The Milan system atypia of undetermined significance: 5-year performance data.

BACKGROUND: The objective of this study was to evaluate the diagnostic performance of the category atypia of undetermined significance (AUS) at the authors' institution based on the Milan System for Reporting Salivary Gland Cytopathology. METHODS: All AUS cases diagnosed at Fimlab Laboratories between January 1, 2018, and December 31, 2022, were included. Histologic verifications were checked until May 31, 2023. The upper-bound and lower-bound risk of malignancy and risk of neoplasm were calculated. The timelines between the pathology laboratory workflow and patient management were also calculated. RESULTS: From 1157 fine-needle aspirations (FNAs), 162 (14.0%) AUS cases were diagnosed in 146 patients, with an average ± standard deviation age of 66.1 ± 14.9 years. There was variation in the AUS percentages, with higher values during the coronavirus disease 2019 pandemic years (15% and 17.5% in 2020 and 2021, respectively). Seventy-five cases (46.3%) had histologic follow-up: 16 were malignant neoplasms, and 36 were benign neoplasms. The upper and the lower bounds of the-risk of malignancy and risk of neoplasm were 21.3% and 69.3% and 9.9% and 32.1%, respectively. The average time from the first FNA with an AUS diagnosis to surgical resection ranged from 6 to 682 days, and the time to the first repeat FNA ranged from 10 to 691 days. CONCLUSIONS: The results indicated higher percentages of AUS cases compared with the reference value, which may be attributed to the impact of the coronavirus disease 2019 pandemic. The risk of malignancy calculated in this study was closer to the reference value from the first edition of the Milan System for Reporting Salivary Gland Cytopathology compared with the second edition.

The diagnostic accuracy of pleomorphic adenoma in fine needle aspiration: Features leading to false positive and false negative diagnoses and the utility of cell blocks.

OBJECTIVE: Fine needle aspiration (FNA) is a well-established tool in preoperative diagnosis of salivary gland lesions with diagnostic accuracy of 90%. Pleomorphic adenoma (PA) is the most common salivary gland tumor comprising 45%-74% of all salivary gland tumors with FNA diagnostic accuracy of 89.5%-96.2%. The aim of the present study was to determine and analyze potential cytomorphological pitfalls and evaluate the diagnostic accuracy in FNA diagnosis of PA. METHODS: Salivary gland specimens with both cytological and histological diagnoses were searched over a 10-year-period (2009-2018) from a laboratory information system of Pathology Department, Fimlab Laboratories, Tampere and matched to determine concordant and discordant PA cases. Sufficient material in histological and cytological sample was found in 401 cases. In 218 cases (54.4%) diagnosis was true-negative PA, in 169 cases (42.1%) diagnosis was true-positive PA and there were 14 discordant cases: 4 false-positive cases and 10 false-negative cases. False-negative cases were reclassified and subgrouped according to The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC). RESULTS: Cytomorphologically, cell type predominance was more often myoepithelial in true-positive cases (65%) and epithelial both in false-negative (70%, p = .007) and false-positive cases (75%, p = .027). Well-formed ducts were present in cytology in all true-positive cases (p < .001). Only 10% of true-positive cases did not show any matrix in cytology (p < .001). Nuclear changes were common in false-negative cases (80%, p = .002) and false-positive cases (75%, p = .003). Beneficial cell block (CB) was more common in true-positive cases (85%) than in false-negative cases (50%, p = .041) or in false-positive cases (50%, p = .116) and a lack of beneficial CB led more often to a false diagnosis (70% false diagnosis without beneficial CB versus 29% false diagnosis with beneficial CB). CONCLUSION: The present study showed diagnostic accuracy of 96.5% for FNA in PA diagnosis. Sensitivity, specificity, positive predictive value and negative predictive value were 94.4%, 98.2%, 97.7%, and 95.6%, respectively. The benefit of CBs was more evident in true-positive cases (85%).

Ectopic thyroid in EBUS: experience from a quality assurance programme.

A diagnostic challenge is presented: Distinguishing ectopic thyroid tissue from metastatic well-differentiated follicular carcinoma in cytological material. Two cases of thyroid tissue in mediastinal lymph nodes were sampled by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Later, the cases were presented in Labquality's nongynecological external quality scheme rounds in the years 2017, 2019, and 2020. The same case was presented two times, both in the 2017 and in the 2020 rounds. The results of the three rounds and the discussion of diagnostic pitfalls of ectopic thyroid tissue are presented. A total of 112 individual laboratories worldwide participated in the external quality assurance rounds with whole-slide scanned images and digital still images of alcohol-fixed Papanicolaou-stained cytospin specimens in the years 2017, 2019, and 2020. Fifty-three laboratories participated in both the 2017 (53 of 70, 75.71%) and the 2020 (53 of 85, 62.35%) rounds. The given Pap classes between rounds were compared. Twelve (12 of 53, 22.6%) of the laboratories gave the same Pap class value, whereas 32 (32 of 53, 60.4%) were in the range of ±1 class difference (Cohen's kappa -0.035, p < 0.637). When comparing the diagnoses, 21 (21 of 53, 39.6%) laboratories gave the same diagnosis in 2017 and in 2020 (Cohen's kappa 0.039, p < 0.625). Thirty-two of the laboratories gave the same diagnosis both in 2017 and in 2020 (Cohen's kappa 0.004, p < 0.979). Ten (10 of 53, 18.9%) laboratories changed their diagnose from malignant to benign, and 11 (11 of 53, 20.8%) changed their diagnose from benign to malignant between the 2017 and the 2020 rounds. In conclusions, the expert reference diagnosis was thyroid tissue in mediastinal lymph node. Thyroid tissue in mediastinal lymph node may be either of ectopic or of neoplastic origin. The diagnostic work-up should include cytomorphological, immunohistochemical, laboratory, and imaging results. If a neoplastic change is excluded, the benign category is the most feasible one. The quality assurance rounds showed a large variability in the given Pap classes. Mirroring the problematic issue both inter- and intralaboratory of such cases both in routine diagnostics and in the classification terminologies is requiring multidisciplinary evaluation approach in the diagnostics.

