Parathyroid cancer (PC) is a rare sporadic or hereditary malignancy whose histologic features were redefined with the 2022 WHO classification. A total of 24 Italian institutions designed this multicenter study to specify PC incidence, describe its clinical, functional, and imaging characteristics and improve its differentiation from the atypical parathyroid tumour (APT).
All relevant information was collected about PC and APT patients treated between 2009 and 2021.
Among 8361 parathyroidectomies, 351 patients (mean age 59.0 ± 14.5; F = 210, 59.8%) were divided into the APT (n = 226, 2.8%) and PC group (n = 125, 1.5%). PC showed significantly higher rates (p < 0.05) of bone involvement, abdominal, and neurological symptoms than APT (48.8% vs. 35.0%, 17.6% vs. 7.1%, 13.6% vs. 5.3%, respectively). Ultrasound (US) diameter >3 cm (30.9% vs. 19.3%, p = 0.049) was significantly more common in the PC. A significantly higher frequency of local recurrences was observed in the PC (8.0% vs. 2.7%, p = 0.022). Mortality due to consequences of cancer or uncontrolled hyperparathyroidism was 3.3%.
Symptomatic hyperparathyroidism, high PTH and albumin-corrected serum calcium values, and a US diameter >3 cm may be considered features differentiating PC from APT. 2022 WHO criteria did not impact the diagnosis.

OBJECTIVE: The purpose of this study was to examine the postoperative clinical course of parathyroid carcinoma to determine factors that predict postoperative recurrence and distant metastasis.
METHODS: In this retrospective study, we included 38 patients with parathyroid carcinoma who received surgical intervention at Itoh Hospital between 1979 and 2020. Clinicopathologic characteristics (age, sex, intact PTH, serum Ca level, operation type, parathyroid weight, parathyroid size, histopathologic findings: vascular invasion, capsular invasion, necrosis, histological type, and Ki-67 staining) were used. The median follow-up observation period was 63.7 months.
RESULTS: Postoperatively, 5 patients (13.2%) developed distant metastasis or had localized recurrence, and 3 patients died (7.9%). The results of the univariate analysis revealed three factors affecting distant metastasis and recurrence, which were Ki-67 (p = 0.0041), the presence or absence of necrosis (p = 0.0163), and tumor weight (p = 00,189). Using the cutoff values obtained by ROC analysis, which were 4.1 for Ki-67 (sensitivity of 80% and specificity of 96.9%) and 4890 mg for tumor weight (sensitivity of 100% and specificity of 60.9%), we calculated the cumulative incidence of recurrence and distant metastasis by the three factors retained. We found that the presence of the three factors was associated with a high possibility of distant metastasis or recurrence during the 5-year follow-up period.
CONCLUSIONS: Three factors, Ki-67, necrosis, and tumor weight in parathyroid carcinoma, may predict outcomes of postoperative recurrence and distant metastasis.

Parathyroid carcinoma (PC) is a rare malignancy without a commonly acknowledged prognostic assessment and treatment system. This study captures how independent prognostic factors and tumor size correlate with outcomes in patients with PC.
The Surveillance, Epidemiology, and End Results database was used to perform a retrospective analysis on PC patients from 2000 to 2018. Univariate and multivariable survival analyses were performed to evaluate cancer-specific survival (CSS) and overall survival (OS), to identify independent prognostic factors in the PC patient population. A generalized additive model was applied to conduct smooth curve fitting and to examine the association between tumor size and relative risk of death.
A total of 590 patients were included. The 5- and 10-year OS were 80.8% and 67.1%, respectively. 5- and 10-year CSS was estimated to be 93.6% and 92.1%, respectively. The association between tumor size and relative risk of death can be generalized as a U-shaped curve. The mortality risk reaches its lowest point when tumor diameter approaches 2cm. At a tumor diameter cutoff of 3cm for CSS and 4cm for OS, there is an abrupt drop in survival rates. Multivariate Cox analysis revealed age, no surgery, and debulking surgery as consistent predictors of lower OS and CSS.
A non-linear correlation between tumor size and death risk has been identified in patients with PC, along with an accurate size threshold at which survival rates sharply decrease. Further investigation is needed to determine if these trends are seen in other malignancies with promising prognoses.

