At an International Society of Urological Pathology consensus conference in 2005, the Gleason grading system for prostatic carcinoma underwent its first major revision. Gleason pattern 4 now includes most cribriform patterns and also fused and poorly formed glands. Our aims were to compare the grade distributions and assess the agreement between biopsy and radical prostatectomy specimens for the modified and conventional Gleason grading. More than 3,000 radical prostatectomy (RP), needle biopsies (NB) and transurethral resection specimens were assigned modified Gleason score (GS). In NB, modified GS 3 + 3 = 6 and 3 + 4 = 7a were almost equally common, while in RP, 3 + 4 = 7a was most common followed by 4 + 3 = 7b. After application of the modified GS on NB, a substantial shift in GS distribution occurred: The proportion of GS 6 and 7 were 48 and 26%, respectively, with conventional Gleason grading as compared to 22 and 68%, respectively, with modified grading. In 368 men, the agreement between NB and RP with a modified GS 6, 7a, 7b and 8-10 in NB was 28, 88, 68 and 64-100%, respectively. The overall agreement improved from 58 to 72% (p < 0.001) compared to conventional GS. The higher agreement with modified Gleason grading may facilitate therapeutic decisions.

To investigate the histogenesis of undifferentiated carcinoma of the prostate with small cell features we analysed the expression of neuroendocrine (NE) markers, the androgen receptor (AR), and prostate-specific antigen (PSA) in 19 undifferentiated carcinomas of the prostate. The proliferative activity (MIB-1/Ki67) of the tumours was examined, and the clinical data reviewed. The results identified two groups: carcinomas in group 1 were positive for PSA and AR and negative for NE markers. The mean MIB-1 labelling index (LI) was 34.8% and the mean serum PSA value 56.4 ng/ml. Two of the 7 patients died within 12 months after tumour diagnosis. The tumours in group 2 were NE differentiated small cell carcinomas (SCC), which were negative for PSA and AR. The mean MIB-1 LI was 82.6% and the mean serum PSA value 7.1 ng/ml. Seven of the 10 patients died between 2 and 12 months after tumour diagnosis. Positive staining for NE markers in combination with negative staining for PSA and AR and a high MIB-1 LI substantiated the diagnosis of a NE-SCC. We suggest that this tumour has a stem cell origin and does not derive from a dedifferentiated adenocarcinoma or from benign NE cells of the prostatic epithelium. This clear distinction of NE-SCC from NE-negative undifferentiated carcinoma is in accordance with the differing biological behaviour and response to therapy of the two tumour entities.

Since the introduction of immunohistochemistry, there is an increasing interest in neuroendocrine (NE) differentiation in prostatic carcinomas. Focal NE differentiation in prostatic adenocarcinomas is a very frequent finding. It is subject of numerous studies, since a negative impact on prognosis and an important role in antiandrogen therapy failure are suspected. NE-differentiated small-cell carcinoma is a very rare tumor comprising 0.5–2% of all prostatic carcinomas. Nevertheless, although very rare, it is of clinical importance because it is one of the most aggressive tumors of the prostate with a very poor prognosis. This review is focused on actual concepts of histogen-esis, cell biology, clinical implications, and possible future therapeutic perspectives of these two tumor entities.

IP is a benign lesion that lacks specific genetic alterations found in exophytic noninvasive papillary urothelial tumors. These lesions could be reactive in nature, perhaps secondary to chronic inflammation or a neoplastic process that lack specific genetic alterations. Nevertheless given the clinical and molecular data of this study a conservative clinical approach is appropriate.