Claudin expression in pulmonary adenoid cystic carcinoma and mucoepidermoid carcinoma.

Background: Although the expression of tight junction protein claudins (CLDNs) is well known in common histological subtypes of lung cancer, it has not been investigated in rare lung cancers. The aim of our study was to examine the expression of different CLDNs in pulmonary salivary gland tumors. Methods: 35 rare lung cancers including pathologically confirmed 12 adenoid cystic carcinomas (ACCs) and 23 mucoepidermoid carcinomas (MECs) were collected retrospectively. Immunohistochemical (IHC) staining was performed on formalin fixed paraffin embedded (FFPE) tumor tissues, and CLDN1, -2, -3, -4, -5, -7, and -18 protein expressions were analyzed. The levels of immunopositivity were determined with H-score. Certain pathological characteristics of ACC and MEC samples (tumor grade, presence of necrosis, presence of blood vessel infiltration, and degree of lymphoid infiltration) were also analyzed. Results: CLDN overexpression was observed in both tumor types, especially in CLDN2, -7, and -18 IHC. Markedly different patterns of CLDN expression were found for ACC and MEC tumors, especially for CLDN1, -2, -4, and -7, although none of these trends remained significant after correction for multiple testing. Positive correlations between expressions of CLDN2 and -5, CLDN3 and -4, and CLDN5 and -18 were also demonstrated. Tumors of never-smokers presented lower levels of CLDN18 than tumors of current smokers (p-value: 0.003). Conclusion: This is the first study to comprehensively describe the expression of different CLDNs in lung ACC and MEC. Overexpression of certain CLDNs may pave the way for targeted anti-claudin therapy in these rare histological subtypes of lung cancer.

Overexpression of sphingosine kinase 1 is associated with salivary gland carcinoma progression and might be a novel predictive marker for adjuvant therapy.

BACKGROUND: Overexpression of sphingosine kinase-1 (SPHK1) has been demonstrated to be associated with the development and progression in various types of human cancers. The current study was to characterize the expression of SPHK1 in salivary gland carcinomas (SGC) and to investigate the association between SPHK1 expression and progression of SGC. METHODS: The expression of SPHK1 was examined in 2 normal salivary gland tissues, 8 SGC tissues of various clinical stages, and 5 pairs of primary SGC and adjacent salivary gland tissues from the same patient, using real-time PCR and western blot analysis. Furthermore, the SPHK1 protein expression was analyzed in 159 clinicopathologically characterized SGC cases by immunohistochemistry. Statistical analyses were performed to determine the prognostic and diagnostic associations. RESULTS: SPHK1 expression was found to be markedly upregulated in SGC tissues than that in the normal salivary gland tissues and paired adjacent salivary gland tissues, at both mRNA and protein levels. Statistical analysis revealed a significant correlation of SPHK1 expression with the clinical stage (P = 0.005), T classification (P = 0.017), N classification (P = 0.009), M classification (P = 0.002), and pathological differentiation (P = 0.013). Patients with higher SPHK1 expression had shorter overall survival time, whereas patients with lower SPHK1 expression had better survival. Importantly, patients in the group without adjuvant therapy who exhibited high SPHK1 expression had significantly lower overall survival rates compared with those with low SPHK1 expression. Moreover, multivariate analysis suggested that SPHK1 expression might be an independent prognostic indicator for the survival of SGC patients. CONCLUSIONS: Our results suggest that SPHK1 expression is associated with SGC progression, and might represent as a novel and valuable predictor for adjuvant therapy to SGC patients.

[Mucoepidermoid tracheo-bronchial tumors in adulthood. A series of 22 cases]. / Tumeurs muco-épidermoïdes trachéo-bronchiques chez l'adulte. À propos d'une série de 22 cas.

INTRODUCTION: Mucoepidermoid tumours (TME) are rare tumours arising from the submucosal glands of the tracheobronchial tree. The majority of these tumours develop in a benign fashion but some of them are malignant. The latter can be easily mistaken for adenosquamous carcinomas. PATIENTS AND METHOD: We have reviewed 22 patients suffering from TME observed over a period of 25 years. Two arose from the trachea and 20 from the cartilaginous bronchi; 12 of these tumours had macroscopic and histological criteria of low-grade malignancy, 4 had macroscopic and 6 macroscopic and microscopic criteria of high grade malignancy. RESULTS: Prognosis of the latter was very poor and no survival observed after 6 years follow-up, a behavior similar to that observed in non-small cell lung carcinomas and adenosquamous carcinomas. CONCLUSION: The best treatment of these orphan tumours remains surgery.

