Paratiroid Tümörleri
Özet
Paratiroid tümörleri, genellikle benign yapıda olmakla birlikte, paratiroid hormonu (PTH) salınımına bağlı hiperkalsemi, hipofosfatemi ve hiperkalsiüri semptomlarıyla karakterize neoplazmlardır. Bu spektrum içerisinde son derece nadir görülen paratiroid kistleri, ince iğne aspirasyonunda berrak sıvı vermesi ve bu sıvıda yüksek PTH konsantrasyonu saptanmasıyla ayırt edilirken; asemptomatik olgularda takip, semptomatik durumlarda ise cerrahi rezeksiyon veya aspirasyon uygulanmaktadır. En sık karşılaşılan primer hiperparatiroidizm nedeni olan paratiroid adenomları, genellikle tek bir bezi tutan benign oluşumlardır ve tanısında ultrasonografi ile 99mTc-sestamibi sintigrafisinden yararlanılarak cerrahi olarak başarıyla çıkarılmaktadır. Primer hiperparatiroidizm vakalarının yaklaşık yüzde 1'ini oluşturan paratiroid karsinomu ise hormonal olarak aktif, agresif seyredebilen nadir bir malignitedir. Karsinom patogenezinde parafibromin proteinini kodlayan HRPT2 mutasyonları merkezi rol oynar ve tanıda histopatolojik olarak kapsüler/vasküler invazyon aranır. Tedavide temel yaklaşım en-blok cerrahi rezeksiyon olup, rezeke edilemeyen durumlarda morbidite ve mortalitenin ana nedeni olan hiperkalsemi; hidrasyon, bifosfonatlar, sinakalset ve denosumab ile kontrol altına alınmaya çalışılmaktadır.
Parathyroid tumors, although predominantly benign, are neoplasms characterized by symptoms of hypercalcemia, hypophosphatemia, and hypercalciuria driven by parathyroid hormone (PTH) overproduction. Within this spectrum, extremely rare parathyroid cysts are distinguished by clear fluid on fine-needle aspiration exhibiting elevated PTH concentrations, managed via observation for asymptomatic lesions or surgical resection and aspiration for symptomatic cases. Parathyroid adenomas, the most common cause of primary hyperparathyroidism, are benign lesions typically confined to a single gland; they are successfully targeted for surgical excision utilizing ultrasonography and 99mTc-sestamibi scintigraphy. Accounting for approximately 1 percent of primary hyperparathyroidism cases, parathyroid carcinoma is a rare, hormonally active malignancy that can pursue an aggressive course. HRPT2 mutations, encoding the parafibromin protein, play a central role in carcinoma pathogenesis, with diagnosis histopathologically reliant on identifying capsular or vascular invasion. The primary therapeutic strategy is en-bloc surgical resection; for unresectable disease, severe hypercalcemia—the chief cause of morbidity and mortality—is managed through hydration, bisphosphonates, cinacalcet, and denosumab.
Referanslar
Pontikides N, Karras S, Kaprara A, et al. Diagnostic and therapeutic review of cystic parathyroid lesions. Hormones (Athens). 2012;11(4):410-8
Ippolito G, Palazzo FF, Sebag F, et al. A single-institution 25-year review of true parathyroid cysts. Langenbecks Arch Surg. 2006;391(1):13-8.
Fortson JK, Patel VG, Henderson VJ. Parathyroid cysts: a case report and review of the literature. Laryngoscope. 2001;111(10):1726-8
Go P, Watson J, Lu Z, et al. Robotic resection of a mediastinal parathyroid cyst. Gen Thorac Cardiovasc Surg. 2017;65(1):52-55
Thompson, Lester DR. "Benign neoplasms of the parathyroid gland." Head and Neck Pathology. Elsevier, 2019. 703-712.
Stojadinovic A, Hoos A, Nissan A, et al. Parathyroid neoplasms: clinical, histopathological, and tissue microarray-based molecular analysis. Hum Pathol. 2003;34(1):54-64
Smith JR, Oates ME. Radionuclide imaging of the parathyroid glands: patterns, pearls, and pitfalls. Radiographics. 2004;24(4):1101-15
Baloch ZW, LiVolsi VA. Pathology of the parathyroid glands in hyperparathyroidism. Semin Diagn Pathol. 2013;30(3):165-779: Wei, Christina H, Avital Harari. “Parathyroid carcinoma: update and guidelines for management.” Current treatment options in oncology, 2012;13,1: 11-23.
Levin KE, Galante M., Clark OH. Parathyroid carcinoma versus parathyroid adenoma in patients with profound hypercalcemia. Surgery, 1987;101(6), 649–660.
Shane E. Clinical review 122: Parathyroid carcinoma. The Journal of clinical endocrinology and metabolism, 2001;86(2), 485–493.
Cetani F, Pardi E, Marcocci C. Parathyroid Carcinoma. Frontiers of hormone research, 2019;51, 63–76.
Lee PK, Jarosek SL, Virnig BA, et al. Trends in the incidence and treatment of parathyroid cancer in the United States. Cancer, 109(9),1736-1741.
