Pleomorphic adenoma is the most common neoplasm of both the major and minor salivary glands. It is composed of an array of tissue types, of both epithelial and mesen- chymal origins, and is regarded as benign in clinical be- havior, but has the potential to undergo malignant trans- formation. Epithelial-myoepithelialcarcinoma (EMC) is a rare biphasic tumor of the salivary glands typically arising in the parotid. Fine needle aspiration cytology is widely used in the initial investigation of salivary gland swellings and whilst the cytological features of this tu- mour have been described they are not well recognized. Epithelial-myoepithelialcarcinoma (EMC) is a rare type of malignant tumor, accounting for about 1% of all sali- vary gland tumors [1,2] and recognizes a typical biphasic pattern: a central ductular structure, often containing eosinophilic material surrounded by clear cells of myoe- pithelial origin. It was firstly described as a glycogen- rich or clear cell adenoma because of the clear cell com- ponent. Donath et al.  noted that the myoepithelial component was an integral part of the tumor and in 1972 he introduced the term epithelial-myoepithelialcarcinoma while describing this entity where he described the clini- copathological features of a case of epithelial-myoe-
Background: Pulmonary epithelial-myoepithelialcarcinoma (P-EMC) is a rare subset of salivary gland-type tumors of the lung. Because of its rarity and unproven malignant potential, the optimal therapy for P-EMC has not been defined. Here, we report a typical case of P-EMC and a review of the literature to consider appropriate treatment. Case presentation: A 54-year-old woman presented with an abnormal lung shadow on a routine chest X-ray. A chest computed tomography (CT) scan verified an 18-mm endobronchial nodule on the middle lobe. We performed a bronchoscopic biopsy, and the patient was diagnosed with P-EMC. After confirming the absence of tumors in the salivary glands, she underwent a right middle lobectomy along with hilar and mediastinal lymph node dissections. Currently, the patient is doing well, without any sign of recurrence 3 years after surgery.
not related to poor differentiation and a worse prognosis, as defined in invasive ductal carcinoma not otherwise spe- cified (IDC NOS) [22-25]. In addition, compared with adenoid cystic carcinoma of salivary, although they have similar morphological and immunological phenotypes and even the same molecular genetic defect, the t(6;9)(q22–23; p23–24) translocation , the biological behavior of breast and salivary ACC is different. The former showed indolent clinical behavior, and the latter showed an ag- gressive course. Adenoid cystic carcinoma of breast pre- sents as a localized disease with a low frequency of axillary lymph node involvement of less than 8%, and rare distant metastases of fewer than 20% [27-30]. Therefore, most cli- nicians recommend a breast-conserving surgical therapy with or without radiotherapy . However, some research performed grading according to the criteria accepted for salivary ACC and suggested that grade 3 (solid growth pattern) may have a higher propensity of recurrence and metastasis . This result has not been confirmed by long- term follow-up data. At the same time, AME of breast has better prognosis comparing with epithelial-myoepithelialcarcinoma of salivary gland .Most of the adenomyoe- pitheliomas of breast behave as benign though rare cases have metastasized . The behavior of malignant adeno- myoepithelioma seemed to be related to the grade of the malignant component and the tumor size [4,5]. In our case, the component of high grade epithelial-myoepithelialcarcinoma might indicate a high frequency of recurrence and metastases. To date, there are limited published data on the biological behavior and long-term clinical outcome of adenoid cystic carcinoma combining with malignant adenomyoepithelioma. As a result, it is necessary for the patient to be closely followed-up and periodically exa- mined following treatment.
Although there is mutual agreement between the dif- ferent authors about considering this neoplasia of low grade malignancy, this kind of tumour has been desig- nated in many different ways, including adenomyoe- pithelioma, epithelial-myoepithelial tumour, epithelial- myoepithelialcarcinoma or epithelial-myoepithelial tumour of uncertain malignant potential. Despite the fact that most cases described until now have presented no local recurrence or metastasis, and taking into account that they are generally of small size and use to lack atypia, remarkable mitotic activity, necrosis or inva- sive features, the metastatic potential found in some of them  would make the term of carcinomaepithelial- myoepithelial adequate, even when the following terms of the patients are relatively short.
pleomorphic adenoma, mucoepidermoid carci- noma, basal cell adenocarcinoma, epithelialmyoepithelialcarcinoma, neuroendocrine car- cinoma and adenocarcinoma, etc. Morphology and immunohistochemistry are very useful. Thyroid carcinoma with tracheal invasion is uncommon and TACC at the level of the thyroid can be misinterpreted as invasive thyroid tumor upon initial diagnosis . 3 cases in our series were found to have upper tracheal wall and thy- roid gland invasion and it was difficult to distin- guish it from thyroid cancer before pathological examination, and TTF-1 is helpful. Because the relatively high extent of p16-positive cases in our series, the differential diagnosis also inclu- des HPV-related carcinoma with adenoid cys- tic-like features, although this small series only identified sinonasal primary sites .
