Recurrent Parathyroid Carcinoma Research Articles

Therapeutic options in the control of refractory hypercalcemia due recurrent parathyroid carcinoma: a case series

Therapeutic options in the control of refractory hypercalcemia due recurrent parathyroid carcinoma: a case series

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.

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

Reticular fibre structure in the differential diagnosis of parathyroid neoplasms

BackgroundTo investigate the characteristics of reticular fibre structure (RFS) in parathyroid adenoma (PTA), atypical parathyroid tumour (APT), and parathyroid carcinoma (PTC), and to assess its value as a diagnostic indicator.MethodsClinical data and pathological specimens of patients with PTA, APT or PTC were collected. Reticular fibre staining was performed to observe the characteristics of RFS. This study evaluated the incidence of RFS destruction in parathyroid tumours, compared RFS destruction between primary PTC and recurrent and metastatic PTC, and explored the association between RFS destruction and clinicopathological features of APT and primary PTC.ResultsReticular fibre staining was performed in 50 patients with PTA, 25 patients with APT, and 36 patients with PTC. In PTA cases, a delicate RFS was observed. In both the APT and PTC groups, incomplete RFS areas were observed. The incidence of RFS destruction was different among the PTA, APT, and PTC groups (P < 0.001, χ2-test), at 0% (0/50), 44% (11/25), and 86% (31/36), respectively. When differentiating PTC from APT, the sensitivity and specificity of RFS destruction were 81% and 56%, respectively. The incidence of RFS destruction was 73% (8/11) in the primary PTC group and 92% (23/25) in the recurrent and metastatic PTC groups. In both the APT group and primary PTC group, no correlation was found between RFS destruction and clinicopathological features.ConclusionRFS destruction may indicate that parathyroid tumours have unfavourable biological behaviours.Reticular fibre staining may be a valuable tool for improving the diagnostic accuracy in parathyroid tumours.

Extensive recurrent parathyroid carcinoma caused by tumour seeding in endoscopic parathyroidectomy

ANZ Journal of SurgeryVolume 93, Issue 4 p. 1117-1118 LETTER TO THE EDITOR Extensive recurrent parathyroid carcinoma caused by tumour seeding in endoscopic parathyroidectomy Yuquan Yuan MD, Yuquan Yuan MD Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China Graduate School of Medicine, Chongqing Medical University, Chongqing, China Contribution: ​Investigation, Writing - original draftSearch for more papers by this authorJunping Zhu MBBS, Junping Zhu MBBS Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China Contribution: Data curation, ResourcesSearch for more papers by this authorQianhui Wang MD, Qianhui Wang MD Department of Pathology, Chongqing General Hospital, Chongqing, China Contribution: Data curationSearch for more papers by this authorSupeng Yin PhD, Supeng Yin PhD Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorFan Zhang PhD, Fan Zhang PhD orcid.org/0000-0002-6758-2856 Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China Graduate School of Medicine, Chongqing Medical University, Chongqing, China Contribution: Conceptualization, Supervision, Writing - review & editingSearch for more papers by this author Yuquan Yuan MD, Yuquan Yuan MD Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China Graduate School of Medicine, Chongqing Medical University, Chongqing, China Contribution: ​Investigation, Writing - original draftSearch for more papers by this authorJunping Zhu MBBS, Junping Zhu MBBS Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China Contribution: Data curation, ResourcesSearch for more papers by this authorQianhui Wang MD, Qianhui Wang MD Department of Pathology, Chongqing General Hospital, Chongqing, China Contribution: Data curationSearch for more papers by this authorSupeng Yin PhD, Supeng Yin PhD Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorFan Zhang PhD, Fan Zhang PhD orcid.org/0000-0002-6758-2856 Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China Graduate School of Medicine, Chongqing Medical University, Chongqing, China Contribution: Conceptualization, Supervision, Writing - review & editingSearch for more papers by this author First published: 13 April 2023 https://doi.org/10.1111/ans.18350Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume93, Issue4April 2023Pages 1117-1118 RelatedInformation

Value of 99m Tc-MIBI SPECT/CT in the localization of recurrent lesions in patients with suspected recurrent parathyroid carcinoma.

