A Rare Case of Chronic Lymphocytic Leukemia Transformed to B-Cell Lymphoma, Unclassifiable, with Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma

Abstract

Richter’s transformation refers to chronic lymphocytic leukemia (CLL) transforming into diffuse large B-cell lymphoma (DLBCL) or classic Hodgkin lymphoma (CHL).  The transformation is associated with TP53 and NOTCH1 mutation, CDKN2A/B deletion, and/or MYC translocation. Here we report a rare case of CLL evolving to B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and classic Hodgkin lymphoma (BCL-U). The patient was a 61-year-old male with long history of CLL who developed right inguinal lymphadenopathy. The lymph node was biopsied and submitted to flow cytometry, immunohistochemistry, cytogenetics, FISH, and NGS molecular profiling. His peripheral blood and bone marrow were also submitted for similar tests.  Our results showed that the peripheral blood and bone marrow were involved by CLL (CD5+, CD23+) with trisomy 12. The lymph node was infiltrated by pleomorphic large lymphoid cells with a subset showing Reed-Sternberg-like lymphoma cells. The lymphoid cells were positive for CD5, CD20, CD45, and CD30. Trisomy 12 was detected, while gene rearrangement for BCL2, BCL6, C-MYC was negative. NGS study on peripheral blood and the lymph node revealed similar mutation profiles (10 mutated genes in a 250 gene panel), including NOTCH1 and CDKN2C mutation. This is the first reported case of CLL transforming to BCL-U. Cytogenetics and molecular profiling confirmed the CLL and BCL-U were clonally related. Among the reported “transformation driving force” mutations, we only detected NOTCH1 mutation. However, we discovered a potential new mutation candidate that might belong to “transformation driving force”: CDKN2C, a molecule closely related to the reported CDKN2A/B.

[N A J Med Sci. 2020;1(1):014-017.   DOI:  10.7156/najms.2020.1301014]

Key Words: Richter’s transformation, chronic lymphocytic leukemia, B cell lymphoma,

unclassifiable, with features intermediate between diffuse large B cell lymphoma

and classic Hodgkin lymphoma, NOTCH1 mutation, CDKN2C mutation