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Objectives: Fine needle aspiration (FNA) plays a crucial role in their initial assessment of salivary gland neoplasms. In the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), the category of Salivary Gland Neoplasm of Uncertain Malignant Potential (SUMP) categorizes lesions with ambiguous features. This study aims to investigate the risk of neoplasm (RON) and risk of malignancy (ROM) within different subgroups of SUMP lesions using data from three large academic institutions., Methods: We analyzed salivary gland (FNA) cases from three academic institutions post-MSRSGC implementation. Salivary gland FNA cases categorized as Milan IVB (SUMP) with subsequent surgical pathology follow-up were analyzed. Cases were divided into basaloid, oncocytic, and clear cell SUMP subtypes, with RON and ROM assessed and compared., Results: Out of 1377 MSRSGC cases, 231 were SUMP (16.8%), with 101 subjected to surgical pathology follow-up. The overall ROM for SUMP was 20.8%, with variations of 10% to 29.5% observed amongst institutions, but no significant difference was observed among three institutions (p = 0.15). Basaloid and oncocytic SUMP displayed 17.1% and 20.5% ROM, respectively, without significant disparity. However, all clear cell SUMP cases were malignant on surgical resection., Conclusions: This study highlights the variability in ROM for SUMP lesions and the significantly higher ROM in SUMP cases with clear cell features. These findings emphasize the importance of accurately subcategorizing SUMP lesions, particularly those with clear cell features, for appropriate clinical management., (© 2024 Wiley Periodicals LLC.)

Background: The Milan System for Reporting Salivary Gland Cytopathology is an effective reporting system for salivary gland fine needle aspirations with well-established risks of malignancy. Salivary gland neoplasm of uncertain malignant potential (SUMP) comprises a heterogenous group of lesions which have features that can be recognized as at least neoplastic but preclude further classification into benign or malignant. In this study, we reviewed the cytomorphologic features of salivary gland fine needle aspirations diagnosed as SUMP at our institution (over the past 6 years) and correlated those with the final diagnosis on surgical follow up., Design: A retrospective search was performed to identify cases classified as SUMP at our institution from January 2018 to February 2024. Cytology slides were reviewed, and cases were subclassified based on key cytomorphologic features into the following categories: (1) basaloid, (2) oncocytic, (3) with clear cell features and (4) mixed features (myoepithelial/oncocytoid/squamoid features). Histologic diagnosis was recorded if available., Results: A total of 36 cases of SUMP were identified; 31/36 had surgical follow up; final diagnosis included 22 benign lesions (2 non-neoplastic and 20 benign neoplasms), and nine malignant lesions. The overall risk of neoplasm and risk of malignancy were 93.5% and 29% respectively, with the oncocytic sub-category recording the highest ROM (42.8%). Mucoepidermoid carcinoma was the most common malignant diagnosis and pleomorphic adenoma the most common benign diagnoses., Conclusions: Our study supports the subclassification of SUMP lesions based on key cytomorphologic features, thereby aiding in refining this ambiguous entity and providing a precise risk assessment., (© 2024 Wiley Periodicals LLC.)

Background: The correlation between Human Papillomavirus (HPV) and salivary gland neoplasms is still controversial. Data in the literature are conflicting, reporting the presence of the HPV-DNA in a significant percentage of cases or none. We investigated the presence of HPV in a series of salivary gland neoplasms using fine needle aspiration cytology (FNAC) samples to explore its potential oncogenic role in salivary gland tumor development., Methods: The study included 66 salivary gland lesions from 65 patients. For all cases, residual cytological material in the needle hub, once direct smears were obtained, was fixed by rinsing the needle in Cytolyt hemolytic and preservative solution (Hologic Inc. Marlborough, MA 01752 USA). The samples fixed in the Cytolyt hemolytic and preservative solution (Hologic Inc. Marlborough, MA 01752 USA) were centrifuged at 252 g, then the sediment was transferred to the Preservcyt solution and used for the detection of HPV-DNA., Results: We found evidence of the presence of HPV in two salivary intraglandular cysts lined by squamous cell epithelium. Furthermore, we also found HPV in three metastatic oropharyngeal squamous cell carcinomas (SCC) located in the parotid gland. Regarding primary salivary gland tumors, the HPV test produced negative results in all cases., Conclusion: HPV testing produced negative results in all primary salivary gland tumors, failing to confirm the potential involvement of HPV infection in the pathogenesis of salivary gland tumors. Instead, the presence of HPV DNA in samples of salivary intraglandular cysts, never reported before, may be an interesting fact, which however requires further evaluation., (© 2024 The Author(s). Diagnostic Cytopathology published by Wiley Periodicals LLC.)

Introduction: Salivary gland neoplasm of uncertain malignant potential (SUMP) is an important diagnostic category of the Milan System for reporting salivary gland cytology (MSRSGC). Further subcategorization by cytomorphologic subtypes has been recommended to risk-stratify cases. In this study, our institutional experience with the risk of neoplasm (RON) and risk of malignancy (ROM) based on cytomorphologic subcategorization of SUMP is reported. We also report the prevalence of malignancy (POM) at our institution., Methods: The pathology database was queried for cases of fine-needle aspiration (FNA) diagnosed as SUMP along with follow-up at our institution from 2018-February 2024. This study was approved by an institutional review board., Results: Of 1159 cases of salivary gland FNA specimens reported as per MSRSGC at our institution, 14.8% (171/1159 cases) were diagnosed as SUMP, with these reports verified by at least 16 cytopathologists. Surgical follow-up was available for 139/171 (81.3%) of these cases, for which the original cytomorphologic subgroups were as follows: 65 (46.8%) basaloid, 48 (34.5%) oncocytic/oncocytoid, 14 (10.1%) myoepithelial, 9 (6.5%) other, 2 (1.4%) clear cell, and 1 (0.7%) mucinous. The POM within SUMP at our institution is within a range of 29.8%-36.7%. When considering all cases, our institutional RON for SUMP was 97.8% (136/139), and the ROM was 36.7% (51/139). Notably, a significant portion of cases (36%, 50/139) underwent review at a daily intradepartmental consensus conference. Analysis revealed that SUMP cases that underwent consensus review had a ROM of 46% (23/50), versus 31.5% (28/89) in independently verified cases (p = .13). Of the cytomorphologic subgroups, basaloid SUMP in particular was more likely to be benign on resection when the case had been independently verified than after consensus review (p = .0082). When considering only the independently verified cases, the ROM for each subgroup was as follows: 38.7% (12/31) in oncocytic/oncocytoid, 20% (9/45) in basaloid, 33.3% (2/6) in myoepithelial, 60% (3/5) in "other", and 100% (1/1) in both mucinous and clear cell (p = .0407)., Conclusion: While the RON is high across all cytomorphologic subgroups of SUMP, the ROM does vary across the groups, with basaloid cytomorphology having the lowest ROM. This effect is seen in independently verified cases but not in cases having undergone consensus review., (© 2024 The Author(s). Diagnostic Cytopathology published by Wiley Periodicals LLC.)

