Parathyroid Carcinoma Presenting with Pathological Fracture: Case Report and Review of the Literature. *#James K. Fortson, MD MPH MBA CPE FACS; *Roger Su, MD; #VijayKumar G. Patel, MBBS FRCS FACS; ^Gillian E. Lawrence, MD; *ENT Associates of South Atlanta, Atlanta, Georgia, USA; #Department of Surgery, Atlanta Medical Center, Atlanta, Georgia, USA; ^Spanishtown Hospital, Jamaica. 5th World Congress of IFHNOS and annual meeting of AHNS New York, 26-30 July 2014 Poster #56121 Please send all correspondence to: Roger Su, MD 1136 CLEVELAND AVE SUITE 611 ATLANTA, GEORGIA 30344 224 425 3931 [email protected]

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Abstract: Background Parathyroid carcinoma is a rare neoplasm representing less than 1% of primary hyperparathyroidism cases. It is often not diagnosed until surgical exploration as a preoperative diagnosis is often not possible. Thus preoperative staging for most patients is not feasible and this may compromise the treatment strategy. Method & Result We report a case of a 29 years old male presenting with avulsion fracture of the right elbow after a trivial fall. Neck exploration revealed enlarged left lobe focally adherent to the larynx and trachea. Final pathology revealed parathyroid carcinoma with focally positive margin at the site of tracheal invasion. Conclusion Parathyroid carcinoma is a rare cause of primary hyperparathyroidism. The etiology of parathyroid carcinoma is usually obscured, and the initial operation offers the best chance for cure.

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Introduction Parathyroid carcinoma is a rare neoplasm accounts for 0.005% of all cancers in the United States. It’s also accounts for less than 1 % of primary hyperparathyroidism cases. Parathyroid cancer occurs in midlife, affect men and women equally. Conditions that appear to result in an increased risk of parathyroid cancer include: Multiple endocrine neoplasia type 1, autosomal dominant familial isolated hyperparathyroidism, and hyperparathyroidism-jaw tumor syndrome due to mutation of CDC73 gene. External radiation exposure also plays a role. Parathyroid carcinoma is known for common metastasis to the bones and lungs.

Case Report We present a case of 29 years old male presenting with avulsion fracture of the right elbow after a trivial fall. Patient was found to have hypercalcemia with serum calcium of 15.6 and PTH > 2000 pg/ml. MRI of the neck revealed large left thyroid mass (4.6 x 4.7 x 5 cm) extending retrosternally and displacing the trachea to the right. A MIBI scintigraphy scan reveled intense isotope activity involving the left thyroid lobe and with no washout at 6 hours suggesting a parathyroid lesion. Neck exploration revealed enlarged left lobe focally adherent to the larynx and trachea. The left inferior parathyroid was not found thus indicating intrathyroid location of the parathyroid tumor. There was no palpable central lymphadenopathy noted therefore a left total thyroid lobectomy and isthmusectomy was performed. Intra operative monitoring of intact PTH revealed excision of gross tumor with PTH dropping to normal levels. Final pathology revealed parathyroid carcinoma with focally positive margin at the site of tracheal invasion. 3 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.

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Discussion Parathyroid carcinoma is a rare neoplasm accounts for 0.005% of all cancers in the United States. It’s also accounts for less than 1 % of primary hyperparathyroidism cases. Parathyroid cancer occurs in midlife, affect men and women equally. Conditions that appear to result in an increased risk of parathyroid cancer include: Multiple endocrine neoplasia type 1, autosomal dominant familial isolated hyperparathyroidism, and hyperparathyroidism-jaw tumor syndrome due to mutation of CDC73 gene. External radiation exposure also plays a role. Parathyroid carcinoma is known for metastasis to the bones and lungs. Patients often have symptoms including bone pain, constipation, fatigue, fractures, frequent thirst and urination, kidney stones, muscle weakness, nausea, poor appetite, and vomiting. Possible signs include hypercalcemia, high parathyroid hormone levels, a large neck mass, and renal and bone abnormalities. Work up includes serum calcium, serum PTH and imaging techniques such as neck ultrasound and 99mTc Sestamibi scan. Fine needle aspiration (FNA) is not recommended because technical difficulties in differentiating benign and malignant disease on cytology specimens, and there is a risk of tumor seeding from the needle track. Pre-operative diagnosis is hard to achieve since it’s difficult to palpate the mass on more than 50% of patients. However, preoperative findings such as severe hypercalcemia (>15mg/dL ) and markedly elevated PTH (PTH > 300 pg/ml) are highly suggestive of parathyroid carcinoma.

