Composite Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Follicular Lymphoma

Introduction: Composite lymphoma is defined as the co-occurrence of two or, rarely, more than two morphologically and/or immunophenotypically different types of lymphoma in the same anatomic site. These lymphomas can arise synchronously or metachronously, and can be clonally related or unrelated. Different combinations of lymphomas have been reported, of which chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (FL) are extremely rare. Methodology: Five cases of composite CLL/SLL and FL were identified in our institution over a period of five years (2010-2014). Immunohistochemistry was performed on all cases. Studies for flow cytometry, cytogenetics, and molecular analysis of B cell clonality were conducted in three, three and two cases, respectively. We had a bone marrow biopsy performed at our institution for staging purposes in two cases. Results: The patients included three males and two females, with a median age of 67 years (range 55-79 years). In all cases, the complete blood count with differential was within normal range. The sites of involvement included lymph node (3 cases), skin (1 case), and breast (1 case). Histologically, the CLL/SLL component showed typical CLL morphology in all cases. The FL component was variable, including grade 1-2 FL in three cases, grade 3 FL in one case and “in situ” FL in one case. All cases showed the typical immunophenotypes for CLL and FL. Molecular studies were positive for immunoglobulin gene rearrangement in two cases. Cytogenetic analysis revealed complex karyotypes in two cases and a normal karyotype in one case. The bone marrow was involved by both CLL and FL in one case and by only CLL in the other case. Conclusion: We present five cases of composite CLL/SLL and FL and study their histologic, immunophenotypic, cytogenetic and molecular features. This is the largest case series ever reported in the literature.