神经纤维瘤病1(NF1)患者发展为多发性神经纤维瘤,8%至15%的患者在其一生中经历恶性周围神经鞘瘤(MPNST)。转型的预测,通常来自丛状神经纤维瘤,在临床和组织学上具有挑战性。在本概述中,在2016年10月的一次共识会议之后,我们概述了神经纤维瘤恶性转化的组织病理学特征和分子机制.仅核异型通常是微不足道的。然而,与非典型的,神经纤维瘤结构丧失,高细胞性,和/或有丝分裂活性>1/50但<3/10的高功率场,这些发现令人担忧的恶性肿瘤。我们建议将“不确定生物潜能的非典型神经纤维瘤(ANNUBP)”一词用于显示至少2种特征的病变。这种诊断应该提示额外的采样,临床相关性,而且可能,专家病理学咨询。目前,此类肿瘤不一致地被诊断为非典型神经纤维瘤或低度MPNST。大多数由神经纤维瘤引起的MPNSTs是高级别肉瘤,诊断困难小。尽管具有3-9个有丝分裂/10个高倍视野的罕见非坏死性肿瘤可以被识别为低度变异。尽管神经纤维瘤含有大量的S100蛋白/SOX10阳性的雪旺细胞和CD34阳性的成纤维细胞,MPNST中两种成分均减少或不存在。p16/CDKN2A表达缺失,升高的Ki67标签,和广泛的p53核阳性也是MPNST的特征,在某种程度上可能已经发生在生物学潜能不确定的非典型神经纤维瘤中。三甲基化组蛋白3赖氨酸27表达的完全丧失可能更可靠,在大约一半的MPNSTs中被免疫组织化学检测到。相关临床病理,放射学,基因研究应该增加我们对神经纤维瘤恶变的认识,希望尽快改善诊断和治疗。
Patients with neurofibromatosis 1 (NF1) develop multiple neurofibromas, with 8% to 15% of patients experiencing malignant peripheral nerve sheath tumor (MPNST) during their lifetime. Prediction of transformation, typically from plexiform
neurofibroma, is clinically and histologically challenging. In this overview, after a
consensus meeting in October 2016, we outline the histopathologic features and molecular mechanisms involved in the malignant transformation of neurofibromas. Nuclear atypia alone is generally insignificant. However, with atypia, loss of
neurofibroma architecture, high cellularity, and/or mitotic activity >1/50 but <3/10 high-power fields, the findings are worrisome for malignancy. We propose the term \"atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP)\" for lesions displaying at least 2 of these features. This diagnosis should prompt additional sampling, clinical correlation, and possibly, expert pathology consultation. Currently, such tumors are diagnosed inconsistently as atypical
neurofibroma or low-grade MPNST. Most MPNSTs arising from neurofibromas are high-grade sarcomas and pose little diagnostic difficulty, although rare nonnecrotic tumors with 3-9 mitoses/10 high-power fields can be recognized as low-grade variants. Although neurofibromas contain numerous S100 protein/SOX10-positive Schwann cells and CD34-positive fibroblasts, both components are reduced or absent in MPNST. Loss of p16/CDKN2A expression, elevated Ki67 labeling, and extensive nuclear p53 positivity are also features of MPNST that can to some degree already occur in atypical neurofibromatous neoplasms of uncertain biologic potential. Complete loss of trimethylated histone 3 lysine 27 expression is potentially more reliable, being immunohistochemically detectable in about half of MPNSTs. Correlated clinicopathological, radiologic, and genetic studies should increase our understanding of malignant transformation in neurofibromas, hopefully improving diagnosis and treatment soon.