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Parathyroid carcinoma: a multicenter review of clinicopathologic features and treatment outcomes.


We conducted a retrospective study of 13 patients with parathyroid carcinoma to assess their clinical characteristics and surgical outcomes. Study parameters included patient demographics, survival, treatment response, and recurrence. We found that all patients who had undergone local tumor excision developed a recurrence, compared with only 33% of those available for follow-up after en bloc tumor resection. Based on these findings, we recommend en bloc tumor resection as the initial treatment of choice for patients diagnosed with parathyroid carcinoma.


Parathyroid carcinoma is an uncommon malignancy that has a poorly understood etiology. It is the rarity of this malignancy that has hampered attempts to study its natural history and underlying biologic basis. What is known about the clinical behavior of this disease has largely been learned from retrospective case series. In addition, multiple literature reviews have been published with the goal of developing an understanding of its clinicopathologic characteristics and biologic behavior.

Despite the rarity of parathyroid carcinoma, it is important that surgeons are aware of its clinical manifestations and appropriate treatment because morbidity and mortality may be significant, We must recognize that the best chance we currently have to manage this cancer is by en bloc tumor resection.

In this article, we describe our retrospective review of the experience with parathyroid carcinoma at three western New York medical institutions, with emphasis on clinical characteristics and treatment outcomes. By reporting this clinical experience and comparing it with information published in the literature, we aim to provide some insight into the underlying biology of parathyroid carcinoma and to develop an understanding of its most appropriate treatment.

Patients and methods

We retrospectively reviewed the charts of 13 patients--9 men and 4 women, aged 23 to 63 years at presentation (mean: 48.3)--who were treated for parathyroid carcinoma between Jan. 1, 1970, and Dec. 31, 2000. Patients were treated at one of three western New York medical institutions: the Roswell Park Cancer Institute in Buffalo, the University of Rochester Medical Center, and the Sisters of Charity Hospital in Buffalo.

The diagnosis of parathyroid cancer was based on evidence of local invasion, cervical or mediastinal lymph node metastasis, and distant metastasis, along with the characteristic histopathology of the primary tumor as described by Schantz and Castleman. (1) These histopathologic characteristics include the presence of a fibrous capsule or fibrous trabeculae, a trabecular or rosette-like cellular architecture, the presence of mitotic figures, and the presence of capsular or vascular invasion.

We documented survival, treatment response, and recurrence. The length of follow-up ranged from 2 to 18 years (median: 6). This study was carried out with institutional review board approval.


Clinical presentation. Three patients presented with a neck mass, 3 with nephrolithiasis, 2 with hoarseness and dysphagia, 2 with bone symptoms, 2 with asymptomatic hypercalcemia, and 1 with mental status changes. All 13 parathyroid carcinomas were functional. Parathyroid hormone (PTH) levels ranged between 1.5 and 22.0 times the upper limit of normal (mean: 15). (PTH measurements are expressed as a value relative to normal because the three medical institutions used different measurement techniques.) Symptomatic hypercalcemia was present in 11 patients; calcium levels ranged from 11.1 to 22.0 mg/dl (mean: 15.0). The preoperative diagnosis was a parathyroid adenoma in 10 patients and a thyroid neoplasm in 3.

Initial pathologic variables. The most common site of origin of the primary tumor was the right inferior gland, which was the case in 7 patients (53.8%) (figure). Tumors originated in the right superior gland, left superior gland, and left inferior gland in 2 patients (15.4%) each. Tumors ranged in size from 1.0 to 6.0 cm (mean: 2.8). All patients presented with localized disease, and no patient had evidence of cervical lymph node metastasis or distant metastasis at the time of the initial diagnosis.

Survival, treatment response, and recurrence. Two patients were lost to follow-up. Of the remaining 11 patients, 8 (72.7%) were alive with no evidence of disease at the time of the last recorded follow-up (table). Two patients died of their disease and 1 died of other causes.

Type of surgery. All 13 patients underwent surgery as their sole treatment modality. Eight patients underwent en bloc resection of the tumor and surrounding structures (7 ipsilateral thyroid lobectomies and 1 subtotal thyroidectomy), and 5 underwent local excision alone. Two patients in the former group also underwent central and/or lateral compartment neck dissection, including 1 who was later lost to follow-up.

