Literature Review: Types of Neuroendocrine Differentiation

Small Cell Carcinoma

Small cell carcinoma of the prostate is rather rare, particularly in its pure form, and accounts for no more than 1 percent of all carcinomas of the prostate. They are aggressive tumors which often present at advanced stages or as metastatic diseases (Erasmus et al, 2002) and occasionally associated with paraneoplastic syndromes (Kawai et al, 2003). Some small cell carcinomas represent recurrent tumors after hormonal therapy for conventional adenocarcinomas of the prostate (Tanaka et al, 2001; Miyoshi et al, 2001; Spieth et al, 2002). More commonly, small cell carcinoma is present as a component of mixed tumors which also contain a component of conventional adenocarcinoma. Histologically, small cell carcinomas of the prostate are similar to the more common small cell carcinomas of the lung. They are characterized by the following features: 1) solid, sheet-like growth pattern, often with areas of tumor necrosis; 2) small, round to spindle cells with scant cytoplasm, high nuclear/cytoplasmic ration and ill-defined borders; 3) hyperchromatic nuclei with finely granular chromatin and nuclear molding; 4) absent or inconspicuous nucleoli, and 5) high mitotic rate (> 10/10 HPF's). (Figure 3A).

The solid growth pattern of small cell carcinoma of the prostate makes distinction of such tumors from Gleason grade 5 adenocarcinomas difficult at times, for which immunohistochemical study may be of help. Small cell carcinomas are often positive for NE markers chromogranin-A (Figure 3B), synaptophysin and NSE although one or more of these markers may be negative in any given case. Like small cell carcinomas of the lung, tumor cells often show dot-like cytokeratin staining pattern and are often positive for TTF-1. In contrast to prostatic adenocarcinoma, tumor cells of small cell carcinoma are usually negative for androgen receptor and PSA but exceptions exist (Kawai et al, 2003). It is important to keep in mind that immunohistochemical profile varies from case to case and morphology remains the gold standard for pathological diagnosis.

The prognosis for small cell carcinomas is poor and the disease is usually rapidly fatal (Papandreou et al, 2002). Hormonal therapy is not effective in treating such tumors and neither is surgery. The general response to chemotherapy, the main form of therapy for small cell carcinoma, is some initial response but progressing to a rather rapid downhill course (Moore et al, 1992, Rubinstein et al, 1997, Helpap, 2002).

Carcinoid Tumors

Carcinoid tumors have also been reported in the prostate, which are exceedingly rare. These tumors show complete NE differentiation and have morphologic features similar to carcinoid tumors of the lung or GI tract. In comparison to small cell carcinomas, the tumor cells have more abundant cytoplasm, rare mitotic figures and no tumor necrosis. Like small cell carcinomas, carcinoid tumors often exist as a component of mixed tumors also containing conventional adenocarcinoma (Ghannoum et al, 2004).

Literature Review Next Section: Focal NED in Prostate Cancer

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