[1759] ETV6 Gene Rearrangement in Soft Tissue and Renal Spindle Cell Tumors of Infants and Neonates: Correlation with Morphology and Clinical Follow-Up Data

L Debelenko, L Young-Gaylor, R Sharma, A Davidoff, J Jenkins, S Raimondi. St. Jude Children's Research Hospital, Memphis, TN

Background: ETV6 gene rearrangement as a result of t(12;15)(p13;q26) is a recurrent chromosomal abnormality in infantile fibrosarcoma (IFS) and cellular congenital mesoblastic nephroma (CMN). Differential diagnosis of the two entities that includes their benign counterparts is sometimes difficult. The role of fluorescent in situ hybridization (FISH) in the differential diagnosis and prognosis of these lesions has not been studied systematically.
Design: We analyzed 27 tumors with the original diagnoses of IFS (n=13), CMN (n=8), infantile hemangiopericytoma (IHP, n=4) and infantile myofibromatosis (IMF, n=2) from the files of our institution. Morphology was blindly re-reviewed by 2 pathologists; current IHC panel for spindle cell tumors with appropriate controls was applied to difficult cases. Interphase FISH with dual color split apart ETV6 probe (DakoCytomation, Denmark) was performed on FFPE sections of the archival material. The treatment and follow up data available for 22 of 27 patients were analyzed in accord with the NIH guidelines on human subject research with an appropriate IRB approval.
Results: Pathology review reclassified 6 of the 27 tumors and revised diagnoses included 10 IFS, 5 cellular CMN, 2 classical CMN, 1 mixed CMN, 3 IHP, 3 IMF, 1 plexiform fibro-histiocytic tumor, 1 malignant peripheral nerve sheath tumor (MPNST) and 1 undifferentiated sarcoma. The ETV6 was re-arranged in 9 of 10 IFS, 2 of 5 cellular CMN, none of 3 classical and mixed CMN, 3 IHP and 3 IMF. Remaining reclassified tumors showed no rearrangement; however, hybridization signals consistent with trisomy 12 were observed in the MPNST as well as in the rearrangement-negative IFS. All IFSs, 3 CMNs, 2 IHPs and 1 IFM were treated with chemotherapy and definitive surgery; 5 CMNs, 1 HPC and 2 IMF - surgery only. All but 1 (MPNST) patients are alive with no evidence of disease in 1-34 yr (mean 11.4 yr, median 9 yr).
Conclusions: Interphase FISH for the ETV6 rearrangement is helpful in differentiating IFS from its mimics and can be routinely used on FFPE. Cellular CMN showed rearrangement in less than half of the cases and the ETV-rearrangement positive cellular CMNs were cured by surgery only even when presented at stage III. Regardless of the rearrangement status both soft tissue and renal infantile fibrous tumors appear to have an excellent prognosis with current treatment modalities.
Category: Pediatrics

Monday, March 22, 2010 11:45 AM

Platform Session: Section H 2, Monday Morning


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