Parathyroid Carcinoma Workup
- Author: Lawrence Kim, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC more...
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.
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.
See the list below:
Imaging studies may be used preoperatively to determine the location of an abnormal parathyroid gland. 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.
- Hand films may show subperiosteal bone resorption of the distal phalanges.
- Skull films have a characteristic "ground glass" or "salt and pepper" appearance.
- In severe cases, plain films reveal the classic bone finding, osteitis fibrosa cystica. It consists of bone cysts with or without pathologic fractures. These cysts are also known as brown tumors.
CT scanning 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. 
See the list below:
Fine-needle aspiration biopsy is not helpful in establishing a diagnosis and may be harmful by causing tumor dissemination.
See the list below:
No preoperative test is currently available to distinguish parathyroid cancer from benign primary hyperparathyroidism reliably.
Diagnosis is based on the histologic appearance of the excised parathyroid gland and clinical indicators such as recurrence or metastases.
The parathyroid glands are usually large (2-10 g).
Tumors are usually encapsulated and often have fibrous septa extending into the gland. 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.
Vascular and extracapsular invasion are common but not universal,
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. Increased expression of another marker, PGP9.5, has also been shown to be highly specific for parathyroid carcinoma. A preliminary study that examined a panel of 34 proteins showed promise in using protein arrays as an aid in diagnosis.
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.
Two staging systems have been developed and externally validated to classify risk in parathyroid carcinoma.[13, 30]
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.
(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
(Nx) - Lymph node not assessed
N0 - No regional lymph node metastases
N1 - Regional lymph node metastases
(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
See the list below:
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
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