[en] Context: McCune Albright syndrome (MAS) is a clinical association of endocrine and non-endocrine anomalies caused by post-zygotic mutation of the GNAS1 gene, leading to somatic activation of the stimulatory alpha subunit of G protein (Gsalpha). Important advances have been made recently in describing pathological characteristics of many MAS-affected tissues, particularly pituitary, testicular and adrenal disease. Other rarer disease related features are emerging. Objective: To study pathological and genetic findings of MAS on a tissue-by-tissue basis in classically and non classically affected tissues. Design: A comprehensive autopsy and genetic analysis Setting: Tertiary referral University Hospital Patients: Adult male patient with MAS and severe disease burden including gigantism Intervention(s): Clinical, hormonal and radiographic studies; gross and microscopic pathology analyses, conventional PCR and droplet digital PCR analyses of affected and non affected tissues Main Outcome Measure: Pathological findings, presence of GNAS1 mutations Results: The patient was diagnosed with MAS syndrome at six years of age based on the association of cafe-au-lait spots and radiological signs of polyostotic fibrous dysplasia. Gigantism developed and hyperprolactinemia, hypogonadotropic hypogonadism and hyperparathyroidism were diagnosed throughout adult period. The patient died at the age of 39 from pulmonary embolism. A detailed study revealed mosaiscism for the p.R201C GNAS mutation distributed across many endocrine and non-endocrine tissues. These genetically implicated tissues included rare or previously undescribed disease associations including primary hyperparathyroidism, and hyperplasia of the thymus and endocrine pancreas. Conclusions: This comprehensive pathological study of a single patient highlights the complex clinical profile of MAS and illustrates important advances in understanding the characteristics of somatic GNAS1 related pathology across a wide range of affected organs.
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