Salivary Gland Mucoepidermoid Carcinoma Research Articles

Analysis of risk factors and construction of nomogram model for local lymph node metastasis in salivary gland mucoepidermoid carcinoma

Objective: To analyze the risk factors affecting regional lymph node metastasis in salivary gland mucoepidermoid carcinoma (MEC) and to establish a nomogram model for individually predicting lymph node metastasis in salivary gland MEC. Methods: The clinical data of 2 152 patients with salivary gland MEC from 1975 to 2020 were collected from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. The collected data were divided into training cohort (1 506 cases) and validation cohort (646 cases) according to the ratio of 7∶3. Single-factor regression and multi-factor logistic regression were used to screen factors related to local lymph node metastasis in salivary gland MEC, with constructing of a nomogram. Calibration curve, receiver operating characteristic (ROC) curve, area under the ROC curve (AUC) and decision curve analysis were used to evaluate model performance in the validation cohort and the total cohort. Statistical tests were performed using SPSS (26.0) and R (4.3.0) software. Results: Multivariate logistic regression results showed that M stage [OR(95%CI):12.360(3.295-46.365), P=0.014], pathological grade Ⅱ、Ⅲ、Ⅳ[OR(95%CI): 1.956(1.329-2.879), 9.654(6.309-14.772), 9.298(6.072-14.238), P<0.001], T staging T2, T3, T4[OR(95%CI): 1.706(0.932-3.124), 3.021(1.790-5.096), 3.311(1.925-5.695), P<0.001], and gender [OR(95%CI):0.759(0.593-0.972), P=0.029] were independent factors affecting local lymph node metastasis in salivary gland MEC. Through verification in the validation cohort and the total cohort, the AUC values were greater than 0.8, and the calibration curve was close to the perfect reference line, proving that the constructed nomogram model had good specificity and sensitivity for predicting local lymph node metastasis in salivary gland MEC. Conclusion: M stage, pathological grade, T stage, and gender are risk factors for predicting regional lymph node metastasis and the established-nomogram has good predictive performance for local lymph node metastasis in salivary gland MEC.

Number of positive lymph nodes affects oncologic outcomes in cN0 mucoepidermoid carcinoma of the major salivary gland.

The survival significance of the number of positive lymph nodes in salivary gland carcinoma remains unclear. Thus, the current study aimed to determine the effect of the number of positive lymph nodes on disease-specific survival (DSS) and overall survival (OS) in cN0 mucoepidermoid carcinoma (MEC) of the major salivary gland. Patients surgically treated for MEC of the major salivary gland between 1975 and 2019 were retrospectively enrolled from the surveillance, epidemiology, and end results database. The total population was randomly divided into training and test groups (1:1). Primary outcome variables were DSS and OS. Prognostic models were constructed based on the independent prognostic factors determined using univariate and multivariate Cox analyses in the training group and were validated in the test group using C-index. A total of 3317 patients (1624 men and 1693 women) with a mean age of 55 ± 20years were included. The number of positive lymph nodes was an independent prognostic factor for both DSS and OS, but the effect began when at least two positive lymph nodes for DSS and three positive lymph nodes for OS were found. Predictive models for DSS and OS in the training group had C-indexes of 0.873 (95% confidence interval [CI] 0.853-0.893) and 0.835 (95% CI 0.817-0.853), respectively. The validation of the test group showed C-indexes of 0.877 (95% CI 0.851-0.902) for DSS and 0.820 (95% CI 0.798-0.842) for OS. The number of positive lymph nodes was statistically associated with survival in cN0 major salivary gland MEC. The current prognostic model could provide individualized follow-up strategies for patients with high reliability.

Abstract P48: Advancing Personalized Anti-Cancer Pharmacotherapy: Magnetic Bioprinting of a Ductal Drug Screening Platform for Salivary Gland Mucoepidermoid Carcinoma

