RESEARCH Immunohistochemical Profile of Urothelial and Small Cell Carcinomas of the Bladder Ma Jesús Fernández-Aceñero & Sharon Córdova & Félix Manzarbeitia & Camino Medina Received: 27 May 2010 / Accepted: 24 November 2010 / Published online: 4 January 2011 # Arányi Lajos Foundation 2011 Abstract Small cell carcinoma of the bladder is an uncommon and rather aggressive bladder tumor, represent- ing less than 1% of all vesical tumors. Small cell carcinoma of different organs has been shown to express markers of neuroendocrine differentiation, and also thyroid transcrip- tion factor 1 (TTF-1). TTF-1 is a transcription factor and its expression has been shown mainly in pulmonary small cell carcinomas and adenocarcinomas and in thyroid tumors. Although it was initially proposed as a useful marker to delineate the origin of metastatic adenocarcinomas from the lung, its expression is being increasingly reported in tumors from different origins. The goal of this review is to analyse the immunohistochemical profile of small cell carcinoma of the bladder and to compare it to classical urothelial cell carcinomas. With this aim we have reviewed the small cell bladder carcinomas diagnosed in a single tertiary hospital in Madrid (Fundación Jiménez Díaz) in the last 12 years. We have found 6 pure small cell carcinomas and performed a wide panel of immunohistochemistry, including cytoker- atins 7 and 20, enolase, chromogranin, synaptophysin, CD56 and TTF-1 to these tumors and also to 30 high grade urothelial cell carcinomas of usual type. Only one of our small cell carcinoma cases showed positivity for TTF-1, while five expressed CD56 and four neuron-specific enolase. None of our cases expressed cytokeratin 20 or 7. To our surprise we found a case of conventional urothelial cell carcinoma expressing focally TTF-1. These results are in accordance with the current literature, although our rate of TTF-1 expression (16.6%) is on the low end of the spectrum. Keywords Urothelial cell carcinoma . Small cell carcinoma . Neuroendocrine tumors . TTF-1 . Immunohistochemistry Introduction Small cell carcinoma of the bladder is a rare aggressive neoplasm, comprising less than 1% of all bladder carcino- mas in most series [1, 2]. These tumors are morphologically identical to their more common pulmonary counterparts and a neuroendocrine origin has been postulated [3]. The frequent association with otherwise usual urothelial cell carcinomas has led some authors to postulate a common origin for both tumors, suggesting small cell presence only represents a dedifferentiation within urothelial cell lesions [4]. Most reports agree that these tumors behave aggre- sively and can kill the patient despite therapy, most like its pulmonary counterpart. Several studies have analysed the immunohistochemical profile of small cell carcinomas of the bladder [5, 6] and showed a variable rate of positivity for neuroendocrine markers and thyroid transcription factor 1 (TTF-1). The aim of the present study is to review our experience with small cell carcinomas of the bladder and to compare them with usual urothelial cell carcinomas. The authors acknowledge no conflict of interest in the elaboration of the present manuscript. M. J. Fernández-Aceñero : S. Córdova : F. Manzarbeitia : C. Medina Department of Surgical Pathology, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Capio Group Spain, Madrid, Spain M. J. Fernández-Aceñero (*) Fundación Jiménez Díaz, Avda Reyes Católicos s/n, 28040 Madrid, Spain e-mail: mgg10167@gmail.com Pathol. Oncol. Res. (2011) 17:519–523 DOI 10.1007/s12253-010-9341-z