Composite Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Mantle Cell Lymphoma; Small Cell Variant: A Real Diagnostic Challenge. Case Presentation and Review of Literature

Abstract

BACKGROUND Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL) both have a common origin arising from mature CD5+ B-lymphocytes. Their distinction is crucial since MCL is a considerably more aggressive disease. Composite lymphoma consisting of CLL/SLL and MCL has been rarely reported. This type of composite lymphoma may be under-diagnosed as the 2 neoplasms have many features in common, both morphologically and immunophenotypically. CASE REPORT We report the case of a 57-year-old male patient who presented with a 4-month history of recurrent abdominal pain and distention with hepatosplenomegaly. Peripheral blood showed a high leukocytes count (46.7×10³/uL) with marked lymphocytosis of 35.0×10³/uL, mostly small mature-looking, with some showing nuclear irregularities, with approximately 3% prolymphocytes. Immunophenotyping by flow cytometry and immunohistochemistry revealed 2 immunophenotypically distinct abnormal CD5+monotypic B-cell populations. Fluorescence in situ hybridization (FISH) on peripheral blood demonstrated IGH/CCND1 rearrangement consistent with t(11;14) in 65% of cells analyzed. Accordingly, based on compilation of findings from morphology, flow cytometry, immunohistochemistry, and FISH, A diagnosis of composite lymphoma consisting of MCL; small cell variant and CLL/SLL was concluded. CONCLUSIONS We describe a case of composite lymphoma of MCL (small cell variant) and CLL/SLL that emphasizes the crucial role of the multiparametric approach, including vigilant cyto-histopathologic examination, immunophenotyping by flow cytometry and immunohistochemistry, as well as genetic testing, to achieve the correct diagnosis.

Figure 1A.

Peripheral blood shows lymphocytosis, mostly small mature-looking, some with irregular nuclear contour and/or inconspicuous nucleolus (inserts). Wright stain 1000×.

Figure 1B.

Flow cytometry on peripheral blood revealed an abnormal population of lambda monotypic B-cells (58%, green) expressing CD19, CD20, CD5, FMC7, and CD79b with partial CD23. The cells are negative for CD10, CD43, and CD200. Analysis showed another kappa monotypic population as well (12%, red) expressing CD19, CD20 (partial dim), CD5, CD23, CD43, and CD200 with dim CD79b. The cells are negative for CD10 and FMC7.

Figure 2.

(A) Bone marrow biopsy shows hypercellular bone marrow with interstitial lymphoid infiltration. Hematoxylin and eosin (H&E) 40×. (B). The lymphocytes are small to medium, H&E 600×. The cells are positive for PAX5 (×200), CD20 (200×), and cyclin D1 (200×) (mantle lymphoma cells).

Figure 3.

Bone marrow biopsy shows large lymphoid aggregates composed mostly of small mature B-cells (CLL cells). Hematoxylin and eosin (H&E) 100×. The cells are positive for PAX5 (100×) and show less positivity for CD20 with many negative or weakly positive cells (100× and 400×). Most of the cells within the aggregates are negative for cyclin D1 (100×), while the cyclin D1 positive cells (mantle lymphoma cells) are at the periphery of the aggregates.

Figure 4.

(A) Fluorescence in situ hybridization (FISH) revealed IGH/CCND1 rearrangement, t(11;14), in 69% of cells analyzed: orange CCND1 11q13; green IGH 14q32. (B) Karyotype shows t(11;14).