[Salivary gland tumors: 2022 WHO blue book and beyond]. / Tumeurs des glandes salivaires : OMS 2022 et au-delà.

In 2022, the 5th edition of the WHO classification of Head and Neck tumors was published online. In the salivary gland chapter, a new benign entity, the keratocystoma, was introduced. The sclerosing polycystic adenosis has been recognized as tumoral and is now termed sclerosing polycystic adenoma. The striated duct adenoma now has its own dedicated chapter. Additionally, a new variant of pleomorphic adenoma, termed "canalicular adenoma-like," has been incorporated. Regarding malignant tumors of the salivary glands, significant doubts now exist regarding the actual existence of oncocytic carcinoma, which has been reclassified among emerging entities. Two new malignant entities have also emerged: microsecretory adenocarcinoma and microcystic sclerosing adenocarcinoma. Finally, primary mucinous adenocarcinoma of the salivary glands has been acknowledged as a distinct entity.

A novel clinically-oriented classification of fine-needle aspiration cytology for salivary gland tumors: a 20-year retrospective analysis of 1175 patients.

BACKGROUND: When determining treatment strategy for a salivary gland tumor, assessing histology and malignancy grade before surgery is essential. Several new diagnostic classification systems for salivary gland cytology have recently been proposed. However, none incorporate histology and grade of malignancy. METHODS: We developed a new cytology classification system that incorporates histology and grade of malignancy of salivary gland tumors (OMC classification), consisting of 11 categories. Our OMC classification was applied to 1175 patients who had preoperative cytology and confirmed final pathological diagnosis available from the past 20 years at our hospital (benign tumor: 981 patients, malignant tumor: 194 patients). RESULTS: Based on the cytology, 729 patients (62.0%) had benign histology (Category 4-1), and 87 patients (7.4%) were diagnosed with grade of malignancy (Category 6-3 + 6-4). Based on the final pathological diagnosis, the accuracy rate of Category 4-1 and Category 6-3 + 6-4 of our classification system was 93.4% and 88.5%, respectively. CONCLUSION: Based on the correct diagnosis rate, the inclusion of histology and grade of malignancy in the salivary gland cytology classification was considered feasible. Thus, the OMC classification system is considered a useful tool when determining the treatment strategy for a salivary gland tumor.

Utility of the Milan system for reporting salivary gland cytopathology during rapid on-site evaluation (ROSE) of salivary gland aspirates.

OBJECTIVE: Rapid on-site evaluation (ROSE) is a fine needle aspiration (FNA) technique for ensuring sampling adequacy and triaging samples. The Milan system for reporting salivary gland cytopathology (MSRSGC) is a standardised reporting system which aims to improve risk stratification. There is scant literature on the diagnostic value and agreement of MSRSGC on ROSE with final cytological diagnosis in salivary gland FNAs. We aimed to assess the concordance of MSRSCG categorisation and diagnosis on ROSE with final cytological and histological diagnosis. METHODS: This prospective study included consecutive salivary gland FNAs for which ROSE was performed over a six-month period. MSRSGC category and diagnosis on ROSE were compared with the final cytological diagnosis and MSRSGC category, and histopathological diagnosis, where available. RESULTS: Sixty salivary gland aspirates were included. The adequacy rate with ROSE was 100%. Using the MSRSGC classification during ROSE, 26 (43.2%) samples were categorised as benign neoplasm, 21 (35%) as malignant neoplasm, 9 (15%) as non-neoplastic, and one each (1.7%) belonged to the remaining four categories. MSRSGC categorisation on ROSE concurred with final the cytological diagnosis in 58/60 cases (96.7%). Discrepancies in MSRSGC categories on ROSE included one atypia of undetermined significance with final report as non-neoplastic, and one non-diagnostic as suspicious for malignancy. Good correlation of MSRSGC categories on ROSE with final histopathological diagnosis (88.9% concordance) was also noted. CONCLUSIONS: MSRSGC on ROSE shows good concordance with final cytology and histopathology diagnosis, indicating that categorisation according to MSRSGC has utility in ensuring that adequate material is obtained and triaged appropriately for the diagnosis of salivary gland aspirates.

Histopathological evaluation of minor salivary gland papillary-cystic tumours: focus on genetic alterations in sialadenoma papilliferum and intraductal papillary mucinous neoplasm.

