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.
"Immunohistochemical examination usually shows negativity for AR as well as for prostate specific antigen (PSA), and positivity for NE markers with varied levels. NE tumors include small-cell carcinoma of the prostate (SCPC) (<0.1% of all diagnosed PCs) (10) as well as exceptionally rare tumors such as large cell NE carcinoma (a few cases worldwide) (11), and low-grade carcinoid, comparable to carcinoid in other locations (12). These tumors can be pure or admixed with prostatic adenocarcinomas. "
[Show abstract][Hide abstract] ABSTRACT: In normal prostate, neuroendocrine (NE) cells are rare and interspersed among the epithelium. These cells are believed to provide trophic signals to epithelial cell populations through the secretion of an abundance of neuropeptides that can diffuse to influence surrounding cells. In the setting of prostate cancer (PC), NE cells can also stimulate surrounding prostate adenocarcinoma cell growth, but in some cases adenocarcinoma cells themselves acquire NE characteristics. This epithelial plasticity is associated with decreased androgen receptor (AR) signaling and the accumulation of neuronal and stem cell characteristics. Transformation to an NE phenotype is one proposed mechanism of resistance to contemporary AR-targeted treatments, is associated with poor prognosis, and thought to represent up to 25% of lethal PCs. Importantly, the advent of high-throughput technologies has started to provide clues for understanding the complex molecular profiles of tumors exhibiting NE differentiation. Here, we discuss these recent advances, the multifaceted manner by which an NE-like state may arise during the different stages of disease progression, and the potential benefit of this knowledge for the management of patients with advanced PC.
Frontiers in Oncology 03/2014; 4:60. DOI:10.3389/fonc.2014.00060
"At least some of the cases with strong expression of NE markers, but morphologically imperfect for SCNC may be classified as large cell neuroendocrine carcinoma, which is very rarely diagnosed pathologically. The largest series of large cell neuroendocrine carcinoma was reported by Evans et al. who collected seven cases.20 Histologically, large cell neuroendocrine carcinoma contained 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. "
[Show abstract][Hide abstract] ABSTRACT: Most prostate cancers (PCas) are classified as acinar type (conventional) adenocarcinoma which are composed of tumor cells with luminal differentiation including the expression of androgen receptor (AR) and prostate-specific antigen (PSA). There are also scattered neuroendocrine (NE) cells in every case of adenocarcinoma. The NE cells are quiesecent, do not express AR or PSA, and their function remains unclear. We have demonstrated that IL8-CXCR2-P53 pathway provides a growth-inhibitory signal and keeps the NE cells in benign prostate and adenocarcinoma quiescent. Interestingly, some patients with a history of adenocarcinoma recur with small cell neuroendocrine carcinoma (SCNC) after hormonal therapy, and such tumors are composed of pure NE cells that are highly proliferative and aggressive, due to P53 mutation and inactivation of the IL8-CXCR2-P53 pathway. The incidence of SCNC will likely increase due to the widespread use of novel drugs that further inhibit AR function or intratumoral androgen synthesis. A phase II trial has demonstrated that platinum-based chemotherapy may be useful for such therapy-induced tumors.
Asian Journal of Andrology 02/2014; 16(4). DOI:10.4103/1008-682X.123669 · 2.60 Impact Factor
"LCNEC is one group of neuroendocrine carcinomas in the lungs and bronchial tubes that was first reported by Travis et al. in 1991 . Since then, it has been occasionally reported in various organs such as the uterus, thymus gland, stomach, bile duct, mammary gland, prostate gland, kidneys, and urinary bladder     . "
[Show abstract][Hide abstract] ABSTRACT: Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is very rare. Definite treatment strategy has not been established and prognosis of the disease is not clear yet. We report a case of primary LCNEC of the urinary bladder here with some review of the literature. The patient was a 84-year-old man. He underwent transurethral resection of bladder tumor (TURBT). Histological examination revealed a rosette arrangement of the tumor cells by HE staining and immunohistochemical study revealed positive CD 56, synaptophysin, and chromogranin A (LCNEC). After TURBT, he has no sign of recurrence for 8 months. We have to strictly observe the progress because LCNEC is very aggressive.
Case Reports in Medicine 04/2013; 2013:804136. DOI:10.1155/2013/804136
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