Parathyroid Carcinoma Patients Research Articles

The prognostic value of lymph node dissection in patients with parathyroid carcinoma.

Surgery is the only curative treatment strategy for parathyroid carcinoma (PC). However, the optimal extent of surgery remains uncertain, particularly regarding whether routine central lymph node dissection (LND) confers a survival advantage to patients with PC. This study aimed to evaluate the prognostic value of LND in PC patients. Patients diagnosed with PC between 2004 and 2018 were identified in the Surveillance, Epidemiology, and End Results (SEER)-18 registries. With inclusion and exclusion criteria, a total of 338 patients were included as cohort 1 to describe the characteristics of PC, while 215 patients were selected as cohort 2 to assess the effect of LND on cancer-specific survival (CSS). Univariate and multivariate Cox proportional hazards regression models were used to identify independent risk factors associated with CSS. Propensity score matching (PSM) was performed to adjust for potential confounding variables. The prognostic value of LND was further analyzed in subgroups stratified by predictors associated with CSS. The 5- and 10-year CSS were 94.4% and 87.9% respectively in cohort 1. LND failed to significantly improve CSS in the entire cohort 2 and the PSM cohort 2. Large tumor size (>40 mm) and distant metastasis were independently associated with poor CSS. Subgroup analyses revealed that LND was not significantly associated with improved CSS in patients with aggressive PC, such as those with a tumor size greater than 40 mm. Unexpectedly, LND may compromise CSS in patients with distant disease (P=0.03). PC is a rare and indolent endocrine malignancy. The presence of large tumors and distant metastases are independent predictors of poor CSS. Routine central LND as part of initial surgery does not significantly improve CSS in PC patients, even for those with large tumors, lymph node metastasis, or distant disease.

A Rare Parathyroid Carcinoma in Young Adult Man: Therapeutic Challenges in Tertiary Hospital with its Limitations

Introduction: Parathyroid carcinoma is a rare malignant neoplasm. The symptoms that arise are related to hyperparathyroid conditions, which are clinically difficult to distinguish between benign and malignant disorders. These conditions make the diagnosis and treatment of parathyroid carcinoma challenging. Case Presentation: : In this case report, a 27-year-old male presented with weak limbs and a history of multiple recurrent fractures. Serum calcium ions and parathyroid hormone levels were increased. A comprehensive history taking, laboratory testing, and radiographic examination were used to confirm the diagnosis of parathyroid cancer. However, a histological study is still necessary to make a certain diagnosis. The patient underwent parathyroidectomy accompanied by intraoperative frozen section examination, then confirmed to have parathyroid carcinoma. Calcium serum evaluations were performed on the patient after surgery. Conclusions: Parathyroid carcinoma is a very rare case. Clinical manifestations and the results of investigations that are not typical and rarely found together in one patient’s condition make the diagnosis of this case very difficult. Although recommendations or standard protocols in the management of parathyroid carcinoma do not yet exist, the results of case reports are expected to increase the knowledge and management of parathyroid carcinoma patients.

Abstract 6265: FLCN variants and their role in parathyroid cancer and atypical parathyroid tumors

