Analysis of B7-H4 Expression Across Salivary Gland Carcinomas Reveals Adenoid Cystic Carcinoma-Specific Prognostic Relevance.

B7-H4 (VTCN1), a member of the B7 family, is overexpressed in several types of cancer. Here we investigated the pattern of expression of B7-H4 in salivary gland carcinomas (SGC) and assessed its potential as a prognostic marker and therapeutic target. Immunohistochemistry (IHC) analyses were performed in a cohort of 340 patient tumors, composed of 124 adenoid cystic carcinomas (ACC), 107 salivary duct carcinomas (SDC), 64 acinic cell carcinomas, 36 mucoepidermoid carcinomas (MEC), 9 secretory carcinomas (SC), as well as 20 normal salivary glands (controls). B7-H4 expression was scored and categorized into negative (<5% expression of any intensity), low (5%-70% expression of any intensity or >70% with weak intensity), or high (>70% moderate or strong diffuse intensity). The associations between B7-H4 expression and clinicopathologic characteristics, as well as overall survival, were assessed. Among all tumors, B7-H4 expression was more prevalent in ACC (94%) compared with those of SC (67%), MEC (44%), SDC (32%), and acinic cell carcinomas (0%). Normal salivary gland tissue did not express B7-H4. High expression of B7-H4 was found exclusively in ACC (27%), SDC (11%), and MEC (8%). In SDC, B7-H4 expression was associated with female gender (P = .002) and lack of androgen receptor expression (P = .012). In ACC, B7-H4 expression was significantly associated with solid histology (P < .0001) and minor salivary gland primary (P = .02). High B7-H4 expression was associated with a poorer prognosis in ACC, regardless of clinical stage and histologic subtype. B7-H4 expression was not prognostic in the non-ACC SGC evaluated. Our comparative study revealed distinct patterns of B7-H4 expression according to SGC histology, which has potential therapeutic implications. B7-H4 expression was particularly high in solid ACC and was an independent prognostic marker in this disease but not in the other SGC assessed.

Recent developments in the pathology of primary pulmonary salivary gland-type tumours.

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.

Clinico-pathological study of esophageal mucoepidermoid carcinoma: a 10-year survival from a single center.

BACKGROUND: Mucoepidermoid Carcinoma of the Esophagus (MECE) is a relatively rare tumor type, with most of the current data derived from case reports or small sample studies. This retrospective study reports on the 10-year survival data and detailed clinicopathological characteristics of 48 patients with esophageal MEC. METHODS: Data were collected from 48 patients who underwent curative surgery for esophageal MEC at the Fourth Hospital of Hebei Medical University between January 1, 2004, and December 31, 2020. These were compared with contemporaneous cases of Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC). Using the Kaplan-Meier method and multivariate Cox regression analysis, we investigated the clinicopathological factors affecting the survival of patients with MEC. RESULTS: The incidence of MECE was predominantly higher in males, with a male-to-female ratio of approximately 7:1. The mid-thoracic segment emerged as the most common site of occurrence. A mere 6.3% of cases were correctly diagnosed preoperatively. The lymph node metastasis rate stood at 35.4%. The overall 1-year, 3-year, 5-year, and 10-year survival rates for all patients were 85.4%, 52.1%, 37.0%, and 31.0%, respectively. Post 1:1 propensity score matching, no significant statistical difference was observed in the Overall Survival (OS) between MEC patients and those with Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC) (P = 0.119, P = 0.669). Univariate analysis indicated that T staging and N staging were the primary factors influencing the prognosis of esophageal MEC. CONCLUSIONS: MECE occurs more frequently in males than females, with the mid-thoracic segment being the most common site of occurrence. The rate of accurate preoperative endoscopic diagnosis is low. The characteristic of having a short lesion length yet exhibiting significant extramural invasion may be a crucial clinicopathological feature of MECE. The OS of patients with MEC does not appear to significantly differ from those with esophageal squamous carcinoma and adenocarcinoma.

E-CADERIN, N-CADERIN, SLUG, SNAIL, and TWIST contribute to epithelial-mesenchymal transition in salivary gland tumors.