Salivary glands have essential roles in maintaining oral health, mastication, taste and speech, by secreting saliva. Salivary glands are composed of several types of cells, and each cell type is predicted to be involved in the carcinogenesis of different types of cancers including adenoid cystic carcinoma (ACC), acinic cell carcinoma (AciCC), salivary duct carcinoma (SDC), myoepithelial carcinoma (MECA) and other histology. In our study, we performed single nucleus RNA-seq on three human salivary gland samples to clarify the gene expression profile of each complex cellular component of the salivary glands and related these expression patterns to expression found in salivary gland cancers (SGC) to infer cell of origin. By single nucleus RNA-seq, salivary gland cells were stratified into four clusters: acinar cells, ductal cells 1, ductal cells 2 and myoepithelial cells/stromal cells. The localization of each cell group was verified by IHC of each cluster marker gene, and one group of ductal cells was found to represent intercalated ductal cells labeled with HES1. Furthermore, in comparison with SGC RNA-seq data, acinar cell markers were upregulated in AciCC, but downregulated in ACC and ductal cell markers were upregulated in SDC but downregulated in MECA, suggesting that markers of origin are highly expressed in some SGC. Cell type expressions in specific SGC histology are similar to those found in normal salivary gland populations, indicating a potential etiologic relationship., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Secretory carcinoma (SC) was originally described as mammary analogue secretory carcinoma (MASC). We present here a case of 33 years old male who came to ENT outpatient department with a complaint of swelling over the left side of his neck for 8 months. On Fine-needle aspiration cytology, an impression of cytomorphological features suggestive of acinic cell carcinoma (Milan category V) was given. Left functional endoscopic sinus surgery was done. On histopathology, a final impression of Secretory carcinoma, the left submandibular gland was given with pathological stage classification as pT2N0Mx. SC of the salivary gland is a rare entity that may pose diagnostic challenges. Awareness of its cytologic features is paramount to achieve an accurate diagnosis. Morphologic interpretation must be supported by an immunohistochemical profile and molecular studies to confirm a diagnosis of SC., (© 2023 Wiley Periodicals LLC.)

Introduction: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) emerged in 2015 as an attempt to establish protocols for a most appropriate follow-up and treatment of patients with salivary gland lesions. Through fine needle aspiration (FNA), a safe and minimally invasive way to obtain cytological samples, the lesion is classified into one of the six categories, which have different risks of malignancy (ROM) and, therefore, different management., Materials and Methods: FNA cytology procedures performed between January 2016 and June 2020 (54 months) at the Pathology Institute of Araçatuba, São Paulo, Brazil, were analyzed by two pathologists with more than 5 years of experience. The ROM for each of the diagnostic categories was determines and compared with the ROM expected by the MSRSGC., Results: A total of 99 FNA of salivary gland lesions were reviewed and retrospectively categorized. Histopathological follow-up was available for 58 of 96 patients (60.42%). The patients age ranged from 23 to 98 years with the mean of 58.15 ± 15.29 years. The parotid gland was the most affected (81.82%). The average size of the lesions was 2.59 cm. The ROM for each category was 16.67%, 0%, 0%, 2.86%, 50%, 100%, 100%, respectively., Conclusion: This is the first Brazilian study describing the application of the MSRSGC in the routine of a private Laboratory out of a cancer center service. Therefore, it is an effective method in the classification of salivary gland lesions, when associated with the MSRSGC, to determine the ROM and its appropriate treatment., (© 2023 Wiley Periodicals LLC.)

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%)., (© 2023 Wiley Periodicals LLC.)

Introduction: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is an established system with reproducible risk of malignancies (ROM) for salivary gland fine needle aspiration (SGFNA). No studies have reviewed the relationship between Milan categories and the resection rate (RR) and time to resection (TTR)., Methods: We searched our database (January 1, 2011 to January 4, 2021) for non-lymphoma SGFNAs and assigned appropriate MSRSGC categories. RR and TTR were calculated and compared for each category. A literature search was performed; RRs and TTRs were compared., Results: Seven hundred and eighty SGFNAs were identified, 333 with follow-up. RR was highest in suspicious for malignancy (SUS, V; 70.6%, n = 12/17), followed by the salivary gland neoplasm of uncertain malignant potential (SUMP, IVb; 69.6%, n = 80/115) and malignant (M, VI; 55.6%, n = 75/135). Among M, primary tumors had a higher RR (65.1%, n = 41/63) than metastases (47.2%, n = 34/72, p = .36). In literature review, SUS had the highest RR (69.3%, n = 233/336) followed by M (61.6%, n = 821/1332) and SUMP (60.2%, n = 632/1050). TTR was shorter in SUS (mean = 32.3 days, median = 25 days). Within the benign neoplasms (BN, IVa), Pleomorphic adenomas (PAs) had a higher RR than Warthin tumors (WTs) (66.3% vs. 37.2%, p < .00001), and a shorter TTR (median = 63 days vs. 90 days)., Conclusions: Tumors classified as SUS had higher RR and at shorter intervals than those classified as SUMP. PAs have higher RRs and more expedient surgery than WTs. Cases classified as M are less likely to undergo follow-up than SUS, perhaps due to a lower RR for metastases., (© 2023 Wiley Periodicals LLC.)

Background: Interpretation of salivary gland cytology often leads to inter-observer variability due to heterogenous and complex nature of these lesions. This creates a dilemma regarding their management by clinicians. Proposal of a universal system of reporting of salivary gland lesions leading to agreement in diagnosis and better understanding among clinicians was the need of the hour. Hence Milan system for reporting salivary gland cytopathology (MSRSGC) was proposed in 2015 by the American society of cytopathology and the International Academy of Cytology. Present study was undertaken to assess inter-observer variability in reporting by conventional system and MSRSGC., Material and Methods: One hundred and seventy-six cases of salivary gland lesions were subjected to fine needle aspiration cytology. Cases were interpreted by two experienced cytopathologists and were reported by both conventional system and MSRSGC. Histopathological correlation was available in 81 cases., Results: Inter-observer variability was noted in six cases reported by conventional system and in two cases by MSRSGC. Moreover three cases out six cases had different management protocols while both cases of Milan system for reporting salivary gland cytology had same management. Thirteen cases diagnosed by Milan system and 17 cases diagnosed by conventional system were discordant with histopathological diagnosis., Conclusion: Milan system for reporting salivary gland cytology has an edge over conventional system of reporting as it provides better agreement among cytopathologists and better management guidelines for clinicians with the added advantage of assessment of risk of malignancy., (© 2022 Wiley Periodicals LLC.)

Background: Ancillary studies are commonly performed on cell blocks prepared from fine-needle aspiration (FNA) specimens. There are limited studies in application of ancillary studies on cell blocks from salivary gland (SG) FNAs. This multi-institutional study evaluates the role of ancillary studies performed on cell blocks in the diagnosis of SG lesions, and their impact on clinical management., Method: The electronic pathology archives of three large academic institutions were searched for SG FNAs with ancillary studies performed on cell blocks. The patient demographics, FNA site, cytologic diagnosis, ancillary studies, and surgical follow-up were recorded. If needed, the cytologic diagnoses were reclassified as per the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC)., Results: 117 SG FNA cases were identified including 3, 10, 11, 6, 23, 4, and 60 cases in MSRSGC categories I, II, III, IVa, IVb, V, VI, respectively with surgical follow-up available ranging from 27% to 100% within each category. Ancillary studies including histochemistry, immunocytochemistry (IHC), and in situ hybridization (ISH) were beneficial in 60%-100% of cases in each category. Risk of malignancy was 100% in both the suspicious for malignancy (V) and malignant (VI) categories. Ancillary studies improved diagnosis in 60% of non-neoplastic cases (II, 6/10), 100% of benign neoplasm cases (IVa, 6/6), and 98.3% of malignant cases (VI, 59/60)., Conclusion: Judicious and case-based ancillary studies performed on SG FNA cell blocks with sufficient material can improve the diagnostic yield by further characterization of the atypical/neoplastic cells, particularly in MSRSGC categories IVa-VI., (© 2022 The Authors. Diagnostic Cytopathology published by Wiley Periodicals LLC.)

