Lymph node metastasis is an adverse pathologic feature that often necessitates post-operative adjuvant radiation therapy or concurrent chemoradiation for salivary gland carcinoma (SGC). While regional metastasis is more common in high grade SGCs, it is rare in low grade (LG) SGCs.

In this retrospective study, we conducted a detailed review of a retrospective cohort of 543 LG-SGCs. Nodal metastasis at presentation and regional recurrence were identified in 7% (n = 38) and 3% (n = 14) of LG-SGCs respectively. The incidence of nodal metastasis varied by tumor histologic subtype, ranging from 0% for epithelial-myoepithelial carcinoma to 10% for polymorphous adenocarcinoma. Compared with LG-SGCs without nodal metastasis, those with regional metastasis were associated with a significantly higher frequency of pT4 disease, larger tumor size, lymphovascular invasion, and perineural invasion. However, clinical outcomes did not differ significantly between the two groups. The 5-year disease-specific survival was 100% and 99% respectively for pN + and pNx/pN0 groups, while the 5-year disease-free survival was 82% and 93% respectively. Among the LG-SGCs that developed regional recurrence to neck lymph nodes, the time between primary resection and recurrent disease ranged from 6 to 233 months (median = 64 months).

Nodal metastasis, though rare, occurs in 7% of patients with LG-SGCs at the time of diagnosis and in 3% as a recurrent disease. It is associated with pT4 disease, larger tumor size, perineural and lymphovascular invasion but does not appear to significantly impact clinical outcomes.

This systematic review aimed to assess the impact of different clinicopathological parameters on the prognosis and survival of mucoepidermoid carcinoma of salivary glands in the pediatric population. It was conducted according to the recommendations of PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis statement). All case reports, case series and observational studies were searched from the following databases: Medline (By PubMed), Web of Science, Scopus and Embase. Cases other than salivary gland mucoepidermoid carcinoma, cases with less than one-year follow-up and articles without any information on recurrence or survival were excluded. Checklist for Analytical Cross-Sectional Studies by The Joanna Briggs Institute was used for risk of bias assessment. Data was extracted and recorded using Excel spreadsheets. Chi-Square test and Kaplan Meier analysis were used. A total of 697 articles were screened, 42 were retrieved for full text screening and 30 articles were selected. Studies with similar methodologies and outcomes were categorized together. The average risk of bias was low. Data was extracted for 143 cases. Prognostic factors that were associated with poor survival outcomes were male gender, TNM staging, tumor grade, margins, lymphovascular and perineural invasion and choice of treatment. Multivariate analysis from all studies were assimilated to calculate an overall predictive strength of each parameter for prognosis and survival. This review concludes that such clinicopathological parameters are valuable prognostic predictors of mucoepidermoid carcinoma of salivary glands in pediatric population and are essential for proper treatment planning and post-treatment quality of life.

Mucoepidermoid carcinoma is a prevalent form of salivary gland cancer that affects the head and neck. The condition presents with various symptoms. Histologically, it is classified into grades based on the types of cells and their level of invasion. Surgical intervention is the primary treatment approach with an excellent prognosis.

This study is a descriptive retrospective cohort hospital-based investigation that aims to examine clinicopathological characteristics and treatment outcomes, including a 5-year survival rate. It utilizes patient records from 2010 to 2021 obtained from the Khartoum Teaching Dental Hospital and the Oral Pathology Lab of the University of Khartoum.

In this study, a total of 48 patients were included. The primary symptom reported by the patients was swelling in 20 (41%) individuals. The most common histological classification was low-grade mucoepidermoid carcinoma in 41 (85.4%) patients. Mucoepidermoid carcinoma predominantly affected minor salivary glands, with the buccal mucosa being the most common site in 16 (33.3%) patients. The most commonly performed type of resection was soft tissue resection in 39 (81.3%) cases. Selective supraomohyoid neck dissection was performed in 45 (93.8%) patients. Regarding the treatment outcomes, 43 patients (89.6%) had negative pathological margins, 43 patients did not experience recurrence, and the overall survival rate was 64.6%.

The study investigated mucoepidermoid carcinoma and found that the majority of patients had low-grade tumors. Soft tissue resection was the most common surgical procedure performed. The overall 5-year survival rate was 64.6%.

Paiva-Correia A, Hellquist H, Apolónio J, Castelo-Branco P. Role of ancillary techniques in the differential diagnosis of salivary gland carcinomas. The diagnosis of salivary gland carcinomas (SGC) rests mainly on histology, but immunohistochemical and molecular investigations are often necessary for differential diagnosis. This review is primarily aimed as a tool for pathologists in non-specialised head and neck hospitals who encounter a limited number of SGC annually. The use of testing an initial antibody panel, which may comprise both positive and negative expression for a suspected entity, and examples of different panels are outlined. We also focused on acinic cell carcinoma (AcCC), which is positive for DOG1 and negative for mammaglobin, whilst secretory carcinoma (SC) is positive for mammaglobin and negative for DOG1. In addition, the exclusive expression of androgen and HER2 in salivary duct carcinoma (SDC) and its use for differential diagnosis are also addressed. This review also highlights the particularities of mucoepidermoid carcinoma (MEC) and its negativity for S100 and SOX10, which distinguishes it from some of its mimics. In laboratories with limited access to antibodies for SGC, we recommend inclusion of mammaglobin. The use of molecular techniques for the diagnosis of MEC (MAML2), SC (ETV6), adenoid cystic carcinoma (MYB), and AcCC (NR4A3) is discussed. We highlight the role of commonly available antibodies for the histological classification of SGC.

This study aims to conduct a major bibliometric analysis of salivary gland disorders, exploring publication characteristics, trends, and influential contributors. The primary objective is to improve understanding of the current state of research in this area and to identify potential directions for future investigation.

A comprehensive study was conducted analysing 11,679 publications from 1980 to 2023 retrieved from the Web of Science Core Collection. The analysis included collaboration across countries, keyword co-occurrence, co-citation networks and clustering. CiteSpace and VOSviewer were used to explore relationships and create visualisations.

The analysis revealed a dynamic landscape of salivary gland research, with the United States leading in both the number of publications (n = 2998) and centrality (0.26). Network analysis unveiled nine clusters, including topics such as parotidectomy and immunohistochemistry. Co-occurrence analysis of keywords highlighted evolving trends, with recent emphasis on terms such as sialendoscopy, cytopathology, and gene fusion. The timeline view illustrated the changing significance of terms over the years, reflecting current areas of interest such as radiomics and mucoepidermoid carcinoma.

This study provides a comprehensive overview of the field, offering insights into influential work, collaborative networks, and emerging trends. The outputs of the analysis can guide researchers and clinicians in shaping future investigations.

Primary pulmonary salivary gland-type carcinomas are rare malignancies arising from minor salivary gland tissue in the lower respiratory tract. Given their rarity, constituting <1% of all primary lung malignancies, their epidemiological features and outcomes remain poorly documented. This study analyzed data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database to identify primary pulmonary salivary gland carcinomas, including the most prevalent tumor types.

