EIF1AX mutation has been identified as a driver mutation for papillary thyroid carcinoma (PTC) by The Cancer Genome Atlas (TCGA) study. Subsequent studies confirmed this mutation in PTC and Anaplastic Thyroid Carcinoma (ATC) but also reported EIF1AX mutation in Follicular nodular disease (FND) and benign thyroid nodules. In this study, we review thyroid nodules with EIF1AX mutation from two institutions: a tertiary care hospital (YNHH, n = 22) and a major cancer referral center (MSKCC, n = 34) and report the varying histomorphology in the context of additional genetic abnormalities and institutional practices. Pathology diagnoses were reviewed according to the WHO 5th edition and correlated with the type of EIF1AX mutation and additional concurrent molecular alterations, if any. Most cases were splice site type mutations. Cases consisted of 9 FND, 7 follicular (FA) or oncocytic adenomas (OA), 2 non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) and 38 follicular-cell derived thyroid carcinomas. Of 8 cases with isolated EIF1AX mutation, 7 were FND, FA or OA (88%) and one was an oncocytic carcinoma (12%). Of 12 cases with EIF1AX and one additional molecular alteration, 9 (75%) were FND, FA or OA, 2 (17%) were NIFTPs and one (8%) was a poorly differentiated thyroid carcinoma. All 36 cases with EIF1AX mutation and ≥ 2 molecular alterations were malignant (100%) and included TP53 and TERT promoter mutations associated with ATC (n = 8) and high-grade follicular cell-derived non-anaplastic carcinoma (HGC, n = 2). Isolated EIF1AX mutation was noted only in thyroid nodules seen at YNHH and were predominantly encountered in benign thyroid nodules including FND. Accumulation of additional genetic abnormalities appears to be progressively associated with malignant tumors.

BACKGROUND: Recently, a new World Health Organization Reporting System for Soft Tissue Cytopathology (WHO System) was introduced. To analyze the value of this system, routine fine-needle aspiration soft tissue tumor (STT) cases were reviewed.
METHODS: Cytology samples of STTs collected between 1954 and 2022 at the Institut Curie were used (2214 cases, including 1376 primary tumors). All specimens were classified according to the predominant cytomorphological pattern and the WHO System. The diagnostic accuracy and risk of malignancy (ROM) in each category were calculated.
RESULTS: Final diagnoses revealed 1236 malignancies and 978 benign or low-risk tumors. The original cytological evaluation led to 21 false-negative results (0.85%) and 29 false-positive results (1.17%). Sensitivity, specificity, positive predictive value, and negative predictive value were 98.3%, 92.1%, 97.5%, and 94.2%, respectively. Overall diagnostic accuracy was 94.2%. The ROM calculated according to the WHO System was 29.87%, 2.49%, 39.62%, 51.43%, 68.42%, and 97.69% in the nondiagnostic, benign, atypical, soft tissue neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant categories, respectively; however, it varied broadly depending on the morphological pattern (62.78% in spindle cell tumors, 84.58% in myxoid tumors, 3.00% in lipomatous tumors, 78.15% in epithelioid tumors, 94.26% in pleomorphic tumors, and 100% in round cell tumors).
CONCLUSIONS: Cytology of STTs is a powerful diagnostic method. Some cytological patterns overlap in different morphological groups, and the possibility of false-negative and false-positive diagnoses may persist. This analysis evidenced utility of the WHO System, especially when combined with morphological pattern assessment. Subclassification in particular diagnostic categories allowed for calculation of the ROM, which is crucial for optimal patient management.

