CD200. Computed tomography scan revealed extensive systemic lymphadenopathy. Bone marrow was nearly entirely replaced by sheets of intermediate blastoid cells (panel B). The karyotype was: 46∼50,XY,+3,add(3)(p12),add(3)(q11.2),−4,−6,add(6)(p21),del(7)(q22q24),+8,inv(8)(p11.2q24)x2,+9,add(9)(p22),−12,t(14;18)(q32;q21.3),+15,−17,+21,+3∼6mar[cp8]/46,XY[12] (panel B, left inset). Fluorescence in situ hybridization studies revealed an IgH-BCL2 fusion signal in 95.5% of interphase nuclei, and double MYC rearrangements plus an extra MYC signal in 92.5% of interphase nuclei (panel B, right and center insets, respectively). The patient was diagnosed with double-hit high-grade B-cell lymphoma/leukemia. He was treated with hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) plus rituximab followed by ofatumumab, and achieved complete remission. Due to disease relapse and progression, he was then treated with ofatumumab EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) and autologous stem cell transplantation. He died 18 months after the initial diagnosis.

MYC/BCL2 double-hit lymphoma is a rare but aggressive lymphoma. With marked leukocytosis as the initial presentation without a previous history of lymphoma, the disease may be misdiagnosed as acute leukemia.

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