Splenic hamartoma in two related patients with BAP1 tumour predisposition syndrome caused by a novel germline BAP1 p.(Gly128Arg) missense variant

BAP1 tumour predisposition syndrome ( BAP1 -TPDS) is a hereditary cancer syndrome caused by heterozygous pathogenic germline variants in BAP1 . BAP1 -TPDS is associated with an increased risk for various malignant tumours, the core of which is uveal and cutaneous melanoma, malignant mesothelioma, and renal cell carcinoma. In BAP1 -TPDS, the majority of disease-causing BAP1 variants are null variants, although missense variants have been reported. We report a patient with BAP1 -TPDS caused by the novel germline BAP1 missense variant NM_004656.4:c.382G > A, p.(Gly128Arg). The patient developed BAP1 -inactivated melanocytic tumours, renal cell carcinoma, and splenic hamartoma, all of which showed nuclear loss of BAP1 expression on immunohistochemistry. An incidental splenic hamartoma was detected in existing tissue slides from the patient’s first-degree relative, who was an obligate carrier for BAP1 -TPDS. To our knowledge, this is the first report of a confirmed BAP1 -deficient splenic hamartoma in a patient with BAP1 -TPDS. It supports expanding the tumour spectrum of BAP1 -TPDS to splenic hamartoma and possibly other benign splenic tumours.