Concurrent development of small lymphocytic lymphoma and lung cancer: A report of two cases and a review of the literature.

Small lymphocytic lymphoma (SLL) is a rare disease subtype which has the same morphological and immunophenotypic features as chronic lymphocytic leukemia (CLL) but does not demonstrate lymphocytosis and grows mainly in the lymph nodes and spleen. As with CLL, SLL patients tend to present with immune abnormalities, and are associated with an increased risk for developing second primary malignancies. We report here two cases of SLL who developed lung cancer concurrently. The biological and clinical features of these two patients were very similar to each other; they both developed SLL with trisomy 12 and lacked lymphocytosis or cytopenia. SLL cells involved nodal areas adjacent to lung adenocarcinoma which expressed PD-L1. One patient received immunochemotherapy including nivolumab and ipilimumab against lung cancer, and notably, transient deterioration of SLL occurred after the second cycle of immunochemotherapy along with the development of immune related adverse events. Immunohistochemical analysis of the SLL samples of the patient revealed that the tumor cells were positive for CTLA-4, suggesting that ipilimumab might have potentially induced the activation of SLL cells by blocking the inhibitory signal mediated by CTLA-4. These clinical findings indicate the potential biological relationship between SLL and lung cancer. According to these observations, we would like to draw attention to the possibility of deterioration of SLL when immune checkpoint inhibitors are used for the treatment of malignancies developed in SLL patients.