BACKGROUND: Transcription factors are important in the epithelial-mesenchymal transition process and are possibly related to the development of a more invasive tumor phenotype. Thus, the objective of this study was to analyze the expression and identify the localization of cellular markers related to the epithelial-mesenchymal transition process in salivary gland tumors. STUDY DESIGN: The expression and localization of E-CADERIN, N-CADERIN, SLUG, SNAIL, and TWIST were evaluated, using immunohistochemistry, in 48 salivary gland tumors, being 17 pleomorphic adenomas (PA), 14 adenoid cystic carcinomas (ACC), and 17 mucoepidermoid carcinomas (MEC). these proteins were compared to clinical and histopathologic parameters. normal gland tissues were included for immunohistochemical comparisons. RESULTS: ACC and MEC cases showed higher expression of SNAIL compared to PA. MEC showed high expression of SLUG and TWIST. Low expression of N-CADHERIN, SNAIL, and TWIST in ACC was frequent in T3 and T4. High expression of TWIST in MEC was more frequent at age ≥ 40 years A positive correlation was only observed between N-cadherin/SNAIL in ACC, between SNAIL/TWIST in MEC, and between SLUG/TWIST in PA. CONCLUSION: This study provided insight into EMT-related proteins (E-cadherin, N-cadherin, SNAIL, SLUG, and TWIST) and their contribution to the maintenance of morphogenesis and the development of the salivary gland tumors and showed a positive correlation among N-CADHERIN/SNAIL in ACC and SNAIL/TWIST in MEC.

Rare but clinically important salivary gland-type tumor of the lung: A review.

Salivary gland-type tumor (SGT) of the lung, which arises from the bronchial glands of the tracheobronchial tree, was first recognized in the 1950s. SGT represents less than 1% of all lung tumors and is generally reported to have a good prognosis. Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are the two most common subtypes, comprising more than 90% of all SGTs. The reported 5-year survival rate of patients with SGT is 63.4%. Because this type of tumor develops in major bronchi, patients with SGT commonly present with symptoms of bronchial obstruction, including dyspnea, shortness of breath, wheezing, and coughing; thus, the tumor is usually identified at an early stage. Most patients are treated by lobectomy and pneumonectomy, but bronchoplasty or tracheoplasty is often needed to preserve respiratory function. Lymphadenectomy in the surgical resection of SGT is recommended, given that clinical benefit from lymphadenectomy has been reported in patients with MEC. For advanced tumors, appropriate therapy should be considered according to the subtype because of the varying clinicopathologic features. MEC, but not ACC, is less likely to be treated with radiation therapy because of its low response rate. Although previous researchers have learned much from studying SGT over the years, the diagnosis and treatment of SGT remains a complex and challenging problem for thoracic surgeons. In this article, we review the diagnosis, prognosis, and treatment (surgery, chemotherapy, and radiotherapy) of SGT, mainly focusing on MEC and ACC. We also summarize reports of adjuvant and definitive radiation therapy for ACC in the literature.

Salivary gland-type cancers: cross-organ demographics of a rare cancer.

BACKGROUND: Salivary gland-type cancers (SGTCs) are histologically heterogeneous and can affect organs other than the salivary glands. Some tumors outside the salivary glands are diagnosed on their unique histological characteristics. Comprehensive cross-organ studies on SGTCs are limited. METHODS: We retrospectively analyzed the data of patients with salivary duct carcinoma (SDC), adenoid cystic carcinoma (AdCC), mucoepidermoid carcinoma (MEC), epithelial-myoepithelial carcinoma (EMC), acinic cell carcinoma (AcCC), and polymorphous adenocarcinoma (PAC) who visited our institution between 2009 and 2019. The primary tumor sites were classified into four categories; major salivary glands, head/neck (H/N) excluding (exc) major salivary glands (MSG) regions, broncho-pulmonary regions, and "others". H/N exc MSG was further divided into three subcategories, nasal/paranasal sinus, oral and pharynx/larynx. RESULTS: We identified 173 patients with SGTCs, with SDC, AdCC, MEC, EMC, AcCC, and PAC accounting for 20%, 42%, 27%, 3%, 8%, and 1% of the cases, respectively. The most frequent primary site was the major salivary glands (64%), followed by H/N exc MSG regions (27%), broncho-pulmonary regions, and "others", thus non-salivary gland origins accounted for 9% of all cases. Patients with SDC, MEC, AcCC, or SGTC of the major salivary glands and broncho-pulmonary regions were more frequently treated by surgery. The overall survival time of the patients with MEC was significantly better than that of patients with SDC or EMC. CONCLUSIONS: This cross-organ study highlights the clinical significance of SGTCs, underscoring the need for developing novel therapies for this rare disease entity.