All patients diagnosed with mucoepidermoid carcinoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma, with the lung designated as the primary site between 1975 and 2019, were subject to analysis. Overall and disease-specific survival were calculated using Kaplan-Meier curves and Cox proportional hazards models.

The study identified 323 mucoepidermoid carcinoma, 284 adenoid cystic carcinoma, and 6 epithelial-myoepithelial carcinoma diagnosed as pulmonary salivary gland-type carcinoma. An analysis of age distribution revealed a unimodal pattern for both mucoepidermoid carcinoma and adenoid cystic carcinoma, with most patients diagnosed after age 40. Most patients were Caucasians (77% for mucoepidermoid carcinoma and 83% for adenoid cystic carcinoma). Both disease-specific and overall survival were worse for patients diagnosed at the age of 60 years or above. Race or sex did not significantly impact patient survival. High-grade mucoepidermoid carcinoma demonstrated a significantly worse prognosis than low or intermediate-grade mucoepidermoid carcinoma.

A comprehensive review of clinical and epidemiological features of pulmonary salivary gland-type carcinomas reveals that the age of diagnosis and tumor grade are the most significant factors in determining patient survival.

Oncocytic adenocarcinoma (OC) of the salivary glands is a rare and controversial entity. It was recently reclassified as "salivary carcinoma NOS and emerging entities" in the 2022 WHO classification of head and neck tumors. The lack of specific molecular alterations and its potential affiliation with other salivary gland carcinomas, such as the oncocytic mucoepidermoid carcinomas (OMEC) or the oncocytic subtype of salivary duct carcinomas (OSDC) justified this reclassification. It is becoming essential to clarify the complex spectrum of potential diagnoses surrounding oncocytic tumors. The objective of this study was to explore the histologic features, as well as the immunohistochemical and molecular profiles, of cases previously diagnosed as OC or OMEC of the salivary glands. This study involved 28 cases of carcinomas with a predominantly oncocytic component. The sex distribution was equal. The median age was 59 years (range 10 to 89). Most of these cases originated from the parotid gland (25/28). The mean tumor size was 2.4 cm (range 0.5 to 6.5). Primary immuno-morphological and mutation/gene fusion profiles reclassified mainly (64.3%, 18/28). Most of them were reclassified in descending order as OSDC (8/18), OMEC (5/18), and OC (2/18). But 3 cases remained unclassified (3/18). The transcriptomic analysis found a proximity of their transcriptomic profile with the OMEC group and a distance from the OSDCs. These findings imply that OC is not distinct but represents oncocytic variants of other salivary carcinomas. It underscores the importance of thorough morphologic, immunohistochemical, and molecular examinations to accurately diagnose carcinomas with predominant oncocytic components in the salivary glands.

Sclerosing mucoepidermoid carcinoma (SMEC) of the salivary glands is a rare variant of low-grade mucoepidermoid carcinoma with scanty cellular atypia characterized by marked fibrosis/sclerosis and a rich inflammatory infiltrate. Herein, we report 25 unpublished cases of SMEC, two of them with prominent eosinophilia (2/25; 8%) and three with abundant IgG4-positive plasma cells (3/25; 12%). In our series of salivary SMEC, molecular analysis using fluorescence in situ hybridization (FISH) and/or next-generation sequencing (NGS) provided evidence of MAML2 gene rearrangement in 18 cases of the 21 analyzable cases tested (86%), while this gene locus was intact in 3 cases (14%). This study focuses on the diagnostic criteria of salivary SMEC given its challenge of abundant collagenous stroma, minimal residual neoplastic areas, and inconspicuous mucous cells. Follow-up data of our cases indicate that salivary SMECs have favorable outcomes. Molecular analysis for MAML2 gene rearrangement suggests that SMECs of salivary glands represent a rare variant of conventional low-grade MECs of salivary glands. In contrast, SMECs of the thyroid gland are genetically distinct from salivary-type thyroid MECs.

Head and neck cancers (HNCs) arise from anatomically adjacent sites and subsites, with varying etiological factors, diagnostic strategies, prognoses, and treatment approaches. While conventional squamous cell carcinoma (SCC) is the most common histology in the head and neck district, HNCs encompass a variety of rare histopathological entities, categorized into epithelial tumors such as salivary gland cancers, sinonasal tumors, neuroendocrine tumors, malignant odontogenic tumors, and SCC variants versus non-epithelial tumors including soft tissue sarcomas, mucosal melanomas, and hematological malignancies. Rare HNCs (R-HNCs) represent a diagnostic and clinical challenge, requiring histopathological expertise, the availability of peculiar molecular analysis, and the personalization of local and systemic treatments, all guided by a multidisciplinary tumor board. Here, we provide a comprehensive literature review on R-HNCs, emphasizing key histopathological and molecular characteristics that are crucial for guiding treatment decisions. An insight about the latest developments in systemic treatments is also reported.

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary tumor. A complete understanding of the high heterogeneity of MEC in histology and genetics would help in accurate diagnosis and treatment. Therefore, We evaluated the clinical features, treatment outcomes, and pathological parameters of 454 MECs and analyzed their genomic features using whole-exome sequencing and whole-transcriptome sequencing. We found that MECs predominantly occurred in females and those in their 4th-5th decades. The parotid gland was the most frequently affected site. All patients underwent complete mass resection with lobectomy; 414 patients were alive without relapse at follow-up, after an average period of 62 months (1-116 months). The disease progressed after initial treatment in 40 patients. The lungs were the most common site of distant metastasis. For classical MECs, histologic gradings of the AFIP, modified Healey, and MSK systems were significantly associated with recurrence and lymph nodal metastasis; these gradings were significantly related to lymph nodal metastasis for the subtypes. Older age, minor salivary gland involvement, clinical symptoms, high TNM stage, high-grade tumor, and improper surgical modality were the main prognostic factors. BAP1 was the most frequently mutated gene in MEC. Mutations in CDKN2A, MET, and TP53 were more frequently found in aggressive tumor phenotypes. MAML2 rearrangement was observed in 42% of patients, and EWSR1 rearrangement in 8%. Specific genetic events (in TP53 and FBXW7) with CRTC1::MAML2 fusion superimposed might be associated with unfavorable prognosis. This study provides new insights into precision therapeutic strategies for MEC.

Mucoepidermoid carcinoma (MEC) is a malignant locally invasive tumour of salivary glands, presumed to arise from reserve cells of salivary gland ducts. It accounts approximately 35% of all malignancies of major and minor salivary glands [1]. MEC arising in minor salivary glands can be located in different areas such as palate, retromolar trigone, floor of mouth, buccal mucosa, lips and tongue. MEC of tongue base are not common but they constitute around 50% of malignant lesions of salivary glands in this region. It presents in fifth and sixth decades of life mostly [1]. We present a rare case of 29 year old woman with low grade mucoepidermoid carcinoma of base of tongue operated by the Trotter procedure with harmonic scalpel - median labio-mandibular glossotomy approach. It's an interesting approach first described by William Trotter in 1920s. It's used by head and neck surgeons for accessing tongue base lesions, pharyngeal wall and cervical spine.