Application of the Milan System for Reporting Salivary Gland Cytopathology in pediatric patients: An international, multi-institutional study.

BACKGROUND: Pediatric salivary gland fine-needle aspiration (FNA) is uncommon with a higher frequency of inflammatory lesions and a small proportion of malignancies. This international, multi-institutional cohort evaluated the application of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and the risk of malignancy (ROM) for each diagnostic category. METHODS: Pediatric (0- to 21-year-old) salivary gland FNA specimens from 22 international institutions of 7 countries, including the United States, England, Italy, Greece, Finland, Brazil, and France, were retrospectively assigned to an MSRSGC diagnostic category as follows: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), or malignant. Cytology-histology correlation was performed where available, and the ROM was calculated for each MSRSGC diagnostic category. RESULTS: The cohort of 477 aspirates was reclassified according to the MSRSGC as follows: nondiagnostic, 10.3%; nonneoplastic, 34.6%; AUS, 5.2%; benign neoplasm, 27.5%; SUMP, 7.5%; SM, 2.5%; and malignant, 12.4%. Histopathologic follow-up was available for 237 cases (49.7%). The ROMs were as follows: nondiagnostic, 5.9%; nonneoplastic, 9.1%; AUS, 35.7%; benign neoplasm, 3.3%; SUMP, 31.8%; SM, 100%; and malignant, 100%. Mucoepidermoid carcinoma was the most common malignancy (18 of 237; 7.6%), and it was followed by acinic cell carcinoma (16 of 237; 6.8%). Pleomorphic adenoma was the most common benign neoplasm (95 of 237; 40.1%). CONCLUSIONS: The MSRSGC can be reliably applied to pediatric salivary gland FNA. The ROM of each MSRSGC category in pediatric salivary gland FNA is relatively similar to the ROM of each category in adult salivary gland FNA, although the reported rates for the different MSRSGC categories are variable across institutions.

The Contributory Role of Cell Blocks in Salivary Gland Neoplasms Fine Needle Aspirations Classified by the Milan System for Reporting Salivary Gland Cytology.

(1) Background: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was introduced in 2018, bringing an organ-specific classification system for salivary gland cytopathology. The aim of present study is to evaluate the MSRSGC prospectively, based on a two-year experience in the tertiary care center pathology department, and evaluate the role of routine cell block (CB) preparation in salivary gland cytopathological diagnostics. (2) Methods: In our institution, the Department of Pathology, Fimlab Laboratories, Tampere, Finland, the MSRSGC has been implemented in salivary gland cytopathology since January 2018 and, over a two-year period (January 2018-December 2019), there were 365 fine-needle aspirations, of which 164 had a surgical follow-up. The CB methods used were Plasma-thrombin, the collection of visible fragments, and the Shandon and in-house methods. (3) Results: The MSRSGC diagnostic figures were as follows: accuracy 87.5%, sensitivity 45.8% and specificity 98.9%. For diagnostic categories of MSRSGC (non-neoplastic, benign neoplasm and malignant neoplasm) (n = 63) diagnostic accuracy was 98.4%, and for undetermined categories (atypia of undetermined significance, salivary gland neoplasm of uncertain malignant potential and suspicious for malignancy) (n = 49) diagnostic accuracy was 73.5%. Non-contributory cell blocks resulted more often in a false negative diagnosis (25%, 3/12) than a true negative diagnosis (10%, 7/73, p < 0.001), and is, most likely, an insufficient cytological diagnosis (86%, 18/21, p < 0.001). (4) Conclusion: The application of MSRSGC and CBs are beneficial in salivary gland cytological diagnosis, increasing diagnostic accuracy and, thus, patients' management and treatment.

Salivary Gland FNA Diagnostics in a Real-Life Setting: One-Year-Experiences of the Implementation of the Milan System in a Tertiary Care Center.

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was introduced in 2018 following other organ specific cytopathological reporting systems and it aimed at bringing a practical, evidence-based, user-friendly classification system with characterization and management algorithms. At the Department of Pathology, Fimlab Laboratories, Tampere, Finland all salivary fine needle aspirations (FNAs) have been given cytopathological diagnoses according to the MSRSGC since January 2018. Analyses of a one-year-period (January 2018-December 2018) consisted of 183 salivary FNA samples from 138 patients with correlation to histopathology in 90 cases with surgical follow-up. The MSRSGC performance in patient based analysis was as follows: accuracy was 90.9%, sensitivity was 61.5%, specificity was 100%, positive predictive value was 100%, and negative predictive value was 89.4%, respectively. Risks of malignancy (ROMs) in MSRSGC categories were: 0.0% (0/15) in non-diagnostic category, 100.0% (1/1) in non-neoplastic category biased by only one falsely-negative lymphoma case, 14.3% (1/7) in atypia of undetermined significance category, 0.0% (0/28) in benign neoplasm category, 27.3% (3/11) in neoplasm of uncertain malignant potential category, and 100% for both suspicious for malignancy (4/4) and malignancy (4/4) categories, respectively. The MSRSGC has been proven as a reliable classification system in salivary gland FNA routine diagnostics in a tertiary care center.