KANK1-NTRK3 fusions define a subset of BRAF mutation negative renal metanephric adenomas

Aida Catic,Lech Mazur,Faruk Skenderi,Ardis Sophian,Dinesh Rakheja,Ondrej Hes,Amina Kurtovic-Kozaric,Jillene Kogan,Stephen Rohan,Michael R Pins

doi:10.1186/s12881-020-01143-6

Abstract

BackgroundMetanephric adenoma (MA) is a rare benign renal neoplasm. On occasion, MA can be difficult to differentiate from renal malignancies such as papillary renal cell carcinoma in adults and Wilms̕ tumor in children. Despite recent advancements in tumor genomics, there is limited data available regarding the genetic alterations characteristic of MA. The purpose of this study is to determine the frequency of metanephric adenoma cases exhibiting cytogenetic aberration t (9;15)(p24;q24), and to investigate the association between t (9,15) and BRAF mutation in metanephric adenoma.MethodsThis study was conducted on 28 archival formalin fixed paraffin-embedded (FFPE) specimens from patients with pathologically confirmed MA. Tissue blocks were selected for BRAF sequencing and fluorescent in situ hybridization (FISH) analysis for chromosomal rearrangement between KANK1 on chromosome 9 (9p24.3) and NTRK3 on chromosome 15 (15q25.3), which was previously characterized and described in two MA cases.ResultsBRAFV600E mutation was identified in 62% of our cases, 9 (38%) cases were BRAFWT, and 4 cases were uninformative. Of the 20 tumors with FISH results, two (10%) were positive for KANK1-NTRK3 fusion. Both cases were BRAFWT suggesting mutual exclusivity of BRAFV600E and KANK1-NTRK3 fusion, the first such observation in the literature.ConclusionsOur data shows that BRAF mutation in MA may not be as frequent as suggested in the literature and KANK-NTRK3 fusions may account for a subset of BRAFWT cases in younger patients. FISH analysis for KANK1-NTRK3 fusion or conventional cytogenetic analysis may be warranted to establish the diagnosis of MA in morphologically and immunohistochemically ambiguous MA cases lacking BRAF mutations.

Highlights

Metanephric adenoma (MA) is a rare benign renal neoplasm
Metanephric adenoma (MA) is a rare benign renal tumor classified under the rubric of metanephric tumors, which include metanephric stromal tumor and metanephric adenofibroma [1]
The majority of MA cases can be diagnosed on routine hematoxylin and eosin (H&E) stained slides

Summary

Introduction

Metanephric adenoma (MA) is a rare benign renal neoplasm. On occasion, MA can be difficult to differentiate from renal malignancies such as papillary renal cell carcinoma in adults and Wilmstumor in children. In some challenging cases MA can be difficult to morphologically differentiate from malignant renal neoplasms [9]; the solid variant of papillary renal cell carcinoma (PRCC) and epithelial-predominant Wilms’ tumor (WT) [10]. The distinction between these renal tumor subtypes can be aided by the use of diagnostic modalities such as immunohistochemistry, cytogenetic studies, and advanced molecular analyses [3]. The correct classification of a renal tumor is critical from a diagnostic standpoint, and from a prognostic and therapeutic standpoint [11, 12]

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Conclusion