Familial hyperparathyroid syndromes involving mutations of HRPT2 (also CDC73), a tumor suppressor, are important to identify because the relatively high incidence of parathyroid malignancy associated with such mutations warrants a specific surveillance strategy. However, there is a dearth of reports describing experience with surveillance and early detection informed by genetic insight into this disorder.Introduction: Familial isolated hyperparathyroidism (FIHP) is a rare cause of parathyroid (PT) tumors without other neoplasms or endocrinopathies. Germline mutations in CASR, MEN1, and rarely, HRPT2 have been identified in kindreds with FIHP. HRPT2 mutations may be enriched in FIHP families with PT carcinoma, underscoring the importance of identifying causative mutations. Materials and Methods: A 13-year-old boy, whose father had died of PT carcinoma, developed primary hyperparathyroidism. A left superior PT mass was identified by ultrasonography and removed surgically. Aggressive histological features of the boy's tumor included fibrous trabeculae, mitoses, and microscopic capsular infiltration. Two years later, under close biochemical surveillance, primary hyperparathyroidism recurred 5 months after documentation of normocalcemia and normal parathyroid status. Ultrasound and MRI identified a newly enlarged right superior PT gland but indicated no recurrent disease in the left neck. Histologic features typical of a benign adenoma were evident after surgical extirpation of the gland. Results: Leukocyte DNA analysis revealed a frameshift mutation in exon 2 of HRPT2. The initial tumor manifested the expected germline HRPT2 mutation, plus a distinct somatic frameshift mutation, consistent with the Knudson "two hit" concept of biallelic inactivation of a classic tumor suppressor gene. Genetic screening of the patient's 7 asymptomatic and previously normocalcemic siblings revealed three with the same germline HRPT2 mutation. One of the siblings newly identified as mutation-positive was noted to be hypercalcemic at the time of the genetic screening. He was found to have a PT adenoma with aggressive features. Two of the five children of another mutation-positive sibling also carry the same HRPT2 mutation. Conclusions: Despite the reported rarity of HRPT2 mutations in FIHP, a personal or family history of PT carcinoma in FIHP mandates serious consideration of germline HRPT2 mutation status. This information can be used in diagnostic and management considerations, leading to early detection and removal of potentially malignant parathyroid tumors.

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Figure 2: (A) Initial resection showing nonkeratinizing squamous epithelium and columnar epithelium (arrow) adjacent to anterior pituitary tissue (hematoxylin and eosin, 40×). (B) Ciliated columnar epithelium with rare goblet cells (arrow) (400×). (C) VE1 immunostain is positive in the squamous epithelium and negative in the columnar epithelium with nonspecific staining of cilia and anterior pituitary tissue (200×). (D) Resection of residual tumor showing nonkeratinizing squamous epithelium with fibrovascular cores (200×).

Increased utilization of prostate-specific antigen screening and prostate imaging has led to detection of smaller indolent tumors that traditional brachytherapy and prostectomy may be too aggressive for. New targeted techniques require greater locational accuracy of tumor detection to guide treatment. Prostate MRIs can be important for initial staging and for guiding targeted biopsies and treatments. We compared the accuracy of local staging of prostate cancer using 1.5 Tesla MRI with endorectal coil (ERC) versus 3 Tesla MRI with pelvic array coil (PAC) to the gold standard of trans-rectal US guided biopsies (TRUS). ERC is uncomfortable and has many imaging artifacts that may limit detection, so we hypothesize that 3 T MRI with PAC will have improved performance. 72 patients underwent prostate MRIs and TRUS prostate biopsies from 2008-2011 (33 were excluded due to prior radiation therapy, 24 patients underwent 1.5 T ERC and 15 underwent 3.0 T PAC.) 3.0 T PAC was trending towards greater sensitivity although we lack the statistical power for significance.