Parathyroid Carcinoma

Abstract

Parathyroid carcinoma is a rare endocrine malignancy. It accounts for 400 cases of parathyroid carcinoma have been reported.5 It is usually a sporadic disease, but familial cases have been described. The largest series comes from the National Cancer database.6 In most series of PHPT, parathyroid carcinoma accounts for 3 cm), irregular, grayish-white, hard tumors often adherent tenaciously to adjacent tissues.2, 4, 60 The finding of gross infiltration of contiguous structures strongly suggest the diagnosis of carcinoma. The histological criteria of parathyroid carcinoma are difficult to define and identify. Schantz and Castleman61 in 1973 established a set of criteria, including thick fibrous bands, mitotic activity, and vascular and capsular invasion. Generally, neoplastic cells (usually chief cells) are arranged in a lobular pattern and separated by dense trabeculae, with mitotic figures. Invasion of the capsule is rather common and, less frequently (10–15%), vascular invasion also occurs.60 Capsular invasion is characterized by a "tongue-like" protrusion through the collagenous fibers and should be distinguished from pseudoinvasion, because of "trapping" of tumor cells within the capsule, which can be found in adenoma.2, 62 The criteria of vascular invasion have been differently defined according to whether capsular vessels or vessels in the surrounding tissues are involved.2, 62, 63 Partial attachment of tumor cells to the wall of the vascular channel or thrombosis should also be present.2, 63 Because metastatic behavior is rare at presentation,64 the diagnosis of parathyroid cancer on the basis of the above morphologic criteria may be difficult at the time of the initial operation. Many of the features described above, such as adherence to surrounding tissues, fibrous bands, trabecular growth, and mitosis, are not pathognomonic of malignancy because they can also be found in parathyroid adenomas. The diagnostic value of capsular and vascular invasion is still debated. Some authors regard vascular invasion as virtually diagnostic of malignancy.2, 64 Thus, controversy and diagnostic uncertainties still exist.2, 62, 63 The distinction between benign and malignant parathyroid tumors is very hard and rarely made at initial histology. Indeed, in a large series of patients with metastatic parathyroid cancers, as many as 50% were initially classified as benign tumors.65 A full discussion of the pathology of parathyroid cancer is beyond the scope of this review. In an attempt to improve diagnostic accuracy, other histological approaches have been studied, but none has yet proven clear diagnostic value.33, 66-72 However, the high rate of HRPT2 abnormalities in parathyroid carcinomas has paved the way for the development of new diagnostic tools (HRPT2 mutational status and/or parafibromin immunostaining) of potential utility, particularly in cases with equivocal initial histology (see below). Investigation of patients who have clinically and biochemically severe, but pathologically benign, parathyroid disease, and those with malignant pathology despite mild clinical features will help to elucidate further the utility of these diagnostic tools as markers for parathyroid carcinoma. The clinical manifestations of parathyroid carcinoma are primarily caused by the effects of markedly elevated serum PTH levels and hypercalcemia rather than by the local infiltration or distant metastases.1, 2 The typical clinical picture is characterized by signs and symptoms of severe hypercalcemia, with renal involvement (nephrocalcinosis, nephrolithiasis, impaired renal function) in up to 80% of patients, and bone involvement (osteitis fibrosa cystica, subperiosteal resorption, "salt and pepper" skull, diffuse osteopenia) in up to 90%.1 On physical examination, up to 76% of patients with parathyroid carcinoma have a palpable neck mass.1 Renal colic is a frequent presenting complaint. Other symptoms include muscle weakness, fatigue, depression, nausea, polydipsia and polyuria, bone pain, and fractures. Recurrent severe pancreatitis, peptic ulcer disease, and anemia can also occur. None of these features is pathognomonic of malignancy. In the majority of cases, the diagnosis of parathyroid carcinoma is made only in retrospect when hypercalcemia recurs because of local spread of tumor or distant metastases. In some patients with parathyroid cancer, a PTH moiety, different from intact PTH(1-84), is produced.73 The clinical implications of this finding in parathyroid carcinoma await additional studies. Rarely, parathyroid carcinomas are nonfunctional.43, 74 They can be misdiagnosed as thyroid or thymic carcinoma because of locally advanced disease (palpable neck mass, dysphagia, hoarseness caused by laryngeal nerve palsy). Immunohistochemistry for PTH, thyroglobulin, thyroid transcription factor 1, and calcitonin may help ascertain the correct diagnosis. The occurrence of metastases is the only unequivocal criterion of malignancy that is generally accepted, but they usually occur late in the course of the disease. At initial presentation, despite clinical features suggesting malignancy, it can be a challenge to differentiate between