ALK -Rearranged Renal Cell Carcinoma : Morphologic Spectrum and Genomic Landscape From a Multi-Institutional Cohort...

Area of Science:

• Oncology
• Genetics
• Pathology

Background:

• Anaplastic lymphoma kinase gene-rearranged renal cell carcinoma (ALK RCC) is rare and morphologically heterogeneous.
• Misdiagnosis as RCC, not otherwise specified, can occur due to its complex presentation.
• Accurate diagnosis is vital as ALK RCC patients may respond to ALK-inhibitors.

Purpose of the Study:

• To characterize the clinicopathologic and immunophenotypic features of ALK RCC.
• To expand the understanding of the morphological and molecular spectrum of ALK RCC.
• To highlight the diagnostic challenges and clinical significance of ALK RCC.

Main Methods:

• Analysis of 16 multi-institutional ALK RCC cases.
• Evaluation of clinical, macroscopic, microscopic, immunohistochemical (IHC), and molecular data (NGS, FISH).
• Assessment of follow-up data.

Main Results:

• ALK RCC exhibits heterogeneous morphology, including solid, tubular, papillary, and epithelioid patterns.
• All tumors were ALK-positive and coexpressed PAX8, KRT7, SDH, and FH.
• Common gene fusions included EML4::ALK, TPM1::ALK, and TPM3::ALK.
• Focal TFE3 immunoreactivity was observed but TFE3 gene rearrangement was absent.

Conclusions:

• ALK RCC is morphologically diverse and can mimic other renal tumors.
• Appropriate IHC and molecular studies are essential to avoid misdiagnosis.
• Confirming ALK gene rearrangement is critical for potential targeted therapy selection.