This study aimed to explore a visual model for predicting the prognosis of patients with parathyroid carcinoma (PC) and analyze related biochemistries in different groups of stage.
The training dataset of 342 patients with PC was obtained from the Surveillance, Epidemiology, and End Results (SEER) database, and the validation dataset included 59 patients from The First Affiliated Hospital of Zhengzhou University. Univariate and multivariate Cox regression analyses were performed to evaluate significant independent prognostic factors. Based on those factors, nomograms and Web-based probability calculators were constructed to evaluate the overall survival (OS) and the cancer-specific survival (CSS) at 3, 5, and 8 years. The concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the nomogram in the training set and validation set. Moreover, biochemistries from the validation set were retrospectively analyzed in different groups of stage by Kruskal-Wallis test.
Age, marital status, tumor size, stage, lymph node status, and radiation were identified as prognostic factors of OS. In contrast, only tumor size and stage were predictive for CSS. The nomogram was developed based on these independent factors. The C-index, ROC curve, calibration curve, and DCA of the nomogram in both training and validation sets showed that the nomogram had good predictive value, stability, and clinical benefit in predicting 3-, 5-, and 8-year OS and CSS in PC patients. Among the 59 PC patients from our hospital, lower albumin (ALB) levels and higher postoperative parathyroid hormone (PTH) levels were found in patients with distant metastasis (Distant vs. Regional ALB levels: p = 0.037; Distant vs. Local ALB levels: p = 0.046; Distant vs. Regional postoperative PTH levels: p = 0.002; Distant vs. Local postoperative PTH: p = 0.002).
The established nomogram application can provide accurate prognostics for patients with PC in the Chinese population, but it must be validated on prospectively collected real-world data.

Introduction: Parathyroid carcinoma (PC) is an extremely rare entity, with a frequency of 0.005% of all malignancies. Most data related to this rare disease are limited to case series and a few database studies. We present a large database study that aims to investigate the demographic, clinical, and pathological factors, prognosis, and survival of PC. Methods: Data of parathyroid carcinoma were extracted from the Surveillance, Epidemiology, and End Results (SEER) diagnosed between 1975 and 2016. Results: PC had a slightly higher incidence in men (52.2%, p < 0.005), the majority of cases affected Caucasians (75.4%, p < 0.005), and the mean age at diagnosis was 62 years. Histologically, 99.7% were adenocarcinomas not otherwise specified (p < 0.005), well-differentiated (p < 0.005), and 2−4 cm (p < 0.001) in size among the patients with available data. In cases with staging provided, most PC were organ-confined (36.8%, p < 0.001). Lymph nodes were positive in 25.2% of cases where lymph node status was reported. The main treatment modality was surgery (97.2%), followed by radiation alone (2%), and very few received chemotherapy alone (0.8%), p < 0.005. Five-year follow-up was available for 82.7% of the cases. Those who underwent surgery only or radiation alone had 5-year survivals of 83.8% and 72.2%, respectively (p < 0.037). Multivariable analysis identified tumor size >4 cm, age > 40 years, male sex, Caucasian race, distant spread, and poorly differentiated grade as independent risk factors for mortality (p < 0.001). Conclusion: PC is a very rare tumor mostly affecting Caucasian individuals in the fifth decade. Older age, poor histologic differentiation, and distant metastasis are associated with a worse prognosis. Surgical resection offers the best survival outcome. To better understand the pathogenesis and factors affecting survival, all PC patients should be enrolled in national and international registries.

BACKGROUND: Parathyroid carcinoma (PC) is a rare but often lethal malignancy for which staging system, prognostic indicators, and treatment guidelines are still not established. We aimed to explore the prognostic parameters and construct a nomogram for cancer-specific survival (CSS) of PC.
METHODS: A retrospective analysis of 604 PC patients in the SEER database from 2001 through 2018 was performed. All the cases were randomly assigned to the training cohort (n = 424) or the validation cohort (n = 180) at a ratio of 7:3. The Kaplan-Meier method and Cox regression model were applied to estimate the CSS and risk factors, and a nomogram was constructed. The predictive accuracy and discriminative ability of the nomogram in CSS were assessed by concordance index (C-index), the area under the curve (AUC) of receiver operating characteristics (ROC), and the calibration curve.
RESULTS: Age at diagnosis > 70 years [hazard ratio (HR): 3.55, 95% CI: 1.07-11.78, p = 0.039] and tumor size > 35 mm (HR 4.22, 95% CI: 1.67-10.68, p = 0.002) were associated with worse CSS. Compared with distant metastasis, localized (HR 0.17, 95% CI: 0.06-0.47, p = 0.001) and regional lesions (HR 0.22, 95% CI: 0.07-0.66, p = 0.007) showed an improved CSS rate. Parathyroidectomy was the recommended treatment (p = 0.02). The C-index of the nomogram was 0.826, and the AUC for 5-, 10-, and 15-year CSS was 83.7%, 79.7%, and 80.7%, respectively. The calibration curve presented good agreement between prediction by nomogram and actual observation.
CONCLUSIONS: Age at diagnosis > 70 years, tumor size > 35 mm, and distant metastasis were independent risk factors for PC-specific mortality. Parathyroidectomy was currently the most recommended treatment for PC. This nomogram provided individualized assessment and reliable prognostic prediction for patients with PC.

