Recurrence Of Parathyroid Carcinoma Research Articles

SAT207 Parathyroid Carcinoma: A Case Report

Abstract Disclosure: K.T. Sy: None. Background: Parathyroid carcinoma is a rare malignancy, accounting for less than 1% of causes of primary hyperparathyroidism. Case reports have mentioned of parathyroid carcinoma arising in patients with prior neck irradiation, in secondary and tertiary hyperparathyroidism and in patients with history of thyroid cancer and parathyroid adenoma. However, none of these reported associations have been completely established. Clinical Case: The is a case of a 59-year old male presenting with hypercalcemia. He was diagnosed with primary hyperparathyroidism secondary to a parathyroid adenoma, underwent parathyroidectomy with resolution of the hypercalcemia. Six years later, patient had recurrence of hypercalcemia with elevated PTH levels. Parathyroid imaging revealed a mild sestamibi-avid focus in the left retrosternal region, suggestive of an ectopic parathyroid gland and radio-guided neck exploration was done with excision of lesion. Histopathological report revealed parathyroid carcinoma. Two years later, there was recurrence of parathyroid carcinoma but mediastinal exploration revealed no lesions consistent with parathyroid carcinoma. Hypercalcemia with hyperparathyroidism persisted, and cinacalet was started but the patient could not tolerate the nausea associated with the medication. Repeat parathyroid imaging revealed sestamibi-avid lesions in the right retroclavicular, left prevascular/retrosternal, and a left paratracheal areas. Surgical exploration was offered but the patient refused. The patient also developed hypertension and low bone density was noted on dual X-ray absorptiometry (DXA) scan. He was started on denosumab 60 mg subcutaneously every 6 months, which was increased to 60mg every month and then 120mg every month to maintain normal calcium levels. The patient also developed chronic kidney disease, eventually requiring hemodialysis for elevated creatinine levels and hypercalcemic crisis. Soon after hemodialysis was started, the patient had a myocardial infarction and eventually expired. Conclusion: Complete surgical resection is the primary mode of therapy in parathyroid carcinoma, although hypercalcemia is the main cause of morbidity and mortality, rather than the tumor burden. The adjuvant use of radiotherapy and chemotherapy are still controversial. Some studies have shown that long term survival is favorable, but recurrences are frequent and patients tend to live a life filled with long-term follow up, multiple laboratory exams and imaging, hospitalizations and frequent reoperations. Mortality is usually due to uncontrollable hypercalcemia, leading to renal failure and cardiac arrhythmias. Presentation: Saturday, June 17, 2023

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.

A retrospective study of the clinical and laboratory predictors and morphological characteristics of the parathyroid carcinoma

Background: there are no specific markers of the parathyroid carcinoma (PC) therefore, the development of algorithms for identifying high-risk patients is an urgent task.
 Aims: to determine the clinical and laboratory predictors of PC and to identify the factors of a poor prognosis.
 Materials and methods: A multicenter retrospective study included 242 patients with primary hyperparathyroidism (PHPT) who were divided into groups: 162 with adenomas, 30 with аtypical adenomas (АА) and 50 patients with PC. Data collection and analysis was carried out from 2017 to 2020. The primary goal assessment of the possibility of PС using preoperative laboratory and instrumental data. The group of PC was divided into subgroups: the patients in recurrences (n=17) and remission (n=33). The level of the total calcium, albumin, alkaline phosphatase (ALP), ionized calcium (Ca ++) in the blood were determined on the automatic biochemical analyzer; the level of parathyroid hormone (PTH) by electrochemoluminescent analyzer. The size of the PG determined by the ellipse formula: V (cm3) = (A B C) 0.49. Statistical analysis was performed with Statistica 13 and SPSS software packages. For multiple comparisons, the Bonferroni correction was applied.
 Results: the group of patients with increased risk of PC include persons with increased level of PTH 443 pg/ml, Ca++ 1.5 mmol/l, total calcium 3.2 mmol/l, ALP 176 IU/L, V of tumors 2.6 cm3, largest size 22.5 mm (p 0,001). Heterogeneous structure is more typical to PC compared to the АА (p = 0,004 and р = 0,011), the same applies to indefinite contour (р = 0,001 и р = 0,011). Pathological mitosis is a prognostically unfavorable factor of recurrence of PC (р=0,007).
 Conclusions: the patients with PC and AA are characterized with more aggressive course of PHPT compared to the group of adenomas.

Clinical Presentation, Treatment, and Outcome of Parathyroid Carcinoma: Results of the NEKAR Retrospective International Multicenter Study.

In this retrospective cohort study, we describe the clinical presentation and workup of parathyroid carcinoma (PC) and determine its clinical prognostic parameters. Primary outcome was recurrence free survival. PC is an orphan malignancy for which diagnostic workup and treatment is not established. Eighty-three patients were diagnosed with PC between 1986 and 2018. Disease-specific and recurrence-free survivals were estimated with the Kaplan-Meier method. Risk factors for recurrence were identified by binary logistic regression with adjustment for age and sex. Thirty-nine tumors underwent central histopathological review. Renal (39.8%), gastrointestinal (24.1%), bone (22.9%), and psychiatric (19.3%) symptoms were the most common symptoms. Surgical treatment was heterogeneous [parathyroidectomy [PTx)] alone: 22.9%; PTx and hemithyroidectomy: 24.1%; en bloc resection 15.7%; others 37.3%] and complications of surgery were frequent (recurrent laryngeal nerve palsy 25.3%; hypoparathyroidism 6%). Recurrence of PC was observed in 32 of 83 cases. In univariate analysis, rate of recurrence was reduced when extended initial surgery had been performed (P = 0.04). In multivariate analysis low T status [odds ratio (OR) = 2.65, 95% confidence interval (CI) 1.02-6.88, P = 0.045], N0 stage at initial diagnosis (OR = 6.32, 95% CI 1.33-30.01, P = 0.02), Ki-67 <10% (OR = 14.07, 95% CI 2.09-94.9, P = 0.007), and postoperative biochemical remission (OR = 0.023, 95% CI 0.001-0.52, P = 0.018) were beneficial prognostic parameters for recurrence-free survival. Despite a favorable overall prognosis, PC shows high rates of recurrence leading to repeated surgery and postoperative recurrent laryngeal nerve palsy and hypoparathyroidism. In view of the reduced recurrence rate in cases of extended surgery, ipsilateral completion surgery may be considered when PC is confirmed.

Parathyroid carcinoma in a 13-year-old girl with a long-term survival

BackgroundParathyroid carcinoma as a cause of primary hyperparathyroidism in children is extremely rare. We report a case of parathyroid carcinoma which occurred in a 13-year-old girl who survived for more than 45 years after the first operation.Case presentationA woman was admitted to our hospital for the treatment of recurrent parathyroid carcinoma in the neck. She had been diagnosed with primary hyperparathyroidism from a fibula fracture and underwent parathyroidectomy at 13 years old. She had no family history of multiple endocrine neoplasia or jaw tumor syndrome. Genetic testing was not performed, and the histopathological diagnosis of the tumor had been parathyroid adenoma at the time. At 22 years old, she showed hypercalcemia after a femur fracture. Pulmonary metastases of parathyroid carcinoma in the bilateral lungs were found and surgically removed. Regarding the clinical course, her diagnosis was corrected from parathyroid adenoma to parathyroid carcinoma. At 33 years old, re-resection of the lung metastases was performed. For 10 years, her serum calcium level stayed within the normal range. However, her serum calcium level and intact parathyroid hormone eventually began to increase. Two masses suspected of being parathyroid carcinoma recurrence were found in the neck when she was 57 years old. En bloc resection was performed. Pathologically, the tumors were diagnosed as parathyroid adenoma. The serum calcium level and intact parathyroid hormone did not decrease after the operation. A 99mTc-methoxy-isobutyl-isonitrile- and 18F-fluorodeoxyglucose-negative, 11C-methionine-positive tumor was detected at the right side of the trachea in the neck. The tumor was removed, along with the thyroid, muscle, and trachea that were involved. The pathological diagnosis was parathyroid carcinoma recurrence. The serum calcium level and intact parathyroid hormone decreased temporarily but had increased again 8 months later. Methionine-positive tumors were found at the right side of the trachea and suspected of being a recurrence. Denosumab reduced her serum calcium level, and radiation successfully suppressed the growth of the recurrent tumors.ConclusionWe have reported a rare case of parathyroid carcinoma in a child who has survived for over 40 years. Positron emission tomography of 11C-methionine was useful for detecting local recurrence. This patient’s long-term survival has been attributed to multimodality treatment including repeated surgery, medication, and radiation.

Atypical Recurrence of Parathyroid Carcinoma Following Infliximab Therapy in a Patient with Ulcerative Colitis

Parathyroid carcinoma (PTC) has a high rate of recurrence, which typically occurs within 5 years of diagnosis involving locoregional sites. Immunosuppressive therapies pose a theoretical increased risk of malignancy. We report an atypical case of PTC recurrence in a patient receiving infliximab therapy for ulcerative colitis (UC). Main diagnostic tests performed included calcium and parathyroid hormone (PTH) levels, computed tomography, and a venous sampling study. A patient with PTC, who was "cured" by parathyroidectomy, presented with recurrent hypercalcemia 21 years after his initial diagnosis. He had recently been diagnosed with UC and was started on infliximab. His serum PTH level was elevated. After negative routine neck imaging studies and sestamibi scan, he underwent selective venous sampling with PTH measurements, which localized the source lesion to the thoracic wall. Subsequent imaging showed multiple left lung and pleural nodules, which were surgically resected. Hypercalcemia abated after surgery, but quickly returned and was recalcitrant to treatment with cinacalcet and zoledronic acid. Further imaging demonstrated recurrent lung metastases, some along the left diaphragm. He underwent 2 additional surgical resections, after which PTH and calcium levels normalized. Infliximab was replaced with vedolizumab for treatment of UC. Atypical presentation of PTC may occur in the context of immunosuppressive therapy. Venous sampling with PTH measurements can aid in localization of atypical metastatic PTC. Additional surveillance for PTC recurrence may be prudent following the initiation of immunosuppressive therapy in patients with a history of PTC.

289O - Spectrum of mitochondrial genomic variation in parathyroid neoplasms by ultra-deep targeted DNA sequencing

BackgroundParathyroid neoplasms are characterized with hypersecretion of parathyroid hormone and potentially exhibit disruption of metabolic pathways. Mitochondria are essential for energy homeostasis and mitochondrial DNA (mtDNA) abnormalities are related to multiple types of malignancies. However, the status of mtDNA mutation and copy number variations in parathyroid carcinoma (PC) is not well known. MethodsUltra-deep targeted sequencing of mitochondrial genome was performed using tissues of 12 PCs and 12 parathyroid adenomas (PAs). Germline variants and somatic mutations in the mitochondrial genome were scanned and analysed in comparison with clinical features. The relative copy number of mtDNA in PCs and PAs was determined via quantitative real-time polymerase chain reaction. ResultsA total of 528 germline variants and 16 somatic mutations were identified in 24 samples of parathyroid neoplasms. All 62 non-synonymous germline variants in coding sequence (CDS) were predicted to be of low pathogenicity in PA and PC samples. Five somatic mutations with high pathogenicity in CDSs were identified in 4 (33.3%, 4/12) PC samples and 1 PA sample (8.3%, 1/12). A somatic mutation in a CDS was correlated with high mtDNA copy number in parathyroid neoplasm (p = 0.004), CDC73 gene mutation (p = 0.017) and PC recurrence (p = 0.024). More C-19 genotypes in the D310 region were found in PA than in the PC samples (3.5% vs 1.9%, p = 0.045). ConclusionsMore somatic CDS mutations with high pathogenicity were identified in PC than in PA. A high mtDNA copy number was found in parathyroid neoplasms with somatic CDS mutations and in PCs with CDC73 mutations and recurrence. Legal entity responsible for the studyThe authors. FundingThis work was supported by the Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS-I2M) (2017-I2M-1-001), Peking Union Medical College Innovative Team Development Program, the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018PT32014) and the 2016 Peking Union Medical College Hospital Science Foundation for Junior Faculty (pumch-2016.2.7). DisclosureAll authors have declared no conflicts of interest.

The Influence of Surgical Extent and Parafibromin Staining on The Outcome of Parathyroid Carcinoma: 20-Year Experience From a Single Institute

Objective: Parathyroid carcinoma (PC) is a rare endocrine malignancy with a poor prognosis. The optimal surgical procedure and prognostic factors for PC remain controversial. Methods: Clinical information and parafibromin staining results from 53 patients with PC were reviewed retrospectively from 1997 to 2018. Immunohistochemical staining for parafibromin was performed on formalin-fixed, paraffin-embedded tissue samples. The influence of clinical parameters, surgical procedure, and parafibromin staining of tumor tissues on prognosis were evaluated. Results: A total of 53 patients with PC were enrolled in this study. The male to female ratio was 1.94:1. En bloc resection was performed as initial surgery for 18 patients (34.0%), and 35 patients (66.0%) underwent local resection. Parafibromin staining was negative in the tumor tissues of 24 PC patients (45.3%). Thirty-three patients suffered from local recurrence or distant metastasis, and overall mortality was 16/53 at a median follow-up time of 80 months (range, 7 to 282 months). Cox proportional hazards analysis showed that negative parafibromin staining (hazard ratio [HR], 4.13; 95% confidence interval [CI], 1.73 to 9.87; P = .001) was related to recurrence or metastasis and that age >50 years (HR, 5.66; 95% CI, 1.58 to 20.31; P = .008) was related to mortality. The extent of resection was not related to recurrence or overall survival. Conclusion: The majority of PC patients have a relatively long survival with multiple recurrences. Absence of parafibromin staining was a factor that influenced PC recurrence. The main factor influencing PC outcomes may be the biological characteristics rather than surgical extent. Abbreviations: CI = confidence interval; DFS = disease-free survival; HR = hazard ratio; OS = overall survival; PC = parathyroid carcinoma; WHO = World Health Organization.

MON-327 A Case of Parathyroid Carcinoma in a Patient with Late Stage Chronic Kidney Disease

Introduction: Parathyroid carcinoma (PC) is rare, representing 0.3-5% of primary hyperparathyroidism cases. Its pathophysiology is incompletely understood. Established predisposing factors are lacking, with the exception of known genetic mutation and possibly radiotherapy. The rarity of PC and the fact that its clinical and biochemical features overlap benign parathyroid disease make pre-operative diagnosis challenging. Often the diagnosis is made post-operatively through histopathology. It has been hypothesized that chronic kidney disease may predispose to PC, given chronic parathyroid stimulus related to hypocalcemia and hyperphosphatemia. Here we describe an unusual case of parathyroid cancer in a man with long-standing secondary hyperparathyroidism related to stage IV chronic kidney disease. Case report: A 70-year-old man with hypertension and stage IV chronic kidney disease (CKD) presented for treatment ofsuspected tertiary hyperparathyroidism. His intact parathyroid hormone (iPTH) was 384 (8-54 pg/ml) and serum calcium 11.3 (8.6-10.2 mg/dl). He initially opted not to pursue surgery. Five months later, he presented to theemergency department with shortness of breath and new onset of hoarseness. He was diagnosedwith left vocal cord paralysis. Neck ultrasound showed a 1.1 X 1.4 x 1.4 cm hypoechoic nodule posterior and inferior to the lower left thyroid gland with internal color flow, and he was referred to surgery. Pre-operative serumcalcium was 10.1 with iPTH 774. Intra operatively, the mass was adherent to the surrounding musculature, thyroid and esophagus. Biopsy suggested parathyroid cancer. He underwent an en bloc resection of the left lower parathyroid mass, left superior parathyroidectomy, and ipsilateral hemithyroidectomy. Intra-operative iPTH dropped from 747 to 245. Pathology was consistent witha 3 cm parathyroid carcinoma. The posterior margin was focally positive for tumor. PTH remained elevated post-operativelyat 249 with a corrected serum calcium of 8.6. PET CT was without evidence of metabolically active disease,and neck ultrasound was unremarkable.The patientdeclined HRPT2 mutation testing. Conclusion: The vast majority of PC cases present with primary hyperparathyroidism. The first case of PC diagnosed in secondary hyperparathyroidism was published in 1982. Most patients with long-standing CKD develop polyclonal hyperplasia. In some cases, a monoclonal form of nodular growth has been reported. This monoclonal transformation may involve somatic mutations, such as in the tumor suppressor gene WT1. Whether such cases could progress to malignancy is conceivable, although as yet unproven. Biochemical monitoring for PC recurrence in patients with underlying secondary hyperparathyroidism is challenging. PTH levels do not normalize after surgery, and PTH resistance may delay the development of recurrence-associated hypercalcemia.