Pleomorphic adenoma of the salivary gland is a well-established and recognized diagnosis; however, pleomorphic adenomas of the breast are rare and can be difficult to diagnose on cytology or intraoperatively. We report a case that was misdiagnosed on a fine needle aspiration and frozen section. The pitfalls, differential diagnoses, and current management are discussed., (© 2022 Wiley Periodicals LLC.)

A 15-year-old male presented to the hospital with a 2-month history of a right parotid mass. Magnetic resonance imaging revealed an encapsulated 3.7 cm mass. Fine-needle aspiration suggested a monomorphic adenoma (prior to utilization of the Milan Classification system). Total parotidectomy was performed with dissection and preservation of the facial nerve. Surgical pathology identified the lesion as sclerosing polycystic adenosis (SPA) after examining the histopathological and immunohistochemistry findings. SPA is a rare lesion which leads to inflammatory changes in the salivary gland. The most common site impacted is the parotid gland but also can affect other major or minor salivary glands. The fibrocystic changes are morphologically like the histological developments of sclerosing adenosis of breast tissue. Those changes consist of fibrosis, apocrine metaplasia, and different degrees of proliferation of ducts, acini, and myoepithelial cells. The pathogenesis of SPA is unknown but recent studies suggest that it could be a neoplasm. Treatment with surgical excision is effective and its' recurrence is rare. This case report details the cytomorphology, histology, and immunohistochemical profile of SPA., (© 2021 Wiley Periodicals LLC.)

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., (© 2022 Wiley Periodicals LLC.)

Due to the heterogenicity and morphological overlap among the broad spectrum of benign and malignant salivary gland lesions, cytopathology result interpretations can be challenging and variable even among the most experienced head and neck pathologist. There was no standardization of cytopathology result reporting until the recently proposed "Milan system for reporting salivary gland cytopathology" (MSRSGC). MSRSGC may offer more clarity and help minimize ambiguity, but surgeons, as part of multidisciplinary teams, do not only rely on the tiered stratification and risk of malignancy assessment. With only the MSRSGC reported, there may be critical information missing from the overall diagnostic evaluation of salivary gland masses. Cytopathologist evaluation, description of findings, and expert interpretation of the fine-needle aspiration cytology along with differential diagnosis can be critical pieces of information, that is, utilized in management discussions with patients and their families. This information needs to be included in every cytopathology interpretation in addition to the MSRSGC classification. In clinical practice, decisions concerning salivary gland tumor management are not based on single examinations but incorporate information from multiple sources including patient histories, clinical symptoms and signs, physical examinations, imaging studies, and when available, cytopathology. Additional cytopathology information will likely help to improve the utility and predictive power of MSRSGC, similar to Bethesda Classification and the predictive importance of nuclear atypia in indeterminate thyroid biopsy material for thyroid neoplasms., (© 2021 Wiley Periodicals LLC.)

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%., Conclusion: 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., (© 2021 Wiley Periodicals LLC.)

Secretory carcinoma (SC) of the salivary gland is a rare distinct clinicopathological entity characterized by the presence of the ETV6-NTRK3 fusion. Although the characteristic cytological features of SC have been recognized, its cytodiagnosis, especially differentiating SC from acinic cell carcinoma, is challenging. Recent studies have revealed that immunohistochemistry for pan-tyrosine receptor kinase (Trk) and nuclear receptor subfamily 4 group member 3 (NR4A3) are specific for SC and acinic cell carcinoma, respectively. However, the usefulness of immunocytochemical detection of these markers in the diagnosis of SC has not been addressed. Hence, the present study aimed to analyze the usefulness of immunocytochemical staining for pan-Trk and NR4A3 in the cytodiagnosis of SC. We enrolled eight patients with a histopathological diagnosis of SC who underwent preoperative fine-needle aspiration cytological examination. The cytological characteristics were reviewed and immunocytochemical staining for pan-Trk and NR4A3 was performed. The characteristic cytological features noted in the patient cohort included neoplastic cell clusters with a sheet-like and papillary cluster arrangement as well as single cells. Additionally, neoplastic cells with mild to moderately enlarged nuclei and small nucleoli, multi-vacuolated cytoplasm, and intracytoplasmic mucin were also observed. The immunocytochemical analyses clearly demonstrated that all eight specimens showed positive nuclear staining for pan-Trk, but were negative for NR4A3 expression. Although all cases of SC do not always show positive immunoreactivity for pan-Trk, immunocytochemical analysis for pan-Trk may be useful for the cytodiagnosis of SC along with assessment of the characteristic cytological features., (© 2021 Wiley Periodicals LLC.)

Background: This study aims to assess in our institutional experience the accuracy of fine needle aspiration cytology (FNAC) in the diagnosis of salivary gland masses (SGM) according to the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and to an in-house system., Methods: The study included 189 FNACs conducted between January 2011 and December 2019. The FNACs, classified according to the in-house system, were reclassified according the MSRSGC. Taking histopathology as gold standard, the measures of diagnostic accuracy of FNAC were determined for suspicion for malignancy (SFM) and malignant categories., Results: According to the in house system, FNAC diagnoses were classified as: 23 (12.2%) non-diagnostic (ND), 23 (12.2%) non-neoplastic (NN), 119 (62.9%) benign neoplasm (BN), 10 (5.2%) indefinite neoplasm (IN), 2 (1.1%) SFM, and 12 (6.4%) malignant (M). Based on the MSRSGC, there were 3 (1.5%) cases of atypia of undetermined significance (AUS) and 7 (3.7%) neoplasms of uncertain malignant potential (SUMP). The number of ND, NN, BN, SFM, and M cases were identical in the two systems. For both systems, the sensitivity, the specificity, the positive predictive value, the negative predictive value, and the accuracy for malignancy diagnosis were 77.8%, 100%, 100%, 97.6%, and 97.8%, respectively., Conclusion: According to the MSRGC and to our in-house reporting system, FNAC is an accurate technique for the diagnosis of malignant salivary tumors with excellent specificity and good sensitivity. However, MSRGC has the advantage of standardization of salivary gland cytology reporting., (© 2020 Wiley Periodicals LLC.)

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%)., Conclusion: 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., (© 2020 Wiley Periodicals LLC.)

Objective: Fine-needle aspiration (FNA) is a key diagnostic method in the evaluation of salivary gland lesions. Secondary tumors of salivary glands represent only 5% of all malignancies of major salivary glands. The goal of our study was to examine the cytological and clinical features of secondary tumors sampled by FNA., Materials and Methods: A series of 36 secondary tumors from the pathology departments of two university hospitals are presented. Clinical referrals to FNA, cytological features, immunohistochemical results, and histopathological diagnoses were reviewed in all cases., Results: The study population consisted of 36 cases (19 males and 17 females) with mean age 70.9 ± 13.0 years (range 41-96 years). The most common site of the metastasis was parotid gland (n = 26). The primary malignancy was known in 17 cases at the time of FNA diagnosis. The most common primary site was skin of head and neck area (11 cases) followed by lungs (n = 5) and tonsils (n = 5), kidney (n = 2) and breast (n = 2) and thyroid gland, gastrointestinal tract and soft tissue, 1 case of each. In 8 cases, the primary site remained unknown. The diagnostic or confirmatory immunocytochemistry was performed on cell blocks in 21 cases., Conclusions: FNA is a reliable technique in the diagnosis of salivary gland secondary malignancies. The knowledge of the personal history of malignancy is essential for the successful immunocytochemical targeted diagnosis without any delay., (© 2020 The Authors. Diagnostic Cytopathology published by Wiley Periodicals LLC.)