AIMS: Minor salivary gland tumours showing a predominant papillary-cystic structure are rare, and constitute a mixture of various types of neoplasm; thus, the histopathological assessment of these tumours poses a significant diagnostic challenge. We aimed to delineate the histological characteristics of these tumours and further mutational aspects with a particular focus on sialadenoma papilliferum (SP) and intraductal papillary mucinous neoplasm (IPMN). METHODS AND RESULTS: We retrieved 28 papillary-cystic tumours of the minor salivary glands, and performed histological re-evaluation and mutation analyses of several key oncogenes. The histological classifications were as follows: SP (n = 10), SP-like intraductal papillary tumour (SP-IPT) (n = 2), IPMN (n = 9), intraductal papilloma, cystadenoma, and cystadenocarcinoma (two, three and two respectively). Whereas SP typically consisted of a combination of exophytic squamous epithelium and endophytic intraductal papillary infoldings, SP-IPT lacked the exophytic component. SP and SP-IPT frequently harboured BRAF V600E mutations (75.0%), which were identified in both squamous and ductal components. IPMN was characterised by a well-demarcated cystic lesion filled exclusively with a papillary proliferation of mucinous cells and a high rate of AKT1 E17K mutations (88.9%). Intraductal papillomas were unilocular cystic lesions with intraluminal papillary growth of bland columnar cells. In contrast, both cystadenomas and cystadenocarcinomas showed a multicystic appearance with a papillary configuration. Cystadenocarcinomas invaded the surrounding tissue and were composed of markedly atypical tumour cells. CONCLUSION: The appropriate interpretation of histological findings and specific genetic alterations (e.g. BRAF V600E and AKT1 E17K in SP and IPMN) would be useful for the correct diagnosis of minor salivary gland papillary-cystic tumours.

[Salivary gland cytopathology: Milan system 2018]. / Cytopathologie des glandes salivaires : le système de Milan 2018.

The salivary glands cytology is one of the most challenging area in cytopathology because of the wide diversity of benign and malignant tumors also because of their heterogeneity. However, fine needle aspiration cytology, with magnetic resonance imaging, represents a first-line examination to guide a possible surgical procedure and its extent. An accurate diagnosis of a specific tumor is sometimes difficult to assess in cytology. Also, as for gynecological, thyroid or urinary cytologies, a panel of experts met to develop a cytological classification of salivary gland lesions associated with a risk of malignancy and management proposals. The Milan System for Reporting Salivary Gland Cytopathology was published in 2018. The French Society of Clinical Cytology (SFCC) offers here an official summarized French version oh this terminology and recommends its use.

Salivary Gland Fine Needle Aspiration and Introduction of the Milan Reporting System.

Fine needle aspiration (FNA) is a well-established procedure for the diagnosis and management of salivary gland lesions despite challenges imposed by their diversity, complexity, and cytomorphologic overlap. Until recently, the reporting of salivary gland FNA specimens was inconsistent among different institutions throughout the world, leading to diagnostic confusion among pathologists and clinicians. In 2015, an international group of pathologists initiated the development of an evidence-based tiered classification system for reporting salivary gland FNA specimens designated the "Milan System for Reporting Salivary Gland Cytopathology" (MSRSGC) that culminated with the publication of the MSRSGC Atlas in February 2018. The MSRSGC consists of 6 diagnostic categories, which incorporate the morphologic heterogeneity and overlap among various non-neoplastic, benign, and malignant lesions of the salivary glands. In addition, each diagnostic category is associated with a risk of malignancy and management recommendations. The main goal of the MSRSGC is to improve communication between cytopathologists and treating clinicians, while also facilitating cytologic-histologic correlation, sharing of data from different laboratories for quality control, and research. Herein, we review the current status of salivary gland cytology and the role of MSRSGC in providing a framework for reporting salivary gland lesions.

Salivary Gland Neoplasms: Does Morphological Diversity Reflect Tumor Heterogeneity.

