ALK-rearranged Renal Cell Carcinoma (ALK-RCC): Evaluation of Histomorphological and Immunohistochemical Features by Analysis of 276 Renal Cell Carcinoma Cases in Turkey

Abstract

Anaplastic lymphoma kinase (ALK) rearrangement-associated renal cell carcinoma (ALK-RCC) is characterized by ALK fusion at chromosome 2p23. It has recently been included as a recognized entity with the 5th edition of the WHO classification urinary and male genital tumor. However, our knowledge about ALK-RCC is limited due to the small number of reported cases. In our study, we aimed to contribute the histomorphological and immunohistochemical features of ALK-rearranged renal cell carcinoma cases. We reviewed 276 cases diagnosed as RCC in order to detect ALKRCCs.We used immunohistochemistry to screen ALK rearrangement and then confirmed the ALK rearrangement by fluorescence in situ hybridization (FISH) method.ALK was immunohistochemically positive in 8 of 276 cases. ALK rearrangement was detected by FISH in 3 of 8 cases. These cases were previously diagnosed as clear cell renal cell carcinoma (CRCC), papillary renal cell carcinoma (PRCC), and chromophobe renal cell carcinoma (ChRCC). Their histomorphological findings were diverse, and all three cases exhibited different immunohistochemical findings. Survival of these patients ranged between 6 to 24 months. ALK immunohistochemical findings were also different in each case as perinuclear, weak cytoplasmic, and membranous.ALK RCCs appear to be very rare tumors with heterogeneous histomorphological and immunohistochemical features. Although immunohistochemistry may be useful to detect ALK positivity, genetic evaluation is required to confirm the diagnosis. With identifying ALK-RCCs, ALK inhibitors, which are currently used in the treatment of lung adenocarcinomas, can be used as a targeted therapy option in ALK-RCCs.