Abstract Parathyroid carcinoma (PC) is rare, poses challenges in definitive diagnosis and treatment, and carries a high rate of recurrence and mortality. Atypical parathyroid tumors (APT) have histopathologic features of malignancy but lack unequivocal evidence of invasion and are of uncertain malignant potential. Analysis of genetic alterations that may play a role in PC development, particularly those that might serve as markers of malignant potential, is important for further understanding this disease. FLCN is a gene found on chromosome 17 that encodes folliculin, a ubiquitously expressed protein with roles in multiple cellular processes such as apoptosis and cell signaling. Inactivating FLCN mutations cause Birt-Hogg-Dubé syndrome (BHD), an autosomal dominant condition characterized by benign fibrofolliculomas, pulmonary cysts and spontaneous pneumothorax, and increased risk of renal cancer. Benign parathyroid tumors had previously been reported in a few BHD patients and recently one study has reported a link between FLCN mutations and parathyroid carcinoma. Germline frameshift mutations in FLCN, accompanied by somatic loss of the normal allele, were reported in two unrelated PC patients, both with clinical features suggestive of BHD, but no established diagnosis of BHD. An identical somatic frameshift FLCN mutation was reported in one PC and one APT. Interestingly, the authors noted low coverage of FLCN on whole exome sequencing, resulting in the failure to detect variants identified by Sanger sequencing, thus raising the possibility that prior studies may have missed FLCN variants. To better understand the frequency of germline or somatic FLCN mutations in PC and APT, we performed Sanger sequence analysis of the entire coding region of the FLCN gene on available tumor DNA from 11 PCs and 15 APTs. We identified no inactivating FLCN mutations in any of the PC or APT samples examined. A germline missense variant, resulting in a p.Gly325Val change, predicted to be benign/tolerated by in silico analyses, was seen in one PC and a synonymous variant (c.1233G>A) was seen in one APT. The absence of pathogenic mutations in our series parathyroid carcinoma and atypical parathyroid tumors suggests that FLCN mutations are rare in these parathyroid tumors. Nevertheless, germline FLCN testing and/or additional screening for BHD-related lesions in parathyroid carcinoma patients merits further consideration and study. Citation Format: Callie Burke, Justin Bellizzi, Jessica Costa-Guda, Andrew Arnold. FLCN variants and their role in parathyroid cancer and atypical parathyroid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6265.

A >50% Intraoperative Parathyroid Hormone Decrease Into Normal Reference Range Predicts Complete Excision of Malignancy in Patients With Parathyroid Carcinoma

IntroductionThe mainstay of successful treatment for parathyroid carcinoma remains complete surgical excision. Although intraoperative parathyroid hormone (ioPTH) monitoring is a useful adjunct during parathyroidectomy for benign primary hyperparathyroidism, its utility for parathyroid carcinoma remains unclear. MethodsA retrospective review of 796 patients who underwent parathyroidectomy with ioPTH monitoring for primary hyperparathyroidism revealed 13 patients with parathyroid carcinoma on final pathology from two academic institutions. A systematic review yielded 5 additional parathyroid carcinoma patients. Complete excision of malignancy, or operative success (eucalcemia ≥6 mo. after parathyroidectomy); operative failure (persistent hypercalcemia <6 mo. after parathyroidectomy); and perioperative complications were evaluated. Comparison of the >50% ioPTH decrease alone to >50% ioPTH decrease into normal reference range was analyzed using Chi-squared, Kolmogorov–Smirnov, Kruskal–Wallis tests. ResultsAll 18 parathyroid carcinoma patients achieved a >50% ioPTH decrease, and 14 patients also had a final ioPTH level decrease into normal reference range. 93% of patients who met normal parathyroid hormone reference range had operative success, whereas only two of the four (50%) patients with parathyroid carcinoma with a >50% ioPTH decrease alone demonstrated operative success. ConclusionsParathyroidectomy guided by a >50% ioPTH decrease into normal reference range may better predict complete excision of malignant tissue in patients with parathyroid carcinoma compared to >50% ioPTH decrease alone. IoPTH monitoring should be used in conjunction with clinical judgment and complete en bloc resection for optimal treatment and success.

Parathyroid carcinoma: Imaging features of initial presentation and recurrence. A single center experience.