Salivary gland tumor classification encompasses a vast list of benign and malignant neoplasms. Their morphological diversity is recognized not only between different entities but also within individual tumors. Tumor categories as described by the World Health Organization reflect, in part, a true genetic heterogeneity (e.g., translocations involving CRTC1 and CRTC3-MAML2 genes in mucoepidermoid carcinoma and MYB-NFIB fusion in adenoid cystic carcinoma). Carcinoma ex pleomorphic adenoma shows diversity in its histological appearance, but recurrent rearrangements on PLAG1 and HMGA2 are common to its benign precursor. More recently, new categories have been defined, like secretory carcinoma with the t(12;15) (p13;q25) ETV6-NTRK3 translocation and clear-cell carcinoma with EWSR1-ATF1 fusion. Recent studies on cribriform adenocarcinoma of minor salivary gland origin and epithelial-myoepithelial carcinoma point to a correlation with their morphological features. All of these advances show that the search of a histogenetic and genetic basis for salivary gland tumors is helping to clarify morphological categories and unraveling new ones. Nevertheless, currently morphology is still the hallmark of tumor classification and the gold standard. The therapeutic options for advanced tumors remain very limited but the discovery of translocation-generated gene fusions and increased knowledge of the genomic information of salivary gland tumors is creating opportunities for the development of specific targeted therapies.

Assessment of salivary gland tumors using MRI and CT: impact of experience on diagnostic accuracy.

RATIONALE AND OBJECTIVES: To analyze the accuracy of radiological diagnosis in MRI and CT studies of salivary gland tumors depending on the radiologist's experience. MATERIALS AND METHODS: Three radiologists with differing experience (R1 > 20, R2 > 11, and R3 > 7 years, respectively) retrospectively reviewed 128 cases (116 MRI, 12 CT studies) with suspected salivary gland tumors regarding dignity and classification using histopathology as a reference standard. Sensitivity, specificity, positive/negative predictive value and inter-observer agreement (using Cohen's κ) were calculated to compare diagnostic performance. RESULTS: Lesions were benign in 87 and in 23 cases malignant. Neoplasia was absent in 18 cases (15 cases without neoplasia and 3 cases without disease). The highest inter-observer agreement for determining dignity using CT was found between R1 and R2 (κ = 0.74, p < 0.001), and the lowest between R2 and R3 (κ = 0.28, p < 0.001). MRI sensitivity/specificity for classifying pleomorphic adenomas was as follows: R1 (100%/100%), R2 (76.92%/87.01%), R3 (43.53%/67.53%), and for CT: R1 (100%/100%), R2 (100%/88.89%), R3 (66.67%/88.89%; for Warthin's tumor using MRI: R1 (100%/97.44%), R2 (68.42%/83.33%), R3 (50.00%/67.95%), and using CT: R1 (100%/100%), R2 (50.00%/100%), R3 (100%/100%; for squamous cell carcinomas using MRI: R1 (100%/100%), R2 (75.00%/97.12%), R3 (75.00%/99.04%), and using CT: R1 (100%/100%), R2 (66.67%/88.89%), R3 (66.67%/66.67%). The highest agreement was found between R1 and R2 for MRI (κ = 0.62, p < 0.001), and the lowest between R1 and R3 at MRI (κ = 0.28, p < 0.001). CONCLUSION: Diagnostic accuracy in the assessment of salivary gland tumors strongly depends on the observer's expertise and increases with higher experience.

Subsets of salivary duct carcinoma defined by morphologic evidence of pleomorphic adenoma, PLAG1 or HMGA2 rearrangements, and common genetic alterations.