Expanding the cytological and architectural spectrum of mucoepidermoid carcinoma: The key to solving diagnostic problems in morphological variants.

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.

Elective nodal dissection for cN0 intermediate-grade parotid mucoepidermoid carcinoma: A NCDB study.

PURPOSE: To determine the occult nodal disease rate and whether elective regional lymph node dissection (RLND) confers any 10-year overall survival (OS) in cN0 intermediate-grade mucoepidermoid carcinoma (MEC) of the parotid gland. MATERIALS & METHODS: The National Cancer Database was reviewed from 2004 to 2016 on adults with cT1-4aN0M0 intermediate-grade parotid MEC undergoing resection with/without RLND. Comparisons between patients with and without RLND were made. Occult nodal rate and 10-year overall survival (OS) were determined. RESULTS: Out of 898 included patients with cN0 intermediate grade parotid MEC undergoing elective RLND, the occult nodal rate was 7.6%. This was significantly different from low-grade (3.9%) and high-grade (25.7%) cN0 disease. When stratified by pT-classification, marginal differences were identified between low-grade and intermediate-grade tumors, whereas high-grade tumors demonstrated increased occult nodal disease with low T-stage (pT1-pT2, 20.4% vs. 5.1%) and high T-stage (pT3-pT4a, 32.1% vs. 17.6%). Patients undergoing elective RLND were more often treated at an academic facility (53.8% vs. 41.2%), had higher pT3-pT4 tumors (19.2% vs. 10.4%), and more frequently underwent total/radical parotidectomy (46.0% vs. 29.9%) with adjuvant radiation therapy (53.8% vs. 41.0%) Cox-proportional hazard modeling did not identify RLND, regardless if stratified by nodal yield or pT-classification, nor nodal positivity as significant predictors of 10-year OS. CONCLUSIONS: The occult nodal disease in intermediate-grade parotid MEC is low and similar to low-grade. Elective RLND may have a limited impact on OS, though its effect on locoregional control remains unknown. LEVEL OF EVIDENCE: III.

SALTT study: A retrospective analysis of 111 SAlivary gland tumors of Lung and Tracheobronchial Tree.

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

Parotid Gland Tumors: Molecular Diagnostic Approaches.

Parotid gland pathology represents a web of differential diagnoses. There are many complex cases that require extensive diagnostic tests for a complete and correct final pathology diagnosis. Currently the official classification of parotid gland tumors extends over more than 40 subtypes. We performed a query of the PubMed database regarding the use of molecular biology tests in performing a better characterization of the tumors in specific cases. By using fluorescence in situ hybridization (FISH), reverse transcription polymerase chain reaction (RT-PCR) or next-generation sequencing, the team managing complex cases can offer a personalized therapeutic solution. We review the molecular differential diagnosis according to published articles in the last 5 years for many types of parotid gland tumors ranging from benign to borderline malign tumors to malign aggressive tumors. Mucoepidermoid carcinoma is a distinct subtype of parotid malignancy that was the subject of a consistent number of articles. However, the molecular biology diagnosis techniques helped more in excluding the diagnosis of mucoepidermoid carcinoma, and probably retrospectively limiting the number of cases with this final diagnosis. In Romania, the molecular biology diagnosis is available only in limited research facilities and should receive more consistent funding that will make it available on a larger scale. The novelty of this scoping review is that we propose an algorithm for molecular differential diagnosis of the tumors that could be encountered in the parotid gland.

Differential Expression of Mucin in Salivary Gland Tumours.

Background and Objectives: Mucin has been implicated via various mechanisms in the development and growth of tumour cells. However, mucin expression studies in salivary gland tumours are limited, especially with samples from minor salivary glands. This study aims to investigate and compare mucin expression in benign and malignant salivary gland tumours of minor and major salivary gland origins. Materials and Methods: Special stains were used to stain neutral mucin (Periodic acid Schiff), sialomucin (Alcian Blue) and sulfomucin (Aldehyde Fuschin) within tissues from six normal salivary glands and 73 salivary gland tumours including 31 pleomorphic adenomas, 27 mucoepidermoid carcinomas, and 15 adenoid cystic carcinomas. A semi-quantitative approach was used to evaluate mucin expression within ductal lumens. Sialomucin was the most expressed mucin in all salivary gland tumours, regardless of origin. Results: A significant difference was observed in the mucin expression between benign and malignant salivary gland tumours, as pleomorphic adenoma showed three times significantly higher expression of sialomucin compared to mucoepidermoid carcinoma and adenoid cystic carcinoma (p = 0.028). Pleomorphic adenomas of major glands showed 42 times significantly higher expression of sialomucin compared to those of minor glands (p = 0.000). Conclusions: Sialomucin content in pleomorphic adenomas of major glands was vastly increased compared to that in minor glands. Differential sialomucin expression in benign and malignant salivary gland tumours suggests a role in diagnosing of borderline salivary gland tumours.

