UNASSIGNED: A deep convolutional neural network (DCNN) model was employed for the differentiation of thyroid nodules diagnosed as atypia of undetermined significance (AUS) according to the 2023 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The aim of this study was to investigate the efficiency of ResNeSt in improving the diagnostic accuracy of fine-needle aspiration (FNA) biopsy.
UNASSIGNED: Fragmented images were used to train and test DCNN models. A training dataset was built from 1,330 samples diagnosed as papillary thyroid carcinoma (PTC) or benign nodules, and a test dataset was built from 173 samples diagnosed as AUS. ResNeSt was trained and tested to provide a differentiation. With regard to AUS samples, the characteristics of the cell nuclei were compared using the Wilcoxon test.
UNASSIGNED: The ResNeSt model achieved an accuracy of 92.49% (160/173) on fragmented images and 84.78% (39/46) from a patient wise viewpoint in discrimination of PTC and benign nodules in AUS nodules. The sensitivity and specificity of ResNeSt model were 95.79% and 88.46%. The κ value between ResNeSt and the pathological results was 0.847 (P<0.001). With regard to the cell nuclei of AUS nodules, both area and perimeter of malignant nodules were larger than those of benign ones, which were 2,340.00 (1,769.00, 2,807.00) vs. 1,941.00 (1,567.50, 2,455.75), P<0.001 and 190.46 (167.64, 208.46) vs. 171.71 (154.95, 193.65), P<0.001, respectively. The grayscale (0 for black, 255 for white) of malignant lesions was lower than that of benign ones, which was 37.52 (31.41, 46.67) vs. 45.84 (31.88, 57.36), P <0.001, indicating nuclear staining of malignant lesions were deeper than benign ones.
UNASSIGNED: In summary, the DCNN model ResNeSt showed great potential in discriminating thyroid nodules diagnosed as AUS. Among those nodules, malignant nodules showed larger and more deeply stained nuclei than benign nodules.

OBJECTIVE: Few cytologically indeterminate thyroid fine-needle aspirations (FNAs) harbor BRAF V600E. Here, we assess interobserver agreement for The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III (atypia of undetermined significance [AUS]) FNAs harboring BRAF V600E and contrast their features with those harboring non-BRAF V600E alterations, with attention to cytopathology experience.
METHODS: Seven reviewers evaluated 5 AUS thyroid FNAs harboring BRAF V600E. To blind reviewers, cases were intermixed with 19 FNAs falling within other TBSRTC categories and in which genetic alterations other than BRAF V600E had been identified (24 FNAs total). Interobserver agreement against both \"index\" and most popular (\"mode\") diagnoses was calculated. Four additional BRAF V600E cases were independently reviewed.
RESULTS: Reviewers included 3 trainees and 3 American Board of Pathology (board)-certified cytopathologists. Board-certified cytopathologists, whose experience ranged from 2 to more than 15 subspecialty practice years, had known AUS rates. BRAF V600E was identified in 5 of 260 (2%) AUS FNAs. Interobserver agreement was higher among cytopathologists with more experience. Mode diagnosis differed from index diagnosis in 6 of 11 cases harboring RAS-like alterations; mode diagnosis was AUS in 4 of 5 BRAF V600E FNAs.
CONCLUSIONS: Atypia of undetermined significance of thyroid FNAs harboring BRAF V600E is uncommon yet relatively reproducible, particularly among pathologists with experience. It is advisable to sequence BRAF across V600 in such cases.

UNASSIGNED: Despite the common use of ultrasound (US)-guided fine-needle aspiration (FNA) for axillary node (AN) in breast cancer patients, only a limited number of studies are available regarding the diagnostic performance of AN-FNA according to the suspicion level based on US findings. This study compares the outcomes of US-guided AN-FNA in breast cancer patients, differentiating between those undergoing staging and surveillance.
UNASSIGNED: A cross-sectional retrospective study with retrospective analysis was conducted on 767 consecutive AN-FNA procedures performed in 2017 at Samsung Medical Center in Seoul, with 654 for staging and 113 for surveillance in breast cancer patients. The radiologists performed axillary US and the specific finding was prospectively classified into the AN-reporting and data system (AN-RADS) category 3-5 before FNA. The malignancy rate of each category was evaluated. The chi-square test, with or without Bonferroni correction, or Fisher\'s exact test was used to compare the malignancy rates between the staging and surveillance groups for each category.
UNASSIGNED: Among the 767 AN-FNAs, 424 (55.3%) were malignant. The malignancy rate was significantly higher in the staging group (59.5%) than in the surveillance group (31.0%, P<0.0001). The distribution of AN-RADS categories differed between the groups (P=0.015), with 4A being the most common. The malignancy rates in categories 3, 4A, 4B, 4C, and 5 were as follows: 5.6%, 36.0%, 77.4%, 87.7%, and 98.4% in the staging group, and 0.0%, 9.7%, 53.3%, 88.9%, and 100% in the surveillance group. The malignancy rate was significantly different between the two groups only in category 4A (P=0.0001).
UNASSIGNED: AN-FNA according to AN-RADS category appears to be an appropriate method for determination of axillary nodal status. Overall malignancy rate of AN-FNA in breast cancer patients was higher in the staging group than in the surveillance group. According to the suspicion level, the difference between two groups was significant only in category 4A.

OBJECTIVE: There is limited literature on sample adequacy for molecular testing in pancreatic ductal adenocarcinoma obtained via endoscopic ultrasound (EUS) fine-needle aspiration (FNA) versus EUS fine-needle biopsy (FNB). We aimed to compare these two modalities regarding sample adequacy for molecular and genomic sequencing.
METHODS: We reviewed all patients with pancreatic ductal adenocarcinoma who underwent EUS at Saint Luke\'s Hospital from 2018 to 2021. The patients were categorized based on the method of EUS tissue acquisition, specifically FNA or FNB. A comprehensive evaluation was conducted for all cases by cytotechnologists.
RESULTS: Out of 132 patients who underwent EUS-guided biopsies, 76 opted for FNA, 48 opted for FNB, and 8 opted for a combination of both. The average number of passes required for FNB and FNA was 2.58 ± 1.06 and 2.49 ± 1.07, respectively (p = 0.704), indicating no significant difference. Interestingly, 71.4% (35) of FNB-obtained samples were deemed adequate for molecular testing, surpassing the 32.1% (26) adequacy observed with FNA (p < 0.001). Additionally, 46.4% (26) of FNB-obtained samples were considered adequate for genomic testing, a notable improvement over the 23.8% (20) adequacy observed with FNA (p = 0.005).
CONCLUSIONS: Although the number of passes required for cytologic diagnosis did not differ significantly between EUS-FNB and EUS-FNA, the former demonstrated superiority in obtaining samples adequate for molecular testing. Tumor surface area and cellularity were crucial parameters in determining sample adequacy for molecular testing, irrespective of the chosen tissue acquisition modality.

Pancreatic ductal adenocarcinoma (PDAC) is the most common (90%) type of solid pancreatic neoplasm. Due to its late presentation and poor survival rate, early diagnosis and timely treatment is of utmost importance for better clinical outcomes. Endoscopic ultrasound provides high-resolution images of the pancreas and has excellent sensitivity in the diagnosis of even small (<2 cm) pancreatic lesions. Apart from imaging, it also has an advantage of tissue acquisition (EUS fine-needle aspiration, FNA; or fine-needle biopsy, FNB) for definitive diagnoses. EUS-guided tissue acquisition plays a crucial role in genomic and molecular studies, which in today\'s era of personalized medicine, are likely to become important components of PDAC management. With the use of better needle designs and technical advancements, EUS has now become an indispensable tool in the management of PDAC. Lastly, artificial intelligence for the detection of pancreatic lesions and newer automated needles for tissue acquisition will obviate observer dependency in the near future, resulting in the wider dissemination and adoption of this technology for improved outcomes in patients with PDAC.