Abstract Mucoepidermoid carcinoma (MEC) is the most common malignant neoplasm of the salivary glands (SG), and it arises from “reserve” stem cells within the ductal network. Recently, our research team has consistently generated acinar-like epithelial SG organoids using a magnetic three-dimensional bioprinting (M3DB) platform. However, 3D ductal constructs with lumenized and functional features have not been established by biofabrication strategies due to challenges related to the lack of epithelial polarity and reproducibility. Consequently, our research unit is developing an in vitro high throughput drug screening platform with bio-printed ductal constructs as avatars of MEC ductal units towards a more effective and personalized anti-cancer pharmacotherapy. M3DB, multiplex immunofluorescence, western blot, and functional assays were performed. M3DB induced the formation of ring-like organoid 3D constructs after the magnetic bioassembly of MEC HTB41 cells overnight. These bio-printed constructs had a lumen formation efficiency of ~70% and contained functional E-cadherin+ cell clusters expressing ZO-1 with mainly K14+ and K5+ ductal progenitor populations with high pro-mitotic activity (Ki-67). These bio-printed ductal-like constructs were then proteomic and functionally evaluated in the presence or absence of 5-fluorouracil (5-FU), a chemotherapy drug. Proteomic assessments revealed changes in cellular antioxidant response (Nrf2) as well as DNA damage repair (γ-H2AX) after 5-FU exposure, potentially safeguarding cells from damage and halting cancer cell cycle progression. Tumor cell invasion capabilities within co-culture in mili-fluidic platforms, and functional evaluation with cholinergic and adrenergic agonists and swelling assays confirmed the 5-FU-induced cytotoxicity, decreased invasion potential, and ductal hypofunction. In summary, our team successfully established novel bio-printed MEC ductal-like avatar platforms that will pave the way for personalized pharmacotherapy and precision oncology in SG malignant tumors. Citation Format: Yamin Oo, Tien T.T. Truong, Toan V. Phan, Khurshid Ahmed, Teerapat Rodboon, Risa Chaisuparat, Glauco R. Souza, Joao N. Ferreira. Advancing Personalized Anti-Cancer Pharmacotherapy: Magnetic Bioprinting of a Ductal Drug Screening Platform for Salivary Gland Mucoepidermoid Carcinoma [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr P48.

Abstract 2999: Evaluation of microRNA expression in metastatic and non-metastatic salivary gland mucoepidermoid carcinoma

Abstract Salivary gland tumors are a heterogeneous group of lesions, being mucoepidermoid carcinoma (MEC) the malignant neoplasm with the highest incidence, occurring mainly in the parotid gland. Characterization of its histological grade (high, intermediate, and low) is important for determining patient prognosis. Metastasis is more common high-grade tumors and can occur at regional lymph nodes or distant sites. Although the mechanisms underlying the metastatic process are largely unknown, large-scale microRNA expression profiling studies of human cancers have demonstrated that dysregulation of miRNA is frequently associated with many cancer types. The aim of this study is to validate the use of microRNA expression for the discrimination of the metastatic potential of MEC samples. Using Real Time RT-PCR (qPCR) we have analyzed the expression of 384 miRNAs and controls in 4 non-metastatic MECs, 3 MECs with lymph node metastasis, 3 MECs with distant metastasis, and 2 non-neoplastic human salivary gland samples. Comparing the expression among these groups we identified 45 differentially expressed miRNAs that may be related with the metastatic potential of these tumors. To validate the microRNA expression associated with the metastatic potential, we selected 7 out of the 45 differentially expressed microRNAs and 7 MEC samples from the different groups of samples. Considering the 7 microRNAs evaluated, we validated that the expression of miR-191 was increased in non-neoplastic samples when compared to MECs with lymph node metastasis and the expression of miR-494 was increased in non-neoplastic samples when compared to MECs with distant metastasis, suggesting that loss of these microRNAs might be involved in the development of metastasis in mucoepidermoid carcinoma. The determination of a miRNA expression profile could provide a better understanding of the molecular basis of MEC and facilitate the determination of diagnosis and prognosis of patients. Citation Format: Maria E. Trevizani, Katia K. Oliveira, Fabio A. Marchi, Daniela Bizinelli, Fernanda V. Mariano, Cibele P. Nagano, Felipe A. Costa, Clovis A. Pinto, Luiz P. Kowalski, Silvia V. Lourenço, Cláudia M. Coutinho-Camillo. Evaluation of microRNA expression in metastatic and non-metastatic salivary gland mucoepidermoid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2999.

