Office-based unsedated small-caliber endoscopy is equivalent to conventional sedated endoscopy in screening and surveillance for Barrett's esophagus: a randomized and blinded comparison.

OBJECTIVES: A major limitation to screening and surveillance of Barrett's esophagus is the complexity, expense, and risk associated with sedation for upper endoscopy. This study examines the feasibility, accuracy, and patient acceptability of office-based unsedated endoscopy as an alternative. METHODS: Of 274 eligible adults scheduled for endoscopic screening for gastroesophageal reflux symptoms or surveillance of Barrett's esophagus at a tertiary care center, 121 underwent unsedated small-caliber endoscopy and conventional endoscopy in a randomized crossover study. The two procedures were compared with regard to histological detection of Barrett's esophagus and dysplasia and biopsy size. Patients answered questionnaires assessing the tolerability of the procedures. RESULTS: The prevalence of Barrett's esophagus was 26% using conventional endoscopy and 30% using unsedated endoscopy (P= 0.503). The level of agreement between the two approaches was "moderate" (kappa= 0.591). Each modality detected four cases of low-grade dysplasia with concordance on one case. The tissue samples collected with unsedated endoscopy were smaller than with conventional endoscopy (P < 0.001). The majority of subjects rated their experience with both procedures as being well tolerated with minimal or no difficulty. When asked which procedure they would prefer in the future, 71% (81/114) chose unsedated small-caliber endoscopy. CONCLUSIONS: Office-based unsedated small-caliber endoscopy is technically feasible, well tolerated, and accurate in screening for Barrett's esophagus, despite yielding a smaller biopsy specimen. This approach bears the potential to eliminate the infrastructure and cost required for intravenous sedation in this application.

Trisomy 8 as the sole cytogenetic abnormality in a case of extraskeletal mesenchymal chondrosarcoma.

Mesenchymal chondrosarcoma is a rare malignant tumor that comprises about 3-10% of all sarcomas. Reports of cytogenetic studies of mesenchymal chondrosarcoma are limited and no consistent cytogenetic abnormality has surfaced. Some mesenchymal chondrosarcomas have a t(11;22) translocation suggesting a relationship with the PNET/Ewing tumor family. We report what to our knowledge is the first case of trisomy 8 as the sole cytogenetic abnormality in a mesenchymal chondrosarcoma.

Merkel cell carcinoma in a malignant pleural effusion: case report.

BACKGROUND: Merkel cell (neuroendocrine) carcinoma is a small round blue cell malignant neoplasm that primarily presents in the skin. The diagnosis of Merkel cell carcinoma in a pleural fluid is challenging because of the morphological similarity to many other malignant neoplasms. Immunohistochemical stains can be essential to establish the diagnosis of Merkel cell carcinoma. CASE PRESENTATION: A 77 year-old woman presented with a mass in her right buttock thought clinically to be a boil or sebaceous cyst. Upon histopathologic review including immunohistochemical analysis, a diagnosis of Merkel cell carcinoma was rendered. Wide-excision and sentinel lymph node biopsy revealed negative margins and no evidence of metastasis. Ten months later she complained of bone pain and a bone scan revealed multiple lesions. An abdominal CT scan revealed a T4 vertebral mass and local radiotherapy was administered. Two months later the patient presented with shortness of breath. A chest radiograph showed an effusion and thoracentesis was performed. The fluid was confirmed to contain metastatic Merkel cell carcinoma by cytology and immunohistochemical analysis. CONCLUSIONS: Merkel cell carcinoma is an aggressive neoplasm that can, despite careful surgical management, occasionally present as a malignant pleural effusion in a relatively short time period. Immunohistochemical analysis can aid in confirming this rare outcome.

Novel markers of pancreatic adenocarcinoma in fine-needle aspiration: mesothelin and prostate stem cell antigen labeling increases accuracy in cytologically borderline cases.

The interpretation of pancreas fine-needle aspiration (FNA) is extremely difficult given the cytologic overlap of neoplastic and reactive processes. Using serial analysis of gene expression, we have discovered 2 new markers of pancreatic adenocarcinoma, mesothelin and prostate stem cell antigen (PSCA), and confirmed their specificity by immunohistochemical labeling. Here we evaluate the potential contribution of immunohistochemical labeling of mesothelin and PSCA to the interpretation of pancreas FNAs. Thirty pancreas FNAs with follow-up data were reviewed. Unstained cell block sections from these aspirates labeled for mesothelin and PSCA using immunohistochemistry were compared with initial cytologic diagnoses and with follow-up diagnoses. On follow-up, 19 patients proved to have cancer, and 11 did not. Initial cytologic diagnosis of malignancy correlated with carcinoma on follow-up in 12 of 12 cases, and initial benign cytologic diagnosis correlated with benign follow-up in 8 of 9 cases (sensitivity, 92%; specificity, 100%). Six of the 9 patients with suspicious cytology were found to have a carcinoma on follow-up. PSCA labeling was present in 16 of the 19 patients who ultimately were proven to have carcinoma; PSCA labeling was absent in 10 of the 11 lesions proven to be benign (sensitivity, 84%; specificity, 91%). Mesothelin labeling was present in 13 of the 19 patients who ultimately were proven to have carcinoma; mesothelin labeling was absent in 10 of the 11 lesions proven to be benign (sensitivity, 68%; specificity, 91%). Five of the 6 cytologically suspicious cases with malignant follow-up labeled for either PSCA or mesothelin (83%), and 2 of the 6 cases labeled for both markers. None of the 3 suspicious cases with benign follow-up labeled for either PSCA or mesothelin. Increasingly, molecular techniques are identifying potential cancer markers that may have diagnostic utility. In this study, immunohistochemical labeling for 2 of these markers, PSCA and mesothelin, appears highly specific for pancreatic adenocarcinoma in FNA specimens and useful in categorizing cytologically suspicious lesions.

