It has been hypothesized that transforming growth factor-beta1 (TGF-beta1) signalling is involved in erectile dysfunction (ED). This study was undertaken to elucidate in detail whether expression of TGF-beta1 and its type II receptor is clinically related to various causes of ED. Fifty-four patients with ED and 24 potent men were the subjects of this study. After multidisciplinary work-up, the ED was classified as psychogenic (n = 6), neurogenic (n = 15), or vasculogenic (n = 33). In every subject, percutaneous cavernous biopsy was performed using a Biopty gun. Masson's trichrome staining was used to quantitate collagen fibres and immunohistochemical staining to evaluate both TGF-beta1 and its type II receptor by scoring the intensity of immunoreactivity (score 0-6). Collagen fibres were significantly more abundant in men with vasculogenic ED (72.7 +/- 17.7%) than in control subjects (43.3 +/- 11.2%) or those with psychogenic (45.0 +/- 12.2%) or neurogenic (51.3 +/- 20.3%) ED (p < 0.01). Expression of TGF-beta1 was significantly greater in vasculogenic ED (4.3 +/- 1.3) than in the control subjects (2.4 +/- 0.9) or psychogenic ED (2.0 +/- 0.6) groups (p < 0.01). Type II receptor expression was also significantly increased in vasculogenic ED (3.9 +/- 1.3) compared with control (2.2 +/- 0.7) and psychogenic (2.2 +/- 0.8) or neurogenic (2.6 +/- 1.3) ED (p < 0.01). Of the ED groups, both the hyperlipidaemia and the atherosclerosis patients showed significantly more fibrosis than those without the condition (p < 0.05). The abundance of collagen fibres correlated well with both TGF-beta1 expression (gamma = 0.81; p < 0.001) and receptor II expression (gamma = 0.83; p < 0.001). These results suggest that TGF-beta1 and its receptor II pathway are involved in cavernous fibrosis and ED in man. Patients with vascular risk factors such as hyperlipidaemia and atherosclerosis are liable to ED by activation of this pathway.

BackgroundMicropapillary variant of urothelial carcinoma (MPUC) showed distinct pathologic features and aggressive behavior. The cytologic findings of MPUC are still indistinct. In this study, we evaluated the cytological findings of MPUC compared with those of high-grade urothelial carcinoma (HGUC).MethodsThe voided urine cytology of 8 cases of MPUC and 8 cases of HGUC was reviewed. Following cytological parameters were evaluated: cellularity, background, number of small, tight papillary clusters, small acinar structure, scattered single cells, cytoplasmic features, nuclear-to-cytoplasmic ratio, nuclear pleomorphism, nuclear membrane irregularity, hyperchromasia, chromatin pattern and nucleoli.ResultsCompared to that of HGUC, cytology of MPUC showed large numbers of small, tight papillary clusters, small acinar structure, few numbers of single cells, and hyperchromatic nuclei. Other parameters were similar between the two groups; both groups showed similar cellularity, dense or vacuolated cytoplasm, moderate to severe nuclear pleomorphism, irregular nuclear membrane, coarse granular chromatin, and small and prominent nucleoli.ConclusionsThe urine cytology of MPUCs showed smaller and tighter papillary cell clusters, more small acinar structures, fewer numbers of scattered single cells, and more hyperchromatic nuclei than that of HGUC. These features can help to distinguish MPUC and HGUC and offer an early cytological diagnosis of MPUC.

Background: Liquid-based cytology (LBC) testing induces morphologic changes due to the use of specific fixatives and preparation techniques, and the cytologies of effusions determined in this manner differ morphologically from those of conventional cytopreparation (CCP) smear methods. We compared the cytologic features of pulmonary small cell carcinoma in effusion fluid using CCP and LBC preparations.Methods: Fifty-three malignant effusion specimens from 36 patients with small cell carcinoma were examined, including 41 LBCs from 27 patients and 12 CCPs from 9 patients.Results: LBC and CCP preparations preserved the typical features of small cell carcinoma, that is, nuclear molding, very high nuclear to cytoplasmic ratio and granular chromatin. The architectural patterns involved small cohesive clusters and chains with nuclear molding, tight three-dimensional clusters, or single cell dispersion were preserved in both preparations. Oval nuclei (83.3% vs 26.8%, P < .001) and a discernable rim of cytoplasm (66.7% vs 26.8%, P = .043) were more frequently identified in CCPs, whereas cellular degeneration and dry artifact were more frequent in LBC preparations (73.2% vs 8.3%, P < .001). LBC had a tendency to show frequent nuclear size variation (51.2% vs 25.0%) than CCP.Conclusion: LBC tends to show more degeneration and dry artifact with exaggerated irregular nuclear shape and nuclear size variation and scanty cytoplasm than CCP.Cytopathologists should be familiar with the cytomorphologic spectrum of this tumor in CCP and LBC prepared effusions. K E Y W O R D Sconventional cytology, effusion, liquid-based cytology, lung cancer, small cell carcinoma

Transforming growth factor (TGF) beta1 has been suggested to have an important role in cavernous fibrosis and resultant erectile dysfunction. For further elucidation of TGFbeta1 signaling in association with cavernous fibrosis, we developed a rat model of cavernous fibrosis using TGFbeta1-producing NIH 3T3 fibroblasts (NIH 3T3-TGFbeta1). The NIH 3T3-TGFbeta1 cells were injected into male Sprague-Dawley rats intracavernously. Masson trichrome staining at 20 days postinjection showed multiple fibrous scars in the rats injected with the NIH 3T3-TGFbeta1 cells (group 3), whereas no histological evidence of cavernous fibrosis was found in the control rats (group 1) or the recombinant human TGFbeta1 protein-injected rats (group 2). Immunohistochemical staining revealed a higher expression of TGFbeta1 and its type II receptor in group 3 than in groups 1 and 2. Electrostimulation of the cavernous nerve revealed that the maximal intracavernous pressure was significantly lower in group 3 than in groups 1 and 2 (P < 0.01). The expression of transgenic TGFbeta1 mRNA continued to 10 days after injection of the cells. The NIH 3T3-TGFbeta1 cells sufficiently induced relatively long-lasting cavernous fibrosis. This novel animal model may contribute to future investigations of the pathogenesis of penile fibrosis associated with TGFbeta1 signaling and the development of new therapeutics targeting this pathway.

Clear cell adenocarcinoma of the urethra is a rare disease entity with an uncertain histogenesis. Here, we present a case of primary clear cell adenocarcinoma of the female urethra with its cytological findings. A 54-year-old woman presented with a painless gross hematuria lasting 3 months. On vaginal sonography, there was a sausage-like, elongated mass in the urethra, measuring 3.8×4.3 cm. The voided urine cytology revealed small clusters of rounded or papillary cells. The necrotic debris and inflammatory cells were present within some clusters of tumor cells. These tumor cells were enlarged and had abundant clear or granular cytoplasm with cytoplasmic vacuoles. The nucleus was granular and contained vesicular chromatin with prominent nucleoli. The hobnail cells and hyaline globules were also present as in a histologic section. The histologic findings were compatible with clear cell adenocarcinoma. The tumor showed distinctive cytological features. Cytologically, however, it is necessary to make a differential diagnosis from other adenocarcinoma or high-grade urothelial carcinoma.