The cell division cycle 73 gene is mutated in familial and sporadic forms of
primary hyperparathyroidism, and the corresponding
protein product parafibromin has been proposed as an adjunct immunohistochemical marker for the identification of cell division cycle 73 mutations and
parathyroid carcinoma. Here, we present data from our experiences using parafibromin immunohistochemistry in parathyroid
tumors since the marker was implemented in clinical routine in 2010. A total of 2019
parathyroid adenomas, atypical
adenomas, and
carcinomas were diagnosed in our department, and parafibromin staining was ordered for 297 cases with an initial suspicion of malignant potential to avoid excessive numbers of false positives. The most common inclusion criteria for immunohistochemistry were marked
tumor weight (146 cases) and/or
fibrosis (77 cases) and/or marked pleomorphism (58 cases). In total, 238 cases were informatively stained, and partial or complete loss of nuclear parafibromin immunoreactivity was noted in 40 cases; 10 out of 182
adenomas (5%), 27 out of 46 atypical
adenomas (59%), and 7 out of 10
carcinomas (70%), with positive and negative predictive values of 85 and 90%, respectively for the detection of atypical
adenomas/
carcinomas versus
adenomas, and 18 and 98%, respectively for
carcinomas versus atypical
adenomas/
adenomas. Male patients with high-proliferative
tumors were overrepresented among cases with aberrant parafibromin immunohistochemistry, and
carcinomas more frequently harbored parafibromin aberrancies than atypical
adenomas and
adenomas (p < 0.001). We conclude that parafibromin immunohistochemistry is a useful marker in the clinical routine when applied on a pre-selected material of cases, with positive immunoreactivity as a confident rule out marker of
malignancy.