Diagnosis Of Parathyroid Carcinoma Research Articles

Parathyroid Carcinomas: A Series of 6 Cases and Literature Review

Parathyroid carcinoma (PC) is a rare endocrine malignancy. We report 6 cases of PCs operated on in our department, during a period of 12 years (2010-2021). All of our patients presented severe hyperparathyroidism, high calcium levels, and very elevated parathormone (PTH) rates. Five were between the fifth and sixth decades of life and 1 patient was 37 years old. The parathyroid gland was only palpable in 1 case. All of our patients underwent cervical ultrasound and 5 of them underwent 99m Tc-MIBI scintigraphy. One of the patients presented bilateral parathyroid masses. All our patients were treated surgically: a parathyroidectomy was performed in all cases. In 1 patient, parathyroidectomy was performed in conjunction with a homolateral loboisthmectomy, as the diagnosis of PC was suspected preoperatively due to pulmonary metastases. The final anatomopathological study revealed PC in all cases. Follow-up was uneventful in 5 cases and 1 patient was lost to follow-up. Clinicians should suspect PC in patients with severe hypercalcemia, extremely elevated PTH levels, large parathyroid lesions, and distant metastases. Complete surgical resection, extended to the homolateral thyroid lobe, remains the recommended treatment.

Parathyroid carcinoma located in the thyroid gland: A case report

BACKGROUND Parathyroid carcinoma (PC) is a difficult-to-diagnose rare disease with low incidence. Relatively accurate preoperative diagnosis is very important in choosing surgical methods and patient prognosis. CASE SUMMARY This study reported the clinical diagnosis and treatment of a rare patient with PC located in the thyroid gland and provided a case reference for the diagnosis and treatment of PC. A case of a 64-year-old male patient who presented to our hospital with systemic muscle and joint pain and palpitations is outlined. Subsequently, the patient was admitted to the Department of Nephrology for the treatment of “multiple myeloma nephropathy pending investigation”. The patient was diagnosed with “primary hyperparathyroidism and hypercalcemic crisis” using thyroid color ultrasound. CONCLUSION The intraoperative frozen section report considered the parathyroid tumor. Surgical tumor resection was promptly performed, and the diagnosis of PC was confirmed.

SAT208 Hypercalcemic Crisis In Metastatic Parathyroid Carcinoma: An Unusual Presentation Of A Rare Endocrine Disease

Abstract Disclosure: A. Barnett: None. T. Sliker: None. R.J. Harper: None. G. Elshimy: None. Introduction: Hypercalcemia can be life-threatening with a wide differential, including parathyroid carcinoma (PC), which accounts for only 0.005% of all malignancies in the U.S. Maintaining an index of suspicion for PC in PTH-mediated hypercalcemia is vital for improving long-term survival and outcomes. Frozen section can be misleading when PC is suspected. We describe a case of hypercalcemia due to recurrent metastatic PC 9 years after initial diagnosis. Case: A 57-year-old male presented for endophthalmitis and altered mentation. Records revealed primary hyperparathyroidism with calcium 11.7 mg/dL, PTH 337 (11.1-79.5pg/mL), and 24-hour urine calcium 810 mg/day. Sestamibi showed right lower parathyroid adenoma and a possible right upper parathyroid adenoma. Right superior parathyroidectomy revealed PC invasive into adipose tissue, increased vascularity and positive margins. A hemithyroidectomy and central neck dissection was performed with intraoperative report noting normal-appearing right inferior parathyroid affixed to thyroid, confirmed by frozen section biopsy. The right inferior parathyroid was minced and re-implanted into the right strap muscle. Patient did not return for follow-up. Recent admission labs showed calcium 15.2 mg/dL, ionized calcium 6.8 (4.5-5.3mg/dL), PTH 546 pg/mL, creatinine 1.54 mg/dL, 25-OH vitamin D 21.64 ng/mL, and phosphorus 1.9 mg/dL. He was treated with intravenous fluids, zoledronic acid, and calcitonin. Due to a high suspicion of locally recurrent or metastatic PC, further imaging obtained. A Neck CT and US showed no abnormalities of right surgical bed or cervical lymphadenopathy. Sestamibi revealed a right lower lung lobe nodule, measuring 2.3cm, with intense immediate and delayed uptake concerning for metastatic or primary lung neoplasm and mild focal retention in the right paratracheal region, suspicious for tumor recurrence. PTHrP was negative. He underwent video-assisted thoracoscopic right lower lobectomy that showed an ovoid, well-circumscribed 2.5 x 2.3 x 2.3cm tumor, which stained positive for PAX-8 and synaptophysin, consistent with PC. Discussion: Clinicians should suspect PC in cases with severe hypercalcemia or absolute PTH above 500mg/dL to allow for better surgical planning. Complete en bloc resection is the standard treatment to improve long-term outcomes and reduce disease recurrence. Diagnosis of PC following incomplete surgical resection has increased recurrence rates of greater than 50%. Our patient’s recurrence was 9 years after diagnosis, but most recurrences occur within 2-3 years and occasionally more than 20 years later. The ipsilateral parathyroid was re-implanted based on frozen section results in this patient, which may have been misleading. Frozen sections of parathyroid tissue are notoriously difficult to distinguish normal parathyroid versus PC and only diagnostic in 15% of cases as described in one case series. To reduce the risk of recurrent disease, physicians shouldn’t entirely depend on these results when there is high suspicion for PC. Presentation: Saturday, June 17, 2023

