Tornóczky Tamás, Kálmán Endre, Kajtár Pál G, Nyári Tibor, Pearson Andrew D J, Tweddle Deborah A, Board Julian, Shimada Hiroyuki
Department of Pathology, Faculty of Medicine, Medical and Health Sciences Center, University of Pécs, Szigeti út 12, H-7643 Pécs, Hungary.
Cancer. 2004 Jan 15;100(2):390-7. doi: 10.1002/cncr.20005.
Among cases of undifferentiated and poorly differentiated tumors in the neuroblastoma (Schwannian stroma-poor) category, the authors histologically identified a group of rare tumors, known as large cell neuroblastomas (LCNs), that are composed of large cells with sharply outlined nuclear membranes and 1-4 prominent nucleoli.
Histologic and immunohistochemical features of LCN were characterized. Morphologic characteristics, clinical features, and MYCN status were compared between LCNs and conventional neuroblastomas documented in the files of two European centers (the Sir James Spence Institute of Child Health, Royal Victoria Infirmary, University of Newcastle, Newcastle upon Tyne, United Kingdom, and the Medical and Health Sciences Center, University of Pécs, Pécs, Hungary).
Of 92 peripheral neuroblastic tumors (pNTs; including neuroblastoma [n = 81]; ganglioneuroblastoma, intermixed [n = 6]; and ganglioneuroblastoma, nodular [n = 5]), 7 (7.6%) qualified as LCN. All 7 LCNs were classified as having unfavorable histology (UH) according to the International Neuroblastoma Pathology Classification. The LCNs were composed of monomorphous undifferentiated neuroblasts and shared certain histologic features, such as a high incidence of high mitosis-karyorrhexis index and a low incidence of calcification, with other neuroblastomas in the conventional UH (c-UH) group. These features were significantly different from those of neuroblastomas in the conventional favorable histology (c-FH) group. On immunohistochemical analysis, LCN tumor cells were positive for neuron-specific enolase (5 of 5 cases), protein gene product 9.5 (5 of 5 cases), synaptophysin (5 of 5 cases), tyrosine hydroxylase (focally in 3 of 3 cases), and NB84 (3 of 5 cases) and negative for CD99. Patients with LCN and patients with c-UH disease had similar clinical features (diagnosis at age > 1 year, often with distant metastasis). The clinical features of these patients also were significantly different from those of patients with c-FH disease. Further analysis demonstrated that the LCN group was significantly different from both the c-UH and c-FH groups with respect to MYCN status (MYCN amplification, 4 of 5 vs. 3 of 17 vs. 8 of 17, respectively; P = 0.023) and survival rate (4-year expected survival, 0% vs. 71% vs. 17%, respectively; P < 0.01).
Because of its unique clinicopathologic features, the authors propose that LCN be recognized as a distinct entity within the undifferentiated and poorly differentiated subtypes of the neuroblastoma category.
在神经母细胞瘤（少施万细胞基质型）类别中未分化和低分化肿瘤病例中，作者在组织学上鉴定出一组罕见肿瘤，称为大细胞神经母细胞瘤（LCN），其由具有轮廓清晰核膜和1 - 4个显著核仁的大细胞组成。
对LCN的组织学和免疫组化特征进行了表征。比较了两个欧洲中心（英国泰恩河畔纽卡斯尔大学皇家维多利亚医院詹姆斯·斯彭斯儿童健康研究所和匈牙利佩奇大学医学与健康科学中心）档案中记录的LCN与传统神经母细胞瘤的形态学特征、临床特征及MYCN状态。
在92例周围神经母细胞瘤（pNT；包括神经母细胞瘤[n = 81]；混合型神经节神经母细胞瘤[n = 6]；结节型神经节神经母细胞瘤[n = 5]）中，7例（7.6%）符合LCN标准。根据国际神经母细胞瘤病理分类，所有7例LCN均被归类为组织学不良（UH）。LCN由单形性未分化神经母细胞组成，与传统UH（c - UH）组中的其他神经母细胞瘤具有某些组织学特征，如高有丝分裂 - 核溶解指数发生率和低钙化发生率。这些特征与传统组织学良好（c - FH）组中的神经母细胞瘤显著不同。免疫组化分析显示，LCN肿瘤细胞神经元特异性烯醇化酶呈阳性（5例中的5例）、蛋白基因产物9.5呈阳性（5例中的5例）、突触素呈阳性（5例中的5例）、酪氨酸羟化酶呈阳性（3例中的3例局部阳性）、NB84呈阳性（5例中的3例），而CD99呈阴性。LCN患者和c - UH疾病患者具有相似的临床特征（诊断年龄>1岁，常伴有远处转移）。这些患者的临床特征也与c - FH疾病患者显著不同。进一步分析表明，LCN组在MYCN状态（MYCN扩增，分别为5例中的4例、17例中的3例、17例中的8例；P = 0.023）和生存率（4年预期生存率，分别为0%、71%、17%；P < 0.01）方面与c - UH组和c - FH组均有显著差异。
由于其独特的临床病理特征，作者建议将LCN识别为神经母细胞瘤类别中未分化和低分化亚型内的一个独特实体。
