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OBJECTIVE: To determine whether early repeat fine needle aspiration biopsy (FNA) has an effect on adequate or atypia of undetermined significance (AUS) cytology rates in thyroid nodules with inadequate or AUS result in the first FNA.
METHODS: Nodules of patients who underwent repeat biopsy due to insufficient or AUS cytology between 2019-2022 were included. Data of the patients and ultrasonographic, cytological and histopathological results of the nodules were recorded. Additionally, the time between the two biopsies was noted. The first was called \"initial\" and the second was called \"rebiopsy\". Five different paired groups were formed according to the time between two consecutive biopsies; before and after 1 month, 45 days, 2 months, 3 months, and 6 months. The groups were compared in terms of adequate and AUS cytological results.
RESULTS: We evaluated 1129 patients with 2187 nodules undergoing FNAB. After excluding nodules with one FNA result and/or missing data, 966 nodules of 628 patients who underwent FNA at least twice were included. Initial cytology was nondiagnostic (ND) in 665 (30.4%) and AUS in 301 (13.8%) nodules. The mean age of the patients was 52.0 ± 11.9 years, and the female sex ratio was 78.8% (n = 495). There were no differences in adequate or AUS rebiopsy results according to the different time interval groups (p > 0.05 for all). AUS result was statistically insignificantly more frequent in nodules with initially AUS nodules when rebiopsy was performed before 1 month in comparison to after 1 month (53.8%, 27.1%; p = 0.054). Accuracy of rebiopsy was also similar in the time intervals groups (p > 0.05 for all).
CONCLUSIONS: In patients with inadequate or AUS initial biopsy, the rate of adequate or AUS cytology results at rebiopsy did not vary with the timing of repeat biopsy indicating that there may be no need to wait 1 month for a repeat biopsy. In patients with suspicious nodules, biopsy might be repeated before 1 month.

UNASSIGNED: This study aimed to investigate ultrasound (US) features of thyroid nodules categorized as nondiagnostic (ND) and atypia of undetermined significance (AUS) according to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) and their potential implications for clinical management.
UNASSIGNED: A retrospective study was conducted on patients who underwent thyroid nodules FNAC between 2019 and 2023. Nodules falling into the ND and AUS categories were analyzed for US features, nodule size, composition, echogenicity, shape, margin, echogenic foci, the distribution of the American College of Radiology\'s Thyroid Imaging Reporting and Data System (ACR TI-RADS) categories, and other parameters. The study included a total of 1,199 patients and 1,252 nodules (ND: 1110; AUS: 142).
UNASSIGNED: No significant differences in age, gender, nodule features, echogenicity, shape, margin, echogenic foci, TI-RADS scores, localization, number of nodules, or thyroid parenchymal disease presence were found between the ND and AUS categories (p > 0.05). Also, no statistically significant difference in nodule size (<10 mm vs. ≥10 mm) existed between the ND and AUS categories (p = 0.475). Both showed predominantly solid composition and hyperechoic/isoechoic echogenicity. High proportions of TI-RADS 4 nodules were observed in both groups, with 727 (65.5%) in ND and 95 (66.9%) in AUS.
UNASSIGNED: This study found no statistically significant differences in US characteristics between the ND and AUS categories, indicating potential similarities in their radiological appearances. Also, no significant difference in nodule size (<10 mm and ≥10 mm) was observed between these categories. Clinical management should consider further investigations, including repeat FNAC, due to the diagnostic challenges and malignancy risk in both categories.

