There are no specific markers for parathyroid carcinoma (PC) therefore, the development of algorithms for identifying high-risk patients is an urgent task.
To determine clinical and laboratory predictors of PC and identify the factors of a poor prognosis.
Materials and methods
A multi-center retrospective study included 242 patients with primary hyperparathyroidism (PHPT) who were divided into these groups: 50 patients with PC, 30 with аtypical adenoma (AA), and 162 with adenoma of the parathyroid glands (PG). We compared clinical, histopathological, immunohistochemical (IHC), and genetic characteristics. Overall survival was assessed using the Kaplan-Mayer estimator. Cut-off for Ki-67 proliferation index was determined by ROC-analysis.
The group of patients with increased risk of the PC included individuals with the levels of intact PTH > 443 pg/ml, Ca++ > 1.5 mmol/l, albumin corrected calcium > 3.2 mmol/l, alkaline phosphatase > 176 IU/l, size of the tumor > 22.5 mm and volume of the tumor > 2.6 cm3, (P < 0.001). Heterogeneous structure is more typical to PC compared to the АА (P = 0, 004 and P = 0, 011), the same applies to indefinite contour (P = 0, 001 и P = 0, 011). The incidence of nuclear atypia was more common in PC and AA compared to benign adenomas (P < 0.001). There difference appeared to show in the frequency of pathological mitoses (P = 0.007) in patients with recurrent РС. The sensitivity of the IHC study of parafibromin expression as a marker of the CDC73 germline mutation is 100% (95% CI: 59%–100%), specificity 86% (95% CI: 73%–95%). The overall five-year survival rate for patients with PC is 87%, ten-year survival rate is 80%, disease-free five-year survival–56%, ten-year–50%. Cut-off for Ki-67 proliferation index as a predictor as increased risk of recurrent PC is 14.5% with PPV = 100% (63 %; 100%), and NPV = 81% (64%; 93%).
We have identified clinical and laboratory predictors of malignant neoplasms of the PG and identified factors of poor prognosis. Genetic study of the CDC73 gene is shown patients with a loss of parafibromin expression in the primary tumor or in metastases of РС according to the results of the IHC study. Patients with a Ki-67 proliferation index above 14.5% require closer follow-up due to the increased risk of РС recurrence. The patients with suspected PC should be timely referred to specialized centers with extensive experience in managing this pathology and thereby improve the patients prognosis.
22 May 2021 - 26 May 2021