Parathyroid Carcinoma Workup

Updated: Aug 03, 2021
  • Author: Lawrence T Kim, MD, FACS, FACE; Chief Editor: Neetu Radhakrishnan, MD  more...
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Laboratory Studies

The laboratory workup for parathyroid carcinoma is the same as that for primary hyperparathyroidism. Simultaneous calcium and parathyroid hormone (PTH) levels should be determined. 

Serum calcium level is usually elevated more markedly than in benign primary hyperparathyroidism.

With regard to parathyroid hormone (intact) testing, parathyroid carcinoma should produce authentic parathyroid hormone; therefore, serum parathyroid hormone levels should be elevated, usually higher than is typical for primary hyperparathyroidism.

In a retrospective chart review of 54 patients undergoing operation for primary hyperparathyroidism from 2000-2014, researchers found that parathyroid carcinoma was associated with higher parathyroid hormone (PTH) (p = 0.005) and with male sex (p = 0.002), compared with atypical parathyroid neoplasms. [28]

A mathematical model has been proposed to predict parathyroid carcinoma, taking into account the calcium and PTH levels and patient age. The model, however, has not been widely validated. [29]  Differential expression of the microRNAs miR-139 and miR-30b has been proposed as a potential strategy for distinguishing parathyroid carcinomas from parathyroid adenomas. [30]



Imaging Studies

Imaging studies may be used preoperatively to determine the location of an abnormal parathyroid gland, however, no single radiological modality has sufficient sensitivity and specificity for localization of parathyroid carcinoma. See Hyperparathyroidism for the rationale of whether to obtain imaging studies for this purpose. Imaging studies may also be used for staging to determine the presence of distant metastases.

Compared with benign parathyroid lesions, parathyroid carcinomas usually display the following characteristics on ultrasound [2] :

  • Larger
  • More hypoechoic
  • Hypervascular
  • Heterogeneous
  • Lobulated, with irregular borders
  • Higher depth/width ratio
  • Greater infiltration into surrounding tissues

Hand radiographs may show subperiosteal bone resorption of the distal phalanges. Skull radiographs demonstrate a characteristic "ground glass" or "salt and pepper" appearance. In severe cases, plain films reveal the classic bone finding, osteitis fibrosa cystica, which consists of bone cysts with or without pathologic fractures. These cysts are also known as brown tumors.

Computed tomography may be helpful in detecting metastatic disease.

Positron emission tomography (PET) scanning may be helpful in staging. False-positive findings due to brown tumors have been reported. [31]

For full discussion, see Imaging in Primary Hyperparathyroidism.


Genetic Testing

In patients with suspected or proven parathyroid cancer, genetic testing for germline CDC73 mutation should be considered to rule out HPT-JT. For example, young patients with unexplained hyperparathyroidism should be considered for genetic screening. [32]

Besides CDC73 mutations that can be detected by conventional mutational analysis, intragenic deletion of CDC73 has also been reported in patients with familial hyperparathyroidism and parathyroid carcinoma. Therefore, intragenic and gross gene deletion should be assessed as a part of genetic analysis in patients with a high index of suspicion but negative CDC73 mutational testing. Partial or complete gene deletion can be detected by methods such as exon array comparative genome hybridization. [2]  



No preoperative test is currently available to distinguish parathyroid cancer from benign primary hyperparathyroidism reliably. Fine-needle aspiration biopsy is not helpful in establishing a diagnosis and may be harmful by causing tumor dissemination. [33] Diagnosis is based on the histologic appearance of the excised parathyroid gland and clinical indicators such as recurrence or metastases.


Histologic Findings

The parathyroid glands are usually large (2-10 g).

Tumors are usually encapsulated and often have fibrous septa extending into the gland (see the image below). The majority of tumors are fibrotic. The parenchyma of the tumor usually has a predominance of chief cells. They are often larger than those typically seen in adenomas and have a bland cytologic appearance. The parenchyma may appear indistinguishable from a benign adenoma.

Photomicrograph of parathyroid carcinoma showing t Photomicrograph of parathyroid carcinoma showing typical fibrotic septae. Histologic diagnosis can be difficult.

Vascular and extracapsular invasion are common but not universal, [15]

Some degree of nuclear atypia is seen commonly, and mitotic figures are usually evident.

Proven lymphatic metastases, though uncommon, are a clear indication of malignancy.

Molecular or genetic markers may prove useful in distinguishing parathyroid cancer from other lesions. The HRPT2 gene product, parafibromin, is often but not always absent in parathyroid carcinoma. [34] Increased expression of another marker, PGP9.5, has also been shown to be highly specific for parathyroid carcinoma. [35] A preliminary study that examined a panel of 34 proteins showed promise in using protein arrays as an aid in diagnosis. [36]

Tumors that exhibit some characteristics of carcinoma but are not definitive are referred to as atypical adenoma or adenoma with suspicious features. The clinical behavior of these entities is not known. [37]



Two staging systems have been developed and externally validated to classify risk in parathyroid carcinoma. [15, 38]

The first is called the differentiated system and is reminiscent of a typical tumor, node, metastasis (TNM) staging system. It divides patients into 4 classes of risk. The second system is simpler and divides patients simply into high and low risk.

Differentiated system

T (tumor)

  • (Tx) - No information available

  • T1 - Evidence of capsular invasion

  • T2 - Invasion of surrounding soft tissues, excluding the vital organs of the trachea, larynx, and esophagus

  • T3 - Evidence of vascular invasion

  • T4 - Invasion of vital organs, such as the hypopharynx, trachea, esophagus, larynx, recurrent laryngeal nerve, carotid artery

N (node)

  • (Nx) - Lymph node not assessed

  • N0 - No regional lymph node metastases

  • N1 - Regional lymph node metastases

M (metastasis)

  • (Mx) - Distant metastases not assessed

  • M0 - No evidence of distant metastases

  • M1 - Evidence of distant metastases


  • Class I - T1 or T2 N0M0

  • Class II - T3 N0 M0

  • Class III - Any T, N1 M0, or T4

  • Class IV - Any N, M1

High/low risk system

Criteria are as follows:

  • Low risk - Capsular invasion combined with invasion of surrounding soft tissue

  • High risk - Vascular invasion and/or lymph node metastases and/or invasion of vital organs and/or distant metastases