Dataset Information

Molecular testing for cytologically suspicious and malignant (Bethesda V and VI) thyroid nodules to optimize the extent of surgical intervention: a retrospective chart review.

ABSTRACT:

Background

Molecular testing has been used for cytologically indeterminate thyroid nodules (Bethesda III and IV), where the risk of malignancy is 10-40%. However, to date, the role of molecular testing in cytologically suspicious or positive for malignancy (Bethesda V and VI) thyroid nodules has been controversial. The aim of this study was to determine whether patients who had molecular testing in Bethesda V and VI thyroid nodules had the optimal extent of surgery performed more often than patients who did not have molecular testing performed.

Methods

A retrospective chart review of 122 cases was performed: 101 patients from the McGill University teaching hospitals and 21 patients from the Hillel Yaffe Medical center, Technion University. Patients included in the study were those with Bethesda V or VI thyroid nodules who underwent molecular testing (ThyGenext® or ThyroseqV3®) (McGill n = 72, Hillel Yaffe n = 14). Patients with Bethesda V or VI thyroid nodules who did not undergo molecular testing were used as controls (McGill n = 29, Hillel Yaffe n = 7). Each case was reviewed in order to determine whether the patient had optimal surgery. This was defined as total thyroidectomy in the presence of either a positive lymph node, extrathyroidal extension, or an aggressive pathological variant of papillary thyroid carcinoma (tall cell, hobnail, columnar cell, diffuse sclerosing, and solid/trabecular) documented on the final pathology report. In all other cases, a lobectomy/hemi/subtotal thyroidectomy was considered as optimal surgery. Chi-squared testing was performed to compare groups.

Results

When molecular testing was done, 91.86% (79/86) of surgeries in the molecular testing group were optimal, compared to 61.11% (22/36) in the control group. At McGill University teaching hospitals and at Hillel Yaffe, 91.67% (66/72) and 92.86% (13/14) of surgeries in the intervention group were considered as optimal, respectively. This compares to 58.62% (17/29) at McGill and 71.43% (5/7) at Hillel Yaffe when molecular testing was not performed (p = .001, p = .186).

Conclusions

In this study, molecular testing in Bethesda V and VI thyroid tumors significantly improved the likelihood of optimal surgery. Therefore, molecular testing may have an important role in optimizing surgical procedures performed in the setting of Bethesda V and VI thyroid nodules. Prospective studies with larger sample sizes are required to further investigate this finding.

SUBMITTER: Hier J

PROVIDER: S-EPMC8082804 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Publications

Molecular testing for cytologically suspicious and malignant (Bethesda V and VI) thyroid nodules to optimize the extent of surgical intervention: a retrospective chart review.

Hier Jessica J Avior Galit G Pusztaszeri Marc M Krasner Joshua R JR Alyouha Noura N Forest Veronique-Isabelle VI Hier Michael P MP Mlynarek Alex A Richardson Keith K Sadeghi Nader N Tamilia Michael M Payne Richard J RJ

Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale 20210428 1

<h4>Background</h4>Molecular testing has been used for cytologically indeterminate thyroid nodules (Bethesda III and IV), where the risk of malignancy is 10-40%. However, to date, the role of molecular testing in cytologically suspicious or positive for malignancy (Bethesda V and VI) thyroid nodules has been controversial. The aim of this study was to determine whether patients who had molecular testing in Bethesda V and VI thyroid nodules had the optimal extent of surgery performed more often t ...[more]

PMID: 33910629

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Project description:Background: Gene panels are routinely used to assess predisposition to hereditary cancers by simultaneously testing multiple susceptibility genes and/or variants. More recently, genetic panels have been implemented as part of solid tumor malignancy testing assessing somatic alterations. One example is targeted variant panels for thyroid nodules that are not conclusively malignant or benign upon fine-needle aspiration (FNA). We systematically reviewed published studies from 2009 to 2018 that contained genetic data from preoperative FNA specimens on cytologically indeterminate thyroid nodules (ITNs) that subsequently underwent surgical resection. Pooled prevalence estimates per gene and variant, along with their respective positive predictive values (PPVs) for malignancy, were calculated. Summary: Our systematic search identified 540 studies that were supplemented by 18 studies from bibliographies or personal files. Sixty-one studies met all inclusion criteria and included >4600 ITNs. Overall, 26% of nodules contained at least 1 variant or fusion. However, half of them did not include details on the specific gene, variant, and/or complete fusion pair reported for inclusion toward PPV calculations. The PPVs of genomic alterations reported at least 10 times were limited to BRAFV600E (98%, 95% confidence interval [CI 96-99%]), PAX8/PPARG (55% [CI 34-78%]), HRASQ61R (45% [CI 22-72%]), BRAFK601E (42% [CI 19-68%]), and NRASQ61R (38% [CI 23-55%]). Excluding BRAFV600E, the pooled PPV for all other specified variants and fusions was 47%. Multiple variants within the same nodule were identified in ∼1% of ITN and carried a cumulative PPV of 77%. Conclusions: The chance that a genomic alteration predicts malignancy depends on the individual variant or fusion detected. Only five alterations were reported at least 10 times; BRAFV600E had a PPV of 98%, while the remaining four had individual PPVs ranging from 38% to 55%. The small sample size of most variants and fusion pairs found among ITNs, however, limits confidence in their individual PPV point estimates. Better specific reporting of genomic alterations with cytological category, histological subtype, and cancer staging would facilitate better understanding of cancer prediction, and the independent contribution of the genomic profile to prognosis.