Parathyroid carcinoma is the rarest endocrine neoplasm with very few published data discussing its imaging appearance with primary focus on ultrasound imaging features. We present our 23 years institutional experience to highlight multimodality imaging evaluation at presentation and at recurrence. Retrospective chart review of clinical and pathological diagnosis of parathyroid carcinoma patients presented for initial or recurrent disease management at M.D. Anderson Cancer Center between the period of January 2000 and February 2023 was performed. Imaging findings on US, CT, PET/CT, and technetium-99m sestamibi were analyzed for initial and local recurrent parathyroid carcinoma. We further assess patterns of distant recurrence and its location. Twenty three patients with pathological and clinical diagnosis of initial (14 patients) or recurrent parathyroid carcinoma (14 patients) were included in this study. US findings of parathyroid carcinoma were larger lesions, increased/irregular vascularity, and non-circumscribed margins. Multiphasic CT findings of parathyroid carcinoma included an arterially enhancing lesion that is hypoenhancing relative to the thyroid and demonstrates no washout on delayed imaging. Highly suggestive findings for recurrent disease included a hypoechoic solid nodule (91.67%) with increased vascularity on ultrasound (81.8%) with corresponding enhancement on CT. Parathyroid carcinoma is a rare malignancy often diagnosed after surgical resection. We provided CT and US imaging features that are helpful in suggesting the diagnosis of parathyroid carcinoma and detection of early local recurrence.

OR05-03 Treatment Of Parathyroid Neoplasia By Pharmacologic cdk4/6 Inhibition

Abstract Disclosure: J. Costa-Guda: None. J. Bellizzi: None. S. Gorka: None. C. Titarenko: None. A. Arnold: None. Parathyroid carcinoma (PC) is a rare, life-threatening malignancy. Despite relatively slow growth, recurrent or metastatic disease is typically incurable and often fatal due to cumulative complications of sustained elevation of parathyroid hormone (PTH) and accompanying hypercalcemia. Medical therapy aids in managing sequelae of hyperparathyroidism (HPT) but non-surgical interventions to reduce tumor burden have been largely ineffective in PC. Cyclin D1 amplification is seen in nearly 30% of PC, making it a key potentially actionable therapeutic target. Importantly, in contrast to other tissue contexts, cyclin D1-driven parathyroid neoplasia has been experimentally demonstrated to depend on cyclin D1’s ability to bind and activate its partner cyclin dependent kinases (cdk). This suggests that parathyroid tumor cells may be more sensitive to alterations in cdk-mediated proliferation control, and thus more responsive to pharmacologic cdk inhibition, compared with other tumor types. We sought to test the efficacy of cdk4/6 inhibitor therapy in cyclin D1-overexpressing parathyroid tumors in a pre-clinical system. We utilized a mouse model, harboring a PTH-CCND1 (PCD) transgene to drive parathyroid-specific cyclin D1 overexpression, which develops hormonally-active parathyroid tumors with known kinetics. Transgenic mice with established hyperparathyroidism and wild type littermates were treated with the cdk4/6 inhibitors palbociclib or abemaciclib for three weeks. While vehicle-treated PCD mice showed a 7% increase in serum calcium (Ca) levels over the course of treatment, Ca decreased by 1.8% and 0.5% in palbociclib- and abemaciclib-treated PCD mice, respectively, from pre-treatment levels. This treatment effect persisted for at least 60 days after discontinuation of treatment. Decreased parathyroid proliferation, as evidenced by 4.7-fold and 17.3-fold fewer Ki-67-positive cells in palbociclib- and abemaciclib-treated PCD mice, respectively, compared with vehicle-treated PCD mice, was also seen. Cdk inhibitor treatment had no effect on Ca or parathyroid cell proliferation in wild type mice. These results demonstrate that palbociclib and abemaciclib can significantly slow the progression of hypercalcemia and parathyroid proliferation in a cyclin D1-driven parathyroid tumor model, suggesting that cyclin D1 overexpressing parathyroid cells may be particularly sensitive to cdk4/6 inhibition. Our findings provide the first evidence of a direct pharmacologic effect in a relevant preclinical system to support the hypothesis that selected HPT patients, eg those suffering from advanced PC with activated cyclin D1, could substantially benefit from cdk4/6 inhibitor therapy. This evidence may aid clinicians in selecting therapeutic interventions, including when considering such drugs for off-label use or inclusion of PC patients in “basket” clinical trials. Presentation: Thursday, June 15, 2023

