Clear Cell Renal Cell Carcinoma With Syncytial Giant Cells: A Case Report With Morphological and Immune-microenvironmental Characterization

<h3>Background/Aim:</h3> Clear cell renal cell carcinoma (ccRCC) is the most frequent kidney cancer, and its clinical course has been improved by the development of new anticancer immunotherapies. A rare variant of ccRCC is characterized by the presence of syncytial giant cells (SGCs), whose biological significance remains unclear. This study aimed to report a case of ccRCC with SGCs and to characterize its immune microenvironment. <h3>Case Report:</h3> We report the case of an 80-year-old man with ccRCC with SGCs who developed a subcutaneous mass in the upper arm after five years. Imaging revealed multiple pulmonary nodules and an enlarging left renal mass. The resected skin lesion was analyzed using histopathology and immunohistochemistry. Resection of the skin lesion confirmed metastatic ccRCC with SGCs. Immunohistochemically, SGCs were strongly positive for PAX8 and weakly positive for keratin, but negative for Iba-1 and CD163, indicating a tumor cell origin. Immune profiling demonstrated marked spatial heterogeneity: SGCs were localized exclusively within a CD8⁺ T cell-poor “cold” area, whereas no SGCs were observed in the T-cell–inflamed “hot” area. TGF-β expression was focally strong in SGCs within the cold area. <h3>Conclusion:</h3> SGCs may represent a terminally differentiated tumor cell variant of ccRCC associated with localized TGF-β-related immunosuppressive niche formation, potentially contributing to tumor immune evasion and progression.