Parathyroid carcinoma is an infrequent clinical entity accounting for 0,5% to 5% of all cases of primary hyperparathyroidism [
The objective of this paper is to elucidate the importance of high clinical suspicion in operative management of parathyroid carcinoma, analyzing retrospectively the cases treated in our service.
A systematic review of pathological reports of our secondary referral hospital was done. From 2003 and 2011 one hundred and forty-four patients were operated for hyperparathyroidism at our service. Histology distribution of patients is reported in Table
Diagnoses in primary hyperthyroidism.
Diagnosis |
|
% |
---|---|---|
Adenoma | 123 | 85,41% |
Hyperplasia | 17 | 11,80% |
Carcinoma | 3 | 2,08% |
Atypical adenoma | 1 | 0,69% |
Main clinical features of patients with parathyroid carcinoma (PC) and atypical adenoma (AA).
Patient 1 (PC) | Patient 2 (PC) | Patient 3 (PC) | Patient 4 (AA) | |
---|---|---|---|---|
Age | 46 | 69 | 64 | 54 |
Gender | F | M | M | M |
Symptoms | Renal + |
Renal + |
Renal + |
Renal − |
Palpable mass | No | No | Yes | Yes |
Calcium (mg/dL) | 14,0 | 13,0 | 14,2 | 13,2 |
PTH (pg/mL) | 898 | 184 | 620 | 475 |
Type of resection |
|
(1) MIVAP |
|
|
Affected gland | Left superior | Left superior | Left inferior | Right inferior |
Tumor size | 2,7 × 1,4 × 2,5 cm | 1,9 × 1,7 × 1,4 cm | 3,6 × 2 × 2,7 cm | 3 × 1,7 × 1,2 cm |
Outcome | Alive, no evidence of disease at 60 months of followup | Alive, surgically treated lung metastasis, rise in calcium/PTH levels without evidence of recurrence at imaging investigations at 36 months of followup | Alive, no evidence of disease at 48 months of followup | Died for other disease |
A 46-year-old women was admitted in our department with diagnosis of primary hyperparathyroidism (PHPT). In her past medical history two episodes of nephrolithiasis were reported, respectively, 3 years and 1 year ago. Since 6 months she reported fatigue, bone and muscular pain, and anxiety. The diagnosis of PHPT was established with calcium and parathormone (PTH) levels of 14,0 mg/dL, and 898 pg/mL respectively. Ultrasound scan identified a left superior thyroid lobe mass measuring 2,7 × 1,4 × 2,5 cm. Tc-99m sestamibi scan confirmed a persistent focus of activity in the same area. During neck exploration a firm grayish mass adherent to left thyroid lobe was found. A left thyroid lobectomy with paratracheal lymphadenectomy was done. Postoperative course was complicated by severe hypocalcaemia that required hospitalization for 10 days for intravenous administration of calcium. Final pathology report was consistent with the diagnosis of parathyroid carcinoma. Histology showed the presence of dense fibrous bands with cells arranged in a trabecular pattern infiltrating into the thyroid tissue; vessel invasion was also evident. At follow up to 5 years the patient was in good clinical conditions and free of recurrence.
A 69-year-old man presented with well-known long history of osteoporosis and renal stone. Laboratory findings showed serum calcium level of 13,0 mg/dL and PTH levels of 184 pg/mL. Ultrasonography of the neck revealed a 1,5 cm extrathyroidal parenchymal lump in the left superior thyroid lobe. Tc-99m sestamibi scan confirmed a persistent focus of activity in the same area. Radio-guided minimally invasive parathyroidectomy (MIVAP) was performed; no intraoperative abnormalities were found. Histological report showed parathyroid carcinoma with foci of capsular and vascular invasion. The patient underwent reoperation three weeks later for left hemithyroidectomy and central compartment lymph node clearance. Histology demonstrated the absence of tumor in the new resected specimen; no lymph node metastasis were found. Immediately after the operation serum calcium and PTH returned to the normal range.
30 months later rise in follow-up serum calcium and PTH levels were noted. Ultrasonography of the neck showed no abnormalities, but Tc-99m sestamibi scan detected marked increased radiotracer activity in the region of lower right lung lobe. CT scan confirmed the presence of 1 cm mass in the lower right lung lobe, then lung lobectomy was done. After operation serum calcium and PTH levels reduced but did not return to normal range (10,7 mg/dL, and 96 pg/mL resp.). Further investigations (neck ultrasonography, neck and chest CT, Tc-99m sestamibi scan and PET scan) fail to demonstrate any site of recurrence or metastasis until now.
A 64-year-old man was referred to our hospital with a diagnosis of PHPT. His history dated back two years with nephrolithiasis complicated by renal impairment and spontaneous fracture of inferior limb. The patient complained for some weeks the presence of a lump in the left neck. Serologies showed a serum calcium level of 14,2 mg/dL and a preoperative intact PTH of 620 pg/mL. Ultrasound identified an hypoechoic nodule 3,6 × 2 × 2,7 cm behind the left lobe of the thyroid. Tc-99m sestamibi scan resulted negative; however a Tl-201-Tc-99m scan located a marked increased radiotracer activity in the region of the inferior left lobe of the thyroid. At surgery a large-firm, hard, and lobulated mass adherent to the thyroid and to the strap muscle was found.