Approach to the Patient With Parathyroid Carcinoma.

Parathyroid carcinoma (PC) is usually associated with severe symptomatic primary hyperparathyroidism (PHPT) and accounts for less than 1% of all cases of PHPT and approximately 0.005% of all cancers. PC most commonly occurs as a sporadic disease and somatic CDC73 mutations can be detected in up to 80% of cases. Approximately 30% of patients harbor a germline mutation of the CDC73 gene. Preoperative diagnosis of PC is difficult because no disease-specific markers are available, and PC should be suspected in patients with severe hypercalcemia and end-organ complications. The diagnosis is based on the evidence of invasive tumor growth at histology and/or metastases. En bloc resection of the tumor, together with the ipsilateral thyroid lobe and adjacent structures, should be performed by an experienced surgeon when PC is suspected. This surgical approach reduces the risk of recurrence and metastasis and offers the highest chance of cure. Nonetheless, PC has a recurrence rate of 40% to 60% and, if feasible, multiple surgical procedures should be performed. When surgery is no longer an option, medical treatment is aimed to reduce hypercalcemia and target organ complications. Targeted agents have been effectively used in a few cases. We describe herein a patient with severe PHPT due to PC and provide a systematic diagnostic and treatment approach. A thorough review of the medical history, a typical clinical and biochemical phenotype and, in some cases, the revision of the histological examination provide the clues for the diagnosis of PC.

Metastatic Parathyroid Carcinoma: A Case Report

Parathyroid carcinoma is a rare clinical entity, characterized by its diagnostic difficulties. We report a case of a 58 year- old male who presented with a history of chronic hypercalcemia, the cervical ultrasound reported a deep left cervical mass, pushing back the left thyroid lobe and the trachea, oval in shape, with clear contours. The thoracic-abdominal-pelvic CT scan showed a left thyro ïd mass plunging into the posterior mediastinum with secondary bone lesions, the patient underwent a total thyroïdectomy with a diagnosis of parathyroid carcinoma on morphological and immunohistochemical studies, he was treated with first line chemotherapy with a good clinical and biological evolution. After the last course of chemotherapy, the patient presented bone pain resistant to analgesics with elevated hypercalcemia.

In-depth proteomic signature of parathyroid carcinoma.