Project description:The aim was to compare the usefulness of selected thyroid sonographic risk-stratification systems in the diagnostics of nodules with indeterminate/suspicious cytology or unequivocal cytology in a population with a history of iodine deficiency. The diagnostic efficacy of ACR-TIRADS (the American College of Radiology Thyroid Imaging Reporting and Data Systems), EU-TIRADS (European Thyroid Association TIRADS), Korean-TIRADS, Kwak-TIRADS, AACE/ACE-AME-guidelines (American Association of Clinical Endocrinologists/ American College of Endocrinology-Associazione Medici Endocrinologi guidelines) and ATA-guidelines (American Thyroid Association guidelines) was evaluated in 1000 nodules with determined histopathological diagnosis: 329 FLUS/AUS (10.6% cancers), 167 SFN/SHT (11.6% cancers), 44 SM (77.3% cancers), 298 BL (benign lesions), 162 MN (malignant neoplasms). The percentage of PTC (papillary thyroid carcinoma) among cancers was higher in Bethesda MN (86.4%) and SM (suspicion of malignancy) nodules (91.2%) than in FLUS/AUS (57.1%, p < 0.005) and SFN/SHT (suspicion of follicular neoplasm/ suspicion of Hürthle cell tumor) nodules (36.8%, p < 0.001). TIRADS efficacy was higher for MN (AUC: 0.827-0.874) and SM nodules (AUC: 0.775-0.851) than for FLUS/AUS (AUC: 0.655-0.701) or SFN/SHT nodules (AUC: 0.593-0.621). FLUS/AUS (follicular lesion of undetermined significance/ atypia of undetermined significance) nodules assigned to a high risk TIRADS category had malignancy risk of 25%. In the SFN/SHT subgroup none TIRADS category changed nodule's malignancy risk. EU-TIRADS and AACE/ACE-AME-guidelines would allow diagnosing the highest number of PTC, FTC (follicular thyroid carcinoma), HTC (Hürthle cell carcinoma), MTC (medullary thyroid carcinoma). The highest OR value was for Kwak-TIRADS (12.6) and Korean-TIRADS (12.0). Conclusions: TIRADS efficacy depends on the incidence of PTC among cancers. All evaluated TIRADS facilitate the selection of FLUS/AUS nodules for the surgical treatment but these systems are not efficient in the management of SFN/SHT nodules.

Project description:ObjectiveThyroid cancer is the third most prevalent cancer among females. Genetic testing based on next-generation sequencing may provide an auxiliary diagnosis to reduce cytologically diagnostic uncertainty. However, commercial multigene tests are not widely available and are not well-tested in the Chinese population.MethodsIn this study, we designed a multigene testing panel and evaluated its performance in 529 cytologically indeterminate thyroid nodules (Bethesda III, IV and V). The molecular data of the DNA mutations and RNA fusions of fine needle aspiration samples were reviewed in conjunction with a clinical diagnosis, pathological reports, and definitive surgery for retrospective analysis. Then, the molecular risk stratification was investigated for its accuracy in malignant risk prediction.ResultsThe overall combined consistency revealed substantial agreement (Kappa = 0.726) with the sensitivity, specificity, positive predictive value, and negative predictive values of 97.80%, 82.14%, 98.99%, and 67.65%, respectively. The most common aberration was BRAFV600E (82.59%), followed by NRAS mutants (4.07%), RET fusions (3.70%), and KRAS mutants (3.15%). Two cases (0.44%) were categorized into a high-risk group, 426 cases (94.67%) were categorized into a BRAF-like group with totally histopathologic papillary patterned tumors, and 22 cases (4.89%) were categorized into a RAS-like group with 14 papillary and eight follicular patterned tumors when the cohort concurrent aberrations were excluded. Potentially aggressive features may be related to concurrent molecular alterations of BRAFV600E with TERTQ302R, and AKT1L52R, NRASG12C, NRASQ61R, and CCDC6-RET fusions.ConclusionsThis study provided a multigene panel for identifying benign nodules from cytologically indeterminate thyroid nodules to avoid unnecessary surgery. We provide further evidence for using molecular risk stratification as a promising predictor of disease outcomes. The results of this study may be limited by the extremely high prevalence of cancer in the cohort for clinical reference.

Dataset Information

Molecular testing for cytologically suspicious and malignant (Bethesda V and VI) thyroid nodules to optimize the extent of surgical intervention: a retrospective chart review.

Background

Methods

Results

Conclusions

Publications

Molecular testing for cytologically suspicious and malignant (Bethesda V and VI) thyroid nodules to optimize the extent of surgical intervention: a retrospective chart review.

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