Single nucleotide polymorphisms (SNPs) are usually the most frequent genomic variants. Directly pedigree-phased multi-SNP haplotypes provide a more accurate view of polymorphic population genomic structure than individual SNPs. The former are, therefore, more useful in genetic correlation with subject phenotype. We describe a new pedigree-based methodology for generating non-ambiguous SNP haplotypes for genetic study. SNP data for haplotype analysis were extracted from a larger Type 1 Diabetes Genetics Consortium SNP dataset based on minor allele frequency variation and redundancy, coverage rate (the frequency of phased haplotypes in which each SNP is defined) and genomic location. Redundant SNPs were eliminated, overall haplotype polymorphism was optimized and the number of undefined haplotypes was minimized. These edited SNP haplotypes from a region containing HLA-DRB1 (DR) and HLA-DQB1 (DQ) both correlated well with HLA-typed DR,DQ haplotypes and differentiated HLA-DR,DQ fragments shared by three pairs of previously identified megabase-length conserved extended haplotypes. In a pedigree-based genetic association assay for type 1 diabetes, edited SNP haplotypes and HLA-typed HLA-DR,DQ haplotypes from the same families generated essentially identical qualitative and quantitative results. Therefore, this edited SNP haplotype method is useful for both genomic polymorphic architecture and genetic association evaluation using SNP markers with diverse minor allele frequencies.

Peritoneal fluid sampling has been recommended during surgery to resect an ovarian or fallopian tube mass, particularly for its staging relevance in ovarian carcinoma. Guidelines specifically for children are not well established, partly because of incomplete knowledge of the test characteristics in this age group. We sought to determine whether peritoneal fluid cytology sampling aids in diagnosis or staging of pediatric uterine adnexal masses. Children who underwent adnexal mass biopsy or excision from 1993 to 2014 were identified via archival review. Accompanying peritoneal fluid (washings or ascites) was assessed to determine whether it provided information beyond that in the accompanying surgical pathology specimen. Of 656 patients who underwent adnexal mass resection, 350 had concurrent cytologic sampling of peritoneal fluid. Median age at surgery was 14 years. Adnexal mass histologic examination showed tumors with malignant potential in 54 (8%) patients. Malignancy was identified in 3 cytology specimens (2 dysgerminomas and 1 mixed germ cell tumor). By today's guidelines, the malignant cytology specimens would have upstaged 1 of the 3 patients, and her therapy may not have changed. Cytology findings did not refine the histologic diagnosis in any benign or malignant case. Our findings demonstrated a low rate of malignancy (<1%) in peritoneal washing/ascites samples accompanying resection of a pediatric adnexal mass. Influencing staging or treatment by cytology sampling was rare in our cohort. Our findings provided benchmark data in an area dominated by adult studies. Furthermore, they may guide recommendations for cytologic fluid collection and processing tailored for pediatric populations.

Our findings show that suction biopsy after pull-through was frequently histologically indeterminate and never definitively positive for residual aganglionosis. When biopsy was histologically indeterminate, rebiopsy was pursued less commonly than may be expected. Our findings emphasize that suction biopsy examination is not a "criterion standard" for residual aganglionosis, but instead a component of a diagnosis that ultimately combines clinicopathologic factors, the constellation of which can sometimes spare patients from a more invasive full-thickness biopsy.