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Histopathology Jan 2024Primary pulmonary salivary gland-type tumours are rare neoplasms that are thought to arise from seromucinous glands that are located in the submucosa of large airways.... (Review)
Review
Primary pulmonary salivary gland-type tumours are rare neoplasms that are thought to arise from seromucinous glands that are located in the submucosa of large airways. These neoplasms have clinical and pathologic features that are distinct from other pulmonary neoplasms. The majority of primary pulmonary salivary gland-type tumours are malignant, with the most common entities being mucoepidermoid carcinoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma. Less commonly seen are myoepithelial carcinoma, hyalinizing clear cell carcinoma, acinic cell carcinoma, secretory carcinoma, salivary duct carcinoma, intraductal carcinoma, and polymorphous adenocarcinoma. Benign salivary gland-type tumours of the lung include pleomorphic adenoma and sialadenoma papilliferum. Morphologic, immunophenotypic, and molecular features of these neoplasms are largely similar to salivary gland tumours elsewhere, and therefore the exclusion of metastatic disease requires clinical and radiologic correlation. However, the differential diagnostic considerations are different in the lung. The distinction of salivary gland-type tumours from their histologic mimics is important for both prognostication and treatment decisions. Overall, salivary gland type-tumours tend to have a more favourable outcome than other pulmonary carcinomas, although high-grade variants exist for many of these tumour types. Recent advances in our understanding of the spectrum of salivary gland-type tumours reported in the lung and their diversity of molecular and immunohistochemical features have helped to refine the classification of these tumours and have highlighted a few differences between salivary gland-type tumours of the lung and those primary to other sites.
Topics: Humans; Salivary Gland Neoplasms; Carcinoma, Adenoid Cystic; Adenoma, Pleomorphic; Carcinoma; Carcinoma, Mucoepidermoid; Carcinoma, Acinar Cell; Salivary Glands; Lung; Lung Neoplasms; Biomarkers, Tumor
PubMed: 37694812
DOI: 10.1111/his.15039 -
American Journal of Stem Cells 2021Cancer stem cells (CSCs) are a unique population of cells found within tumors that are able to self-renew, restore the original heterogeneity of a tumor following... (Review)
Review
Cancer stem cells (CSCs) are a unique population of cells found within tumors that are able to self-renew, restore the original heterogeneity of a tumor following treatment, and show increased tumorigenic potential when compared to other cancer cells. It is thought that they are responsible for the recurrence of tumors as well as the resistance to treatment that is seen clinically. CSCs are known to be involved in head and neck cancer (HNCs) specifically, as evidence for their existence can be found in head and neck squamous cell carcinoma (HNSCC), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC), among others. Here, findings from various approaches to identifying and targeting CSCs and their downstream effectors in HNC are summarized, with an emphasis on recent advancements. Prognostic and therapeutic markers are discussed for each specific type of HNC, and novel treatment strategies and current clinical trials involving CSCs are detailed as well. The information provided here is intended to further the research on this important topic and lead to clinical impact in the battle against HNC.
PubMed: 34552815
DOI: No ID Found -
Cancer Medicine May 2023Mucoepidermoid carcinoma (MEC) of the breast is an extremely rare salivary gland-type tumor characterized by epidermoid, basaloid, intermediate, and/or mucinous cells...
Mucoepidermoid carcinoma (MEC) of the breast is an extremely rare salivary gland-type tumor characterized by epidermoid, basaloid, intermediate, and/or mucinous cells arranged in solid and cystic patterns. Despite their triple-negative phenotype, breast MECs are generally considered low-risk malignancies but their biology is largely unexplored; therefore, guidelines for clinical management are lacking. Here, we sought to characterize the molecular landscape of breast MECs. Thirteen cases were histologically reviewed, characterized for tumor-infiltrating lymphocytes (TILs), and were subjected to immunohistochemistry for programmed death-ligand 1 (PD-L1, clone 22C3), EGFR, and amphiregulin (AREG). Rearrangements in MAML2 and EWSR1 were investigated by fluorescent in situ hybridization. Targeted next-generation sequencing of 161 genes was performed on eight cases. Most MECs had low histological grade (n = 10, 77%), with the presence of TILs (n = 9/12; 75%) and PD-L1 combined positive score ranging from 10 to 20 (n = 4/6; 67%). All cases showed EGFR and AREG overexpression and were fusion negative. Enrichment of genetic alterations was observed in PI3K/AKT/mTOR and cell cycle regulation pathways, while only one case harbored TP53 mutations. This is the first study providing extensive molecular data on breast MECs and the largest collection of cases available to date in the literature. Breast MECs lack TP53 mutations found in high-grade forms of triple-negative breast cancers and MAML2 or EWSR1 rearrangements pathognomonic of salivary MECs. Triple-negativity and PD-L1 positivity suggest a window of opportunity for immunotherapy in these patients. The EGFR/AREG axis activation, coupled with the mutational patterns in PI3K/AKT/mTOR and cell cycle pathways warrants caution in considering MECs as low-risk neoplasms.
