Clinical and genetic analysis of atypical parathyroid adenoma compared with parathyroid carcinoma and benign lesions in a Chinese cohort

Abstract

ContextThe malignant potential and molecular signature of atypical parathyroid adenoma (APA) remain elusive. Data from Asia are still lacking.Design and settingThis was a retrospective study on a large APA cohort in a single center from mainland China.MethodsA total of 320 patients with primary hyperparathyroidism (PHPT), containing 79 APA, 79 Parathyroid cancer (PC) and 162 benign lesions cases, were enrolled after surgery for collection of clinical data and genetic analysis.ResultsAPA patients showed earlier mean onset age than benign group (46.9 ± 17.1 vs. 52.0 ± 14.3 yrs). Less bone involvement and gastrointestinal symptoms were presented in APA compared to PC (35.4% vs. 62.0%, and 17.7% vs. 41.8%), while more urolithiasis was seen in APA than in benign lesions (57.0% vs. 29.6%). The APA group had moderate hypercalcemia (mean 3.02 ± 0.44mmol/L) with elevated serum PTH (median 593.0pg/ml) and proportion of hypercalcemic crisis as 22.8%, all higher than those of benign lesions but lower than those of PC group. The recurrence/no remission rate of the APA group was significantly lower than that of the PC and similar to the benign group (5.1% vs. 31.6% vs. 3.1%). Germline CDC73 mutation was the most common molecular abnormality in both PC and APA subjects. APA patients with nonsynonymous germline variants showed earlier onset age (28.5 ± 16.9 vs. 48.1 ± 17.7 yrs) and more cases developing no remission/recurrence (25.0% vs. 0.0%).ConclusionsPatients with APA presented clinical and biochemical characteristics much less severe than PC and resembling the benign neoplasms, with a relatively good prognosis. Germline gene variations were associated with earlier onset and probably more recurrence of PHPT in APA.

Recurrence and mortality rate in an Italian multi-center case series of parathyroid atypical adenomas and carcinomas

“…Conversely, in a recent paper, Chen et al. ( 19 ), reported that patients with AA presented clinical characteristics much less severe than PC. However, the same Authors showed that prevalence of nephrolithiasis/calcinosis and fragility fractures, as well as BMD values at lumbar and femoral sites were not significantly different between the two groups.…”

“…Concerning the biochemical presentation, our patients showed marked hypercalcemia associated with PTH levels higher than 10 times the upper normal range. Only few studies on small series compared biochemical features of PC and AA ( 11 – 14 , 19 ), reporting in the majority, though not all of them ( 11 , 19 ), similar PTH and calcium levels. Accordingly, we found no differences in the biochemical profile of the studied groups, indicating that PTH and calcium levels are not able to discriminate between PC and AA.…”

Chirurgische Therapie kritischer Hyperkalzämien und hyperkalzämischer Krisen

“…Bei der Suche nach einer oder mehreren vergrößerten Nebenschilddrüsen im Rahmen eines PHPT ist bei kritischer Hyperkalzämie häufig mit einer ektopen, auch intrathorakalen Lage beteiligter NSD zu rechnen [5]. Umgekehrt werden ektop gelegene NSD-Adenome und Nebenschilddrüsenkarzinome oft erst diagnostiziert, wenn sie zu einer kritischen Hyperkalzämie oder hyperkalzämischen Krise geführt haben [37,41].…”

“…intrathorakal mittels CT nachgewiesen [4,43]. NSD-Karzinome, die ebenfalls bei kritischer Hyperkalzämie häufiger diagnostiziert werden als bei gering erhöhten Serum-Kalzium-und Serum-Parathormonwerten [38,41,44], sind meist über 3 cm groß und weisen schon im Ultraschall intratumoröse Fibrosen und auch kleine Zysten auf [33].…”

“…Dieses Verhältnis ändert sich jedoch bei Betrachtung der Gruppe mit kritischer Hyperkalzämie und hyperkalzämischer Krise. Hier werden vermehrt atypische Adenome und NSD-Karzinome gefunden [41,43,48,49,55,56,57]. So berichteten Gurrado et al [53] in einer Literaturrecherche von 499 Patient*innen mit hyperkalzämischer Krise, dass bei 32 von 318 Patient*innen (10,1 %) ein NSD-Karzinom nachgewiesen wurde.…”