(HealthDay News) – Cowden syndrome (CS)/CS-like patients with PTEN mutations, SDHx variations, and KLLN epimutations are at increased risk of epithelial thyroid cancers, according to a study published in the December 1 issue of the Journal of Clinical Endocrinology & Metabolism.

Joanne Ngeow, MB, BS, MRCP, from the Cleveland Clinic, and colleagues compared the incidence, clinical, and histological characteristics of epithelial thyroid cancers in 2,723 CS/CS-like individuals, with respect to their PTEN, SDHx, and KLLN status. All participants underwent comprehensive PTEN analysis. Those without PTEN mutations/variations, and with elevated manganese superoxide dismutase levels, underwent SDHx mutation analysis. A subset of participants without PTEN or SDHx mutation/deletion/variant/polymorphism were analyzed for KLLN epimutations. Demographic and clinical information, gene-specific thyroid cancer histologies, and adjusted standardized incidence rates were the main outcome measures.

The investigators found that 664 participants had thyroid cancer. The standardized incidence rates for thyroid cancer were 72, 63, and 45 for pathogenic PTEN mutations, SDHx variants, and KLLN epimutations, respectively. Pathogenic PTEN mutations were present in all of the six participants diagnosed under 18 years of age (16.7% of all PTEN mutations). In cases with PTEN mutations, follicular thyroid cancer was overrepresented compared with participants with SDHx and KLLN alterations. PTEN frameshift mutations were found in 31 and 17% of patients with and without thyroid cancer, respectively.

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“CS/CS-like patients have elevated risks of follicular thyroid cancer due to PTEN pathogenic mutations and of papillary thyroid cancer from SDHx and KLLN alterations. Children presenting with thyroid cancer should be tested for PTEN mutations,” the authors write.

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