Topics: Humans; DNA-Binding Proteins; Trans-Activators; B7-H1 Antigen; In Situ Hybridization, Fluorescence; Carcinoma, Mucoepidermoid; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Nuclear Proteins; Transcription Factors; Salivary Gland Neoplasms; ErbB Receptors; TOR Serine-Threonine Kinases; Biomarkers, Tumor
PubMed: 36916425
DOI: 10.1002/cam4.5754 -
Mucoepidermoid carcinoma of the head and neck: CRTC1/3 MAML 2 translocation and its prognosticators.European Archives of... May 2022Mucoepidermoid carcinoma (MEC) of the head and neck is a prevalent malignant salivary gland tumour with a reported good outcome. The aim of this study was to report the...
PURPOSE
Mucoepidermoid carcinoma (MEC) of the head and neck is a prevalent malignant salivary gland tumour with a reported good outcome. The aim of this study was to report the outcome in our centre.
METHODS
A retrospective chart analysis with survival analyses was performed combined with fluorescence in situ hybridization (FISH) analysis to assess CRTC1/3 MAML 2 fusion gene presence.
RESULTS
Sixty-four cases of MEC were identified. Median age at presentation was 51.4 years with a predominance for parotid gland involvement. Five, 10- and 20- year disease-free survival was 98%, 90% and 68%, respectively. Overall survival was 94%, 90% and 64%, respectively. Local recurrence was seen up to 14 years after primary diagnosis; distant metastases were diagnosed up to 17 years later. The overall recurrence rate was less than 20 per cent. CRTC1/3 MAML 2 fusion gene presence showed no survival benefit.
CONCLUSION
MEC of the head and neck has a favorable outcome with the exception of high-grade MEC. PNI and nodal involvement are not rare. CRTC1/3 MAML 2 fusion gene presence showed no survival benefit. The tendency for late onset of loco-regional and distant recurrence should not be underestimated.
Topics: Carcinoma, Mucoepidermoid; DNA-Binding Proteins; Humans; In Situ Hybridization, Fluorescence; Nuclear Proteins; Retrospective Studies; Salivary Gland Neoplasms; Trans-Activators; Transcription Factors; Translocation, Genetic
PubMed: 34405264
DOI: 10.1007/s00405-021-07039-2 -
Advances in Anatomic Pathology Jul 2022This review focuses on the heterogenous group of clear cell neoplasms of salivary glands and attempts to identify major differential diagnostic features. Within the head... (Review)
Review
This review focuses on the heterogenous group of clear cell neoplasms of salivary glands and attempts to identify major differential diagnostic features. Within the head and neck region, clear cells are found most commonly in salivary gland tumors, but may also be seen in tumors of squamous or odontogenic epithelial origin, primary or metastatic carcinomas, benign or malignant melanocytic lesions, or benign or malignant mesenchymal tumors. Clear cells occur fairly commonly among a wide variety of salivary gland neoplasms, but mostly they constitute only a minor component of the tumor cell population. Clear cells represent a major diagnostic feature in two salivary gland neoplasms, epithelial-myoepithelial carcinoma and hyalinizing clear cell carcinoma. In addition, salivary gland neoplasms composed predominantly of clear cells could also include clear cell variants of other salivary neoplasms, such as mucoepidermoid carcinoma and myoepithelial carcinoma, but their tumor type-specific histologic features may only be available in limited nonclear cell areas of the tumor. Diagnosing predominantly clear cell salivary gland tumors is difficult because the immunoprofiles and morphologic features may overlap and the same tumor entity may also have a wide range of other histologic presentations. Many salivary gland tumors are characterized by tumor type-specific genomic alterations, particularly gene fusions of the ETV6 gene in secretory carcinoma, the MYB and MYBL1 genes in adenoid cystic carcinoma, the MAML2 gene in mucoepidermoid carcinoma, the EWSR1 gene in hyalinizing clear cell carcinoma, and others. Thus, along with conventional histopathologic examination and immunoprofiling, molecular and genetic tests may be important in the diagnosis of salivary gland clear cell tumors by demonstrating genetic alterations specific to them.
Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Mucoepidermoid; Humans; Salivary Gland Neoplasms; Salivary Glands
PubMed: 35249992
DOI: 10.1097/PAP.0000000000000339 -
Indian Journal of Otolaryngology and... Oct 2022Pleomorphic adenoma (PA) is the most common salivary gland tumor, accounting for 54-76% of all salivary gland neoplasms. Extensive squamous metaplasia in PA can be...
Pleomorphic adenoma (PA) is the most common salivary gland tumor, accounting for 54-76% of all salivary gland neoplasms. Extensive squamous metaplasia in PA can be mistaken for malignancy, including low grade mucoepidermoid carcinoma and squamous cell carcinoma. Here, we present an unusual case of PA with extensive squamous metaplasia and keratin cyst formations in a minor salivary gland, and discuss its microscopic features, including the immunohistochemical characteristics, and differential diagnosis of this uncommon presentation.
PubMed: 36452717
DOI: 10.1007/s12070-020-02039-w -
Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi... Jan 2022Warthin-like mucoepidermoid carcinoma (MEC) is a recently identified MEC variant of the salivary gland. MEC morphologically mimics Warthin tumor (WT) but harbors the...
Warthin-like mucoepidermoid carcinoma (MEC) is a recently identified MEC variant of the salivary gland. MEC morphologically mimics Warthin tumor (WT) but harbors the same chromosomal translocation t (11; 19) (q21; p13) as MEC. Thus, differential diagnosis is crucial. MEC involving WT is extremely rare in salivary glands. In this study, we reported a case of Warthin-like MEC, a case of MEC co-existing with WT, and a case of mucinous metaplasia in WT. We also discussed the possible link between WT and MEC.
PubMed: 38597001
DOI: 10.7518/hxkq.2022.01.016 -
Laryngoscope Investigative... Jun 2022Mucoepidermoid carcinoma (MEC) is the most common malignancy of the parotid gland, but the outcome depends on the histological grade. Therefore, the aim of this study...
OBJECTIVE
Mucoepidermoid carcinoma (MEC) is the most common malignancy of the parotid gland, but the outcome depends on the histological grade. Therefore, the aim of this study was to evaluate MEC on the basis of histological grade.
STUDY DESIGN
Retrospective analysis.
METHODS
We performed a retrospective analysis of data from patients whose initial treatment for MEC of the parotid gland was performed at our department between 1999 and 2021. We examined the association between the Armed Forces Institute of Pathology (AFIP) grade and outcome.
RESULTS
The AFIP grades were as follows: low, 26 cases; intermediate, 9 cases; and high, 31 cases. About 50% of cases were correctly diagnosed as malignant, and both grade and histology were accurately determined by fine-needle aspiration cytology in 20% of cases. The 5-year disease-free survival rate was 95.5% and 53.8% in the low-/intermediate- and high-grade cases, respectively. In the high-grade group, cases with recurrence were found to have a higher rate of lymph nodes metastasis than cases without recurrence. Furthermore, in this high-grade group, total sacrifice of the facial nerve did not reduce local recurrence. However, radical resection in the cases without tumor invasion to the nerve has decreased the local recurrence rate. The CRTC1-MAML2 fusion gene was expressed in 42.3% of low-/intermediate- and 14.3% of high-grade cases.
CONCLUSIONS
The survival rate in MEC was quite different between the low-/intermediate- and high-grade cases. However, the rate of correct assessment of the grade by fine-needle aspiration cytology was poor. In high-grade cases, total sacrifice of the facial nerve may improve the rate of local recurrence in cases without invasion of the main trunk of the nerve. Expression of the CRTC1-MAML2 fusion gene could be helpful in not only the assessment of grade but the prediction of recurrence.
LEVEL OF EVIDENCE
4.
PubMed: 35734046
DOI: 10.1002/lio2.809 -
Journal of Oral Pathology & Medicine :... Nov 2023Mucoepidermoid carcinoma is a rare salivary gland malignant tumour. This study aimed to investigate inflammatory and immune signatures of mucoepidermoid carcinoma by...
BACKGROUND
Mucoepidermoid carcinoma is a rare salivary gland malignant tumour. This study aimed to investigate inflammatory and immune signatures of mucoepidermoid carcinoma by identifying potential proteo-transcriptomic biomarkers towards the development of precision immuno-oncology treatment strategies.