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

There are few data regarding the clinical outcome of patients with parathyroid carcinoma (PC) and atypical adenoma (AA) after surgery. Aim of our study was to investigate disease recurrence and mortality rate as well as their predictors in a series of patients with PC or AA. Clinical and biochemical parameters, histological features, incidence of disease recurrence and mortality rate were retrospectively assessed in 39 patients (51% males, mean age 56.2 ± 17.2 years) diagnosed with PC (n=24) or AA (n=15) and followed up for 6.8 ± 5.0 years after surgery. No differences in baseline characteristics were registered between the two groups, except for higher KI67 values in PC than AA (6.9 ± 3.9% vs 3.4 ± 2.1%, p<0.01). Eight patients (21%) experienced recurrence after a mean follow-up of 5.1 ± 2.7 years, with higher relapse rate in PC than AA (25% vs 13%), though this difference did not reach statistical significance. Mortality rate was 10% in the whole sample, without significant differences between PC and AA. Relapsing cases had been undergone the most extensive surgery more frequently and they had a higher mortality rate in comparison to non relapsing patients (38% vs 6% and 38% vs 3%, respectively, p<0.03 for both). In comparison to survivors, deceased patients were submitted to the most extensive surgery more frequently (50% vs 9%), they were older (74.8 ± 4.6 vs 53.2 ± 16.3 years), and they had higher KI67 values (11.7 ± 4.9 vs 4.8 ± 2.8, p<0.03 for all comparisons). During seven-year follow-up after surgery, no significant differences in recurrence and mortality rate were observed between PC and AA patients. Death was associated with disease relapse, older age and higher KI67 values. These findings suggest a similar and careful long-term follow-up in both parathyroid tumors, especially in older patients, and emphasize the need of further studies in large cohorts to throw light on this crucial clinical issue.

A nomogram for predicting overall survival in patients with parathyroid cancer: A novel web-based calculator

BackgroundParathyroid carcinoma is a rare endocrine malignancy. Considering that clinicians develop appropriate treatment strategies based on patients' survival expectations. Therefore, the present study aimed to develop a survival prediction model to guide clinical decision-making. MethodsWe retrospectively analyzed 362 parathyroid carcinoma patients diaagnosed in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Correlations between outcome events and variables were analyzed using univariate and multifactorial Cox regression, and variables screened by the multifactorial Cox risk proportional model were used to construct a survival prediction model. The model was evaluated using Receiver Operating Characteristic (ROC) curves, decision curve analysis (DCA), and C-index and calibration curves. ResultsUnivariate and multifactorial COX analyses revealed five independent prognostic factors for parathyroid carcinoma patients, which were subsequently used to develop the nomogram prediction model. In the training cohort, the C-index of the nomogram in predicting the overall survival (OS) was 0.747 (0.686–0.808), the area under the receiver operator characteristics curve(AUC)values of the nomogram in prediction of the 3, 5, and 10-year OS were 0.718 (0617-0.819), 0.711 (0.614–0.808) and 0.706 (0.610–0.803), respectively. In the validation cohort, the C-index was 0.740 (0.645–0.835), The AUC for 3, 5, and 10-years OS were 0.736 (0.584–0888), 0.698 (0.551–0.845) and 0.767 (0.647–0.887), respectively. The C-index, time-dependent ROC curve, calibration curve, and DCA showed that the Nomogram had a clear advantage. ConclusionThe developed nomogram can be applied in clinical practice to help clinicians to assess patient prognosis.

Genetic and Epigenetic Alterations in Parathyroid Neoplasms.

