First report of synchronous papillary, medullary, and thymic carcinomas in a patient carrying a germline heterozygous MUTYH mutation.

MUTYH-associated polyposis (MAP) is an autosomal recessive tumor syndrome caused by biallelic mutations in the MUTYH gene, primarily associated with an increased risk of colorectal adenomas and carcinoma. However, the tumor spectrum in heterozygous MUTYH mutation carriers remains poorly defined. Here, we report the first case of a patient with a germline heterozygous MUTYH mutation who developed metachronous multiple primary tumors. The patient initially presented with a thyroid collision tumor (synchronous papillary thyroid carcinoma and medullary thyroid carcinoma) at age 55. Two years later, he was diagnosed with non-keratinizing squamous cell carcinoma of the thymus, accompanied by left cervical lymph node metastasis of papillary thyroid carcinoma (PTC). Subsequent next-generation sequencing of the lymph node metastasis revealed a novel heterozygous MUTYH frameshift mutation, c.848delT (p.M283Rfs*3), which was confirmed to be of germline origin by Sanger sequencing of the patient's normal thyroid tissue. This case expands the disease spectrum associated with heterozygous MUTYH carriers and enhances the understanding of the phenotypic heterogeneity of tumors in this population.