Performance of Afirma genomic sequencing classifier vs gene expression classifier in Bethesda category <scp>III</scp> thyroid nodules: An institutional experience

Background Molecular testing (MT) of thyroid fine‐needle aspiration (FNA)‐derived genetic material is commonly used to assess malignancy risk for indeterminate cases. The Bethesda System for Reporting Thyroid Cytopathology (TBS) provides limited guidance for the appropriate use of category III (atypia of undetermined significance [AUS]). The authors combined MT with cytomorphology to monitor AUS diagnoses in a cytopathology laboratory. Methods Neoplasia‐associated genetic alterations (NGAs) were determined by MT of preoperative FNA biopsies or resected malignancies and were categorized as BRAF V600E mutations, RAS‐like mutations (HRAS, NRAS, or KRAS mutations or non‐V600E BRAF mutations), or other mutations. Results Among 7382 thyroid FNA biopsies, the AUS rate was 9.3% overall and ranged from 4.3% to 24.2% among 6 cytopathologists (CPs) who evaluated >150 cases. The ratio of specimens falling into TBS category III to specimens falling into category VI (malignant) (the III:VI ratio) was 2.4 overall (range, 1.1‐8.1), and the ratio of specimens falling into TBS categories III and IV (follicular neoplasm or suspicious for follicular neoplasm) combined (III+IV) to specimens falling into category VI (the [III+IV]:VI ratio) was 2.9 overall (range, 1.4‐9.5). MT was performed on 588 cases from 560 patients (79% women) with a median age of 56 years (range, 8‐89 years). BRAF V600E mutation was the most common (76% of cases) in TBS category VI and was rare (3%) in category III. RAS‐like mutations were most common in TBS categories III (13%), IV (25%), and V (suspicious for malignancy) (17.5%). The NGA rate in AUS cases fell between 5% and 20% for 5 of 6 CPs and did not correlate with the III:VI ratio or the (III+IV):VI ratio. Conclusions Lack of correlation between the NGA rate and easily calculable diagnostic ratios enables the calibration of diagnostic thresholds, even for CPs who have normal metrics. Specifically, calculation of the NGA rate and the III:VI ratio may allow individual CPs to determine whether they are overcalling or undercalling cases that other CPs might otherwise recategorize.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Combining molecular testing and the Bethesda category III:VI ratio for thyroid fine‐needle aspirates: A quality‐assurance metric for evaluating diagnostic performance in a cytopathology laboratory

Gokozan

Dilcher

Alperstein

et al. 2021

“…21,22,39 In fact, the majority of NIFTP cases are cytologically diagnosed in the indeterminate categories, with 31% in AUS/FLUS, 26.6% in FN/SFN, and 24.3% in SFM. 38 It is important to underline that a morphological diagnosis of NIFTP on cytology material alone cannot be rendered, and in fact, it can only be included among the possible differential diagnoses for FNAC. 22,39 Different papers have analyzed the genetic alterations in NIFTP.…”

Section: Cancer Cytopathologymentioning

confidence: 99%

“…The indeterminate categories and their ROMs have also been affected by the introduction of NIFTP, which seems to have a significant impact on the cytological classification among the different categories 21,22,39 . In fact, the majority of NIFTP cases are cytologically diagnosed in the indeterminate categories, with 31% in AUS/FLUS, 26.6% in FN/SFN, and 24.3% in SFM 38 . It is important to underline that a morphological diagnosis of NIFTP on cytology material alone cannot be rendered, and in fact, it can only be included among the possible differential diagnoses for FNAC 22,39 .…”

Section: Radiologymentioning

confidence: 99%

“…Similar results of a decrease in the ROM are documented in AUS/FLUS lesions with a Hürthle cell pattern. [35][36][37] Zhang et al 38 compared these classifiers in terms of diagnostic performance and effect on the clinical management of indeterminate thyroid nodules. In their series, these authors found that, compared with GEC, GSC demonstrated an increased benign call rate (77.3% vs 52%), a decreased rate of surgery (31.4% vs 51.2%), and greater malignant histological confirmation (29% vs 9.8%) associated with a suspicious Afirma result, as well as improved specificity (82.8% vs 54.5%), an improved positive predictive value (29% vs 9.8%), and improved diagnostic accuracy (83.9% vs 56.7%), while maintaining high sensitivity and a high negative predictive value.…”

Section: Cancer Cytopathologymentioning

confidence: 99%

See 1 more Smart Citation

Preoperative diagnosis of thyroid nodules: An integrated multidisciplinary approach