UNASSIGNED: After liquid-based cytology (LBC) technique developed for cervical cytology, it has been used for nongynecological samples and has been very successful. It offers having extra slides of the samples for further examination and ancillary tests. Moreover, cell blocks can be formed from the residue material. The study aimed to evaluate the importance of preparing a second LBC slide or a cell block from the residue material of thyroid fine needle aspiration (FNA) samples to reach a definitive diagnosis in cases diagnosed as nondiagnostic (ND) after the first slide.
UNASSIGNED: Seventy five cases diagnosed as ND after the first slide were included in study. For 50 cases, the second LBC slides were prepared (LBC group); for 25 cases, cell block was performed from residue material (CB group). Two groups were compared in terms of reaching a definitive diagnosis.
UNASSIGNED: At the end of secondary procedures, a definitive diagnosis was reached in a total of 24 cases (32%). Twenty of 50 cases (40%) in LBC group reached a definitive diagnosis while four cases (16%) in the CB group reached a definitive diagnosis. Achieving a definitive diagnosis was found statistically higher in the LBC group in which the second slide was formed compared to the CB group (P =0.036).
UNASSIGNED: Preparing a second slide with LBC method is more purposive than preparing a cell block from the residue material of thyroid FNA samples. Reducing the percentage of ND cases will protect patients from complications and morbidity that may arise from repeated FNA.

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.
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.
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).
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.

The first Bethesda classification category of thyroid fine-needle aspiration biopsy (FNAB) is nondiagnostic (ND), which indicates that the specimen\'s cellularity is inadequate for evaluation. This work investigated the effect of needle diameter size on ND rates by comparing diagnostic outcomes of FNAB samples collected with 23-, 25-, and 27-gauge needles.
This was a retrospective analysis of samples collected from patients undergoing FNAB between 2018 and 2021. It was conducted in an otolaryngology department in a university teaching hospital.
Of the 699 aspirations, 144, 335, and 220 were performed using 23-, 25-, and 27-gauge needles, respectively. ND rates increased significantly when using 27-gauge compared with 23- to 25-gauge needles (P = .002), and a significantly lower ND rate was found for the 25-gauge needle compared with the 27-gauge needle (P = .001). Furthermore, increased nodule size was associated with reduced ND rate (odds ratio, 0.801; 95% confidence interval, 0.691-0.929).
The 25-gauge needles are superior to 27-gauge needles in reducing ND rates of thyroid nodule FNAB specimens. Future prospective studies should be performed to confirm these findings.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) reports a 25% rate of malignancy (ROM) for the Milan I: Nondiagnostic (ND) category. We clarify the ROM of ND salivary gland fine-needle aspirations (SGFNAs) based on our institutional experience and review of the literature.
METHODS: Overall risk of malignancy (OROM) and that for those with surgical/flow cytometric follow-up (FROM) for each category and \"all-comers\" were calculated for Emory SGFNAs from January 2010 through March 2021. From a literature review of 50 articles using MSRSGC, distribution of diagnoses, rates of follow-up, FROM, and OROM by category were calculated. FROMs and OROMs between ND FNAs and all-comers were compared. Milan I rate was compared with the ratio of Milan I OROM to all-comer OROM.
RESULTS: Of 819 SGFNAs at Emory, 12.8% (n = 105/819) were ND. Thirty-two had known follow-up, with 12 (37.5%) being malignant. Nonmucinous cyst contents accounted for 26.7% of ND SGFNAs (n = 28/105); all 7 with surgical follow-up were benign. Of 50 MSRSGC studies, 18.2% (n = 2384/13,129) of SGFNAs were classified as ND, 26.6% (n = 635/2384) with known follow-up. Total FROM and OROM for ND FNAs (15.7% and 4.1%, respectively) were significantly lower than those for all-comers (24.9% and 11.4%, respectively) (p < .001). There was no relationship between rate of ND SGFNA and ND ROM.
CONCLUSIONS: The ND category is associated with a lower ROM than that of all-comer SGFNA patients. The \"true\" ROM for ND SGFNAs is likely best estimated by the 4.1% OROM. SGFNAs showing nonmucinous cyst contents have a particularly low ROM. Rate of ND SGFNAs does not influence ND ROM.

