Department of Anatomical Pathology, Laboratory Medicine Program, University Health Network and University of Toronto, Toronto, ON, Canada.
Department of Clinical Laboratory Genetics, Laboratory Medicine Program, University Health Network and University of Toronto, Toronto, ON, Canada.
Histopathology. 2019 Aug;75(2):247-253. doi: 10.1111/his.13875. Epub 2019 Jul 2.
Pure large-cell neuroendocrine carcinoma (LCNEC) is an uncommon but well-recognised primary tumour of the colorectum. It is characterised by large cells organised in a discernible neuroendocrine pattern with >20 mitoses per 10 high-power fields (HPFs), and/or a Ki67 index of >20%, and coagulative tumour necrosis is invariably present. These features are supplemented by positivity for neuroendocrine immunohistochemical markers. The aim of this study was to highlight three primary LCNECs of the colorectum.
All three patients were elderly females, aged 79, 85 and 89 years, who presented with ascending colon (two) tumours and a rectal tumour. All three tumours were large, ulcerated, polypoid masses (85, 76 and 55 mm; average size 72 mm) and were pT3N2. Histologically, the tumours were composed of packets and nests of cells with rosettes; other areas were in sheets composed of large cells. The mitotic counts were 23/10 HPFs, 27/10 HPFs and 24/10 HPFs, respectively. There was no mucosal dysplasia, precursor adenoma or associated adenocarcinoma component. All cases contained mainly peritumoral lymphoid aggregates, with smaller numbers of intratumoral lymphocytes. Synaptophysin, chromogranin (less intensely) and epithelial markers were expressed in all cases in the majority of the tumour cells. The Ki67 proliferative indices were 95%, 100%, and 80%, respectively. Two patients survived for 48 and 72 months, whereas the third is alive after 12 months without evidence of recurrence.
These unusual primary colorectal LCNECs with an accompanying lymphoid component are characterised by loss of MLH1/PMS2, BRAF mutation, microsatellite instability, and Epstein-Barr virus negativity. The patients also have better overall survival than those with LCNECs lacking an accompanying lymphoid component.
纯大细胞神经内分泌癌（LCNEC）是一种罕见但公认的结直肠原发性肿瘤。它的特点是大细胞以可识别的神经内分泌模式排列，每 10 个高倍视野（HPF）中有超过 20 个有丝分裂，或 Ki67 指数>20%，并且总是存在凝固性肿瘤坏死。这些特征通过神经内分泌免疫组织化学标志物的阳性表达得到补充。本研究的目的是强调结直肠的三个原发性 LCNEC。
所有三名患者均为老年女性，年龄分别为 79 岁、85 岁和 89 岁，均患有升结肠癌（2 例）和直肠肿瘤。所有三个肿瘤均为大的、溃疡性、息肉样肿块（85、76 和 55mm；平均大小 72mm），且均为 pT3N2。组织学上，肿瘤由细胞包块和巢组成，形成玫瑰花结；其他区域则由大细胞组成的片状结构组成。有丝分裂计数分别为 23/10 HPFs、27/10 HPFs 和 24/10 HPFs。没有黏膜发育不良、前体腺瘤或相关腺癌成分。所有病例均主要含有肿瘤周围的淋巴样聚集物，肿瘤内淋巴细胞较少。所有病例中的大多数肿瘤细胞均表达突触素、嗜铬粒蛋白（表达较弱）和上皮标志物。Ki67 增殖指数分别为 95%、100%和 80%。两名患者分别存活 48 个月和 72 个月，而第三名患者在 12 个月后无复发迹象仍存活。
这些罕见的伴有淋巴样成分的原发性结直肠 LCNEC 具有 MLH1/PMS2 缺失、BRAF 突变、微卫星不稳定性和 EBV 阴性的特点。与缺乏伴随淋巴样成分的 LCNEC 相比，这些患者的总体生存情况更好。