Mucoepidermoid bronchial tumors: a review of 34 operated cases.

OBJECTIVE: Pulmonary mucoepidermoid tumors are commonly included with adenoid cystic carcinoma and carcinoid tumors under the misleading rubric 'bronchial adenomas'. These neoplasms are extremely rare and little is known about their oncologic behaviour. They are considered to be of high, or low malignancy. METHODS: During a 16-year-period 34 consecutive patients (24 male and 10 female with an average age of 53 years) underwent surgery for pulmonary mucoepidermoids in our clinic (0.5% of all resected lung tumors). Fourteen patients were complaint free, in the others obstructive symptoms dominated. In 23 patients the tumors were located in the upper lobes. In 24 cases lobectomy, in four instances limited resection and in six cases pneumonectomy were performed without hospital mortality. RESULTS: Twenty-nine tumors proved to be high grade and five low grade malignancy by histology. In the latest group the 5-year-survival amounted to 80% (all of these tumors were observed in stage T1-2 N0), on the other hand, however, that rate accounted only 31% at high grade malignant mucoepidermoids. There was no 5-year-survivor among patients having N2-disease (n=5). CONCLUSION: Mucoepidermoid tumors have to be treated by radical surgery with lymph node sampling and dissection. Patients with low grade tumors can be expected to be cured following complete resection, on the other hand, however, in cases of high grade malignant neoplasms surgery results in significantly worse prognosis. Careful histological typing plays a key role in prediction of late results.

Childhood bronchial mucoepidermoid tumors.

A very rare case of a childhood bronchial mucoepidermoid tumor is presented. A 4-year-old girl was hospitalized with prolonged pneumonia. Computed tomography of the chest showed a tumor with calcifications in the right upper lobe. Subsequently, the patient underwent right upper lobectomy. Histologically, the tumor was a low-grade mucoepidermoid tumor originating from the bronchus. Three years postoperatively there has been no evidence of disease. A review of the literature indicates that 30 cases of bronchial mucoepidermoid tumors in children have been reported. Symptoms result from associated bronchial obstruction. Children with recurrent or prolonged pneumonia should undergo aggressive diagnostic investigation by chest tomography or bronchoscopy. Appropriate therapy for childhood bronchial mucoepidermoid tumor is total resection of the lesion while sacrificing as little of the normal lung tissue as possible.

Nuclear pseudoinclusions in a case of parotid mucoepidermoid carcinoma.

Mucoepidermoid carcinoma is a common malignant salivary gland tumor characterized by cellular and architectural heterogeneity. Nuclear pseudoinclusions have not been previously described in this salivary gland tumor. This is a description of the cytologic and histologic findings of a parotid mucoepidermoid carcinoma with nuclear pseudoinclusions.

Mucoepidermoid tumor of the lung: CT appearance.

Mucoepidermoid tumor of the lung is a rare endobronchial neoplasm with a wide spectrum of appearance. We present a case report and describe the plain film and computed tomography (CT) findings.

Malignant sialogenic tumours of the larynx.

Laryngeal manifestations of malignant sialogenic neoplasias are rare. This paper documents the clinical features, treatment, biological behaviour and prognosis of 15 cases of malignant sialogenic tumours of the larynx that were reviewed in a retrospective clinical and histopathological study. The 15 cases of malignant sialogenic tumours of the larynx were diagnosed at the University Hospital, Eppendorf, over a period of 33 years (1965-1998). Forty per cent were adenoid cystic carcinomas, 33 per cent mucoepidermoid carcinomas and 27 per cent were poorly differentiated adenocarcinomas. Local tumour resection, if necessary in combination with bilateral neck dissection and post-operative radiotherapy, was associated with a five-year survival rate in 80 per cent of the mucoepidermoid carcinoma cases. Adenoid cystic carcinoma was associated with a less favourable five-year survival rate of 33 per cent. Low-differentiated adenocarcinomas were associated with the least favourable prognosis with a five-year survival rate (25 per cent). The prognosis for these tumours is thus poorer than for squamous cell carcinomas with the same localization and TNM status.

