UCSF

Multiple primary malignancies (MPMs) are more than one synchronous (within 6-month interval) or metachronous (more than 6-month interval) cancers diagnosed in a patient in the same or different organ system. We present a challenging case of a 72-year-old male who presented with sinus congestion refractory to medical treatment and was found to have a hard palate swelling. The biopsy revealed diffuse large B cell lymphoma (DLBCL). Subsequent staging positron emission/computed tomography (PET/CT) scans showed another hypermetabolic mass in the anterior mediastinum, the pathology of which confirmed the presence of synchronous small cell lung cancer (SCLC). The patient received a combination of chemotherapy and radiation for both masses. Interval PET/CT scans done six months from the initial diagnoses showed an improvement in both masses, but also revealed an initially missed 2 cm solid right renal mass suggestive of synchronous renal cell carcinoma (RCC), which was confirmed by biopsy and treated with cryoablation. Targeted genomic profiling tests subsequently revealed six germline variants (ERCC4 P472L, FGFR4 T179M, FGFR4 G388R, FLT3 A953V, MSH2 Q397E and RAD52 S407G) as well as a variety of somatic variants in different tissue samples. This case highlights the diagnostic and therapeutic challenges in managing patients with MPMs and the potential complex clinical significance of germline and somatic variants.