Diagnosing parathyroid carcinoma (PC) is complicated and controversial that early diagnosis and intervention are often difficult. Therefore, we aimed to elucidate the protein signatures of PC through quantitative proteomic analyses to aid in the early and accurate diagnosis of PC. We conducted a retrospective cohort study. We performed liquid chromatography with tandem mass spectrometry using formalin-fixed paraffin-embedded samples. For the analyses, 23 PC and 15 parathyroid adenoma (PA) tissues were collected from 6 tertiary hospitals in South Korea. The mean age of the patients was 52 years, and 63% were women. Proteomic expression profiling revealed 304 differentially expressed proteins (DEPs) with a cut-off of P < .05 and fold change >1.5. Among DEPs, we identified a set of 5 proteins that can discriminate PC from PA: carbonic anhydrase 4 (CA4), alpha/beta hydrolase domain-containing protein 14B (ABHD14B), laminin subunit beta-2 (LAMB2), CD44 antigen (CD44), and alpha-1-acid glycoprotein 1 (ORM1) that exhibited the highest area under the curve of 0.991 in neural network model. The nuclear percentage of CA4 and LAMB2 in immunohistochemistry was significantly lower in PC tissue than in the PA (CA4: 2.77 ± 1.96%, 26.2 ± 3.45%, P < .001; LAMB2: 6.86 ± 3.46%, 38.54 ± 4.13%, P < .001). The most enriched canonical pathways in PC included glycoprotein-6 signaling and mammalian target of rapamycin (mTOR). We identified key proteins differentially expressed between PC and PA using proteomic analyses of parathyroid neoplasms. These findings may help to diagnose PC accurately and elucidate potential therapeutic targets.

Parathyroid Carcinoma with Low Values of Elevated Parathyroid Hormone: A Case Report

Parathyroid Carcinoma (PC) is a rare endocrine malignancy, accounting for &lt;1% of sporadic Primary Hyperparathyroidism (PHPT) cases. A preoperative and even intraoperative diagnosis of PC is rarely reported due to its close resemblance to parathyroid adenoma with respect to symptoms- hypercalcaemia, renal stones and/or failure, osteoporosis, and cardiac/neurocognitive dysfunction. The mean serum calcium in PC is reported to be greater than 14 mg/dL along with serum Parathyroid Hormone (PTH) levels often above 1000 pg/mL. When serum PTH levels are 10 times the upper limit of the normal, it is considered diagnostic of PC. Surgical en-bloc resection without capsular breach is the only definitive cure for PC. The present case report included two patients who presented with features of single parathyroid glandular enlargement, hypercalcaemia, its consequences and with normal ionised calcium, but relatively low levels of elevated serum PTH (&lt;300 pg/mL). They were operated and identified postoperatively as having PC. This rare presentation of PC where the preoperative serum PTH values were lower than usually seen in carcinoma, should alert endocrinologists and surgeons that lower levels of elevated serum PTH do not primarily exclude the possibility of carcinoma.

Parathyroid Carcinoma in A Young Adult Parathyroid Carcinoma

A 21-year-old woman with no pathological history, who consults for a routine check-up. Neck examination revealed a 2-centimeter hard cervical swelling and shoulder tumor was palpated. Laboratory: hypercalcemia, Parathyroid Hormone (PTH) very high at 1312pg/ml, that is, more than 15 times normal. Technetium-99m-sestamibi scintigraphy showed an area of abnormal MIBI fixation on the right lower parathyroid projection. Right upper and lower parathyroidectomy with right lobectomy and surrounding adipose tissue was performed. The postoperative course was marked by normalization of serum calcium and PTH. The pathology was in favor of a parathyroid carcinoma. The diagnosis of parathyroid carcinoma is usually established by the combination of radiological and histological signs. The severity of this pathology is due to severe hypercalcemia and the risk of recurrence and distant metastasis that justify prolonged surveillance.

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.

Diagnostic significance of parafibromin expression in parathyroid carcinoma

Parathyroid carcinomas are difficult to distinguish from adenomas according to the current diagnostic criteria. The judgment of local infiltration is subjective and inconsistent. Existing studies have found that the CDC73 gene encoding parafibromin is related to the occurrence of parathyroid carcinomas. This study is aimed at investigating whether the immunohistochemistry of parafibromin is helpful in distinguishing malignant from benign parathyroid tumors. A total of 53 patients with parathyroid carcinoma from Peking Union Medical College Hospital were included. Metastasis was found in 17 of 53 patients. In addition, another 53 patients with parathyroid adenomas were included as controls. Appropriate sections were stained with an immunohistochemical autostainer. Three senior pathologists evaluated the sections and analyzed their clinicopathological features independently. The loss of parafibromin expression only occurred in malignant tumors, including all carcinomas with metastasis (17/17) and 14 of 36 carcinomas with only local infiltration. All staining results of adenomas (53/53) were positive. Considering invasion as the gold standard of malignancy, the sensitivity of parafibromin staining is 58%, and the specificity is 100%. If the gold standard is changed to metastasis, the sensitivity becomes 100%, and the specificity becomes 84%. By analyzing clinicopathological features with metastasis and parafibromin staining, it is found that local-infiltrative carcinomas with positive staining results have better biological behaviors than carcinomas that lack parafibromin expression. Parafibromin staining is highly recommended as an auxiliary method in the diagnosis of parathyroid carcinoma.