Accurate preoperative localization of tumor-bearing lesions is crucial for the successful surgical management of suspected recurrent parathyroid carcinoma. The purpose of this study was to evaluate the diagnostic value of 99m-technetium-labeled methoxyisobutylisonitrile ( 99m Tc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) and cervical ultrasound, individually and in combination, for preoperative localization of recurrent/metastatic lesions. We also analyzed the value of 99m Tc-MIBI SPECT/CT in detecting ectopic lesions in patients with suspected recurrent parathyroid carcinoma. Twenty-nine patients with suspected recurrent parathyroid carcinoma were included in this retrospective cohort study. Patients underwent preoperative 99m Tc-MIBI SPECT/CT and cervical ultrasound. The reference standard was postsurgical histopathology. The sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy of the two diagnostic modalities alone and in combination were analyzed. Of the 29 patients, histopathological results revealed 48 metastases/recurrent lesions in 26 patients. The diagnostic value of 99m Tc-MIBI SPECT/CT, cervical ultrasound, and the two modalities in combination were compared for the 27 patients who underwent new cervical surgery. Patient-level analysis of the combined use of 99m Tc-MIBI SPECT/CT and cervical ultrasound had the highest sensitivity (100.00%) and accuracy (96.30%). At the lesion level, 99m Tc-MIBI SPECT/CT had the highest specificity and PPV, at 100.00% respectively, whereas the combined use of 99m Tc-MIBI SPECT/CT and cervical ultrasound had the highest sensitivity, at 97.62%. Moreover, 99m Tc-MIBI SPECT/CT detected six ectopic lesions, and five of them showed increased 99m Tc-MIBI uptake. The combined use of 99m Tc-MIBI SPECT/CT and cervical ultrasound is the most efficient strategy in the diagnosis of parathyroid carcinoma relapse, whereas 99m Tc-MIBI SPECT/CT is the preferred method for localizing and analyzing cervical and extra-cervical lesions before the new surgery.

ASO Author Reflections: Extended En Bloc Reoperation: A Potential Curative Operation for Recurrent or Persistent Parathyroid Carcinoma.

ASO Author Reflections: Extended En Bloc Reoperation: A Potential Curative Operation for Recurrent or Persistent Parathyroid Carcinoma.

Extended En Bloc Reoperation for Recurrent or Persistent Parathyroid Carcinoma: Analysis of 31 Cases in a Single Institute Experience.

Parathyroid carcinoma (PC) is a rare malignancy that is difficult to eradicate completely after recurrence. We assessed the efficiency of extended en bloc resection (EEBR) in the management of recurrent or persistent PC. In this observational cohort study, 31 patients who underwent reoperations for recurrent or persistent PC were enrolled after 2-9 surgeries by other medical teams. EEBRs, which provided the oncologic resection by removing all possible tumor-bearing scar tissues, were adopted in 25 patients. The other 6 with gross infiltration into the upper aerodigestive tract (UAT) underwent less radical procedures for unwillingness to sacrifice laryngeal function. The 5-year overall survival (OS) rate after EEBR was 59.6% compared with 16.7% after less radical procedures, with an improved median expected survival time of 90.0 months compared with 13.0 months after local excision. EEBR exhibited a favorable local control of relapses in 84.0% of patients after a median follow-up period of 27.0 months, 40.0% even achieved disease-free survival, although 56.0% had subsequent distant metastases (DMs) and suffered a worse 5-year OS of 36.7% in contrast with 100.0% in the absence of DM (p = 0.011). UAT invasion, rather than age, number of previous operations, or preoperative PTH levels, was the unique independent factor associated with both DM (HR = 5.466, p = 0.006) and mortality (HR = 7.606, p = 0.011). EEBRs provide better outcomes than other conventional surgical approaches and might offer a second chance of cure for patients with recurrent or persistent PC in the absence of DM.

