Dorota Słowińska-Klencka

The studies on the effectiveness of various TIRADS in the diagnostics of thyroid nodules differ in the method of ultrasound image assessment: real time (rtUS) vs. static ultrasonography (stUS). The aim of the study was to evaluate the impact of those two methods on the categorization of nodules in EU-TIRADS. Three experienced raters assessed 842 nodules in routine rtUS and reassessed with the use of sUS. Reproducibility of the assessment of malignancy risk features and categorization of nodules with EU-TIRADS was estimated with Krippendorff’s alpha coefficient (Kα). The reproducibility of EU-TIRADS categories on sUS in relation to rtUS was in range 70.9–76.5% for all raters (Kα: 0.60–0.68) with the highest reproducibility for category 3 (80.0–86.5%) and the lowest for category 5 (48.7–77.8%). There was a total disagreement of the identification of microcalcifications on sUS in relation to rtUS, a strongly variable reproducibility of marked hypoechogenicity (12.5–84.6%, Kα: 0.14–0.48) and a tendency toward more frequent identification of the non-oval shape on sUS. The percentage of agreement for each pair of raters in assigning the EU-TIRADS category on sUS was in the range 71.6–72.3% (Kα: 0.60–0.62). The method of sonographic image evaluation influences the nodule’s feature assessment and, eventually, the categorization within EU-TIRADS.

The aim of the study was to analyze the diagnostic usefulness of the combined assessment of the ultrasound risk category of the nodule (evaluated with EU-TIRADS system), the presence of BRAF V600E mutation and the expression of selected microRNAs (miR-146b, miR-221 and miR-222) in Bethesda category III thyroid nodules, separately for cases with nuclear atypia (AUS-nuclear) and cases with other types of atypia (AUS-other). We evaluated 161 nodules (66 AUS-nuclear and 95 AUS-other) with known results of postoperative histopathological examination. The rate of cancer and the rate of PTC among cancers were nearly three times higher in the AUS-nuclear than the AUS-other group. For AUS-nuclear nodules, the most effective diagnostic panel included, in addition to repeat FNA, the assessment of BRAF V600E mutation and the expression of miR-146b and miR-222 (sensitivity: 93.5%, specificity: 80.0%). For AUS-other nodules, a two-step procedure was most effective: at the first stage, forgoing surgical treatment in subjects with a benign repeat FNA outcome, and, at the second stage, the assessment of miR-222 expression and the EU-TIRADS category (sensitivity: 92.3%, specificity: 76.8%). The optimal use of molecular methods in the diagnostics of category III thyroid nodules requires a separate approach for nodules with nuclear atypia and nodules with other types of atypia.

The aim of the study was to examine the benefits of the joint use of repeat FNA (rFNA) and EU-TIRADS in category III nodules in relation to the kind of atypia: nuclear vs. architectural (denoted by AUS and FLUS respectively). The study included 127 AUS and 1739 FLUS nodules with a known category of EU-TIRADS. Repeat FNA was performed in 82 AUS and 934 FLUS nodules of which 57 and 515 were excised, respectively. AUS nodules had higher malignancy risk than FLUS nodules. EU-TIRADS showed higher accuracy for AUS nodules, the opposite to rFNA, that had higher accuracy for FLUS nodules. The combined criterion for AUS nodules (at least rFNA-V or EU-TIRADS-4) maximized sensitivity (92.3%) with acceptable specificity (70.0%); OR: 28.0. In the case of FLUS nodules, the combined criterion (rFNA-V or EU-TIRADS-5) maximized specificity (95.2%) with 57.7% sensitivity and a low percentage (13.9%) of positive nodules, OR: 27.0. In both types of nodules, the low risk category in EU-TIRADS and benign result of rFNA excluded cancer. Concluding, category III nodules with and without nuclear atypia differ in their risk of malignancy and, consequently, diagnostic criteria adopted for the evaluation of these nodules with rFNA and EU-TIRADS should be specific to AUS and FLUS nodules.

