Biomedical subjects
Publications and source records attributed to K R Cleary.
Small cell undifferentiated carcinoma of the pancreas is a rare neoplasm: Only 12 cases have previously been documented. This paper describes the clinical evolution, immunohistochemical profile, and ultrastructural features of a case occurring in a 37-year-old woman.
Most hereditary non-polyposis colorectal cancer (HNPCC) is due to germline mutations in DNA mismatch repair genes. Tumors arising as a result of these mutations display instability in microsatellites, which are short tandem repeats of DNA that are distributed throughout the genome. Although a subset of sporadic colorectal carcinomas also have microsatellite instability (MSI), the phenotype is a useful screening test in identifying patients with HNPCC caused by mutations in mismatch repair (MMR) genes. Studies have shown that some microsatellite markers are more efficient than others in identifying tumors with MSI. Furthermore, the frequency of instability can be assessed by categorizing patients into high (MSI-H, >/= 30-40% positive markers), low (MSI-L), and microsatellite stable (MSS) groups. Using a panel of 28 microsatellite markers, tumor and normal DNA from 10 HNPCC patients was used to identify the five most efficient markers for detecting MSI (BAT26, D2S123, FGA, D18S35, and TP53-DI). Each of the five markers detected MSI in 80-100% of the cases examined. We then expanded the sample size to 17 tumors from HNPCC patients. Each case had evidence for a mutation in either hMSH2 or hMLH1. We compared the efficiency of our panel of five best markers with another panel of five markers (BAT25, BAT26, D2S123, D17S250, and D5S346) identified as being efficient markers for detection of MSI at a recent NCI workshop. Our five selected markers were more efficient (85% vs. 79%) in detecting MSI. However, using either panel, 100% of the cases fell into the MSI-H category and the probability of misclassifying an MSI-H case as MSI-L is very low (0.002-0.008). We also examined four cases meeting the Amsterdam criteria for HNPCC, but with no evidence for mutation in either the hMSH2 or hMLH1 gene. With our panel, three were classified as MSI-H, while only two were classified as such with the NCI reference panel. The probability of misclassifying an MSI-L case as an MSI-H, using a panel of five markers is high (0.263).
OBJECTIVE: To describe a rare case of sarcoidosis diagnosed after surgical resection of an adenoma in a patient with Cushing's disease. METHODS: We present a case report and discuss the only other similar case identified from the published medical literature. RESULTS: In a 33-year-old woman with symptoms of cortisol excess (including progressive weight gain, proximal muscle weakness, ecchymoses, and amenorrhea), laboratory studies showed serum cortisol values consistent with Cushing's syndrome. After inferior petrosal sinus sampling, the patient underwent surgical resection of an adenoma in the right aspect of the anterior pituitary gland. Maintenance corticosteroid therapy was implemented, and the signs and symptoms of Cushing's disease began to resolve. Five months postoperatively, multiple erythematous lesions developed on the patient's arms and legs. Skin biopsy specimens demonstrated noncaseating granulomas, and sarcoidosis was diagnosed. Two months later, the lesions resolved spontaneously without therapy other than continued corticosteroid replacement. CONCLUSION: Physicians should be aware that unusual postoperative symptoms in a patient who has undergone successful treatment of Cushing's syndrome may be attributable to the emergence of another corticosteroid-responsive disease such as sarcoidosis.