Hepatobiliary mucoepidermoid carcinoma is a rare malignant tumor comprising mucous, intermediate, and epidermoid cells. Herein, we presented a case of primary liver mucoepidermoid carcinoma preoperatively misdiagnosed as conventional intrahepatic cholangiocarcinoma. A 67-year-old male was admitted to our hospital. Preoperative laboratory tests showed increased aspartate transaminase, alanine transaminase, and carbohydrate antigen 19-9. Abdominal Computer Tomography revealed a 4.8 × 4.9 cm liver mass in segment VI. A preliminary diagnosis of intrahepatic cholangiocarcinoma was made, with undergoing partial hepatectomy. However, on histopathology, the tumor comprised a mixture of epidermoid, mucous, and intermediate cells with diffuse infiltrating at the tumor margin. On special stains, mucous and intermedia cells were positive for mucicarmine and Alcian blue, whereas epidermoid cells were positive for Keratin 5/6 and p63. Intermediate cells are also positive for p63. All tumor cells were positive for Keratin 7. The Ki-67 index was 35%. The final diagnosis was primary hepatic mucoepidermoid carcinoma. Although rare, hepatic mucoepidermoid carcinoma should be considered in the intrahepatic cholangiocarcinoma differential diagnosis. We reviewed previous studies and found that hepatobiliary mucoepidermoid carcinoma is more likely to originate from the biliary tract adjacent to the tumor.

Salivary gland neoplasms characterized by abundant mucin production are rare but have long been recognized. Due to their scarcity, precise classification has long eluded these mucin-rich tumors. Recent molecular discoveries, however, have shed considerable light on the genetic underpinnings of mucin-rich salivary gland neoplasms. This manuscript will review the most up-to-date information on this fascinating group of salivary gland neoplasms.

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor. Varying sized cysts and sheets composed of three cell types (epidermoid, intermediate, and mucous cells) with varying degrees of atypia form the characteristic histological appearance of MEC. MEC frequently contains a wide variety of modified tumor cells and can be entirely cystic or completely solid. Under these circumstances, MEC requires critical differentiation from many mimickers, ranging from simple cysts and benign tumors to high-grade carcinomas. Tumor-associated lymphoid proliferation and sclerotic changes in the stroma also contribute to diagnostic difficulties. Several well-known diagnostically challenging variants (oncocytic, clear cell, spindle cell, and sclerosing) exist in MEC. With the advent of studies on specific CRTC1/3::MAML2 fusion genes in MEC, newly proposed subtypes have emerged, including Warthin-like and non-sebaceous lymphadenoma-like MECs. In addition to the recently defined mucoacinar variant with a serous cell phenotype, MEC devoid of squamous differentiation has also been reported, implying the need to reconsider this basic concept. In this article, we outline the general clinical features and MAML2 status of conventional MEC and review the cytoarchitectural subtypes, with an emphasis on a pitfall in the interpretation of this histologically diverse single entity.

Glandular odontogenic cysts (GOCs) and dentigerous cysts may show mucous metaplasia. Central mucoepidermoid carcinoma is very rare and mostly associated with dental cysts. It is hypothesized that odontogenic cysts showing mucus differentiation in their lining, have a propensity to transform into MEC. The present study is the first attempt to explore the relationship between odontogenic cysts [GOCs and dentigerous cysts with mucus metaplasia (DCMM)] and MEC by evaluating immunoexpression of MUC5AC and MUC2. Immunoexpression of MUC5AC and MUC2 was evaluated semiquantitatively in GOCs (20 cases), DCMMs (20 cases), and MECs (20 cases). The percentage of positive cells, intensity, and localization of immunoexpression were assessed for each marker in all cases. Of GOCs, DCMMs, and MECs cases, 85%, 70%, and 80%, respectively, were immunopositive for MUC5AC. Strong cytoplasmic immunoreactivity for MUC5AC was noted, particularly in mucous cells present diffusely within MECs. However, the immunoreactivity was limited to the epithelial lining of GOCs and DCMMs. Most of the MECs (60%) showed more than 25% positivity for MUC5AC, followed by GOCs, and the least in DMMCs. Mild cytoplasmic and nuclear positivity of MUC2 was noted only in epithelial lining cells of 70% GOCs and 45% DCMMs. Whereas, 55% of MECs displayed moderate to strong cytoplasmic and membranous immunopositivity for MUC2 exclusively within mucous cells. As MECs showed strong MUC5AC immunoreactivity in mucous cells, immunoexpression of MUC5AC in odontogenic cysts with mucus cells can possibly explain the pathogenesis of MEC from cysts. However, the variable expression of MUC2 did not give any strong evidence regarding its role as a marker.

Mucoepidermoid carcinoma (MEC) is a common malignancy arising in the parotid gland. The diagnosis of MEC is typically based on its morphological features alone, characteristically containing mucocytes, intermediate cells and epidermoid cells. However, when cystic degeneration is diffuse, it is challenging to distinguish MEC from other benign cystic tumors. This is a case report of a 58-year-old Caucasian man who presented with a parotid mass. H&E sections of the mass reveal multiloculated cysts lined by bland-looking epithelium with only rare papillary architectures. The papillary proliferation contains mucocytes, and epidermoid cells highlighted by the p63 immunohistochemistry study. The diagnosis was confirmed by FISH result of positive MAML2 (11q21) rearrangement. Patient underwent parotidectomy and is disease-free 6 months post-surgery. MEC with cystic degeneration is a common diagnostic pitfall which can mimic many benign lesions in the salivary gland. We present a rare case with MEC with extensive cystic change, its molecular and pathologic findings and review the diagnostic features of MEC, its benign mimickers and useful tools for distinguishing these entities.

Primary pulmonary salivary gland-type tumours (PPSGT) are rare lung neoplasms arising from submucosal seromucinous glands in the central airway.

We retrospectively analysed the clinicopathological features of 111 PPSGTs diagnosed at our institute between 2003 and 2021. The mean age at diagnosis was 43.8 years(range 6-78 years) and a male-to-female ratio of 2:1. On imaging, 92 % of cases had centrally located tumours and 37.3 % were early stage. The histopathological types included 70 cases (63 %) of mucoepidermoid carcinoma (MEC), 31 cases (27.7 %) of adenoid cystic carcinoma (ADCC), two cases of myoepithelial carcinoma, one case each of acinic cell carcinoma (ACC), clear cell carcinoma (CCC), epithelial myoepithelial carcinoma (EMC) and 5 others [including adenocarcinoma of minor salivary gland origin(n = 3), carcinoma with sebaceous differentiation(n = 1) and poorly differentiated carcinoma of salivary gland type(n = 1)]. The size of the tumours found in the resection specimens ranged from 1 cm to 13 cm, with an average size of 4.9 cm. High-risk attributes such as lymphovascular invasion (LVI), perineural invasion (PNI), pleural involvement, positive resection margins, and nodal metastasis were identified in 15.3 %, 15.3 %, 13.6 %,15.2 % and 6.7 % of cases, respectively. These attributes were found to be more frequent in ADCC than in MEC. Surgery was the main treatment modality [68/84 (80 %) cases]. ADCC cases had more recurrence and distant metastasis than MEC cases. The 3- year overall-survival (OS) and recurrence-free survival(RFS) were better in patients with age lesser than 60 years(p-value <0.0001), low pT stage (p-value 0.00038) and lower grade of MEC(p-value-0.0067).