A lymphoid-rich stroma is a common finding in salivary gland tumors. Several reports documented this association with acinic cell carcinoma (ACC). However, cytologic studies reporting this phenomenon are rare and mainly confined to sporadic single case reports. We present the cytologic features of two cases of ACCs of the parotid gland displaying a lymphoid-rich background and discuss the cytologic differential diagnoses of this uncommon ACC variant., (© 2020 Wiley Periodicals LLC.)

To generate a reliable preclinical model system exhibiting the molecular features of salivary adenoid cystic carcinoma (ACC) whose biology is still unclear due to the paucity of stable cell cultures. To develop new in vitro and in vivo models of ACC, the techniques of organoid culture and patient-derived tumor xenograft (PDX), which have attracted attention in other malignancies in recent years, were applied. Tumor specimens from surgically resected salivary ACC were proceeded for the preparation of PDX and organoid culture. The orthotopic transplantation of patient-derived or PDX-derived organoids was demonstrated into submandibular glands of NSG mice and those histology was evaluated. PDX-derived organoid cells were evaluated for the presence of MYB-mediated fusion genes and proceeded for in vitro drug sensitivity assay. Human ACC-derived organoids were successfully generated in three-dimensional culture and confirmed the ability of these cells to form tumors by orthotopic injection. Short-term organoid cell cultures from two individual ACC PDX tumors were also established that maintain the characteristic MYBL1 translocation and histological features of the original parent and PDX tumors. Finally, the establishment of drug sensitivity tests on these short-term cultured cells was confirmed using three different agents. This is the first to report an approach for the generation of human ACC-derived organoids as in vitro and in vivo cancer models, providing insights into understanding of the ACC biology and creating personalized therapy design for patients with ACC., (© 2020 Union for International Cancer Control.)

Background: Adenoid cystic carcinoma (AdCC) is an uncommon malignancy of the salivary gland characterized by slow growth, increased risk of recurrence and poor prognosis. The annual incidence in the United States is approximately 1200 cases per year and rarely involves the body cavities., Case Presentation: We present a case of a 48-year-old male diagnosed with AdCC of the left submandibular gland. He received his last chemotherapy in 2006 and presented with pleural metastasis. After undergoing pleurectomy and decortication procedure, pericardial fluid and biopsies from the chest wall, sixth rib, diaphragm, pleural cavity and pericardium were sent for pathologic evaluation. A diagnosis of metastatic adenoid cystic carcinoma was confirmed, including in the pericardium, pericardial fluid and diaphragm., Conclusion: AdCC of the submandibular gland is a malignant tumor with a high mortality rate. It is very rare for AdCC to metastasize to the pericardium and diaphragm. Metastasis to uncommon sites such as seen in our case with metastases to the pericardium and diaphragm shows the aggressive and unpredictable nature of this tumor, requiring close follow up, and indicating the need for molecular profile analysis and biomarker-stratified clinical trials., (© 2020 Wiley Periodicals LLC.)

Background: Salivary gland lymphadenoma (LAD) is a rare benign neoplasm comprising sebaceous (SLAD) and nonsebaceous (NSLAD) types. Despite established histologic criteria, limited data on cytomorphology, tumor heterogeneity, and overlap with other entities make the diagnosis of LAD by fine needle aspiration (FNA) challenging. We describe a multi-institutional cohort of 14 LADs with cytology, clinical, radiologic, and histopathologic data., Methods: Our cohort included nine SLAD and five NSLAD with corresponding histopathology. Mean patient age and M:F ratio were 60.4 years (range 45-86 years) and 1:2 for SLADs and 57.4 years (range 42-80 years) and 1:1.5 for NSLADs, respectively. One NSLAD patient had a germline predisposition for Cowden syndrome. Glass slides and whole slide images of air-dried Diff-Quik (DQ), alcohol-stained Papanicolaou smears (Pap) and cellblocks were reviewed for key cytomorphologic findings., Results: FNAs from SLAD and NSLADs demonstrated vacuolated and basaloid epithelial clusters within a lymphoid background. Vacuolated cells from SLAD showed sebaceous cells with microvesicular cytoplasm indenting a central nucleus. Vacuolated cells from NSLAD were columnar with eccentric nuclei, corresponding to abluminal glandular cells. SLADs were classified using the Milan System for Reporting Salivary Gland Cytopathology as nondiagnostic (11.1%), nonneoplastic (44.4%), atypia of uncertain significance (AUS) (22.2%), and salivary gland neoplasm of uncertain malignant potential (SUMP) (22.2%). NSLADs were classified as AUS (40%), SUMP (40%) and Benign Neoplasm (20%)., Conclusion: Although rare, knowing the cytologic features of salivary LAD is important to avoid diagnostic pitfalls. Vacuolated cells can be prominent in both SLAD and NSLAD aspirates. Diagnostic issues arise from insufficient sampling of all tumor components leading to marked variation in diagnostic classification of LAD., (© 2020 Wiley Periodicals LLC.)

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., Conclusion: 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., (© 2020 Wiley Periodicals LLC.)

Objectives: Adenoid cystic carcinoma (ACCA) is an uncommon primary malignancy of salivary glands and rarely nonsalivary tissue. This study aims to evaluate the diagnostic accuracy of ACCA on fine needle aspiration (FNA) material and the associated challenges., Methods: A search on electronic pathology database from 2006 to 2016 at The Johns Hopkins Hospital found 83 cytology specimens diagnosed as ACCA, 49 with histology follow-up., Results: Fifty-two females and 31 males were found ranging from 37 to 95 years old (mean 62.5). The tumor size was 1 to 11.5 cm (mean 3.4). FNAs were performed on 46 salivary glands (54.88%), 12 head and neck masses (14.45%), 9 lymph nodes (10.84%), 9 tracheas/lungs (10.84%), 4 vaginal/perineum/gluteal masses (4.82%), and one for each kidney, liver and abdominal/pelvic mass (1.21%). 83 FNA diagnoses revealed 3 nondiagnostics (3.61%), 20 neoplasms with unspecified features (24.10%), 30 basaloid neoplasms (36.14%), 18 ACCA (21.69%), and 12 other malignancies (14.46%). The accuracy of FNA in diagnosis of ACCA comparing to histologic follow-up in 49 cases was 87.5% sensitivity, 66.67% specificity, with 92.11% positive predictive value and 54.55% negative predictive value. The most common mimicker was pleomorphic adenoma., Conclusion: ACCA can be diagnosed not only in the salivary gland FNAs, but also respiratory tract, intra-abdominal, kidney, and gynecologic regions. FNA is a preferred technique to assess mass lesions. However, a diagnosis of ACCA on FNA material should be rendered with caution since there are benign and malignant neoplasms with overlapping features. Awareness of prior medical history and ancillary studies can improve the diagnosis., (© 2020 Wiley Periodicals LLC.)

Background: Fine needle aspiration cytology is an important diagnostic tool in salivary gland cytopathology. However, cytology of salivary gland neoplasms shows diversity with morphological overlap, heterogeneity and subjective variability, posing diagnostic challenge. Nuclear cytomorphometric image analysis turns the subjective criteria into quantitative parameters, which may aid not only in differentiating between benign and malignant tumours but also can aid in categorising challenging cases with morphological overlap., Methods: A retrospective analysis of Papanicolaou stained fine needle aspirate smears from 50 patients with salivary gland neoplasms, with available follow-up histopathology, was performed. The aspirates were categorised in to three neoplastic categories of Milan system for reporting salivary gland cytology (MSRSGC) that is benign neoplasm, salivary gland neoplasm with uncertain malignant potential, and malignant. The smears were subjected to cytomorphometric image analysis using Image Pro Software (version 10). Each nucleus was analysed for 13 parameters including aspect ratio, intensity, diameter, perimeter, roundness, area, Feret diameter, circularity, radii, Fournier description and chromatin texture characteristics such as margination, heterogeneity and clumpiness. The data obtained was compared through relevant statistical methods., Results: The comparative morphometric data obtained for parameters using ANOVA, for the three categories showed statistically significant P values (<0.001). The post hoc test (Games-Howel) test also showed significant P values (<.001)., Conclusion: Cytomorphometric image analysis is an important tool in diagnosis of salivary gland neoplasms and can improve the diagnostic accuracy for better treatment and improved prognosis. However, more studies with larger sample size may be needed in future for further affirming its role., (© 2020 Wiley Periodicals LLC.)

Background: Polymorphous adenocarcinoma (PAC) is a rare malignant tumor of the minor salivary glands. It has an infiltrative growth, variable architectural patterns, neurotropism and cellular monomorphism. Approximately 75% of the cases show a specific mutation in the protein kinase D1 (PRKD1) gene. Reflecting the rarity of the tumor and intraoral location, the cytologic experience is limited with few reported series. In this study we analyze our cytologic experience to determine if a preoperative diagnosis is possible., Methods: A retrospective study of 11 patients with PAC in which a cytologic study was available. A review of the literature was also performed., Results: Our study shows that PAC has relatively constant cytological features. The analysis of the cytological literature although it shows some heterogeneity, also reveals repetitive cytological findings. Smears are cellular with irregular groups some showing pseudopapillary branching morphology. Monolayered clusters and small acinar structures are also present. Most cases have small metachromatic globules embedded within the groups determining a cylindromatous pattern. Tumoral cells are small and uniform with scarce to moderate cytoplasm. Nuclei are round and oval with occasional grooves and small nucleoli., Conclusion: PAC has characteristic cytological features that together with its location in minor salivary gland must make us consider it preoperatively. It may resemble basal cell adenoma and epithelial-rich pleomorphic adenoma so we should be cautious in the final diagnosis. Whenever possible, the characteristic cytomorphology of PCA should make us evaluate the mutational status of PRKD1 gene since it may permit a more accurate diagnosis., (© 2020 Wiley Periodicals LLC.)

Background: Salivary gland fine needle aspiration (FNA) has a well-established role in the evaluation of salivary gland lesions. The Milan system for reporting salivary gland cytopathology (MSRSGC) was developed in 2018 to accomplish a standardized reporting across institutions. This classification is predominantly based on the use of direct smears. This single center study aims to evaluate and further validate the MSRSGC based on the sole use of cell blocks and carry out a risk assessment based on follow up histopathology., Methods: A total of 359 FNA specimens from 343 patients processed as cell blocks between 2012 and 2018 were retrieved, with histologic follow-up available in 235 cases. The cytological diagnosis were reclassified according to the MSRSGC categories: non-diagnostic, non-neoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SFM), and malignant. The use of ancillary immunohistochemistry or molecular testing was recorded. The risk of malignancy (ROM) was calculated for each diagnostic category., Results: Overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 92.9%, 75.9%, 97.9%, 91.7%, and 95%, respectively. The ROM for the non-diagnostic, non-neoplastic, AUS benign neoplasms, SUMP, SFM and malignant categories were 13.8%, 14.2%, 30%, 6.3%, 20.8%, 60%, and 100%, respectively., Conclusion: This large single center retrospective series further validates the MSRSGC. The proposed diagnostic classification is reproducible with use of cell blocks. Discrepancies in number of cases per category and ROM are based on cross-institution variabilities, pre-FNA diagnostics (imaging) and ancillary tests., (© 2020 Wiley Periodicals LLC.)

Background: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is based on risk stratification. We presented our experience with fine-needle aspiration cytology (FNAC) for the diagnosis of salivary glands lesions by applying the MSRSGC categorization to the cytological diagnoses, and determined risk of malignancy (ROM) for each category., Methods: Fine-needle aspiration cytology of salivary gland lesions performed over a 6-year period was retrieved. FNAC results were retrospectively categorized according to the MSRSGC criteria, and correlated with corresponding histologic follow-up. ROM for each diagnostic category was calculated., Results: A total of 208 FNAC of salivary gland lesions were reviewed and retrospectively categorized as: non-diagnostic (ND) 23 (11%), non-neoplastic (NN) 54 (26%), atypia of undetermined significance (AUS) 10 (4.8%), benign neoplasms (BN) 77 (37%), salivary gland of uncertain malignant potential (SUMP) 13 (6.3%), suspicious for malignancy (SM) 7 (3.4%), and malignant (M) 24 (11.5%). Histopathological follow-up was available for 84 of 208 cases (40.4%). Overall concordance rate between FNAC and histology was 78.8%. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated as 93.3%, 94.6%, 82.4%, and 98.2%, respectively. Diagnostic accuracy to distinguish benign from malignant disease was 94.4%. ROM for each category was ND 0%, NN 0%, AUS 75%, BN 2.2%, SUMP 28.6%, SM 50%, and M 100%., Conclusion: Fine-needle aspiration cytology continues to be an accurate diagnostic tool for most salivary gland neoplasms showing classical morphologic features. However, difficult cases with unusual or overlapping features will occur. In these situations, the use of MSRSGC risk-stratification could be helpful to define appropriate management., (© 2020 Wiley Periodicals LLC.)

Background: The Milan system for Reporting Salivary Gland Cytopathology (MSRSGC) was published in 2018. Since then, many authors have published their institutional experience by retrospectively assigning salivary gland fine-needle aspiration cases to each of the MSRSGC categories and calculated their risk of malignancy (ROM) accordingly., Methods: We reviewed all published articles available online in English that used the MSRSGC since or near its publication. We calculated the risk of neoplasm and ROM for each diagnostic category. In addition, the false-negative and false-positive rates from all studies were examined., Results: Thirty-seven articles were identified in the English literature; 2 were published in 2017, 14 in 2018, 18 in 2019, and 3 in 2020. The total number of cases was 16 394, and 8 468 had surgical follow-up. The mean ROM was 16.9% for category I, 10.5% for category II, 39.3% for category III, 2.9% for category IVa, 39.4% for category IVb, 84.2% for category V, and 97.5% for category VI. The mean false-negative rate for MSRSGC categories II and IVa was 4.5%. Similarly, the mean false-positive rate for MSRSGC categories V and VI was 5.1%., Conclusion: A tiered classification scheme of MSRSGC is helpful in effectively guiding clinical management of patients with salivary gland lesions. The reported mean ROM for each category in most studies is within the recommended range published by the MSRSGC., (© 2020 Wiley Periodicals LLC.)