Malignant and Benign Tracheobronchial Neoplasms: Comprehensive Review with Radiologic, Bronchoscopic, and Pathologic Correlation.

Tracheobronchial neoplasms are much less common than lung parenchymal neoplasms but can be associated with significant morbidity and mortality. They include a broad differential of both malignant and benign entities, extending far beyond more commonly known pathologic conditions such as squamous cell carcinoma and carcinoid tumor. Airway lesions may be incidental findings at imaging or manifest with symptoms related to airway narrowing or mucosal irritation, invasion of adjacent structures, or distant metastatic disease. While there is considerable overlap in clinical manifestation, imaging features, and bronchoscopic appearances, an awareness of potential distinguishing factors may help narrow the differential diagnosis. The authors review the epidemiology, imaging characteristics, typical anatomic distributions, bronchoscopic appearances, and histopathologic findings of a wide range of neoplastic entities involving the tracheobronchial tree. Malignant neoplasms discussed include squamous cell carcinoma, malignant salivary gland tumors (adenoid cystic carcinoma and mucoepidermoid carcinoma), carcinoid tumor, sarcomas, primary tracheobronchial lymphoma, and inflammatory myofibroblastic tumor. Benign neoplasms discussed include hamartoma, chondroma, lipoma, papilloma, amyloidoma, leiomyoma, neurogenic lesions, and benign salivary gland tumors (pleomorphic adenoma and mucous gland adenoma). Familiarity with the range of potential entities and any distinguishing features should prove valuable to thoracic radiologists, pulmonologists, and cardiothoracic surgeons when encountering the myriad of tracheobronchial neoplasms in clinical practice. Attention is paid to any features that may help render a more specific diagnosis before pathologic confirmation. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Primary mucoepidermoid carcinoma of the external auditory canal with a CRTC1::MAML2 fusion: A case report and a review of literature.

Mucoepidermoid carcinoma is a malignant neoplasm of exocrine glands that arises predominantly in salivary glands. It is seldom encountered as a primary cutaneous neoplasm, and in those patients, it often involves the external auditory canal. Given their rarity, they can pose a diagnostic challenge and prompt extensive workup. In salivary glands, mucoepidermoid carcinomas commonly harbor CRTC1/3::MAML2 fusions; however, genetic alterations of primary cutaneous neoplasms are less characterized, with previous studies reporting CRTC1 rearrangements in the absence of MAML2 aberrations. Herein, we report a case of a primary cutaneous mucoepidermoid carcinoma of the external auditory canal with a CRTC1::MAML2 rearrangement. We also review the clinical, morphologic, and molecular features of this neoplasm and compare them to those reported in the literature and to histopathologic mimics.

Polar Vessel: A New Ultrasound Sign for Complementary Diagnosis of Major Salivary Gland Adenoid Cystic Carcinoma.

OBJECTIVES: To investigate the characteristic ultrasonographic findings of adenoid cystic carcinoma (ACC) in major salivary glands and identify the value of polar vessel in color Doppler flow imaging (CDFI) for the diagnosis of ACC. METHODS: From January 2017 to December 2021, 76 patients with parotid and submandibular gland tumors, including 14 patients with ACC, as confirmed by surgery and histopathology, were enrolled. Their clinicopathologic information and ultrasound (US) features were recorded and analyzed. The performance of polar vessel in CDFI for differentiating ACC from non-ACC (benign tumors and mucoepidermoid carcinoma [MEC]) was analyzed. RESULTS: ACC in the major salivary gland was more likely to be associated with pain symptoms (P = .027) and unclear borders and rough edges in grayscale US (P = .002, .015, respectively) than benign tumors. Compared to MEC, ACC tended to feature a homogeneous internal echo (P = .008). ACC of the major salivary gland had a significantly higher incidence of polar vessel sign than that of non-ACC (benign tumors and MEC) (P < .0001, .0001, respectively). The polar vessel sign showed good performance in distinguishing between ACC and non-ACC, with an area under the receiver operating characteristic curve of 0.857, a sensitivity of 71.4%, a specificity of 100%, and an accuracy of 94.7%. Positive predictive value and negative predictive value were calculated at 100% and 93.9%, respectively. CONCLUSIONS: The US sign of polar vessel has high diagnostic efficiency, and it may have important potential for use as a new complementary sign for the diagnosis of ACC in major salivary glands.