Fine-needle aspiration (FNA) results classified as the nondiagnostic category of the Milan system for reporting salivary gland cytopathology (MSRSGC) may be infrequently encountered in children. Clinical management may be challenging due to lack of data regarding outcomes and underlying causes.
We retrospectively analyzed 106 consecutive pediatric salivary gland FNAs (2000-2020; 45% performed under image guidance). The outcomes of patients with nondiagnostic results were analyzed. Clinical parameters, FNA procedural parameters, and histopathologic parameters were compared between diagnostic and nondiagnostic cases. A root cause analysis was performed using the fishbone diagram and the 5 Whys method.
A total of 103 initial FNAs were identified. The nondiagnostic rates for initial and repeat biopsy were 16% (16/103) and 67% (2/3), respectively. Initial nondiagnostic FNAs were most frequently managed by clinical/radiologic follow-up only (56%, 9/16), followed by direct surgery (19%, 3/16) and repeat FNA (19%, 3/16). By histologic and clinical/radiologic follow-up, the risk of malignancy for nondiagnostic cases was zero. Palpation guidance (P < .05), inadequate sampling determined by rapid on-site evaluation (P < .01), and lesions with cystic, vascular, or diffuse nature (P < .05) were significantly associated with nondiagnostic results. By root cause analysis, proceduralist sampling error and lack of ultrasound guidance were the most common primary and secondary causes, respectively.
Pediatric salivary gland lesions of the nondiagnostic MSRSGC category have minimal risk of malignancy and may be successfully managed by clinical/radiologic follow-up. The root causes for nondiagnostic results were often multifactorial and primarily related to proceduralist sampling, characteristics of the lesions, and lack of ultrasound guidance.

We compared American Thyroid Association (ATA) guidelines, Korean (K)-Thyroid Imaging, Reporting and Data Systems (TIRADS), EU-TIRADS, and American College of Radiology (ACR) TIRADS in diagnosing malignancy for thyroid nodules with nondiagnostic/unsatisfactory cytology. Among 1143 nondiagnostic/unsatisfactory aspirations from April 2011 to March 2016, malignancy was detected in 39 of 89 excised nodules. The minimum malignancy rate was 7.82% in EU-TIRADS 5 and 1.87-3.00% in EU-TIRADS 3-4. In the other systems, the minimum malignancy rate was 14.29-16.19% in category 5 and ≤3% in the remaining categories. Although the EU-TIRADS category ≥ 5 exhibited the highest positive likelihood ratio (LR) of only 2.214, category ≥ 5 in the other systems yielded the highest positive LR of >5. Receiver operating characteristic (ROC) curves of all systems to predict malignancy were located statistically above the diagonal nondiscrimination line (P for ROC curve: EU-TIRADS, 0.0022; all others, 0.0001). The areas under the ROC curve (AUCs) were not significantly different among the four systems. The ATA guidelines, K-TIRADS, and ACR TIRADS may be useful to guide management for nondiagnostic/unsatisfactory nodules. The EU-TIRADS, although also useful, exhibited inferior performance in predicting malignancy for nondiagnostic/unsatisfactory nodules in Korea, an iodine-sufficient area.

OBJECTIVE: The Bethesda System for Reporting Thyroid Cytopathology is a uniform method used worldwide to report thyroid fine-needle aspiration (FNA) outcomes. This study focuses on the Nondiagnostic/Unsatisfactory category, designated as Bethesda1 (B1). The documented risk of malignancy for B1 nodules can vary significantly, implying this category is not homogenous and might be composed of different subtypes. Our hypothesis was that B1 subgroups (blood only, insufficient thyrocytes, cyst content) will vary in their malignancy rate.
METHODS: The study design was observational and retrospective. The study population included 154 patients in the Galilee Medical Center who underwent FNA examination of the thyroid gland from 2013-2018 and had a B1 result. We looked at the final diagnosis of malignant or benign for patients who underwent surgery and calculated the malignancy rate for each subgroup.
RESULTS: Malignancy rates were higher in the Blood subgroup than in the other subgroups, and higher in the Thyrocytes subgroup than in the Cyst subgroup (P < .05). All malignancies were papillary thyroid carcinomas. There was no significant difference in the malignancy rate when we further divided the B1 samples into 2 groups based on the presence of epithelial cells. Many repeat FNA tests resulted in a different B1 subgroup.
CONCLUSIONS: The different malignancy rates suggest that individual management approaches should be considered for each B1 subgroup.