BACKGROUND: The authors hypothesized that histogenetic classification of salivary duct carcinoma (SDC) could account for de novo tumors and those with morphologic or molecular evidence (pleomorphic adenoma gene 1 [PLAG1], high-mobility group AT hook 2 [HMGA2] rearrangement, amplification) of pleomorphic adenoma (PA). METHODS: SDCs (n = 66) were reviewed for morphologic evidence of PA. PLAG1 and HMGA2 alterations were detected by fluorescence in situ hybridization (FISH). PLAG1-positive tumors were tested by FISH for fibroblast growth factor receptor 1 (FGFR1) rearrangement. Thirty-nine tumors were analyzed using a commercial panel for mutations and copy number variations in 50 cancer-related genes. RESULTS: On the basis of combined morphologic and molecular evidence of PA, 4 subsets of SDC emerged: 1) carcinomas with morphologic evidence of PA but intact PLAG1 and HMGA2 (n = 22); 2) carcinomas with PLAG1 alteration (n = 18) or 3) HMGA2 alteration (n = 12); and 4) de novo carcinomas, without morphologic or molecular evidence of PA (n = 14). The median disease-free survival was 37 months (95% confidence interval, 28.4-45.6 months). Disease-free survival and other clinicopathologic parameters did not differ for the subsets defined above. Combined Harvey rat sarcoma viral oncogene homolog/phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit α (HRAS/PIK3CA) mutations were observed predominantly in de novo carcinomas (5 of 8 vs 2 of 31 tumors; P = .035). Erb-B2 receptor tyrosine kinase 2 (ERBB2) copy number gain was not observed in de novo carcinomas (0 of 8 vs 12 of 31 tumors; P = .08). Tumor protein 53 (TP53) mutations were more common in SDC ex pleomorphic adenomas than in de novo carcinomas (17 of 31 vs 1 of 8 tumors; P = .033). CONCLUSIONS: The genetic profile of SDC varies with the absence or presence of pre-existing PA and its cytogenetic signature. Most de novo SDCs harbor combined HRAS/PIK3CA mutations and no ERBB2 amplification. Cancer 2016;122:3136-44. © 2016 American Cancer Society.

[Grading of head and neck neoplasms]. / Grading von Tumoren der Kopf­Hals­Region.

Tumors of the head and neck form a heterogeneous group of benign and malignant neoplasms with significant differences in biological behavior and therapeutic strategies. Squamous cell carcinomas (SCC) of the larynx, pharynx and oral cavity represent the most frequent and, thus, clinically most important malignant neoplasms in this anatomical region. Similar to other neoplasms, grading of head and neck malignancies is based on evaluation of the tumor histology usually including both architectural and cytological features; however, the current consensus grading for head and neck SCC is of limited prognostic and therapeutic value and the reproducibility is low. Therefore, novel grading criteria have been proposed that are based on additional parameters, such as the type of tumor growth pattern at the invasive front (so-called tumor budding). These novel algorithms, however, have not yet been officially endorsed into guidelines. Salivary gland (SG) neoplasms, although less frequent, constitute a second important pathologically and clinically complex group of tumors at this location. In contrast to SCC, grading of these tumors is of high clinical importance. Based on the large variety of carcinoma entities of the SG, both entity-specific (e. g. mucoepidermoid carcinoma) algorithms but also algorithms, which are solely based on the recognition of a specific carcinoma variant with subsequent automatic assignment of the tumor grade (e. g. acinic cell carcinoma and salivary duct carcinoma) are in use. In the sinonasal tract, grading is important for non-intestinal type adenocarcinoma and esthesioneuroblastoma. In this article the most important grading schemes and criteria for head and neck malignancies are presented and their prognostic and therapeutic implications are discussed.

Salivary Gland Cancers: Biology and Systemic Therapy.

Salivary gland tumors are a relatively rare and heterogeneous group of tumors with variable pathologic and phenotypic characteristics. The lack of clinical outcomes data and randomized controlled trials pertaining to them makes it difficult to formulate definitive treatment protocols that could help with making decisions regarding choice of therapy. Most studies involving systemic chemotherapy have not shown promising patient outcome results. With recent advances in molecular technology, however, it is now possible to identify specific genetic alterations and biomarkers as possible targets for therapeutic purposes. For example, in mucoepidermoid carcinomas, one of the most common types of malignant salivary gland tumors, a commonly seen genetic translocation [t(11;19)(q21;p13), which involves the CRTC1 and MAML2 genes] has been found to be associated with improved survival, making it a possible prognostic marker. Also, this translocation gives rise to a fusion protein that appears to render tumors highly sensitive to epidermal growth factor receptor (EGFR) inhibition. However, the results of phase II trials of EGFR inhibitors-as well as other targeted agents--in salivary gland tumors have been disappointing: there has been some disease stabilization but no objective responses. There remains a need for well-designed prospective clinical studies to improve management of these tumors.

Update in salivary gland cytopathology: Recent molecular advances and diagnostic applications.

