BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is widely accepted and endorsed by professional societies. Although several studies focusing on the MSRSGC have been published, few have been prospective studies. The objective of this study was to evaluate the effectiveness of the MSRSGC in cytopathology practice.
METHODS: A comprehensive literature search was conducted to identify all prospective studies on the MSRSGC. The risk of malignancy (ROM), risk of neoplasm, and diagnostic accuracy for each diagnostic category were calculated. Data were tabulated in Microsoft Excel, and analyses were performed with the Open Meta-Analyst program.
RESULTS: Seven prospective and seven retrospective studies were identified. The total number of fine-needle aspirations (FNAs) was 1587 in the prospective studies and 1764 in the retrospective studies. The ROM values for the nondiagnostic, nonneoplastic, atypia of undetermined significance, benign neoplasm, salivary gland neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant categories in prospective versus retrospective studies were 21.0% versus 26.6%, 9.4% versus 8.1%, 34.9% versus 39.6%, 2.4% versus 2.1%, 36.6% versus 31.2%, 86.0% versus 66.0%, and 97.0% versus 96.7%, respectively. Sensitivities, specificities, and diagnostic odds ratios were 83.1% (95% confidence interval [CI], 71.1%-90.8%) versus 89.1% (95% CI, 83.6%-92.9%), 98.4% (95% CI, 96.6%-99.3%) versus 94.9% (95% CI, 91.9%-96.9%), and 310.7 (95% CI, 121.2-796.6) versus 218.8 (95% CI, 107.3-438.1).
CONCLUSIONS: This meta-analysis indicated that the MSRSGC works well in FNA cytopathology practice and improves diagnostic accuracy in all diagnostic categories. The ROMs of prospective studies were in concordance with the MSRSGC reference values.

BACKGROUND: Fine needle aspiration cytology is often used for the initial diagnosis and management of patients with salivary gland tumors. Because of its global usage, a consensus classification schema was devised in 2018 to initiate universal reporting of salivary gland cytology specimens, termed the Milan system for reporting salivary gland cytopathology (MSRSGC) and composed of distinct diagnostic categories. Few retrospective studies have been undertaken to review the MSRSGC within institutions.
METHODS: We analyzed salivary gland fine needle aspirations during a 10-year span from 2011 to 2021, categorized each cytology case to fit the MSRSGC, and subsequently reviewed the corresponding surgical resections, if indicated, to determine the rate of malignancy (ROM) and rate of neoplasia.
RESULTS: Our ROM was higher (>10%) for the following MSRSGC categories: non-neoplastic, atypia of undetermined significance, and suspicious for malignancy. Also, our data correlated well with the following MSRSGC categories: nondiagnostic, neoplasm-benign, salivary gland neoplasm of uncertain malignant, and malignant.
CONCLUSIONS: Although the data were indicative of the ROM for surgically resected salivary gland lesions, the ROM for non-neoplastic lesions could truly be lower given that most lesions in this category will not undergo surgical resection. Additionally, determination of the rate of neoplasia could a tool that could be used to further guide our clinical colleagues.

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a standard, evidence-based classification system for salivary gland fine-needle aspiration (SG-FNA). Since it was published in 2018, many researchers across the world have applied this uniform reporting system to their cohorts.
The authors comprehensively reviewed cohort studies conducted since publication of the MSRSGC and performed a meta-analysis. The risk of neoplasm and the risk of malignancy (ROM) were calculated for each diagnostic category, and their diagnostic efficacy was evaluated.
Thirty-five studies were included in the meta-analysis. The total number of SG-FNAs was 10,706, and 7168 of those had histopathologic follow-up. The ROM for each category was: nondiagnostic, 11.4%; nonneoplastic, 10.9%; atypia of undetermined significance, 30.5%; neoplasm-benign, 2.8%; neoplasm-salivary gland neoplasm of uncertain malignant potential, 37.7%; suspicious for malignancy, 83.8%; and malignant, 97.7%. Low-level heterogeneity was observed in ROM estimation. The sensitivity, specificity, and diagnostic odds ratio for differentiating malignant and benign lesions were 88.0%, 98.5% and 520.3, respectively.
The reporting of SG-FNA using the MSRSGC demonstrated high diagnostic accuracy. The ROM for each category was generally concordant with the recommendations, except for the suspicious for malignancy category, which was significantly higher than the reference value. The tiered, standardized classification system would benefit the clinical management of salivary gland lesions.

