Stem cell marker-positive stellate cells and mast cells are reduced in benign-appearing bladder tissue in patients with urothelial carcinoma.

Survival after invasive bladder cancer has improved less than that of other common non-skin cancers. In many types of malignancy, treatment failure has been attributed to therapy-resistant stem-like cancer cells. Our aim was therefore to determine identities of stem cell marker-positive cells in bladder cancer tissue and to investigate possible associations between these cells and different forms of bladder neoplasia. We investigated tissue from 52 patients with bladder neoplasia and 18 patients with benign bladder conditions, from a cohort that had been previously described with regard to diagnosis and outcome. The samples were analysed immunohistologically for the stem cell markers aldehyde dehydrogenase 1 A1 (ALDH1) and CD44, and markers of cell differentiation. The majority of stem cell marker-positive cells were located in connective tissue, and a smaller fraction in epithelial tissue. Stem cell marker-positive cells exhibiting possible stem cell characteristics included cells in deeper locations of benign and malignant epithelium, and sub-endothelial cells in patients with or without neoplasia. Stem cell marker-positive cells with non-stem cell character included stellate cells, mast cells, endothelial cells, foamy histiocytes, and neurons. Significantly, ALDH1+ stellate cells and ALDH1+ mast cells were reduced in number in stroma of benign-appearing mucosa of bladder cancer patients. The stem cell markers ALDH1 and CD44 label several types of differentiated cells in bladder tissue. ALDH1+ stellate cells and mast cells appear to be reduced in stroma of normal-appearing mucosa of bladder cancer patients, and may be part of a "field effect" in cancer-near areas.

Diagnosis of intraurothelial neoplasia. Interobserver variation and the value of individual histopathologic attributes.

OBJECTIVE: To determine interobserver variation in histopathologic diagnosis of carcinoma in situ (CIS) and dysplasia (collectively intraurothelial neoplasia [IUN]) of the bladder and identify histomorphologic features important for diagnosis. STUDY DESIGN: A total of 272 consecutive bladder tissue samples were re-evaluated blindly by two general pathologists and one uropathologist for IUN. Discrepancies were resolved jointly. Fifteen histopathologic attributes were evaluated for prediction of diagnosis. Followup revealed recurrence and progression rates for each diagnostic category. RESULTS: Thirty-six percent of specimens contained no evaluable flat mucosa; 51% percent of specimens from papillary urothelial neoplasia (PUN) cases showed CIS. General pathologists detected 56-69% of CIS and 8-42% of dysplasia. Histopathologic features most predictive for CIS were nuclear size, variation in nuclear shape, loss of maturation, loss of polarity, and architectural disorder. None of these individually or in combination exceeded general pathologists' diagnostic accuracy. IUN was not predictive of recurrence or progress. CONCLUSION: Using material mostly consisting of flat mucosa gratuitously provided in PUN resection specimens, IUN carries no prognostic value. General histopathologists detect IUN poorly to moderately, and the five most discriminatory histomorphologic features are insufficient for diagnosis. Interobserver agreement for dysplasia is dismal. Absent flat mucosa in PUN resections predicts recurrence.

Simplification of grading papillary urothelial neoplasia using a reduced set of diagnostic features.

OBJECTIVE: To determine whether a reduced set of the histopathologic features used in internationally accepted classifications is capable of accurately grading papillary urothelial neoplasms (PUN). STUDY DESIGN: All surgical specimens from urinary bladders received during a 2-year period were reexamined by an expert uropathologist for assessing the accuracy of original nonexpert PUN grading and staging. Thirteen histopathologic features entailing 32 attributes were evaluated with regard to prediction of expert grade. Patients were followed for 35-59 months (mean, 47). RESULTS: A total of 88 PUN specimens could be analyzed completely including follow-up specimens. Agreement between original and expert grade was 71% for low-grade and 87% for high-grade PUN, with overall kappa = 0.53. The histomorphologic features most predictive of expert grade were architectural disorder, variability of nuclear enlargement, and absence of umbrella cells. Neither individual histomorphologic attributes nor their combinations were as predictive of expert pathologist grade as original diagnoses. CONCLUSION: Improvements in PUN grading and prognostication are not likely to be accomplished by only reducing the number of histomorphologic features currently recommended by the World Health Organization and International Society of Urological Pathology.

Malignant lymphoma of the tongue with unusual cytology in a pleural effusion: a case report.

BACKGROUND: The diagnosis of maligan phoma (ML) in pleural effusions is often difficult. In some cases, the cytomorphology of lymphoma cells in pleural fluid differs from the histomorphology ofthe primary tumor. We report a case of ML cells in the pleural fluid with a cytomorphology and immunocytochemistry different from the morphology and immunophenotype of the original site in the tongue. CASE: A 61-year-old male was admitted with an infiltration of the tongue. The biopsy result was ofa large, B cell ML, supported by immunohistochemistry. No pleural effusion was observed at that time. Fifteen months later a small, subcutaneous tumor appeared on the abdomen, and pleural fluid was detected. Cytology revealed cells with different morphology and immunophenotype than the histomorphology and immunohistochemistry of the primary infiltrate in the tongue. CONCLUSION: The cytologic diagnosis of pleural efflsions with lymphoid cells is always difficult. One should keep in mind that in some cases the cytomorphology and even the immunopheno-type may vary from the picture of the primary tumor.

Insulin producing primary ovarian carcinoid tumor.

Carcinoid tumors are slow growing and originate most frequently from gastrointestinal tissue 1. They may also appear in genital tissue like the ovaries. Primary ovarian carcinoid tumors are rare and contribute to less than 0.1% of all ovarian carcinomas 2. We report the first case of insulin producing primary carcinoid tumor of the ovary, initially presented with amnesia and hypoglycemia and subsequently successfully treated with surgery.