Salivary gland tumors (SGT) are notorious for their extraordinary diversity and for the morphological overlap that exists between many of these entities. Fine-needle aspiration biopsy (FNAB) has a well-established role in the evaluation of patients with a salivary gland lesion, helping to guide clinical management. However, salivary gland FNAB has several limitations and does not allow for a specific diagnosis in some cases. For these reasons, salivary gland FNAB is considered one of the most challenging areas in cytopathology. Over the last decade, new salivary gland entities have been recognized, enlarging SGT diversity and complexity even more. In addition, a subset of SGT, including common entities such as pleomorphic adenoma and uncommon new entities such as mammary analog secretory carcinoma, have been characterized cytogenetically by the presence of specific translocations. The molecular consequences of these translocations and their potential prognostic and therapeutic values are not yet well characterized. However, these translocations and their resulting fusion oncogenes and oncoproteins can be used as diagnostic clues in salivary gland FNAB material in order to overcome the limitations of cytomorphological evaluation alone. In this review, we focus on SGTs currently known to harbor translocations and fusion genes, including uncommon and recently recognized entities, and discuss their potential application to salivary gland FNAB.

Searching for mammary analogue [corrected] secretory carcinoma of salivary gland among its mimics.

Mammary analog secretory carcinoma of salivary gland is a recently described entity with unique morphologic, clinical, and genetic characteristics, including the characteristic t(12;15)(p13;q25) with ETV6-NTRK3 translocation found in secretory carcinomas of the breast. Before their initial description, these salivary gland tumors were generally diagnosed as acinic cell carcinoma or adenocarcinoma. For the purpose of this study, all cases of salivary gland acinic cell carcinoma, cribriform cystadenocarcinoma, and adenocarcinoma, not otherwise specified (NOS), diagnosed over a 10-year period were retrieved from our surgical pathology files. There were a total of 11 cases diagnosed as acinic cell carcinoma, 10 cases of adenocarcinoma, NOS, and 6 cases of cribriform cystadenocarcinoma. All slides were reviewed by two pathologists (AP, CGF) and tumors that show morphologic features of mammary analog secretory carcinoma according to the recent literature were selected. This process narrowed down the initial number to six cases originally diagnosed as acinic cell carcinoma, three cases originally diagnosed as adenocarcinoma, NOS, and one case originally diagnosed as cribriform cystadenocarcinoma. The 10 cases were subjected to immunohistochemistry for S-100, mammaglobin, and ANO1, as well as fluorescence in situ hybridization analysis for t(12;15)(p13;q25) with ETV6-NTRK3 fusion rearrangement. The ETV6-NTRK3 gene rearrangement was detected in three tumors. These three tumors, initially diagnosed as acinic cell carcinomas, stained positive for S-100 and mammaglobin, and negative for ANO1 by immunohistochemistry. Two of the three patients were male (2/3). In summary, mammary analog secretory carcinoma is a newly described diagnostic entity that should be in the differential diagnosis of salivary gland tumors that morphologically mimic other neoplasms, mainly acinic cell carcinomas. They differ from conventional acinic cell tumors immunohistochemically and molecularly. Positivity for mammaglobin and S-100, and negativity for ANO1 are useful screening tools before confirmatory molecular studies.

[Cutaneous adnexal and salivary gland tumours. Similarities and differences]. / Hautadnex- vs. Speicheldrüsentumoren. Analoges und Divergentes.

Despite major discrepancies in basic microscopic anatomy, remarkable similarities are manifest within the wide spectrum of cutaneous adnexal and salivary gland tumors. In this study salivary gland and adnexal tumors were identified and investigated with respect to similarities in histology, terminology and pathogenesis. Histological similarities of certain types of salivary gland tumors relate to eccrine, apocrine and rarely sebaceous (but not trichofollicular) types of adnexal tumors. The most striking similarity was found with salivary gland pleomorphic adenoma and cutaneous mixed tumor. Multistep carcinogenesis starting with intraductal carcinoma, identified in carcinoma ex pleomorphic adenoma is identical to that found in cutaneous carcinoma ex spiradenoma. Further histological and terminological similarities are shown for mucinous and mucoepidermoid carcinoma, for lymphadenoma and lymphoepithelial carcinoma, for sebaceous adenoma and carcinoma, for adenoid-cystic carcinoma, as well as for salivary gland basal cell adenoma versus cutaneous spiradenoma. Manifest diagnostic problems related to histologically similar salivary gland and adnexal tumors are rare and are topographically limited to the parotid and oral areas.

