History: A 12 year-old boy was referred for evaluation of hyperthyroidism. He had a multinodular thyroid with multiple lesions similar to the one illustrated. On physical examination, he had multiple hyperpigmented skin macules. What is your diagnosis?
Comment: This thyroid nodule is well delineated and non-invasive; it has papillary architecture but the papillae are organized and arranged in a centripedal fashion within follicles (1). The papillae are true papillae with fibrovascular cores lined by follicular epithelium; however, there are no nuclear features of papillary carcinoma. In the situation where a biopsy has been performed, there is extensive uptake of hemosiderin by the hyperactive follicular epithelial cells. The histological appearance is similar to that of Graves’ disease but these are focal lesions with surrounding uninvolved parenchyma that may show involution or atrophy. These lesions are benign follicular adenomas that are hyperfunctioning due to clonal mutation of GNAS or TSHR; they give rise to clinical or subclinical hyperthyroidism. In this patient, there were multiple lesions all resembling this; the presentation at a young age with multiple nodules and skin hyperpigmentation should prompt investigation for McCune-Albright disease which is due to germline mosaic GNAS activating mutation (2).
1. Asa SL. Survival Guide to Endocrine Pathology. Virginia: Innovative Science Press; 2020.
2. Salpea P, Stratakis CA. Carney complex and McCune Albright syndrome: an overview of clinical manifestations and human molecular genetics. Mol Cell Endocrinol 2014 Apr 5;386(1-2):85-91.
This case was provided by Sylvia Asa, MD, PhD, a Professor of Pathology at Case Western Reserve University and an Endocrine Pathologist at University Hospitals, Cleveland Ohio. She is also the author of the Survival Guide to Endocrine Pathology, published by Innovative Science Press. You can order your copy at: