, Melissa Yssel, MB ChB, FC Path(SA) Chem 139, and Wendy M. Zakowicz, BS 79 Purpose: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. Methods: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25-30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration.

Calretinin appears to be a useful marker to distinguish ONBs from other SRBCTs of the sinonasal tract, particularly when staining is moderate/strong and extensive. The calretinin-positive, p63-negative phenotype is fairly specific for ONB. The addition of these 2 IHC stains may aid in the diagnosis of sinonasal SRBCTs that are poorly differentiated, have inconclusive conventional IHC, or are found in small biopsies.

Involvement of the falx cerebri in infants with stage 4 neuroblastoma is thought to be rare. The falx is derived from the neural crest and thus may be a location for primary neuroblastoma. Its propensity for metastasis is unknown. Management of neuroblastoma in this location is potentially challenging. We describe two children less than 18 months of age who were successfully managed with chemotherapy alone (without radiation or surgery) for falx involvement with neuroblastoma.

Parents are very supportive of tissue research, including genetic research. A majority of parents would prefer restricting research to pediatric conditions, and to be informed of results, even if of uncertain significance. These findings may assist Institutional Review Boards in assessing parentally perceived risks of research, and researchers in providing consent elements that support parents and adolescents in making fully informed choices.