Preoperative molecular testing in thyroid nodules with Bethesda VI cytology: Clinical experience and review of the literature

Abstract

Risk assessment is critical to determine the timing of elective surgeries and preserve valuable resources in time of pandemic. This study was undertaken to better understand the potential value of molecular testing to risk‐stratify thyroid nodules with malignant cytology (Bethesda VI). Systematic review of the literature contributed 21 studies representing 2036 preoperative specimens. The BRAF p.V600E substitution was detected in 46% to 90% of cases with a pooled positivity rate of 70% (95% confidence intervals: 64%‐76%). None of the studies used comprehensive oncogene panels. Retrospective analysis of 531 clinical specimens evaluated with the next‐generation sequencing ThyGeNEXT Thyroid Oncogene Panel identified a total of 436 gene alterations. BRAF mutation rate was 64% in specimens tested as part of standard clinical care and 75% in specimens from cross‐sectional research studies (P = .022). Testing for additional actionable gene alterations such as TERT promoter mutations or RET and NTRK gene rearrangements further increased the diagnostic yield to 78%‐85% and up to 95% when including the ThyraMIR Thyroid miRNA Classifier. These data support the role of molecular cytopathology in surgical and therapeutic decision‐making and warrant additional studies.

Fusion Oncogenes Are Associated With Increased Metastatic Capacity and Persistent Disease in Pediatric Thyroid Cancers

“…1 This observation has led to discussions as to whether identification of oncogenic alterations could be used to stratify therapy, including the extent of surgery, lobectomy versus total thyroidectomy, as well as central compartment lymph node dissection. 2,3…”

“…1 This observation has led to discussions as to whether identification of oncogenic alterations could be used to stratify therapy, including the extent of surgery, lobectomy versus total thyroidectomy, as well as central compartment lymph node dissection. 2,3 With the reduced costs of next-generation sequencing (NGS), the use of somatic cancer gene panel analysis in pediatric patients with differentiated thyroid cancer (DTC) has expanded with current data showing a shifted distribution of driver alterations with a higher incidence of oncogenic fusions rather than point mutations in children and adolescents compared with adults. 4,5 Similar to the TCGA-based molecular subtype classification system on the basis of messenger RNA expression signatures, we sought to determine whether oncogenic subtyping on the basis of identified mutations or fusions predicts phenotypic behavior and outcomes in pediatric patients with DTC.…”

What Is New in Biomarker Testing at Diagnosis of Advanced Non-Squamous Non-Small Cell Lung Carcinoma? Implications for Cytology and Liquid Biopsy

“…At the moment, most of the major studies use tissue samples for NTRK status assessment [109][110][111]. However, detection can be possible with cytological samples and even liquid biopsies [109,[112][113][114][115]. Several techniques of detection have been developed, including immunohistochemistry (IHC), molecular biology approaches (NGS and RT-PCR), and multiplex digital colorcoded barcode technology on tissue sections .…”

“…Depending on the quality and quantity of the nucleic acids extracted from the sample, false negative results can be obtained [78,81,109,119,121]. Depending on the case, these approaches could be performed with cytological samples, but only a few studies in this area have been performed to date and studies comparing cytological and tissue samples are strongly needed [109,[112][113][114][115]. The detection of NTRK fusions can also be envisaged with a liquid biopsy, but the sensitivity of such an approach is still unknown and needs to be determined.…”

MicroRNA profiling predicts positive nodal status in papillary thyroid carcinoma in the preoperative setting

“…In this context, the scientific evidence is much more limited and restricted to genomic biomarkers. Among those, the 2 most relevant are represented by BRAF and TERT promoter mutations, the former affected by a low specificity and the latter by a low sensitivity 3‐6 …”