High-grade Mucoepidermoid Carcinoma Research Articles

Abstract 3911: A FGFR-p53 developmental signaling axis drives progression of salivary cancer

Abstract Mucoepidermoid carcinoma (MEC) is the most frequently occurring salivary gland (SG) malignancy. Treatments for high grade (HG) MEC are lacking due to a limited understanding of its diverse histological and clinical features. Consequently, patients with non-resectable HG MEC are often treated with adjuvant radiotherapy and suffer from increased rates of recurrence and metastasis with poor 5-year survival rates (30-50%) as compared to low grade (LG) MEC (76-95%). We previously demonstrated a role for IGF-1 signaling, an important mediator for SG development and branching morphogenesis, in MEC pathogenesis (Musicant et al, 2021). Here, we analyzed transcriptome profiles shared between fetal and adult normal parotid (PAR) tissues with MEC tumors to investigate programs involved in MEC progression. Using this information, we developed the first genetically engineered mouse model (GEMM) of advanced HG MEC via targeted oncogene expression in SG ductal cells. MEC samples from 21 PAR tumors (8 LG/13 HG), 8 age-matched normal, and 3 fetal PAR glands aged between 22-24 weeks of gestation (Saitou et al, 2020) were retrospectively collected from UCSF or UNC Surgical Pathology. RNAseq was performed on FFPE samples using Illumina HiSeq. Differential gene expression, gene set enrichment analyses (GSEA), and alternative splicing analyses were compared between fetal/normal/MEC according to tumor grade and CRTC1 (CREB-regulated transcription coactivator 1)/MAML2 (Mastermind-like 2) (C1/M2) status. Based on these analyses, we developed a GEMM combining C1/M2 expression with TP53 loss. GEMM tumors were subjected to RNAseq and reviewed by two independent pathologists for diagnostic confirmation of HG MEC.GSEA revealed significant overlap between MEC tumors and fetal SG for genes governing proliferation and developmental pathways associated with branching morphogenesis. Interestingly, upregulation of the negatively regulated p53 target FOXM1 along with a mutant-p53 gene signature (Troester et al, 2006) revealed that p53 dysregulation in HG tumors phenocopies that seen in fetal SG. Cre-inducible expression of C1/M2 alone was insufficient to induce MEC-like lesions when targeted to distinct salivary cell types (ductal Krt14-CreER, acinar Mist1-CreER, serous demilune Dcpp1-CreER). However, p53 alteration (Tp53KO) with ductal C1/M2 expression drove MEC formation with histological and molecular features of human HG-MEC. Notably, transcriptome profiles implicate an FGFR-p53 developmental signaling axis in MEC progression. Our autochthonous GEMM recapitulates advanced HG-MEC in vivo providing the field with a powerful platform for identifying pathways for developing targeted therapies. Taken together, the integrated bioinformatics and mouse modeling of this study provide a critical step toward elucidating salivary MEC progression and suggest a role for FGFR targeted therapies in the treatment of non-resectable HG MEC. Citation Format: Julia M. Billington, Adele M. Musicant, Jessica L. Cote, Jennifer Modliszewski, Yi-Hsuan Tsai, Luane J. Landuau, John Powers, Renee Betancourt, Radhika Sekhri, Ricardo J. Padilla, Juan C. Hernandez-Prera, David N. Hayes, Trevor G. Hackman, Omer Gokcumen, Sarah M. Knox, Jimena Guidice, Antonio L. Amelio. A FGFR-p53 developmental signaling axis drives progression of salivary cancer [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 3911.

Exploring Immunological Effects and Novel Immune Adjuvants in Immunotherapy for Salivary Gland Cancers.

