The utility of immunohistochemistry (IHC) for fumarate hydratase (FH) and S-(2-succino)-cysteine (2SC) has been investigated to differentiate FHDRCC. Recently, IHC for aldo-keto reductase family 1 member B10 (AKR1B10) was reported as a novel and precise diagnostic marker for FHDRCC. This study aims to confirm the diagnostic efficacy of AKR1B10 IHC in FHDRCC and to characterize the genotypic and phenotypic features of FHDRCC in Taiwanese patients.

We analyzed 9 tumor samples diagnosed with FHDRCC by surgical pathology, as well as by FH and 2SC IHC. AKR1B10 IHC was applied to the tumor samples and their adjacent normal renal parenchyma . Furthermore, we used whole-exome sequencing to investigate genetic variants in the FH gene and other co-occurring oncogenic alterations in 9 patients, including 7 who underwent tumor–normal paired analysis and 2 who underwent tumor-only analysis.

Among the tumor samples, 6 showed diffuse positivity, 2 showed focal positivity, and 1 was negative. Among the normal renal parenchyma samples, 8 were negative and 1 showed focal positivity. From the genomic analyses, we found that all 9 patients carried FH gene mutations. Among the 7 patients who underwent tumor-normal paired analysis, all had germline FH mutations and 1 also had somatic FH mutation. For the remaining 2 patients, it was not possible to determine whether their FH mutations were germline or somatic. Additional oncogenic alterations in genes were also identified.

This study highlights the utility of AKR1B10 IHC as a diagnostic tool for FHDRCC, demonstrating high sensitivity and specificity. Moreover, our genomic analyses provide insights into the genetic basis of FHDRCC among Taiwanese patients, revealing FH gene variants along with other co-occurring oncogenic alterations.