Genomic profiling and precision medicine in complex ameloblastoma.

BACKGROUND: Ameloblastoma may present a significant treatment challenge in the locally advanced, recurrent and metastatic setting. Comprehensive genomic profiling (CGP) can identify targetable genomic alterations to aid in treatment. METHODS: Ameloblastoma samples were sequenced using hybrid-capture based sequencing. A systematic literature review was performed to examine outcomes in studies employing targeted treatment in ameloblastoma. RESULTS: We reviewed 14 cases of Ameloblastoma using CGP. There were six patients with activating BRAF mutations, five with PIK3CA, five with SMO, four with FGFR2, one with EGFR, and one with ROS1. All cases were MSI stable and the median TMB was 2.5 mutations/Mb. A separate literature review of clinical outcomes in ameloblastoma showed a predominance of at least partial response to targeted treatment (7/12 cases). CONCLUSION: CGP is helpful in identifying specific driver mutations in patients with complex ameloblastoma. Targeted treatment has been employed with success in achieving treatment response.

A rare case of insulinoma presenting with postprandial hypoglycemia.

BACKGROUND: Although fasting hypoglycemia has historically been considered the hallmark of insulinoma, postprandial hypoglycemia has also been occasionally reported as the predominant feature. We report a rare case of an insulinoma diagnosed in an individual presenting exclusively with postprandial hypoglycemia without fasting hypoglycemia. CASE REPORT: A 47-year-old woman with medical history of migraine, depression, hypercholesterolemia, iron deficiency anemia, and peptic ulcer disease presented with complaints of frequent episodes of dizziness, blurring of vision, and anxiety over the past 4 months. These episodes usually occurred 1-2 hours after eating and resolved with ingestion of sugary foods. Home glucometer readings during typical symptoms were 47-64 mg/dL. Physical exam revealed a healthy-appearing middle-aged female with BMI of 28. Laboratory data after an overnight fast showed serum blood glucose 77 mg/dL and AM cortisol 9.6 (5-25 µg/dl). Hemoglobin A1C, thyroid function tests, IGF-1, liver function tests, and kidney function were in normal range. She was instructed to bring a typical meal to the clinic for monitoring of postprandial glucose levels. Three hours after ingestion of the meal, she developed typical adrenergic symptoms during which laboratory analysis revealed a serum glucose level of 44 mg/dL, C-peptide of 2.9 (0.8-3.1 ng/ml), insulin level of 32 (0-17 µIU/lt), negative sulfonylurea screen, and insulin antibodies. She was treated with 15 grams of oral glucose, which alleviated her symptoms. Medical therapy with acarbose was attempted, but did not lead to significant reduction in hypoglycemic events. CT abdomen/pelvis confirmed the presence of a tumor in the tail of the pancreas. The patient subsequently underwent partial pancreatectomy, splenectomy, and lymph node resection, with resolution of symptoms. Histopathological analysis confirmed insulinoma. CONCLUSIONS: We present a rare case of an insulinoma in the setting of verified postprandial hypoglycemia with elevated insulin and C-peptide levels. Although insulinomas typically present with fasting hypoglycemia, it is important to consider insulinoma in the differential diagnosis of patients presenting exclusively with postprandial hypoglycemia.

Trastuzumab for the treatment of salivary duct carcinoma.

OBJECTIVE: Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with high mortality and poor response to treatment. A significant fraction of SDCs are HER2 positive. This retrospective review examines HER2 testing in SDC and the outcome of trastuzumab-based therapy in adjuvant and palliative settings. METHODS: A total of 13 patients with SDC and HER2/neu expression by immunohistochemistry of 1-3+ were treated with trastuzumab in adjuvant (n = 8) or palliative (n = 5) setting. Adjuvant therapy consisted of concurrent radiation and chemotherapy with weekly paclitaxel, carboplatin, and trastuzumab (TCH) for 6 weeks followed by TCH for 12 weeks and trastuzumab alone for 1 year. Palliative treatment for metastatic disease consisted of TCH every 3 weeks for 6 cycles followed by trastuzumab for variable time periods with or without second-line chemotherapy for progression. All patients had fluorescence in situ hybridization testing for HER2/neu gene amplification. RESULTS: The median duration of follow-up was 27 months (range: 8-48 months). In all, 62% of adjuvant patients (5/8) had no evidence of disease more than 2 years from completion of therapy. All patients with metastatic disease (5/5 patients) responded to treatment with TCH. One patient achieved a complete response and remains with no evidence of disease 52 months after initiation of TCH. The median duration of response was 18 months (range: 8-52 months). CONCLUSION: HER2/neu positivity and treatment with trastuzumab correlated well with long-term survival and response in our patients. Based on this data, we propose that HER2/neu status be examined routinely in all patients with SDCs and the treatment be directed accordingly.