Basal cell adenoma with myoepithelial cell-derived “stroma”: A new major salivary gland tumor entity

The light microscopic, immunohistochemical, and ultrastructural features of a unique variant of tubular-trabecular basal cell adenoma are described. The unusual feature of the six examples reported is the richly cellular “stroma” composed of spindle cells coursing between the anastomosing cords of epithelial tumor cells. Immunohistochemistry of all six cases and electron microscopy of two examples illustrated the biphasic differentiation of the epithelial portion of this form of basal cell adenoma, with a central core of duct luminal cells bordered on either side by one or more layers of modified myoepithelial cells. By light microscopy, the features and arrangement of cells in “stromal” regions of this tumor convey a fibroblastic derivation. However, this population of cells stains strongly for S-100 protein, ultrastructurally displays excessive external lamina production, intercellular junctions, and a growth pattern unlike fibroblasts, and is involved in the formation of extracellular mucinous materials. Such aspects indicate a second population of neoplastic myoepithelial cells in this tumor. Thus, this form of tubulartrabecular basal cell adenoma displays tricellular differentiation and, perhaps, may be considered either a hybrid basal cell adenoma and myoepithelioma or a cellular pleomorphic adenoma.     

Basal cell adenoma with myoepithelial cell-derived "stroma": a new major salivary gland tumor entity

The light microscopic, immunohistochemical, and ultrastructural features of a unique variant of tubular-trabecular basal cell adenoma are described. The unusual feature of the six examples reported is the richly cellular "stroma" composed of spindle cells coursing between the anastomosing cords of epithelial tumor cells. Immunohistochemistry of all six cases and electron microscopy of two examples illustrated the biphasic differentiation of the epithelial portion of this form of basal cell adenoma, with a central core of duct luminal cells bordered on either side by one or more layers of modified myoepithelial cells. By light microscopy, the features and arrangement of cells in "stromal" regions of this tumor convey a fibroblastic derivation. However, this population of cells stains strongly for S-100 protein, ultrastructurally displays excessive external lamina production, intercellular junctions, and a growth pattern unlike fibroblasts, and is involved in the formation of extracellular mucinous materials. Such aspects indicate a second population of neoplastic myoepithelial cells in this tumor. Thus, this form of tubular-trabecular basal cell adenoma displays tricellular differentiation and, perhaps, may be considered either a hybrid basal cell adenoma and myoepithelioma or a cellular pleomorphic adenoma.     

Functional Histology of Salivary Gland Pleomorphic Adenoma: An Appraisal

The complex microstructure of salivary gland pleomorphic adenoma is examined in relation to function. Events related to secretion of macromolecules and absorption, responses to the altered microenvironment and controversies concerning epithelial–mesenchymal transition versus modified myoepithelial differentiation are explored. Their effects on tumor cell phenotypes and arrangements are emphasized. Heterotopic differentiation and attempts at organogenesis are also considered. The approach allows interpreting microstructure independently of histogenetic perceptions, envisaging the tumor cells as a continuum, endorsing luminal structures as the principal components, and defining pleomorphic adenoma as a benign epithelial tumour characterized by variable epithelial–mesenchymal transition, secretion/differentiation and metaplasia.     

Myoepithelial Carcinoma Ex Pleomorphic Adenoma of the Maxillary Sinus: A Case Report and Review of Literature

Myoepithelial carcinoma ex pleomorphic adenoma is defined as a malignant epithelial neoplasm arising from a primary or recurrent benign pleomorphic adenoma. This type of tumor comprises 3.6% of all salivary gland tumors and 12% of malignant ones. Clinically, it most commonly presents as a firm mass in the parotid gland. The development of this neoplasm in the sinonasal and nasopharyngeal regions is extremely rare and only few cases are reported in the literature. The prognosis of myoepithelial carcinoma is variable. Marked cellular pleomorphism, high mitotic rate, and high proliferative activity correspond to a poor prognosis. In this article, the authors report the histopathological features of a clinical case of a 64-years-old patient with a large median maxillary neoplasm diagnosed as myoepithelial carcinoma/ex-pleomorphic adenoma. The tumor was resected and subjected to secondary reconstruction using a revascularized free fibula flap. The myoepithelial derivation of neoplastic cells was demonstrated by immunohistochemical positivity for S-100 protein (strong and diffuse), cytokeratin 14 (strong and diffuse), and GFAP (focal).     

