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Journal of Clinical Oncology, Vol 26, No 24 (August 20), 2008: pp. 4039-4041 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.15.9038
Metastatic Parathyroid Carcinoma to the Liver Treated With Radiofrequency Ablation and Transcatheter Arterial EmbolizationDivision of Oncologic Surgery, City of Hope, Duarte, CA
Department of Diabetes, Endocrinology, and Metabolism, City of Hope, Duarte, CA
Department Pathology, City of Hope, Duarte, CA
Division of Oncologic Surgery, City of Hope, Duarte, CA A 71-year old male was initially seen at another institution with asymptomatic hypercalcemia discovered on interval laboratory examination for hypercholesterolemia. His serum calcium level (Ca) was 13.9 mg/dL at presentation. He had no prior personal or family history of endocrine neoplasia. Physical examination revealed no significant abnormalities. A serum parathyroid hormone (PTH) level was obtained and was markedly elevated (393 pg/mL; upper limit of normal, 75 pg/mL). A preoperative computed tomography (CT) scan of the neck was obtained and revealed findings suggestive of an enlarged parathyroid gland near the right lower pole of the thyroid gland. A 99mTc-sestamibi scan was subsequently performed and demonstrated no evidence of abnormal uptake. Based on these findings, the patient underwent bilateral neck exploration with excision of an enlarged right superior parathyroid gland believed to be an adenoma. During the immediate postoperative period, the Ca normalized (8.7 mg/dL) but the PTH level remained elevated (353 pg/mL). The patient's hospital course was otherwise uncomplicated, and he was subsequently discharged home. Final pathologic examination of the resected specimen revealed a 1.2-cm well-differentiated parathyroid carcinoma with microscopically positive surgical margins. Approximately 1 month after surgery, the patient was noted to have symptomatic hypercalcemia (Ca, 12.7 mg/dL), with new onset depression, constipation, confusion, and nocturia. His PTH remained persistently elevated (266 pg/mL). The patient was referred to an endocrinologist and was treated medically with bisphosphonate injections and cinacalcet, an oral calcimimetic. Positron emission tomography, CT (Fig 1), and magnetic resonance imaging studies were then performed and revealed multiple bilateral liver lesions consistent with metastatic disease. CT-guided liver biopsy and subsequent ultrasound-guided core biopsy were attempted but were nondiagnostic. At this time, the patient was referred to our institution for further evaluation and management. To obtain a tissue diagnosis, a laparoscopic liver biopsy was performed, which confirmed the presence of metastatic parathyroid carcinoma. Hematoxylin and eosin stains (Fig 2) in low power (10x) demonstrate liver parenchyma involved by metastatic parathyroid carcinoma with vascular invasion (left); nuclear pleomorphism, atypical mitotic figures (arrows) and apoptotic bodies are shown in higher power (60x) on the right. Given the presence of widespread bilateral hepatic disease with approximately fifteen discrete lesions, curative intent resection was not entertained. However, surgical debulking was planned for palliation given the refractory nature of the patient's symptomatic hypercalcemia. Therefore, approximately 6 months following his initial neck exploration, the patient underwent exploratory laparotomy. Given the intrahepatic location of the lesions, the palliative nature of the operation, and the high number of lesions, an ablative approach was preferred, and ten lesions were successfully treated via radiofrequency ablation (RFA). The patient tolerated this procedure without difficulty and his hospital course was uneventful. His serum calcium decreased to 10.3 mg/dL and his PTH level to 115 pg/mL. Because residual hepatic disease was primarily in the right lobe of the liver, bland TAE of the right hepatic artery was performed. The procedure and recovery were again uncomplicated. The patient was seen one month after the procedure, at which time his Ca was 8.7 mg/dL, and his symptoms had resolved. He was still maintained on bisphosphonate injections and cinacalcet, although the doses of both medications were greatly decreased. He is currently being followed by his primary care physician and, as of his last follow-up approximately 4 months after surgery, he remains asymptomatic with a PTH level of 53 pg/mL and Ca of 9.3 mg/dL.
