ORIGINAL ARTICLE Prostate cancer with small-cell morphology: An immunophenotypic subdivision CONSTANTINA PETRAKI 1 , MICHAEL VASLAMATZIS 2 , KALLIOPI PETRAKI 1 , KYRIAKOS REVELOS 1 , NEKTARIOS ALEVIZOPOULOS 2 , PANAGIOTIS PAPANASTASIOU 3 & ALKIVIADIS GREGORAKIS 3 Departments of 1 Pathology, 2 Oncology and 3 Urology, Evangelismos Hospital, Athens, Greece Abstract Objective. To study the immunophenotypic characteristics and clinical outcome of morphologically undifferentiated prostatic carcinoma with small-cell morphology (U-PC-SCM). Material and methods. Sixteen patients with U-PC-SCM were enrolled. The streptavidin  /biotin complex immunohistochemical method was used on paraffin-embedded tissue sections to test positivity for prostate-specific antigen, prostate-specific acid phosphatase, CD57, androgen receptors, CK8-18, epithelial membrane antigen, carcinoembryonic antigen, CD56, neuron-specific enolase, chromogranin, synaptophysin, serotonin, various hormones, thyroid transcriptional factor-1 and Ki-67/MIB1. Results. Based on immunophenotypic criteria, we identified two groups of patients. The final diagnosis was U-PC (Gleason score 10) in Group 1 (n  /9) and pure or mixed neuroendocrine small-cell carcinoma in Group 2 (n  /7). Group 1 underwent total androgen blockade (TAB) with no major response and had a median survival of 9 months. In Group 2, three patients underwent TAB, two of whom died of progressive disease. The third patient showed a partial response (PR) for 18 months but eventually relapsed with liver metastatic lesions. He was then treated with cisplatin /etoposide and showed a PR for 3 months and survived for 5 months after the initiation of the second-line chemotherapy (CTH) treatment. The other four patients received six cycles of cisplatin /etoposide. There were two complete responses of ! /14 and ! /22 months, respectively and 2 PRs of 11 and 17 months, respectively, the partial responders surviving for 14 and 21 months, respectively. Conclusion. U-PC-SCM with a neuroendocrine immunophenotype is a histogenetically distinct entity with different clinical and laboratory manifestations which responds well to a cisplatin /etoposide CTH regimen. Key Words: Chemotherapy, neuroendocrine differentiation, prostate cancer, small-cell morphology Introduction Poorly differentiated (Gleason score 10) adenocarci- noma of the prostate may have the morphology of an anaplastic (‘‘undifferentiated’’) small-cell carcinoma (SCC). In the great majority of cases, this distinct histological diagnosis concerns carcinomas with distant metastases which, until recently, were all treated with total androgen blockade (TAB) with a poor response and a low survival rate [1  /3]. Recently, with the introduction of immunohisto- chemistry, it seems that ‘‘undifferentiated’’ prostate carcinomas with small-cell morphology (U-PC- SCM) form a heterogeneous group, and that the subgrouping has a therapeutic prognostic signifi- cance [3,4]. The aim of this study is to distinguish those U-PC-SCMs with the immunophenotype of a neuroendocrine SCC, which should be treated in the same way as pulmonary and extrapulmonary SCC. The clinical, morphological and immunophenotypic characteristics of the tumours of 16 patients are studied, the treatment results are evaluated and a comparison is made with data from the literature. Material and methods Among 1650 adenocarcinomas of the prostate that were diagnosed in the Pathology Department of Evangelismos Hospital between January 1998 and December 2002, 16 cases (0.97%) of U-PC-SCM (Gleason score 10), with varying percentages of Correspondence: Constantina Petraki, Phedriadon 109, 11364 Athens, Greece. Tel:  /30 210 8628895. Fax:  /30 210 8628790. E-mail: nellitsa@vip.gr Scandinavian Journal of Urology and Nephrology, 2005; 39: 455  /463 (Received 18 May 2004; accepted 20 May 2005) ISSN 0036-5599 print/ISSN 1651-2065 online # 2005 Taylor & Francis DOI: 10.1080/00365590500199855