Abstract：
This study investigated the clinicopathological, immunohistochemical, and molecular features of primary leptomeningeal melanocytic neoplasms (LMNs). Twelve LMN cases were retrospectively reviewed. We performed Fluorescence in-situ hybridization (including a 4-probe FISH assay with CDKN2A and MYC assay) and Next-Generation sequencing analyses on available cases. Histologically, 2 tumours were classified as melanocytomas (MC), 2 as intermediate-grade melanocytomas (IMC), and 8 as leptomeningeal melanomas (LMM). Two rare cases of LMM were associated with large plaque-like blue nevus. One MC case was associated with Ota. Ten cases (83.3%) showed melanocytic cells with benign features diffusely proliferating within the meninges. The Ki-67 in three categories differed (MC 0-1%, IMC 0-3%, LMM 3-10%). 57.1% of LMM cases (4/7) were positive for FISH. Nine of 10 tumours harboured activating hotspot mutations in GNAQ, GNA11, or PLCB4. Additional mutations of EIF1AX, SF3B1, or BAP1 were found in 40%, 30%, and 10% of tumours, respectively. During the follow-up (median = 43 months), 5 LMM patients experienced recurrence and/or metastasis, 3 of them died of the disease and the other 2 are alive with the tumour. Our study is by far the first cohort of LMN cases tested by FISH. In addition to morphological indicators including necrosis and mitotic figures, using a combination of Ki-67 and FISH helps to differentiate between IMC and LMM, especially in LMM cases with less pleomorphic features. SF3B1 mutation is first described in 2 cases of plaque-type blue nevus associated with LMM. Patients with SF3B1 mutation might be related to poor prognosis in LMN.
摘要：
这项研究调查了临床病理，免疫组织化学，和原发性软脑膜黑素细胞肿瘤（LMNs）的分子特征。对12例LMN病例进行回顾性分析。我们对可用病例进行了荧光原位杂交（包括CDKN2A和MYC测定的4探针FISH测定）和下一代测序分析。组织学上,两个肿瘤被归类为黑素细胞瘤（MC），两个是中级黑素细胞瘤（IMC），八个为软脑膜黑色素瘤（LMM）。2例罕见的LMM与大的斑块状蓝痣有关。一例MC病例与Ota有关。10例（83.3%）黑素细胞在脑膜内弥漫性增生。Ki-67在三个类别中有所不同(MC0-1%，IMC0-3%，LMM3-10%)。57.1％（4/7）的LMM病例FISH阳性。10个肿瘤中有9个在GNAQ中具有激活热点突变，GNA11或PLCB4。EIF1AX的其他突变，SF3B1或BAP1在40%中发现，30%,10%的肿瘤，分别。在随访期间（中位数=43个月），5例LMM患者出现复发和/或转移，其中三人死于这种疾病，另外两人还活着。到目前为止，我们的研究是FISH测试的第一批LMN病例。除了形态学指标包括坏死和有丝分裂图，使用Ki-67和FISH的组合有助于区分IMC和LMM，特别是在多形性特征较少的LMM病例中。SF3B1突变首先在两例与LMM相关的斑块型蓝痣中描述。SF3B1突变可能与LMN患者预后不良有关。