Use Of Temozolomide In Parathyroid Carcinoma With Negative Mgmt Promoter Methylation

Introduction: Parathyroid carcinoma (PC) is a rare malignancy with a high rate of recurrence and metastasis. Case: A 63-year-old man with a 13-year history of recurrent PC requiring 5 operations, including parathyroidectomies, thyroidectomy, and neck dissections presented with polyuria, polydipsia, and worsening rib pain. He had been recently treated with 6 monthly octreotide injections and maximal dose cinacalcet for gradually rising Ca/PTH levels. Tests revealed serum Ca 13.1mg/dL (8-10.5mg/dL), PTH 1750pg/mL (11-90 pg/mL), and serum Cr 3.34mg/dL (0.5-1.3mg/dL). Imaging identified tumor in the right 6th rib (3.6cm lytic lesion), and soft tissue lesions in the left thyroid bed (3 masses, the largest 1.6cm) and the suprasternal notch (1.1cm). He underwent rib resection (metastasectomy) and PTH declined from 2334pg/mL to 671pg/mL. Although metastasectomy improved the PTH level, Ca levels began to rise from the residual tumor. A multidisciplinary team deemed the risk of complications from repeat neck surgery to be prohibitively high. Temozolomide (TEM) (150-200mg/m2/d x 5d, q28d) was instituted 3 months after the rib resection. 13 months later, PTH has stably ranged from 600-800 pg/mL with a normal serum Ca of 9.8mg/dL. Recent imaging shows stable disease in the neck, without distant disease. Discussion: The mainstay of therapy for initial and recurrent/metastatic PC is surgery. Inoperable disease has a poor prognosis because of lack of effective systemic therapies. Radiation and chemotherapy have not shown much efficacy. Results of treatment with octreotide have not been encouraging. Anti-PTH immunotherapy and Lutathera are promising but require further investigation. Usually, no targetable mutation is found. Anti-angiogenic TKI’s (sorafenib, lenvatinib) have been used with varying success. An exciting therapy used in this patient is TEM, an alkylating agent used for CNS tumors, neuroendocrine tumors (NET) and aggressive pituitary tumors. A previous report described successful use of TEM in a case of metastatic PC, whose tumor harbored high O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, a known predictor of positive response in CNS tumors. Promoter methylation is an epigenetic alteration that leads to low MGMT enzyme activity & enhances the cytotoxicity of TEM. Some studies in NET demonstrated tumor response irrespective of MGMT status. This leads to the question of whether the same is true in PC. Our patient has radiographic/biochemical stable disease on TEM, and a surprising retrospective discovery was that the MGMT promoter was unmethylated. This is a unique case of PC which seems to be responding to TEM despite absent promoter methylation. Further studies are warranted, as the incidence of PC is rising over the past decades. In the interim, clinicians could consider using TEM for in-operable PC irrespective of MGMT methylation status.

Treatment strategy of recurrent parathyroid carcinoma

Treatment strategy of recurrent parathyroid carcinoma

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.