Parathyroid carcinoma - a study of 29 cases.

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. 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. 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. 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.

Mathematical model for preoperative differential diagnosis for the parathyroid neoplasms

Background and objectivePreoperative diagnosis of parathyroid carcinoma (PC) is critical for the determination of the scope of surgical intervention. Nowadays, specific diagnostic markers for differentiation of PC and benign tumors are unknown, and less than half of patients with PC undergo necessary en bloc surgery. The aim of this study was to develop the instrument for preoperative diagnosis of PC. MethodsA multi-center retrospective study included 242 patients with primary hyperparathyroidism: 50 patients with PC, 30 with аtypical adenoma (AA), and 162 with adenoma of the parathyroid glands. ResultsPatients with PC and AA had higher levels of PTH, ionized and albumin-corrected calcium, ALP, volume and the largest diameter of neoplasm, and the higher frequency of GFR decrease less than 60 ml/min/1.73 m2 compared to patients with adenoma. The frequency of low-energy fractures was higher in the carcinoma group versus the adenoma group (32% vs 8%). Heterogeneous structure and indefinite contour of glands detected by US were more typical for PC than for AA and adenomas. The mathematical model was developed using CatBoost gradient boosting algorithm for the noninvasive preoperative differential diagnosis of PC, AA, and adenoma. ConclusionsModel can predict adenoma with PPV 100% and PC with PPV 81–92%. Using model clinicians could plan extended en bloc resection for PC and selective parathyroidectomy for adenoma. If AA is predicted, he has to make a decision on the choice of the necessary volume of PTE based on his experience, because AA are the zone of uncertainty.

Preoperative prediction of parathyroid carcinoma in an Asian Indian cohort.

Parathyroid carcinoma (PC) requires preoperative prediction for appropriate surgical management. Differentiation from symptomatic primary hyperparathyroidism (sPHPT) cohort is difficult. Patients with sPHPT from a tertiary-care center, Western India, including Cohort-A (n= 19 [10/M; 9/F]) with PC and Cohort-B (n= 93 [33/M; 60/F] with benign parathyroid lesions) were compared to derive predictors for differential diagnosis. There were no differences in clinical or biochemical parameters between the two cohorts. Comparison of CECT parameters showed that irregular shape, tumor heterogeneity, infiltration, short/long-axis ratio >0.76, and long-diameter >30 mm had high negative-predictive value and intratumoral calcification had 100% positive-predictive value to diagnose PC; whereas there were no differences in contrast-enhancement patterns. Long diameter, short/long-axis ratio, and heterogeneity were significant predictors on multivariate analysis. It is difficult to predict diagnosis of PC in an Indian sPHPT cohort based on clinical and biochemical parameters, whereas CECT parathyroid-based parameters can aid in diagnosis.

Gene expression profile in metastatic and non-metastatic parathyroid carcinoma.