BACKGROUND: The World Health Organization (WHO) classification system revised the Papanicolaou Society of Cytopathology (PSC) system for reporting pancreaticobiliary cytopathology. To better stratify intraductal and/or cystic neoplasms by cytologic grade, the neoplastic, other category was replaced by two new categories: pancreaticobiliary neoplasm, low-risk/grade (PaN-Low) and pancreaticobiliary neoplasm, high-risk/grade (PaN-High). Low-grade malignancies were placed in the malignant category, and benign neoplasms were placed in the benign/negative for malignancy category.
METHODS: An institutional pathology database search identified patients who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic lesions from January 2015 to April 2022. The absolute risk of malignancy (ROM) was determined by histologic and/or clinical follow-up of at least 6 months, and overall survival rates were calculated across diagnostic categories, comparing the WHO and PSC systems.
RESULTS: In total, 1012 cases were reviewed and recategorized. The ROM for the WHO system was 8.3% for insufficient/inadequate/nondiagnostic, 3.2% for benign/negative for malignancy, 24.6% for atypical, 9.1% for PaN-Low, 46.7% for PaN-High, 75% for suspicious for malignancy, and 100% for malignant. Comparatively, the ROM for the PSC system was 7.4% for nondiagnostic, 3.0% for negative for malignancy, 23.1% for atypical, 0% for neoplastic, benign, 7.3% for neoplastic, other, 75% for suspicious for malignancy, and 100% for malignant. The WHO system demonstrated superior stratification for overall survival.
CONCLUSIONS: The WHO system significantly improves the stratification of ROM and overall survival across diagnostic categories by introducing the PaN-Low and PaN-High categories and reassigning low-grade malignancies to the malignant category. Analyzing EUS-FNA samples with the WHO system provides critical insights for guiding clinical management.

UNASSIGNED: The \"International System of Reporting Serous Fluid Cytology (TIS)\" together with cytomorphology promotes the use of ancillary techniques to resolve difficulties in reporting serous fluid cytology.
UNASSIGNED: To classify serous effusion fluid samples received at our department in line with \"TIS\", indicating the risk of malignancy (ROM), and directing appropriate usage of ancillary testing.
UNASSIGNED: Prospective study carried out from October 2021 to September 2022. The study included all pleural, ascitic, and pericardial fluid samples, reported according to \'TIS\'. Flow cytometry and immunocytochemistry were ancillary methods utilized to assist in reporting. Cases with available history and convincing correlations didn\'t require further assessment.
UNASSIGNED: A total of 1200 serous effusion samples were evaluated including 604 pleural, 591 ascitic, and 5 pericardial fluid samples. After categorization, there were 23 samples in non-diagnostic (ND, 1.9%), 575 in negative for malignancy (NFM, 47.91%), 44 in atypia of undetermined significance (AUS, 3.66%), 64 in suspicious for malignancy (SFM, 5.33%), and 494 in malignant category (MAL, 41.16%). Ancillary studies were beneficial in the recategorization of 26% (11/44) AUS cases, 29.6% (19/64) SFM cases, and it helped refine tumor characteristics in 35.42% (175/494) cases categorized as malignant. Final ROM calculated for each category: ND 25%, NFM 18.6%, AUS 66.6%, SFM 88%, and MAL 100%.
UNASSIGNED: Serous fluid is an easily obtainable sample that can provide opportunities for ancillary testing with clinical implications. In AUS and suspicious category although, diagnostic yield is increased however, a larger number of cases are required to obtain definite results.

BACKGROUND: This study aims to develop a diagnostic model to help physicians determine whether thyroid nodules categorized as atypia of undetermined significance (AUS) in category III of the Bethesda system are benign or malignant preoperatively. To create a diagnostic model for predicting thyroid nodules\' benign or malignant with AUS cytology based on clinical, ultrasonographic, and cytopathological findings.
METHODS: This is a retrospective cohort study involving patients (>19) at risk of thyroid cancer who had thyroidectomy after an AUS cytology. The dataset consists of 53 variables 204 nodules from 183 patients. Binary logistic regression and factor analysis methods were used to identify risk factors for malignancy. Finally, four prediction models were developed using different approaches, based on clinical, pathological clinical + pathological, and the factors.
RESULTS: A total of 88 (48.1%) of 183 patients diagnosed with AUS were benign and 95 (51.9%) the malignant. After determining risk factors, four prediction models were developed based on different approaches to assist physicians in deciding to detect AUS nodules early. It was seen that bilaterality was found to be a risk factor for malignancy in the clinical model (pbilaterality  = .03) and it was also seen that the pathological variables pale chromatin and irregular contours in the oncocyte variables were risk factors for malignancy (ppalechromatin  = .02, pirregularcontoursintheoncocyte  = .04). The best model obtained sensitivity and specificity values are 73% and 87% based on clinical and pathological variables.
CONCLUSIONS: This comprehensive study may provide a more in-depth understanding of AUS and make a notable contribution to healthcare professionals before surgery.

