Thyroid Nodules with Indeterminate FNAC According to the Italian Classification System: Prevalence, Rate of Operation, and Impact on Risk of Malignancy. An Updated Systematic Review and Meta-analysis

Abstract

A thyroid nodule classified as indeterminate on fine-needle aspiration cytology (FNAC), hereafter referred to as an indeterminate thyroid nodule (ITN), represents a clinical dilemma. The Italian Consensus for the Classification and Reporting of Thyroid Cytology (ICCRTC) divides ITNs into low- and high-risk categories (i.e., TIR3A and TIR3B, respectively) to better manage patients. This study aimed to achieve high-evidence estimates of the prevalence, rate of operation, and risk of malignancy of ITNs, including TIR3A and TIR3B ITNs. This systematic review was conducted according to MOOSE to retrieve all original studies citing ICCRTC. The last search was performed in February 2022. The risk of bias of the included studies was assessed. Separate proportion meta-analyses were performed with a random-effect model using OpenMeta[Analyst]. The online search processed 271 studies, and 33 were finally considered. First, the cancer prevalence among ITNs was 32.4%. Second, the cancer prevalence among TIR3As was 12.4%, with heterogeneity (I2 90%) explained by a linear correlation between sample size and cancer rate (p = 0.009). Third, the cancer prevalence among TIR3Bs was 44.4%, with heterogeneity (I2 75%) explained by the inverse correlation between sample size and cancer rate (p = 0.031). Fourth, the prevalence of ITNs, TIR3A, and TIR3B among FNACs was 29.6%, 12.6%, and 12.9%, respectively, with sample size and TIR3B prevalence being inversely correlated (p = 0.04). Fifth, the operation rates of ITNs, TIR3A, and TIR3B were 54.3%, 48.3%, and 75.2%, respectively, and the sample size and TIR3A operation rate were inversely correlated (p = 0.010). These data strongly support the division of ITNs into low- and high-risk subcategories. Importantly for clinical practice, the cancer rate among ITNs is significantly influenced by the study sample size.

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study

“…There were some interesting additional findings in our study. First, according to a recent meta-analysis, 36 the occurrence of thyroid cancer in patients with indeterminate thyroid nodules appears to be substantially higher than the 5–30% originally described by Cibas and Ali in the Bethesda system for reporting thyroid cytopathology. 14 In our study, nearly 40% of patients with indeterminate thyroid nodules had thyroid cancer.…”

Solitary and multiple thyroid nodules as predictors of malignancy: a systematic review and meta-analysis

“…A more substantial problem, however, arises when the results of cytological evaluation are indeterminate, and physicians are left withsurgery as the only option to definitively diagnose any malignancy. However, given that surgical evaluation for all cases of indeterminate thyroid nodules is neither clinically possible nor recommended, it is imperative to establish variables such as nodularity as risk factors for malignancy in order to better clinically assess individual patient risk for cancer [44]. It has been estimated that if surgery is performed for all indeterminate cases of FNAC, thyroid cancer will be found in only 10-40% of the cases [45], making the rest of the surgeries needless and futile.…”

An Indeterminate for Malignancy FNA Report Does Not Increase the Surgical Risk of Incidental Thyroid Carcinoma

“…In previous experiences, the incidence of ITCs not detected by imaging ranged from 2.3 to 13%, with differences partly due to heterogeneity in terms of iodine supply and US-FNA diagnostic performance among different regions [ 3 , 22 ]. In our series, we collected 652 patients with an indeterminate cytological diagnosis (19.9%, 652/3270 vs. 29.6% in a recent Italian review), classified into BSRTC categories III and IV at 13.8% (451/3270) and 6.1% (201/3270) [ 35 ]. Patients who underwent surgery accounted for 25% (163/652), with lower surgery rates for class III and IV cases as compared to the literature (14.2%, 64/451 and 49.2%, 99/201, respectively) [ 35 ].…”

“…In our series, we collected 652 patients with an indeterminate cytological diagnosis (19.9%, 652/3270 vs. 29.6% in a recent Italian review), classified into BSRTC categories III and IV at 13.8% (451/3270) and 6.1% (201/3270) [ 35 ]. Patients who underwent surgery accounted for 25% (163/652), with lower surgery rates for class III and IV cases as compared to the literature (14.2%, 64/451 and 49.2%, 99/201, respectively) [ 35 ]. These findings can be explained by the recent clinical trend of implementing a more conservative approach by a follow-up of repeated FNA or molecular analyses, especially for indeterminate lesions with slow growth velocity and relatively small size (our series average diameter: 22.5 mm).…”

“…These findings can be explained by the recent clinical trend of implementing a more conservative approach by a follow-up of repeated FNA or molecular analyses, especially for indeterminate lesions with slow growth velocity and relatively small size (our series average diameter: 22.5 mm). Thyroid cancer was detected in 28.8% of cases (47/163), compared with the overmentioned review data of 32.4% [ 35 ]. Starting from 163 patients who underwent surgery for a cytological indeterminate diagnosis and selecting only cases with indeterminate nodules that subsequently proved to be benign on histologic examination, we found 22 ITCs (13,5%, 22/163), and all carcinomas turned out to be PTMCs, as already reported in the literature ( Table S1 ) [ 1 , 2 , 3 , 22 ].…”