Parathyroid carcinoma is notoriously difficult to diagnose with confidence in borderline cases. Commonly there is a long lag time between diagnosis and clinical evidence of malignant behavior even in histopathologically straightforward lesions. There is therefore a need for a novel adjunctive marker to assist in the diagnosis of carcinoma. Parafibromin is the protein encoded by the putative tumor suppressor gene HRPT2. Mutations predicted to inactivate parafibromin were first detected in the germline of patients with hyperparathyroidism-jaw tumor (HPT-JT) syndrome. Subsequently, somatic mutations have been identified in the majority of sporadic carcinomas. We performed immunohistochemistry for parafibromin on 115 parathyroid tissues comprising 4 HPT-JT-related tumors (3 adenomas and 1 carcinoma), 11 sporadic parathyroid carcinomas, 79 sporadic adenomas, 3 multiple endocrine neoplasia 2A-related adenomas, 2 sporadic primary hyperplasias, 2 multiple endocrine neoplasia (MEN)-1–related hyperplasias, 6 secondary hyperplasias, 4 tertiary hyperplasias, and 4 normal parathyroid glands. There was complete absence of nuclear staining in 3 of 4 (75%) HPT-JT–related tumors and 8 of 11 (73%) sporadic parathyroid carcinomas and focal weak staining in 1 of 4 HPT-JT tumors and 2 of 11 sporadic parathyroid carcinomas. Only 1 parathyroid carcinoma exhibited diffuse strong nuclear expression of parafibromin. In contrast, 98 of 100 non-HPT-JT–related benign parathyroids showed diffuse strong nuclear positivity and 2 of 100 showed weak positive staining. We conclude that, in the correct clinical and pathologic context, complete absence of nuclear staining for parafibromin is diagnostic of parathyroid carcinoma or an HPT-JT–related tumor.
*Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, Australia
†Department of General, Visceral and Vascular Surgery
‡Institute of Pathology, Martin Luther University, Halle-Wittenberg, Germany
§Department of Human Genetics, University of Michigan, Ann Arbor, MI
∥Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, Sydney, Australia
This work was supported by the Australian National Health and Medical Research Council .
Reprints: Anthony J. Gill, FRCPA, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW 2065. Australia (e-mail: email@example.com).
Deborah J. Marsh is supported by a Career Development and Support Fellowship from the Cancer Institute NSW. Viive M. Howell is supported by an Australian National Health and Medical Research Council CJ Martin Postdoctoral Fellowship.