OBJECTIVE: To evaluate the diagnostic performance of Milan system for reporting salivary gland cytopathology (MSRSGC) in two southern China tertiary cancer centers and investigate the impact of rapid on-site evaluation (ROSE) on FNAC performance.
METHODS: Five hundred and forty-nine patients who underwent FNAC for salivary lesions with surgical follow-up from two centers were enrolled in this retrospective cohort study. All slides were recategorized using MSRSGC after consensus on diagnostic criteria for each category. The diagnostic performance of FNAC for salivary lesions was evaluated and compared and the impact of ROSE on FNAC performance was analyzed.
RESULTS: The distribution of cases per category based on the MSRSGC criteria in the whole series was as followed: ND 49 (8.9%), NN 76 (14.4%), BN 262 (47.7%), AUS 20 (3.6%), SUMP 43 (7.8%), SM 21 (3.8%), M 78 (14.2%). The SUMC series had significantly more ND distributions than JXCH did (16.2% vs. 0, p = .000). Risk of malignancy for each category in the total series was as followed: 42.9% for ND, 9.2% for NN, 3.8% for BN, 30.0% for AUS, 23.3% for SUMP, 81.0% for SM, and 94.9% for M. When ND and AUS/SUMP were excluded, the sensitivity, specificity, PPV, NPV, and accuracy were 84.0%, 97.1%, 89.9%, 95.1%, and 94.0%, respectively; sensitivity, specificity, PPV, NPV, and accuracy were comparable between the two centers.
CONCLUSIONS: FNAC using MSRSGC provides a good tool in preoperative evaluation for salivary lesions in southern China. ROSE improves its diagnostic performance by reducing the ratio of the ND category.

Fine-needle aspiration cytology (FNAC) represents an important diagnostic tool for the workup of salivary gland (SG) lesions. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a six-tiered system for standardizing diagnoses and improvement of communication between pathologists and clinicians, providing risk of malignancy (ROM) rates for every category. The aims of the present study were (i) to validate the use of MSRSGC in a large series of SG FNAC in a tertiary center in Switzerland, (ii) to determine ROM for each category and compare them with data from MSRSGC and similar studies, and (iii) to investigate whether there were relevant differences of non-diagnostic results between fine-needle aspirations (FNA) performed by cytopathologists compared to non-cytopathologists.
The files of the department of Pathology in the University Hospital Zurich (UHZ) were searched for SG FNAC between 2010 and 2019. The MSRSGC guidelines were applied retrospectively. Furthermore, ROM, risk of neoplasia (RON), sensitivity, and specificity were calculated based on the cases with histopathological follow-up.
A total of 2156 SG FNAC including 753 cases with histopathological follow-up were evaluated. Generally, ROM was within the range of values provided by MSRSGC, with some minor deviations. Sensitivity was 94.6%, and specificity was 99.3%.
Our study confirms the usefulness of MSRSGC. In addition, it provides a detailed insight into the wide spectrum of SG FNAC. Finally, we showed that the rate of non-diagnostic FNA was significantly lower in FNAs performed by cytopathologists compared to non-cytopathologists.