SUN-922 An Indolent Recurrent Parathyroid Carcinoma - A Case Report

IntroductionParathyroid carcinoma is a rare endocrine malignancy with reported incidence from 0.5 to 5% of primary hyperparathyroidism (1). Etiologies include prior neck irradiation, adenoma or hyperplastic parathyroid gland. Molecular pathogenesis includes RB gene overexpression, low P53, loss of APC and especially HRPT2 tumor suppressor gene. It has low malignant potential, but tends to recur locally or spread to contiguous areas. Here, we present a case of a recurrent parathyroid carcinoma that recurred after 17 years.Clinical CaseThe patient is a 56 YO female with Stage 1 breast cancer status post bilateral mastectomy who had underwent resection of a 2.5cm low-grade left lower parathyroid carcinoma in 1997 after 10 years of primary hyperparathyroidism. At that time of resection, iPTH was 2500 pg/ml and calcium level greater than 15 mg/dl. She presented with hypercalcemia (Calcium 11.5 mg/dl, PTH 67.1 pg/ml) again after 17 years. Work-up showed a 2.3 cm suspected parathyroid lesion in the left neck. She underwent removal of the left upper parathyroid gland along with a right enlarged parathyroid gland, as intra-operative PTH did not decline. Pathology confirmed parathyroid carcinoma with capsular invasion and muscle infiltration of the left gland and adenoma of the right gland. Repeat imaging in a month showed persistent parathyroid activity in the left neck. She had removal of the left upper parathyroid and a left paratracheal mass excision with pathology confirming recurrent parathyroid carcinoma. After 4 years, her PTH and calcium levels rose. Sestamibi imaging showed abnormal activity in a 1.1 cm soft tissue mass near the sternal notch. The patient underwent complete excision of the left suprasternal mass and the left sternohyoid muscle with pathology confirming recurrent parathyroid carcinoma with lympho-vascular and perineural invasion. Follow-up Sestamibi imaging after a month showed no abnormal activity with recent labs of calcium level 10mg/dl and PTH 25 pg/ml.ConclusionRecurrent parathyroid carcinoma remains a challenge. Complete resection of the lesion along with care to avoid capsule rupture to prevent local seeding remains the treatment strategy. The main cause of morbidity and mortality is the sequelae of uncontrolled hypercalcemia rather than tumor burden. Management of hypercalcemia includes hydration, bisphosphonates and cinacalcet. Even though it is not radiosensitive, neck radiation after surgery may be helpful in preventing tumor regrowth. Clinical trials using nivolumab and ipilimumab are being conducted to treat parathyroid carcinoma (2).Reference1. Givi, B., & Shah, J. P. (2010). Parathyroid carcinoma. Clinical oncology, 22(6), 498–5072. Long, K. L., & Sippel, R. S. (2018). Current and future treatments for parathyroid carcinoma. International Journal of Endocrine Oncology, 5(01), IJE06

MON-920 Pediatric Parathyroid Carcinoma Presenting With Acute Progressive Genu Valgum

BACKGROUND: Parathyroid carcinoma (PC) is exceptionally rare in children and its clinical features are poorly understood. Available reports have identified that very high serum calcium and parathyroid hormone levels would be expected in this disease. Definitive therapy for PC requires en bloc resection of the parathyroid tumor to reduce the risk of disease recurrence. Unfortunately, there are very few treatment options for metastatic PC and patients with recurrent PC have a high risk of mortality related to their disease. Because of the rarity of the condition, there are very limited data including pediatric patients. Case: A previously healthy 13-year-old girl initially presented to primary care with bilateral foot and ankle pain in the context of acute and progressive genu valgum, referred to the orthopedic clinic. Lab evaluation prompted by imaging demonstrated severe hypercalcemia (15.6 mg/dL) and hyperphosphatasia (Alkaline phosphatase 2056 units/L). She was urgently referred to our clinic where we found her to have a firm right sided neck mass within the thyroid. Lab testing at that time confirmed profound hyperparathyroidism (PTH 2970 pg/mL). Neck ultrasound confirmed the presence of a 5.8 cm hypoechoic lesion adjacent to the right lower lobe of the thyroid. The patient received IV fluid resuscitation before undergoing urgent parathyroid surgery. The parathyroid lesion was grossly adherent to the thyroid gland and she received en bloc resection of the tumor and right lobe of the thyroid. Post-operatively, PTH rapidly declined to <3.4 and she developed a prolonged hypocalcemic phase. PTH function improved, but she continued to require high doses of calcium carbonate to address hungry bone syndrome over subsequent weeks. Comprehensive evaluation included testing for genetic mutations, deletions, and duplications in CASR, CDC73, CDKN1B, MEN1 and RET, all of which were negative. Extensive genetic testing of the parathyroid tumor did not identify any specific mutations which have been previously associated with PC. Six months post-operatively, her labs have vastly improved, although she has clinical evidence of PTH resistance and her alkaline phosphatase has not yet normalized. Neck ultrasound, F-18 FDG PET/MRI imaging and Sestamibi scans show no evidence of persistent disease. Conclusions: While parathyroid carcinoma is extremely rare in pediatric patients, the diagnosis must be considered in cases of hypercalcemia with marked elevations in PTH and palpable neck mass. Although rarely described, bone changes related to PC may be dramatic and may result in lasting morbidity - including genu valgum requiring surgical intervention as well as prolonged hungry bone syndrome and metabolic bone disease. Genu valgum is a unique pediatric feature of this disease because this may only evolve in individuals whose physes are open.