Myoepithelialcarcinoma was described previously as malignant mixed tumor, however, exclusive myoepithelial differentiation makes it a distinctly separated tumor in pathology . According to the WHO classification, myoepithelialcarcinoma is referred to those lesions ‘’composed almost exclusively of tumor cells with myoe- pithelial differentiation’’. Therefore, a tumor containing frequent true luminal differentiation should be excluded from the category of purely myoepithelialcarcinoma ’’ . Myoepitheliaomas and their malignant counterpart, myoepithelialcarcinoma are distinct concepts from ade- nomyoepitheliomas . Malignant adeno-myoepithe- lioma, adeno-myoepithelioma (combination of adenoma and myoepithelioma), epithelialmyoepithelial adenoma, and epithelial-myoepithelialcarcinoma are the terms having exactly the same meaning . However, when the myoepithelial cells were the major component of breast adenomyoepithelioma, it is usually called myoe- pithelial carcinoma.
Primary salivary gland type tumors of lung are very rare, accounting for 0.1-0.2% of all lung tumors . These tumors usually arise from the epithelium of tracheobronchial submucosal glands. These tumors can display the same spectrum of histological variability as their sali- vary gland counterparts and are accordingly classified by the World Health Organization (WHO) criteria for salivary gland tumors, includ- ing mucoepidermoid carcinoma, adenoid cystic carcinoma, epithelial-myoepithelialcarcinoma, acinic cell carcinoma, oncocytoma, benign myoepithelioma, and mixed tumors of both benign and malignant nature. Various benign and malignant tumors of these structures have been described in the lung. Primary myoepithe- lial carcinoma of the lung is an extremely rare, with only eight known prior cases reported in the literature to date [2-8]. Herein, we report a case of primary myoepithelialcarcinoma of the lung, including clinical and histopathological features, clinical prognosis, and diagnostic and therapeutic approaches, and a review of the literature.
detection kits were purchased from PerkinElmer (Boston, MA, USA). HRP-labeled goat antirabbit and goat anti- mouse IgG were obtained from Pierce Biotechnology (Rockford, IL, USA). Mammary epithelial basal medium (MEBM) without phenol red and mammary epithelial growth medium (MEGM) SingleQuots were purchased from Lonza (Basel, Switzerland). HyClone FBS was ob- tained from GE Healthcare Life Sciences (Logan, UT, USA). CB17/Icr/Hsd scid severe combined immunodefi- ciency (SCID) mice were purchased from Harlan Labora- tories (Indianapolis, IN, USA). Masson’s Trichrome Stain Kit, biotinylated streptavidin-HRP secondary antibody, and 3,3′-diaminobenzidine tetrahydrochloride were obtained from Dako (Carpinteria, CA, USA). Human breast tissue microarray (BR8011) from US Biomax (Rockville, MD, USA). ImmPRESS™ antimouse IgG, normal horse serum, ImmPACT™ NovaRED™ substrate, avidin-biotin complex- HRP complex, and VectaMount mounting medium were obtained from Vector Laboratories (Burlingame, CA, USA). Sequencing grade modified trypsin was purchased from Promega (Madison, WI, USA). The Dionex μ- precolumn C18 reversed-phase cartridge and Acclain Pep- Map100 C18 reversed-phase analytical column were pur- chased from Thermo Fisher Scientific (Sunnyvale, CA, USA). High-performance liquid chromatography (HPLC) grade water and acetonitrile (Optima) were purchased from Fisher Scientific (Pittsburgh, PA, USA). Bradford protein assay kits were obtained from Thermo Fisher Scientific. Bovine serum albumin, antibiotics, monoclonal anti-α-smooth muscle actin (anti-αSMA), Triton X-100, protease inhibitor cocktail, and all other chemicals, unless otherwise stated, were purchased from Sigma-Aldrich (St. Louis, MO, USA). Antihuman CK17 antibody, clone E3, was purchased from Dako.
mined that the patient had right fallopian tube carcinoma with atypical cells present in the left fallopian tube. The operative procedure progressed to complete surgical staging (including total hysterectomy, bilateral oophorectomy, pelvic and para-aortic lymphadenectomy, and omentectomy). Tubal specimens are shown in Figure 4. The patient was discharged in good physical condition.
Lugol’s solution is an inexpensive, widely available solution comprising a mixture of iodine and potassium iodide. This vital stain is absorbed by glycogen-containing, nonkeratinized, squamous epithelium, the normal tissue type in the esophagus. Lugol’s-stained tissue characteristically turns green-brown. The intensity is partly dependent on the amount of glycogen present within the epithelium. Inflammatory or dysplastic squamous epithelium, squamous cell carcinoma, and columnar epithelium do not stain with Lugol’s solution. This stain is used as a 1% or 2% solution in a volume of 20 to 50 ml sprayed through endoscopic catheters.