Secretory carcinoma (SC) of the salivary gland is a rare entity with limited published literature on cytomorphology. The authors present the largest cohort to date of SC fine-needle aspiration (FNA) cases.
FNA cases of histologically confirmed SC were retrospectively retrieved from 12 academic institutions in the United States, Italy, Finland, and Brazil. The collated data included patient demographics, imaging findings, cytopathologic diagnoses according to the Milan System for Reporting Salivary Gland Cytopathology, cytomorphologic characteristics, and immunohistochemical/molecular profiles.
In total, 40 SCs were identified (male-to-female ratio, 14:26) in patients with a mean age of 52 years (age range, 13-80 years). Ultrasound imagining revealed a hypoechoic, ovoid, poorly defined, or lobulated mass. The most common primary site was the parotid gland (30 of 40 tumors). Regional lymph node metastasis (9 patients) and distant metastasis (4 patients; brain, liver, lungs, and mediastinum) were noted. Two patients died of disease. FNA smears were cellular and demonstrated mainly large, round cells with intracytoplasmic vacuoles or granules and round-to-oval nuclei with smooth nuclear contour, minimal irregularities, and prominent nucleoli arranged predominantly in clusters, papillary formations, and single cells. The background was variable and contained inflammatory cells, mucin, or proteinaceous material. The diagnoses were malignant (19 of 38 tumors; 50%), suspicious for malignancy (10 of 38 tumors; 26%), salivary gland neoplasm of uncertain malignant potential (7 of 38 tumors; 18%), and atypia of undetermined significance (2 of 38 tumors; 6%) according to the Milan System for Reporting Salivary Gland Cytopathology. Two malignant cases (2 of 40 tumors; 5%) were metastases. The neoplastic cells were immunoreactive for S100 (23 of 24 tumors), mammaglobin (18 of 18 tumors), GATA-3 (13 of 13 tumors), AE1/AE3 (7 of 7 tumors), and vimentin (6 of 6 tumors). ETV6-NTRK3 fusion was detected in 32 of 33 tumors by fluorescence in situ hybridization (n = 32) and next-generation sequencing (n = 1).
Familiarity with cytomorphologic features and the immunohistochemical/molecular profile of SC can enhance diagnostic accuracy.

The term \"Atypia\" has been employed to describe a wide spectrum of cytomorphologic features associated with reactive/inflammatory processes as well as those suspicious for neoplasms in cytology. Similar to other cytopathology reporting systems, the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has reserved the atypical category for cytology specimens lacking quantitative and/or qualitative cytomorphologic features to be diagnosed with confidence as either non-neoplastic or neoplastic. In MSRSGC, the atypical category is associated with a risk of malignancy and recommendation for clinical management. In this review, we discuss the value of atypical diagnostic category of MSRSGC in both cystic and non-cystic salivary gland lesions by evaluating our institutional case cohort.

OBJECTIVE: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a recently published evidence-based categorization system for salivary gland fine-needle aspiration (FNA). We applied MSRSGC to Japanese cases and evaluated its utility.
METHODS: A total of 480 FNA cases were reviewed. We recategorized each case into one of the MSRSGC categories. The risk of neoplasm (RON) and the risk of malignancy (ROM) for each diagnostic category in MSRSGC, and the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for malignancy and for neoplasms were calculated for cases with histological follow-up. In addition, the overall ROM (O-ROM) was calculated for all FNA cases.
RESULTS: RON, ROM, and O-ROM rates were as follows - non-diagnostic: 51.3, 5.1, and 1.0%; non-neoplastic: 0, 0, and 0%; atypia of undetermined significance: 83.9, 12.9, and 7.3%; neoplasm, benign: 100, 0, and 0%; salivary gland neoplasm of uncertain malignant potential: 100, 32.1, and 23.7%; suspicious for malignancy: 100, 85.7, and 60%; and malignant: 100, 100, 81.8%. The sensitivity, specificity, and accuracy with (without) indeterminate cases for malignancy were 65 (100), 99 (99), 92% (99%) and PPV and NPV were 96 and 100%, respectively, and those for neoplasms were 84 (100), 100 (100), 85% (100%), and PPV and NPV were 100 and 100%, respectively.
CONCLUSIONS: The MSRSGC is useful for stratification of ROM and for promoting the performance of salivary gland FNA. The MSRSGC could be easily introduced in Japan and may improve the Japanese salivary gland FNA status.

Cystic salivary gland lesions present diagnostic challenges on fine-needle aspiration (FNA) specimens that are related to sampling limitations and a broad differential diagnosis. This study evaluated the benefit of applying the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) to a series of cystic salivary gland lesions.
The pathology archives at the Johns Hopkins Hospital were searched to identify cystic salivary gland FNA specimens over a 19-year period (2000-2018). Patient demographics, cytomorphologic features, and clinical and surgical follow-up were recorded. The MSRSGC was applied to the cases. The risk of malignancy (ROM) and the risk of neoplasia (RON) were calculated for each category.
One hundred seventy-eight cases were identified (96 males and 82 females) with a mean age of 53 years (range, 4-90 years). After the MSRSGC was applied, there were 52 nondiagnostic cases (29.2%), 80 nonneoplastic cases (44.9%), 35 cases of atypia of undetermined significance (AUS; 19.7%), 3 benign neoplasms (1.7%), 3 salivary gland neoplasms of uncertain malignant potential (SUMP; 1.7%), 4 cases suspicious for malignancy (SFM; 2.2%), and 1 malignant case (0.6%). One hundred fifty-six of the 178 patients (87.6%) had follow-up data available. The RON and ROM values for cases with surgical follow-up were 33.3% (3 of 9) and 22.2% (2 of 9) for the nondiagnostic category, 42.9% (9 of 21) and 19% (4 of 21) for the nonneoplastic category, 76.5% (13 of 17) and 29.4% (5 of 17) for the AUS category, 100.0% (2 of 2) and 50.0% (1 of 2) for the SUMP category, and 100% (2 of 2) and 100% (2 of 2) for the SFM category, respectively.
Applying the MSRSGC to cystic salivary gland lesions improves patient management by preventing unnecessary surgery for nonneoplastic conditions. The ROM was highest in the SFM category (100%), which was followed by the SUMP, AUS, nondiagnostic, and nonneoplastic categories. Less than adequate specimens may increase the diagnosis of AUS.