Parathyroid carcinoma is a rare malignancy with an estimated prevalence of 0.005% in the general population.1 The diagnosis is usually confirmed after excision of a suspected parathyroid adenoma in the setting of primary hyperparathyroidism. Although often of relatively low malignant potential, parathyroid carcinomas tend to invade locally and commonly recur in locoregional patterns after surgical resection.2,3 Unlike benign adenomas, parathyroid carcinomas are usually associated with severe, symptomatic hypercalcemia, often with end–organ dysfunction in the form of renal insufficiency and hyperparathyroid bone disease.1,2,4-9 The most effective and lone curative therapy is en bloc resection of the tumor along with the ipsilateral thyroid lobe and any adherent resectable structures. Cervical nodes are involved in 15% to 30% of cases, and modified radical neck dissection at the time of initial exploration is warranted in such instances.7,10,11 Approximately 30% of patients will have distant metastatic disease at the time of presentation, most commonly to the lungs.7,10-13 Additional, less common sites of distant involvement include the liver, with relatively rare involvement of bone, pleura, brain, and other sites.6-9 A significant number of patients will also have distant recurrence after resection of the primary disease.14 These individuals present a unique management dilemma because the natural history of parathyroid cancer is such that mortality is usually secondary to the metabolic consequences of hypercalcemia rather than malignant spread.3 Therefore, even in the setting of incurable disease, intervention for palliation is frequently necessary to prevent or delay the consequences of excessive PTH secretion. Given the rarity of parathyroid carcinoma, randomized trials to evaluate therapeutic options are lacking. As a result, management decisions are largely based on evidence from retrospective studies and individual case reports. This is particularly evident in parathyroid carcinoma with metastatic hepatic disease, for which no large retrospective case series has been published. Although no prospective studies exist, successful surgical resection of hepatic and pulmonary metastases with resolution of hypercalcemia has been described.15,16 The management of metastatic disease not amenable to resection is more challenging, as therapeutic options are limited and chemotherapy is generally ineffective.6 A wide spectrum of ablative procedures and regional therapies are currently available for the palliation of solid metastatic hepatic malignancies. However, the collective experience with any one approach is extremely small for metastatic parathyroid cancers. Laparoscopic microwave ablation of hepatic metastases from parathyroid cancers has been described previously.17 Other nonsurgical techniques, such as embolization, have been performed with limited success in localized and/or ectopic parathyroid adenoma,18-20 but their use in metastatic parathyroid carcinoma has not been described. TAE and chemoembolization have been used with some success in other metastatic tumors of the liver, particularly those of neuroendocrine histology, such as carcinoid lesions.15-18 This prior experience provides the rationale and precedent for the application to metastatic parathyroid carcinoma. To our knowledge, this is the first report of metastatic hepatic disease from parathyroid carcinoma successfully treated via a multimodal approach incorporating RFA and TAE. Accordingly, we believe that RFA and TAE, either alone or in combination, should be added to the fairly limited list of therapeutic options for metastatic parathyroid carcinoma. Given our treatment results, RFA and TAE should be strongly considered as routine adjuncts for the palliation of PTH hypersecretion and hypercalcemia in metastatic parathyroid carcinoma to the liver. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES 1. Hundahl SA, Fleming ID, Fremgen AM, et al: Two hundred eighty-six cases of parathyroid carcinoma treated in the U.S. between 1985-1995: A National Cancer Data Base report—The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 86:538-544, 1999[CrossRef][Medline] 2. Shane E, Bilezikian JP: Parathyroid carcinoma: A review of 62 patients. Endocr Rev 3:218-226, 1982 3. Rawat N, Khetan N, Williams DW, et al: Parathyroid carcinoma. Br J Surg 92:1345-1353, 2005[CrossRef][Medline] 4. Cohn K, Silverman M, Corrado J, et al: Parathyroid carcinoma: The Lahey Clinic experience. Surgery 98:1095-1100, 1985[Medline] 5. Hakaim AG, Esselstyn CB Jr: Parathyroid carcinoma: Fifty-year experience at The Cleveland Clinic Foundation. Cleve Clin J Med 60:331-335, 1993[Medline] 6. Sandelin K, Thompson NW, Bondeson L: Metastatic parathyroid carcinoma: Dilemmas in management. Surgery 110:978-986, 1991[Medline] 7. Schantz A, Castleman B: Parathyroid carcinoma: A study of 70 cases. Cancer 31:600-605, 1973[CrossRef][Medline] 8. Wynne AG, van Heerden J, Carney JA, et al: Parathyroid carcinoma: Clinical and pathologic features in 43 patients. Medicine (Baltimore) 71:197-205, 1992[Medline] 9. Wang CA, Gaz RD: Natural history of parathyroid carcinoma: Diagnosis, treatment, and results. Am J Surg 149:522-527, 1985[CrossRef][Medline] 10. McCance DR, Kenny BD, Sloan JM, et al.: Parathyroid carcinoma: A review. J R Soc Med 80:505-509, 1987[Medline] 11. Shane E: Clinical review 122: Parathyroid carcinoma. J Clin Endocrinol Metab 86:485-493, 2001 12. Obara T, Fujimoto Y: Diagnosis and treatment of patients with parathyroid carcinoma: An update and review. World J Surg 15:738-744, 1991[CrossRef][Medline] 13. Eurelings M, Frijns CJ, Jeurissen FJ: Painful ophthalmoplegia from metastatic nonproducing parathyroid carcinoma: Case study and review of the literature. Neuro Oncol 4:44-48, 2002 14. Kebebew E: Parathyroid carcinoma. Curr Treat Options Oncol 2:347-354, 2001[Medline] 15. Vogl T, Eichler K, Zangos S, et al.: Preliminary experience with transarterial chemoembolization (TACE) in liver metastases of uveal malignant melanoma: Local tumor control and survival. J Cancer Res Clin Oncol 133:177-184, 2007[CrossRef][Medline] 16. Burger I, Hong K, Schulick R, et al.: Transcatheter arterial chemoembolization in unresectable cholangiocarcinoma: Initial experience in a single institution. J Vasc Interv Radiol 16:353-361, 2005[Medline] 17. Giroux MF, Baum RA, Soulen MC: Chemoembolization of liver metastasis from breast carcinoma. J Vasc Interv Radiol 15:289-291, 2004[Medline] 18. Ruszniewski P, O'Toole D: Ablative therapies for liver metastases of gastroenteropancreatic endocrine tumors. Neuroendocrinology 80:74-78, 2004 (suppl)[CrossRef][Medline]
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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