The exact etiology of parathyroid carcinomas (PC) is still unknown. Their associations have with several inherited syndromes or specific genetic lesions have been established. The management of PC is challenging for clinicians. The complexity of molecular phenotypes increases with tumor aggressiveness. Lack of parafibromin on immunohistochemistry staining and HRPT2 mutation would be helpful in differentiation of carcinoma from adenoma. Lack of parafibromin expression, the gene product of HRPT2 is now used as a diagnostic, prognostic, and predictive marker for parathyroid carcinoma. The epigenetic alteration, for example, DNA methylation and modifications in the chromatin structure, are known as significant events involved in the parathyroid tumorigenesis. We suggest that adjuvant genetic and epigenetic target therapy should be considered in treatment of the patients with PC.

Patterns and Predictors of Cervical Lymph Node Metastasis in Parathyroid Carcinoma.

Simple SummaryParathyroid carcinoma (PC) is a rare endocrine malignancy with poor outcomes. Surgery remains the mainstay of PC treatment. However, due to the rarity of this malignancy, the optimal extent of PC surgery remains inconclusive, including whether to perform central lymph node dissection (LND). In the present study, we reported the patterns and predictors of cervical lymph node metastasis in PC based on a cohort of 68 PC patients. The results showed that the percentage of cervical lymph node metastasis in PC was 19.4% at initial surgery and 25.0% including reoperations for recurrencies. High-risk Schulte staging and CDC73 abnormalities were identified as risk factors for cervical lymph node metastasis. Central LND should be considered during remedial surgeries performed after previous local resection of PC for patients with high risk factors.Background: Parathyroid carcinoma (PC) is a rare endocrine malignancy with poor outcomes. Over 60% of PC patients experience repeated disease recurrence or metastasis. The significance of cervical lymph node dissection (LND) for PC remains inconclusive. Methods: PC patients diagnosed at Peking Union Medical College Hospital between 1992 and 2021 were reviewed retrospectively. Clinical data, initial tumor histological staging, parafibromin histochemical staining results, Ki67 index, CDC73 gene mutation status and outcome information were collected systemically. The risk factors for recurrence and lymph node or distant metastasis were explored. Results: Sixty-eight PC patients receiving LND were enrolled. Cervical lymph node metastasis was identified in 19.4% of patients at initial surgery and 25.0% of patients including reoperations for recurrences. The independent risk factor for PC recurrence was a Ki67 index ≥ 5% (HR4.41, 95% confidence interval (CI)1.30–14.95, p = 0.017). Distant metastasis was an independent prognostic factor for PC patient overall survival (HR 5.44, 95% CI 1.66–17.82, p = 0.005). High-risk Schulte staging (p = 0.021) and CDC73 abnormalities (p = 0.012) were risk factors for cervical lymph node metastasis. Conclusion: Most PCs were slow-growing, but lymph node metastasis was not rare. For patients planning to undergo remedial surgery after previous local resection of PC, central LND is suggested for tumors with high-risk Schulte staging or CDC73 abnormalities.

Case series of diagnosis and surgery challenges in parathyroid carcinoma.

IntroductionParathyroid carcinoma (PC) is a rare malignancy that accounts for 1 % of cases of hyperparathyroidism. Data regarding PC in Indonesia are scarce, which poses challenges to diagnosis and treatment. This study aims to describe a series of PC cases from a tertiary health care center over 12 years.Presentation of casesRetrospective data of six patients with hyperparathyroidism diagnosed with PC between 2008 and 2020 were reviewed. Clinical presentation, diagnosis, management, and short-term outcomes of PC were analyzed. All six PC patients were diagnosed postoperatively. Four of the patients presented with symptomatic hypercalcemia, and two presented with neck swelling. Elevated serum parathyroid hormone was observed in five patients. Only two patients had imaging results corresponding to PC characteristics. Ipsilateral parathyroidectomies were performed on 5 patients where invasion and metastasis are not evident. Four frozen section samples suggested PC, and two suggested parathyroid adenoma. Further histopathologic examination confirmed a diagnosis of PC in all patients. No metastasis to the adjacent lymph nodes or distant target organs was found during surgery.DiscussionPreoperative diagnosis of PC remains challenging. Suspicion of PC is appropriate in the presence of severe hypercalcemia, elevated parathyroid hormone level, and a mass observed either during imaging or intraoperatively.ConclusionIpsilateral parathyroidectomy seems to be feasible compared to total resection in order to preserve function and structure. Incomplete excision may lead to an increased risk of recurrence, emphasizing the importance of routinely following up on PC cases.

