Rare Presentation of Sequential Mucosa-Associated Lymphoid Tissue Lymphoma, Follicular Lymphoma, and Chronic Lymphocytic Leukemia: A Case-Based Review

Introduction: Occurrence of 2 (or more) Hodgkin's and non-Hodgkin's lymphoma concordantly or sequentially in a single patient is very rare. Case: An 88-year-old Italian male with a history of mucosa-associated lymphoid tissue (MALT) lymphoma in remission and indolent follicular lymphoma under surveillance, presented with acute autoimmune hemolytic anemia (AIHA). While initially speculated to be secondary to follicular lymphoma relapse, stable mesenteric lymphadenopathy compared to prior CT abdomen/pelvis and smudge cells on peripheral smear prompted further evaluation. Peripheral blood flow cytometry indicated a mature B-cell neoplasm, which was confirmed to be chronic lymphocytic leukemia (CLL) with a bone marrow biopsy. Minimal improvement was observed with high-dose steroids, IV immunoglobulin, and rituximab therapy, ultimately leading to hospice care. Discussion: A population-based cancer registry study calculated the prevalence of sequential or composite lymphomas to be only 0.44%. Their occurrence can be explained by the common precursor cells hypothesis, chronic antigenic stimulation, and microenvironmental dependence. Possibly shared fundamental genetic alterations and acquired distinct secondary events lead to divergent clonal evolution. Limited data are available on the incidence of sequential lymphomas, and our case emphasizes the need for large, multicentric studies to stratify their risk factors, clinical implications, and suspicion index.