Clinically critical impact of molecular genetic studies in pediatric solidtumors

Background. Standard cytogenetic techniques are time-consuming and often no t informative with solid tumors. In contrast, the reverse transcriptase-pol ymerase chain reaction (RT-PCR) is a readily available technique that can r apidly detect tumor-specific chromosomal rearrangements, even in small biop sy specimens. We present cases depicting the importance of including molecu lar diagnostic studies in the routine evaluation of pediatric solid tumors. Procedure. We used RT-PCR to detect chimeric transcripts specific for majo r pediatric solid tumors, including peripheral primitive neuroectodermal tu mor (pPNET), alveolar rhabdomyosarcoma (ARMS), and desmoplastic small round -cell tumor (DSRCT). We reviewed six recent cases in which the initial diag nosis was changed by the results of RT-PCR. Results, Highly unusual or nons pecific clinical and/or histopathologic findings led to the initial diagnos es of neuroblastoma in three patients and DSRCT, leukemia, and carcinoma in one patient each. The final diagnoses after RT;PCR studies were pPNET in t hree patients, ARMS in two patients, and DSRCT in one patient. RT-PCR resul ts led to early corrections in the diagnosis in hive patients, but four pat ients received treatment not considered optimal for the neoplasms ultimatel y diagnosed, including three who, despite presenting with localized tumors that have a >70% cure rate with standard therapy, have died or are dying of disease. Conclusions. Molecular genetic studies on solid tumors can clarif y the diagnosis in seemingly straightforward as well as in overtly problema tic cases. These diagnostic distinctions are now critical as disease-specif ic and risk-directed therapies have emerged. Med. Pediatr. Oncol. 33:530-53 5, 1999. (C) 1999 Wiley-Liss, Inc.