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It is often not diagnosed till surgical exploration for primary hyperparathyroidism as preoperative diagnosis is often not possible. Thus preoperative staging for most patients is not feasible and this may compromise the treatment strategy. Aggressive excision with radical “en bloc” resection is the only effective treatment since the role of radiation is not well established. Due to the rarity of this malignancy there is currently no AJCC staging. When locally invasive disease or metastases are present, chemotherapy and radiation therapy have been used with varying degrees of success. However, radiation therapy for inoperable cases is ineffective. Case reports of adjuvant radiation therapy have shown some promise. Recurrent disease occurs in more than 50% of patients. Surgical resection is the primary mode of therapy for recurrence, as well as palliation for the metabolic derangement caused by hyperparathyroidism. Reoperations are rarely curative, and chemotherapy and external beam radiation treatments are ineffective.

Conclusion Parathyroid carcinoma is a rare cause of primary hyperparathyroidism. It is a slow-growing but tenacious malignancy. The etiology of parathyroid carcinoma is usually obscured, possible causes includes radiation-induced malignant change in the parathyroid gland and Multiple Endocrine Neoplasia type I.

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The initial operation offers the best chance for cure thus pre-op suspicion and intra-operative recognition of the parathyroid cancer is essential. Initial operation should be bloc resection of the tumor to avoid rupture of the tumor capsule and spillage of tumor cells. Role of radiation is not well established. Repeat resection of local recurrent tumors or distant metastases is effective for palliation of recurrent cases. In inoperable cases few palliative treatment options exist, although treatment with calcimimetics, especially calcitonin, can effectively control hypercalcemia by inhibiting bone resorption may in some patients. This type of new medications holds promise in patients with recurrent parathyroid carcinoma.

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Reference 1. Wei CH, Harari A. Parathyroid carcinoma: update and guidelines for management. Curr Treat Options Oncol 2012; 13:11. 2. Obara T, Fujimoto Y. Diagnosis and treatment of patients with parathyroid carcinoma: an update and review. World J Surg 1991; 15:738. 3. Ruda JM, Hollenbeak CS, Stack BC Jr. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003. Otolaryngol Head Neck Surg 2005; 132:359. 4. Lee PK, Jarosek SL, Virnig BA, et al. Trends in the incidence and treatment of parathyroid cancer in the United States. Cancer 2007; 109:1736. 5. Carpten JD, Robbins CM, Villablanca A, et al. HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet 2002; 32:676. 6. Sharretts JM, Simonds WF. Clinical and molecular genetics of parathyroid neoplasms. Best Pract Res Clin Endocrinol Metab 2010; 24:491. 7. Shattuck TM, Välimäki S, Obara T, et al. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med 2003; 349:1722. 8. Howell VM, Haven CJ, Kahnoski K, et al. HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours. J Med Genet 2003; 40:657. 9. Simonds WF, Robbins CM, Agarwal SK, et al. Familial isolated hyperparathyroidism is rarely caused by germline mutation in HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome. J Clin Endocrinol Metab 2004; 89:96.

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10. Cetani F, Pardi E, Borsari S, et al. Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors. J Clin Endocrinol Metab 2004; 89:5583.

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Figure 1: MRI of the neck shows a large mass in left thyroid displacing the trachea. 73x82mm (72 x 72 DPI)

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Figure 2: Tumor visible intraoperatively 307x350mm (72 x 72 DPI)

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Figure 3: Gross pathology 219x314mm (72 x 72 DPI)

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Figure 4: Positive surgical margin 173x225mm (72 x 72 DPI)

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Figure 5: Invasion through capsule 227x200mm (72 x 72 DPI)

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Figure 6: Vascular invasion 204x215mm (72 x 72 DPI)

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Parathyroid carcinoma presenting with pathologic fracture: case report and review of the literature.

Parathyroid carcinoma is a rare neoplasm representing ...
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