[Mucoepidermoid bronchial tumor with an unusual radiologic presentation]. / Une tumeur bronchique muco-épidermoïde à présentation radiologique originale.

We report a case of low-grade malignant mucoepidermoid bronchial tumor in a 21-year-old woman who presented with hemoptysis. There was a striking radiological presentation with a unilateral clear radiograph. Lung scintigraphy demonstrated perturbed ventilation and perfusion of the left lung. Pulmonary angiography only showed diminished peripheral vascularization. The main vessels were clear. These anomalies fit the radiological category of air trapping accompanied by probably hypoxic pulmonary vasoconstriction. Mucoepidermoid tumors account for only 0.5-1% of all primary lung tumors. They are found in adults as well as in children. There are two clear-cut histological forms with very different prognosis. The tumors of high-grade malignancy are considered as undifferentiated carcinomas and should be treated as such. The prognosis is much better for tumors of low-grade malignancy and current treatment is surgical in the absence of recurrence after isolated endoscopic treatment.

[Mucoepidermoid tracheobronchial tumors. Apropos of a series of 11 cases]. / Tumeurs muco-épidermoïdes trachéobronchiques. A propos d'une série de 11 cas.

Mucoepidermoid tumours (TME) are rare tumours which develop at the level of the submucous bronchial glands of the tracheobronchial tree. The majority of these tumours develop in a benign fashion but some of them are malign. Amongst these many are probably confused with adenosquamous bronchial cancers. We have reviewed eleven patients suffering from TME who were observed over a period of twelve years. Two of these tumours were at the level of the trachea: nine others were at the level of the bronchial cartilaginous trachea. Seven of these tumours had the macroscopic and histological criteria of low grade malignancy and four corresponded to those tumours said to show high grade malignancy. The only death concerned a patient with a tracheal tumor of high grade malignancy but the death occurred immediately after laser therapy to relieve obstruction in a patient with acute asphyxia. None of the other patients died of tumour progression and the longest follow up (eleven years of survival) involved a patient with a bronchial form and a high grade malignancy with glandular invasion. Even mucoepidermoid tumours of high grade malignancy have a good prognosis and it is a cardinal point to clearly distinguish these forms from adenosquamous cancers. Nevertheless it has been suggested that adenosquamous and mucoepidermoid carcinomas could have a common origin and be the extremes of the same overall disorder just as the image we have of neuroendocrine tumours whose spectrum extends from carcinoid tumours to small cell cancers.

[The problem of lymph nodes in malignant epithelial tumors of the parotid gland]. / Il problema linfonodale nei tumori epiteliali maligni della parotide.

Cervical lymph-node treatment in parotid gland epithelial malignancies is still debated. According to Literature, three different strategies (surgery, radiotherapy, "wait and see") have all been proposed theoretically, particularly when dealing with N0 cases. The present study was designed to evaluate the results of different lymphonode treatment strategies in 57 parotid gland carcinomas followed at the ENT Clinic of the University of Ferrara. The most frequent hystological patterns appeared to be the adenoidcystic carcinoma (33.3%) and the mucoepidermoid tumor (21.1%). Total parotidectomy was the treatment of choice in all cases. Ipsilateral neck dissection was performed in 14 cases (24.5%), 5 cases being N0. In 27 patients (47.4%) postsurgical radiotherapy was applied: in 7 cases on T and in 20 on both T and N.T recurrences were 7, while those of N and of both T and N were respectively 2 and 2. No occult metastases were found in N0 dissected patients. The results obtained led the Authors to the following conclusions: -neck dissection is fundamental in treatment of clinical adenopathies in any parotid gland malignancy: -postsurgical radiotherapy on the neck is the treatment of choice in all N0 carcinomas except in cases of acinic cell and mucoepidermoid carcinomas, where a "wait and see" policy seems to be more suitable.

[A rare case of bronchial mucoepidermoid tumor]. / Vzácný prípad mukoepidermoidního tumoru bronchu.

The authors describe a rare case of a mucoepidermoid bronchial tumour in a young patient. The main clinical manifestation was relapsing bronchopneumonia behind the stenosis. The authors analyze in detail the histological characteristics of the tumour and its behaviour and present a review of the literature.

Characterization of stem-like cells in mucoepidermoid tracheal paediatric tumor.