Update on the medical management of parathyroid carcinoma

Parathyroid carcinoma is a rare endocrine malignancy with an increasing rate of incidence. Most parathyroid carcinoma patients will develop local recurrence or metastases leading to poor prognosis. Medical management is the mainstay of treatment for patients with unresectable parathyroid carcinoma. However, the therapeutic outcome of medical management remains unsatisfactory restricted by limited options and efficacy. With the deepening of research, several novel drugs have been reported to be applied in the treatment of parathyroid carcinoma. Calcimimetics and receptor activator for nuclear factor-κB ligand inhibitors aiming to control hypercalcemia have been applied in the endocrine therapy of parathyroid carcinoma. Besides, preliminary studies have shown the therapeutic effects of targeted therapy and immunotherapy on parathyroid carcinoma. These new drugs have shed light on this clinical dilemma; however, their clinical efficacy remains to be determined. In this article, the recent progress in the medical management of parathyroid carcinoma is updated.

A Nomogram Predicting the Overall Survival and Cancer-Specific Survival in Patients with Parathyroid Cancer: A Retrospective Study.

PurposeThis 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.MethodsThe 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.ResultsAge, 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).ConclusionThe 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.

Parathyroid Carcinoma: Incidence, Survival Analysis, and Management: A Study from the SEER Database and Insights into Future Therapeutic Perspectives.

Simple SummaryParathyroid carcinoma (PC) is a rare endocrine malignancy and an uncommon cause of primary hyperparathyroidism. It is more common in older Caucasians, with a slight male predominance. Among the patients with available data in a large national cancer registry of the U.S. population, PC was usually 2–4 cm in size, histologically defined as well-differentiated adenocarcinoma, and localized to the native glands with negative lymph nodes. The overwhelming majority (>95%) of the patients underwent surgery, with the remaining few receiving radiation or chemotherapy. The 5-year survival rate after surgery was 84%. Factors such as large tumor size (>4 cm), older age (>40 years), male sex, Caucasian race, distant spread, and poor tumor differentiation were associated with an increased risk of death.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.

Management and Outcome of Parathyroid Carcinoma-Induced Primary Hyperparathyroidism: A Single-Centre Experience.

Background Parathyroid carcinoma (PC) is the rarest endocrine cancer and an infrequent cause of primary hyperparathyroidism (PHPT), responsible for less than 1% of cases. Due to its rarity, treatment is challenging. Methods A retrospective cohort study on 462 patients referred for parathyroidectomy to Thyroid and Parathyroid Unit at Santi Paolo e Carlo Hospital, Milan, Italy, from 2011 to 2021. We identified and individually described the patients affected with PC. Then, we split all patients treated for PHPT into four groups based on the cause: PC, adenoma, atypical adenoma, and hyperplasia. Patients' demographics, preoperative evaluation results, intraoperative findings, and outcomes for the PC group were compared with groups of PHPT due to benign causes. Results Eight cases of PC were identified, five males and three females. Seven cases presented with symptoms of hypercalcemia and one with a neck mass. Five underwent en bloc resections and three local excisions. Histopathological features showed capsular invasion in four patients, capsular and soft tissue invasion in three patients, and vascular invasion in one case. No patients had distant metastasis. One patient was classed as high risk based on the Schulte classification system. All patients treated for PC were alive and disease-free at a mean follow-up of 38.4 months. When compared with other PHPT patients, PC patients were more frequently male and had higher preoperative blood calcium and PTH and lower phosphate levels, larger and heavier parathyroids excised, lower postoperative calcium, and a higher rate of postoperative hypoparathyroidism. Conclusion Our study highlights some aspects valuable to suspect PC and differentiate PHPT-PC from benign causes of PHPT preoperatively. Preoperative suspicion of malignancy is essential to guarantee the best course of treatment for patients. Although limited for size and follow-up, the excellent outcome of our series seems to support the value of both surgery extension and risk class according to the Schulte classification as possible prognostic factors for recurrence.