Background: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was recently proposed. Herein, we retrospectively applied this nomenclature system to salivary gland lesions sampled by ultrasound-guided fine-needle aspiration (FNA)., Methods: All cases of salivary gland FNA with available surgical follow-up, in the period from 2014 to 2017 at our institution were reviewed and reclassified according to one of the six categories of the MSRSGC, blind to the surgical outcome. Overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated, as well as risks of neoplasm (RON) and risk of malignancy (ROM) for each of the proposed categories., Results: There were 104 salivary gland lesions, with a female predominance (57.7%), most cases from the parotid gland (89.4%). Mean age was 53.2 years. Distribution of the specimens according to the Milan System was as follows: 19.2% nondiagnostic (ND), 8.7% non-neoplastic (NN), 9.6% atypia of undetermined significance (AUS), 40.4% benign neoplasm (BN), 14.4% salivary gland neoplasm of uncertain malignant potential (SUMP), 1.9% suspicious for malignancy (SFM), and 5.8% malignant. Sensitivity, specificity, PPV, and NPV using MSRSGC were calculated as 75%, 98.4%, 88.9%, and 95.3%, respectively. RON/ROM for each category were 60%/15% for ND, 44.4%/0% for NN, 90%/40% for AUS, 100%/9.5% for BN, 100%/13.3% for SUMP, 50%/50% for SFM and 100%/100% for malignant., Conclusion: The use of the Milan System proved to be a useful method to predict the risk of neoplasm and malignancy in the sample studied, with high sensitivity and specificity., (© 2020 Wiley Periodicals, Inc.)

Background: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) provides a standardized reporting system for salivary gland fine-needle aspiration (SGFNA). We review the clinical utility of the MSRSGC at a tertiary care cancer center by assessing the rates of malignancy (ROM) among different categories., Methods: A retrospective search was performed to retrieve all SGFNA cases performed at our institution between 1/1/07 and 12/31/18. The initial primary diagnoses were recorded and cases were then assigned to appropriate MSRSGC categories. ROM was then calculated for all categories., Results: A total of 976 cases were identified, and 373 with follow-up. The ROM was 19.7% (192/976) for all-comers and 51.3% (192/374) among cases with follow-up. Using MSRSGC, SGFNA showed a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 65.6%, 87.4%, 100%, and 72.6%, respectively. ROM for MSRSGC categories I, II, III, IVa, IVb, V, and VI were 20.7%, 30.0%, 45.8%, 3.3%, 50.7%, 100%, and 100%, respectively. Utilizing MSRSGC resulted in a nondiagnostic rate of 14.4%. The nondiagnostic rate was lower when the procedure was performed by pathologists vs nonpathologists (12.9% vs 15.8%) but was comparable when rapid on site evaluation (ROSE) was performed (12.9% vs 11.6%)., Conclusion: In our patient population, MSRSGC resulted in a perfect PPV and moderate NPV. Utilizing MSRSGC results in a higher nondiagnostic rate due to the inclusion of cases with benign elements or cyst contents only in this category. Performing ROSE is more important in attaining an adequate sample than the specialty of the person performing SGFNA., (© 2019 Wiley Periodicals, Inc.)

Background: Many prior institutional and multi-institutional studies have applied the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) retrospectively to their specimens to determine the risk of malignancy (ROM) of each category. Most of these studies focused on general assessment of the system and risk classification. However, there seems to be less focus on the category of atypia of undetermined significance (AUS) that could be attributed to the low number of cases that could fit into this category. Herein, we present a bi-institutional experience with this category., Methods: A computerized search of the databases was performed to identify all salivary gland fine-needle aspiration (FNA) in two institutions over a period of 12 years. The final diagnosis of each case was reclassified based on MSRSGC, and histology follow-up was retrieved., Results: Sixty AUS cases (out of 1560 salivary gland FNA) were identified with a rate of 3.8%. Forty cases (66%) had a subsequent tissue material. Correlation with histology revealed that the estimated ROM is 37.5% (15/40) and the overall ROM is 25% (15/60). Fifty percent of the cases had a prominent lymphoid component and most commonly represented lymphomas, reactive lymph node or sialadenitis., Conclusion: The AUS category is a heterogeneous group of lesions with predominant lymphoid-rich entities. Some variability exists between institutions with most having higher ROM than the suggested 20% by the MSRSGC atlas., (© 2019 Wiley Periodicals, Inc.)

Background: Milan System for Reporting Salivary Gland Cytology (MSRSGC) was introduced to standardise the terminology and reporting of salivary gland cytology. The purpose of our study was to compare the conventional system and the proposed Milan System to look for concordance rates in cytohistopathologic correlation and any value addition to the conventional system., Methods: This was a retrospective cross sectional observational study. The fine needle aspiration cytology (FNAC) were reported in the conventional manner and were correlated with the surgical specimen. The cyto-histopathological correlation was studied to look for concordance rates. FNAC were retrospectively reviewed and were categorised according to the Milan system. These reports were correlated with surgical specimen category wise and concordance rates, risk of neoplasm (RON), risk of malignancy (ROM) were calculated., Results: Salivary gland FNAC done during the study period was 323 in number and histopathological correlation was available for 153 cases. The concordance rate of type specific diagnosis was 80.3% as per conventional system. With the application of Milan system, the concordance rates rose to 88.07% with an improvement of 6.67%(excluding non-diagnostic). RON and ROM for non-diagnostic (I)-50%, 50%; non-neoplastic (II)-22%,0%; atypia of unknown significance (III)-66%, 11%; benign neoplasm (IVA)-98%, 3%; salivary gland neoplasm of uncertain malignant potential (IVB)-93%,14%; suspicious for malignancy (V)-100%, 60% and malignant (VI) was 100%, 94%., Conclusion: The broad categorisation provided by the Milan system represents the gross rate of malignancy and helps in deciding the management plan and eventual surgical plan. Thus, it adds value to conventional reporting of salivary gland cytology., (© 2019 Wiley Periodicals, Inc.)

Background: Fine needle aspiration (FNA) cytology has been widely used in the preoperative evaluation of salivary gland lesions. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a tiered risk-stratification scheme designed to standardize reporting and facilitate decision making. We aimed to clarify the validity and diagnostic utility of the MSRSGC-based classification of salivary gland lesions., Methods: A total of 1020 salivary gland FNA specimens were retrieved between 2008 and 2017, with histologic follow-up data available for 349 specimens. Within the present retrospective study, each specimen with follow-up data was reclassified according to the MSRSGC diagnostic categories: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), and malignant. The risk of malignancy (ROM) was calculated based on the histologic follow-up data., Results: The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the MSRSGC-based classification of the malignant potential of salivary gland lesions were 80.1%, 70.4%, 99.2%, 90.5%, and 96.7%, respectively. The ROM calculated for specimens assigned to the nondiagnostic, nonneoplastic, AUS, benign neoplasm, SUMP, SM, and malignant categories were 8.6%, 15.4%, 36.8%, 2.6%, 32.3%, 71.4%, and 100%, respectively., Conclusion: The present results confirm the validity and diagnostic utility of MSRSGC, supporting its use in clinical practice to help devise adequate management strategies for salivary gland lesions., (© 2019 Wiley Periodicals, Inc.)