Recurrence. Among the 11 patients who were available for follow-up, 7 experienced a recurrence.

All 5 patients who had undergone local excision alone achieved normalization of their serum calcium level during the postoperative period. However, all 5 were diagnosed with recurrent disease between 1 and 6 years later (mean: 2.3). One of these patients died of a distant (lung) metastasis. The other 4 underwent en bloc resection at the site of their local recurrence along with hemithyroidectomy and central compartment neck dissection; one of these patients also underwent a lateral compartment neck dissection. Three of the 4 patients were rendered disease-free by further surgery, but the other died of locally advanced disease.

Recurrences developed in 2 of the 5 patients who underwent en bloc resection plus ipsilateral thyroid lobectomy (including 1 subtotal thyroidectomy). The remaining patient--who underwent en bloc resection, ipsilateral lobectomy, and central and lateral compartment neck dissection--id not experience a recurrence. Thus, the overall recurrence rate following en bloc resection was 33% (2/6). The 2 patients who experienced a recurrence underwent excision of the tumor, hemithyroid resection, and central and lateral compartment neck dissection. Both were alive without evidence of disease at the last recorded follow-up.


Parathyroid carcinoma was first described by de Quervain 100 years ago. (2) Even so, the optimal management of this infrequently encountered endocrine malignancy remains controversial. It is the rarity of this cancer that has made it difficult to investigate. Although the true incidence of parathyroid carcinoma is unknown, it has generally been reported to account for 1 to 3% of reported cases of hyperparathyroidism. (3,4)

Etiology. The underlying etiology of parathyroid carcinoma has not yet been defined. Investigators have just recently begun to develop an understanding of the molecular mechanisms that underlie this malignancy. It is believed that abnormalities of the cyclin D1 oncogene, (5) the p53 tumor suppressor gene, (6) and the retinoblastoma tumor suppressor gene (7) play a role in the evolution of parathyroid carcinoma. It has been reported that patients with a history of familial hyperparathyroidism, (8) multiple endocrine neoplasia syndrome type I, (9) and hereditary hyperparathyroidism--jaw tumor syndrome (10) are more predisposed to developing parathyroid carcinoma. None of the patients in our series had a personal or family history of any of these disorders. As well, none of our patients had a history of end-stage renal disease (11) or head and neck irradiation, (12) both of which have been reported to play a role in parathyroid carcinoma tumorigenesis.

Comparisons with other reports. Koea and Shaw recently published a review of 372 cases of parathyroid carcinoma that had been reported in the world literature between 1933 and 1999. (3) The clinicopathologic characteristics we observed in our patient population are consistent with many of the findings described in that report. The average age of both populations was 48 years. On the other hand, Koea and Shaw found no predilection toward either sex, while the male-to-female ratio in our study was 2.25 to 1. They also reported that the most common clinical presentation was a palpable neck mass, which was present in up to 52% of those patients at the initial diagnosis; in our population, 23% of patients (3/13) presented with a palpable neck mass.

Multiple case reports have suggested that the lower parathyroid glands are predisposed to carcinoma development. (3,4) It is not clear why the inferior glands, which are derived from the third branchial arch, would tend to undergo carcinomatous change more often than do the superior glands, which are derived from the fourth branchial arch. However, we made the same observation in our study, in which 9 of the 13 primary tumors (69.2%) originated in an inferior gland (figure).

The presence of a cervical or mediastinal lymph node metastasis or a distant metastasis from a parathyroid carcinoma at the initial presentation has rarely been reported. In their review of 372 cases, Koea and Shaw found only 10 cases of regional nodal metastasis and 9 cases of distant metastasis? In a National Cancer Data Base (NCDB) study, Hundahl et al found that 286 cases of parathyroid carcinoma had been treated at surveyed centers in the United States between 1985 and 1995. (13) Among the 105 cases in which the patient's lymph node status was reported, only 16 (15.2%) involved nodal metastasis. Therefore, it is not surprising that none of the patients in our study had either a nodal or distant metastasis at initial presentation.

