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.

Differences in site-specific incidence and relative survival of cutaneous and mucocutaneous genital squamous cell carcinoma in Germany, 2007-2015.

Direct comparisons of the incidence and survival of cutaneous vs mucocutaneous genital squamous cell carcinomas (SCCs) are lacking even though they may bring important insights. We aimed to compare incidence rates and survival of cutaneous and mucocutaneous genital SCCs head-to-head, using the same source population, cancer registry methodology and statistical methods in a population of predominantly white Caucasian descent. Using data (2007-2015) from the population-based cancer registry of North Rhine-Westphalia, (population of 18 million people), we estimated age-specific and age-standardized (old European standard) incidence rates and age-standardized relative 5-year survival of SCC with the period approach for the period 2012 to 2015. Overall, 83 650 SCC cases were registered. The age-standardized incidence rates (per 100 000 person-years) of cutaneous SCCs were 36.5 (SE 0.17) and 17.0 (SE 0.11) among men and women, respectively, with corresponding rates for mucocutaneous genital skin, 1.3 (SE 0.03) and 4.5 (SE 0.06) for men and women, respectively. In all age groups, incidence rates of mucocutaneous genital SCCs were higher in women than men. Men had higher cutaneous SCC incidence at all nongenital subsites than women, with the exception of the lower extremities. Five-year relative survival was considerably lower for mucocutaneous genital SCCs (men: 71%, women: 75%), especially of the scrotal skin (67%) and labia majora (62%) than for SCC of nongenital skin (men: 93%, women: 97%). Given their relatively high incidence together with a lower survival probability, future studies are warranted to establish therapies for advanced mucocutaneous genital SCC, such as immune checkpoint inhibition.

Mucoepidermoid Parotid Gland Tumor Found on Follow-up Radioiodine Scan for Differentiated Papillary Thyroid Cancer.

This report presents a case of focal uptake in the right parotid gland found on a follow-up whole-body radioiodine scan 1 y after successful ablation of differentiated papillary thyroid carcinoma. After the parotid tumor had been excised, it was proven histopathologically to be a low-grade mucoepidermoid tumor. This case illustrates a 131I focus that was false-positive for thyroid carcinoma. The short period between radioiodine treatment and development of this parotid tumor creates doubt about a causal relationship. Induction of salivary gland tumors by radiation has been reported primarily in the setting of external radiotherapy. In the large volume of thyroid carcinoma patients treated with radioiodine across the world, such an occurrence has been rare.

P63 Positive Mucoepidermoid Tumor of the Lacrimal Sac with Associated Papilloma.

We report a case of a 44-year-old man who presented with a left medial canthal mass and epiphora. Imaging was suggestive of a mass continuous with the nasolacrimal sac. Subsequent surgical exploration revealed a mass adherent to bone with invasion of the lacrimal system. Histological examination revealed a squamous/transitional cell papilloma overlying a low-grade mucoepidermoid carcinoma (MEC). Complete surgical resection was completed and pathology confirmed the diagnosis. This is the first case in which a MEC has been reported concurrently with an overlying papilloma, providing support for the hypothesis that MECs arise from papillomas in the lacrimal sac. Additionally, the tissue stained positive for p63, which is congruent with MEC immunoreactivity in the salivary gland. The description of these unique histopathological findings may assist in definitive diagnosis and improve our understanding of the pathophysiology underlying lacrimal sac MEC tumors.

[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.

Expression and clinical implications of P53, P63, and P73 protein in malignant tumor of the parotid gland.

BACKGROUND/AIM: To investigate the expression of P53, P63, and P73 proteins in malignant parotid gland tumors and adjacent nonneoplastic tissues and the association between the 3 proteins and their clinical characteristics. MATERIALS AND METHODS: A total of 40 pairs of paraffin-embedded malignant parotid gland tumors and adjacent nonneoplastic tissues were collected. We detected P53, P63, and P73 protein expression by immunohistochemistry. Statistical analysis was performed by using the chi-square test. RESULTS: P53, P63, and P73 protein expression in malignant parotid gland tumors was higher than their expression in adjacent nonneoplastic tissue (P = 0.030, 0.001, and 0.001, respectively). Expression of P53, P63, and P73 proteins was not associated with age, sex, or lymph node metastasis (P > 0.05). Expression of P53 and P73 proteins, instead of the P63 protein, was correlated to the degree of malignancy (P = 0.026 and 0.018, respectively). There was no significant difference among the P53, P73, and P63 proteins in malignant parotid gland tumors (P > 0.05). In the follow-up, only one patient died of colon cancer. CONCLUSION: Our results suggest that the P53, P63, and P73 proteins may play a role in the development of malignant parotid gland tumors and provide data for their diagnosis.

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.

CRTC1/MAML2 gain-of-function interactions with MYC create a gene signature predictive of cancers with CREB-MYC involvement.

