脊索瘤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向骨骼。我们报告了一例74岁男性患者的高级别上皮样肿瘤,涉及膝关节的滑膜和软组织。初步活检尚无定论,但建议诊断为未知来源的转移性透明细胞癌。然而,影像学检查未发现任何原发性病变.切除标本由卵形至多边形细胞的巢和薄片组成,具有明显的细胞边界,透明或轻度两性的细胞质,和圆形到椭圆形的核,偶尔可见嗜酸性核仁。罕见的非典型有丝分裂,坏死区,并注意到奇怪的原子核。活检和切除标本进行了广泛的分子遗传分析,包括甲基化分析。DKFZ肉瘤分类器将甲基化类脊索瘤(去分化)分配为0.96的校准评分,此外,在拷贝数变异图中注意到SMARCB1基因座的丢失。为了验证这些发现,随后进行T-brachyury和SMARCB1免疫染色,显示弥漫性核阳性和肿瘤细胞完全丧失,分别。为了评估SWI/SNF缺陷型肿瘤中T-brachyury免疫阳性的患病率,并评估其对低分化脊索瘤的特异性,我们分析了23个SMARCB1-或SMARCA4缺陷型肿瘤,所有这些都是负面的。合并所有可用数据后,包括没有任何常规脊索瘤的形态学特征,该病例被诊断为低分化脊索瘤。如本文所示,甲基化分析在一些精心选择的无法分类的软组织肿瘤的诊断过程中的应用可能会导致此类极其罕见的软组织肿瘤的检出率提高,并使其能够更好地表征。
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.