Correlation Between Demographic Features and PD-L2 Expression in Mucoepidermoid Carcinoma of Salivary Glands

OBJECTIVE: This study was conducted to determine PD-L2 expression and its association with grading in patients with mucoepidermoid carcinoma METHODOLOGY: : This descriptive study was conducted over a period of 1 year after taking approval from Institutional Ethical Review board. A total of twenty-four cases of MEC were recruited from different tertiary health care hospitals in Lahore and Multan. Data consisting of demographics and clinical features was collected. Histopathological analysis was done according to Seethala's grading system. Immunohistochemistry (IHC) was performed to observe PD-L2 expression. Data was analyzed by using SPSS 25 RESULTS: : The mean age was 30.08±12.8 years and there were 41.7% males and 58.3% females. Most common site of involvement was found to be parotid gland. A total of (54.2%) cases were of low grade. Strong PD-L2 expression was observed in 12(50%) cases while in 5(21%) cases there was week expression. No significant association of PD-L2 expression with grade of tumor was observed. CONCLUSIONS: Among salivary gland tumors, Mucoepidermoid carcinoma is emerging as most frequently diagnosed malignancy. These tumors originate mainly from parotid glands usually during fourth decade of life. As preliminary data generated from current research has highlighted the expression of PD-L2 in malignant MEC. The expression of PD-L2 was observed in all of the tissue specimens in the current study as detected through IHC irrespective of the grade of the tumor KEYWORDS: Programmed cell Death 1 Ligand 2 (PD-L2), Mucoepidermoid Carcinoma (MEC), ImmunohistoChemistry (IHC).

Evaluation of Immunohistochemical Expression of P53 and Pcna in Pleomorphic Adenoma, Mucoepidermoid and Adenoid Cystic Carcinomas of Salivary Glands

Salivary gland tumours are uncommon with a broad heterogeneity. The most common benign tumour is the pleomorphic adenoma, whereas mucoepider moid carcinoma and adenoid cystic carcinoma predominate among the malignancies. The aim of this study was to describe the tissue expression of p53 and PCNA protein in pleomorphic adenoma, mucoepidermoid carcinoma and adenoid cystic carcinoma and to compare their expression among the studied tumors. The study enrolled (45)formalin –fixed, paraffin- embedded tissue blocks of salivary gland tumors, diagnosed as pleomorphic adenoma, mucoepidermoid carcinoma and adenoid cystic carcinoma (15 cases for each ) and evaluated the immunohistochemical expression of P53 and PCNA proteins. The study revealed positive p53 protein expression in (60%) of muocoepidermoid carcinoma cases and (20%) of adenoid cystic carcinoma cases, while only one case (6.7%) of pleomorphic adenoma was P53 posi tive. The immunopositivity of PCNA protein expression was f ound in (100%) of both mucoepidermoid carcinoma and adenoid cystic carcinoma cases and (66.7%) of pleomorphic adenoma c ases.The results of this study demonstrated that inactivation of p53 protein may play an im portant role in the activation of PCNA with increasing the proliferati on activity of MEC and ACC.

Identifying potential immuno-oncology targets in salivary gland mucoepidermoid carcinoma based on inflammatory status and treatment response.

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. 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. 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. 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.

Effects of bisphenol A on murine salivary glands and human tumor cell lines

Bisphenol A (BPA) is an endocrine-disrupting chemical with a potential role in endocrine cancers. However, the effects of BPA on the salivary glands have been barely explored. We investigated the impact of in vivo sub-chronic exposure to BPA and its in vitro effects on human salivary gland mucoepidermoid carcinoma cell lines. Male and female mice were exposed to BPA (30 mg/kg/day). Sublingual and submandibular salivary glands from an estrogen-deficiency model were also analyzed. BPA concentration in salivary glands was evaluated by gas chromatography coupled to ion trap mass spectrometry. Immunohistochemical analysis using anti-p63 and anti-α-SMA antibodies was performed on mouse salivary gland tissues. Gene expression of estrogen receptors alpha and beta, P63 and α-SMA was quantified in mouse salivary gland and/or mucoepidermoid (UM-HMC-1 and UM-HMC-3A) cell lines. Cell viability, p63 and Ki-67 immunostaining were evaluated in vitro. BPA disrupted the tissue architecture of the submandibular and sublingual glands, particularly in female mice, and increased the expression of estrogen receptors and p63, effects that were accompanied by significant BPA accumulation in these tissues. Conversely, ovariectomy slightly impacted BPA-induced morphological changes. In vitro, BPA did not affect the proliferation of neoplastic cells, but augmented the expression of p63 and estrogen receptors. The present data highlight a potential harmful effect of BPA on salivary gland tissues, particularly in female mice, and salivary gland tumor cells. Our findings suggest that estrogen-dependent pathways may orchestrate the effects of BPA in salivary glands.