It is crucial to have an acquaintance with the morphologic spectrum and immunophenotypic characteristics of PPSGT to recognize them in this unusual location. In tandem, it is crucial to differentiate them from conventional primary non-small cell lung carcinoma, as the management protocols and prognostic implications differ significantly.

Warthin-like Mucoepidermoid carcinoma (MEC) is a new and rare morphological variant of MEC, with only a few case reports in the literature. The clinicopathological, molecular features and bio-behaviors of Warthin-like MEC has not been studied extensively. We reappraisal all Warthin-like MEC patients diagnosed and treated at our hospital.

Patient characteristics including clinicopathological features, genetic aberrations, treatment, and prognostic information were assessed and evaluated.

Twenty-nine Warthin-like MEC patients were identified, 19 patients were female (65.5 %), and 10 were male (34.5 %). The patients' age varied widely from 8 to 68 years (mean 42.3 years). Genetic aberrations of MAML2 rearrangement were detected in all Warthin-like MEC patients, which suggesting this genetic event is the unique feature of Warthin-like MEC. Twenty-five patients (86.2 %) were assessed as having a low-stage disease (I/II), and four (13.8 %) as having high-clinical stage disease (III/IV). More than half of the patients (16/29) underwent only partial sialoadenectomy; 2 patients underwent extended sialoadenectomy, and 11 patients underwent extended sialoadenectomy with cervical lymph node dissection. After a median follow-up time of 73 months (5-128 months), Twenty-eight patients were alive without recurrence at the end of the follow-up period, one patient died 1 year after surgery due to lung metastasis.

Our data suggested that most Warthin-like MEC exhibited mild clinicopathological course and less aggressive bio-behavior, and an aggressive bio-behavior seemed to be very rare. In addition, in the salivary gland, MAML2 rearrangement seems to be a unique molecular feature of salivary Warthin-like MEC.

Mucoepidermoid carcinoma (MEC) is a malignant tumor with diverse morphologies, some of which have poor prognostic indicators and others that challenge the grading system. This study investigated the expression of PD-L1 in different grades and phenotypes of MEC.

The present study was carried out on twenty-four archival formalin-fixed, paraffin-embedded blocks of salivary MEC. Fluorescence in situ hybridization was used to detect MAML2 rearrangement in MEC cases to be included. The studied cases were then subcategorized based on their grading and phenotype and immunohistochemically stained for PD-L1.

PD-L1 expression in MEC varied, with some variants showing moderate to strong immunoexpression, while others did not express it at all. In the Warthin-like MEC, some tumors show high expression of PD-L1, while in the same pattern, a few cases showed low or no expression. Intraosseous MEC exhibited moderate PD-L1 expression. Sclerosing MEC featured lower PD-L1 expression, from weak to moderate. Oncocytic MEC displayed relatively low PD-L1 expression levels (weak to moderate).

The histomorphologic features of MEC may predict clinicopathologic behavior, and subtyping MEC may pose a significant therapeutic value, particularly for intraosseous MECs and clear-cell MECs. PD-L1 expression is a good predictor of survival outcomes in MECs.

Mucoepidermoid carcinoma (MEC) is the most common malignant lesion of salivary glands. A number of histologic grading systems are in use for MEC with variable agreement between them.

This study was aimed at comparison of four grading systems for MEC: two qualitative (modified Healy and MSKCC grading) and two quantitative (AFIP and Brandwein grading). A retrospective search for diagnosed cases of MEC over eight years yielded 11 cases with adequate clinical details and histologic slides available for review. All cases were reviewed and graded as per the four grading systems. An inter-system agreement was assessed, and Kaplan-Meier analysis was performed to correlate the grading with clinical outcomes.

A general agreement between all four grading systems was seen in 72.7% of cases. Brandwein grading assigned the highest percentage of high grades (18.2%), whereas Memorial Sloan-Kettering Cancer Center (MSKCC) assigned the highest percentage of low-grade MEC (72.7%). The agreement between MSKCC and modified Healy was highest at 90% of cases. There was generally a poor agreement between MSKCC and Brandwein grading systems. The MSKCC grading system showed a significant correlation with disease-free survival in MEC patients.

Hence, the MSKCC grading system might serve as a better histologic grading system with a predictive value for the biologic behavior of the tumor. Further larger studies are required to validate these findings and implement the uniform use of MSKCC grading for MEC of salivary glands.

Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. This study was designed to identify valuable prognosticator in MEC.

Histopathologic analysis, immunohistochemistry, and in situ hybridization were performed on 128 carcinomas diagnosed as MEC of the head and neck.

Expression of p16 was found in 96 cases (76%) of MEC. Lymphoid stroma was identified in 63 cases (49%). There was a significant correlation between loss of p16 expression and absence of lymphoid stroma. Expression of p16 was significantly associated with better clinicopathologic features. Lymphoid stroma was significantly associated with lower histologic grade. Overall survival (OS) was significantly longer in cases expressing p16 (P = 0.00096) and lymphoid stroma cases (P = 0.0023). Multivariate analysis revealed loss of p16 expression as negative prognosticators for OS.

Our data showed p16 expression and the presence of lymphoid stroma were significantly associated with good clinical outcomes. Testing for these factors could lead to better prognostication and treatment of patients with MEC.

We aimed to characterize the histology and the clinicodemographic features of mucoepidermoid carcinoma (MEC), showing continuity with the oral surface mucosa.

We reviewed 138 cases of intraoral MEC to identify cases that showed continuity with the surface mucosa and compared their clinicodemographic findings with those of MECs not showing continuity. We compared the sex ratio using the 2-sample Z-test and compared the age distribution using the 2-sample Kolmogorov-Smirnov test.

Of the 138 cases examined, 14 showed continuity with the surface mucosa. Their histology showed surface mucosa with an apparent transition to an infiltrating tumor with mucous, intermediate, and epidermoid tumor cells growing in solid and cystic patterns. Their clinical appearance ranged from firm submucosal nodules to erythematous to ulcerated lesions. They showed a strong female predilection (6:1) and sharply bimodal age distribution, with sharp peaks in the fourth and seventh decades.

Mucoepidermoid carcinomas that show continuity have a demographic pattern distinct from that of conventional MECs, showing a striking female predilection and bimodal age distribution and suggesting a difference in etiology. Pathologists should remain aware that MEC in the oral cavity can have a histologic appearance of surface origin to reach the correct diagnosis.

