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Parathyroid Carcinoma Workup

  • Author: Lawrence Kim, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
Updated: Dec 01, 2015

Laboratory Studies

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.[24]


Imaging Studies

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.
  • Radiographs
    • 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. [25]

Other Tests

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.

Histologic Findings

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,[13]

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.[26] Increased expression of another marker, PGP9.5, has also been shown to be highly specific for parathyroid carcinoma.[27] A preliminary study that examined a panel of 34 proteins showed promise in using protein arrays as an aid in diagnosis.[28]

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.[29]



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.

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

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
Contributor Information and Disclosures

Lawrence Kim, MD Professor, Department of Surgery, Division of Surgical Oncology, University of North Carolina at Chapel Hill School of Medicine

Lawrence Kim, MD is a member of the following medical societies: Association for Academic Surgery, Association of VA Surgeons, International Association of Endocrine Surgeons, Society of Surgical Oncology, Society of University Surgeons, American Association of Clinical Endocrinologists, American Association of Endocrine Surgeons, American College of Surgeons, Southwestern Surgical Congress

Disclosure: Received income in an amount equal to or greater than $250 from: Affinergy, LLC.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Jules E Harris, MD, FACP, FRCPC Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Jules E Harris, MD, FACP, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Society of Hematology, Central Society for Clinical and Translational Research, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Additional Contributors

Sanjiv S Agarwala, MD Chief of Oncology and Hematology, St Luke's Cancer Center, St Luke's Hospital and Health Network; Professor, Temple University Shool of Medicine

Sanjiv S Agarwala, MD is a member of the following medical societies: American Association for Cancer Research, American Head and Neck Society, European Society for Medical Oncology, American Society of Clinical Oncology, Eastern Cooperative Oncology Group

Disclosure: Received honoraria from BMS for speaking and teaching; Received consulting fee from Novartis for consulting; Received consulting fee from Merck for consulting.


Wendy Hu, MD Consulting Staff, Department of Hematology/Oncology and Bone Marrow Transplantation, Huntington Memorial Medical Center

Wendy Hu, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Blood and Marrow Transplantation, American Society of Hematology, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

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