A case of hereditary breast and ovarian cancer syndrome of initially presented as cancer of unknown primary with lymph node metastases unveiled by genetic analysis

Cancer of unknown primary (CUP) is a heterogeneous disease concept involving various malignant tumors. Understanding its pathophysiology is often difficult, together with its treatment. Here, we present a case of CUP with abdominal lymph node enlargement and elevated carbohydrate antigen 125 levels. It initially resembled a favorable prognosis type similar to ovarian cancer, but metastases were observed in cervical lymph nodes, indicating a somewhat atypical CUP compared to the typical ovarian cancer-like CUP. We identified a germline Breast Cancer 1 (BRCA1) p.L63* variant through a family history inquiry and BRCA analysis, indicating hereditary breast and ovarian cancer syndrome. The patient achieved near-complete remission with platinum-based therapy followed by poly (ADP-ribose) polymerase (PARP) inhibitor. The variant has shown sensitivity in both clinical and pathogenic reports in the ClinVar database of the National Institutes of Health. No clinical studies reported on the efficacy of PARP inhibitors specific to this variant, but our case demonstrated the sensitivity of platinum-based therapy followed by PARP inhibitor. Reports of CUP in hereditary breast and ovarian cancer syndrome are very rare, with only a single report in the literature.