Detection of the ETV6-NTRK3 chimeric RNA of infantile fibrosarcoma/cellular congenital mesoblastic nephroma in paraffin-embedded tissue: Application to challenging pediatric renal stromal tumors

We report the development of a reverse transcriptase polymerase chain react ion assay that reliably detects the ETV6-NTRK3 chimeric RNA characteristic of infantile fibrosarcoma and the cellular variant of congenital mesoblasti c nephroma (CMN) in formalin-fixed, paraffin-embedded tissue blocks. The 18 8 base pair polymerase chain reaction fusion product was detected in 11 of 12 cases of cellular CMN from which a larger sized control RNA band could b e amplified, and even in 7 of 8 cases in which the control band was not det ectable. A variety of other tumors that are in the histologic differential diagnosis of cellular CMN yielded negative results, including four classic CMNs, four rhabdoid tumors of the kidney, and four clear cell sarcomas of t he kidney, confirming the assay's specificity. We further demonstrate the a ssay's utility by illustrating two cases of molecularly confirmed cellular CMN that mimicked rhabdoid tumor and clear cell sarcoma of the kidney. In c ontrast to previous reports, five mixed CMNs that had both classic and cell ular areas all lacked the ETV6-NTRK3 fusion transcript. These results sugge st that cases morphologically defined as mixed CMN may represent a mixed gr oup of genetically distinct entities.