Chordoma是一种罕见的具有脊索分化的恶性肿瘤，通常影响年轻患者的轴骨骨骼。我们报告了一例74岁男性患者膝盖滑膜和软组织涉及的高级别上皮样肿瘤。初步活检结果不确定，但建议诊断为原发不明的转移性透明细胞癌。然而，影像学检查未显示出任何原发病变。切除标本由可辨别细胞边界的卵圆形至多边形细胞群和片状细胞组成，细胞质清晰或轻微的淡染性，核呈圆形至卵圆形，偶见明显的嗜酸性核仁。注意到罕见的非典型有丝分裂、坏死区域和畸形核。活检和切除标本进行了广泛的分子遗传学分析，包括甲基化分型。DKFZ肉瘤分类器将甲基化类别诊断为脊索瘤（分化程度低），校准分数为0.96，并且复制数变异图谱中观察到SMARCB1基因座的缺失。为验证这些发现，进行了T-Brachyury和SMARCB1免疫染色，结果表明肿瘤细胞弥漫核阳性，SMARCB1完全丧失。为了评估SWI/SNF缺陷肿瘤中T-Brachyury免疫阳性的患病率，并评估其对差分程度较差的脊索瘤的特异性，我们分析了一系列23个SMARCB1或SMARCA4缺陷肿瘤，均为阴性。在整合所有可用数据的基础上，包括在传统脊索瘤中不存在任何形态特征的情况下，将该例诊断为差分程度较差的脊索瘤。正如本文所揭示的，在对某些经过精选的无法分类的软组织肿瘤进行诊断过程中，利用甲基化分型可能会提高这些极其罕见的软组织肿瘤的检出率，并使其更好地表征。© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chordoma is a rare malignant tumor with notochordal differentiation, usually affecting the axial skeleton of young patients. We report a case of a high-grade epithelioid tumor involving the synovium and soft tissues of the knee in a 74-year-old male patient. The preliminary biopsy was inconclusive, but a diagnosis of metastatic clear-cell carcinoma of unknown origin was suggested. However, imaging studies did not reveal any primary lesions. The resection specimen consisted of nests and sheets of oval to polygonal cells with discernible cell borders, clear or lightly amphophilic cytoplasm, and round to oval nuclei with occasional well-visible eosinophilic nucleoli. Rare atypical mitoses, necrotic areas, and bizarre nuclei were noted. The biopsy and resection specimens underwent a wide molecular genetic analysis which included methylation profiling. The DKFZ sarcoma classifier assigned the methylation class chordoma (dedifferentiated) with a calibrated score of 0.96, and additionally, a loss of SMARCB1 locus was noted in the copy number variation plot. To verify these findings, T-brachyury and SMARCB1 immunostaining was performed afterward, showing diffuse nuclear positivity and complete loss in the tumor cells, respectively. To assess the prevalence of T-brachyury immunopositivity among SWI/SNF-deficient tumors and to evaluate its specificity for poorly differentiated chordoma, we analyzed a series of 23 SMARCB1- or SMARCA4-deficient tumors, all of which were negative. After incorporating all the available data, including the absence of any morphological features of conventional chordoma, the case was diagnosed as poorly differentiated chordoma. As illustrated herein, the utilization of methylation profiling in the diagnostic process of some carefully selected unclassifiable soft tissue neoplasms may lead to an increased detection rate of such extremely rare soft tissue tumors and enable their better characterization.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.