Surgical treatment of recurrent parathyroid carcinoma with invasion of the upper aerodigestive tract

To evaluate the factors contributed to the recurrence of parathyroid carcinoma with the invasion of the upper aerodigestive tract and the outcomes of reoperation. Six cases reviewed, in which the age ranged from 32 to 79 years old. The initial diagnoses and surgical procedures, the sites and surgical treatment of the recurrent disease, and the chemical markers, such as parathyroid hormone (PTH) and serum calcium, were retrospectively studied. The preoperative PTH levels ranged from 860 to 2830 ng/L. In 4 patients the recurrence diseases were founded in the tracheoesophageal groove, of them one with invasion of the larynx only and one with invasion of the larynx and pharynx in addition to the trachea and esophagus involvement. Selective neck dissection for level II, III, IV and VI was taken in all cases in addition to the removal of the local recurrent diseases. Recurrent laryngeal nerves were so badly embedded in tumor tissue that they were intentionally resected in 4 patients although they were functionally normal before operation. Prophylactic tracheostomy was carried out in 5 cases. PTH level dropped more than 70% of that prior the operation at 10 min after the removal of the tumor-bearing tissues and to normal range within the first 2 hours postoperatively, and hypocalcemia disappeared in 2 days postoperatively. All cases experienced significant improvement in symptoms and signs in the first three days postoperatively. PTH and serum calcium levels were within normal range in 4 cases during the follow-up of 11 to 40 months, while hyperparathyroidism was encountered 8 and 11 months postoperatively in other 2 cases, respectively. Esophageal fistula, chylous fistula and dehiscence of sternotomy developed in 3 cases separately. Of 5 patients with tracheostomy, the tracheostomy tubes were removed two weeks in 4 cases and six weeks in the other one after operation. Recurrent parathyroid carcinoma even with invasion of the upper aerodigestive tract still has promising surgical outcomes. Both the precise localization of the recurrent diseases and the intraoperative PTH assay are importance to the successful treatment of these diseases.

Subcutaneous local recurrence of parathyroid carcinoma

Subcutaneous local recurrence of parathyroid carcinoma

A Case of Parathyroid Carcinoma Underwent Radiation Therapy on the Metastatic Bone Lesions

Parathyroid carcinoma is a rare malignancy that is responsible for only 0.5 to 4% of all cases of primary hyperparathyroidism. Surgery is the only curative treatment. We report a case of a 46-year-old woman referred for a severe osteoporosis with frequent bone fracture associated with hypercalcemia. Initially, though she had multiple osteolytic lesions, we thought that the lesions were brown tumors resulting from hyperparathyroidism. The patient underwent surgery and was diagnosed with parathyroid carcinoma. After surgery, her intact PTH level normalized for brief period of time, but it was again elevated at 6 weeks after surgery. We suggest that the multiple osteolytic lesions were metastases because there was no evidence of local recurrence of parathyroid carcinoma, and the lesions looked like metastases on CT and PET-CT. The patient was treated with radiation therapy on the lumbar vertebra, one a site of the metastatic lesions. After radiotherapy, her serum intact PTH was decreased.