Although mucoepidermoid carcinoma (MEC) is the most diagnosed malignancy of the salivary gland, it rarely localises to the bronchus, accounting for only 0.1-0.2% of all primary lung malignancies. Of those pulmonary MECs, most are found in segmental or lobar bronchi, and they are rarely found in mainstem bronchi, highlighting the novelty of this presentation for thoracic specialists. We present a case report of a seven-year-old female who underwent a carinal resection and a right upper lobectomy for the management of an endobronchial MEC causing right middle lobe (RML) obstruction. Intraoperatively, an exophytic mass originating from the junction of the right main bronchus and bronchus intermedius was identified, causing a partial obstruction of the RML bronchus. Frozen sections demonstrated clear margins and follow-up bronchoscopies have been unremarkable. Given their rarity, endobronchial MECs can be diagnostically difficult and cause uncertainty with respect to their management. Low-grade tumours have a much more favourable prognosis than their high-grade counterparts, with surgical resection being the gold standard of care. Therefore, the index of suspicion, time to diagnosis, and definitive treatment are critical to the outcome.

Multiple 3-tiered grading systems exist for mucoepidermoid carcinoma (MEC), leading to controversial results on the frequency and prognostic values of each grade. We aimed to identify prognostic histologic factors and to evaluate grading schemes in this retrospective study of 262 resected primary head and neck MECs. The rate of nodal metastasis was 8.4%. Large tumor size, tumor fibrosis, infiltrative border, lymphovascular invasion, perineural invasion, atypical mitosis, mitotic index (MI) ≥4/2 mm 2 (4/10 HPFs), necrosis, and pT4 stage were associated with increased risk of nodal metastasis. The 5-year recurrence-free survival (RFS) was 95%. Significant prognostic factors for RFS included infiltrative border, tumor-associated lymphoid stroma, architectural patterns (macrocystic, microcystic, and noncystic), anaplasia, atypical mitosis, MI, necrosis, lymphovascular invasion, margin, pT stage, and tumor size. Nuclear anaplasia, high mitotic rate, and ≥25% microcystic component were significant independent prognostic factors on multivariate survival analysis. There was no significant difference between low-grade (LG) and intermediate-grade (IG) MECs in terms of risk of nodal metastasis and outcomes using all 4 known grading systems. Rather, high-grade MEC was consistently associated with an increased risk of nodal metastasis at presentation and decreased RFS and distant metastasis-free survival (DMFS) compared with the LG/IG MECs. We therefore recommend simplifying MEC grading to a 2-tiered grading scheme using MI and/or tumor necrosis. Using a 2-tiered grading, high-grade histology independently predict RFS, and is associated with a 25% risk of nodal metastasis, a 5-year RFS of 76%, and a 5-year DMFS of 76%, whereas LG MEC has a nodal metastasis rate of 7.0%, 5-year RFS of 97% and 5-year DMFS of 99%.

The World Health Organization classification of tumors of the breast recognizes several special type carcinomas and benign lesions with features comparable to those of salivary gland tumors.

To discuss the histologic, immunophenotypic, molecular, and clinical features of salivary gland-like carcinomas of the breast. These breast tumors are often negative for hormone receptors and human epidermal growth factor receptor 2 (HER2), that is, triple-negative, but they generally have a much better prognosis than triple-negative breast carcinomas of no special type. We compare the immunophenotypic, molecular, and clinical features of these breast tumors with their salivary gland counterparts, highlighting similarities and differences. We also discuss benign salivary gland-like breast tumors. Finally, we highlight recent developments in understanding the molecular pathogenesis of these breast tumors and novel ancillary studies that can be used to support their diagnosis.

A literature review was conducted, and papers were selected for further analysis and discussion by the authors of this review based on their novelty, applicability, and impact in the field.

Breast tumors that exhibit morphologic overlap with salivary gland tumors have been recognized by pathologists for decades, but the similarities and differences in their molecular pathogenesis have not been understood until more recently. These developments have led to novel diagnostic tools and further knowledge of these rare breast lesions.

Mucoepidermoid carcinoma is the commonest primary malignant salivary gland tumor in both children and adults and constitutes around 2.8-16% of all salivary gland tumors. There is a wide age range of 3 to 95 years with a mean age of 47 years. We reported a case of 85 years old female patient, who presented to the department of Surgical Oncology, Srinivasan Medical College and Hospital, Trichy, with history of right parotid swelling for past 25 years, who had undergone Superficial parotidectomy 10 years back, followed by recurrence of tumor with huge increase in size, around 20 cm in greatest dimension. Right Completion Radical Parotidectomy with Modified Radical neck dissection type 1 with Cervical Rotation Flap cover was done and histopathological examination of the surgical specimen confirmed as high grade Mucoepidermoid carcinoma. Following surgery, the patient's outcome is better, uneventful with periodic regular follow-up.

Autophagy is a cellular survival mechanism involved in several human diseases, but its participation in the development of salivary gland tumors is not fully understood. This study investigated the immunoexpression of autophagy-related proteins (autophagy-related 7 [Atg7], microtubule-associated protein 1 light chain 3A [LC3A], microtubule-associated protein 1 light chain 3B [LC3B], protein p62 [p62], and phosphorylated mammalian target of rapamycin [p-mTOR]) in pleomorphic adenoma (PA), polymorphous adenocarcinoma (PAC), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC) of salivary glands.

Twenty PAs, 20 PACs, 20 MECs, and 14 ACCs were selected. The percentages of cytoplasmic and nuclear positivity for autophagy-related proteins in neoplastic cells were assessed and correlated with histopathological parameters.

Cytoplasmic immunoexpression of Atg7 was observed in all groups, with high median percentages of positivity. Regarding LC3A and LC3B, cytoplasmic immunoexpression was found in most PACs (95%) and in all cases of PA, MEC and ACC, with the highest percentages of positivity in PACs and PAs (p < 0.005). ACCs exhibited lower cytoplasmic immunoexpression of p-mTOR (p < 0.005) and lower nuclear expression of p62 (p < 0.05) when compared to PAs, PACs and MECs. Low nuclear immunoexpression of Atg7, LC3A and p-mTOR and absence of nuclear staining for LC3B were observed in all groups. Regarding histopathological parameters of PAs, MECs and ACCs, there were no significant differences in the expression of autophagy-related proteins. In all groups, positive correlations were observed between the immunoexpression of some autophagy-related proteins (p < 0.05).

The results suggest the participation of autophagy in the pathogenesis of PA, PAC, MEC, and ACC of salivary glands. Upregulation of autophagy and reduced nuclear translocation of p62 may contribute to the aggressive biological behavior of salivary gland ACC.

Salivary gland tumors most commonly involve the parotid gland. Among all the tumors, 80% are benign and of all the benign tumors 80% originate from the parotid gland. The pleomorphic adenoma is the most common benign tumor whereas the mucoepidermoid carcinoma is the most prevalent malignant tumor. Mucoepidermoid carcinoma is a diagnostic challenge on FNAC with a high false negative rate. A 17-year-old female presented with slow-growing painless swelling below the right ear for two years. The history and clinical examination appeared to be benign parotid swelling. The further investigation proceeded and fine needle aspiration cytology was performed. A case of the parotid lump which has shown the pleomorphic adenoma of the parotid gland on cytology. Surgical resection was done and a post-operative specimen of the parotid gland showed mucoepidermoid carcinoma on histopathology. FNAC is not always reliable in the case of mucoepidermoid carcinoma of the parotid gland, especially in the low-grade type. The confirmatory diagnosis can be made only after the histopathological examination.