Analysis of Elastic Tissue in Histological Variants of Pleomorphic Salivary Adenoma seen at the Lagos University Teaching Hospital over a period of 35 Years.

BACKGROUND: Pleomorphic salivary adenoma (PSA), is known for its morphologic diversity. While reports of elastic tissue in PSA have been documented, the distribution of this tissue in histological variants of the tumour has not been documented. Perhaps such features may influence biological behaviour of these variants. OBJECTIVE: To classify PSA in our series into histological variants, and determine possible variation in elastic tissue distribution in them. METHODS: Eighty eight histologically diagnosed cases of PSA in the oral biopsy archives of the department of Oral Biology and Pathology, Lagos University Teaching Hospital, were retrieved. New H&E sections were cut to reconfirm diagnosis and Verhoeff-Van Gieson's stained sections were cut for demonstration of elastic tissue. Seifert et al.'s (1976) histological classification was applied and elastic tissue presence was determined and quantified for each case. Parameters studied included; sex, age, site, histological subtypes and presence of elastic tissue. Statistical analysis was undertaken using the EPI-INFO version 3.4. RESULTS: Male:female ratio was 1:1.3. Most cases (63.6%) occurred in the age group of 21-40 years. Generally, palate (42.0%) was the most commonly affected site, while 53.4% of cases were in the minor salivary glands. Seifert et al. classified subtype II lesions were the most frequently observed (39.7%) and elastic tissue was confirmed in 91.0% of cases. No association was noted between proportion of elastic tissue and histological variants. CONCLUSION: Seifert et al subtype II was the most frequently observed and no association was observed between proportion of elastic tissue and the histological variant of PSA.

Salivary duct carcinomas can be classified into luminal androgen receptor-positive, HER2 and basal-like phenotypes.

AIMS: The aim of this study was to devise a molecular classification for salivary duct carcinomas (SDCs) based on the similarities between SDCs and breast carcinomas and on characteristics of the microarray-based gene expression profiling-defined molecular subtypes of breast cancer. METHODS AND RESULTS: Forty-two pure salivary duct carcinomas, 35 of which contained an in-situ component as defined by histological review and/or immunohistochemical analysis, were stained with antibodies for oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and cytokeratin (CK) 5/6. Based on these markers, tumours were classified into HER2, luminal androgen receptor-positive, basal-like, luminal and indeterminate phenotype. Analysis revealed that 16.7%, 69%, 4.8%, 9.5% and 0% were of HER2, luminal androgen receptor-positive, basal-like, indeterminate and luminal phenotype, respectively. The in-situ and invasive components displayed the same molecular subtype in all but one case. CONCLUSION: Salivary duct carcinomas can be classified into molecular subgroups approximately equivalent to those in the breast. We also report on the existence of a subgroup of bona fide pure salivary duct carcinomas that have a 'basal-like' phenotype. Understanding the phenotypic complexity of SDCs may help to expedite the identification of novel therapeutic targets for these aggressive tumours.

[Changes of the World Health Organization 2022 classification (5th edition) of salivary glands tumors].

Pathological diagnosis of salivary gland tumors is one of the most challenging areas in all head and neck surgical pathology. The classification of salivary gland tumors was updated in the 5th edition of the World Health Organization Classification of Head and Neck Tumours, most of which were based on their molecular pathological characteristerics. This new classification features a description of several new entitiesamong benign and malignant neoplasms, salivary gland tumors with updated naming or diagnostic criteria, and lesions deleted from this section, etc.This present review focuses on the updates and changes in the new classification of salivary gland tumors, and provides some reference for head and neck surgeons and pathologists.

Genomic Analysis of Salivary Gland Cancer and Treatment of Salivary Gland Cancers.

Salivary gland cancer is a heterogenous group of tumors that presents challenges with both diagnosis and therapy. Recent advances in the classification of salivary gland cancers have led to distinct histologic and genomic criteria that successfully differentiate between cancers with similar clinical behavior and appearance. Genomic abnormalities have led to the emergence of targeted therapies being used in their therapy with drastic improvements in outcomes as well as reductions in treatment-related toxicity. Dramatic results seen with molecular targets, such as HER2, TRK, and others, indicate that this approach has the potential to yield even better treatments for the future.