Critical Appraisal of Histologic Grading for Mucoepidermoid Carcinoma of Salivary Gland: Is an Objective Prognostic 2-tiered Grading System Possible?

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) ≥4/2mm 2 (4/10HPFs), 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%.

Two Head and Neck Carcinomas With Squamous and Mucinous Components and Human Papillomavirus Associations: Maxillary Mucoepidermoid Carcinoma ex Sinonasal Schneiderian Papilloma and Tonsillar Invasive Stratified Mucin Producing Carcinoma (ISMC).

Carcinomas of the head-and-neck region with squamous and glandular/mucinous features constitute a heterogeneous group, with a significant minority of tumors showing an human papillomavirus (HPV) association. The differential diagnosis is usually between mucoepidermoid carcinoma (MEC) and adenosquamous carcinoma. We present here two tumors that exemplify both the challenges of diagnostic classification, as well as the complex relationship to HPV: (a) a low risk HPV positive/p16 negative carcinoma that is most consistent with a relatively typical intermediate grade mucoepidermoid type carcinoma with complete MEC phenotype (three cell types), originating from intranasal sinonasal papillomas with exophytic and inverted patterns, and invading surrounding maxillary compartments, and (b) a p16 and keratin 7 (KRT7) positive carcinoma of the right tonsil, characterized by stratified squamous and mucinous cell (mucocyte) features. Whereas the first tumor represents a typical MEC ex-Schneiderian papilloma, the second is morphologically most consistent with the, novel for this anatomic location, diagnosis of "invasive stratified mucin producing carcinoma" (ISMC), pointing to an analogy to similar, high-risk HPV-driven malignancies recently described in the gynecologic (GYN) and genitourinary (GU) areas. Both tumors, despite their mucoepidermoid-like features had no connection to salivary glands and lacked the MAML2 translocation typical of salivary gland MEC, pointing to a mucosal/non-salivary gland origin. Using these two carcinomas as examples, we attempt to address questions related to: (a) the histological distinction between MEC, adenosquamous carcinoma, and ISMC, (b) similarities and differences between these histological entities in mucosal sites versus morphologically similar salivary gland tumors, and (c) the role of HPV in these tumors.

Immunoexpression of Autophagy-Related Proteins in Salivary Gland Tumors: An Exploratory Study.

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.

Epidemiological and clinical characteristics of synchronous lung metastasis in major salivary gland mucoepidermoid carcinoma.

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.

Abstract 3763: microRNAs associated with metastatic potential in salivary gland mucoepidermoid carcinoma

Abstract Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the salivary glands. Metastatic spread occurs in up to 80% of high-grade tumors and it is a strong predictor of poor outcome, however, the mechanisms underlying this process are largely unknown. Large-scale microRNA expression profiling studies of human cancers have demonstrated that dysregulation of miRNA is frequently associated with many cancer types. The aim of this study was to investigate the microRNA profile in metastatic versus non-metastatic MECs. Using Real Time RT-PCR (qPCR) we have analyzed the expression of 384 miRNAs and controls in 4 non-metastatic MECs, 3 MECs with lymph node metastasis, 3 MECs with distant metastasis, and 2 non-neoplastic human salivary gland samples. The microRNA profile was able to discriminate between non-neoplastic and tumor samples and between metastatic and non-metastatic tumors. Considering non-neoplastic samples and non-metastatic MECs, 12 microRNAs were differentially expressed. The non-neoplastic versus lymph node metastasis MEC analysis demonstrated that 10 microRNAs were differentially expressed. Considering non-neoplastic versus distant metastasis MECs, 3 microRNAs were differentially expressed: 1 down-regulated and 2 up-regulated. Comparing non-metastatic MECs versus lymph node metastasis MECs we observed 17 up-regulated microRNAs. Considering non-metastatic MECs versus distant metastasis MECs, 2 microRNAs were up-regulated. One microRNA is differentially expressed between lymph node metastasis MECs and distant metastasis MECs. Our results suggest that microRNA profiles could discriminate the metastatic potential of salivary MECs and might be helpful in diagnostic and prognostic evaluation of patients. Citation Format: Maria Eduarda S. Trevizani, Katia K. Oliveira, Fabio A. Marchi, Daniela Bizinelli, Fernanda V. Mariano, Cibele P. Nagano, Felipe A. Costa, Clóvis A. Pinto, Luiz P. Kowalski, Silvia V. Lourenço, Cláudia M. Coutinho-Camillo. microRNAs associated with metastatic potential in salivary gland mucoepidermoid carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3763.

