Sugawa Masahiro, Fukuoka Kohei, Mori Makiko, Arakawa Yuki, Tanami Yutaka, Nobusawa Sumihito, Hirato Junko, Nakazawa Atsuko, Kurihara Jun, Koh Katsuyoshi
1Department of Hematology/Oncology and.
2Department of Radiology, Saitama Children's Medical Center, Saitama.
J Neurosurg Pediatr. 2022 May 20;30(2):232-238. doi: 10.3171/2022.4.PEDS21542. Print 2022 Aug 1.
Embryonal tumor with multilayered rosettes (ETMR) is one of the childhood central nervous system tumors with the poorest prognosis; thus, establishing an optimal treatment strategy is essential, However, because of the low incidence and molecular heterogeneity of the tumor, the optimal treatment has not yet been determined. In this study the authors evaluated the prognostic impact of a multimodal treatment approach in patients with ETMR.
The authors evaluated 4 patients with ETMR at their institution who showed varied clinical features and also conducted clinical characterization and prognostic analysis of previously reported cases of the ETMR-presenting locus 19q13.42 with a chromosome 19 microRNA cluster (C19MC) amplification, which is known to be a diagnostic hallmark of the tumor.
Of the 4 patients with ETMR in the authors' institution, in 1 case the patient's tumor showed a neuroblastoma-like appearance without multilayered rosettes; however, the diagnosis was confirmed by the presence of amplified C19MC. From a clinical standpoint, 2 patients who underwent gross-total resection (GTR) of the tumor and chemotherapy followed by high-dose chemotherapy (HDC) had long-term complete remission with or without local irradiation. In the multivariate analysis of 43 cases with C19MC-altered ETMR reported in the literature, HDC and local irradiation were significantly correlated with better event-free survival (HR 0.17, p = 0.0087; HR 0.17, p = 0.010) and overall survival (OS) (HR 0.29, p = 0.023; HR 0.28, p = 0.019), respectively. GTR was also correlated with better OS (HR 0.40, p = 0.039).
This case series demonstrated pathological and clinical heterogeneity among ETMR cases and the diagnostic importance of the molecular genetic approach among embryonal tumors, particularly during infancy. Based on the results of the analysis of molecularly uniformed ETMR cases, multimodal treatment may play a significant role in the prognosis of these tumors.
具有多层菊形团的胚胎性肿瘤（ETMR）是儿童中枢神经系统肿瘤中预后最差的肿瘤之一；因此，制定最佳治疗策略至关重要。然而，由于该肿瘤发病率低且分子异质性高，最佳治疗方案尚未确定。在本研究中，作者评估了多模式治疗方法对ETMR患者预后的影响。
作者评估了其机构中4例具有不同临床特征的ETMR患者，并对先前报道的位于19q13.42且伴有19号染色体微小RNA簇（C19MC）扩增的ETMR病例进行了临床特征分析和预后分析，已知C19MC扩增是该肿瘤的诊断标志。
在作者机构的4例ETMR患者中，1例患者的肿瘤表现为无多层菊形团的神经母细胞瘤样外观；然而，C19MC扩增证实了诊断。从临床角度来看，2例接受肿瘤全切除（GTR）及化疗随后进行大剂量化疗（HDC）的患者，无论是否接受局部放疗，均实现了长期完全缓解。在对文献报道的43例C19MC改变的ETMR病例进行的多变量分析中，HDC和局部放疗分别与更好的无事件生存期（HR 0.17，p = 0.0087；HR 0.17，p = 0.010）和总生存期（OS）（HR 0.29，p = 0.023；HR 0.28，p = 0.019）显著相关。GTR也与更好的OS相关（HR 0.40，p = 0.039）。
该病例系列证明了ETMR病例之间的病理和临床异质性以及分子遗传学方法在胚胎性肿瘤诊断中的重要性，尤其是在婴儿期。基于分子特征一致的ETMR病例的分析结果，多模式治疗可能对这些肿瘤的预后起到重要作用。
