Carney complex with PRKAR1A variant and breast/fibrolamellar carcinomas

Abstract Carney complex is a rare multiple neoplasia syndrome caused primarily by inactivating variants in the PRKAR1A gene, which encodes the regulatory subunit type I alpha of protein kinase A. Although classically associated with myxomas, lentigines, and endocrine tumors, the full tumor spectrum related to PRKAR1A loss of function is not completely defined. Here, we report a patient with a molecularly confirmed diagnosis of Carney complex carrying a de novo PRKAR1A (NM_002734.5):c.348+1G>A splice-site variant. In addition to typical manifestations, the patient developed two uncommon malignancies: invasive breast carcinoma (luminal B-like) at a young age and fibrolamellar hepatocellular carcinoma lacking the DNAJB1–PRKACA fusion typically found in sporadic cases. The coexistence of these two rare tumors in a single carrier of a pathogenic PRKAR1A variant expands the phenotypic variability associated with this condition and supports the possibility that PRKAR1A loss contributes to oncogenesis beyond the classical endocrine and mesenchymal tissues. This Data Report provides clinically relevant documentation of an unusual tumor presentation associated with a pathogenic PRKAR1A variant and underscores the importance of ongoing clinical surveillance in affected individuals.