Mucoepidermoid Carcinoma of Breast Presenting as Abscess-like Pus Discharging Mass; A Rare Tumour With Unusual Presentation

Background: Mucoepidermoid carcinoma (MEC) breast is a very rare triple negative breast cancer with relatively better overall prognosis. They have histomorphological and immunohistochemical features similar to the salivary gland MEC. Literature suggests that they also carry molecular characteristics similar to the salivary gland MEC. Case Presentation: A 73-years-old woman presented with complaints of painful, foul smelling pus discharging mass in right breast. Patient underwent therapeutic incision and drainage along with diagnostic biopsy. On histopathology, diagnosis of MEC, high grade was made. Conclusion: Primary MEC is a very rare triple negative breast cancer (TNBC) usually with much better survival outcome in comparison to other TNBCs. However, the index case had locally advanced disease with unique presentation leading to an alternative initial management.

LAMB3 and TACSTD2, both highly expressed in salivary gland mucoepidermoid carcinoma, represent potential diagnostic biomarkers and therapeutic targets

Salivary mucoepidermoid carcinoma (MEC) is the most common malignant tumor in major and minor salivary glands. The CRTC1-MAML2 or CRTC3-MAML2 gene arrangements, which occur in up to 80% of primary salivary glands with MEC, are the major oncogenic drivers of MEC carcinogenesis. However, the molecular consequences of these fusions remain unknown. We sought to identify the key functional genes involved in MEC, then characterize biomarkers with potential therapeutic relevance. We analyzed the gene expression profiles of two primary tumors (fusion-positive HCM-MEC020T and fusion-negative HCM-MEC030T); we compared them with the profiles of the established cell line HCM-MEC010 (derived from CRTC1-MAML2 fusion-positive MEC) and fibroblast cells derived from an HCM-MEC010 patient (non-tumor control cells). Fifty-three genes were identified as commonly expressed genes among the top 500 highly expressed genes in MEC but not in fibroblasts. Among these 53 genes, we focused on LAMB3 and TACSTD2, which are not predicted to be CRTC1/CRTC3-MAML2 target genes. LAMB3 (laminin subunit beta-3) is the basement membrane protein in normal salivary glands. TACSTD2 encodes a membrane protein associated with calcium signaling. To investigate the relationship between gene expression patterns and MEC pathological grade, we performed immunohistochemical staining of 13 MEC samples. LAMB3 and TACSTD2 proteins were expressed in the tumor cells of MEC samples (LAMB3, 12/13; TACSTD2, 13/13) but not in surrounding stromal cells. Although there were no statistically significant differences in LAMB3 or TACSTD2 expression among pathological grades, further studies are needed to elucidate the value of LAMB3 and TACSTD2 in clinical applications.

Mire and Pelage-Mucoepidermoid Carcinoma Salivary Gland

Mucoepidermoid carcinoma of salivary gland is a frequently encountered, malignant neoplasm arising from salivary gland epithelium constituted of mucous cells, intermediate cells and epidermoid cells. Tumefaction is associated with specific chromosomal translocation t(11;19)(q14-21;p12-13) and CRTC1(MECT1)-MAML2 genetic fusion. Median age of disease emergence is 49 years and a mild female preponderance is observed. Neoplasm predominantly incriminates major salivary glands as the parotid gland. Tumefaction depicts a solid, cystic or dual configuration and is composed of neoplastic epidermoid cells demonstrating solid nests, sheets or cellular cords along with varying proportion of epidermoid cells, intermediate cells or mucocytes. Tumour cells appear immune reactive to pan-cytokeratin, CK5/6, p63, p40, epithelial membrane antigen(EMA), CK7 or CK14. Membrane bound mucins appear immune reactive to MUC1, MUC2, MUC4, MUC5AC and MUC5B. Mucoepidermoid carcinoma requires segregation from neoplasms such as pleomorphic adenoma with squamous cell and mucinous cell metaplasia, necrotizing sialometaplasia, Warthin tumour with squamous metaplasia, acinic cell carcinoma, mammary analogue secretory carcinoma (MASC), primary or secondary squamous cell carcinoma or salivary duct carcinoma. Preoperative assessment with ultrasonography or fine needle aspiration cytology may be beneficially employed. Tumefaction may be subjected to comprehensive surgical eradication with excision of broad perimeter of uninvolved, circumscribing soft tissue.