Parathyroid carcinoma (PC) is one of the rarest and aggressive malignancies of the endocrine system. In some instances, the histological diagnosis remains uncertain unless there is evidence of gross local invasion or secondary spread. The identification of molecular markers could improve the diagnostic accuracy of these lesions. The expression of 740 genes involved in the tumor progression processes was assessed in 8 parathyroid adenomas (PAs), 17 non-metastatic and 10 metastatic PCs using NanoString technology. Clustering analysis and Ingenuity Pathway Analysis (IPA) were interrogated to compare the gene expression profiles among the three analyzed groups and to evaluate the potential role of differentially expressed genes, respectively. The 103 differentially expressed genes between metastatic PCs and PAs are able to discriminate perfectly the two groups from a molecular point of view. The molecular signatures identified in non-metastatic PCs vs PAs and in metastatic PCs vs non-metastatic PCs comparisons, although with some exceptions, seem to be histotype-specific IPA reveals that hepatic fibrosis/hepatic stellate cell activation and GP6 signaling pathway are involved in malignant behavior of parathyroid tumors, whereas the activation of the HOTAIR regulatory pathway are involved in the metastatization process. Our investigation identified differentially expressed genes in non-metastatic PCs mainly encoding ECM proteins and in metastatic PCs driving endothelial-to-mesenchymal transition or encoding mediators of angiogenesis. The identified genes might be promising molecular markers potentially useful in the clinical practice for the early diagnosis and prognosis of PC.

SUN-934 A Rare Case of Hyperparathyroidism - Parathyroid Carcinoma, Atypical Adenoma, or Both?

Introduction: Parathyroid carcinoma (PC) is a rare endocrine malignancy. It accounts for <1% cases of primary hyperparathyroidism (PHPT). We present a rare case of concurrent PC and atypical parathyroid adenoma (PA). Case presentation: A 72-year-old woman presented with 1-week history of generalized weakness, confusion, and auditory hallucinations. Her medical history was significant for PHPT known for 5 years, CAD and CHF. The patient appeared mildly volume depleted and was tachycardic (105/min). The rest of her physical exam was unremarkable. Calcium (Ca) was 15.1 mg/dL (8.4–10.2 mg/dL) and intact PTH 451.9 pg/mL (12–88 pg/mL). Her condition improved with aggressive fluid replacement, pamidronate, and cinacalcet. A sestamibi scan revealed increased uptake of bilateral parathyroid tissue. Fine needle aspiration (FNA) revealed PA. Surgical treatment was postponed for control of cardiac comorbidities. One month later, she presented again with symptomatic hypercalcemia. Her Ca was 16.1 md/dL and PTH 761.5 pg/mL. Initial medical management was followed by subtotal parathyroidectomy – three masses were removed (one on the right and two on the left). Final pathology revealed PC within the left parathyroid, the others were consistent with hypercellular parathyroid tissue. One month later, the patient underwent left hemithyroidectomy, right parathyroidectomy, and central neck dissection. PTH level dropped to 2.4 pg/mL and Ca level was 7.6 mg/dL after surgery. She was discharged home on Ca and vitamin D supplements. Pathology was sent to a referral cancer center and revealed PC vs. atypical PA within the right parathyroid. Discussion: PC is a rare endocrine malignancy. Further, there are not many cases of synchronous PC and PA or multifocal PC. Diagnosing PC preoperatively is challenging since it shares overlapping characteristics with PA. Patients with malignancy commonly present with larger tumor size, higher level of Ca (>14.6 mg/dL), and PTH (5-fold higher than the upper limit of normal). Our patient had a history of multiple admissions due to symptomatic HC. She had no palpable neck masses on exam. Her initial FNA was consistent with PA. Hence, we presumed that her hypercalcemia was caused by PA. Establishing a definitive diagnosis of PC by frozen sections intraoperatively is difficult. Histopathologic findings of atypical cells, high mitotic rate, and cellular invasions can suggest the diagnosis, though they are often negative. Even postoperatively, pathologists often disagree on cytologic interpretation. However, differentiating PA and PC is important since earlier and more aggressive treatment is needed to reduce the morbidity and mortality in case of malignancy.

Cerebral metastases of parathyroid carcinoma: a case report and literature review

Parathyroid carcinoma (PC) is an uncommon endocrine tumor. At first presentation, the diagnosis of PC by morphologic analysis is challenging. Indeed, approximatively 50% of metastatic PCs were categorized as benign at the time of first resections. However, single brain metastasis rarely occurs in PC patients and could represent a further obstacle for PC diagnosis in the absence of other symptoms. The present report describes the clinicopathological features of a case of PC intracranial metastases in a 60-year-old woman, who presented space-brain occupying symptoms as a first manifestation. To the best of our knowledge, only ten cases with brain metastasis were reported in the literature.