Salivary gland cancer (SGC) is rare and comprises over 20 histological subtypes. Recently, clinical experience regarding immunotherapies for SGCs has been accumulating, yet their efficacy remains controversial. Understanding the tumor microenvironment (TME), including the expression of immune checkpoint molecules in SGC, is crucial to optimizing immunotherapy. In this review, we demonstrate that high-grade mucoepidermoid carcinoma and salivary duct carcinoma generally exhibit immune-hot TME with high immune cell infiltration, frequent genetic mutations, and robust immune checkpoint molecule expression. In contrast, adenoid cystic carcinomas exhibit an immune-cold TME. While the reported efficacy of immune checkpoint inhibitors (ICIs) for SGCs is generally poor, several studies showed promising clinical efficacy of ICIs, with an objective response rate ranging from 20.0-33.3%, indicating that ICIs might be beneficial for a specific population of SGC. Molecule-targeted therapies including anti-human epidermal growth factor receptor 2 and anti-androgen receptor therapies have shown promising clinical efficacy against SGC. Recent evidence indicates that these molecules could be targets for antigen-specific immunotherapies including chimeric antigen receptor-T therapy and cancer vaccines. This review discusses the current understanding and future directions of immunotherapies for SGCs, including ongoing clinical trials.

Survival Impact of Elective Neck Dissection and Adjuvant Radiation in N0 High-Grade Mucoepidermoid Carcinoma.

We aim to evaluate the role of elective neck dissection (END) and adjuvant radiation on survival in N0 high-grade mucoepidermoid carcinoma (MEC). Retrospective cohort study. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. All patients diagnosed with high-grade MEC with node-negative disease (N0) from 2004 to 2018 were included. Demographic, clinicopathologic, treatment, and outcomes were analyzed. Kaplan-Meier survival curves were used to evaluate 5-year disease-specific survival (DSS) and 5-year overall survival (OS). Multivariate Cox regression analysis was used to control for confounders. A total of 310 patients with high-grade MEC and N0 (clinical and pathologic) disease were identified. The parotid was the most common primary site (266, 86%). Of included patients, 133 (42.9%) were T3-T4 tumors and 212 (68%) received adjuvant radiation. END was performed on 223 (71.9%) of cases. END in T3-T4 high-grade MEC led to significant improvements in DSS (74.3% vs 34.0%, P < .01) and OS (55.2% vs 20.5%, P < .01) as compared to no END. Subanalysis shows that in patients who received neck dissections and were pathologic N0, adjuvant radiation had no impact on DSS (84.0% vs 72.1%, P = .45) and OS (52.1% vs 55.8%, P = .91). Benefits persisted when controlling for confounders using multivariate Cox proportional regression. Patients with T3-T4 high-grade MEC who underwent END and found to be pathologically node-negative (pN0) had significantly improved 5-year DSS and 5-year OS than patients who were cN0 and did not undergo END. Importantly, although 68% of patients received adjuvant radiation, we show no benefit of this treatment modality on outcomes in pN0 high-grade MEC.

A high-grade breast mucoepidermoid carcinoma without MAML2 rearrangement: A case report and literature review.

Mucoepidermoid carcinoma (MEC) of the breast is an extremely rare primary breast tumor. Between 1979 and June 2022, only 50 cases were reported. The pathological morphology and biological behavior of breast MEC remain poorly understood. A 47-year-old female was presented with a 10-day-old left breast mass detected by physical examination. Ultrasonography could not distinguish whether the breast tumor was benign or malignant. After a biopsy of a breast tumor excision specimen, combined with immunohistochemical results, the patient was diagnosed with high-grade mucoepidermoid breast carcinoma. The patient underwent a modified radical mastectomy for her left breast. The patient was still free from local recurrence or metastases at 1-year follow-up. A high-grade MEC case without MAML2 rearrangement shows good recovery without complications. The diagnosis was confirmed by histomorphology and immunohistochemical markers. It is sometimes necessary to distinguish it from adenosquamous, adenoid cystic, or mucinous carcinoma. The primary treatment is surgical resection, and the prognosis is closely related to the pathological grade.

High-grade HER2-positive mucoepidermoid carcinoma of the breast: a case report and review of the literature