Introduction: Fine-needle aspiration cytology (FNAC) of salivary glands is a well-established technique that plays a critical role in the preoperative diagnosis of lesions. Despite its clinical utility, it remains one of the most challenging areas in cytopathology. This is because there is no consensus on how to report salivary gland cytopathology, which has resulted in inconsistent terminology and confusion in communication among cytopathologists and clinicians. A risk stratification of FNA diagnostic categories has been recently proposed to be useful in reporting., Materials and Methods: A retrospective study of FNAC of salivary gland lesions reported from 2014 to 2017 was performed. The performance of the cytology reporting system was evaluated with histological diagnosis serving as the gold standard. The aspirates were then categorized according to the Milan system. Furthermore, the risk of malignancy was calculated for all diagnostic categories., Results: A total of 899 salivary gland aspirates were evaluated: 2.2% were nondiagnostic, 55.8% indicated nonneoplastic lesions, and 40.4% indicated neoplastic lesions. Histopathology was available for 172 cases. FNA had a sensitivity of 72.3% and a specificity of 92.6% with an overall diagnostic accuracy of 91.4% for differentiating malignant from benign tumors., Conclusion: A tiered classification scheme as proposed by the Milan system may prove helpful in effectively guiding clinical management of patients with salivary gland lesions. Our experience with this system helps to pave the way for the adoption of the Milan System for Reporting Salivary Gland Cytopathology., (© 2019 Wiley Periodicals, Inc.)

Background: Fine-needle aspiration cytology (FNAC) is a noninvasive, safe, cost-effective, diagnostic procedure for the evaluation of salivary gland lesions and the selection of patients for surgery. The aim of this study was to analyze the risk of malignancy (ROM) according to the Milan reporting system of salivary gland FNA specimens using a liquid-based cytology (LBC) technique., Methods: The cytological diagnosis of 459 cases between 2014 and 2017 was revised according to the Milan reporting system. The FNAC results of 129 cases with a histological diagnosis were compared with respect to the final diagnosis. The ROM for each category calculated., Results: The ROM was high in the indeterminate and malignant categories, while the ROM in the benign neoplasm category was low. Sensitivity and specificity analyzed in two different ways were 95.1% and 88.8%, 81%, and 77.7%, respectively., Conclusions: When salivary gland lesions are evaluated together with clinical and radiological data, the LBC technique can be applied to salivary gland specimens based on the high diagnostic sensitivity and specificity in liquid-based samples reported according to the Milan system., (© 2019 Wiley Periodicals, Inc.)

Background: Fine needle aspiration cytology (FNAC) plays a pivotal role in evaluating salivary gland (SG) tumors. Several studies have shown diagnostic utility of MILAN system for reporting salivary gland cytopathology (MSRSGC) by examining risk of malignancy but only an occasional study has focused on interobserver variability. Hence, the present study was undertaken to assess the agreement among cytopathologists with varying experience in SG cytopathology using MSRSGC and to re-evaluate discordant cytohistological diagnoses for possible causes of misinterpretation., Methods: All SG lesions subjected to FNAC over a period of 3½ years were studied. The cases were critically reviewed by 2 pathologists with variable experience in cytopathology using MSRSGC and concordance level among them was calculated. Cytohistological discordant diagnoses were reclassified and possible causes of misinterpretation during routine reporting were evaluated., Results: Of 150 SG aspirates categorized according to MSRSGC, diagnostic disagreement between 2 pathologists was found in 10. Unweighted Cohen's Kappa score between consultant and resident was 0.812 (high). Among 55 cases with histological correlation, cytohistological discordance was seen in 12. True pitfalls constituted 50% of discordant cases while rest 50% were attributed to practical issues (turnaround time and heavy case load) during routine reporting., Conclusion: MSRSGC can be used with good reproducibility between observers with variable cytopathology experience. Heterogeneous nature of SG neoplasm is a known pitfall in FNA diagnosis of SG neoplasms. During routine reporting turnaround time, heavy case load and reporting by cytopathologists with variable experience add on to challenges faced in reporting cytopathology of SG neoplasm., (© 2019 Wiley Periodicals, Inc.)

Background: In 2018, the Milan System for Reporting Salivary Gland Cytopathology was published defining a diagnostic categorization scheme with known malignancy risks and clinical follow up recommendations. Inter-observer reproducibility of the categories was not defined., Methods: Salivary gland fine-needle aspirations (FNA) were reviewed over a 5 year period and classified by three independent observers. Inter-observer reproducibility was estimated using observed agreement and chance corrected agreement (Cohen's kappa)., Results: Four hundred and eight cases were reviewed with chance corrected agreement of 0.42 for the original Milan System and 0.48 for a modified system using "similar follow up" categories. Categories 4A and 6B showed substantial agreement (kappa =0.71 and 0.72)., Conclusion: The Milan System shows moderate over all agreement between observers. Strongest inter-observer agreement was seen for categories 4A and 6B., (© 2019 Wiley Periodicals, Inc.)

Introduction: Fine needle aspiration (FNA) has been widely utilized in establishing the nature of salivary gland lesions and guiding the clinical management. This study aimed to determine the accuracy of FNA in detecting salivary gland neoplasms and malignancies, employing the "Milan System for Reporting Salivary Gland Cytopathology" (MSRSGC)., Method: A systematic search was conducted. The data on FNA and histologic diagnosis were extracted and categorized based on the MSRSGC and risk of malignancy (ROM) was calculated. The risk of publication bias and level of heterogeneity were evaluated. A mixed-effects model was used to estimate FNA accuracy. Meta-regression was conducted to assess the potential effect of different variables on FNA accuracy., Results: Ninety-two studies with a total of 16 456 FNA with surgical follow-up were included. ROM was estimated as 17%, 8%, 34%, 4%, 42%, 58%, and 91%, in nondiagnostic, nonneoplastic, atypia of undetermined significance, benign neoplasm, salivary gland neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant groups, respectively. High level of heterogeneity was detected (P-value <.001). Including cases with definite FNA diagnosis of neoplasm or malignancy, summary estimates of FNA sensitivity, specificity, diagnostic odds ratio, and positive and negative likelihood ratio in detecting neoplasms and malignancies were 96.9%, 95.3%, 636.8, 20.5, and 0.03, and 80.5%, 97.9%, 189.5, 37.8, and 0.2, respectively. Meta-regression showed several variables significantly impacting FNA accuracy; however, subgroup analysis did not reduce the level of heterogeneity., Conclusion: FNA can be used as a reliable diagnostic tool in the preoperative evaluation and management of salivary glands lesions. Concise of abstract is using Milan system for reporting salivary gland FNA could increase FNA reliability, facilitate communication, and improve patient care., (© 2018 Wiley Periodicals, Inc.)

IgG4-related disease (IgG4-RD) can affect various organs, and the pancreas and salivary gland are representative examples. We report a rare case of IgG4-RD of the paratestis. A 74-year-old man presented with left scrotal swelling. Scrotopuncture drainage and cytology confirmed a clear, yellow retention liquid (130 mL) with many small, similar lymphocytes and a few plasmacytes. Many lymphoid cells were immunopositive for CD3 on a cell block section, indicating that a predominant type of lymphoid cells was T cell. There were also some CD20 immunopositive cells and a few IgG4 immunopositive cells. Two months later the left scrotal swelling had returned, and he underwent radical inguinal orchiectomy. Microscopically, there was considerable lymphoplasmacytic inflammatory infiltration, fibrosis and abundant IgG4 immunopositive cells in the paratesticular region. The histopathologic and immunohistochemistry findings were consistent with IgG4-RD. However, the abundant T cells in the scrotal fluid complicated the cytological diagnosis in our case., (© 2018 Wiley Periodicals, Inc.)