SAT-102 ECTOPIC MEDIASTINAL PARATHYROID CARCINOMA ACCOMPANYING BY PARATHYROID HYPERPLASIA IN A HEMODIALYTIC PATIENT

Parathyroid carcinoma is a rare cancer, and the development under secondary hyperparathyroidism is also clinically infrequent. The diagnosis of parathyroid carcinoma under secondary hyperparathyroidism may be difficult due to a radiological similarity between parathyroid carcinoma and adenoma. Moreover, if hemodiaytic patients only show parathyroid hyperplasia without parathyroid adenomatous change by uncontrolled hyperphosphatemia, maligant change of parathyroid gland may be rarely developed. We report an interesting case showing an ectopic mediastinal parathyroid carcinoma related with uncontrolled secondary hyperparathyroidism and parathyroid hyperplasia in patient with end-stage renal disease (ESRD) undergoing hemodialysis. N/A (This abstract is a case report) A 30-year-old man on maintenance hemodialysis due to chronic rejection of transplanted kidney showed a recurrently high level of serum intact parathyroid hormone (iPTH) without remarkable decreases despites of intensive medications including intravenous calcitriol and lanthanum carbonate. Parathyroid scan revealed parathyroid hyperplasia in the both upper portions of thyroid. Ultrasound did not show extrathyroidal nodular lesions. Firstly, simultaneous use of cinacalcet and calcitriol was implemented, and we performed a follow-up scan due to persistently uncontrolled hyperparathyroidism and hypercalcemia. When compared with prior parathyroid scan, it showed more increased parathyroid hyperplasia in the same area, and new hot lesions in left lower portion of thyroid and right upper paratracheal area in mediastinum were newly shown. Computed tomography (CT) of neck showed multiple nodular lesions in the mediastinal area, compatible with ectopic parathyroid adenoma, along with hyperplasia on both upper and left lower parathyroid glands. Firstly, we referred to thoracic surgery for the mediastinal mass. The preoperative laboratory results were as follows: serum calcium, 10.4 mg/dL; serum iPTH, 1150 pg/mL. The mediastinal masses with diameters of less than 2.2 cm were removed and histologically compatible with parathyroid carcinoma. Serum iPTH did not postoperatively decrease, but serum calcium decreased. We performed a 18F-fluorodeoxyglucose positron-emission tomography-CT scan for parathyroid gland and distant metastases of parathyroid carcinoma. It revealed no locoregional and distant metastases of parathyroid carcinoma except remained parathyroid hyperplasia. We recommended total thyroidectomy immediately due to uncontrolled secondary hyperparathyroidism. After one month, the patient was performed total thyroidectomy and serum iPTH level was normalized after the operation. The pathologic results after total thyroidectomy showed only parathyroid hyperplasia without adenomatous changes and it also revealed no locoregional metastatic lesion of parathyroid carcinoma. A diagnosis of parathyroid carcinoma without a confirmative surgery is difficult particularly in uncontrolled secondary hyperparathyroidism without parathyroid adenoma. Moreover, an ectopic mediastinal parathyroid carcinoma under same condition may be easily underdiagnosed. Thus, dialytic patients with refractory secondary hyperparathyroidism irregardless of existence of parathyroid adenoma should perform a radiologically close follow-up, even if the first scan show only parathyroid hyperplasia.

Parathyroid Carcinoma-An Experience of the Enigma Over 10 Years.

Introduction:Parathyroid carcinoma (PC) is an uncommon clinical entity. Identification and appropriate treatment of PC remains a challenge. In this study, we explore clinico-radiological features suggestive of PC, the utility of Castleman's histopathological criteria for the diagnosis of PC and discuss the MD-Anderson prognostic stratification system for PC.Methods:Retrospective analysis (case series) of patients who were treated at our tertiary oncology institution between January 2009 and December 2018 with an eventual diagnosis of PC.Results:The study group comprised 15 patients. The most common presentation was related to the musculoskeletal system (n = 9, 60%). In one of the cases, ultrasound features were recorded to be suspicious of PC. The highest histopathological correlation with PC was found with capsular and vascular invasion (n = 12, 80%). The primary tumor was found in inferior parathyroid glands in most cases (n = 12, 80%). The average tumor size was 2.47 cm. Six patients (40%) received adjuvant radiotherapy (RT). Three patients (20%) developed recurrence, all having distant metastasis. Overall survival (OS) at 3 years was 92.31% and disease-free survival (DFS) of 76.61%.Conclusion:The presence of certain features on ultrasonography might suggest PC preoperatively. Among Castleman's criteria, capsular invasion and vascular invasion had a maximum association with PC in our series. At present, there is no evidence to routinely give adjuvant RT to all patients with PC.