Wang CA, Gaz RD. Natural history of parathyroid carcinoma. Diagnosis, treatment, and results. American journal of surgery, 1985;149(4), 522–527.
Ruda JM, Hollenbeak CS, Stack BC. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003. Official journal of American Academy of Otolaryngology-Head and Neck Surgery, 2005;132(3), 359–372.
Singh ON, Sebo TJ, Thompson GB, et al. Prevalence of parathyroid carcinoma in 348 patients with multiple endocrine neoplasia type 1 - case report and review of the literature. Clin Endocrinol (Oxf). 2016;84(2):244-249.
Christakis I, Busaidy NL. Parathyroid carcinoma and atypical parathyroid neoplasms in MEN1 patients; A clinico-pathologic challenge. The MD Anderson case series and review of the literature. International journal of surgery, 31, 10–16.
(Wynne AG, van Heerden J, Carney JA, ET AL. Parathyroid carcinoma: clinical and pathologic features in 43 patients. Medicine, 1992;71(4), 197–205
Quinn CE, Healy J, Lebastchi et al. Modern experience with aggressive parathyroid tumors in a high-volume New England referral center. Journal of the American College of Surgeons, 220(6), 1054–1062.
Obara T, Fujimoto Y. Diagnosis and treatment of patients with parathyroid carcinoma: an update and review. World journal of surgery, 1991;15(6), 738–744.
Shane E, Bilezikian JP. Parathyroid carcinoma: a review of 62 patients. Endocrine reviews, 1982;3(2), 218–226.
Schantz A, Castleman B. Parathyroid carcinoma. A study of 70 cases. Cancer, 1973;31(3), 600–605.
Truran PP, Johnson SJ, Bliss RD, et al. Parafibromin, galectin-3, PGP9.5, Ki67, and cyclin D1: using an immunohistochemical panel to aid in the diagnosis of parathyroid cancer. World journal of surgery, 38(11), 2845–2854.
Simonds WF, Robbins CM. Familial isolated hyperparathyroidism is rarely caused by germline mutation in HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome. The Journal of clinical endocrinology and metabolism, 89(1), 96–102.
Pandya C, Uzilov AV, Bellizzi J, et al. Genomic profiling reveals mutational landscape in parathyroid carcinomas. JCI insight, 2(6), e92061.
Shattuck TM, Välimäki S, Obara, et al. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. The New England journal of medicine, 349(18), 1722–1729.
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. The Journal of clinical endocrinology and metabolism, 89(1), 96–102.
Landry CS, Wang TS, Asare EA, et al. Parathyroid. In: AJCC Cancer Staging Manual, 8th, Amin MB (Ed), Springer, 2017. p.903
Asare EA, Sturgeon C, Winchester DJ, et al. Parathyroid Carcinoma: An Update on Treatment Outcomes and Prognostic Factors from the National Cancer Data Base (NCDB). Annals of surgical oncology, 22(12), 3990–3995.
Shane E. Parathyroid carcinoma. The Journal of Clinical Endocrinology & Metabolism, 2001;86(2), 485-493.
Munson ND, Foote RL, Northcutt RC, et al. Parathyroid carcinoma: is there a role for adjuvant radiation therapy?. Cancer, 98(11), 2378–2384.
Harari A, Waring A, Fernandez-Ranvier G, et al Parathyroid carcinoma: a 43-year outcome and survival analysis. The Journal of clinical endocrinology and metabolism, 96(12), 3679–3686.
Kebebew E. Parathyroid carcinoma. Current treatment options in oncology, 2(4), 347–354.
Sandelin K, Thompson NW, Bondeson L. Metastatic parathyroid carcinoma: dilemmas in management. Surgery, 1991;110(6), 978–988.
Sandelin K, Auer G, Bondeson L, et al. Prognostic factors in parathyroid cancer: a review of 95 cases. World journal of surgery, 16(4), 724–731.
Kebebew E, Arici C, Duh QY, Clark, OH. Localization and reoperation results for persistent and recurrent parathyroid carcinoma. Archives of surgery, 2001;136(8), 878–885.
Busaidy NL, Jimenez C, Habra, MA, et al. Parathyroid carcinoma:a 22-year experience. Head & neck, 26(8), 716–726.
Limberg J, Stefanova D, Ullmann TM, et al. The Use and Benefit of Adjuvant Radiotherapy in Parathyroid Carcinoma: A National Cancer Database Analysis. Annals of surgical oncology, 28(1), 502–511.
Silverberg SJ, Rubin MR, Faiman C, et al. Cinacalcet hydrochloride reduces the serum calcium concentration in inoperable parathyroid carcinoma. The Journal of clinical endocrinology and metabolism, 92(10), 3803–3808.
Calandra DB, Chejfec G, Foy BK, et al. Parathyroid carcinoma: biochemical and pathologic response to DTIC. Surgery, 1984;96(6), 1132–1137.
Hoelting T, Weber T, Werner J, et al. Surgical treatment of parathyroid carcinoma (Review). Oncology reports, 8(4), 931–934.
