Undifferentiated carcinoma of the prostate with small cell features: immunohistochemical subtyping and reflections on histogenesis

Abstract

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.

Unusual subtypes of prostate cancer

“…Defined in this way, smallcell carcinoma is an uncommon prostatic tumor, but with important and distinctive clinicopathologic characteristics. [77][78][79][80][81][82][83][84][85][86][87] Clinically, small-cell carcinoma may arise de novo and be identified at the time of initial diagnosis. More often, however, the small-cell component manifests itself late in the course of a patient with documented metastatic prostate cancer.…”

“…3,19 It is important to remember that the diagnosis does not require proof of neuroendocrine differentiation by immunohistochemistry or electron microscopy, although the small-cell component often shows the characteristic dot-like cytokeratin immunopositivity and positivity for one or more neuroendocrine markers (chromogranin, synaptophysin, etc). 80,84,88 In over one-half of cases, a typical acinar component is present and in some instances apparent merging of one pattern with the other is seen (Figure 16). The acinar component is PSA-and PAP-positive, while the small-cell component is generally negative with these markers.…”

Carcinoma prostático de células pequeñas. Una histología atípica

“…Sin embargo la teoría más aceptada en la actualidad es la que asienta su origen en una célula madre o stem cell totipotencial del tejido prostático periureteral, que se diferenciaría a este tipo tumoral. Apoyarían este hecho datos como la ausencia de expresión de PSA, de receptores de andrógenos y el elevado nivel de proliferación observado en estas células 7 . Aunque la mayoría de los casos son de novo, hay un pequeño porcentaje de pacientes con diagnóstico de adenocarcinoma que presentan recurrencia …”

Small cell carcinoma of the prostate after high-dose-rate brachytherapy for low-risk prostatic adenocarcinoma

“…Neuroendocrine differentiation is characterized by the focal neuroendocrine cells commonly observed in conventional prostatic adenocarcinoma, but may also occur as rarer entities, including small cell carcinoma (SCC), carcinoid-like tumors and Paneth-like cells (3,4). Approximately 1% of prostate cancer in biopsies is reported to be SCC or neuroendocrine carcinoma, which is an aggressive form of cancer (5,6). The clinical features of SCC of the prostate include a markedly enlarged prostate, a disproportionately low prostate-specific antigen (PSA) level in the presence of metastatic disease, unresponsiveness to hormone therapy, visceral metastases and a high proportion of lytic to blastic bone lesions (7)(8)(9).…”