Fine-needle aspiration (FNA) cytology has been widely used for the diagnosis of breast cancer lesions with the objective of differentiating benign from malignant masses. However, the occurrence of unsatisfactory samples and false-negative rates remains a matter of concern. Major improvements have been made thanks to the implementation of rapid on-site evaluation (ROSE) in multidisciplinary and integrated medical settings such as one-stop clinics (OSCs). In these settings, clinical and radiological examinations are combined with a morphological study performed by interventional pathologists. The aim of our study was to assess the diagnostic accuracy of the on-site cytopathology advance report (OSCAR) procedure on breast FNA cytologic samples in our breast OSC during the first three years (April 2004 till March 2007) of its implementation. To this goal, we retrospectively analyzed a series of 1820 breast masses (1740 patients) radiologically classified according to the American College of Radiology (ACR) BI-RADS lexicon (67.6% being either BI-RADS 4 or 5), sampled by FNA and immediately diagnosed by cytomorphology. The clinicoradiological, cytomorphological, and histological characteristics of all consecutive patients were retrieved from the hospital computerized medical records prospectively registered in the central information system. Histopathological analysis and ultrasound (US) follow-up (FU) were the reference diagnostic tests of the study design. In brief, we carried out either a histopathological verification or an 18-month US evaluation when a benign cytology was concordant with the components of the triple test. Overall, histology was available for 1138 masses, whereas 491 masses were analyzed at the 18-month US-FU. FNA specimens were morphologically nondiagnostic in 3.1%, false negatives were observed in 1.5%, and there was only one false positive (0.06%). The breast cancer prevalence was 62%. Diagnostic accuracy measures of the OSCAR procedure with their 95% confidence intervals (95% CI) were the following: sensitivity (Se) = 97.4% (96.19-98.31); specificity (Sp) = 94.98% (92.94-96.56); positive predictive value (PPV) = 96.80% (95.48-97.81); negative predictive value (NPV) = 95.91% (94.02-97.33); positive likelihood ratio (LR+) = 19.39 (13.75-27.32); negative predictive ratio (LR-) = 0.03 (0.02-0.04), and; accuracy = 96.45% (95.42-97.31). The respective positive likelihood ratio (LR+) for each of the four categories of cytopathological diagnoses (with their 95% CI) which are malignant, suspicious, benign, and nondiagnostic were 540 (76-3827); 2.69 (1.8-3.96); 0.03 (0.02-0.04); and 0.37 (0.2-0.66), respectively. In conclusion, our study demonstrates that the OSCAR procedure is a highly reliable diagnostic approach and a perfect test to select patients requiring core-needle biopsy (CNB) when performed by interventional cytopathologists in a multidisciplinary and integrated OSC setting. Besides drastically limiting the rate of nondiagnostic specimens and diagnostic turn-around time, OSCAR is an efficient and powerful first-line diagnostic approach for patient-centered care.

BACKGROUND: Pathologic evaluation of sentinel lymph node biopsy (SLNB) samples is crucial for axillary staging in patients newly diagnosed with breast cancer. Patients with pathologic evidence of nodal metastasis scheduled for upfront surgery typically also undergo axillary lymph node dissection (ALND). Although SLNB is the gold standard method for detecting nodal metastasis, axillary lymph node fine-needle aspiration biopsy (FNAB) utility has not been thoroughly explored.
METHODS: Ultrasound-guided axillary lymph node FNAB samples along with concurrent ipsilateral breast tissue samples were searched and reviewed. The control group included histologic findings of axillary dissection or intraoperative SLNB results.
RESULTS: A total of 354 axillary lymph node FNAB samples with matched histology were included. Of these, 187 (52.8%) were positive for metastatic carcinoma of breast origin; 143 (40.4%) were negative for metastasis; 12 (3.4%) showed atypical cells; six (1.7%) were suspicious for metastasis; and six (1.7%) were nondiagnostic because of a lack of lymphoid tissue and malignant cells. Of the 143 negative FNAB samples, 22 (15.4%) were positive on either intraoperative SLNB or ALND. When only the positive and negative FNAB samples were accounted for (n = 330; 93.2%), overall diagnostic sensitivity and specificity were 89.4% and 99.2%, respectively.
CONCLUSIONS: Although axillary SLNB is the standard procedure for detecting nodal metastasis of breast origin, axillary lymph node FNAB appears to be a suitable alternative in a significant proportion of patients. A standard SLNB should be performed in cases of negative axillary lymph node FNAB findings, particularly nodes with abnormal imaging findings.