BackgroundMucoepidermoid carcinoma of the breast is a rare special type of salivary gland-like tumor of the breast, usually displaying triple-negative phenotype. To date, only 64 cases have been reported in the English literature. Herein, we report the first case of mucoepidermoid carcinoma of the breast with human epidermal growth factor receptor 2 gene amplification.Case presentationA 58-year-old Caucasian woman treated with breast-conserving surgery, radiotherapy, and chemotherapy for an invasive breast carcinoma of no special type, relapsed 20 years later in the ipsilateral left breast. Histological examination of the core needle biopsy of the relapse deferred to the surgical specimen for the definitive diagnosis, because of the broad differential diagnosis. On the resected specimen we observed the presence of a poorly differentiated carcinoma with mucoepidermoid carcinoma of the breast typical features consisting of epidermoid, intermediate and mucinous cells lacking true keratinization, in keeping with the latest World Health Organization diagnostic criteria. The mucoepidermoid carcinoma of the breast was weakly estrogen receptor and androgen receptor positive and progesterone receptor negative, but exceptionally showed human epidermal growth factor receptor 2 gene amplification. Mastermind-like transcriptional coactivator 2 gene translocations were not detected by fluorescent in situ hybridization. The patient received adjuvant chemotherapy with anti-human epidermal growth factor receptor 2 therapy but no endocrine therapy. After 61 months of follow-up, no signs of local or distant recurrence were observed.ConclusionsMucoepidermoid carcinoma of the breast is a very rare entity. Despite being most frequently triple negative, the standard evaluation of receptor status is mandatory, as well as strict application of World Health Organization diagnostic criteria for correct patient management.

Pleural recurrence 21 years after complete resection of thymic mucoepidermoid carcinoma: a case report

BackgroundThymic mucoepidermoid carcinomas (MECs) are extremely rare malignant neoplasms. We describe a rare case of a MEC with a high histological grade in a patient who survived for more than 20 years after the initial surgery, focusing on the clinical course and recurrence pattern.Case presentationA woman underwent surgical resection of a high-grade thymic MEC at another hospital 21 years ago. At the age of 79, she was referred to our hospital with an abnormal opacity incidentally found on her chest radiograph during a health check-up. After the percutaneous biopsy diagnosed thymic MEC, surgical resection was planned based on imaging findings, considering pulmonary metastasis. Intraoperatively, a large tumor and several nodules were detected within the parietal pleura; furthermore, pleural dissemination of the MEC was diagnosed by intraoperative rapid histological evaluation. We completed an exploratory thoracoscopic procedure without performing resection. She did not wish to undergo adjuvant therapy after surgery. Currently, the tumor is growing slowly, but the patient is asymptomatic and is being followed up without treatment intervention.ConclusionWe encountered a rare case of pleural recurrence 21 years after complete resection of thymic MEC. Whether surgical resection, including volume reduction surgery, should be used as a treatment strategy for thymic carcinoma with dissemination requires further discussion.

High Grade Mucoepidermoid Carcinoma on Parotid Gland: Case Report and Literature Review

High Grade Mucoepidermoid Carcinoma on Parotid Gland: Case Report and Literature Review

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.

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%.

Primary High-Grade Mucoepidermoid Carcinoma Lung Mimicking Endobronchial Papilloma: A Case Report and Review of Literature

Primary mucoepidermoid carcinomas (MECs) of the lung are rare and present a diagnostic challenge. MEC lung comes under the broad classification of primary salivary gland type tumours of the lung. It usually involves large airways and presents clinically and radiologically with non-specific features. We report the case of a 26-year-old female patient wherein an initial clinicoradiological consideration of tuberculosis and biopsy report of endobronchial papilloma led to misdiagnosis and treatment delay. Flexible bronchoscopic biopsy confirmed the diagnosis of MEC following which patient underwent curative pulmonary sleeve resection with good post-operative outcome. Final histopathology revealed high-grade MEC, stage as pT2N0, and thus, patient is receiving cisplatin-based adjuvant chemotherapy. More studies and reporting of such cases are needed to formulate guidelines and avoid delay in management.

Head and neck mucoepidermoid carcinoma: does AFIP histological grading correlate with rate of nodal metastases?

The aim of this study is to retrospectively evaluate the presentation of head and neck mucoepidermoid carcinoma at the Royal Melbourne Hospital and identify the significance of AFIP histological grading on the risk of neck metastasis and cancer free survival. This study is a retrospective cohort analysis of patients treated for head and neck mucoepidermoid carcinoma at the RMH between 2005 and 2022. Patient demographics, treatment, pathology, in particular the AFIP histological grading of the primary tumour, and outcomes were collected and tabulated. Time to recurrence was recorded, and survival outcomes were calculated with Kaplan-Meier method. Comparisons were made on different histological grading and regional metastases. Thirty-three patients were identified and thirty met the inclusion criteria. There was an age range of 18-77 years (median 54 years) with no significant sex difference. Our patients had a 94% 5-year survival and an 86% 10-year survival. Thirteen patients had elective neck dissection and 2 out of 13 (15%) of the patients had positive neck disease. Of the two patients with regional metastasis, the primary tumour was graded as intermediate and low grade. No high-grade MEC patients had regional metastasis. Mucoepidermoid carcinoma of the head and neck is associated with a good disease-specific and overall survival despite the presence of regional metastasis. The AFIP histological grading system did not have a statistically significant correlation to the incidence of nodal metastasis.