Background: Adenoid cystic carcinoma (ACC) arises at sites where seromucinous or sweat gland epithelium is present and commonly affects the salivary glands. Rarely it can occur at extra-salivary locations., Methods: A retrospective analysis of 19 cases of ACC diagnosed on fine needle aspiration cytology (FNAC) over a period of 15 y (2002-2016) was made., Results: Of 19 total cases, there were 10 salivary and 9 extra-salivary ACCs. Extra-salivary tumours were seen in 2 cases each in trachea, tongue and in one case each in bronchus, lung, subcutaneous tissue, maxillary antrum, and external auditory canal. The age ranged from 14-80 y (mean: 49.5 y), 10 patients were male and 9 were female. The smears were highly cellular in 11 cases, moderately cellular in 5 cases while 3 cases were paucicellular. Multilayered dense clusters, tissue fragments, dispersed cells and cup-shaped fragments were seen. Relatively uniform cells with high nuclear: cytoplasmic ratio, hyperchromatic nuclei, irregular margins, and nuclear moulding were observed. Variable sized hyaline globules, finger-like hyaline material, hyaline cylinders, and hyaline cords were noted. The cytologic diagnosis of ACC was rendered in 13 cases while in 6 cases it was one of the differential diagnosis including monomorphic adenoma, membranous variant of basal cell adenoma, adnexal tumour, polymorphous adenocarcinoma, and pleomorphic adenoma (PA)., Conclusions: Cytologists must be aware of varied locations where ACC can occur. A diagnosis of ACC must not rely exclusively on the occurrence of hyaline globules but necessitates a close scrutiny of cellular and nuclear features to avoid diagnostic pitfalls., (© 2018 Wiley Periodicals, Inc.)

Background: Recently a new system for reporting salivary gland fine-needle aspiration (FNA) cytology was proposed, the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC). Herein, we evaluated diagnostic accuracy of salivary gland FNA, comparing the system previously used in our hospital with the Milan system., Methods: Salivary gland specimens obtained between 2011 and 2017 were reclassified according to MSRSGC. Risk of malignancy for each diagnostic category was determined. Diagnostic yield of both classifications was evaluated., Results: The cases (n = 388) were classified according to the old system: nondiagnostic (n = 28), benign (n = 246), atypical (n = 36), neoplastic (n = 57), suspicious for malignancy (n = 7) and malignant (n = 14). The lesions were distributed according to the MSRSGC: nondiagnostic (n = 28), non-neoplastic (n = 89), atypia of undetermined significance (n = 39), benign neoplasm (n = 156), neoplasm of uncertain malignant potential (n = 55), suspicious for malignancy (n = 7) and malignant (n = 14). When considering only benign and malignant cases, both classifications showed the same sensitivity (62.5%), specificity (100%) and similar accuracy (95.8%). Comparison between the two systems showed no significant difference., Conclusions: Salivary gland FNA has high diagnostic accuracy and assists clinical management independently of the reporting system used, however, in some cases, the use of Milan system could be beneficial, since it allows an enhanced category stratification., (© 2018 Wiley Periodicals, Inc.)

Background: Fine needle aspiration (FNA) is widely used in the diagnosis of salivary gland lesions. Salivary gland FNAs are often difficult to diagnose because of morphologic heterogeneity, a small but significant number of the FNAs yield "atypical" diagnosis. However, systematic evaluation of the risk of malignancy (ROM) of the atypical diagnoses across institutions and the variability of ROM among institutions are still lacking., Methods: Salivary gland FNAs from five tertiary medical centers of United States, Europe and China were reviewed. Cases with "atypical" diagnosis and histological follow-up were included in this study. The diagnostic category of "atypical" was adopted from Milan System for Reporting Salivary Gland Cytopathology (MSRSGC, personal communication)., Results: Among the 12,606 salivary gland FNAs, 504 (4.0%) cases were reported as "atypical", with 154 cases (30.6%) having histological follow-ups. Histological follow-ups revealed 94 malignant tumors (61.0%, 57 lymphomas, 33 carcinomas, 2 sarcomas, 1 metastatic melanoma, 1 metastatic neuroblastoma), 33 benign tumors (21.4%), and 25 benign lesions (16.2%). ROM in the subset of "atypical" cases with histological follow-up from different institutions vary from 73.08% to 0.00%, the Pearson chi 2  = 24.38 and P < .001., Conclusions: More than half of the subset of "atypical" salivary gland FNAs with histological resection turned out to be malignant tumors; another one-fourth were benign neoplasms. Further, the highly variable ROMs of the "atypical" category amongst different institutions likely reflect the variable practices at each individual institution., (© 2017 Wiley Periodicals, Inc.)

Background: Lymphoid enhancer binding factor 1 (LEF-1) has recently been reported as a potential immunohistochemical (IHC) marker for basal cell adenoma (BCA) and other salivary gland tumors, which may contribute to an increased accuracy in differentiating basaloid salivary gland neoplasms. We evaluated the utility of LEF-1 in fine needle aspiration (FNA) and resection specimens to distinguish pleomorphic adenoma (PA), BCA, basal cell adenocarcinoma (BCAC), and adenoid cystic carcinoma (ACC) as well as in non-neoplastic salivary gland (NNSG)., Methods: Cases including 66 PA (35 FNA, 31 resections), 12 BCA (5 FNA, 7 resections), 42 ACC (11 FNA, 31 resections), 1 BCAC FNA, and 10 NNSG (5 FNA, 5 resections) were obtained and stained for LEF-1., Results: On cell block (CB), 51% of PA and 60% of BCA were LEF-1 positive while 91% of ACC were LEF-1 negative. Among resections, there was a higher percentage of LEF-1 positive PA (84%) and BCA (86%), and a higher percentage of LEF-1 negative ACC (97%). LEF-1 staining had a low to moderate sensitivity for detecting benign basaloid neoplasms on FNA CB and resection specimens (52.5% and 84%, respectively), but a higher specificity (92% and 97% respectively), and positive predictive value (95% and 97% respectively)., Conclusion: When comparing benign (PA and BCA) and the most common malignant basaloid salivary gland tumor (ACC), positive LEF-1 favors a benign neoplasm. Additional studies with LEF-1, specifically including other rare basaloid salivary gland neoplasms are needed to further clarify the role of LEF-1 in diagnosing these lesions on FNA., (© 2017 Wiley Periodicals, Inc.)

We report one case of metastatic synovial sarcoma (SS) to the parotid gland in a 93-year-old male. The patient had undergone upper left pulmonary lobectomy with mediastinal lymphadenectomy for SS of the lung 5 years before. The cytopathologic presentation and the immunocytochemical findings on the FNA sample were suggestive of a spindle cell myoepithelioma, while a SYT rearrangement was identified by a FISH performed on a cytological smear of the lesion. The diagnosis was further confirmed also by positive immunocytochemical expression of TLE1 on a section from the obtained cell block. The cytologic and immunophenotypic findings are shortly discussed in view of the reported immunophenotypic inconsistency of SS and of its differential diagnosis with spindle cell myoepithelioma of the salivary glands.The importance of the recently described TLE1 staining and its close correlation to SYT rearrangement is briefly discussed., (© 2017 Wiley Periodicals, Inc.)