Cytomorphology and Clinicopathologic Correlation of TFE3-Rearranged Renal Cell Carcinoma (TFE3-rRCC)

Summary: Introduction: TFE3-rRCC harbors gene fusions involving TFE3 with one of many different partner genes. Due to their diverse morphologies, the differential diagnosis is quite broad and challenging. focusing on the cytomorphology and clinicopathologic correlation of TFE3-rRCC are sparse. Materials and Methods: Thirteen cytology cases of TFE3-rRCC 11 patients were retrieved, comprising 7 primary and 6 metastatic cases. Preliminary diagnoses rendered during rapid on-site evaluation were RCC/cancer/adenocarcinoma in 12 cases and naked nuclei in 1 case. Results: FNA and touch preparation revealed columnar or polygonal cells arranged in various patterns, 3-dimensional, nested, individual, papillary, sheet, and tubular/acinar. Tumor cells exhibited enlarged eccentric, round or oval nuclei, possibly situated peripherally, and with conspicuous to prominent nucleoli. Tumor cells had a moderate amount of granular or vacuolated cytoplasm. Macrophages, hyalinized fibrosis, or necrosis were occasionally seen. Core histology often showed papillae with surface-oriented nuclei. Tumor cells were also arranged in nest, sheet, and tubular patterns with similar nuclear and cytoplasmic characteristics as seen in cytology. Tumor cells demonstrated immunoreactivity to TFE3 (100%), AMACR (100), PAX8 (86%), CA9 (56% focally), CD10 (75%), CK7 (22% focally), and CD117 (25% patchy). FISH or fusion NGS tests showed TFE3 rearrangement. Metastasis was observed in 8/11 cases (73%). 64% of patients underwent nephrectomy, while 36% received chemotherapy/targeted therapy. Conclusions: It is crucial to recognize the cytomorphology and histomorphology of TFE3-rRCC for timely diagnosis and the effective treatment of this aggressive subtype of RCC.