Performance of repeat cytology with reflex ThyroSeq genomic classifier for indeterminant thyroid cytology

O’Conor, Christopher J.; Dash, Rajesh; Jones, Claudia; Jiang, Xiaoyin “Sara”

doi:10.1002/cncy.22552

Cited by 9 publications

(7 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Proceeding with molecular testing in this context provided resolution to the indeterminate cytology of the initial FNA in approximately 60% of cases and averted the need for yet another biopsy due to the ND cytology of the repeat FNA. Prior reports of repeat FNA‐based molecular testing, including our earlier analysis of Afirma GEC cases from 2013 to 2017, have suggested that ND cytology on repeat FNA may limit the usefulness of molecular testing on the concurrent sample 11,35 . However, our current analysis of our entire Afirma GEC and GSC cohort through January 2021 supports the concept that submitting samples for molecular testing is still reasonable in this scenario, given the (1) persistently low‐to‐intermediate (9%) NIFTP and/or cancer risk, and (2) relatively high rate of satisfactory Afirma test results in this subset.…”

Section: Discussionsupporting

confidence: 57%

Risk stratification of cytologically indeterminate thyroid nodules with nondiagnostic or benign cytology on repeat FNA: Implications for molecular testing and surveillance

Hall

Hartzband

VanderLaan

et al. 2023

Cancer Cytopathology

View full text Add to dashboard Cite

Background Evidence guiding the management of cytologically indeterminate thyroid nodules with nondiagnostic (ND) or benign cytology on repeat fine‐needle aspiration (FNA) is limited. This study evaluates the utility of molecular testing and estimates the risk of noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) and cancer among such nodules. Methods This was a retrospective single‐institution review of thyroid nodules from adults that were classified as atypia of undetermined significance (AUS) or follicular neoplasm (FN) on initial FNA and underwent repeat FNA for cytology and Afirma testing (June 2013–July 2021). The association between repeat FNA cytology and RNA yield for Afirma was determined. Histologic outcomes were integrated with Afirma results to define end points for each nodule. Results A total of 691 AUS and FN nodules underwent repeat FNA and Afirma testing. Diagnostic Afirma results were obtained in 98% of cases overall and in 91% of nodules with ND cytology on repeat FNA. Using combined molecular and histologic end points, the NIFTP and/or cancer prevalence for nodules with ND cytology on repeat FNA was 9% (95% confidence interval [CI], 0.042–0.182), falling between those nodules classified as benign (5%; 95% CI, 0.029–0.094) and those classified as AUS or FN (18%; 95% CI, 0.140–0.218) on repeat FNA, although not reaching statistical significance from either subgroup (p = .38 and .10, respectively). Conclusions AUS and FN nodules that are ND on repeat FNA have low but nonnegligible risk of NIFTP and/or cancer and may benefit from molecular testing, given the low test failure rate in this subgroup. Conversely, AUS and FN nodules reclassified as benign on repeat FNA have a very low risk of NIFTP and/or cancer and are unlikely to benefit from molecular testing.

show abstract

Section: Discussionsupporting

confidence: 57%

Risk stratification of cytologically indeterminate thyroid nodules with nondiagnostic or benign cytology on repeat FNA: Implications for molecular testing and surveillance

Hall

Hartzband

VanderLaan

et al. 2023

Cancer Cytopathology

View full text Add to dashboard Cite

show abstract

“…The structure was non-tender and was palpable only after singing. Fine needle aspiration of the lesion showed Bethesda category III cytology; molecular testing [14] found a missense c.1358T > C mutation in the TSH receptor gene [15] with variant allele frequency of 46%, negative for gene fusions or copy number variants.…”

Section: Resultsmentioning

confidence: 99%

Convergence of specified RUNX2, SALL1, and SAMD9 variants permits normal global immune and endocrine function despite bone marrow hypocellularity and reduced ovarian reserve