Eloy¹,

Russ²,

Suciu³

et al. 2022

Self Cite

Because of the coronavirus disease 2019 pandemic, the joint session between the European Society of Pathology Working Groups of Endocrine Pathology and Cytopathology, initially scheduled in Glasgow (United Kingdom) for September 1, 2020, was converted into a virtual meeting that took place on December 8, 2020. Chaired by Catarina Eloy (Porto, Portugal) and Philippe Vielh (Paris, France), this session was entitled "Diagnosis of Thyroid Nodules: An Integrated Multidisciplinary Approach." The title reflects how a combined approach is critical to helping us better characterize thyroid nodules preoperatively. Gilles Russ (Paris, France), a radiologist specializing in thyroid ultrasonography, described the various systems for stratifying the risk of malignancy (ROM) in adults, and he was followed by Voichita Suciu (Villejuif, France), an interventional cytopathologist, who reported the extensive experience of the one-stop clinic set up at the Gustave Roussy Cancer Center. Three additional cytopathologists focused on specific thyroid cytopathology issues: Sarah J. Johnson (Newcastle Upon Tyne, United Kingdom) illustrated new entities and potential pitfalls, Esther Diana Rossi (Rome, Italy) talked about indeterminate cytology (especially atypia), and Liron Pantanowitz (Ann Arbor, Michigan) discussed the potential of using both molecular and artificial intelligence (AI) tools. This report summarizes the main ideas and data shared between speakers and attendees during this successful session. RadiologySince the late 2010s, thyroid ultrasound (US) has evolved in 2 directions. First, risk stratification of thyroid nodules with US emerged as a new concept. Second, during the same period, thermal ablation was applied for treating large thyroid nodules and cancer recurrences. In 2017, the European Thyroid Association issued guidelines for US malignancy risk stratification in adults: the European Thyroid Imaging and Reporting Data System (EU-TIRADS). 1 Those guidelines include a standardized illustrated lexicon and report to improve interobserver description agreement. The core of the system is the score that allows a quantitative approach to ROM. It ranges from 1 to 5 with an increasing ROM: 1 is for normal, 2 is for benign (ROM ≈ 0%), 3 is for low risk (ROM ≤ 4%), 4 is for intermediate risk (ROM = 6%-17%), and 5 is for high risk (ROM = 26%-87%). Determining the score is mainly based on looking for features of high suspicion (a taller than wide shape, irregular margins, microcalcifications, and marked hypoechogenicity) and, if none of these are present, on the echogenicity of the solid component of the lesion. A score of 2 corresponds to simple cysts and mainly spongiform nodules. Elsewhere, similar systems have been issued, including the British Thyroid Association System, 2 the American College of Radiology Thyroid Imaging and Reporting Data System (ACR-TIRADS), 3 the American Thyroid Association System, 4 and the Korean Thyroid Imaging and Reporting Data System (K-TIRADS). 5 Besides malignancy risk stratification, these syst...

Performance of Afirma genomic sequencing classifier and histopathological outcome are associated with patterns of atypia in Bethesda category III thyroid nodules

Jin

Lew

Pantanowitz

et al. 2022

Self Cite

Background:Data on Afirma’s genomic sequencing classifier (GSC) performance in atypia of undetermined significance (AUS) subcategories is limited. This study investigated GSC performance in AUS nodules with architectural atypia (AUS‐A), cytological atypia (AUS‐C), architectural and cytological atypia (AUS‐AC), and predominantly Hürthle cells (AUS‐HC).Methods:This study retrieved consecutive thyroid nodules having a recurrent cytologic diagnosis of AUS with qualifiers and a concurrent GSC diagnostic result. All nodules were followed by either surgical intervention or clinical and/or ultrasound monitoring (≥6 months). GSC benign call rate (BCR), rate of histology‐proven malignancy, and diagnostic parameters of GSC were calculated for individual AUS subcategories. Statistical analysis was performed using the Fisher exact test.Results:A total of 135 AUS nodules fulfilled inclusion criteria, including 79 AUS‐A, 9 AUS‐C, 29 AUS‐AC, and 18 AUS‐HC. BCR was 72.2%, 66.7%, 44.8%, and 77.8% in AUS‐A, AUS‐C, AUS‐AC, and AUS‐HC, respectively. AUS‐A showed a greater BCR than AUS‐AC (p < .05). All GSC‐benign nodules were considered benign on clinical or surgical follow‐up. Among GSC‐suspicious nodules, histology‐proven malignancies represented 4.5% of AUS‐A, 0% of AUS‐C, 56.3% of AUS‐AC, and 25.0% of AUS‐HC cases. AUS‐AC demonstrated a higher malignant rate compared with AUS‐A (p < .05). GSC offers 100% NPV and a wide range (5%–56%) of PPV across all AUS subcategories. AUS‐AC demonstrated a greater PPV compared with AUS‐A (p < .05).Conclusion:BCR of GSC and malignant rates associated with suspicious GSC may differ in various AUS subcategories. GSC‐suspicious nodules with both architectural and cytologic atypia are more likely to be malignant. These findings may improve clinical triage and/or management of patients with AUS thyroid nodules.