Salivary gland secretory carcinoma (SC), previously mammary analog SC, is a low-grade malignancy characterized by well-defined morphology and an immunohistochemical and genetic profile identical to SC of the breast. Translocation t(12;15)(p13;q25) resulting in the ETV6 :: NTRK3 gene fusion is a characteristic feature of SC along with S100 protein and mammaglobin immunopositivity. The spectrum of genetic alterations for SC continues to evolve. The aim of this retrospective study was to collect data of salivary gland SCs and to correlate their histologic, immunohistochemical, and molecular genetic data with clinical behavior and long-term follow-up. In this large retrospective study, we aimed to establish a histologic grading scheme and scoring system. A total of 215 cases of salivary gland SCs diagnosed between 1994 and 2021 were obtained from the tumor registries of the authors. Eighty cases were originally diagnosed as something other than SC, most frequently acinic cell carcinoma. Lymph node metastases were identified in 17.1% (20/117 cases with available data), with distant metastasis in 5.1% (6/117). Disease recurrence was seen in 15% (n=17/113 cases with available data). The molecular genetic profile showed ETV6 :: NTRK3 gene fusion in 95.4%, including 1 case with a dual fusion of ETV6 :: NTRK3 and MYB :: SMR3B . Less frequent fusion transcripts included ETV6 :: RET (n=12) and VIM :: RET (n=1). A 3-tiered grading scheme using 6 pathologic parameters (prevailing architecture, pleomorphism, tumor necrosis, perineural invasion (PNI), lymphovascular invasion (LVI), and mitotic count and/or Ki-67 labeling index) was applied. Grade 1 histology was observed in 44.7% (n=96), grade 2 in 41.9% (n=90), and grade 3 in 13.5% (n=29) of cases. Compared with low-grade and intermediate-grade SC, high-grade tumors were associated with a solid architecture, more prominent hyalinization, infiltrative tumor borders, nuclear pleomorphism, presence of PNI and/or LVI, and Ki-67 proliferative index >30%. High-grade transformation, a subset of grade 2 or 3 tumors, seen in 8.8% (n=19), was defined as an abrupt transformation of conventional SC into high-grade morphology, sheet-like growth, and a tumor lacking distinctive features of SC. Both overall survival and disease-free survival (5 and 10 y) were negatively affected by tumor grade, stage, and TNM status (each P <0.0001). SC is a low-grade malignancy with predominantly solid-microcystic growth patterns, driven by a gene fusion, most commonly ETV6 :: NTRK3 . There is a low risk for local recurrence and a good overall long-term survival, with a low risk for distant metastasis but a higher risk for locoregional lymph node metastasis. The presence of tumor necrosis, hyalinization, PNI and/or LVI, and positive resection margins correlate with higher tumor grade, less favorable prognosis, and increased mortality. The statistical results allowed us to design a 3-tiered grading system for salivary SC.

To analyze the risk factors for synchronous lung metastases (LM) in patients with major salivary gland mucoepidermoid carcinoma (MaSG-MEC).

MaSG-MEC patients were extracted from the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2014. Descriptive statistics were used to examine the baseline characteristics of the patients. We examined the association between risk factors and synchronous LM using Chi-squared tests. The primary study outcomes were overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier survival curves were compared using the log-rank test. Hazard analysis was conducted using the Cox proportional hazards model.

A total of 701 patients were analyzed, which including 8 patients (1.1%) with synchronous LM, and 693 patients without synchronous LM (98.9%). Lower T or N classification, and highly differentiated disease were associated with a significantly lower risk of LM and multivariate logistic regression analysis showed that lower T classification were associated with a significantly lower risk of LM (P < 0.05, respectively). Elderly Caucasian male patients with poorly differentiated disease, multiple sites of metastases and no surgical therapy to primary tumor were more likely to reduce life expectancy.

By analyzing data from a large cohort, lower T or N classification and highly differentiated disease were associated with a significantly lower risk of LM. Elderly Caucasian male patients with poorly differentiated disease, multiple sites of metastases and no surgical therapy to primary tumor were more likely to reduce life expectancy. More accurate assessments of LM will be imperative for early diagnosis and treatment in patients who harbored with higher T or N classification and poorly differentiated disease.

Various prognostic factors are associated with the survival of patients with parotid mucoepidermoid carcinoma (MEC). The aim of this systematic review is to summarize the clinical and pathologic prognostic factors on survival outcomes in patients with parotid MEC.

Articles published from database inception to July 2020 on OVID Medline, OVID Embase, Cochrane Central, and Scopus.

Studies were included that reported clinical or pathologic prognostic factors on survival outcomes for adult patients with parotid MEC. Data extraction, risk of bias, and quality assessment were conducted by 2 independent reviewers.

A total of 4290 titles were reviewed, 396 retrieved for full-text screening, and 18 included in the review. The average risk of bias was high, and quality assessment for the prognostic factors ranged from very low to moderate. Prognostic factors that were consistently associated with negative survival outcomes on multivariate analysis included histologic grade (hazard ratio [HR], 5.66), nodal status (HR, 2.86), distant metastasis (HR, 3.10-5.80), intraparotid metastasis (HR, 13.52), and age (HR, 1.02-6.86). Prognostic factors that inconsistently reported associations with survival outcomes were TNM stage, T classification, and N classification.

Histologic grade, nodal status, distant metastasis, intraparotid metastasis, and age were associated with worse survival outcomes. These prognostic factors should be considered when determining the most appropriate treatment and follow-up plan for patients with parotid MEC.

The differential diagnosis of mucoepidermoid carcinoma (MEC) from neoplasm undergoing mucinous features brings more pitfalls to pathologists. Combining specific MAML2 gene rearrangement and histological characteristics may be the solution.

Twenty-five tumors with mucinous components were selected for differential diagnosis of MEC. All the cases were detected for MAML2 gene rearrangement. The cases diagnosed as MEC were classified into four variants: classic, oncocytic, Warthin-like, and nonclassified, and they were graded using the Brandwein system. The histological characteristics of non-MECs were summarized for differential diagnosis. Univariate survival analysis was performed on MECs.

There were 16 MECs; 62.5% were MAML2 rearranged. For the low-, intermediate-, and high-grade MECs, the rate of rearrangement was 83.3%, 100%, and 28.6%, respectively. Both the oncocytic and Warthin-like MECs were MAML2 rearranged. For the classic and nonclassified MECs without MAML2 rearrangement, non-keratinized squamoid cells and distinctive mucinous cells were essential diagnostic criteria. On survival analysis, all the disease progression occurred in high-grade MECs (p = 0.038). Nine cases were diagnosed as non-MECs: pleomorphic adenoma with mucinous metaplasia showed no ex-capsular involvement; metaplastic Warthin tumor appeared with overt keratinization and residual oncocytic bilayered epithelium; mix squamous cell and glandular papilloma showed an endobronchial papillary growing pattern; adenosquamous carcinoma was accompanied by squamous carcinoma in situ of the overlying mucosa. All the non-MECs were negative for MAML2 rearrangement.

