Search

Additional file2 Supplementary Figures: Provides additional data analysis supporting claims and conclusions drawn throughout the paper

We are presenting a compelling case of a 61-year-old female with a history of appendiceal mucinous adenocarcinoma (AMA) with a new complaint of irritative lower urinary tract symptoms. Magnetic resonance imaging (MRI) showed a semi-circumferential, T2 hyperintense, rim enhancing, and lacking restricted diffusion lesion involving the urethra and infiltrating the right perineal and internal obturator muscles. The suspected differential diagnosis was urethral malignancy, based on her cancer history and MRI findings. After interdisciplinary consensus, the patient underwent excision of the lesion, and pathology was consistent with metastasis from the primary tumor. The urethra is a rare site of primary malignancy and metastatic disease. In particular, a non-contiguous metastatic disease involving the urethra is exceedingly rare. To the best of our knowledge, this is the first report of an AMA metastasizing to the urethra.

BACKGROUND: Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC), caused by heterozygous germline pathogenic variants in the FH, confers an increased risk for cutaneous and uterine leiomyomas and renal cancer. METHODS: About 13,722 advanced cancer patients, including 560 with renal cell carcinoma, had germline analysis performed in the context of tumor-normal sequencing under an IRB approved protocol. RESULTS: We report two unrelated individuals with early onset kidney cancer who both carried the c.914C>T (p.Phe305Ser) germline variant in the FH. Both tumors exhibited loss of FH staining by immunohistochemistry and/or positive 2SC staining. Subsequent familial testing discovered that a daughter of a proband who carried the variant had both cutaneous and uterine leiomyomas. CONCLUSION: This combination of evidence suggests that the FH c.914C>T (p.Phe305Ser) is pathogenic for HLRCC.