Parathyroid carcinoma tends to be a functional endocrine malignancy that produces PTH; only 7 cases of nonfunctional carcinomas have been described. (3) All of our patients had functional tumors. The lack of endocrine function is considered to be a prognosticator of a poor outcome. Patients with parathyroid carcinoma also tend to present with marked hypercalcemia (>14.0 mg/dl), which was the case in 11 of our patients. In all, the demographic and clinical characteristics of our patient population were similar to others reported in the world literature.

Management. Surgery is the mainstay of management. Radio- and/or chemotherapy as a primary treatment for parathyroid carcinoma has been used to treat patients who were not surgical candidates, but results have been uniformly poor. The role of chemotherapy and/or radiotherapy as an adjuvant to surgery is currently unclear. (3,4)

The extent of surgery for parathyroid carcinoma has been a topic of controversy. Our experience supports the notion that, compared with local excision, en bloc resection results in better control of local disease and better long-term survival. Our finding in this regard is consistent with the results of a survival analysis included in the review by Koea and Shaw. (3) They compared the outcomes of 104 patients who had been treated with en bloc resection and 179 patients who had been treated with local tumor excision alone; long-term survival was significantly better in the en bloc resection group (89 vs. 53%; p<0.0001). Koea and Shaw also reported that 83 of the 92 local recurrences (90.2%) that occurred following local excision were ultimately fatal. (3) Moreover, Kebebew et al reported that the rate of surgical morbidity following reoperation for parathyroid carcinoma was 17%. (14) The NCDB study demonstrated that only 26.9 to 39.2% of patients were being treated with en bloc resection. (13) Still, many investigators before and since have supported en bloc resection. (15-19)

Proper en bloc resection involves the removal of all adjacent structures invaded by the tumor, the resection of the ipsilateral thyroid lobe and isthmus along with the central compartment lymph nodes, and the removal of any contiguous tissues to which the tumor is adherent. Resection of the recurrent laryngeal nerve and partial resection of the trachea or esophagus are required when these structures have been invaded by tumor. Any lesser of an operation can lead to either the leaving of residual disease or the development of parathyrosis, both of which predispose the patient to the development of local recurrence. (14-19) Some investigators have advocated routine ipsilateral radical neck dissection for all patients with parathyroid carcinoma. (20) Because lymph node metastasis is uncommon, nodal dissection is performed only on grossly diseased lateral nodal compartments. (3,4) In our study, the importance of en bloc tumor resection is best appreciated by the fact that every patient who had undergone local tumor resection alone developed recurrent disease and required further surgery.

The rarity of parathyroid carcinoma notwithstanding, it is essential that surgeons consider it in the differential diagnosis when evaluating a patient with hyperparathyroidism. It is also important to be aware that choosing en bloc tumor resection as the initial operation offers these patients the best chance for cure.
Table. Clinicopathologic characteristics of 13 adults with
parathyroid carcinoma treated over 30 years at three western
New York medical institutions

 Tumor size En bloc Disease
Pt. Age/sex origin (cm) resection recurrence Outcome

 1 55/M RS 2.3 Yes No DOC
 2 55/M RI 5.5 Yes No AWNED
 3 50/M LS 2.0 Yes Yes AWNED
 4 46/M RI 3.3 No Yes AWNED
 5 46/M LI 1.0 No Yes AWNED
 6 63/F RI 2.5 No Yes DOD
 7 41/M RI 5.0 Yes No AWNED
 8 54/F RS 4.0 Yes Yes AWNED
 9 37/M RI 1.0 No Yes AWNED
10 23/M LS 1.0 No Yes DOD
11 48/M RI 6.0 Yes No AWNED
12 47/F RI 1.0 Yes ? ?
13 63/F LI 1.5 Yes ? ?

Abbreviations: RS = right superior gland; RI = right inferior gland;
LS = left superior gland; LI = left inferior gland; DOC = died of
other causes; AWNED = alive with no evidence of disease; DOD = died
of disease; ? = lost to follow-up.


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(2.) de Quervain F. Parastruma maligna aberrata. Deutsche Zeitschrift Fuer Chirurgie 1904;100:334-52.

(3.) Koea JB, Shaw JH. Parathyroid cancer: Biology and management. Surg Oncol 1999;8:155-65.

