Neuroendocrine differentiation of prostate cancer: a review

Abstract

Neuroendocrine cells are one of the epithelial populations in the prostate. Neuroendocrine differentiation (NED) has been observed in prostate cancer. In addition to small cell neuroendocrine carcinomas and carcinoid tumors of the prostate, prostatic adenocarcinomas may have NED. The incidence and clinical relevance of NED in prostatic adenocarcinoma is not clearly understood because of conflicting results in the reported studies, and evaluation of NED is not routinely performed in clinical practice. This review is an overall synthesis with an aim to develop a more comprehensive understanding and practical approach towards the current knowledge of neuroendocrine differentiation. In this review we are stratifying these lesions into separate subtypes based on histologic parameters such as tumor morphology, neuroendocrine cell density and distribution and clinical parameters. We also want to identify current controversies and confusing issues not totally resolved in this topic for further investigations. Eventually a clearer understanding of this phenomenon and appropriate handling NED in prostate cancer will benefit clinical practice.

Keywords: Neuroendocrine differentiation; prostate.

Figure 1

Generally, neuroendocrine cells cannot be recognized in a benign prostatic gland with routine H&E staining (A). However, the neuroendocrine immunostains such as chromogranin (B) or synaptophysin (C) can highlight the neuroendocrine cells which are typically situated in the basal cell compartment with cell processes projecting into the layer of luminal cells.

Figure 2

Small cell carcinoma of the prostate seen on a needle core biopsy (A). Similar to pulmonary counterpart, these tumor cells display characteristic “small blue cell” appearance (B), confirmed by neuroendocrine marker synaptophysin (C).

Figure 3

Large cell neuroendocrine carcinoma of the prostate shows typical “salt-and-pepper” chromatin patterns, but the tumor cells are much larger than the ones in small cell carcinoma (A). Neuroendocrine marker such as chromogranin (B) is necessary.

Figure 4

Carcinoid tumor of the prostate is rare, and can be either primary or secondary to a metastasis from the gastrointestinal tract. Carcinoid tumor (A) is characteristized by large islands of cells with low nuclear grade and salt and pepper chromatin. Neuroendocrine markers such as synaptophysin (B) are positive although these immunomarkers are not usually needed to confirm the diagnosis given its classic morphologic features.

Figure 5

Prostatic adenocarcinoma with neuroendocrine differentiation on H&E (A) which is confirmed by strong positive staining for chromogranin (B).

Figure 6

Higher Gleason grade prostatic adenocarcinoma with no obvious histological evidence of neuroendocrine differentiation on H&E (A) but with positive staining for chromogranin (B) and NSE (C).

Figure 7

Paneth cell differentiation of prostatic adenocarcinoma is characterized by the presence of large eosinophilic granules in the cytoplasm of tumor cells (A), which are positive for neuroendocrine markers such as chromogranin (B).