Huge parathyroid carcinoma: Clinical considerations and literature review
© Chiofalo et al; licensee BioMed Central Ltd. 2005
Received: 07 February 2005
Accepted: 23 June 2005
Published: 23 June 2005
Parathyroid carcinoma is a rare malignancy, with an incidence of 0.5 to 4% of all cases of primary hyperparathyroidism. Surgery is the only curative treatment.
We report the case of a 66-year-old man referred for a large suspicious substernal goitre associated with severe hypercalcemia due to hyperparathyroidism. After normalization of serum calcium levels, patient underwent surgery. The voluminous cervicomediastinal firm mass could not be removed through the cervical incision; therefore a cervicothoracic approach was employed. Histopathology revealed a giant parathyroid cancer of 450 grams. A review of the literature was also undertaken to summarize the current treatment approaches for this rare malignancy.
Parathyroid cancer is usually not recognized either preoperatively or intra-operatively. En bloc resection of the tumour with the adjacent tissue is the treatment of choice and it is very important to avoid the rupture of the capsule during operation. Neither tumour size, nor the lymph node status appears to play a role in prognosis. The management of parathyroid carcinoma is a challenge even for experienced surgeons.
Parathyroid Carcinoma (PC) is a rare malignancy with an incidence of 0.5 to 4% in all patients surgically treated for primary hyperparathyroidism [1, 2]. Generally the tumour is solitary, although recently a double parathyroid carcinoma has been reported . This tumour has a high probability to recur locally and to spread to regional nodes and distant sites. It is difficult to diagnose parathyroid cancer preoperatively. Often local invasion at operation and subsequent histological examination reveal malignancy and differentiation from a benign parathyroid adenoma can be difficult even after histological examination. However, the presence of some signs such as profound hypercalcemia, markedly elevated levels of parathormone and a clinically palpable cervical mass can raise suspicion preoperatively of a malignant lesion [1, 2, 4, 5].
We report the case of a patient admitted to our department for a large substernal goitre suspected to be a thyroid cancer, associated with severe hyperparathyroidism.
Preoperative laboratory values
Postoperative laboratory values
2.30 mg/dl (0.60 – 1.30)
4.00 mg/dl (0.60 – 1.30)
825 U/L (50 – 140)
500 U/L (50 – 140)
14.2 mg/dl (8.4 – 10.5)
6.3 mg/dl (8.4 – 10.5)
3.1 mg/dl (2.5 – 5.0)
2.4 mg/dl (2.5 – 5.0)
1828 pg/ml (10.0 – 65.0)
20.9 pg/ml (10.0 – 65.0)
The patient was vigorously hydrated and bisphosphonates were given preoperatively to control hypercalcemia. Eight days later the serum calcium level decreased to 10.4 mg/dl. With the above clinical findings, the patient underwent surgical neck exploration.
At surgery a voluminous cervicomediastinal firm mass was found that could not be removed via the superior thoracic strait; therefore a complete sternotomy was performed. The surgical findings revealed an ovoid, grayish-yellow, hard mass, measuring 12 × 9 × 8 cm, adherent to the base of the left lobe of the thyroid, extending to the anterior upper mediastinum; the recurrent laryngeal nerve was laterally displaced but not invaded. Therefore en bloc resection of the mass along with the total thyroid gland and the connective tissue apparently involved in the tumour was performed. All the lymphoid tissue from the ipsilateral tracheoesophageal groove to the upper mediastinum was removed
At follow-up, three, six, nine and 12 months after surgery, the patient was disease-free with normal levels of PTH and calcaemia and improvement of the bone disease symptoms. Whole body positron emission tomography (PET) performed one year after surgery was negative.
Parathyroid carcinoma is a rare disease and the preoperative diagnosis is often difficult because clinical manifestations are similar, although more often severe than in patients with parathyroid adenomas. Parathyroid carcinomas are generally larger and firmer than parathyroid adenomas. The clinical manifestations of hyperparathyroidism are usually more severe, and serum levels of calcium, PTH and alkaline phosphatase are significantly higher than in patients with adenoma. Patients with parathyroid carcinoma have a high incidence of renal dysfunction, osteoporosis and gastrointestinal symptoms [1, 2, 4].