The application of combining MAML2 rearrangement and histological characteristics is helpful in the differential diagnosis between MEC and other tumors with mucinous components.

This study aimed to compare the immunoexpression profile of tumor stem cell (TSC) biomarkers CD44, aldehyde dehydrogenase 1 (ALDH1), OCT4, and SOX2 in salivary gland tumors (SGTs).

Sixty tissue specimens of SGTs, including 20 pleomorphic adenomas, 20 adenoid cystic carcinomas (ACCs), and 20 mucoepidermoid carcinomas, in addition to 4 samples of normal glandular tissue, were subjected to immunohistochemistry. The expression of the biomarkers in the parenchyma and stroma was evaluated. Data were analyzed statistically by nonparametric tests (P < .05).

Higher parenchymal expression of ALDH1, OCT4, and SOX2 was observed in pleomorphic adenomas, ACCs, and mucoepidermoid carcinomas, respectively. Most ACCs did not express ALDH1. Higher immunoexpression of ALDH1 in major SGTs (P = .021) and of OCT4 in minor SGTs (P = .011) was found. Immunoexpression of SOX2 was related to lesions without myoepithelial differentiation (P < .001) and malignant behavior (P = .002). Furthermore, OCT4 was related to myoepithelial differentiation (P = .009). CD44 expression was related to a better prognosis. Stromal immunoexpressions of CD44, ALDH1, and OCT4 were higher in malignant SGTs.

Our findings suggest the participation of TSCs in the pathogenesis of SGTs. We emphasize the need for further investigations into the presence and role of TSCs in the stroma of these lesions.

Salivary gland cancers (SGCs) are diagnosed using histopathological examination, which significantly contributes to their progression, including lymph node/distant metastasis or local recurrence. In the current World Health Organization (WHO) Classification of Head and Neck Tumors: Salivary Glands (5th edition), malignant and benign epithelial tumors are classified into 21 and 15 tumor types, respectively. All malignant tumors have the potential for lymph node/distant metastasis or local recurrence. In particular, mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (AdCC), salivary duct carcinoma, salivary carcinoma, not otherwise specified (NOS, formerly known as adenocarcinoma, NOS), myoepithelial carcinoma, epithelial-myoepithelial carcinoma, and carcinoma ex pleomorphic adenoma (PA) are relatively prevalent. High-grade transformation is an important aspect of tumor progression in SGCs. MEC, AdCC, salivary carcinoma, and NOS have a distinct grading system; however, a universal histological grading system for SGCs has not yet been recommended. Conversely, PA is considered benign; nonetheless, it should be cautiously treated to avoid the development of metastasizing/recurrent PA. The aim of this review is to describe the current histopathological aspects of the prognostic factors for SGCs and discuss the genes or molecules used as diagnostic tools that might have treatment target potential in the future.

Patients with advanced/recurrent mucoepidermoid carcinoma (MEC) have a poor prognosis. This study aimed to establish and characterize human mucoepidermoid carcinoma cell lines from the initial surgical specimen and biopsy specimen upon recurrence from the same patient to provide a resource for MEC research. MEC specimens from the initial surgical procedure and biopsy upon recurrence were used to establish cell lines. The established cell lines were cytogenetically characterized using multi-color fluorescence in situ hybridization and detection, and the sequence of the CRTC1-MAML2 chimeric gene was determined. Furthermore, the susceptibility of head and neck mucoepidermoid carcinoma to standard treatment drugs such as cisplatin, 5-fluorouracil, and cetuximab was investigated. We successfully established unique MEC cell lines, AMU-MEC1, from an initial surgical specimen and AMU-MEC1-R1 and AMU-MEC1-R2 from the recurrent biopsy specimen in the same patient. These cell lines exhibited epithelial morphology and developed in vitro-like cobblestones. They shared eight chromosomal abnormalities, including der(19)ins(19;11)(p13;?), which resulted in a chimeric CRTC1-MAML2 gene, indicating the same origin of the cell lines. The susceptibility of all cell lines to cisplatin and 5-fluorouracil was low. Interestingly, EGFR dependency for cell growth decreased in AMU-MEC-R1 and AMU-MEC-R2 but was retained in AMU-MEC1. These cytogenetic and biochemical findings suggest that the established cell lines can be used to investigate the disease progression mechanisms and develop novel therapeutics for MEC.

Lacrimal gland mucoepidermoid carcinoma is very rare. It has a high risk of recurrence and metastasis, however, it rarely metastasizes to the contralateral eye in clinical practice. Here, we present a case of a 52-year-old man with lacrimal gland mucoepidermoid carcinoma who developed multiple recurrences and metastases of another eye and other sites throughout the body after receiving surgical intervention and regular radiotherapy, which will be of ophthalmic interest and unique. Clinical features, imaging findings, histopathology, treatments, and outcomes of this very rare case are provided. A literature review of previously published cases of this disease is performed, with an emphasis on the latest diagnosis and treatment. The prognosis of tumor recurrence and metastasis is poorer, surgery with a negative margin in conjunction with adjuvant therapies is crucial for preventing local recurrence and distant metastasis and enhancing the survival rate.

Chrysin is a flavonoid found abundantly in substances, such as honey and phytochemicals, and is known to exhibit anticancer effects against various cancer cells. Nevertheless, the anticancer effect of chrysin against oral cancer has not yet been verified. Furthermore, the mechanism underlying autophagy is yet to be clearly elucidated. Thus, this study investigated chrysin-mediated apoptosis and autophagy in human mucoepidermoid carcinoma (MC-3) cells. The change in MC-3 cell viability was examined using a 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide cell viability assay, as well as 40,6-diamidino-2-phenylindole, annexin V, and propidium iodide staining. Western blotting was used to analyze the proteins related to apoptosis and the mitogen-activated protein kinase (MAPK) pathway. In addition, the presence or absence of autophagy and changes in the expression of related proteins were investigated using acridine orange staining and Western blot. The results suggested that chrysin induced apoptosis and autophagy in MC-3 oral cancer cells via the MAPK/extracellular signal-regulated kinase pathway. Moreover, the induced autophagy exerted a cytoprotective effect against apoptosis. Thus, the further reduced cell viability due to autophagy as well as apoptosis induction highlight therapeutic potential of chrysin for oral cancer.

Mucoepidermoid carcinomas (MECs) are a form of salivary gland malignancy. They are classified according to histological grade and perineural invasion (PNI). In another cancer subtypes, positive-PNI suggests increased poor prognosis; however, the role of isolated positive-PNI salivary gland MEC can still be better investigated as a risk factor. This study investigated whether isolated PNI is independently associated with poor outcomes. Retrospective study, cohort case-series, single-center hospital from 2009 to 2019. Patient demographics, primary tumor, intervention, and survival data are included. Univariate, multivariate, and Kaplan-Meier survival curve analyses were used for comparison.The study group consisted of 32 patients (15 PNI-positive tumors, and 17 PNI-negative tumors), all admitted for surgery. Univariate analysis showed differences in grade (p = 0.038), positive margins (p = 0.034), soft tissue invasion (p < 0.001), pathological stage (p = 0.014), recurrence (p = 0.015), distant metastasis (p = 0.015) and MEC related death (p = 0.015). The risk in PNI-positive patients to develop soft tissue invasion and positive surgical margins was OR = 8.57 and OR = 4.88, respectively. Multivariate analysis found age differences (p = 0.038), with OR = 1.08. The Disease Specific Survival (DSS) was worst in the PNI-positive group (log-rank p-value = 0.0011), where the probability of dying occurred in the 12-24 months period (log-rank p-value = 0.002). PNI-positive salivary gland MEC is an independent prognostic factor, with poor DSS, increased locoregional recurrence, close correlation with a more aggressive pattern of the disease, and should be reviewed as a high grade histological criteria. Our findings may imply changes in the clinical approach with a more aggressive attitude in the overall treatment.

