[YWHAE-rearranged clear cell sarcoma of kidney: a clinicopathological analysis of seven cases]

Objective: To investigate the clinicopathological features and molecular genetic alterations of the YWHAE-rearranged clear cell sarcoma of the kidney (CCSK), and to improve the diagnostic and differential diagnostic accuracy of the subtype of renal clear cell sarcoma. Methods: A retrospective analysis was performed on 7 cases of YWHAE-rearranged CCSK diagnosed and treated at the Shanghai Children's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China and the Children's Hospital of Fudan University, Shanghai, China between January 2018 and October 2023.Their clinicopathological characteristics were analyzed using HE staining, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS). Patient survival was assessed based on follow-up data. Results: Of the 7 patients with YWHAE-rearranged CCSK, 4 were male and 3 were female, aged 1.0-7.0 years, with an age of 2.0 (1.6, 6.0) years. The primary symptom was predominantly an abdominal mass (6 cases), with 1 case presented with abdominal pain and vomiting. All tumors were unilateral (left side in 3 cases, and right side in 4 cases). Preoperative imaging suspected Wilms tumor in all cases. Histologically, the classic type (4/7) and spindle cell type (2/7) were predominant while one case showed a mixed classic and epithelioid pattern. Vascular invasion was present in 3 cases, and lymph node metastasis was identified in 1 case. IHC results showed diffuse positivity for cyclin D1, bcl-2, and SATB2 in all cases, with varying expression of BCOR. FISH with break-apart probes analyses confirmed YWHAE (17p13) gene fusions in all cases. NGS performed in 2 cases revealed the presence of YWHAE::NUTM2 fusions, accompanied by mutations in FBXW7 or CREBBP gene. There were 5 Stage-Ⅲ cases and 2 Stage-Ⅳ cases. Postoperative follow-up ranged from 20 to 69 months and showed 3 patients with metastasis or recurrence. One of them also developed chronic renal failure. Conclusions: YWHAE-rearranged CCSK exhibits morphological heterogeneity and aggressive behaviors. Definitive diagnosis relies on molecular testing (such as FISH or NGS), which is crucial for differential diagnosis and prognostic evaluation. This subtype of CCSK is commonly associated with advanced clinical stage and early metastasis/recurrence, highlighting the necessity for improving risk stratification and clinical management.