A Heterogeneous Phenotypic Presentation of a PALB2 Mutation Carrier With Multiple Metachronous Primary Malignancies:...

The Partner and Localizer of BRCA2 (PALB2) gene is a tumor suppressor gene with a role in DNA repair. Pathogenic autosomal dominant mutations of this gene significantly increase lifetime cancer risk, particularly breast and pancreatic cancers. We present a case of a 71-year-old African American woman without a known family history of malignancy found to have a heterozygous PALB2 mutation following the diagnoses of metachronous colorectal adenocarcinomas and multiple gynecologic cancers. After the discovery of the mutation, the patient underwent resection of a pancreatic head adenocarcinoma. Moreover, following an incidental discovery of evolving right-breast microcalcifications on a routine mammogram, the patient is pending a biopsy procedure for further investigation. Her positive mutation results prompted genetic testing in her family, leading to the detection of the mutation in both her daughter and granddaughter. This case highlights the importance of hereditary cancer evaluation and multigene testing in patients with multiple primary malignancies. While pancreatic cancer is an established PALB2-associated malignancy, the colorectal, uterine, and vulvar cancers observed in this patient should be interpreted cautiously, as their association with PALB2 remains unestablished. Identification of a pathogenic variant can guide risk-appropriate surveillance and cascade testing.