The Sikl Department of Pathology, Faculty of Medicine and University Hospital in Pilsen, Charles University, Prague, Czech Republic.
Bioptical Laboratory, Ltd., Pilsen, Czech Republic.
Virchows Arch. 2024 Apr;484(4):621-627. doi: 10.1007/s00428-023-03620-8. Epub 2023 Aug 18.
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.
软骨肉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骨骼。我们报告了一例 74 岁男性患者膝关节滑膜和软组织中高级别上皮样肿瘤。初步活检结果不确定，但提示为来源不明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。切除标本由巢状和片状的椭圆形至多边形细胞组成，细胞边界清晰，细胞质透明或轻度嗜酸性，圆形至椭圆形核，偶见明显嗜酸性核仁。罕见的非典型有丝分裂、坏死区和奇异核。活检和切除标本进行了广泛的分子遗传学分析，包括甲基化分析。DKFZ 肉瘤分类器将甲基化分类为软骨肉瘤（去分化），校准得分为 0.96，并且在拷贝数变异图中还注意到 SMARCB1 基因座缺失。为了验证这些发现，随后进行了 T-brachyury 和 SMARCB1 免疫染色，分别显示肿瘤细胞弥漫性核阳性和完全缺失。为了评估 T-brachyury 免疫阳性在 SWI/SNF 缺陷性肿瘤中的普遍性，并评估其对低分化软骨肉瘤的特异性，我们分析了 23 例 SMARCB1 或 SMARCA4 缺陷性肿瘤，所有肿瘤均为阴性。在综合所有可用数据后，包括没有任何常规软骨肉瘤的形态学特征，该病例被诊断为低分化软骨肉瘤。如本文所示，在一些精心选择的未分类软组织肿瘤的诊断过程中使用甲基化分析可能会提高此类极其罕见的软组织肿瘤的检出率，并能够更好地对其进行特征描述。
