Pleomorphic mantle cell lymphoma mimicking diffuse large B‐cell lymphoma in peripheral blood and bone marrow
Authors: Madhu Ouseph, Geraldine S. Pinkus, David M. Dorfman
Journal: American Journal of Hematology (2019)

A 73-year-old woman, with a history of breast carcinoma treated with surgery and radiation therapy 9 years earlier followed by adjuvant endocrine therapy, presented with night sweats, weight loss, and left upper quadrant abdominal pain. The clinical examination was significant for splenomegaly (8 cm below the costal margin) and bilateral cervical, supraclavicular, and inguinal lymphadenopathy. Laboratory testing revealed a white blood count of 7.48 K/uL with 18% large, atypical, lymphocytes, including cells with irregular nuclear contours and nucleoli (left upper panels), hemoglobin of 12.4 g/dL, platelet count of 77 K/uL, and serum lactate dehydrogenase of 884 U/L. NM PET CT demonstrated marked splenomegaly (23 cm) with diffuse FDG uptake, an FDG avid omental nodule, diffuse skeletal uptake, as well as generalized lymphadenopathy with FDG avidity. A bone marrow aspirate contained large, atypical lymphoid cells similar to those in the peripheral blood (22% by differential count; right upper panel) suggestive of diffuse large B-cell lymphoma. Flow cytometric analysis of both peripheral blood and bone marrow aspirate demonstrated a population of cells, including cells with increased forward and side scatter, that was positive for B cell markers CD19 and CD20, coexpressed T-cell marker CD5 and CD38(dim), exhibited bright monotypic staining for surface immunoglobulin lambda, and was negative for CD10, CD23, CD11c, and other T cell markers. The bone marrow biopsy contained an interstitial infiltrate of atypical lymphocytes that accounted for 30% of cellularity. Double immunostaining revealed that these cells were positive for B-cell marker BSAP (brown nuclear staining) and CD5 (red cytoplasmic staining; left lower quadrant), Cyclin D1 (brown nuclear staining) and CD20 (red cytoplasmic staining; right lower quadrant). Additional immunostaining of the lymphoid infiltrate was positive for SOX11 (data not shown). Cytogenetic analysis of the bone marrow revealed a complex female karyotype, 46,XX,t(11;14) (q13;q32),add(16)(q24)[2][cp5]/45,XX,-9,del(10)(q22q24),der(11)t(11;14), add(14)(q32)[cp3]/47,XX, +3[cp2]/46,XX,t(12;13)(q21;q14)[2]/46,XX[cp8], that included a t(11;14)(q13;q32) translocation, the hallmark of Cyclin D1 (CCND1)-IGH gene rearrangement, in 8 of 20 metaphases. Next generation sequencing-based molecular studies showed the presence of ATM and TP53 somatic mutations. The overall findings were consistent with the pleomorphic variant of mantle cell lymphoma. The patient is undergoing treatment with bendamustine and rituximab. The pleomorphic variant of mantle cell lymphoma, an uncommon subtype, is composed of intermediate to large sized cells and resembles diffuse large B-cell lymphoma. Similar to other subtypes of mantle cell lymphoma, it can involve the bone marrow, peripheral blood, spleen, and other organs. The neoplastic cells are positive for B-cell markers, with coexpression of T-cell marker CD5, and overexpression of Cyclin D1, an important regulator of cell cycle progression, and transcription factor SOX11. The t(11;14) translocation is seen in virtually all cases of mantle cell lymphoma, including the pleomorphic variant. Other chromosomal abnormalities may be found, including tetraploidy and somatic mutations involving TP53 at 17p13. Typically, the pleomorphic variant of mantle cell lymphoma has high proliferation activity and an aggressive clinical course. Although diffuse large B-cell lymphoma may be CD5-positive and rarely can express Cyclin D1, it is negative for t(11;14) and does not express SOX11.