Role of biliary brush cytology in primary sclerosing cholangitis.

OBJECTIVE: To assess the role of brush cytology in the routine evaluation of patients with primary sclerosing cholangitis (PSC). STUDY DESIGN: From January 1995 to June 2000, 64 brush cytology specimens were obtained from 21 patients who had at least one cytologic sample obtained during endoscopic retrograde cholangiography. All patients had a diagnosis of primary sclerosing cholangitis. Cases were classified as benign, atypical or malignant according to major cytologic criteria (nuclear contour and chromatin irregularities) and minor cytologic criteria (polarity, cellularity, nuclear enlargement, mitosis, increased nuclear/cytoplasmic ratio) used by us to diagnose biliary brush cytology. Follow-up was available in all cases. RESULTS: Diagnoses were benign (13), atypical (5) and malignant (3) on cytology. Follow-up of the 13 benign cases showed bile duct stones (2), gallbladder adenocarcinoma at cholecystectomy (1), ascending cholangitis (1) and clinically/cytologically by benign follow-up (9). Five of 13 benign cases had subsequent liver transplantation for liver failure, with explants showing changes of primary sclerosing cholangitis. Of the 3 malignant cases, 1 had carcinoma in situ on biopsy, with the explanted liver showing high grade dysplasia; the second patient had cholangiocarcinoma on explant; and the third had hepatocellular carcinoma on liver five needle aspiration. The 5 patients with atypical cytology were reclassified on review as reactive (3) and atypical not otherwise specified (2). Follow-up showed benign disease in 3 of 3 atypical cases reclassified as reactive; 2 of 2 reclassified as atypical not otherwise specified showed low grade dysplasia in the explant. CONCLUSION: The overall incidence of malignancy was low (3 of 21) in patients with PSC. Bile duct brushing is a sensitive method of detecting neoplasia in the setting of PSC when well-defined cytologic criteria are applied.

Reclassification of "atypical" diagnoses in endoscopic retrograde cholangiopancreaticography-guided biliary brushings.

OBJECTIVE: To evaluate the usefulness of reclassifying "atypical" diagnoses in reporting biliary cytology using strict morphologic criteria. STUDY DESIGN: Cytologic specimens from 139 patients (direct, alcohol-fixed smears or cytocentrifuge preparations) were evaluated. Diagnoses were benign (70), atypical (36) and malignant (33). Using strict criteria--major (nuclear contour, chromatin pattern) and minor (polarity, cell types, nuclear size, nuclear grooves, nucleoli, mitosis, nuclear/cytoplasmic [N/C] ratio)--atypical cases were reevaluated and reclassified. Follow-up (F/U) was available on all cases. RESULTS: Atypical cases, (36) were reclassified as malignant (26), atypical favor benign (2)/reactive (3) and atypical, not otherwise specified (NOS) (5). Cases reclassified as malignant showed irregular nuclear contours, chromatin irregularities and rare mitosis. Nuclear enlargement, nucleoli and cellularity varied widely in all groups. N/C ratio was increased in most reclassified malignant cases. All 26 malignant reclassifications correlated with F/U of malignancy. Benign and reactive cases (5) were negative for malignancy on F/U (4), and in 1 case a metastatic carcinoma involving the biliary tree was found. In the 5 atypical (NOS) cases, F/U showed malignancy (3) and pancreatitis (2). Cytocentrifuge preparations made in our laboratory were of superior quality when compared to other methods of cell preparation. CONCLUSION: Irregularities in nuclear membrane and abnormal chromatin pattern were the most consistently useful features correlating with malignancy. The sensitivity and specificity of biliary brush cytology can be enhanced by using strict cytomorphologic criteria and proper collection and fixation, all of which decrease atypical diagnoses.

Prevention/reversal of choline deficiency-induced steatohepatitis by a peroxisome proliferator-activated receptor alpha ligand in rats.

Nonalcoholic steatohepatitis, often associated with obesity and diabetes, is a common liver condition in the U.S. Individuals with steatohepatitis are not eligible for liver donation and may be at increased risk from developing complications following lobectomy. If steatosis and steatohepatitis can be treated medically, these individuals can become eligible for living donor transplants and segmental resection of the liver for treatment of primary or metastatic liver diseases. Because rats fed a choline-deficient diet (CDD) develop morphological changes in the liver similar to that observed in nonalcoholic steatohepatitis, we examined the effect of ciprofibrate, a potent peroxisome proliferator activated receptor alpha (PPAR alpha) ligand and inducer of fatty acid oxidation systems in the liver, on reversal of steatosis. Rats fed CDD for 2 weeks developed marked fatty change with mild hepatitis and marked increase in serum aminotransferases and liver triacylglycerols. Concurrent administration of CDD and ciprofibrate resulted in the prevention of fatty change. Rats that were fed CDD for 2 weeks followed by feeding CDD containing ciprofibrate for 1 or 2 weeks resulted in marked reduction of fatty change and normalization of serum aminotransferases. Compared with the CDD group, all groups that received ciprofibrate showed several-fold increase in mRNA and protein levels of several PPAR alpha target genes. In addition, electron microscopic examination showed marked peroxisome proliferation in the hepatocytes. The results of these studies clearly demonstrate that the severity of CDD-induced fatty change and hepatitis in rats can be rapidly decreased by ciprofibrate and suggest the therapeutic potential of PPAR alpha ligands in the treatment of nonalcoholic steatohepatitis in humans to rapidly reverse liver changes.

Extensive myxoid change in well-differentiated papillary mesothelioma of the pelvic peritoneum.

We present a unique case of papillary mesothelioma of the pelvic peritoneum with extensive myxoid change in a 44-year-old woman. The patient presented with lower abdominal pain; imaging studies revealed a pelvic mass. Microscopic examination of the surgically resected specimen showed extensive areas of myxoid stroma and only focal areas of classical papillary mesothelioma. A small biopsy of this lesion might have been misinterpreted as a soft tissue neoplasm with myxoid stroma or pseudomyxoma peritonei. It is suggested that mesothelioma with myxoid change should be included with differential diagnoses of myxoid lesions of the peritoneum.