Preoperative and intraoperative suspicion is important in planning the effective surgical treatment: the complete resection of the tumour at the first neck exploration is reported to provide the best chance of cure. The optimal surgical treatment is en bloc resection with ipsilateral thyroid lobectomy and removal of any enlarged or abnormal lymph nodes. Most of the authors emphasize the importance of an aggressive initial approach in reducing local and distant recurrences [4, 6–12]. Particular attention must be given to avoid rupture of the tumour during surgery, because of the very high risk of local seeding and persistent or recurrent disease [4, 13]; in these cases, local surgical excision is useful for palliation but is rarely curative [14, 15].
The management of the recurrent laryngeal nerve is more controversial but it should be resected only when it is not functioning preoperatively or is invaded by tumour [1, 4, 15, 16]. The clinical behaviour of parathyroid carcinoma is variable, some patients are cured, others have an indolent course; recurrent or persistent disease occurs in about 50% of cases; usually the tumour recurs within 3 years after initial operation, although much longer intervals have been described [4, 6, 17, 18]. Surgery is the treatment of choice even for recurrent and persistent disease when the site of tumour can be localized: lung metastases are the most frequent type of recurrences after local recurrences; Hundley et al, have recently reported a case of resection of multiple PC lung metastases 20 years after the initial neck surgery, with a significant improvement of clinical and metabolic complications after removal of metastatic parathyroid cancer from both lungs .
Recently some authors have reported a role for adjuvant radiation therapy. Neck and mediastinum adjuvant irradiation has been reported to be useful in reducing the risk of loco-regional disease progression and in improving survival [16, 22–24]. Other reports suggest a positive effect of radiotherapy for palliating symptoms of hypercalcaemia in inoperable patients [23–25].
In our case, although the laboratory data revealed marked hyperparathyroidism and the patient had all the signs and symptoms of severe hyperparathyroidism, none of the preoperative localizing studies raised suspicion of the presence of a parathyroid carcinoma. The slow growth of the mass and the preoperative FNAB suggested a large substernal goitre with malignant transformation; only the postoperative histological exam revealed a diagnosis of parathyroid cancer.
This is an interesting case because of the large size of the parathyroid cancer with regional nodal metastases without any evidence of distant metastases or local recurrence one year after initial surgery. In the literature parathyroid cancers ranges from 1.5 to 6 cm in diameter and from 1.5 to 27 grams in weight [18, 26]. A case of giant paratyroid carcinoma of 1200 grams with nodal involvement, presenting as a substernal goitre has been reported; it was "en bloc" resected and the patient was alive and disease free after 4 years . The tumour size does not appear to play a role in the prognosis; the larger tumours in fact don't seem more likely to recur than the smaller ones. In the experience recently reported by Clayman neither local invasiveness seems to correlate with likelihood of recurrence [16, 28]. Our case too confirms that many biologic factors involved in the clinical course of parathyroid cancer remain unclear. Most of the parathyroid cancers are diagnosed after surgery and often only after reoperation for local or distant recurrence; many patients have a good clinical course despite the type of the initial operation; others have recurrent or persistent hypercalcemia and severe metabolic complications that can be difficult to control and often result in death . The outcome of the patients with parathyroid carcinoma depends on the biologic features and on the management of the recurrent disease more than on initial therapy. In the future an understanding of molecular pathogenesis of this rare malignancy could provide a means for early diagnosis and new treatment strategies. [16, 29].
Based on current knowledge, clinicians should consider parathyroid carcinoma in differential diagnosis when patients present with severe hyperparathyroidism and a palpable cervical mass. When there is an intraoperative suspicion of malignancy, a complete surgical resection should be undertaken with special attention to avoid the rupture of the capsule of the tumour. We believe this approach offers the best chance for a successful outcome.
We thank Mrs Jane Bryce for her kind collaboration in the review of the manuscript Patient consent was obtained for publication of this case report
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