Abstract: Background Chordoid neoplasms refer to tumors appearing to have histological features of embryonic notochord, which is characterized by cords and lobules of neoplastic cells arranged within myxoid matrix. Because of radiological and histological similarities with myxoid matrix and overlapping immunohistochemical profile, chordoma, chordoid meningioma, chordoid glioma, and rare extraskeletal myxoid chondrosarcoma enter in the radiological and histological differential diagnosis at the site of skull base. However, there is always a great challenge for histopathologists to make an accurate diagnosis when encountering a chordoid neoplasm within or near the central nervous system. The aim of this study is to investigate and summarize the radiological, histological features and immunohistochemical profiles of chordoid neoplasms in skull base, and to find a judicious panel of immunostains to unquestionably help in diagnostically challenging cases. Methods A total of 23 cases of chordoid neoplasms in skull base, including 10 chordomas, 5 chordoid meningiomas, 3 chordoid gliomas and 5 extraskeletal myxoid chondrosarcomas, were collected from the First Affiliated Hospital, Sun Yat-sen University and Guangdong Tongjiang Hospital. MRI examination was performed on the patients before surgical treatment. Microscopical examination and immunohistochemical staining study using vimentin (Vim), pan-cytokeratin (PCK), epithelial membrane antigen (EMA), S?100 protein (S-100), glial fibrillary acidic protein (GFAP), D2-40, Galectin-3, CD3, CD20, Ki-67 were performed on the samples of cases. The clinicopathological data of the patients was also analyzed retrospectively. Results Most of chordomas were localized in the clivus with heterogeneous hyperintensity on T₂WI scanning. The breakage of clivus was observed in most cases. Histologically, the tumor cells of chordoma exhibited bland nuclear features and some contained abundant vacuolated cytoplasm (the so-called physaliferous cells) within myxoid matrix. Areas of cartilage presented in individual cases. The tumor cells of chordoma were diffusely immuno-positive for PCK and EMA. Chordoid meningioma is characterized by a homogeneous contrast-enhancing mass with dural tail sign. The epithelioid cells were arranged in cords and clusters within a myxoid matrix, which was highly reminiscent of chordoma. The ratio of myxoid component and conventional meningioma was different in tumors. EMA was detectable in all chordoid meningiomas, and 4/5 cases were positive for D2-40. That was a finding which was helpful in distinguishing chordoid meningioma from chordoma. Chordoid gliomas were localized in the third ventricle with homogeneous enhancement on MRI examination. The tumors were composed of clusters and cords of epithelioid tumor cells within a variably mucinous stroma containing lymphoplasmacytic infiltratation. The most distinctive immunohistochemical feature of chordoid gliomas is their strong diffuse reactivity for GFAP. EMA and PCK positive expression can also be seen focally in individual cases. Although extraskeletal myxoid chondrosarcomas share the similar radiological and histological appearance with chordoma, all chondrosarcomas in the present study are completely negative for epithelial markers except for immuno-positivity of S-100 focally. In addition, Galectin-3 can be detected in most of chordoid neoplasms in skull base. Conclusion The specific localization and MRI features of tumors are useful diagnostic clues for the differential diagnosis of chordoid neoplasms in skull base. However, combining with histological features, a panel of selected immunostains, including PCK, EMA, GFAP, S-100 and D2-40, is helpful in making an accurate diagnosis for those diagnostically challenging cases which usually appear to have atypical radiological features or in an unusual site. Ki-67 index and Galectin-3 are not recommended to use as diagnostic markers for chordoid neoplasms of skull base because of their less neoplastic specificity.

Key words: Chordoma, Meningioma, Glioma, Skull base neoplasms, Magnetic resonance imaging, Immunohistochemistry

摘要： 研究背景 脊索样肿瘤系指具有原始脊索形态特点的肿瘤性病变，常规HE 染色表现为短梭形或上皮样肿瘤细胞特征性地呈条索状或簇状分布于淡蓝色黏液样基质中。颅底是发生脊索样肿瘤比较集中的部位，主要包括脊索瘤、脊索样脑膜瘤、脊索样胶质瘤和骨外黏液样软骨肉瘤。由于影像学表现和组织病理学表现存在重叠，颅底脊索样肿瘤的影像学和组织病理学鉴别一直是临床诊断的难点，极易误诊。笔者对各种颅底脊索样肿瘤的发生部位、MRI影像学表现和组织病理学特点进行回顾分析，以期提高对此类肿瘤诊断的准确性。方法 对发生于颅底的10 例脊索瘤、5 例脊索样脑膜瘤、3 例脊索样胶质瘤和5 例骨外黏液样软骨肉瘤病例的影像学、组织形态学及免疫组织化学表型进行回顾分析。结果 脊索瘤主要发生于斜坡伴骨质破坏，T₂WI 呈高信号和“蜂房征”，组织形态学可见脊索样特征和“液滴”状细胞，免疫组织化学染色显示上皮性标志物广谱细胞角蛋白和上皮膜抗原呈弥漫性强阳性。脊索样脑膜瘤位于鞍旁海绵窦，边界清楚，T₁WI 呈等或稍低信号、增强后呈均匀强化，并可见典型的“脑膜尾征”；肿瘤组织中黏液样基质和典型脑膜瘤区域比例不均匀，间质中浸润的淋巴细胞数目不等，除表达上皮膜抗原外，D2-40 表达阳性率为4/5。脊索样胶质瘤好发于第三脑室，增强后呈均匀致密强化灶、边界锐利；上皮样肿瘤细胞间有大量炎性细胞浸润，除胶质纤维酸性蛋白恒定表达阳性外，广谱细胞角蛋白和上皮膜抗原均有不同程度表达。骨外黏液样软骨肉瘤也位于斜坡，影像学和组织病理学特征均与脊索瘤相似，但不表达或仅灶性表达上皮性标志物，Galectin-3 在肿瘤组织中均有不同程度的表达。结论 颅底脊索样肿瘤有各自较明确的解剖学定位和影像学特征，有助于临床诊断。对于易混淆的病例，除注意观察组织形态学特点外，免疫组织化学染色广谱细胞角蛋白、上皮膜抗原、胶质纤维酸性蛋白、S-100 蛋白和D2-40 组合最适宜鉴别诊断。Ki-67 抗原标记指数不能作为肿瘤分型的依据，Galectin-3 特异性较差，不建议在脊索样肿瘤的鉴别诊断中应用。

关键词: 脊索瘤, 脑膜瘤, 神经胶质瘤, 颅底肿瘤, 磁共振成像, 免疫组织化学