BACKGROUND: Parathyroid carcinoma is a rare condition and accounts for < 1% of cases of sporadic primary hyperparathyroidism. It accounts for 0.005% of all cancers. Often the differentiation between adenoma and carcinoma is challenging and requires multidisciplinary cooperation. Complete surgical resection is the treatment of choice. We present a retrospective analysis of 29 patients who were surgically treated for parathyroid cancer.
METHODS: Between the years 1983 and 2018, 71 (7.0%) patients were treated for suspicion of parathyroid cancer among a group of 1019 operated for primary hyperparathyroidism.
RESULTS: We confirmed the diagnosis of parathyroid cancer in 29 (2.8%) patients, 12 men and 17 women, aged 27 to 77 years, mean 55.1 years. That constituted 43.9% of the 71 patients with initial suspicion of cancer diagnosis. All operated patients were under long-term observation.
CONCLUSIONS: A diagnosis of parathyroid carcinoma should always be considered during surgery in patients diagnosed with primary hyperparathyroidism, especially in patients with severe hypercalcaemia, significantly enlarged neck circumference, and concomitant diseases of the renal and skeletal system. Parathyroid carcinoma is rarely definitively diagnosed preoperatively or even intraoperatively, and the final diagnosis can be made exclusively after operation. The optimal treatment is a complete surgical resection at a reference centre - specialized in parathyroid surgery - to improve outcomes and provide the best chance of recovery.

OBJECTIVE: To compare the serum miRNA expression profiles between patients with benign and malignant parathyroid tumours.
BACKGROUND: Despite recent advances in molecular biology, a histological tissue biopsy is still the method of choice used to diagnose most cancers. The preoperative cytology is not an applicable method for diagnosis of parathyroid cancer (PC); therefore, huge interest exists in terms of finding alternative methodologies to seek specific cancer biomarkers.
METHODS: A retrospective cross-sectional study.
METHODS: Serum samples of patients with PC (n = 13) and parathyroid adenoma (PA) (n = 11), age (p = .999) and sex (p = .999) were matched and examined via the simultaneous comparative expression analysis of 754 microRNAs (miRNAs). The «TaqMan OpenArray Human MicroRNA Panel» (Applied Biosystems) was used to conduct real-time PCRs using the «QuantStudio 12К Flex» station (Life Technologies).
RESULTS: According to the results of a pilot study, significant changes in expression levels between the PC group and the PA group (control) (p < .05) were observed for 17 miRNAs. Among them, the downregulation of miRNA-342-3p met the Benjamini-Hochberg adjustment criteria for multiple comparisons (p = .02).
CONCLUSIONS: Serum miRNA-342-3p could be a promising biomarker for PC to improve diagnosis and prognosis.

BACKGROUND: Primary hyperparathyroidism (PHPT) is caused by parathyroid adenoma, primary parathyroid hyperplasia, or parathyroid carcinoma. For some patients with PHPT controlling serum calcium levels is critical.
METHODS: We conducted an open-label, single-arm, 52-week, phase III study in Japanese patients with hypercalcemia due to PHPT to demonstrate efficacy and safety of evocalcet, a new calcimimetic. Patients with intractable PHPT (n = 13), postsurgical recurrence (n = 2), and parathyroid carcinoma (n = 3) were enrolled. Evocalcet administration started at a dose of 2 mg once or twice daily and was titrated to achieve the target serum corrected calcium (cCa) concentration (≤ 10.3 mg/dL) for two consecutive weeks (maximal dose 24 mg/day).
RESULTS: Fourteen patients achieved the target (77.8%; 95% confidence interval [CI] 52.4-93.6). The lower limit of 95% CI exceeded the predetermined reference limit (11%), and thus, efficacy was confirmed. Of 18 patients, 12 (66.7%; 95% CI 41.0-86.7) showed decreased serum cCa of ≥ 1.0 mg/dL from the baseline for two consecutive weeks during the titration phase. Sixteen patients entered the maintenance phase, and 15 patients completed the study. Treatment-emergent adverse events (TEAEs) were recorded in 18/18 patients (100%) and drug-related TEAEs in 8/18 (44.4%). The most commonly observed drug-related TEAE was nausea (2/18 patients). No unexpected drug-related TEAEs were observed. All drug-related TEAEs were mild in severity. No patient discontinued the study because of drug-related TEAEs.
CONCLUSIONS: Evocalcet demonstrated long-term effectiveness in reducing serum cCa concentrations and safety without any unexpected drug-related TEAEs in PHPT patients.

Both DNA flow and image cytometry are methods that can be used for the quantitative determination of cellular DNA content. Objective, quantitative analysis of cellular morphology can also be obtained using image cytometry. Data thus generated have been shown to be of diagnostic and prognostic use in the study of many solid tumors and would be of particular value in the evaluation of endocrine tumors that show a poor correlation between their histology and biological behavior. The main application of these techniques to endocrine tumors has been in the analysis of thyroid nodules, although a limited number of studies of parathyroid, pituitary, adrenal, and pancreatic neuroendocrine tumors and tumors of the dispersed neuroendocrine system have been reported. Review of these studies shows that in the endocrine organs DNA and morphometric measurements have a very limited role in the diagnosis of individual cases, but are important as prognostic variables. The high incidence of abnormal DNA content in histologically benign lesions of the endocrine glands has important biological implications. Further investigation of this phenomenon may help to elucidate the process of endocrine tumorigenesis.