Sills¹,

Harrity²,

Wood³

2022

Preprint

View full text Add to dashboard Cite

Background RUNX2, SALL1 and SAMD9 are independently assorted genes responsible for multisystem actions where disruption often results in severe developmental or functional impairment. Alteration in any of these ‘master regulators’ is usually diagnosed in early childhood when missed milestones, anatomical dysmorphia, or chronic infection/immune impairment initiate cross-disciplinary evaluation. Methods New variants were recently discovered in all three genes during SARS-CoV-19 hospitalization in an otherwise healthy 46,XX adolescent. Our research expands the clinical characterization for this unusual convergence based on medical records covering the 5 year interval before admission. Results Diffuse bone marrow hypocellularity without cytogenetic derangement was present, with no anemia or reduction in total immunoglobulin production. However, bone age was below mean by 1.5yrs and multiple dental anomalies were documented. Macrocytosis and elevated serum creatinine were consistent findings. Ovaries and uterus appeared undersized with collapse of endogenous estradiol output leading to secondary amenorrhea by age 13yrs. Besides oral contraceptives, no other daily hormone treatment was required. A TSH receptor gene mutation of uncertain significance was also identified. Conclusions This is the first work to correlate immunoglobulin patterns, bone marrow and dental morphology, hematology/renal screening, pelvic anatomy, ovarian reserve data and thyroid features with coincident variants in RUNX2, SALL1 and SAMD9. While the expected impact from each mutation alone would normally be adverse, this study suggests a milder phenotype can prevail when these three variants occur together. Nevertheless, focused monitoring is appropriate given the uncertain status of this unique combination of mutations.

show abstract

“…With a cancer/NIFTP prevalence of 28%, the NPV was 97% [CI, 93%-99%] and PPV was 66% [CI, 56%-75%] (34) (Table 1). There have been 10 independent studies assessing the performance of TSv3 (46,47,(58)(59)(60)(61)(62)(63)(64)(65). A recent meta-analysis by Lee at al.…”

Section: The Role Of Molecular Diagnostics In Itn For Benign Vs Malig...mentioning

confidence: 99%

Molecular diagnostics in the evaluation of thyroid nodules: Current use and prospective opportunities

Patel

Klopper

2023

Front. Endocrinol.

View full text Add to dashboard Cite

Thyroid cancer is the most common endocrine malignancy with an estimated 43,800 new cases to be diagnosed in 2022 and representing the 7th most common cancer in women. While thyroid nodules are very common, being identified in over 60% of randomly selected adults, only 5-15% of thyroid nodules harbor thyroid malignancy. Therefore, it is incumbent upon physicians to detect and treat thyroid malignancies as is clinically appropriate and avoid unnecessary invasive procedures in patients with benign asymptomatic lesions. Over the last 15-20 years, rapid advances have been made in cytomolecular testing to aid in thyroid nodule management. Initially, indeterminate thyroid nodules, those with Bethesda III or IV cytology and approximately a 10-40% risk of malignancy, were studied to assess benignity or malignancy. More recently, next generation sequencing and micro-RNA technology platforms have refined the diagnostic capacity of thyroid nodule molecular testing and have introduced opportunities to glean prognostic information from both cytologically indeterminate and malignant thyroid nodules. Therefore, clinicians can move beyond determination of malignancy, and utilize contemporary molecular information to aid in decisions such as extent of surgery and post-therapy monitoring plans. Future opportunities include molecularly derived information about tumor behavior, neo-adjuvant treatment opportunities and response to thyroid cancer therapies.

show abstract

Performance of repeat cytology with reflex ThyroSeq genomic classifier for indeterminant thyroid cytology

Cited by 9 publications

References 29 publications

Risk stratification of cytologically indeterminate thyroid nodules with nondiagnostic or benign cytology on repeat FNA: Implications for molecular testing and surveillance

Risk stratification of cytologically indeterminate thyroid nodules with nondiagnostic or benign cytology on repeat FNA: Implications for molecular testing and surveillance

Convergence of specified RUNX2, SALL1, and SAMD9 variants permits normal global immune and endocrine function despite bone marrow hypocellularity and reduced ovarian reserve

Molecular diagnostics in the evaluation of thyroid nodules: Current use and prospective opportunities

Contact Info

Product

Resources

About