hyperparathyroidism caused by parathyroid carcinoma and that caused by its much more common benign counterpart. Because better outcomes are associated with complete resection of the tumor at the time of initial surgery, it is important to establish the correct diagnosis at the time the patient presents. Features that might lead to suspect a parathyroid cancer in a patients with PHPT are listed here and in Table 2. Male sex: there is no sex preference, whereas the female:male ratio in PHPT favors women by a ratio of 3–4:1 Relatively young age: the average age of a patient with parathyroid cancer is 50 yr, about 10 yr younger than the usual patient with benign PHPT. Markedly elevated serum calcium and PTH: Serum calcium levels are within 1 mg/dl above the upper normal limit in most patients with parathyroid adenomas and >14–15 mg/dl in most patients with parathyroid carcinoma. PTH levels are markedly elevated in patients with parathyroid carcinoma and only slightly elevated in those with adenomas. Bone and renal involvement: the combination of both renal and bone manifestations at the time of presentation suggests the possibility of parathyroid carcinoma. In benign PHPT, overt bone disease is unusual, and concomitant skeletal and renal involvement is uncommon. Size and appearance of the parathyroid lesion: parathyroid carcinomas are usually >3 cm and may be palpable. The tissue is hard and gray-white and adherent to adjacent structures. Parathyroid adenomas are smaller, dark brown, and firm but not hard. Alkaline phosphatase activity is also higher in patients with parathyroid carcinoma than in those with adenoma in whom serum levels are generally close to the upper limit of the normal range. α- and of human may be elevated in patients with parathyroid cancer but not in those with benign levels were found to be elevated in a of with parathyroid carcinomas, in contrast to a control of patients with benign In the elevated was the form of that is associated with malignancy in and Moreover, of might be of such as and benign PHPT presents with markedly elevated serum calcium and overt a clinical that was common but is now seen in most the clinical distinction between benign and malignant disease may be It is to have a high of particularly when concomitant kidney and bone disease are present than to the for by to cancer in the diagnosis. PHPT, called many clinical features with parathyroid carcinoma. In of the of serum calcium and PTH that are common in parathyroid parathyroid cancer should be in diagnosis of this Parathyroid cancer should also be in patient without a of prior neck surgery who presents with recurrent laryngeal nerve Immunohistochemistry is used to improve the of the diagnosis of parathyroid carcinoma. has involved the use of proliferation of cell cyclin has been shown in parathyroid carcinoma with but among these tumor has the utility of this approach. expression of an of and expression have been shown in carcinomas. The association between these abnormalities and high has been to the likelihood of of HRPT2 gene abnormalities to be a more diagnostic of or mutation at the HRPT2 gene and loss or of parafibromin have been reported in the large majority of parathyroid carcinomas but very rarely in (Fig. To date, are in equivocal cases, where this have the greatest diagnostic utility (Table It is important to that the diagnostic potential of these on common in parathyroid cancer and in benign disease. Because benign parathyroid disease is much more common than parathyroid cancer, a that has a rate in benign parathyroid disease if have clinical The value of the may be therefore, if the HRPT2 is to cases that are The of parafibromin and HRPT2 gene abnormalities the likelihood of a on this it to all parathyroid tumors in which the diagnosis is for abnormalities of both the HRPT2 gene and its of parafibromin A diffuse nuclear is present in most parathyroid cells Parathyroid The majority of cells show a nuclear Parathyroid carcinoma. cells show no nuclear from with from the of Parathyroid carcinoma typically an course because the tumor has a rather low malignant At initial presentation, very few patients show involvement of or distant 60 Parathyroid carcinoma recurs locally and to contiguous structures in the occur late in the course of the disease with spread to and in frequency by metastases Rarely, distant metastases occur in and The of HRPT2 mutations in patients with apparently sporadic parathyroid as germline 37, 45, 46 suggests that a subset of these patients might have HPT-JT syndrome or This observation has implications for the of recurrent disease in parathyroid cancer. a patient a recurrence of parathyroid cancer, in to the likelihood that the carcinoma has a new tumor should be because parathyroid tumo

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Cited by papers we hold 2

• Commentary: Case Report: Abdominal Lymph Node Metastases of Parathyroid Carcinoma: Diagnostic Workup, Molecular Diagnosis, and Clinical Management · 2021
  Not checked
• Recurrent hyperparathyroidism due to parathyroid and pulmonary tumors showing features of parathyroid adenoma · 2020
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