METHODS
A total of 30 biopsies obtained from patients diagnosed with mucoepidermoid carcinoma between 2013 and 2022 were analysed after H&E staining for scoring of histological inflammatory stroma subtypes and inflammatory hotspots with QuPath. Multiplex immunofluorescence staining and NanoString nCounter PanCancer IO 360™ panel were used to assess stroma and tumour inflammation signatures in high grade mucoepidermoid carcinoma cases in the tumour microenvironment via proteomics and transcriptomics, respectively.
RESULTS
Inflammatory cells within the histological inflammatory stroma inflammatory (HIS-INF/hot) tumour neighbourhoods were greater compared to the histological inflammatory stroma-immune desert (HIS-ID/cold) (p = 0.001). A similar trend was observed between treatment non-responders and responders in stroma neighbourhoods (p = 0.0625) and in stroma-to-interface inflammatory hotspots (p = 0.0081), indicating an augmented inflammatory response in hot tumours and non-responders. Furthermore, there were striking differences in the expression of pan-immune leukocyte marker CD45 between responders and non responders particularly in the tumour neighbourhoods (p = 0.0341), but such were not robust for PD-1 and macrophage fractions. Additionally, transcriptomic analysis revealed key differences in leukocyte activation profiles between responders and non-responders.
CONCLUSION
This preliminary report unveils the importance of assessing immune leukocyte cellular fractions and pathways for future prognostic biomarker discoveries in mucoepidermoid carcinoma as per the involvement of CD45-driven inflammatory and immune mediators in high grade mucoepidermoid carcinoma in non-responders to treatment. These findings will potentially contribute to the development of novel personalised immunotherapies.
Topics: Humans; Carcinoma, Mucoepidermoid; Salivary Gland Neoplasms; Prognosis; Salivary Glands; Tumor Microenvironment
PubMed: 37756121
DOI: 10.1111/jop.13488 -
American Journal of Ophthalmology Jul 2022In this study, we evaluated the clinicopathologic and molecular characteristics of lacrimal apparatus mucoepidermoid carcinoma (MEC) to define its typical diagnostic... (Observational Study)
Observational Study
PURPOSE
In this study, we evaluated the clinicopathologic and molecular characteristics of lacrimal apparatus mucoepidermoid carcinoma (MEC) to define its typical diagnostic features.
DESIGN
Retrospective observational case series.
METHODS
Institutional pathology records between 2011 and 2021 were searched for all cases of lacrimal apparatus MEC.
RESULTS
A total of 2 male and 6 female patients ranging in age from 18 to 83 years (median 56, mean 54) were included. Six lacrimal apparatus MECs were found in the lacrimal gland, and 2 cases occurred in the lacrimal sac and nasolacrimal duct. Histologically, there were 6 cases of conventional MEC, 1 clear-cell variant of MEC, and 1 oncocytic variant of MEC for a total of 8 cases. There were 3 low-grade cases and 5 high-grade cases. All 8 cases were evaluated via immunohistochemistry, and the results were positive (scores 1-4) for pankeratin, 34betaE12, p63, p40, CK7, CK8, and CK19, with a relatively higher expression of p63 observed in high-grade MEC. The presence of human papillomavirus (HPV) type 6 DNA was found in 4 patients. MAML2 fluorescence in situ hybridization was positive for MAML2 rearrangement in 3 lacrimal gland tumors (2 low-grade and 1 high-grade). Six tumors were managed with radical resection, and 2 patients underwent orbital exenteration. Postoperative radiation therapy was delivered to 6 patients, and chemotherapy was administered to 1 patient.
CONCLUSIONS
MECs of the lacrimal apparatus are rare tumors, and the rate of MAML2 translocations is lower than that in salivary MECs. Lacrimal gland and lacrimal sac MECs may not be of the same subtypes intrinsically because of the difference in MAML2 translocation, anatomy, and clinical course. The etiologic function of HPV type 6 infection should be explored in lacrimal apparatus MECs. Radical surgery is the treatment of choice. The description of these unique findings may assist in the definitive diagnosis of and improve our understanding of lacrimal apparatus MEC.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Mucoepidermoid; Eye Neoplasms; Female; Humans; In Situ Hybridization, Fluorescence; Lacrimal Apparatus; Male; Middle Aged; Papillomavirus Infections; Retrospective Studies; Salivary Gland Neoplasms; Trans-Activators; Translocation, Genetic; Young Adult
PubMed: 35288069
DOI: 10.1016/j.ajo.2022.03.008