Parathyroid carcinoma tends to invade the surrounding structures and to spread to regional lymph nodes (30% of cases); it may also disseminate hematogenously, with lung (40%), liver (10%) and bones metastases [4]. The prognosis is quite variable, although it usually has a slow, indolent but progressive course because of the rather low malignant potential, with a reported cumulative 5 and 10-year survival of 86% and 49%, respectively [2].

The most important factor affecting prognosis is the completeness of tumor resection; thus, the most effective treatment is surgery [4, 12]. However, since patients generally die from metabolic complications of uncontrollable hypercalcemia rather than from tumor burden, medical treatment aimed to lower hypercalcemia has a pivotal role. Furthermore, whenever possible, severe hypercalcemia should be corrected before surgery because of the risk of arrhythmias during anesthesia induction.

Hypercalcemia should be treated with urgent and aggressive restoration of fluid volume (these patients are significantly dehydrated). Loop diuretics (furosemide) are given to increase renal calcium excretion. Bisphosphonates (drugs that inhibit osteoclast-mediated bone resorption by incorporation into the bone matrix) are effective but they lose efficacy over time [4]. Pamidronate, infused in doses of 30–90 mg/day over 2–4 hours, is effective, at least transiently: responses last for 1–3 weeks and the treatment can be repeated. However, possible complications of bisphosphonates are represented by avascular necrosis of the jaw and acute renal failure.

Recently, new drugs (calcimimetics) have been developed for PTH-related hypercalcemia. Cinacalcet acts as an effective allosteric modulator of calciumsensing receptors that are responsible for the regulation of PTH secretion. It binds to the calcium receptors on the surface of parathyroid cells and increases the receptor sensitivity to extracellular calcium and subsequently reduces serum PTH and calcium levels. Cinacalcet is administrated orally (30–60 mg) and it is well tolerated; however, it does not modify the course of parathyroid cancer. Therefore, it cannot replace surgical intervention in the case of resectable disease. This drug can potentially alleviate the consequences of hypercalcemia in patients with widely metastatic disease or renal insufficiency.

Thus, the gold standard therapy is the radical surgery, with an en bloc resection of the primary lesion at the time of the initial operation [12, 19–21], with the excision of the adjacent ipsilateral thyroid lobe in continuity with the tumor, along with minimal manipulation, in order to achieve a complete resection with disease-free margins (Fig. 15.4). Any capsular rupture of the tumor and neoplastic spillage should be avoided, since seeding leads to recurrence [1, 12]. The removal of the ipsilateral normal parathyroid has also been suggested, in order to eliminate a possible adjacent source of PTH secretion that could be a confounding factor in case of recurrence [1]. This strategy may also reduce the risk of metachronous multiglandular involvement in the case of HPT-JT-related parathyroid carcinoma, which represents one third of the cases of apparent sporadic parathyroid carcinoma [11]. The recurrent laryngeal nerve — in the absence of an unequivocal sign of infiltration — should be preserved by means of a careful dissection, whenever possible; therefore, the knowledge of the preoperative status of the vocal cord mobility is very useful. To the contrary, if the nerve is infiltrated, its sacrifice might be necessary.