A 54-year-old man with symptoms of weakness, lethargy, bone pain secondary to osteoporosis and palpable neck mass was admitted in our department. PHPT diagnosis was established based on the serum calcium and intact PTH level of 13,2 mg/dL, and 475 pg/mL respectively. Ultrasound scan and Tc-99m sestamibi scan of the neck identified a mass behind the right thyroid lobe. At surgery a gray-white fibrous capsule adherent to the base of the inferior right lobe of the thyroid was found; therefore an
Parathyroid carcinoma is a rare cause of PHPT. Its rarity limits reports to small institutional series with occasional reviews of all experiences reported in the literature. The majority of patients with parathyroid carcinoma present in their fifties, and unlike parathyroid adenoma or hyperplasia which predominantly affect women, parathyroid carcinoma appears to be equally distributed between genders [
The diagnosis of parathyroid carcinoma in the absence of regional or distant metastases is a challenging issue. Parathyroid carcinomas, as opposed to other endocrine tumors that become less hormonally active when malignant, are hyperfunctional and characterized by severe elevations of serum calcium with associated renal and bone symptoms. Symptoms and signs are related with the metabolic consequence of hypercalcaemia, then patients usually present with a severe form of hyperparathyroidism at diagnosis, such as bone disease, renal disease, or hypercalcemic crisis, in contrast to relatively asymptomatic presentation of benign parathyroid disease. Very few cases of nonfunctional parathyroid cancers have been reported in the literature accounting for approximately 1.9% of parathyroid tumors and represent a prognostic indicator of poor outcome [
Typical features of PHPT secondary to parathyroid carcinoma versus parathyroid benign disease.
Parathyroid carcinoma | Parathyroid benign disease | |
---|---|---|
Average age | 48 | 55 |
Female/male ratio | 1 : 1 | 3,5 : 1 |
Tumor size >3 cm | Frequent | Very rare |
Serum calcium | 14–16 mg/dL | 11-12 mg/dL |
PTH | Markedly elevated | Mildly elevated |
Asymptomatic | <2% | 40–80% |
Palpable neck mass | 38% | <2% |
Hoarseness | 1–14% | None |
Renal and skeletal involvement | 30–50% | <5% |
Hypercalcemic crisis | 14% | <2% |
Intraoperative findings | Lobulated firm mass, surrounded by fibrous grayish-white capsule that adheres tenaciously to thyroid lobe or adjacent cervical tissues | Soft, oval, and brownish red |
(From ref. [
Diagnosis is not made easily even on histology. Schantz and Castleman have established the criteria for the histological diagnosis of parathyroid carcinoma. These are the presence of 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 [
The intraoperative diagnosis of parathyroid cancer could also be not easy. Whereas parathyroid adenomas tend to be soft, oval, and brownish red to tan in appearance, the macroscopic operative features of parathyroid carcinoma are characterized by lobulated firm mass, surrounded by fibrous grayish-white capsule that adheres tenaciously to thyroid lobe or adjacent cervical tissues (strap muscles, recurrent laryngeal nerve, esophagus, and trachea). Of the 358 patients in the series reported by Koea and Shaw the diagnosis of carcinoma was made or suspected intraoperatively by the surgeon in 178 (49,8%) because of invasion of the surrounding tissues [
The overall survival at 5-year and 10-year was 85% and 49%, respectively, in this series. Further studies report similar 5 years survival rate with higher 10 years survival rate (77%), probably related to improvements in overall general supportive medical care and prevention of fatal hypercalcemia [
For this reason the recent practice of minimally invasive parathyroidectomy, which is appropriate in the vast majority of patients with PHPT, should be altered in suspicious situations.
Some authors reported that despite infiltration macroscopically or adherence of the tumor to adjacent structures is often associated with malignant tumors, it could be sometimes present in benign lesions [
Although the reported incidence of cervical lymph node metastasis is <20% the most of authors recommended routine dissection of trachea-esophageal groove, but an extensive lateral neck dissection is indicated only when there is macroscopic spread to the anterior cervical nodes [
The patient who succumbed to parathyroid carcinoma typically died from metabolic consequences and not directly from malignant growth. For this reason surgical treatment to debulk parathyroid carcinoma, if possible, is indicated. Before reoperation a vigorous effort to locate the recurrent carcinoma is essential thereafter aggressive re-resection of neck recurrence or metastasis despite is often palliative and may offer improvement of symptoms for a long time [
In conclusion the preoperative evaluation of a patient with severe hypercalcemia and high PTH levels should include the possible diagnosis of parathyroid carcinoma, especially in symptomatic patients or in case of palpable neck mass. The surgeon will often report that dissection of the mass was surprisingly difficult in the patient with parathyroid carcinoma, with unexpected adherence to the surrounding soft tissues. In case of preoperative high suspicion of parathyroid carcinoma or intraoperative findings of firm adherent mass, an