Perioperative Nursing of Patients with Reoperation of Recurrent Parathyroid Carcinoma Invading the Upper Digestive or Respiratory Tract.

Objective The aim of this study was to summarize the perioperative nursing care of patients with recurrent parathyroid carcinoma. Methods A retrospective analysis of 10 patients with recurrent parathyroid carcinoma was performed. The clinical data, diagnosis, treatment process, and nursing process (including clinical nursing intervention of various complications) were analyzed. The nursing experience and methods were discussed, summarized, and analyzed. Results A total of 10 patients were reviewed (male : female 7 : 3; aged 48.6 ± 14.60 years). The mean interval between the initial operation and reoperation was 2.23 ± 1.65 years. The mean number of operations was 4.00 ± 1.41. Invasion of the trachea or esophagus was evident in 7 patients, larynx in 6 patients, recurrent laryngeal nerve in 1 patient, and cyclic cartilage in 2 patients. Serum calcium range was 3.20–4.68 mmol/L, and parathyroid hormone (PTH) range was 860–2830 pg/ml at admission. 6 patients underwent prophylactic tracheostomy, 2 patients underwent partial laryngectomy, and 2 patients underwent total laryngectomy. 1 patient experienced temporary water-electrolyte disorder and hypoproteinemia. The median serum calcium was 2.28 mmol/L (1.66–3.18 mmol/L) and median PTH level was 82.60 pg/ml (63.70–900.00 pg/ml) postoperatively. Serum PTH and calcium were still higher than the upper limit of normal in 2 patients after surgery. 2 of the other 8 patients relapsed within 8–11 months, and 6 patients remained normal for 11–40 months. Conclusion For patients with reoperation of recurrent parathyroid carcinoma, high-quality, reasonable, and careful perioperative nursing ensured a successful operation and optimized outcome.

Preliminary exploration of potential molecular therapeutic targets in recurrent and metastatic parathyroid carcinomas.

Parathyroid carcinoma (PC) is a rare endocrine malignancy. Surgical resection is curative for local lesions, while effective therapies are lacking for recurrent or metastatic PCs. To study whether targeted therapies could be applied in recurrent or metastatic PCs, potential therapeutic targets were identified with next-generation sequencing (NGS). DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) sections from 19 recurrent or metastatic PC samples. A panel of 560 genes was sequenced with NGS to identify genomic alterations at an average sequencing depth of 581×. In total, 190 genomic alterations were identified. Nine PC samples (47%) harbored at least one potentially actionable genomic alteration including in the after genes: ROS1 (5/19; 26%), PTEN (3/19; 16%), TSC1 (2/19; 11%), PIK3CA (1/19; 5%), AKT1 (1/19; 5%), MTOR (1/19; 5%), ERBB2 (1/19; 5%), NTRK1 (1/19; 5%), IDH1 (1/19; 5%) and FGFR3 (1/19; 5%). CDC73 mutations were detected in 9/19 (47%) PC samples. Additional recurrent genomic alterations were identified in MSH2 (15/19; 79%), AR (9/19; 47%), BCR (8/19; 42%), SLC45A3 (6/19; 32%), MAGI1 (5/19; 26%), ZNF521 (4/19; 21%), KMT2C (4/19; 21%) and NOTCH4 (4/19; 21%). Our study identified a relatively high frequency of potentially actionable genomic alterations in PC patients in a Chinese population for the first time. A series of recurrent mutant genes was detected as well. Our study contributes to both the selection of novel targeted therapies for PC and further molecular understanding of this refractory malignancy.

