ES05ROUTINE PARAFIBROMIN IMMUNOHISTOCHEMISTRY OF LARGE PARATHYROID ADENOMAS IS NOT AN EFFECTIVE SCREENING STRATEGY FOR CARCINOMA

Purpose Parathyroid carcinoma (PC) is rare and accounts for less than 1% of all cases of primary hyperparathyroidism (PHPT). The definitive histopathologic diagnosis of PC requires unequivocal invasion or metastasis which may be absent at first presentation. As a result, many cases of PC can only be diagnosed retrospectively. Parafibromin is the protein encoded by HRPT2 which is mutated and not expressed in many parathyroid carcinomas. Given that PCs generally weigh more than parathyroid adenomas (PA)s, we hypothesized that amongst large PAs there may be a high incidence of occult PC which could be identified by negative staining for parafibromin. Methodology 57 parathyroid glands weighing greater than 2 grams excised from 1998–2006 were identified from the University of Sydney Endocrine Surgical Database. Two specimens with a histopathologic diagnosis of PC were excluded. Immunohistochemical staining for parafibromin was performed on the remaining 55 PAs. Results Of the 55 specimens stained for parafibromin only one definite negative stain was detected. This case was originally classified as an “atypical adenoma” because it showed nuclear and architectural atypia without unequivocal evidence of invasive growth. In view of the negative staining for parafibromin it therefore probably represents occult carcinoma. There has been no evidence of recurrence or metastasis after 6.5 years. Conclusions Complete loss of staining for parafibromin is very rare in giant parathyroid adenomas suggesting that occult carcinoma is equally rare. As a result routine immunohistochemical staining for parafibromin does not appear to be an effective screening test for carcinoma in large PA without histopathologic features of PC.     

BRAF<Superscript>V600E</Superscript> Mutation is Associated with Decreased Disease-Free Survival in Papillary Thyroid Cancer

Background

The BRAF ^V600E mutation is a recognised molecular marker in papillary thyroid cancer (PTC), reported incidence from 30 to 80 %. BRAF^V600E aberrantly activates the MAPK pathway, a central regulator of cell growth and proliferation. Previous studies have reported conflicting data regarding the impact of BRAF^V600E on clinicopathological features of PTC. The study aims to determine whether BRAF^V600E is useful as a prognostic biomarker in PTC.

Methods

A cohort study of patients undergoing surgery for PTC was undertaken. The primary outcome measure was disease-free survival. Secondary outcome measures were tumour size, nodal positivity and radioactive iodine ablation rate. All cases were re-examined to confirm PTC. Immunohistochemistry for BRAF^V600E was performed on tissue microarrays. A single endocrine pathologist, blinded to clinicopathological data, interpreted staining.

Results

496 patients with PTC were included, and 309 (62 %) were BRAF^V600E positive. Tumour size was similar for BRAF^V600E-positive and -negative tumours (21.3 vs. 23.2 mm, p = 0.23). BRAF^V600E-positive patients were significantly older at first operation (mean age 45 versus 49 years, p = 0.003). BRAF^V600E-positive PTCs had a higher rate of disease recurrence (12.9 vs. 5.6 %, p = 0.004), lymph node metastasis (44 vs. 29.4 %, p = 0.004) and extra-thyroidal extension (44 vs. 22 %, p < 0.001). Five-year disease-free survival was 89.6 % for BRAF^V600E positive and 96.3 % for negative tumours, p < 0.001. There was no difference between groups for vascular invasion or multifocality. The mean follow-up was 57 months for both groups.

Conclusion

BRAF^V600E in PTC predicts an increased risk of lymph node metastasis, extra-thyroidal extension and reduced disease-free survival. It is an additional useful prognostic biomarker.

     

Parathyroid Autotransplantation during Total Thyroidectomy—Does the Number of Glands Transplanted Affect Outcome?

Parathyroid autotransplantation is a technique for ensuring the continued function of parathyroid tissue at the time of total thyroidectomy (TT). The aim of this study was to ascertain whether the number of parathyroids transplanted affects the incidence of temporary and permanent hypoparathyroidism. A retrospective cohort study included all patients undergoing a TT in a single unit between July 1998 and June 2003. The number of parathyroids transplanted, the final pathology, and the incidence of temporary and permanent hypoparathyroidism were documented. Fisher’s exact test was used for statistical analysis. A total of 1196 patients underwent a TT during the 5 years studied. Of these, 306 (25.6%) had no parathyroids transplanted, 650 (54.3%), 206 (17.2%), 34 (2.8%) had 1,2, or 3 glands autotransplanted, respectively. The incidence of temporary hypoparathyroidism was 9.8% for no gland transplants, 11.9%, 15.1%, and 31.4% for 1,2,and 3 gland transplants, respectively (p < 0.05). The incidence of permanent hypoparathyroidism was 0.98%, 0.77%, 0.97%, and 0%, respectively (p = NS). The incidence of temporary hypoparathyroidism was higher when surgery was performed for Graves’ disease. Temporary hypocalcemia is closely related to the number of autotransplanted parathyroids during TT. The long-term outcome is not affected by the number of parathyroids autotransplanted. A “ready selective” approach to parathyroid autotransplantation is an effective strategy for minimizing the rate of permanent hypoparathyroidism.