Utility of Intraoperative Frozen Sections during Thyroid Surgery

Objective. To describe the usefulness of intraoperative frozen section in the diagnosis and treatment of thyroid nodules where fine needle aspirate biopsies have evidence of follicular neoplasm. Study Design. Retrospective case series. Methods. All patients have a fine needle aspirate biopsy, an intraoperative frozen section, and final pathology performed on a thyroid nodule after initiation of the Bethesda System for Reporting Thyroid Cytopathology in 2009 at a single tertiary referral center. Sensitivity, specificity, positive predictive value, and negative predictive value are calculated in order to determine added benefit of frozen section to original fine needle aspirate data. Results. The sensitivity and specificity of the frozen section were 76.9% and 67.9%, respectively, while for the fine needle aspirate were 53.8% and 74.1%, respectively. The positive and negative predictive values for the fine needle aspirates were 25% and 90.9%, respectively, while for the frozen sections were 27.8% and 94.8%, respectively. There were no changes in the operative course as a consequence of the frozen sections. Conclusion. Our data does not support the clinical usefulness of intraoperative frozen section when the fine needle aspirate yields a Bethesda Criteria diagnosis of follicular neoplasm, suspicious for follicular neoplasm, or suspicious for malignancy at our institution

Clinical Study Utility of Intraoperative Frozen Sections during Thyroid Surgery

Objective. To describe the usefulness of intraoperative frozen section in the diagnosis and treatment of thyroid nodules where fine needle aspirate biopsies have evidence of follicular neoplasm. Study Design. Retrospective case series. Methods. All patients have a fine needle aspirate biopsy, an intraoperative frozen section, and final pathology performed on a thyroid nodule after initiation of the Bethesda System for Reporting Thyroid Cytopathology in 2009 at a single tertiary referral center. Sensitivity, specificity, positive predictive value, and negative predictive value are calculated in order to determine added benefit of frozen section to original fine needle aspirate data. Results. The sensitivity and specificity of the frozen section were 76.9% and 67.9%, respectively, while for the fine needle aspirate were 53.8% and 74.1%, respectively. The positive and negative predictive values for the fine needle aspirates were 25% and 90.9%, respectively, while for the frozen sections were 27.8% and 94.8%, respectively. There were no changes in the operative course as a consequence of the frozen sections. Conclusion. Our data does not support the clinical usefulness of intraoperative frozen section when the fine needle aspirate yields a Bethesda Criteria diagnosis of follicular neoplasm, suspicious for follicular neoplasm, or suspicious for malignancy at our institution

Haploinsufficiency of SOX5 at 12p12.1 is associated with developmental delays with prominent language delay, behavior problems, and mild dysmorphic features

SOX5 encodes a transcription factor involved in the regulation of chondrogenesis and the development of the nervous system. Despite its important developmental roles, SOX5 disruption has yet to be associated with human disease. We report one individual with a reciprocal translocation breakpoint within SOX5, eight individuals with intragenic SOX5 deletions (four are apparently de novo and one inherited from an affected parent), and seven individuals with larger 12p12 deletions encompassing SOX5. Common features in these subjects include prominent speech delay, intellectual disability, behavior abnormalities, and dysmorphic features. The phenotypic impact of the deletions may depend on the location of the deletion and consequently which of the three major SOX5 protein isoforms are affected. One intragenic deletion involving only untranslated exons was present in a more mildly affected subject, was inherited from a healthy parent and grandparent, and is similar to a deletion found in a control cohort. Therefore, some intragenic SOX5 deletions may have minimal phenotypic effect. Based on the location of the deletions in the subjects compared to the controls, the de novo nature of most of these deletions, and the phenotypic similarities among cases, SOX5 appears to be a dosage-sensitive, developmentally important gene

Molecular analysis expands the spectrum of phenotypes associated with GLI3 mutations.

A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining 93 probands here. This includes 19 probands (12 mutations) who fulfilled clinical criteria for GCPS or PHS, 48 probands (16 mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), 21 probands (6 mutations) with features of PHS or GCPS and oral-facial-digital syndrome, and 5 probands (1 mutation) with nonsyndromic polydactyly. These data support previously identified genotype-phenotype correlations and demonstrate a more variable degree of severity than previously recognized. The finding of GLI3 mutations in patients with features of oral-facial-digital syndrome supports the observation that GLI3 interacts with cilia. We conclude that the phenotypic spectrum of GLI3 mutations is broader than that encompassed by the clinical diagnostic criteria, but the genotype-phenotype correlation persists. Individuals with features of either GCPS or PHS should be screened for mutations in GLI3 even if they do not fulfill clinical criteria

Molecular analysis expands the spectrum of phenotypes associated with GLI3 mutations

A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining 93 probands here. This includes 19 probands (12 mutations) who fulfilled clinical criteria for GCPS or PHS, 48 probands (16 mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), 21 probands (6 mutations) with features of PHS or GCPS and oral-facial-digital syndrome, and 5 probands (1 mutation) with nonsyndromic polydactyly. These data support previously identified genotype-phenotype correlations and demonstrate a more variable degree of severity than previously recognized. The finding of GLI3 mutations in patients with features of oral-facial-digital syndrome supports the observation that GLI3 interacts with cilia. We conclude that the phenotypic spectrum of GLI3 mutations is broader than that encompassed by the clinical diagnostic criteria, but the genotype-phenotype correlation persists. Individuals with features of either GCPS or PHS should be screened for mutations in GLI3 even if they do not fulfill clinical criteria