De novo familial adenomatous polyposis associated thyroid cancer with a c.2929delG frameshift deletion mutation in APC: a case report and literature review

Background Germline mutations in the APC gene located on chromosome 5q 21–22 can lead to familial adenomatous polyposis (FAP) and the development of colorectal cancer (CRC) if left untreated. As a rare extracolonic manifestation, thyroid cancer is diagnosed in about 2.6% of FAP patients. The genotype–phenotype correlation in FAP patients with thyroid cancer remains unclear. Case presentation We present a 20-year-old female of FAP with thyroid cancer as the initial manifestation. The patient was asymptomatic and developed colon cancer liver metastases 2 years after the diagnosis of thyroid cancer. The patient underwent multiple surgical treatments in several organs, and regular colonoscopy with endoscopic polypectomy was performed. Genetic testing demonstrated the c.2929delG (p.Gly977Valfs*3) variant in exon 15 of the APC gene. This represents a previously undescribed APC mutation. This mutation causes loss of multiple structures on the APC gene including the 20-amino acid repeats, the EB1 binding domain, and the HDLG binding site, which may be pathogenic through β-catenin accumulation, cell cycle microtubule dysregulation, and tumor suppressor inactivation. Conclusions We report a de novo FAP case with thyroid cancer presenting atypically aggressive features harboring a novel APC mutation and review APC germline mutations in patients with FAP-associated thyroid cancer.