Increased Chymase-Positive Mast Cells in High-Grade Mucoepidermoid Carcinoma of the Parotid Gland

It has long been known that high-grade mucoepidermoid carcinoma (MEC) has a poor prognosis, but the detailed molecular and biological mechanisms underlying this are not fully understood. In the present study, the pattern of chymase-positive mast cells, as well as chymase gene expression, in high-grade MEC was compared to that of low-grade and intermediate-grade MEC by using 44 resected tumor samples of MEC of the parotid gland. Chymase expression, as well as chymase-positive mast cells, was found to be markedly increased in high-grade MEC. Significant increases in PCNA-positive cells and VEGF gene expression, as well as lymphangiogenesis, were also confirmed in high-grade MEC. Chymase substrates, such as the latent transforming growth factor-beta (TGF-β) 1 and pro-matrix metalloproteinase (MMP)-9, were also detected immunohistologically in high-grade MEC. These findings suggested that the increased chymase activity may increase proliferative activity, as well as metastasis in the malignant condition, and the inhibition of chymase may be a strategy to improve the poor prognosis of high-grade MEC of the parotid gland.

SIMULTANEOUS DIAGNOSIS OF ERYTHRODERMIC POIKILODERMATOUS MYCOSIS FUNGOIDES AND MUCOEPIDERMOID CARCINOMA OF THE RIGHT MAXILLARY SINUS

Background: Poikilodermatous mycosis fungoides (pMF) is a very rare variant of cutaneous T lymphoma. We describe a rare case of erythrodermic poikilodermatous MF associated with mucoepidermoid carcinoma of the right maxillary sinus. Case report: A 66-year-old patient was admitted to the dermatology department for a dry pruritic and poikilodermic erythroderma that had been evolving for two years. He also reported a right unilateral nasal obstruction evolving for one and a half years. Histological examination showed an orthokeratotic epidermis and an edematous superficial and middle dermis, with a thick band of lymphocytic infiltrate in the subepidermis. This infiltrate was made of atypical lymphoid elements of mixed CD3+, CD4+, and CD8+ T phenotype with epidermotropism, allowing for diagnosis of poikilodermic MF to be made. A Deep biopsy of the right maxillary sinus had concluded a high-grade mucoepidermoid carcinoma. Conclusion: Although it is impossible to demonstrate a causal relationship between erythrodermic poikilodermatous MF and our patients mucoepidermoid carcinoma, this observation illustrates that in case of dissociated evolution under treatment of a poikilodermatous erythrodermic MF, the search for a second cancer is desirable. The association between poikilodermatous erythrodermic MF and Hematologic or Solid malignancies, requires long-term follow-up and conditions the prognosis of patients.

Huge Recurrent Mucoepidermoid Carcinoma of Parotid - a Rare Presentation.

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 20cm 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.

Clinicopathological practice in the differential diagnosis of mucoepidermoid carcinoma from neoplasms with mucinous component.

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.

Role of Cross-sectional Imaging in Evaluation of Parotid Gland Tumours: A Pictorial Review