BACKGROUND: The suggested atypia of undetermined significance (AUS) rate for thyroid fine-needle aspiration biopsies is 10% or less. Prompted by a high institutional AUS rate, we examined using molecular testing results (MTR) as a potential quality metric tool to reduce the AUS rate. We correlated MTR with AUS cytologic findings, surgical pathology follow-up, and individual pathologist AUS rates.
METHODS: Demographic data, cytologic diagnoses, MTR, and surgical pathology diagnoses were retrospectively obtained. MTR were classified as either positive or negative. AUS rates and MTR proportions were compared among pathologists. The cytomorphologic features of 143 AUS cases were assessed and correlated with MTR.
RESULTS: Between 2017 and 2022, 710 of 3247 thyroid fine-needle aspirations were classified as AUS, with a yearly average rate of 22% (range = 19%-26%). AUS cases included: 331 (47%) with architectural atypia; 204 (29%) with oncocytic (Hürthle cell) atypia; 99 (14%) with combined architectural and cytologic atypia; and 76 (10%) with isolated cytologic atypia. Most AUS cases with molecular testing had negative MTR (360/492, 73%). AUS with cytologic atypia had higher positive MTR risk (logarithm of odds ratio = 1.27, 95% credible interval [0.5-2.04], P = 0.001). The average positive MTR rate by pathologist was 21.5% (range 0%-35%); higher positive MTR rates had better correlation with subsequent neoplastic/malignant histologic diagnoses. The MTR sensitivity for malignant disease was 89% and the negative predictive value was 91%.
CONCLUSIONS: MTR analysis reveals the importance of cytologic atypia as a determinant of malignancy risk in AUS cases. Periodic analysis of MTR data alongside individual pathologist AUS rates can help refine diagnostic criteria and potentially reduce AUS overuse.

Thyroid cancer is the most common malignancy of the endocrine system. Fine-needle aspiration (FNA) biopsy of thyroid nodules has become the gold standard procedure, in terms of cost and efficacy, for guiding clinicians towards appropriate patients\' management. One challenge for cytopathologists is to accurately classify cytological specimens as benign or malignant based on cytomorphological features. In fact, with a frequency ranging from 10% to 30%, nodules are diagnosed as indeterminate. In recent years, the mutational landscape of thyroid tumors has been extensively described, and two molecular profiles have been identified: RAS-like (NRAS, HRAS, and KRAS mutations; EIF1AX mutations; BRAF K601E mutation; and PPARG and THADA fusions) and BRAFV600E-like (including BRAFV600E mutation and RET and BRAF fusions). The purpose of this review is to discuss the latest molecular findings in the context of indeterminate thyroid nodules, highlighting the role of molecular tests in patients\' management.

Objectives: Benign category of Bethesda classification is generally well known to carry a false-negative rate of 0-3%. The current study was designed to investigate the rate of false-negative cytology in patients who underwent thyroidectomy for presumably benign thyroid diseases. Predictive risk factors for false results and malignancy were evaluated along with cytology-histology discrepant cases.Materials and methods: Females who underwent thyroidectomy between May 2014 and December 2022 were included. Demographics, ultrasound (US) features, fine-needle aspiration (FNA) diagnosis, surgical indications and outcomes, final histology reports, risk factors, and malignancy rate were recorded. Cytology-histology discrepant cases were further evaluated for interpretation errors and risk factors. Statistical analyses were performed using Fisher\'s exact and Mann-Whitney U tests.Results: Of 581 women with a benign thyroid disease who underwent thyroidectomy, 91 was diagnosed as incidental carcinoma (15.6%) and most was T1a (4.9 ± 2.7 mm, 95.6%). Final histology reports revealed mostly papillary carcinoma (93.4%). Predictors of malignancy such as age, family history, previous radiation exposure, and iodine-deficient diet did not help in risk stratification (p > 0.05, for each). However, FNA taken during pregnancy was determined as a risk factor (n = 7, 7.6%, p < 0.05) since it may cause a delay in diagnosis. Cytology-histology discrepant cases were seen to be mostly due to sampling errors (45%, p < 0.05), followed by misinterpretations (37.3%, p < 0.05). There was no reason for discrepancy in 17.5%, and this was linked to inherent nature of thyroid nodule with overlapping cytologic features. Best identifiable risk factor for misinterpretation was pregnancy as well (n = 5, 14.7%, p < 0.05).Conclusions: Risk of malignancy in a presumably benign thyroid disease should not be ignored. Radiology-cytology correlation by an experienced dedicated team may help in decreasing sampling errors. Physiologic changes caused by pregnancy may shade malignant transformation in thyrocytes, and it would be appropriate to be cautious about benign FNA taken during this period.