A nationwide study on parathyroid carcinoma

Background: Parathyroid carcinoma (PC) is rare and diagnostically challenging. Reported outcomes are rather poor and the incidence might be increasing.Material and methods: We performed a nationwide study on all cases (n= 32) diagnosed in 2000–2011 in Finland, and compared clinical and histopathological characteristics and outcome to atypical parathyroid (APA; n= 28) and parathyroid adenomas (PA; n= 72). The incidence in years 1955–1999 was compared to that in 2000–2013.Results: Preoperatively, calcium and parathyroid hormone concentrations were higher in PC compared to APA and PA (1.76, 1.56 and 1.44 mmol/l, p < .001; and 989, 355 and 160 μmol/l, p < .001, respectively). Calcium was ≤1.77 mmol/l for all PAs. Hospitalization (44% vs. 22% and 3%, respectively, p = .01), renal (50% vs. 48% vs. 22%, respectively, p = .01) and bone (47% vs. 15% vs. 38%, respectively p = .002) manifestations were more common. PC and APA tumors were larger than PA (p < .001). Histopathological characteristics of PC compared to PA are increased mitotic activity (p= .001), chief cells (p = .003), diffuse growth pattern (p < .001), higher Ki67 (p< .001) and negative parafibromin (p < .001). One PC (1/18) and one APA (1/16) patient had a CDC73 mutation. After 6.7 (2–13.9) years of follow-up, 9.4% of PC had residual, 21% recurrent disease and 12.5% died of disease. Overall mortality did not differ between subgroups (p = .094). Recurrent PC was characterized by vascular invasion, lymph node metastases, high mitotic activity, necrosis and negative parafibromin. Incidence increased from 1.42 (range 0.52–2.14) to 7.14 (range 3.42–10.38)/10.000.000/years; (p < .001).Conclusions: PC associates with severe primary hyperparathyroidism and must be suspected if calcium ≥1.77 mmol/l. The prevalence of CDC73 germline mutations in PC and APA in Finland is 6%. PC has distinct histopathological characteristics and its incidence has increased over the past decades.

Recurrent parathyroid carcinoma and the need for molecular profiling to aid in prognostication and therapeutics.

e17012 Background: Parathyroid carcinoma (PC) is rare, has high morbidity and poor overall survival. Surgery is the mainstay of treatment but recurrence is common. There are no known therapeutic options and efforts to ascertain prognostic factors are restricted by rarity of disease. We report the largest single institution experience and aim to identify prognostic clinicopathologic features associated with aggressiveness of disease. Methods: Retrospective review of PC patients from 1981 to 2014 at a tertiary cancer center was done. Those with a final pathology diagnosis of carcinoma, atypia or neoplasm on were included. Clinicopathological data was analyzed for predictors of disease recurrence. Limited molecular profiling on a subset of patients was done. Cox regression was used for univariate analysis with p ≤ 0.05 considered significant. Results: 87 patients met inclusion criteria. Median follow up was 5 yrs [IQR 3-8]. 36 patients (41%) underwent local resection, while 48 (55%) had en bloc resection. 30(35%) developed recurrent or persistent disease with > 85% requiring ≥ 3 surgeries for palliation or cure. Univariate analysis of clinicopathological data showed only mitotic index (MI) of ≥ 1 was predictive of disease recurrence (PFS) (p = 0.03) with a trend towards decreased overall survival (OS) (p = 0.06). Extent of initial surgery had no bearing on PFS or OS. 8 patients with recurrent disease had molecular profiling. 2 had no discernible mutations, 2 had TP53 mutation. Others mutations identified were CDC73, CTNNB1, KDM5C, NF1 and TLR4. Conclusions: High MI is prognostic of disease recurrence in PC. Radical resection at initial surgery did not improve PFS. Other clinicopathologic features of PC fail to precisely identify risks for recurrent disease. In the subset of patients with limited therapeutic options, genomic profiling is needed to identify prognostic and targetable mutations and drive research aimed at creating novel therapeutics. Variables Values median [IQR] Age (yr) 58 (47-66) Gender n(%) Male 34(39) Female 53(61) Final Pathology n(%) Carcinoma 56(64) Neoplasm 17(20) Atypia 10(12) PTH at diagnosis (pg/ml) 381 [203-1536] Ca+ at diagnosis (mg/dl) 12.9 [12-14.5] 10 year OS 67% 10 year PFS 56%