Stem cells contribute to regeneration of tissues and organs. Cells with stem cell-like properties have been identified in tumors from a variety of origins, but to our knowledge there are yet no reports on tumor-related stem cells in the human upper respiratory tract. In the present study, we show that a tracheal mucoepidermoid tumor biopsy obtained from a 6 year-old patient contained a subpopulation of cells with morphology, clonogenicity and surface markers that overlapped with bone marrow mesenchymal stromal cells (BM-MSCs). These cells, designated as MEi (mesenchymal stem cell-like mucoepidermoid tumor) cells, could be differentiated towards mesenchymal lineages both with and without induction, and formed spheroids in vitro. The MEi cells shared several multipotent characteristics with BM-MSCs. However, they displayed differences to BM-MSCs in growth kinectics and gene expression profiles relating to cancer pathways and tube development. Despite this, the MEi cells did not possess in vivo tumor-initiating capacity, as proven by the absence of growth in situ after localized injection in immunocompromised mice. Our results provide an initial characterization of benign tracheal cancer-derived niche cells. We believe that this report could be of importance to further understand tracheal cancer initiation and progression as well as therapeutic development.

High-grade oncocytic mucoepidermoid carcinoma of the minor salivary gland origin: a case report with immunohistochemical study.

An oncocytic mucoepidermoid carcinoma arising from the minor salivary gland origin is extremely rare. We report on a 44-year-old man with a high-grade oncocytic mucoepidermoid carcinoma originating in the minor salivary gland of the posterior mandible. All tumor cells showed the expected pattern of immunoreactivity, with positive results for the antimitochondrial antibody and p63, and negative results for the androgenic receptor antibody. Microscopically, the tumor was considered to be a high-grade carcinoma in the grading systems of the Armed Forces Institute of Pathology and Brandwein. The patient underwent a partial mandibulectomy, and the lesion was reconstructed with a right fibula osteofasciocutaneous flap under general anesthesia. The patient is currently under long-term follow-up.

Mucoepidermoid tumors of the bronchus. Ultrastructural and immunohistochemical study. Histiogenic correlations.

UNLABELLED: Bronchial mucoepidermoid tumors are uncommon neoplasms, morphologically similar to their salivary gland counterpart. The histogenesis is controversial. The aim of this study is to identify myoepithelial cells and speculate on their role in the origin of these tumors. METHODS AND RESULTS: Sixteen bronchial mucoepidermoid tumor surgical specimens were formalin-fixed, paraffin-embedded and studied using a panel of nine antibodies in order to identify a myoepithelial differentiation. Additional antigens against several cytokeratins were performed in four cases and five of the biopies were studied using the electron microscopy. The different types of cells of the primary bronchial mucoepidermoid tumor (mucous luminal, intermediate and squamous) reacted strongly against AE1, CK7, 34bE12 and weakly with AE3, CK18 and CK8/18/19. S-100, alpha-smooth muscle actin, muscle actin HHF35 and alpha-actinin were consistently negative in all cell types. CD10 was positive in very few cells in just one case. CONCLUSION: The immunohistochemical and the ultrastructural study of bronchial mucoepidermiod tumors support a ductal unit origin, without a myoepithelial participation.

Cadherin and catenin expression in mucoepidermoid carcinoma: correlation with histopathologic grade, clinical stage, and patient outcome.

BACKGROUND: Alteration of cadherin and catenin expression is associated with loss of differentiation, acquisition of an invasive phenotype, and poor prognosis in many types of cancers. The roles of cadherins and catenins in mucoepidermoid carcinoma (MEC) are not fully understood. METHODS: Based on immunohistochemical studies, the expressions of E-, N-, and P-cadherins and alpha-, beta-, and gamma-catenins in MEC were investigated, and correlations with clinicopathologic parameters were evaluated. RESULTS: These six molecules were strongly expressed in normal ductal epithelium but increased or decreased immunoreactivities of those proteins in MEC were frequently observed, especially for E-cadherin and alpha-catenin. The immunoactivity of beta-catenin showed significant correlation with grade (P = 0.05) and stage (P < 0.0001). beta-Catenin expressions are also correlated with gamma-catenin expression (P = 0.006) according to cross-table analysis. Survival analysis indicated that stage, grade, and beta-catenin expressions had significant correlation with survival. CONCLUSION: Aberrant beta-catenin expression may play an important role in the histologic differentiation and tumor staging of MEC.