More than 95% of all carcinomas of the prostate are referred to as acinar, microacinar, usual, or conventional type. A minority have been classified as variants. Variants can vary in histologic appearance and divergent differentiation compared with usual acinar adenocarcinoma. Some variants constitute different types of carcinoma and are not adenocarcinomas. Variants that represent a challenge to diagnose include the deceptively benign-looking atrophic, pseudohyperplastic, microcystic, and foamy gland variants. The signet ring-like, pleomorphic giant cell, and sarcomatoid variants have worse prognosis than usual acinar adenocarcinoma. Some variants can occur after therapy, such endocrine and radiation therapy: squamous neoplasms, neuroendocrine tumors, sarcomatoid carcinoma (ie, carcinosarcoma), and pleomorphic giant cell variant. Neuroendocrine prostate cancer is an aggressive variant of prostate cancer that often arises in later stages of castration-resistant prostate cancer. We review some of the main morphologic features of variants of epithelial and neuroendocrine tumors of the prostate. Variants that can be a challenge in making a final diagnosis include deceptively benign-looking forms. Others have a worse prognosis than the usual acinar adenocarcinoma. Some variants can be seen after therapy and some constitute different types of carcinoma arising in the prostate and are not adenocarcinomas. Several mechanisms are involved in neuroendocrine differentiation and may represent future therapeutic targets in advanced disease.