BACKGROUND: The Milan system for reporting salivary gland cytopathology (MSRSGC) aims to standardize terminology, facilitate communication, and optimize management by providing risk of malignancy (ROM) for each category. Our retrospective cohort aims to study the reproducibility of reporting using the MSRSGC and to calculate the ROM for each category.
METHODS: Cases of fine needle aspiration (FNA) of salivary glands and related cervical lymph nodes were retrieved from our files between 2015 to 2019. From a total of 63 cytology cases, 57 cases had available material for cytological reexamination of which 45 cases had follow up data. All cases were reviewed independently by two pathologists and reclassified based on the MSRSGC. The reclassification of cases for both pathologists was compared and the ROM for each diagnostic category was calculated.
RESULTS: The 57 cases were studied. Both pathologists had initial concordance in classification of 52 of 57 cases. The remainder five cases were concurred upon after combined review. The cases were classified as: Non Diagnostic (ND); (n = 8), Non Neoplastic (NN); (n = 7), Atypia of Undetermined Significance (AUS); (n = 8), Neoplasm Benign (NB) (n = 10), Salivary Gland Neoplasm of Uncertain Malignant Potential (SUMP) (n = 5), Suspicious for Malignancy (SM) (n = 1) and Malignant (M) (n = 18). The ROM was: ND: (33.3%); NN: (0%); AUS (33.3%); NB (0%); SUMP (25%); SM (100%) and M (100%).
CONCLUSIONS: Applying the MSRSGC is reproducible which facilitates standardization of reports and stratifying cases preoperatively. In general, the ROM for our cases was close to that reported in the literature.

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has established distinct diagnostic categories for reporting cytopathological findings, and each is associated with a defined risk of malignancy (ROM). However, the ROM is applied at the overall category level and is not specific for particular morphological entities within a category. Here, the diagnostic performance of the MSRSGC for pleomorphic adenoma (PA) and Warthin tumor (WT) is reported.
The pathology archives of 11 institutions from 4 countries were retrospectively searched to identify all salivary gland fine-needle aspiration (FNA) biopsies with a differential or definitive diagnosis of PA or WT and all resection specimens with a diagnosis of PA or WT; only paired cases were included. All FNA diagnoses were retrospectively classified according to the MSRSGC.
A total of 1250 cases met the inclusion criteria, and they included 898 PA cases and 352 WT cases. The ROM in the benign neoplasm category was 3.0% and 1.3% for cases with a differential or definitive diagnosis of PA and WT, respectively. The ROM in the salivary gland neoplasm with uncertain malignant potential (SUMP) category was 2.7% and 18.8% for PA and WT, respectively (P = .0277). The diagnostic accuracy for PA and WT was 95.1% and 96.1%, respectively.
The diagnostic accuracy for PA and WT on FNA is high. Furthermore, these findings highlight the difference in the ROMs associated with 2 specific differential diagnoses in the SUMP category: basaloid neoplasms and oncocytoid neoplasms.

BACKGROUND: South Africa has a very high prevalence of HIV/AIDS. Salivary gland lesions are common in HIV-infected patients. The aim of this study was to determine the pathologic entities diagnosed on fine-needle aspiration (FNA) of salivary gland masses in an HIV-infected study population that now has free access to antiretroviral (ARV) therapy and how this differs from the pathologic entities before the advent of widespread ARV availability, and if the Milan system for reporting salivary gland cytopathology (MSRSGC) can be applied to HIV-infected patients.
METHODS: A retrospective review was performed on confirmed HIV-infected patients who underwent FNA of salivary gland masses over a two-year period.
RESULTS: A total of 360 patients underwent FNA of salivary gland masses within the designated time frame, 58.3% (210) females and 41.7% (150) males. Patient ages ranged from 7 months to 67 years with a mean age of 36.9 years. The parotid gland was the most biopsied salivary gland at 55.3% (199). The most common diagnosis made in patients on antiviral therapy was lymphoepithelial cyst while that in patients not on antiviral therapy was infectious (including abscess and mycobacterial infection). The most frequent neoplasms were non-Hodgkin lymphoma, pleomorphic adenoma and squamous-cell carcinoma.
CONCLUSIONS: Patients on ARV therapy had higher CD4 counts, fewer infectious lesions, and more reactive and benign salivary gland lesions. Patients not on treatment had significantly lower CD4 counts and were frequently diagnosed with infectious processes. The MSRSGC is well-suited for use in HIV-infected patients.