(4.) Shane E. Clinical review 122: Parathyroid carcinoma. J Clin Endocrinol Metab 2001;86:485-93.

(5.) Vasef MA, Brynes RK, Sturm M, et al. Expression of cyclin D1 in parathyroid carcinomas, adenomas, and hyperplasias: A paraffin immunohistochemical study. Mod Pathol 1999; 12:412-16.

(6.) Cryns VL, Rubio MP, Thor AD, et al. p53 abnormalities in human parathyroid carcinoma. J Clin Endocrinol Metab 1994;78:1320-4.

(7.) Cryns VL, Thor A, Xu HJ, et al. Loss of the retinoblastoma tumor-suppressor gene in parathyroid carcinoma. N Engl J Med 1994;330: 757-61.

(8.) Wassif WS, Moniz CF, Friedman E, et al. Familial isolated hyperparathyroidism: A distinct genetic entity with an increased risk of parathyroid cancer. J Clin Endocrinol Metab 1993;77:1485-9.

(9.) Wu CW, Huang CI, Tsai ST, et al. Parathyroid carcinoma in a patient with non-secretory pituitary tumor: A variant of multiple endocrine neoplasia type-I? Eur J Surg Oncol 1992;18:517-20.

(10.) Kakinuma A, Morimoto I, Nakano Y, et al. Familial primary hyperparathyroidism complicated with Wilms' tumor. Intern Med 1994;33:123-6.

(11.) Miki H, Sumitomo M, Inoue H, et al. Parathyroid carcinoma in patients with chronic renal failure on maintenance hemodialysis. Surgery 1996;120:897-901.

(12.) Christmas TJ, Chapple CR, Noble JG, et al. Hyperparathyroidism after neck irradiation. Br J Surg 1988;75:873-4.

(13.) Hundahl SA, Fleming ID, Fremgen AM, Menck HR. Two hundred eighty-six cases of parathyroid carcinoma treated in the U.S. between 1985-1995: A National Cancer Data Base Report. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 1999;86:538-44.

(14.) Kebebew E, Arici C, Duh QY, Clark OH. Localization and reoperation results for persistent and recurrent parathyroid carcinoma. Arch Surg 2001;136:878-85.

(15.) Fujimoto Y, Obara T, Ito Y, et al. Surgical treatment of ten cases of parathyroid carcinoma: Importance of an initial en bloc tumor resection. World J Surg 1984;8:392-400.

(16.) Obara T, Fujimoto Y. Diagnosis and treatment of patients with parathyroid carcinoma: An update and review. World J Surg 1991;15: 738-44.

(17.) Obara T, Okamoto T, Kanbe M, Iihara M. Functioning parathyroid carcinoma: Clinieopathologic features and rational treatment. Semin Surg Oncol 1997;13:134-41.

(18.) Favia G, Lumachi F, Polistina F, D'Amico DF. Parathyroid carcinoma: Sixteen new cases and suggestions for correct management. World J Surg 1998;22:1225-30.

(19.) Hakaim AG, Esselstyn CB, Jr. Parathyroid carcinoma: 50-year experience at The Cleveland Clinic Foundation. Cleve Clin J Med 1993;60:331-5.

(20.) Holmes EC, Morton DL, Ketcham AS. Parathyroid carcinoma: A collective review. Ann Surg 1969;169:631-40.

From the Department of Surgery, St. Paul's Hospital, University of British Columbia, Vancouver (Dr. Wiseman); the Department of Head and Neck Surgery (Dr. Rigual, Dr. Hicks, Dr. Lore, Dr. Douglas, and Dr. Loree) and the Department of Pathology (Dr. Tan), Roswell Park Cancer Institute, Buffalo, N.Y.; and the University of Rochester (N.Y.) Medical Center (Dr. Popat and Dr. Jacobson).

Reprint requests: Sam Wiseman, MD, Department of Surgery, St. Paul's Hospital, Burrard Bldg., Room C-302, 1081 Burrard St., Vancouver, BC V6Z- 1Y6. Phone: (604) 806-9108; fax: (604) 806-8666; e-mail:

The authors received no financial support for this study.
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Author:Loree, Thom R.
Publication:Ear, Nose and Throat Journal
Geographic Code:1CANA
Date:Jul 1, 2004
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