Expresión de la mucina asociada a membrana MUC-1/ y su relación con Ki67 en el carcinoma mucoepidermoide de glándulas salivales

Background: Salivary gland tumors are rare and with different malignant potential. Immunohistochemistry is useful, especially Ki67, a marker of cell proliferation, for its prognostic information. On the other side, the mucin MUC-1 is overexpressed and loses its exclusively apical membranous localization and is aberrantly glycosylated in mucoepidermoid carcinoma of salivary glands. In the present work, we investigated the quantitative expression of tumor proliferative index and localization and overexpression of MUC-1 in the mucoepidermoid carcinoma of the human salivary glands, not studied is these organs, to determine their relationship with the histological grade and prognosis. Methods: H/E staining and immunohistochemistry with MUC-1 and Ki67 antibodies was performed on 10 cases. Results: The markings of the mucoepidermoid carcinoma depended on the histological grade; in low- grade tumors with MUC-1 only 10 to 25% of the cells were labeled, in contrast to high- grade tumors, with 75 to 90% labeled cells. They also differed in cell proliferation; in the low-grade tumors was 15% and in high-grade tumors it was greater than 30%. Conclusion: MUC-1 overexpression is significantly higher in high-grade mucoepidermoid carcinoma, as is Ki67 marking, results that are associated with tumor prognosis.

Immunohistochemical Expression of EZH2 in Mucoepidermoid Carcinoma of Salivary Glands

Immunohistochemical Expression of EZH2 in Mucoepidermoid Carcinoma of Salivary Glands

Case Report on Mucoepidermoid Carcinoma of Salivary Gland

Background: The most prevalent kind of salivary gland cancer is mucoepidermoid carcinoma. The main clinical signs of Salivary gland mucoepidermoid carcinoma region is characterized by a lump in the face, neck, discomfort in the mouth, or trouble swallowing. The initial therapy is the surgical removal of the whole tumor .and in the final stage of chemotherapy, radiation therapy is also used. A 43year old male came to the medicine unit with complaints of edema all over the right-side face below the right ear since from 1 year. loss of appetite and disturbance in sleeping patterns. As per the patient’s verbalization, he was apparently all right before a year, and after that, he started to show swelling over the right side of the face and below the right ear for 1 year, for he took treatment in the primary health care center. But after 4 months it was not relieved so again, he went to the private hospital where he has treated with anti-inflammatory medications but still got no relief. Later this swelling was associated with the loss of appetite and disturbance in sleeping patterns now after a year he came to the tertiary care hospital for management. Salivary gland cancer represents 5% of total head and neck tissue cancers. tumors. Small salivary gland tumors, which make up 10% to Approximately Malignant salivary gland neoplasms make up 15% of all cases. The second most frequent cancer type is mucoepidermoid carcinoma. tiny tumors of the salivary glands are common. (12–40 percent worldwide).

Case Report on Mucoepidermoid Carcinoma of Salivary Gland

Background: The most prevalent kind of salivary gland cancer is mucoepidermoid carcinoma. The main clinical signs of Salivary gland mucoepidermoid carcinoma region is characterized by a lump in the face, neck, discomfort in the mouth, or trouble swallowing. The initial therapy is the surgical removal of the whole tumor .and in the final stage of chemotherapy, radiation therapy is also used. A 43year old male came to the medicine unit with complaints of edema all over the right-side face below the right ear since from 1 year. loss of appetite and disturbance in sleeping patterns. As per the patient’s verbalization, he was apparently all right before a year, and after that, he started to show swelling over the right side of the face and below the right ear for 1 year, for he took treatment in the primary health care center. But after 4 months it was not relieved so again, he went to the private hospital where he has treated with anti-inflammatory medications but still got no relief. Later this swelling was associated with the loss of appetite and disturbance in sleeping patterns now after a year he came to the tertiary care hospital for management. Salivary gland cancer represents 5% of total head and neck tissue cancers. tumors. Small salivary gland tumors, which make up 10% to Approximately Malignant salivary gland neoplasms make up 15% of all cases. The second most frequent cancer type is mucoepidermoid carcinoma. tiny tumors of the salivary glands are common. (12–40 percent worldwide).