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HER-2/Neu overexpression is seen in 20% to 30% of invasive breast carcinomas and has been reported in as many as 80% of high-grade infiltrating carcinomas. Earlier studies have suggested that 100% of the tumor cells in mammary Paget disease show overexpression of HER-2 protein. We undertook this study to assess HER-2 status of mammary Paget disease and of the underlying breast carcinoma, when present, by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Formalin-fixed, paraffin-embedded tissue from 20 cases of mammary Paget disease were analyzed for HER-2 status by IHC and FISH. IHC for estrogen receptor (ER) was also performed. The patients ranged in age from 34 to 88 years, with a mean age of 62 years. Eighty percent of the cases showed strong overexpression (3+) of HER-2 protein by IHC, and all of these cases showed more than 5-fold amplification of the HER-2 gene by FISH. The remaining 4 cases, which were negative for HER-2/Neu by IHC, showed no amplification by FISH. All of the latter cases expressed ER, whereas no case that overexpressed HER-2 expressed ER. Sixteen cases had an underlying tumor, which was in situ in 6 cases. The underlying tumors were identical to the Paget disease with respect to their HER-2/Neu overexpression by both IHC and FISH. HER-2 overexpression was identified in 80% of our cases of Paget disease. There was 100% concordance between HER-2 protein overexpression by immunohistochemistry and gene amplification in both the Paget and the underlying tumor. Moreover, all of the cases negative for HER-2 overexpression expressed ER, whereas those positive for HER-2 did not.

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At the present time fine-needle aspiration (FNA) is considered a routine diagnostic procedure in evaluating neoplastic vs. nonneoplastic lesions in many organs, with high sensitivity and specificity. The purpose of this study was to assess the utility of FNA in areas of diagnostic difficulty and its limitations in evaluating bone lesions in patients with a previous history of malignancy. From 1989 to 2000, 249 CT-guided FNAs of bone lesion were performed at our institutions; 187/249 (75.1%) patients had a previous history of malignancy. Aspirated material was air-dried for Diff-Quik stain or fixed in ethanol for Papanicolaou staining. Subsequent surgical tissue was available in 69/187 (36.9%) of the cases. There were 114 males and 73 females, ages 14-86 yr (mean, 64 yr). The primary tumor site was lung 49, genitourinary 46, breast 31, gastrointestinal 28, hematopoietic 26, soft tissue/skin 5, and thyroid 2. There were 125 FNAs of the vertebral spine, 19 from the pelvis, 11 from the ribs, 9 from the sternum, 5 from the femur, and 18 from miscellaneous bone sites. Out of 187, 166 (88.7%) were malignant aspirates confirming the patients' primary malignancies. The most common malignancy encountered was adenocarcinoma, 126/187 (67.4%). Surgical tissue was available for review in 69 patients and the results were in agreement with the FNAs diagnosis in all cases. Nine out of 187 (4.8%) cases were diagnosed as marrow elements on cytological material. These patients have been followed for 1-9 yr and have failed to reveal signs or symptoms of clinical recurrence. Three out of 187 (1.6%) cases showed osteomyelitis. Nine out of 187 (4.8%) were unsatisfactory specimens, with biopsy follow-up available in four cases, showing three metastatic tumors and one case of osteomyelitis. FNA of metastatic bone lesions is a major step in pretreatment diagnosis. On satisfactory specimens, the cytological diagnosis viewed in the clinical-radiological context proves to be similar to surgical diagnosis. FNA is an excellent technique with a high accuracy rate in assessing metastatic bone lesions.

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Bile aspiration during endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography has been used as a diagnostic tool in the evaluations of pancreatic and biliary tree strictures for the last two decades. However, recently biliary tract brush cytology has become the method of choice in evaluating pancreatic/biliary tract abnormalities. The aim of this study was to evaluate the accuracy of pancreatobiliary lesions by an endobiliary cytotechnique. From 1993-1999, 278 pancreatobiliary brushings were performed at our institutions. Cytologic material was air-dried for Diff-Quik stain or fixed in ethanol for Papanicolaou staining. The cytologic diagnoses were classified in three categories: 1) benign, 2) atypical/suspicious, or 3) malignant. Subsequent surgical biopsy was available in 87 (31%) patients. There were 150 males and 128 females with a mean age of 63 yr (range 22-97); 167 (60%) were benign cases. Follow-up surgical material was available in 39 cases, seven of which showed adenocarcinoma; 67 of all cases (24%) were atypical/suspicious cases. Follow-up surgical material was available in 31 cases, 17 (55%) of which showed adenocarcinoma; 32 cases (12%) were malignant cases. Follow-up surgical material was available in 15 cases. All 15 cases were in agreement with the cytologic diagnosis. Twelve (4%) cases were unsatisfactory for cytologic examination. Follow-up surgical material was available in two cases. One case showed mucinous cystadenoma of the pancreas. The other case showed benign duct epithelium. Our study shows a sensitivity of 68% and a specificity of 100%. Of the atypical cases, 55% were malignant on follow-up biopsy. Brush cytology of pancreatobiliary strictures is the most widely used technique in the diagnosis of carcinoma, with a high degree of specificity.

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