ALK rearrangement in TFE3-positive renal cell carcinoma: Alternative diagnostic option to exclude Xp11.2 translocation carcinoma

Abstract

Anaplastic lymphoma kinase (ALK)-rearranged renal cell carcinoma (RCC) is a rare subtype of RCC with gene fusion involving ALK at 2p23. It was first included in the renal tumor classification system by WorldHealth organization (WHO) as a distinct emerging/provisional renal entity in 2016. To date, only a few cases of ALK-RCC have been reported. Here, we report an exceptional case of ALK-RCC in a 15-year-old girl and review the literature. The patient presented with gross hematuria and a tumor measured 7 cm × 6 cm was found in the left kidney by imaging examination. Then a laparoscopic radical nephrectomy combined with local lymph node dissection was performed. The pathologic stage of the tumor was pT1bN1Mx and postoperative pathology showed that the tumor corresponded to WHO/ISUP grade 3-4. Immunohistochemistry (IHC) demonstrated moderate nuclear expression of TFE3 protein. Interestingly, ALK gene rearrangement rather than TFE3 gene rearrangement was observed by fluorescence in situ hybridization (FISH). Now the girl is still alive without evidence of recurrence for 10 months follow-up. In conclusion, the positive expression of nuclear TFE3 in immunohistochemistry may be deceptive, the detection of ALK could be a diagnostic option if TFE3 was negative in FISH study. Large-scale and long-term studies are still needed to explore the biological behavior and molecular characteristic of ALK-RCC.

Keywords: ALK; FISH; HOOK1; Renal cell carcinoma; TFE3; Translocation.