Do patients with atypical parathyroid adenoma need a close follow-up?

Context Atypical parathyroid adenomas (APAs) are neoplasms with uncertain malignant potential but lack unequivocal histological signs of malignancy. Objective To retrospectively evaluate the clinical and biochemical profiles of patients with APA, the outcome after parathyroidectomy (PTX), and the presence of CDC73 germline and somatic mutations. Design Monocentric study on consecutive patients undergoing PTX for primary hyperparathyroidism (PHPT) between June 2000 and December 2020. Patients Fifty-eight patients with a confirmed histopathological diagnosis of APA. Age and sex-matched controls with parathyroid adenoma (PA) were also included. Results Fifty-four patients had sporadic PHPT and four familial isolated hyperparathyroidism (FIHP). Thirty-four patients (59%) had a symptomatic disease. Serum calcium and PTH levels were significantly higher in symptomatic compared to asymptomatic patients (P=0.048 and 0.008, respectively). FIHP patients were younger than the sporadic counterpart (30±17yr vs. 55±13 yrs). APA patients had significantly higher serum calcium and PTH levels and lower 25(OH)D concentration, BMD and T-score at 1/3 distal radius compared to those with PA. Four of 56 APA patients displayed a CDC73 germline mutation. No somatic CDC73 mutation was identified in 24 tumor specimens. The mean follow-up after surgery was of 60±56.4 months. All but six patients (90%), five with apparently sporadic PHPT and one with FIHP, were cured after surgery. Conclusions The large majority of patients with APA, despite a moderate/severe phenotype, have a good prognosis. Germline CDC73 mutation-positive patients had a higher rate of persistent/recurrent disease. CDC73 gene alterations do not seem to have a relevant role in the tumorigenesis of sporadic APA.