The aim of this study was to evaluate the risk of malignancy (RoM) in category III thyroid nodules of the Bethesda system in patients with and without Hashimoto thyroiditis (HT) and to analyze whether obtaining category III with a repeat FNA (rFNA) increases RoM. The study included 563 HT and 1250 non-HT patients; rFNA was performed in 349 and 575 patients, and surgical treatment in 160 and 390, respectively. There was no difference in RoM between HT and non-HT patients in the whole examined population (lower limit of RoM), nor in operated patients (upper limit of RoM), HT: 5.0–17.5%, non-HT: 4.7–15.1%. RoM in patients with AUS nodules (with nuclear atypia) was similar in both groups (HT: 21.7–40.0%, non-HT: 16.9–41.4%), as it was in patients with FLUS nodules (with architectural atypia) (HT: 3.5–13.3%, non-HT: 4.0–13.0%). In patients from both groups together, with category III diagnosed twice and AUS identified at least once, RoM was 16.7–50.0% and it was higher than that in patients with FLUS nodule diagnosed twice: 3.2–13.0% (p < 0.005). Concluding, RoM in category III nodules is not affected by the presence of HT. Subcategorization of category III nodules (FLUS vs. AUS) may provide guidance toward further follow-up or surgery in both groups.

The aim of the study was to validate thyroid US malignancy features, especially the nodule’s shape, and selected Thyroid Imaging Reporting and Data Systems (EU-TIRADS; K-TIRADS; ACR-TIRADS, ATA guidelines) in patients with or without Hashimoto’s thyroiditis (HT and non-HT groups). The study included 1188 nodules (HT: 358, non-HT: 830) with known final diagnoses. We found that the strongest indications of nodule’s malignancy were microcalcifications (OR: 22.7) in HT group and irregular margins (OR:13.8) in non-HT group. Solid echostructure and macrocalcifications were ineffective in patients with HT. The highest accuracy of nodule’s shape criterion was noted on transverse section, with the cut-off value of anteroposterior to transverse dimension ratio (AP/T) close to 1.15 in both groups. When round nodules were regarded as suspicious in patients with HT (the cut-off value of AP/T set to ≥1), it led to a three-fold increase in sensitivity of this feature, with a disproportionally lower decrease in specificity and similar accuracy. Such a modification was effective also for cancers other than PTC. The diagnostic effectiveness of analyzed TIRADS in patients with HT and without HT was similar. Changes in the threshold for AP/T ratio influenced the number of nodules classified into the category of the highest risk, especially in the case of EU-TIRADS.

Purpose: Equivocal categories (III, IV, V) of the Bethesda System for Reporting Thyroid Cytology (BSRTC) are characterized by high variability of the estimated risk of malignancy. The aim of the study was to analyze the reproducibility of classification of nodules into an equivocal category and the frequency of malignancy (FoM) observed in such categories. Methods: Five experienced cytopathologists from three centers (A, B, C) independently performed reclassification of smears obtained from 213 thyroid nodules with equivocal routine cytology and known results of the postoperative histopathological examination. Results: The interobserver agreement among all cytopathologists was poor, with a Krippendorff’s alpha coefficient equaling 0.34. The intra-center agreement was higher than the inter-center (fair vs poor). Pathologists of the center A classified smears into categories II and III significantly less often and categories IV and V more often than pathologists of centers B and C. The joint FoM of nodules classified into any of categories IV–VI (regarded as an indication for surgery) was different among centers (A: 40.0%, B: 66.7%, C: 80.6%). The FoM of category III nodules with features of nuclear atypia (AUS) in center B and C was two times higher than that of other nodules of category III (FLUS), while in center A the FoM was similar. Conclusions: The use of published data on the risk of malignancy in nodules of particular BSRTC categories without concern for the uniqueness of the diagnostic center may lead to erroneous conclusions.

