Recurrent Metastasized Parathyroid Carcinoma—Long‐Term Remission After Combined Treatments With Surgery, Radiotherapy, Cinacalcet, Zoledronic Acid, and Temozolomide

Abstract

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism with rather poor prognosis. Apart from surgery, no evidence‐based treatments exist. A 48‐year‐old woman presented with weight loss, nausea, constipation, hypercalcemic crisis, and a recurrent neck tumor 5 years after primary surgery of a parathyroid tumor that primarily was classified as an adenoma. Histopathological reevaluation of the original tumor revealed the correct diagnosis to be parathyroid carcinoma (PC). The patient underwent surgery of the recurrent tumor, which was locally invasive with metastatic spread to the mediastinum and neck lymph nodes. Computed tomography demonstrated large lytic bone lesions in both iliac bones including, on the right, a soft tissue mass compatible with bone metastasis. The patient was treated with cinacalcet, repeated zoledronic acid infusions, and temozolomide cycles for 1 year. She underwent two additional neck surgeries for PC and sternotomy for resection of mediastinal metastases. Massive osteolytic lesions in both femoral necks caused imminent fracture risk and therefore both femurs were prophylactically stabilized by intramedullary nail. Serum calcium normalized after the third neck surgery, cinacalcet was discontinued, and parathyroid hormone gradually normalized during continued treatments with temozolomide, adjuvant radiotherapy, and zoledronic acid, with no signs of active disease on imaging and normal biochemistry. The patient remains in remission 17 years after successful combined treatments for recurrent, metastasized PC. The parathyroid tumor tissue demonstrated high O 6 ‐methylguanine DNA methyltransferase (MGMT) promoter methylation status, a known predictor of positive temozolomide treatment response in other tumors. In addition, synergistic effects of multiple treatments may have accounted for the favorable response. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: New and future perspectives for parathyroid carcinoma

“…Other agents have also been investigated in PC. One notable case in particular is a single patient with metastatic PC whose tumor harbored high O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status was reported to achieve long-term remission for 17 years after multiple lines of treatment with surgery, radiation, zolendronic acid, cinacalcet, and temozolomide (Storvall et al 2019a). Successful treatment in this patient could be from synergistic effects of combined therapies.…”

Parathyroid carcinoma. The experience of treatment of 15 patients and a review

“…Имеются единичные сообщения об эффективности мультикиназного ингибитора сорафениба при лечении метастатического РПЩЖ [14]. Сообщается о применении темозоламида у 1 больного РПЩЖ [29]. При ведении пациентов с рецидивным / метастатическим РПЩЖ важно контролировать уровень кальция, так как гиперкальциемия сама по себе снижает выживаемость.…”

“…При хронической гиперкальциемии традиционно используют золедроновую кислоту или деносумаб. В последние годы все более активно используют кальцимиметик цинакальцет [10], который снижает и уровень кальция, и уровень ПТГ, а также обладает антипролиферативной активностью [29].…”

“…У 25 % пациентов возникают отдаленные метастазы [9]. Имеются также сообщения о развитии отдаленных метастазов после удаления «аденомы» ПЩЖ [27,29]. Возможно, оценка продукции парафибромина при иммуногистохимическом исследовании позволила бы выделить из всех пациентов с «аденомами» именно тех, кому требуется длительное наблюдение.…”

A rare case of three years disease free survival in a locally advanced parathyroid carcinoma successfully excised by complete surgical resection

“…Recent literature suggests that it accounts for only 0.5–5% of all the cases of primary hyperparathyroidism, with less than 1000 cases reported in the literature since it was first discovered in 1904 [ [3] , [4] , [5] ]. It may arise sporadically or less commonly, in conjunction with genetic endocrine syndromes such as multiple endocrine neoplasia (MEN) type 1, type 2A, and hyperparathyroidism jaw-tumor syndrome (HPT-JT) [ [6] , [7] , [8] ]. Diagnosis is usually difficult and challenging due to the absence of clinical and radiological characteristics that reliably distinguish benign from malignant disease [ 1 , 2 , 6 ].…”