Coexistence of ARNT::ALK and TPM3::ALK doublegene fusion in an ALK -rearranged renal cell carcinoma with osse
Mark Oliver, William M Rehrauer, William R Sukov, Catherine Bodnar, Christopher J Lacriola, Molly A Accola, Erica F Reinig, Meghan G Lubner, Wei Huang, Rong Hu, Elizabeth L Koehne, Yang ZongAbstract
Objectives
ALK-rearranged renal cell carcinoma (RCC) is an exceedingly rare subtype of molecularly defined RCC. Since the first reports of VCL::ALK rearrangement in 2 pediatric cases with sickle cell trait, ALK fusions with multiple non-VCL partners have been identified in ALK-rearranged RCCs from patients without sickle cell trait. Given the rarity of this subtype of RCC, continued reporting of individual cases is essential to better our understanding of the heterogenous clinicopathologic features of ALK-rearranged RCC.
Methods
Here we report the histologic, immunophenotypic, and molecular characteristics of an adult case of ALK-rearranged RCC.
Results
The tumor not only displayed diverse histologic growth patterns in a mucinous background but also exhibited a small focus of intratumoral osseous metaplasia at the periphery. Besides an atypical signal pattern found in a fluorescence in situ hybridization assay, a novel ARNT::ALK fusion with unusual breakpoints mapped to exon 19 for ALK was identified by targeted next-generation sequencing and subsequently confirmed by Sanger sequencing. More interestingly, molecular tests demonstrated the coexistence of TPM3::ALK and ARNT::ALK doublegene fusion. To our knowledge, the case presented here is the first case of ALK-rearranged RCC harboring 2 coexisting ALK fusions in the same renal tumor.
Conclusions
Our case demonstrated a mixed growth pattern and overlapping morphology of ALK-rearranged RCC, harboring 2 concomitant ALK fusions. It provides additional evidence for promiscuous fusion partner usage and multiple breakage hotspots of ALK rearrangements.