Parathyroid carcinoma (PC) and atypical parathyroid tumors (APT) are incompletely understood and pose challenges in definitive diagnosis. FLCN sequence variants have recently been linked to PC and APT. Inactivating mutations in the ubiquitously expressed FLCN tumor suppressor gene, encoding folliculin, cause Birt-Hogg-Dubé syndrome (BHD), a rare tumor predisposition syndrome. Germline inactivating FLCN variants, accompanied by somatic allelic loss, were reported in 2 unrelated patents with PC, both with clinical features, but no diagnosis, of BHD. Somatic frameshift variants of likely pathogenicity were reported in 1 patient with PC and 1 with APT. On the other hand, neither PC nor APT has been reported in sizeable BHD series. To better understand the frequency of FLCN variants in PC and APT, we analyzed a series of 10 patients with sporadic PC and 14 with APT by direct Sanger DNA sequencing. We identified no inactivating FLCN mutations in any of the PC or APT samples examined. A germline missense variant (p.Gly325Val), predicted as benign/tolerated, was seen in 1 PC and a synonymous variant in 1 APT. The absence of pathogenic mutations detected in our series of PC and APT further suggests that FLCN variants are rare in these tumors. Nevertheless, the potential roles of FLCN in the pathogenesis of PC and APT merits further consideration and study.
Keywords: Birt-Hogg-Dube syndrome; atypical parathyroid tumor; hyperparathyroidism; parathyroid carcinoma.
© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.