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

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

Mucoepidermoid Carcinoma Ex Pleomorphic Adenoma of Lacrimal Gland: Case Report and Review of Literature.

Carcinoma ex pleomorphic adenoma (Ca ex PA) is defined as an infiltrative carcinoma arising from a primary or recurrent benign pleomorphic adenoma. Ca ex PA with the histologic subtype mucoepidermoid carcinoma is extremely uncommon. Only 2 previous reports in the lacrimal gland have been documented. We reported a 55-year-old lady with a firm, solid, nontender mass in the supralateral quadrant of the right orbit at the area of the lacrimal gland. After wide excision of mass, pathology revealed high-grade mucoepidermoid carcinoma Ex pleomorphic adenoma. To reduce tumor recurrence 60 Gray radiation was delivered to the orbital cavity. She is still tumor-free 1 year after completion of treatment.

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-ß) 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.

Establishment of Mucoepidermoid Carcinoma Cell Lines from Surgical and Recurrence Biopsy Specimens.

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.

[Primary salivary gland tumors from a pathology perspective : Morphomolecular peculiarities and diagnostic and therapeutic challenges]. / Primäre Speicheldrüsentumoren aus Sicht der Pathologie : Morphomolekulare Besonderheiten und diagnostisch-therapeutische Herausforderungen.

Similar to tumors of other organs, salivary gland neoplasms were historically viewed as a single neoplastic entity and mostly treated as such. Accordingly, only the clinical tumor stage, and not the histological subtype, was considered to be of significant prognostic impact. However, over the years, several distinct sub-entities have been characterized based on morphological features, such as adenoid cystic carcinoma, mucoepidermoid carcinoma, acinic cell carcinoma, and salivary duct carcinoma. Most importantly, the nosology of salivary gland carcinomas has undergone a dynamic "splitting" on the basis of morphological, immunophenotypic, and molecular characteristics, so that 21 independent carcinomas are now listed in the current World Health Organization (WHO) classification. Moreover, it has become evident that splitting of these carcinoma subtypes no longer represents a "pathologist's hobby," but carries significant prognostic and therapeutic relevance for optimized cancer surgery and potentially systemic therapy. The current review summarizes the major features of salivary gland tumors, both benign and malignant, and gives an account of their classification systems and genetic profiles.

Rearrangement of KMT2A Characterizes a Subset of Pediatric Parotid Mucoepidermoid Carcinomas Arising Metachronous to Acute Lymphoblastic Leukemia.

Introduction: Metachronous mucoepidermoid carcinomas (MMEC) may occur in association with childhood leukemias and lymphomas. We compared molecular abnormalities of MMEC in patients with ALL with the abnormalities found in primary mucoepidermoid carcinomas (MECs) in pediatric cases and young adults. Materials and methods: Immunohistochemical stains for p63 and SOX10, molecular alterations in MAML2 and KMT2A genes detected by FISH and/or next-generation sequencing were studied in 12 pediatric MMECs secondary to ALL and six primary MECs in pediatric patients and young adults. Follow-up information of patients in both groups was obtained. Results: KMT2A rearrangements were detected in pediatric MMECs, and they were associated with remarkable histomorphological changes, including deposits of abundant stromal collagen and intratumoral lymphoid proliferations. No KMT2A rearrangements were found in primary MECs. The prognosis of MMEC in patients with ALL, especially in KMT2A-rearranged cases, was worse than in primary MECs. Kruskal-Wallis test showed a statistically significant difference in overall survival between KMT2A-rearranged MMECs and KMT2A-intact MMECs in cases with ALL (p = 0.027). Conclusion: KMT2A-rearranged MMECs in ALL patients may have inherently more aggressive behavior, even when the histomorphology of MMEC suggests a low-grade malignancy.