ALK-TPM3 rearrangement in adult renal cell carcinoma: Report of a new case showing loss of chromosome 3 and literature review

Seven cases of translocation-associated renal cell carcinoma involving ALK ( ALK -tRCC) were referenced in the last World Health Organization's classification (2016), in a group of emerging/provisional RCC. The first three cases were pediatric, medullary-based, associated with sickle-cell trait and showed a fusion of ALK with VCL . Thirteen cases have been further described. They displayed clinical, morphological and genomic heterogeneity. Most of them occurred in adults. None of the patients was affected by sickle-cell disease. We report a new case of ALK -tRCC in a 55-year-old woman. Genomic profile showed losses of chromosomes 3, 9 and 14, anomalies often observed in clear cell RCC. VHL mutation or morphological features suggesting a clear cell RCC were not detected. We identified an unbalanced rearrangement of ALK and TPM3 . Review of the literature identified similar features in our case and previously published cases: heterogeneous solid architecture, eosinophilic cells, mucinous cytoplasmic elements, rhabdoid cells and intracytoplasmic lumina. These elements may constitute the basis of a pathological definition of ALK -tRCC. Their observation in a RCC should lead to perform molecular detection of ALK rearrangement. This may have a crucial importance for metastatic patients treatment since ALK rearrangements confer sensitivity to tyrosine kinases inhibitors such as crizotinib.