Pediatric Parathyroid Carcinoma: A Case Report and Review of the Literature.

Primary hyperparathyroidism (PHPT) is a rare endocrine disease in the pediatric population. Sporadic parathyroid adenomas remain the most common cause of pediatric PHPT. Parathyroid carcinoma (PC) is an extremely rare cause of pediatric PHPT. We report a 16-year-old boy presenting with a nonhealing fragility fracture of the right leg along with florid features of rickets. Examination revealed a neck mass, mimicking a goiter. Biochemical findings were consistent with PHPT. Imaging was suggestive of a right inferior parathyroid mass infiltrating the right lobe of thyroid. The patient underwent en bloc surgical excision of the parathyroid mass along with the right lobe of thyroid. Histopathology was suggestive of a PC. He achieved biochemical remission with normalization of serum calcium and parathyroid hormone levels. At follow-up, there was no biochemical or imaging evidence of recurrence or metastasis. Genetic analysis revealed heterozygous germline deletion of CDC73. An extensive literature search on PC was conducted, with an emphasis on the pediatric population. Thirteen cases of pediatric PC were identified. The median age of presentation was 13 years; there was no sex predilection. All cases were symptomatic; 31% had a visible neck mass. The median serum calcium and intact parathyroid hormone levels were 14.3 mg/dL and 2000 pg/mL, respectively. All patients underwent surgical excision, with 27% showing metastatic relapse. Our findings indicate that the preoperative features that could point toward a diagnosis of PC in a child with PHPT are a tumor size of >3 cm, thyroid infiltration on imaging, and severe hypercalcemia at presentation.

Circular RNA profile of parathyroid neoplasms: analysis of co-expression networks of circular RNAs and mRNAs

ABSTRACTCircular RNAs (circRNAs) are a recently identified class of non-coding RNAs that participate in multiple biological processes and tumour progression. However, circRNA expression pattern in parathyroid neoplasms remains unknown. The circRNA profile of 6 parathyroid carcinomas (PCs), 6 parathyroid adenomas (PAs) and 4 normal parathyroid tissues was assessed by a microarray. Bioinformatic analyses were performed to investigate potential core circRNAs via co-expression network. CircRNA and corresponding mRNA expression were validated in a cohort of parathyroid neoplasms by RT-qPCR and fluorescence in situ hybridization (FISH). Compared to normal parathyroid, 5310 and 1055 circRNAs were differentially expressed in PC and PA tissues, respectively. The differential expression of 4 circRNAs (hsa_circRNA_0035563 (p = 0.006), hsa_circRNA_0017545 (p = 0.009), hsa_circRNA_0001687 (p = 0.005) and hsa_circRNA_0075005 (p = 0.001)) and 4 mRNAs (MYC, FSCN1, ANXA2 and AKR1C3) between PC and PA tissues were confirmed by RT-qPCR. In addition, high expression of hsa_circ_0035563 was related to CDC73 mutations (p = 0.022) and recurrence in PC patients (p = 0.042). Furthermore, hsa_circ_0075005 helped distinguish PCs from benign lesions using FISH, and the area under the curve was 0.779 (p = 0.013). Our findings describe the circRNA profile of PC for the first time and suggest that circRNAs and mRNAs interact in parathyroid tumourigenesis. This study demonstrates that hsa_circ_0075005 and MYC mRNA may be used for the differential diagnosis of PC and PA. The expression levels of hsa_circ_0035563 are related to CDC73 mutations and recurrence in malignancy, highlighting the significance of this parameter in prognosis of PC patients.