Scibetta N., Unti E. U.O.C. di Anatomia ed Istologia Patologica, A.R.N.A.S. Ospedali Civico e G. di Cristina, Palermo

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1 Small cell carcinoma of the urinary bladder: a case report. 1) Scibetta N. 2)Unti E. U.O.C. Di Anatomia ed Istologia Patologica A.R.N.A.S. Ospedali Civico e G. di Cristina, Scibetta N., Unti E. OBJECTIVES Primary small cell carcinoma (SCC) of the urinary bladder is very rare and shows aggressive biological behavior and poorer prognosis than transitional cell carcinoma (TCC); 50% of them have areas of TCC. The authors reports herein a case of SCC of the urinary bladder with emphasis on immunohistochemistry and histogenesis. METHODS The patient was an 79 year-old man who presented hematuria for 2 months. Cystoscopy revealed an ulcerated solid lesion at dome, 5 cm in the greatest dimension.the examination of urinary citology specimen, prepared using cytocentrifuge technique and stained with May-Grunwald-Giemsa, Papanicolau and hematoxylin and eosin methods showed many small hyperchromatical cells similar lymphocites, mostly isolated or formed small groups. Focal molding was also noted in clusters. The cytomorphological pattern was interpreted as small and blue round cell tumor, but differential diagnosis was difficult. A bladder biopsy were performed. The patient underwent cystoprostatectomy. RESULTS Microscopically the tumor seemed to have invaded through the muscolaris propria into the adjacent fat. The bladder tumor is SCC in about 90% and TCC high grade (HG) in about 10% of the tumor. The SCC consisting of small cells with hyperchromatic nuclei, inconspicuous nucleoli, molded nuclei, scant cytoplasm. The TCC consisting in HG neoplasm. In addition to histological features, immunohistochemical stain were performed and the tumor cells of the SCC component were positive for synaptophysin, chromogranin, NSE, CD56, CAM5.2, CKAE1/AE3, CK8, CK18, negative for p63, TTF1, CK7, CK20, CD45, CK19, CK14, CK5/6, CK34BE12, CD117, PDGFRA, whereas the HG TCC stained selectively for CK7 and CK20. There were 4 out of 14 bilateral lymph-nodes involved only by the TCC.

2 Light microscopic examination shows small hyperchromatical tumor cell sheets invading through the muscolaris propria into the adjacent fat

3 High grade urothelial carcinoma High grade urothelial carcinoma with active mitosis

4 The right half of the section is small cell carcinoma component of the bladder tumor. The left half of the section is the high grade urothelial carcinoma The small cell carcinoma component demonstrated synaptophysin positivity. The urothelial component is negative

5 Small cell carcinoma component: positivity for CD56 The high grade urothelial carcinoma component of the bladder tumor demonstrated CK 7 positivity. The small cell carcinoma component is negative.

6 Lymph nodes involved by the urothelial component, positive for CK 7 CONCLUSIONS Malignant trasformation of neuroendocrine cells demonstrated in normal bladder and a unified concept of histogenesis of bladder cancer with a common origin from a multipotent mucosal stem cell are proposed. In our case a mixed SCC and TCC, with only lymph node metastases by TCC, and the expression of cytokeratin CAM5.2 in the small cell component supports the hypotesis of urotelial origin of SCC (metaplastic theory). Future molecular studies may delineate the relationship and, thus, pathogenesis of various form of bladder cancer may allow investigators to develop targeted therapy. References 1)Tadashi Terada, Small cell carcinoma of the urinary bladder, Int JClinExp Pathol.2012;5(6): )Donna E Hansel, Zhongfa Zhang, David Petillo and Bin T Teh, Gene profiling suggests a common evolution of bladder cancer subtypes, BMC Medical Genomics 2013 Oct 17;6:42.