This mechanism of stratification from the apical side is in contrast to that observed in other epithelial organs in which stratification initiates exclusively from basally positioned cells (Lechler and Fuchs, 2005). Within the embryonic skin, stratification initiates when cells rotate their division axis from parallel with the ECM to perpendicular, thereby generating suprabasal cells (Lechler and Fuchs, 2005). Suprabasal cells proliferate and differentiate apically until terminal differentiation, cell death and eventual sloughing off of the body (Fuchs, 2007). The organization of the lung epithelium is also regulated by the angle of the mitotic spindle and oncogenic signals disrupt normal lung structure in part by changing spindle angle (Tang et al., 2011). Oncogenic stimuli can also induce multilayered epithelial structures through migration of cells into the luminal space (Leung and Brugge, 2012; Yagi et al., 2012). Accordingly, we anticipate that our observed mechanism of vertical apical cell divisions might be most common in cancers in which the driving molecular event is deregulated RTK signaling. 3D culture models of mammary cancer have also provided insight into the cellular response to ERBB2 activation. Ubiquitous expression of ERBB2 was sufficient to induce stratification in mature acini of non- transformed mammary epithelial cells (MCF10A) (Muthuswamy et al., 2001). Mosaic expression of ERBB2 in mature MCF-10A acini resulted in cell migration into the lumen (Leung and Brugge, 2012). However, MCF-10A cells do not form tight junctions or establish
The tumor shows various growth pattern like diffuse sheets, well defined nests, cords, trabeculae and also as individual cells. Glandular differentiation may be well developed to barely detectable. The individual tumor cells are usually large and pleomorphic compared to that of classical invasive lobular carcinoma. The tumor shows prominent nuclei and nucleoli and increased mitotic figures. About 60% of the cases shows areas of necrosis. The amount of stroma varies from scant to abundant desmoplastic stroma. Elastic tissue are present in about 90% of cases. The presence of chalky streaks on gross examination is due to the presence of elastosis involving the vessel and duct walls .About 60% of the cases show calcification. The interphase between the tumor and stroma shows mononuclear cell inflammatory infiltrates. 12
In a dramatic twist, we found a changing pattern in the relative frequencies of these two dominant thyroid malignancies over time: 65.1% of the cancers in the first half of this study (1997-2007) were follicular carcinomas, constituting 77.8% of follicular carcinomas, while in the second half (2008-2018), 63.0% were papillary carcinomas constituting 73.9% of all papillary carcinoma. In other words, as the incidence of follicular carcinoma wanes, there is seen the waxing of that of papillary carcinoma with the passage of time. A review of thyroid carcinomas on the African continent in 20 literatures, [28-47] published between 1952 and 2014, corroborated this finding (Table 3). In these studies, cancers occurring between 1952 and 1998 were predominantly of the follicular subtype, while those occurring between1999 and 2014 were predominantly papillary carcinomas (Table 3). The reason for this change in pattern can be attributed to iodination. Iodine deficiency has been implicated in the higher frequency of thyroid disease [49,50,51] and follicular carcinoma (not papillary) . Owing to the high prevalence of iodine deficiency in the past, a global action was initiated by the United Nation incorporating it into the millennium development goals . This
Case presentation: We report a case of myoepithelialcarcinoma combined with myoepithelioma occurring in the soft tissue of the right forearm of an 84-year-old Arabian man. We describe the clinical, radiological and pathological features dominated by histological polymorphism. We will also describe the proposed histological criteria of malignancy and the major role of immunohistochemistry in positive and differential diagnosis. We finally mention the therapeutic arsenal available.