Radiological evaluation of the parotid gland neoplasms is a major challenge for radiologists, due to the wide variety of imaging features and differential diagnosis. Though Ultrasonography (USG) combined with guided Fine Needle Aspiration Cytology (FNAC) is the primary diagnostic modality, Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) play an important role in the evaluation of patients presenting with suspected neoplastic lesions of the parotid gland. Cross-sectional imaging data of seven patients were selected and reviewed in detail. CT and MRI imaging had been done on patients referred to Radiology Department for clinically suspected parotid tumours. All of them underwent surgical excision and histopathological examination postimaging. Benign tumours usually arise from superficial lobe and exhibit strong signal intensity on T2 weighted images with well-defined margins. Lobulated margins with T2 dark rim are characteristic of pleomorphic adenoma. Hyperdense lesion with cystic changes with occasional bilateralism favour Warthin’s tumour. Most of the malignant parotid tumours involve deep lobe and appear as low signal lesion on T2 weighted imaging with ill-defined margins. Locally aggressive features like subcutaneous/deep infiltration strongly suggests malignancy. Cross-sectional imaging feature of carcinoma ex pleomorphic adenoma is variable from focally aggressive to totally aggressive tumourigenesis. Few malignant tumours like high-grade Mucoepidermoid Carcinoma (MEC) and Adenoid Cystic Carcinoma (AdCC) can show tendency towards perineural spread. Although histopathological examination is required for definitive diagnosis, few pathology-specific imaging findings on cross-sectional imaging can help in localising and characterising the parotid lesions and categorising innocuous benign from sinister malignant lesions and thus narrow down the differential diagnosis.

High-grade pulmonary mucoepidermoid carcinoma supplied by the pulmonary artery and vein in a 6-year-old child: a case description and literature analysis

High-grade pulmonary mucoepidermoid carcinoma supplied by the pulmonary artery and vein in a 6-year-old child: a case description and literature analysis

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.

Adenosquamous Carcinomas and Mucinous Adenocarcinoma of the Minor Salivary Glands: Immunohistochemical and Molecular Insights

There is confusion about the diagnosis, histogenesis and taxonomical efforts regarding adenosquamous carcinomas (ASCs) and mucinous adenocarcinomas (MACs), especially with calls for reconsidering the nature of high-grade mucoepidermoid carcinoma (MEC). This study aims to compare the genetic profiles of ASCs and MACs that have been previously reported in the literature and investigate if either ASC or MAC is closer in genetic mutations to high-grade MEC. Systematic searches in the NCBI, Web of Science, and Scopus databases were performed between January 2000 and August 2022. The retrieved genetic mutations were processed and annotated. Protein–protein network analysis was conducted for each neoplasm. The results were viewed and discussed in terms of molecular oncogenesis of ASCs and MACs at different topographies. Molecular profile mapping was conducted by annotating all the retrieved genes for each neoplasm using genetic network analysis (Cystoscape software program). The genetic profile of each lesion was compared to that of high-grade MEC. To conclude, both genetic profiles do not tend to intersect specifically with high-grade MEC, except for the generic mutations commonly detected in all high-grade head and neck tumors. However, the availability of data on the molecular profile of each lesion limits the generalizability of the findings of this study.

Mucoepidermoid carcinoma may be devoid of squamoid cells by immunohistochemistry: expanding the histologic and immunohistochemical spectrum of MAML2- rearranged salivary gland tumours.

Mucoepidermoid carcinoma (MEC) is historically defined by a mix of squamoid, intermediate, and mucous cells, but we have recently encountered several cases lacking immunoreactivity for squamous markers p40, p63, and CK5/6 despite MAML2 fusions. This study will characterise these unique tumours. Ten MEC were collected arising from the parotid gland (n=4), submandibular gland (n=2), nasopharynx (n=1), base of tongue (n=1), bronchus (n=1), and trachea (n=1). Six tumours were low-grade, two intermediate-grade, one high-grade, and one demonstrated low-grade areas with high-grade transformation. Four cases were oncocytic, four had clear-cell features, two had spindle cell features, and one high-grade MEC had prominent solid, cord-like, and micropapillary features. The tumours were negative for p40 (10/10), p63 (10/10), and CK5/6 (9/9). Targeted RNA sequencing demonstrated CRTC1::MAML2 in five cases, CRTC3::MAML2 in two, and a novel MAML2::CEP126 in the unusual high-grade case. In two cases with insufficient RNA, MAML2 fluorescence insitu hybridisation (FISH) showed rearrangement. Genetically-confirmed MEC may lack overt squamous differentiation by histology and immunohistochemistry. While most cases harboured canonical fusions and fit within the spectra of MEC variants with oncocytic, clear cell, and/or spindle cell features, one had a novel MAML2::CEP126 fusion and unusual morphology. In MEC without squamoid cells, the use of immunohistochemistry may hinder, rather than aid, the correct diagnosis. In such cases, MAML2 analysis is most useful. The historical definition of MEC as a carcinoma with squamoid, intermediate and mucous cells should be revisited.