Molecular detection of the ETV6-NTRK3 gene fusion differentiates congenital fibrosarcoma from other childhood spindle cell tumors

Congenital fibrosarcoma (CFS) is a pediatric spindle cell tumor of the soft tissues that usually presents before the age of 2 years. Although these tu mors display histologic features of malignancy and frequently recur, they h ave a relatively good prognosis and only rarely metastasize. CFS must there fore be differentiated from more aggressive spindle cell sarcomas that occu r during childhood, particularly adult-type fibrosarcoma (ATFS), which can have an identical morphology. CFS must also be distinguished from benign bu t cellular fibroblastic lesions of the same age group, including infantile fibromatosis (IFB) and myofibromatosis (MFB). Unfortunately, standard patho logic examination often does not differentiate CFS from these other conditi ons. The authors recently identified a novel chromosomal translocation in C FS, t(12;15)(p13;q25), which gives rise to an ETV6-NTRK3 gene fusion. They subsequently developed reverse transcription-polymerase chain reaction (RT- PCR) assays that can detect ETV6-NTRK3 fusion transcripts in CFS frozen or paraffin-embedded tumor specimens. To confirm the use of this assay in the differential diagnosis of CFS, they have screened a larger series of childh ood pediatric spindle cell lesions for ETV6-NTRK3 gene fusions, including 1 1 cases of CFS, 13 malignant spindle cell turners (including ATFS), and 38 benign spindle cell tumors (including IFB and MFB). Of the 11 cases diagnos ed as CFS, 10 showed the ETV6-NTRK3 gene fusion, whereas none of the 51 oth er malignant or benign spindle cell tumors demonstrated this fusion gene. T hey also compared their RT-PCR findings with those of conventional cytogene tics and with immunohistochemical detection of the ETV6-NTRK3 protein using antisera to NTRK3. They conclude that RT-PCR analysis is superior to these techniques for the detection of the ETV6-NTRK3 gene fusion in pediatric sp indle cell tumors, and it is a reliable and specific modality for the diagn osis of CFS.