Large cell neuroendocrine carcinoma of prostate: a clinicopathologic summary of 7 cases of a rare manifestation of advanced prostate cancer.
ABSTRACT Neuroendocrine (NE) differentiation in prostate cancer is typically detected by immunohistochemistry as single cells in conventional adenocarcinoma. Prostatic NE tumors, such as carcinoid or small cell carcinoma, are rare and large cell NE carcinoma (LCNEC) is described only in case reports. We identified 7 cases of LCNEC and compiled their clinicopathologic characteristics. In 6 cases, there was a history of adenocarcinoma treated with hormone therapy for a mean of 2.4 years (range: 2 to 3 y). The remaining case was de novo LCNEC. LCNEC was incidentally diagnosed in palliative transurethral resection specimens in 5 cases. The mean patient age at diagnosis with LCNEC was 67 years (range: 43 to 81 y). LCNEC comprised solid sheets and ribbons of cells with abundant pale to amphophilic cytoplasm, large nuclei with coarse chromatin and prominent nucleoli along with brisk mitotic activity and foci of necrosis. In 6 cases, there were foci of admixed adenocarcinoma, 4 of which showed hormone therapy effects. LCNEC was strongly positive for CD56, CD57, chromogranin A, synaptophysin, and P504S/alpha methylacyl CoA racemase. There was strong bcl-2 overexpression, expression of MIB1, and p53 in >50% of nuclei, focally positive staining for prostate specific antigen and prostatic acid phosphatase and negative androgen receptor staining. Follow-up was available for 6 patients, all of who died with metastatic disease at mean of 7 months (range: 3 to 12 mo) after platinum-based chemotherapy. LCNEC of prostate is a distinct clinicopathologic entity that typically manifests after long-term hormonal therapy for prostatic adenocarcinoma and likely arises through clonal progression under the selection pressure of therapy.
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ABSTRACT: Small cell carcinoma of the prostate (PSCC) is a rare and highly aggressive malignancy with a dismal prognosis. Most patients present with advanced disease, including metastases to bone, viscera, and the central nervous system. Histologically, PSCC is indistinguishable from its pulmonary counterpart. Although PSCC may occur in pure form, as in small cell lung carcinoma, it also occurs in conjunction with conventional glandular prostate carcinoma, and may evolve from conventional adenocarcinoma during the course of hormonal therapy. Immunohistochemical staining is extremely helpful in establishing the diagnosis, a prerequisite, as in small cell lung cancer, for optimal therapeutic strategy. Currently, combinations of surgical resection, chemotherapy, and radiation therapy represent the main treatment options. Improvement in survival may depend upon the identiﬁcation of new molecular markers to facilitate earlier diagnosis and the development of novel targeted therapies. This review will discuss general aspects of PSCC, focusing on ways in which our understanding of PSCC has been advanced by studies of the histopathologic, immunohistochemical and molecular alterations in this disease.Histology and histopathology 11/2014; · 2.24 Impact Factor
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ABSTRACT: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that commonly arises in later stages of castration resistant prostate cancer (CRPC) The detection of NEPC has clinical implications as these patients are often treated with platinum chemotherapy rather than with androgen receptor targeted therapies. The poor molecular characterization of NEPC accounts in part for the lack of disease specific therapeutics. Several mechanisms are involved in NE differentiation, including inflammation and autophagy, and may actually represent future therapeutic targets for advanced NEPC patients. Furthermore, a growing body of evidence suggests a potential role of circulating tumor cells in the early diagnosis and treatment of NEPC. Here we summarize the recent findings on NEPC pathogenesis and we discuss the ongoing clinical trials and future perspectives for the treatment of NEPC patients. Copyright © 2014. Published by Elsevier B.V.Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 11/2014; 1846(2):630-637. DOI:10.1016/j.bbcan.2014.10.008 · 7.58 Impact Factor
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ABSTRACT: Large cell neuroendocrine carcinoma (LCNEC) of the ovary is a rare diagnosis and only a few dozen cases have been reported in the literature. It is characterized by large pleiomorphic cells with large round or oval nuclei, presence of mitoses and staining for neuroendocrine (NE) markers such as chromogranin A, synaptophysin, neuron specific enolase. This editorial gives a brief overview of this histologic type of ovarian carcinomas. LCNEC of the ovary is a pathologic entity that may not be diagnosed purely on clinical grounds due to the similarity of its clinical features with those of the more common epithelial ovarian cancers. Nevertheless the diagnosis is worth-making from a practical point of view in order to consider treatments tailored towards the NE component if it is dominant or it becomes dominant during the natural evolution of the disease. Establishment of an international tumor registry with an accompanying tumor tissue bank of ovarian LCNEC could be a means of obtaining further knowledge on clinical characteristics and advance research on this rare entity. This will further inform on treatment strategies and could identify future molecular treatment targets.05/2014; 5(2):36-8. DOI:10.5306/wjco.v5.i2.36