Renal cell carcinoma with ALK-TPM3 gene fusion and ALK amplification: A case report and literature review

Background: Anaplastic lymphoma kinase (ALK)-rearranged renal cell carcinoma (ALK-RCC) is a rare molecularly defined tumor entity included in the fifth edition of the World Health Organization Classification of Tumors. It is characterized by rearrangement of the ALK gene with various fusion partner genes, which most commonly results in oncogenic fusion proteins leading to ALK activation.

Case presentation: A 30-year-old Chinese man underwent partial nephrectomy for a left renal tumor measuring 5 cm in diameter. Histologically, the tumor is pleomorphic and arranged in papillary, tubular, and solid patterns. At high magnification, abundant eosinophilic cytoplasm, obvious cytoplasmic vacuolation, and displaced nuclei were observed. Immunohistochemistry revealed diffuse positivity for PAX8,CK7,CAIX, and ALK(D5F3). Fluorescence in situ hybridization (FISH) showed ALK amplification and break-apart in tumor cells. ALK-TPM3 gene fusion and ALK amplification were detected by next-generation sequencing.

Conclusion: We report the first case of ALK-RCC with concurrent ALK amplification and fusion. This article presents the clinical data, morphology, immunohistochemistry, and molecular characteristics of this case, with the aim of enhancing the clinical and pathological understanding of ALK-RCC among clinicians and pathologists.