Parathyroid Carcinoma

Parathyroid carcinoma is a very rare cancer, accounting for 0.5% to 5% of all causes of primary hyperparathyroidism. Parathyroid carcinoma has an equal frequency of occurrence in both genders, usually in the fifth decade of life. Preoperative diagnosis of parathyroid carcinoma is difficult due to a lack of clinical findings, laboratory results, or radiological characteristics specific to the disease. Though, parathyroid carcinoma patients usually present with severe hypercalcemia at the time of diagnosis. Complete en-bloc resection is the mainstay of the treatment. The adjuvant therapy such as radiotherapy or chemotherapy has not shown effective in the treatment of parathyroid carcinoma. Keywords: Parathyroid; Carcinoma; Neoplasm; Parathyroid glands; Hyperparathyroidism

Parathyroid Carcinoma in Tertiary Referral Centre: A 12-Year Case Series

Background: Parathyroid carcinoma (PC) is a rare malignancy that is difficult to diagnose preoperatively, and when it is suspected from clinical features and laboratory results, en-bloc resection is performed. Objective: To retrospectively review the prevalence, clinical presentations, laboratory findings, management modalities, and treatment outcomes of PC cases in the present study tertiary referral hospital. Materials and Methods: Patients with PC that attended the present center between 2008 and 2019 were included. Demographic data, clinical presentations, preoperative laboratory results, management, and outcomes were retrospectively reviewed. Results: Ten of 102 cases (9.8%) of the primary hyperparathyroidism were diagnosed as PC. Five were male (50%), and the mean age at diagnosis was 47.90±15.50 years. All PC patients presented with renal or bony manifestations, and five out of nine (45.5%) had palpable neck mass. Mean preoperative parathyroid hormone and serum calcium were 1,688.56±858.84 pg/mL and 15.30±3.27 mg/dL, respectively. In eight of these PC cases (80%), en-bloc resection was performed, and six patients underwent postoperative radiation treatment. Two patients died due to uncontrolled hypercalcemia with distant metastasis at 5.5- and 8-years after diagnosis. Conclusion: The prevalence of PC among primary hyperparathyroidism is as high in Thailand as in other Asian countries. En-bloc resection is performed when clinical presentations and laboratory results are suggestive of PC. Postoperative radiation is considered in selected cases. Intractable hypercalcemia is the main cause of death. Keyword: Parathyroid cancer; Parathyroid carcinoma; Primary hyperparathyroidism; Hypercalcemia; Parathyroid carcinoma case series

Surgical Disparities of Parathyroid Carcinoma: Long-Term Outcomes and Deep Excavation Based on a Large Database.

Purpose Parathyroid carcinoma (PC) is an uncommon endocrine disease, and surgery is considered the only potential cure. PC does not have a mature staging system because of the small number of PC patients. Our aim is to further investigate the prognostic factors associated with PC and explore the optimal extent of resection for PC patients. Methods Univariate and multivariate Cox regression analyses were conducted to explore the influence of relevant factors on cancer-specific survival (CSS) and overall survival (OS). Survival curves were generated using the Kaplan–Meier method and analyzed using the log-rank test. The mortality rates per 1,000 person-years were calculated to evaluate patients' follow-up data. We also performed subgroup analysis based on the extent of resection. Results The extent of resection was related to both CSS and OS, whereas race and extent of disease had a significant positive correlation with OS (all P < 0.05). Patients who underwent parathyroidectomy had remarkably better CSS and OS than patients who did not undergo definitive treatment. Conclusion The extent of resection is related to CSS and OS in patients with PC. No significant difference in prognosis was observed between patients who underwent parathyroidectomy and those who underwent en bloc resection, which may provide useful parameters for the treatment of PC.