Chimeric oncoproteins created by chromosomal translocations are among the most common genetic mutations associated with tumorigenesis. Malignant mucoepidermoid salivary gland tumors, as well as a growing number of solid epithelial-derived tumors, can arise from a recurrent t (11, 19)(q21;p13.1) translocation that generates an unusual chimeric cAMP response element binding protein (CREB)-regulated transcriptional coactivator 1 (CRTC1)/mastermind-like 2 (MAML2) (C1/M2) oncoprotein comprised of two transcriptional coactivators, the CRTC1 and the NOTCH/RBPJ coactivator MAML2. Accordingly, the C1/M2 oncoprotein induces aberrant expression of CREB and NOTCH target genes. Surprisingly, here we report a gain-of-function activity of the C1/M2 oncoprotein that directs its interactions with myelocytomatosis oncogene (MYC) proteins and the activation of MYC transcription targets, including those involved in cell growth and metabolism, survival, and tumorigenesis. These results were validated in human mucoepidermoid tumor cells that harbor the t (11, 19)(q21;p13.1) translocation and express the C1/M2 oncoprotein. Notably, the C1/M2-MYC interaction is necessary for C1/M2-driven cell transformation, and the C1/M2 transcriptional signature predicts other human malignancies having combined involvement of MYC and CREB. These findings suggest that such gain-of-function properties may also be manifest in other oncoprotein fusions found in human cancer and that agents targeting the C1/M2-MYC interface represent an attractive strategy for the development of effective and safe anticancer therapeutics in tumors harboring the t (11, 19) translocation.

Subungual tumors: clinicopathologic correlation with US and MR imaging findings.

Various types of tumors can affect the subungual space, including benign solid tumors (glomus tumor, subungual exostosis, soft-tissue chondroma, keratoacanthoma, hemangioma, lobular capillary hemangioma), benign cystic lesions (epidermal and mucoid cysts), and malignant tumors (squamous cell carcinoma, malignant melanoma). Imaging plays an important role in the detection and differentiation of subungual tumors because of their small size, nonspecific clinical manifestations, and functional significance. Ultrasonography (US)-in particular, high-resolution US with color Doppler studies-provides useful information regarding tumor size, location, shape, and internal characteristics (cystic, solid, or mixed), but it is limited in the further characterization of tissue. Magnetic resonance (MR) imaging has an important role in categorizing tumors according to their anatomic location, pathologic origin, and signal characteristics. There is some overlap between the US and MR imaging features of subungual tumors; however, certain features can allow accurate diagnosis and expedite management when correlated with clinical and pathologic findings.

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.

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 lung tumor appearing as an abscess on the scrotum.

The authors present the case of a 52-year-old man who had recurring scrotal abscesses resulting in oncotomy being carried out seven times within 2 years. Eventually, it was dissected out totally. Histology proved anaplastic cancer metastasis. The primary tumor was detected in the bronchia; moreover, metastases were found in other organs as well. The patient died 6 weeks after the first diagnosis. We intended to draw attention to frequently occurring scrotal inflammation and thus the underlying diseases. We emphasize the importance of histology examinations.

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.

Mucoepidermoid tumors of the lung: analysis of 11 cases.

BACKGROUND: Mucoepidermoid tumors (METs) of the trachea and bronchi are rare. They derive from the minor salivary gland tissue of the proximal tracheobronchial tree, and their clinical behaviors are still controversial. Herein, we analyze 11 cases of MET to investigate its clinicopathological characteristics. METHODS: The medical records and pathological examinations of patients diagnosed with MET from May, 1995 to May, 2001 at the Division of Thoracic Surgery in Taipei Veterans General Hospital were retrospectively reviewed. RESULTS: There were 11 patients (7 male and 4 female) aged from 19 to 79 years, with a peak at the seventh and eighth decade. The mean age at diagnosis was 58.9 years, and 9 of these 11 patients were symptomatic. No surgical mortality occurred. Three patients with low-grade tumors were all young females (less than 30 years). They were all alive without evidence of disease recurrence until the date of analysis, whereas the 5-year survival of 8 patients with high-grade tumors was only 25%. Six patients with high-grade tumors received adjuvant therapy, but their prognoses remained poor. CONCLUSIONS: In the current study, METs occurred more frequently in male patients. Young female patients were preponderant to have low-grade tumors and therefore associated with better prognosis. Histological grading of the MET and the ability to achieve an anatomic resection are 2 most important factors that affect prognosis. Adjuvant therapy seems not to be effective in patients with high-grade MET.

Surgical treatment of other bronchial tumors.

Bronchial gland tumors (bronchial carcinoids, adenoid cystic carcinoma, mucoepidermoid carcinoma are the most common), benign tumors and other rare primary malignant neoplasms present as endobronchial tumors. This article discusses the surgical treatment of each of these tumors individually.

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.

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.