A comparison of EUS features between CD-117 positive GI stromal tumors and CD-117 negative GI spindle cell tumors.

BACKGROUND: GI stromal tumors are spindle cell tumors that stain positive for immunohistochemical CD-117 (c-kit). Prognostic factors for malignancy include size (> or =4 cm), mitotic index (5 mitotic figures/50 high-powered fields), and ulcerated, cystic, or necrotic areas within the tumor. The purpose of this study was to compare these features in c-kit positive vs. c-kit negative tumors. METHODS: All patients referred for EUS of submucosal lesions were identified, and histopathology, including immunohistochemical staining, was reviewed to determine all diagnoses of GI stromal tumors. Size, echo pattern, and presence of cystic spaces and ulceration were recorded as diagnosed by EUS. Histopathologic diagnoses were made by FNA or endoscopic submucosal-mucosal resection. If surgical resection followed, the surgical diagnosis, staining pattern, mitotic index, and presence of ulceration, necrosis, and nuclear atypia were recorded. RESULTS: Forty patients (21 men, 19 women; 38 white, 2 African American; mean age 58 +/- 2.6 years) had 46 EUS procedures performed for evaluation of spindle cell tumors. Seventeen stained positive for c-kit (mean age, 59 +/- 3.6 years; range 19 to 80 years) and 12 negative (mean age, 57 +/- 3.8 years; range 31 to 76 years); 11 were not stained for c-kit (excluded from analysis). On EUS, 7 were ulcerated, 3 cystic, and 6 were larger than 4 cm. This group of findings was observed in 12 patients, 11 of whom had c-kit positive tumors (11/17 vs. 1/12; p = 0.006). Tumors positive for c-kit were larger (42.4 +/- 5.5 mm vs. 19.0 +/- 5.9 mm; p = 0.005). There were 13 c-kit positive tumors in the stomach, 2 in the duodenum, and 1 each in the esophagus and at the gastroesophageal junction. Of the 12 c-kit negative tumors, 8 were located in the esophagus and 1 at the gastroesophageal junction (9/12 vs. 2/17; p < 0.01). Surgical resection was performed on 13 patients, 12 of whom had c-kit positive tumors, and 3 of these 12 tumors had greater than 5 mitoses per 50 high-powered field. CONCLUSIONS: If a GI stromal tumor is suspected, EUS-FNA with immunohistochemical staining should be performed for CD-117 (c-kit). C-kit tumors are more likely to have malignant features and should be resected or subjected to close clinical follow-up.

Sclerosing hemangioma of the lung in a young woman with cutaneous melanoma: the role of electron microscopy in preventing an erroneous diagnosis of metastasis.

A young woman with a melanoma of the left forearm was found to have a right lung mass. This was initially interpreted as metastatic melanoma on the basis of clinical, radiographic, and light microscopic features, together with positive staining of tumor cells with antibody HMB-45. Electron microscopic examination performed for confirmation of the diagnosis revealed no evidence of melanocytic differentiation. Instead, there were features suggestive of the alternative diagnosis of sclerosing hemangioma (SH). This diagnosis was confirmed with additional immunocytochemical stains. To the authors' knowledge this is the first report of HMB-45 positivity in SH. This case illustrates a potentially disastrous diagnostic pitfall in interpreting lung tumors in patients with melanoma, and the vital role of electron microscopy in resolving conflicting and/or misleading immunocytochemical results.

K-ras, p53, and DPC4 (MAD4) alterations in fine-needle aspirates of the pancreas: a molecular panel correlates with and supplements cytologic diagnosis.

Between January 1997 and February 2000, 101 fine-needle pancreatic aspirates were obtained. After a cytologic diagnosis was made, possible molecular alterations were determined on the 94 aspirates with adequate tissue using a molecular panel (K-ras, p53, and DPC4 [MAD4] genes). The 94 aspirates were categorized as follows: diagnostic of adenocarcinoma, 48 (51%); atypical (suggestive of but not diagnostic of adenocarcinoma), 19 (20%); negative for adenocarcinoma, 25 (2 7%); diagnostic of a neoplasm other than adenocarcinoma, 2 (2%). Clinical follow-up revealed that 3 patients (12%) with negative cytologic diagnoses and 12 patients (63%) with atypical cytologic diagnoses had adenocarcinoma. Of 63 with a final diagnosis of adenocarcinoma, 42 (67%) had an alteration in at least 1 of the genes analyzed. In contrast, only 2 (6%) of 31 patients without adenocarcinoma had an alteration in 1 gene on the panel. Overall, the molecular analyses supported the diagnosis of adenocarcinoma in 6 (32%) of 19 aspirates originally diagnosed as atypical by cytology alone. A molecular panel that includes the K-ras, p53, and DPC4 (MAD4) genes correlates with and can supplement traditional cytologic diagnosis of pancreatic fine-needle aspirates.