Coexistence of ARNT::ALK and TPM3::ALK doublegene fusion in an ALK-rearranged renal cell carcinoma with osseous metaplasia.
Mark Oliver, William M Rehrauer, William R Sukov et al.
✦ AI-curated · Sources linked
Case in brief
An adult patient had an ALK-rearranged renal cell carcinoma. The tumor showed varied growth patterns in a mucinous background, with a small peripheral focus of osseous metaplasia. Fluorescence in situ hybridization showed an atypical signal pattern. Targeted next-generation sequencing identified an ARNT::ALK fusion with an unusual ALK breakpoint at exon 19; Sanger sequencing confirmed this finding. Molecular testing also detected a coexisting TPM3::ALK fusion in the same tumor. The report describes the tumor’s histologic, immunophenotypic, and molecular features.
What made this case unusual
Two ALK fusions, ARNT::ALK and TPM3::ALK, coexisted in one renal tumor. The case also combined diverse growth patterns, mucinous background, peripheral osseous metaplasia, and an atypical FISH signal pattern.
Diagnostic / clinical pearl
In an ALK-rearranged renal cell carcinoma, an atypical FISH pattern need not capture the full fusion profile; targeted sequencing can identify coexisting ALK fusion partners, with orthogonal confirmation used in this case.
Why it matters
The findings add a documented example of multiple ALK fusion partners and varied ALK breakpoints in renal cell carcinoma, expanding the described molecular and morphologic spectrum.