Salivary gland mucoepidermoid carcinoma (MEC) poses a considerable risk of locoregional and distant metastasis after conventional treatments. There is an evident need for specifying prognostic biomarkers to identify patients who are in need of more intensive and prolonged follow-ups. This study aimed to assess the mucin 1 (MUC1) expression level and its potential regulatory microRNAs in salivary gland MEC and their prognostic potentials.

The expression of MUC1 in salivary gland MEC tissues was assessed in 47 samples using immunohistochemistry. Related microRNA (miR-145 and miR-21) were evaluated using quantitative Reverse Transcription PCR. The associations between MUC1 and microRNAs expressions and clinicopathological parameters were investigated.

MUC1 expression levels positively correlated with histologic grade (p < 0.001), clinical stage (p = 0.04), risk of nodal metastasis (p = 0.02), as well as the likelihood of opting for radical treatment (p = 0.01). Increased expression of miR-21 (p < 0.001) and decreased expression of miR-145 (p < 0.001) were observed in MECs compared to normal salivary gland tissue. MiR-145 negatively (p = 0.01) and miR-21 positively (p = 0.01) correlated with MUC1 overexpression. Based on the univariate cox proportional hazard model, histologic grade and MUC1 expression level were significantly associated with disease-free, cancer-specific, and overall survival. However, the multivariable cox proportional hazard model indicated tumor grade as the only prognostic factor associated with disease-free survival.

Our results support the tumor suppressor role of miR-145 and the oncogenic role of miR-21 in salivary gland MEC. Also, MUC1 and miR-145 overexpression, as well as miR-21 suppression, show promising association with histologic tumor grade and clinical stage.

Fine-needle aspiration (FNA) cytology is widely used in clinical practice as a simple and minimally invasive test for parotid tumors that allows for preoperative estimation of benignancy and malignancy, histological type, and malignancy grade and can be performed on an outpatient basis. In recent years, cell blocks prepared with core needle biopsy (CNB) and liquid-based cytology (LBC) have increased the reliability of immunostaining and molecular biological testing, leading to improved diagnostic accuracy. In 2018, the Milan System for Reporting Salivary Gland Cytology was introduced, but it does not include malignancy grade or histological type, so we proposed the Osaka Medical College classification as a more clinically based cell classification that includes both types of information, and we have reported on its usefulness. This review gives an overview of the history and use of FNA and describes CNB and LBC and the two classification systems.

Pulmonary mucoepidermoid carcinoma (PMEC) is the most common malignant salivary gland tumor in the lungs and accounts for 0.1-0.2% of all lung malignancies in adults. It has no specific epidemiological or clinical characteristics. Correct diagnosis requires the combined examinations of images, laboratories, pathology, and immunohistochemistry (IHC) as well as molecular characteristics. PMEC tumors are characterized by squamous, intermediate, and mucus-secreting cells. Currently, histological appearance, mitotic frequency, cellular atypia, and necrocytosis allow the classification of PMEC into low grade or high grade. Molecular changes are crucial to pathological diagnosis. The driver of PMEC seems to be the fusion protein MECT1-MAML2 that is generated from a genetic mutation in t (11; 19) (q21; p13), while other gene mutations are also reported. However, no treatment of PMEC exists so far; surgical excision is still the primary treatment, while the efficacies of chemotherapy or radiotherapy are undefined. Tyrosine kinase inhibitor (TKI) therapy and immunotherapy showed to have significant therapeutic effects but require more investigation and better understanding. This review focuses on the clinical characteristics, imaging and pathologic features, immunohistochemical examination, mutation analysis, differential diagnosis, prognosis, and treatment of PMEC.

Mucoepidermoid Carcinomas (MEC) represent the most common malignancies of salivary glands. Approximately 50% of all MEC cases are known to harbor CRTC1/3-MAML2 gene fusions, but the additional molecular drivers remain largely uncharacterized. Here, we sought to resolve controversy around the role of human papillomavirus (HPV) as a potential driver of mucoepidermoid carcinoma. Bioinformatics analysis was performed on 48 MEC transcriptomes. Subsequent targeted capture DNA sequencing was used to annotate HPV content and integration status in the host genome. HPV of any type was only identified in 1/48 (2%) of the MEC transcriptomes analyzed. Importantly, the one HPV16+ tumor expressed high levels of p16, had high expression of HPV16 oncogenes E6 and E7, and displayed a complex integration pattern that included breakpoints into 13 host genes including PIK3AP1, HIPI,&nbsp;OLFM4,SIRT1, ARAP2, TMEM161B-AS1, and EPS15L1 as well as 9 non-genic regions. In this cohort, HPV is a rare driver of MEC but may have a substantial etiologic role in cases that harbor the virus. Genetic mechanisms of host genome integration are similar to those observed in other head and neck cancers.

Thymic mucoepidermoid carcinoma (MEC) is a rare tumor, and its characteristics remain to be clarified. Here we investigated 20 cases of thymic MEC to systematically characterize its clinical, histopathologic, and molecular features. The median age of the patients was 56 years (range, 19 to 80 y), there was a slight male predilection (3:2), and 44% of the patients were asymptomatic at diagnosis. The median tumor size was 6.8 cm in diameter, 55% were pT1 tumors, and 50% were TNM stage I tumors. When 4 tumor grading systems for salivary MEC (Armed Forces Institutes of Pathology, Brandwein, modified Healey, and the Memorial Sloan-Kettering) were employed, low-grade, intermediate-grade, and high-grade tumors accounted for 35% to 70%, 5% to 25%, and 25% to 50%, respectively. Many histologic variants were noted, and 70% of the cases were classified as nonclassic variants. MAML2 rearrangement was detected in 56% of cases, and the fusion partner was CRTC1 in all cases. CRTC1-MAML2 fusion was associated with lower pT classification and lower TNM stage. The overall survival rate of all patients was 69% and 43% at 5 and 10 years, respectively. Worse overall survival was associated with higher pT stage, higher TNM stage, residual tumors, greater tumor size, high-grade tumor histology (Armed Forces Institutes of Pathology and Memorial Sloan-Kettering, but not the other 2), and with the absence of CRTC1-MAML2 fusion. Of note, none of the patients with CRTC1-MAML2 fusion-positive tumors died during the follow-up. In conclusion, the clinicopathologic and molecular findings of thymic MEC presented here are expected to contribute to the management of this rare tumor.