The aim of the study was to identify a possible relation between various ultrasonographic (US) appearances of Hashimoto′s thyroiditis (HT) and the risk of obtaining an alarming cytology of coexisting nodules. The study included 557 patients with HT, who had been referred for fine needle aspiration biopsy (FNA). We divided US patterns of HT (UP-HT) into eight groups: (a) Hypoechoic (compared to submandibular glands), homogeneous/fine echotexture; (b) hypoechoic, heterogeneous/coarse echotexture; (c) marked hypoechoic (darker than strap muscles), heterogeneous/coarse echotexture; (d) heterogeneous echotexture with hyperechoic, fibrous septa; (e) multiple, discrete marked hypoechoic areas (sized as 1 to 6 mm); (f) normoechoic pseudo-nodular areas; (g) echostructure similar to connective tissue; (h) thyroid parenchyma with no signs of HT. Indications for a surgical treatment resulting from the FNA outcome (categories IV–VI of Bethesda System for Reporting Thyroid Cytopathology) were identified only in patients with variants b, c, and e of UP-HT, but merely the “multiple, discrete marked hypoechoic areas” variant significantly increased the odds of obtaining such cytology (OR:5.7). The presence of the “normoechoic pseudo-nodular areas” variant significantly increased the odds for the benign cytology (OR:1.7). There are significant differences in the frequency of obtaining an alarming cytology in relation to the UP-HT variant.

The aim of this study was to compare the diagnostic effectiveness of EU-TIRADS in two groups of nodules with equivocal cytology (categories III-V of Bethesda system), with and without Hürthle cells (HC and non-HC). The study included 162 HC and 378 non-HC nodules with determined histopathological diagnosis (17.9% and 15.6% cancers). In both groups calculated and expected risk of malignancy (RoM) for high, intermediate and benign risk categories of EU-TIRADS were concordant. RoM for low risk category was higher than expected in both groups, but especially in HC (HC: 13.9%, non-HC: 7.0%, expected: 2–4%). The majority of cancers in HC of that category were follicular thyroid carcinomas (FTC) and Hürthle cell thyroid carcinoma (HTC) (60.0% vs. non-HC: 16.7%). The diagnostic efficacy of EU-TIRADS was lower in HC (the area under the receiver operating characteristics curve (AUC): 0.621, sensitivity (SEN): 44.8%, specificity (SPC): 78.9% for high risk threshold) than in non-HC (AUC: 0.711, SEN: 61.0%, SPC: 77.7%). AUC was the highest for category V (AUC > 0.8, both groups) and the lowest for category IV (inefficient, both group). If intermediate risk category was interpreted as an indication for surgery, 25% of cancers from category III and 21.4% from category IV would not be treated in the HC group (0.0% and 7.4% from non-HC group, respectively). EU-TIRADS does not aid making clinical decisions in patients with cytologically equivocal HC nodules, particularly those classified into category IV of Bethesda System for Reporting Thyroid Cytopathology (BSRTC).

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.

Purpose The aim was to find whether the presence of Hürthle cells (HC) in a smear influences the categorization of FNA results or the risk of malignancy (RoM) of particular categories of cytological diagnosis. Methods 25,220 FNA performed in a single center in years 2005–2017 were analyzed. Almost all the examined patients were exposed to moderate iodine deficiency for most of their lives. The distribution of FNA outcome categories was compared between two groups: with or without HC (HC and non-HC). The RoM was evaluated on the basis of postoperative histopathological examination (3082 patients). Results HC were found in 7.5% of diagnostic FNA. HC nodules were classified into categories II (78.2% vs. 91.9%, p < 0.0000) and VI (0.4% vs. 1.2%, p = 0.0017) less often than non-HC nodules, but more frequently to categories III (14.4% vs. 5.8%, p < 0.0000), IV (11.2% vs. 0.9%, p < 0.0000) and V (1.5% vs. 0.8%, p = 0.0013). There were no significant differences in RoM between HC and non-HC nodules. The RoM in HC and non-HC nodules of particular categories of the Bethesda system was as follows: II: 1.8% vs. 0.8%, III: 9.7% vs. 3.8% when only the last FNA was considered and 10.8% vs. 6.4% when the category III in any performed FNA was considered; IV: 12.7% vs. 10.9%; V: 41.7% vs. 58.2%; and VI: 100% vs. 96.9%. Conclusions HC nodules are classified into categories of equivocal cytological outcomes more often than nodules without HC. Nevertheless, the presence of HC in a smear does not significantly affect the RoM of FNA categories.