Parathyroid Carcinoma Treatment & Management

Updated: Aug 29, 2018
  • Author: Lawrence Kim, MD, FACS, FACE; Chief Editor: Neetu Radhakrishnan, MD  more...
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Treatment

Approach Considerations

The diagnosis of parathyroid carcinoma is usually not known prior to surgery.  The usual indication for surgery is primary hyperparathyroidism. Unusually severe hyperparathyroidism or a palpable mass should trigger suspicion for parathyroid carcinoma. Often, however, the first indication of parathyroid carcinoma is the discovery of a hard mass during surgical exploration. Frozen section may be useful to confirm parathyroid tissue as opposed to a thyroid mass, but it is not usually sufficient to diagnosis parathyroid carcinoma.

 

 

 

 

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Medical Care

Medical therapy is primarily geared toward management of hypercalcemia, which is often quite severe. Treatment is similar to that of hypercalcemia due to other causes. At initial presentation, and for rapid treatment of severe hypercalcemia, volume loading and diuresis with a calcium-wasting loop diuretic is the treatment of choice.

In most cases, volume expansion with normal saline and diuresis with furosemide is adequate treatment. Bisphosphonates may also be used for short-term control of the hypercalcemia but often are ineffective for long-term control in patients with metastatic disease. Calcitonin may be used for short periods, usually in conjunction with a bisphosphonate. It usually loses effectiveness rapidly. 

Hypercalcemia associated with parathyroid carcinoma is often severe and refractory to medical treatment. Treatment with denosumab (120 mg/month) has been effective in controlling hypercalcemia that is resistant to bisphosphonates and cinacalcet. [37, 38] However, hypercalcemia due to parathyroid cancer is often resistant to long-term medical management and is usually the cause of death in patients with metastatic disease. 

No effective medical therapy for parathyroid carcinoma is known and medical care is limited to the control of hypercalcemia (if necessary). Trials of chemotherapeutic agents have been generally disappointing. This tumor is sufficiently rare that controlled trials are impossible.  

Preliminary laboratory data from archived tumor samples show that a proportion of parathyroid carcinomas exhibit tumor-infiltrating lymphocytes and are positive for programmed death ligand–1 (PDL-1). This suggests the possibility that immunotherapy might be useful in a subset of patients. [39] However, this has not been tested.

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Surgical Care

At present, resection of the parathyroid cancer is the only effective treatment.

Preoperative care

Because the hypercalcemia caused by parathyroid cancer is often severe, preoperative medical intervention to control hypercalcemia is often required. Volume expansion with isotonic saline and diuresis with furosemide is often adequate. Take care to ensure that any volume contraction is corrected before the operation.

Operative management

The goal of the initial operation is to remove the tumor en bloc with any adherent tissue, the ipsilateral thyroid lobe, and any enlarged lymph nodes. Recommendations on the precise extent of the dissection cannot be made because of the rarity of this condition, but an en bloc excision with negative margins and removal of the involved lymph nodes is standard. Prophylactic lateral neck dissection is not indicated. [40]

Because the diagnosis of malignancy is usually uncertain before the operation, the initial approach is the same as for benign primary hyperparathyroidism. Make a standard collar incision. While approaching the parathyroid, be alert for evidence of invasion into surrounding tissue or gland firmness that might indicate malignancy. If any indication of malignancy is noted, perform an en bloc excision as described above.

Regional lymph node metastases are uncommon. [12]  However, if any regional lymph nodes are enlarged, perform a compartmental lymphadenectomy.

See Parathyroidectomy

Postoperative care

Postoperative care is generally the same as with surgery for benign hyperparathyroidism. Bone hunger may be quite profound and require substantial doses of postoperative calcium.

Resection of recurrence

Reoperation for local and regional recurrence is indicated and may provide substantial palliation from hypercalcemia, in some cases for many years. Resection or ablation of pulmonary or hepatic metastases also may provide palliation. Long-term cure after a recurrence is virtually unknown.

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Consultations

Referral to an experienced parathyroid surgeon is advised; surgical removal is the mainstay of treatment. Medical care of the hypercalcemia can be difficult and complex and should be managed by an endocrinologist. An interventional radiologist may be consulted for palliative treatment with percutaneous ablation or embolization of metastatic lesions.

External beam radiation therapy (EBRT) is controversial. Postoperative EBRT may decrease local recurrence, but the evidence for this is not strong. [18]  EBRT may also be used in specific circumstances for treatment of a metastasis. In general, however, parathyroid carcinoma is relatively resistant to radiation therapy.

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Prevention

Germline CDC73 analysis in individuals with HPT-JT syndrome , familial isolated hyperparathyroidism or malignant parathyroid histology, and young individuals with pHPT enables optimal clinical management of pHPT as well as surveillance for development of parathyroid carcinoma. [10]   First-degree relatives of patients with parathyroid cancer or HPT-JT should also be genetically screened for CDC73 mutation (when mutation is known) or periodically screened for primary hyperparathyroidism. [1]

Screening for HPT-JT associated tumors should begin in early childhood in asymptomatic patients with germline CDC73 gene mutation found through genetic testing. Screening includes biochemical testing every 6–12 months, and panoramic dental imaging and renal ultrasound every 5 years. The follow up schedule should be individualized. [1]

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Long-Term Monitoring

After surgical treatment, periodic follow-up with serum calcium determinations is mandatory. If serum calcium begins to rise, elevation of parathyroid hormone level can confirm recurrence.

Once suspected, the location of the recurrence should be determined:

  • Neck imaging with CT scan, MRI, or ultrasound is indicated.

  • PET scanning may detect distant metastases but its accuracy in this disease is not clearly defined.

  • A chest radiograph is indicated, but a chest CT scan may reveal pulmonary metastases missed on plain radiograph.

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