Evans Andrew J, Humphrey Peter A, Belani Jay, van der Kwast Theodorus H, Srigley John R
Department of Pathology and Laboratory Medicine, University Health Network, Mt Sinai Hospital, Toronto, Ontario, Canada.
Am J Surg Pathol. 2006 Jun;30(6):684-93. doi: 10.1097/00000478-200606000-00003.
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.
前列腺癌中的神经内分泌（NE）分化通常通过免疫组织化学在传统腺癌中作为单个细胞被检测到。前列腺NE肿瘤，如类癌或小细胞癌，较为罕见，而大细胞NE癌（LCNEC）仅在病例报告中有描述。我们鉴定出7例LCNEC，并汇总了它们的临床病理特征。6例有腺癌病史，接受激素治疗的平均时间为2.4年（范围：2至3年）。其余1例为新发LCNEC。5例LCNEC在姑息性经尿道切除标本中偶然被诊断出来。诊断为LCNEC时患者的平均年龄为67岁（范围：43至81岁）。LCNEC由实性片状和条索状细胞组成，细胞具有丰富的淡染至嗜双色性细胞质、大核、粗染色质和明显核仁，同时有活跃的有丝分裂活性和坏死灶。6例中有混合性腺癌灶，其中4例显示出激素治疗效果。LCNEC对CD56、CD57、嗜铬粒蛋白A、突触素和P504S/α甲基酰基辅酶A消旋酶呈强阳性。有强烈的bcl-2过表达、MIB1表达，且>50%的细胞核中有p53表达，前列腺特异性抗原和前列腺酸性磷酸酶呈局灶性阳性染色，雄激素受体染色阴性。6例患者有随访资料，所有患者在接受铂类化疗后平均7个月（范围：3至12个月）死于转移性疾病。前列腺LCNEC是一种独特的临床病理实体，通常在前列腺腺癌长期激素治疗后出现，可能是在治疗的选择压力下通过克隆进展产生的。