Use of denosumab in parathyroid carcinoma with refractory hypercalcemia

### Learning Point for Physicians This case illustrates the difficulties in treating hypercalcemia caused by parathyroid carcinoma. However, there are various choices of treatment and in recalcitrant cases, denosumab should be considered as a therapeutic option. It is important to know the vitamin D status of the patient and to monitor for hypocalcemia post treatment. Parathyroid carcinoma is rare; accounting for ∼1% of all the causes of primary hyperparathyroidism.1 When the tumor is no longer amenable for surgery, medical therapy to control the hypercalcemia becomes the main focus of management. Unfortunately, parathyroid carcinoma mediated hypercalcemia is often severe and more resistant to medical therapy. We report a case of parathyroid carcinoma with refractory hypercalcemia treated with denosumab. A 26-year-old lady with recurrent parathyroid carcinoma initially presented in April 2012 with symptoms of hypercalcemia, a serum calcium of 4.0 mmol/l with …

Recurrent Parathyroid Carcinoma Appearing as FDG Negative but MIBI Positive

A 44-year-old woman with recurrent parathyroid carcinoma (PTC) presents with moderately elevated parathyroid hormone and ionized calcium levels. Dual-phase Tc-MIBI SPECT study of the neck and chest demonstrated 2 new foci in keeping with neoplastic seeding. A restaging whole-body F-FDG PET/CT showed no evidence of FDG uptake in the region of the MIBI-positive foci or any evidence of distant metastases. The role of F-FDG PET/CT for imaging PTC is still somewhat limited because of the rarity of this disease. We present a case highlighting a potential pitfall for FDG PET in detecting PTC.

Parathyroid carcinoma in a 30-year-old man: a diagnostic and management challenge

Parathyroid carcinoma is a rare endocrine malignancy, accounting for less than 1% of cases of primary hyperparathyroidism. Patient-related factors such as age and sex, as well as the biological features and management of the cancer, influence mid-term and long-term survival. We report a case of a young man with an unusual presentation of parathyroid carcinoma. The patient presented with left thigh swelling, which had been present for 6 months without other symptoms of hypercalcemia. On computed tomography scan a hypodense lesion, 30 × 20 × 20 mm in size, was seen in the posterior thyroid. There was no evidence of cervical lymphadenopathy or local infiltration. On a Sestamibi scan, a hot spot was seen in the lower pole of left thyroid lobe. Cervical neck exploration was performed. The patient subsequently underwent surgery and a parathyroid tumor was excised. The tumor was adherent to the thyroid capsule, but there was no evidence of invasion. After surgery, the patient’s calcium and parathyroid hormone levels normalized, but histology confirmed parathyroid carcinoma with capsular and vascular invasion. The patient was offered reoperation, but declined, and developed recurrent parathyroid carcinoma 2 years later. In this report, we aim to present the challenges in managing parathyroid carcinoma and discuss factors that might contribute to future locoregional recurrences. This case also highlighted several issues, including the challenge of ascertaining the diagnosis before surgery and the dilemma of reoperation after simple excision.