Germany has a long history of insufficient iodine supply and thyroid nodules occur in over 30% of the adult population, the vast majority of which are benign. Non-invasive diagnostics remain challenging, and ultrasound-based risk stratification systems are essential for selecting lesions requiring further clarification. However, no recommendation can yet be made about which system performs the best for iodine deficiency areas. In a German multicenter approach, 1211 thyroid nodules from 849 consecutive patients with cytological or histopathological results were enrolled. Scintigraphically hyperfunctioning lesions were excluded. Ultrasound features were prospectively recorded, and the resulting classifications according to five risk stratification systems were retrospectively determined. Observations determined 1022 benign and 189 malignant lesions. The diagnostic accuracies were 0.79, 0.78, 0.70, 0.82, and 0.79 for Kwak Thyroid Imaging Reporting and Data System (Kwak-TIRADS), American College of Radiology (ACR) TI-RADS, European Thyroid Association (EU)-TIRADS, Korean-TIRADS, and American Thyroid Association (ATA) Guidelines, respectively. Receiver Operating Curves revealed Areas under the Curve of 0.803, 0.795, 0.800, 0.805, and 0.801, respectively. According to the ATA Guidelines, 135 thyroid nodules (11.1%) could not be classified. Kwak-TIRADS, ACR TI-RADS, and Korean-TIRADS outperformed EU-TIRADS and ATA Guidelines and therefore can be primarily recommended for non-autonomously functioning lesions in areas with a history of iodine deficiency.

BACKGROUND: The Milan system reporting salivary gland cytopathology (MSRSGC) is a tiered classification scheme that is based on risk stratification. The aim of the current study was to assess the risk of malignancy (ROM) and risk of neoplasia (RON) in each of the diagnostic categories proposed by the MSRSGC.
METHODS: A retrospective analysis and categorization according to the MSRSGC was made of salivary gland fine needle aspirations (FNA) performed from January 2007 to December 2017. The FNA cytology results were correlated with subsequent histological follow-up.
RESULTS: A total of 578 FNAs were evaluated and histopathology was available for 198 cases (34.2%). The RON and ROM for individual diagnostic categories were: Non-diagnostic: 52.2% to 13%, non-neoplastic: 21.4% to 10.7%, atypia of undetermined significance: 74% to 22.2%, benign neoplasm: 100% to 1.1%, salivary gland neoplasm of uncertain malignant potential: 93.3% to 53.3%, suspicious for malignancy (SFM): 100% to 100%, and malignant: 100% to 100%. A diagnosis of \'SFM\' or \'malignant\' with FNA cytology carried a 100% risk for malignancy, while a diagnosis of \"non-neoplastic,\" \"benign neoplasm\" reduced the probability of malignancy to 3.4%.
CONCLUSIONS: The MSRSGC is useful for the management of salivary gland lesions as it can successfully differentiate between benign and malignant cases. It will bring uniformity in salivary gland FNA cytology reporting across various institutions globally.

The diagnosis and management of salivary gland tumors in pediatric patients can be challenging. The utility of fine-needle aspiration (FNA) cytopathology and the performance of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) in this age group have not been systematically assessed. The paucity of data has contributed to the controversial role of FNA cytopathology in the presurgical management of these patients.
The authors retrospectively analyzed 104 pediatric salivary gland FNAs (2000-2020). A correlation with the available histopathologic follow-up (n = 54) was performed. The distribution percentages, the risk of neoplasm (RON), and the risk of malignancy (ROM) were assessed for each category of the MSRSGC.
The overall sensitivity, specificity, negative predictive value, and positive predictive value of pediatric salivary gland FNAs were 80%, 97%, and 92%, respectively. The RON values for the nondiagnostic, nonneoplastic, atypia of undetermined significance, benign neoplasm, salivary gland neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant categories were 60%, 11%, 100%, 100%, 100%, 100%, and 100%, respectively, whereas the ROM values were 0%, 11%, 100%, 6%, 67%, 100%, and 100%, respectively. The percentage of nonneoplastic FNAs was greater in comparison with the adult population (52% vs 8%). All neoplasms in patients aged 0 to 10 years were malignant, whereas benign neoplasms occurred only in patients aged ≥11 years; this supported an inverse correlation between age and malignancy rate in salivary gland neoplasms.
FNA cytopathology demonstrates excellent diagnostic performance in differentiating malignant and benign pediatric salivary gland lesions. The MSRSGC is a valuable tool for standardization of the reporting and preoperative risk stratification of these lesions.