Purpose: A reliable method for diagnosing parathyroid carcinoma has remained elusive over the years, resulting in its under-recognition and suboptimal therapy. Obtaining an accurate diagnosis has become an even more pressing matter with recent evidence that germline HRPT2 gene mutations are found in patients with apparently sporadic parathyroid carcinoma. There is a high prevalence of HRPT2 gene mutations and biallelic inactivation in parathyroid carcinoma. We hypothesize that loss of parafibromin, the protein product of the HRPT2 gene, would distinguish carcinoma from benign tissue.Experimental Design: We generated a novel antiparafibromin monoclonal antibody and performed immunostaining on 52 definite carcinoma specimens, 6 equivocal carcinoma specimens, 88 benign specimens, and 9 hyperparathyroidism-jaw tumor (HPT-JT) syndrome-related adenomas from patients with primary hyperparathyroidism from nine worldwide centers and one national database.
Results:We report that the loss of parafibromin nuclear immunoreactivity has 96% sensitivity [95% confidence interval (CI), 85-99%] and 99% specificity (95% CI, 92-100%) in diagnosing definite carcinoma. Inter-observer agreement for evaluation of parafibromin loss was excellent, with unweighted kappa of 0.89 (95% CI, 0.79 -0.98). Two equivocal carcinomas misclassified as adenomas were highlighted by parafibromin immunostaining. One of these tumors has since recurred, satisfying criteria for a definite carcinoma. Similarly, eight of nine HPT-JT syndromerelated adenomas showed absent nuclear immunoreactivity.Conclusions: Parafibromin is a promising molecular marker for diagnosing parathyroid carcinoma. The similar loss of parafibromin immunoreactivity in HPT-JT syndrome-related adenomas suggests that this is a pivotal step in parathyroid tumorigenesis.
Scarless (in the neck) endoscopic thyroidectomy is not a minimally invasive technique but a maximally invasive one that involves a longer operative time and greater postoperative pain. What it does provide is a safe excision of the thyroid pathology with the absence of a scar in the neck. However, there is a steep learning curve. With experience and newer surgical instruments, the operative time and postoperative pain might decrease.
Prophylactic and therapeutic neck dissections are used to control or eliminate local nodal disease in patients with thyroid cancer. The purpose of this study was to evaluate the results and complications of neck dissection. From 1992 to 1999 a series of 115 consecutive neck dissections were performed in 74 patients (32 men, 42 women; mean age 48 years) with thyroid cancer and nodal metastases. Operations included central compartment, lateral modified, and suprahyoid dissection with and without total or completion thyroidectomy. Sixty-four percent of the patients had papillary, 4% follicular, and 32% medullary thyroid cancer. Complications included transient hypocalcemia (23%) defined by a postoperative serum calcium level of <2.0 mmol/L (8.0 mg/dl), one neck hematoma (0.9%), and one cardiac death (0.9%). There were no permanent recurrent nerve palsies. Hypocalcemia occurred more frequently when neck dissection was combined with total thyroidectomy than without it (p <0.005). In this group, the incidence of hypocalcemia was higher after central, than lateral, neck dissection. When neck dissection was performed without thyroidectomy, there was no difference in the rates of hypocalcemia between central, lateral, or central with lateral neck dissection (p = NS). Hypocalcemia did not increase with repeated neck dissections (p = NS). Permanent hypoparathyroidism occurred in 0.9%. There were no complications after suprahyoid dissection. The median duration of hospitalization was 1 day. Therapeutic neck dissection or repeated neck dissection can be performed relatively safely in patients with thyroid cancer. Hypocalcemia occurs most frequently when neck dissection is combined with total thyroidectomy.
Symptoms were more common in patients with primary hyperparathyroidism versus thyroid controls, but were not different between those patients who met the NIH criteria for parathyroidectomy and those who did not. Patients in both parathyroid groups benefited symptomatically after successful parathyroidectomy.
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