Clinical relevance of molecular diagnosis in childhood rhabdomyosarcoma

Rhabdomyosarcoma may be divided into three subtypes-embryonal, alveolar, an d undifferentiated sarcoma-which can be distinguished by molecular analysis . The authors applied reverse transcriptase-polymerase chain reaction analy sis (RT-PCR) to analyze tumor samples from 14 children with rhabdomyosarcom a for the presence of the chimeric PAX3-FKHR transcript resulting from the translocation t(2;13)(q35,q14). Both fresh and paraffin-embedded tissues we re used. In only nine specimens was the RNA intact for the analysis. The ch imeric transcript was identified in seven samples: four alveolar type, one embryonal type, and two undifferentiated sarcoma. Histologic review was per formed in the three samples with discordance between the molecular and hist ologic findings. A sample from a patient with a diagnosis of embryonal rhab domyosarcoma on presentation and expression of PAX3-FKHR fusion transcript yielded a small focus of alveolar rhabdomyosarcoma and was reclassified as alveolar rhabdomyosarcoma. One of the samples from a patient with undiffere ntiated sarcoma was redefined as alveolar subtype; the diagnosis of the sec ond undifferentiated sarcoma remained unchanged, in accordance with the his tologic diagnosis. These findings further support the recommendation that molecular analysis b e included in the diagnostic workup of childhood small round cell tumors to reach a more accurate diagnosis for tailoring of specific treatment.