Clinical Characteristics of Primary Hyperparathyroidism: 15-Year Experience of 457 Patients in a Single Center in China.

ObjectivePrimary hyperparathyroidism (PHPT) is a common endocrine disorder of calcium metabolism. However, data concerning a large cohort of PHPT patients in the Chinese population are scarce. Thus, the objective of this study was to determine the general clinical signatures of 457 Chinese PHPT patients and explore the clinical characteristic differences between benign and malignant PHPT.MethodsA single-center retrospective study was designed. Medical records between preoperation and postoperative follow-up, were assessed and statistical analysis of the clinical data was performed.ResultsPatients with PHPT aged 12–87 years, with a mean onset age of 56.16 ± 14.60 years, were included. Most patients (68.7%) in our center had symptomatic patterns described as bone pain (74.8%), urolithiasis (25.5%), fatigue (17.5%), and pathological fracture (13.1%), but an increasing tendency has been established in the proportion of patients with asymptomatic forms. Correlation analysis revealed that patients with higher serum levels of parathyroid hormone (PTH) and calcium presented higher serum levels of bone turnover markers (BTMs) and lower 25-hydroxy-vitamin D (25OHD) values (P<0.001). Gains in bone mineral density (BMD) at L1–4, the femoral neck and the total hip were observed 1–2 years after parathyroidectomy (9.6, 5.9, and 6.8%). Parathyroid carcinoma patients presented prominently higher serum PTH and calcium levels and BTMs and lower BMD at femoral neck and total hip than benign PHPT patients (P<0.05), while no significant differences in age, sex, and serum 25OHD concentration were observed between benign and malignant PHPT patients.ConclusionsPHPT should be paid attention to in the patients with bone pain. While, BMD and BTMs can differentiate parathyroid carcinoma from parathyroid adenoma and hyperplasia to some extent. In addition, anti-osteoporosis drugs could be used when necessary to avoid hip fractures in patients with parathyroid carcinoma.

Expression profile of serum-related exosomal miRNAs from parathyroid tumor.

The expression pattern of exosomal miRNAs derived from parathyroid tumor is still unknown. In the present work, we aimed to examine the differences on microRNA (miRNA) expression, present in serum exosomes, by comparing parathyroid carcinoma (PC) and parathyroid adenoma (PA). MiRNA expression profile of serum exosomes, derived from 4 PC patients and 4 PA patients, were analyzed by next-generation sequencing technology. The differential expressions of target miRNAs were further verified in both serum exosomes and tissues of PC/PA patients by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Lastly, receiver operating characteristic (ROC) curves were plotted to investigate the efficiency of target exosomal miRNAs in distinguishing PC patients from PA controls. Multiple differentially expressed miRNAs of serum exosomes were screened out by sequencing. Based on this screening, hsa-miR-146b-5p (p = 0.0846), hsa-miR-27a-5p (p = 0.0412), hsa-miR-93-5p (p = 0.73), hsa-miR-381-3p (p = 0.1239) and hsa-miR-134-5p (p = 0.0694) were upregulated in the serum exosomes of PC patients. These results were validated by qPCR, where the trend on differential miRNA expression was consistent with the sequencing results. Specifically, the expression of exosomal hsa-miR-27a-5p was able to clearly distinguish PC patients from PA controls, and related analysis indicated that the area under the ROC curve was 0.8594 (p = 0.0157). Here we present, for the first time, the miRNA expression profile of serum exosomes derived from PC patients. Based on this result, we presently suggest that the exosomal hsa-miR-27a-5p may serve as a putative tumor marker for preoperative identification of PC and PA subjects.