Recurrent EGFR alterations in NTRK3 fusion negative congenital mesoblastic nephroma.

OBJECTIVES

To identify oncogenic driver mutations in congenital mesoblastic nephroma (CMN) cases lacking - fusion and discuss their diagnostic value.

DESIGN

The institutional pathology database was queried for cases with a morphologic diagnosis of CMN. Cases positive for rearrangement or with unavailable blocks were excluded. Four cases met the inclusion criteria and were sequenced by next-generation sequencing. Three additional cases were contributed by our collaborators.

RESULTS

Three of four internal cases harbor an kinase domain duplication (KDD), which is known to be oncogenic yet exceedingly rare in other histologies. All three outside cases are positive for alterations, including KDD in two and a splicing site mutation in one. The splicing site mutation is predicted to be EGFR activating. One of the outside cases was a retroperitoneal mass without a clear site of origin. A diagnosis of CMN is suggested based on exclusion of differential diagnoses by expert consultation and detection of KDD.

CONCLUSIONS

EGFR activation, predominantly via KDD, is a common recurrent genetic alteration in CMN lacking fusions. CMN can be molecularly classified into fusion type, EGFR activation type and others.