Putting morphology to the test: An established classification scheme reliably stratifies salivary gland cytology by risk of malignancy with substantial interobserver agreement.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology describes several salivary gland fine-needle aspiration cytology (SGFNAC) morphologies developed by Griffith et al. Basaloid neoplasms are pleomorphic (PB) or monomorphic with fibrillary (MBFib), hyaline (MBHy), or other (MBOther) matrix. Oncocytoid neoplasms can be pleomorphic (PO), demonstrate granular and/or vacuolated cytoplasm (OGV), or be monomorphic with mucinous (MOMuc), cystic (MOCyst), or other (MOOther) background. In the current study, the authors explore interobserver agreement (IOA) and risk of malignancy (ROM) for these subcategories. METHODS: The study included 169 SGFNAC cases with surgical follow-up. Four reviewers categorized these cases using the criteria of Griffith et al. with consensus determined by majority. For all morphologic categories, IOA (using the Fleiss kappa) and ROM were calculated. RESULTS: ROMs for basaloid categories were: PB: 100% (1 of 1 case); MBHy: 71.4% (5 of 7 cases); MBFib: 50.0% (3 of 6 cases); and MBOther: 47.4% (9 of 19 cases). ROMs for oncocytoid neoplasms were: OGV: 100% (10 of 10 cases); MOMuc: 92.3% (12 of 13 cases); PO: 88.9% (8 of 9 cases); MOOther: 33.3% (5 of 15 cases); and MOCyst: 0 (0 of 1 case). The system demonstrated substantial agreement overall (κ = 0.69). For basaloid neoplasms, the IOA results were: MBHy: κ = 0.59; MBFib: κ = 0.41; MBOther: κ = 0.41; and PB: κ = 0.11. For oncocytoid neoplasms, the IOA results were: MOMuc: κ = 0.88; OGV: κ = 0.67; PO: κ = 0.63; MOOther: κ = 0.57; and MOCyst: κ = 0.18. CONCLUSIONS: The SGFNAC scheme proposed by Griffith et al. and incorporated into the Milan System for Reporting Salivary Gland Cytopathology demonstrated substantial agreement overall, with particularly high agreement for the MOMuc, OGV, PO, and MBHy categories. The PB and MOCyst categories demonstrated slight agreement and may be improved by revised criteria. The PB, PO, MOMuc, and OGV categories demonstrated high ROM, and the latter 2 categories might best be classified as suspicious for malignancy.

Utility of the Milan system for reporting salivary gland cytopathology: A retrospective 5 years study.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is an established technique for preoperative diagnosis of salivary gland lesions; however, lack of a uniform reporting system has been a handicap. The main aims of this study were to evaluate the utility of the - "The Milan System for Reporting Salivary Gland Cytopathology" (MSRSGC) and ascertain the risk of malignancy (ROM) for each category. METHODS: All salivary gland FNACs over 5 years (January 2014-December 2018) were reviewed and assigned a diagnostic category from the MSRSGC. Clinical data were taken from Cytology records. Cytodiagnosis was correlated with histopathology wherever available and ROM was calculated. RESULTS: A total of 120 salivary gland FNACs were studied. Age ranged between 5 and 85 years, male:female ratio was 2:1 and parotid was the commonest gland aspirated. Cases were reclassified as I non-diagnostic (2.5%), II non-neoplastic (15%), III atypia of uncertain significance-AUS (1.7%), IV A neoplasm benign (50%), IV B neoplasm of uncertain malignant potential (12.5%), V suspicious for malignancy (5%), and VI malignant (13.3%). Follow-up was available in 70 (58.3%) cases. The sensitivity, specificity, negative predictive value, and positive predictive value were 92.3%, 100%, 100%, and 98.27% respectively. ROM was non-neoplastic (0%), AUS (50%), neoplasm benign (0%), neoplasm of uncertain malignant potential (28.6%), suspicious for malignancy (100%), and malignant (100%). CONCLUSION: Salivary gland FNAC is a reliable diagnostic tool and the "Milan system" will further increase FNA reliability, help risk stratification, and improve patient care.