Additional file 1: Supplementary material. Figure S1. Promoter efficacy in primary cultures of myoepithelial and luminal cells. a Representative images of GFP expression in myoepithelial and luminal cells 48 h following infection with neuraminidase-treated lentiviral particles driving GFP expression under either human/mouse CMV, human/mouse EF1 α , CAG, PGK and UBC promoters. Scale bar = 20 μ m. b Mean fluorescence intensity (MFI) values of myoepithelial and luminal cells 48 h post-infection with lentiviral particles as in (a). Images and values are representative of cells derived from two donors. Figure S2. Spheroids formed in Matrigel cultures express markers of both luminal and myoepithelial cells. Expression of cytokeratin (CK) 8 and P-cadherin in spheroids formed in Matrigel from co- culture of isolated myoepithelial and luminal cells over 21 days. Images are representative of cells derived from at least three donors. Scale bar = 20 μ m. Figure S3. Objective and systematic calculation of cell and spheroid volumes. Representative workflow of spheroid analysis. Raw DAPI z-sections (a) are converted into greyscale images and a greyscale distribution profile (b). Greyscale images are then converted to binary images using a calculated threshold to indicate cell presence (c). The pixels that indicate cells are then translated into a geometrically accurate point cloud using the known image resolutions (d). Further post-processing using density-based spatial clustering of applications with noise (DBSCAN) is performed to identify the main body of cells (e). The point cloud representing the main spheroid is then extracted (f). The alpha-shape algorithm is applied using thresholds set as a function of the image resolutions to form triangulated bodies that represent the cells and body (g). The volumes of these bodies are then calculated alongside the resultant cell/body ratio. (PDF 1342 kb)
Myoepithelial neoplasms are tumors composed almost exclusively of cells with myoepithelial differentiation. Most behave in a benign fash- ion and are designated myoepithelioma. Myo- epithelialcarcinoma (MC), also known as malig- nant myoepithelioma, is the malignant counter- part of benign myoepitheliom, and is distin- guished from benign myoepithelioma by its infiltrative, destructive growth . Myoepithelial neoplasms account for about 1.5% of all sali- vary tumors, and MC is even rarer, representing about 10% of myoepitheliomas [1-3]. However, myoepitheliomas show a wide spectrum of morphologic and immunophenotypic variation, resulting in difficulties in their diagnosis. They remain underrecognized and might not be as rare as has been reported. The tumor cells of myoepithelioms can be quite diverse, including spindled, stellate, epithelioid, plasmacytoid, basaloid, oncocytic, or clear cells [1-3]. In 2012, Esteva et al. reported 2 cases of unrecognized
cells. Ductal myoepithelial cells are spindle shaped and oriented parallel to the long axis such that they form a continuous layer around the luminal cells, especially in the ducts (Fig. 1); upon contraction the myoepithelial cells decrease the length and increase the diameter of the ducts to eject the milk . In contrast, acinar myoepithelial cells are stellate shaped, forming a discontinuous basket-like network around the luminal cells, although during pregnancy and lactation the myoepithelial cell body and processes extend to fully encompass the expanded alveolar epithelial cells . Functionally, myoepithelial cells are a hybrid of both smooth muscle (‘myo’) and epithelial cells (Table 1). Like muscle cells, myoepithelial cells express filamentous smooth muscle actin and smooth muscle myosin, and exhibit contractile properties; like epithelial cells, myoepithelial cells express intermediate filaments (the epithelial keratins) [4-6] and have cadherin-mediated cell–cell junctions [1,4,7,8]. Structurally, myoepithelial cells form distinct desmosomes with both luminal cells and other myoepithelial cells, generate gap junctions and cadherin–cadherin interactions with other myoepithelial cells, and adhere to the basement membrane (BM) via hemidesmosomes [9-12].
However, this lesion was by no means new; for example, a description was given in the seminal book on breast disease by Azzopardi : ‘There is another, more common form of clinging carcinoma in which the lesion shows no evidence of having originated as a comedo cancer and this is indeed the most difficult type to recog- nize. The involved structures are lined by a single or a few layers of neoplastic cells…, showing orientation towards the lumen, whilst there is no obvious necrosis.’ In his description, Azzopardi points out that usually several lobules are involved; that the cytoplasm may show lumenal blebbing; and that the myoepithelial layer is usually incon- spicuous (in contrast to adenosis), and that trabecular bars and bridges may be present, which are helpful in diagnosing this lesion. He even describes the granular cal- cifications originating from inspissated lumenal contents, which are the reason for pick-up on mammography. The microcalcifications that lead to the excision of these lesions are usually fine and granular with multinodular/ lobular arrangements, and often involve an area of several centimetres.
cancer cell migration and invasion, the exact mechanisms by which ECM1 promoted tumor progression remained unclear. HCC is one of the most common malignant tu- mors in China, but few patients have chance to radical exci- sion, postoperative recurrence rate is extremely high, and migration and invasion are the main factors of recurrence of HCC. In the migration of tumor involving a variety of regulatory mechanism, EMT is one of the important mech- anisms, which was first discovered at key transition steps during embryogenesis and was the critical event that medi- ated tumor metastasis . EMT refers to the epithelial cells in certain cases to the phenomenon of mesenchymal cells; the main features for the loss of epithelial phenotype and the get of mesenchymal phenotype result in heightened cell motility and invasiveness through diminished cell–cell and cell–matrix adhesion, reorganization of the cyto- skeleton, and remodeling of the ECM [24–26]. Vimentin has been recognized as a very important marker for EMT, and its overexpression has been strongly associated with metastatic phenotype and poor prognosis. More and more evidence suggest that EMT plays an extremely important role during the process of the spread of cancer of HCC [27, 28].