Carcinosarcoma (malignant mixed tumor) of the parotid: Report of a case with a pure rhabdomyosarcoma component

Background. Carcinosarcoma or true malignant mixed tumor of the parotid gland is extremely rare, accounting for <1% of all salivary gland malignancies. Methods. A 63-year-old woman presented with a 5-cm right parotid mass which was resected with a radical parotidectomy and infratemporal fossa dissection. Results. The tumor contained two distinctive histologic patterns, that of a poorly differentiated ductal carcinoma and a pleomorphic rhabdomyosarcoma. Additionally, a residual focus of pleomorphic adenoma was present peripherally, Immunohistochemical and electron microscopic studies confirmed the skeletal muscle differentiation. Conclusions. The pattern of combined rhabdomyosarcoma and ductal carcinoma has not been previously reported and adds further evidence to the myoepithelial derivation of these tumors. © 1994 John Wiley & Sons, Inc.     

Histogenesis of benign pleomorphic adenoma (mixed tumor) of the major salivary glands. An ultrastructural and immunohistochemical study

Twenty-two benign pleomorphic adenomas of the major salivary glands were studied by transmission electron microscopy and immunohistochemical techniques (three cases) in order to characterize the cell types comprising the epithelial and so-called mesenchymal regions of the tumors. Light- and electron-microscopic studies showed the tumors to consist of variable mixtures of neoplastic ductular epithelial cells, rare acinar cells, and metaplastic myoepithelial cells. Many of the loosely organized "stromal cells" contained structures indicative of their myoepithelial origin, e.g., perinuclear tonofilaments, ectoplasmic actin microfilaments, and remnants of basement membrane. Polyclonal antikeratin antisera strongly stained ductular epithelial and myoepithelial cells, squamoid cell nests, and periductular myoepithelial cells, whereas myxoid and chondroid cells were less intensely stained. Monoclonal cytokeratin antibody AE1 stained only the ductular epithelial cells in both the normal glands and tumors. In contrast, S-100 protein, which is present only in scattered acinar cells and myoepithelial cells in the normal parotid gland, was found in the ductular and periductular myoepithelial cells, isolated myxoid cells, and chondroid and cartilagenous cells in the tumors. Actin was found in all the cell types of the tumor but staining was strongest in the ducts. Double immunofluorescence staining for cytokeratin and vimentin revealed coexpression of both types of intermediate filaments in occasional normal acinar and intercalated duct myoepithelial cells, and in some cells in the myxoid and chondroid regions of the tumors. In the tumors, vimentin was present in occasional periductular myoepithelial cells, stellate myxoid cells, and especially in chondroid cells and chondrocytes. Our findings indicate that benign pleomorphic adenomas of the major salivary glands are pure epithelial cell tumors. The histologic complexity of these neoplasms is due to the ability of the neoplastic ductular myoepithelial cell to modulate its morphologic appearance and intermediate filament composition, and to produce large amounts of matrix substances. We further postulate that these tumors arise from neoplastically transformed intercalated ducts.     

Myoepithelial cells in salivary gland tumors—revisited

It is an interesting parallel that the myoepithelial cell with its hybrid epithelial and mesenchymal structural and functional phenotype has a dual role in such salivary gland tumors as pleomorphic adenoma. This cell is responsible for considerable proportions of the epithelial component of this tumor, including squamous metaplasia, and is also the agent principally involved in the synthesis, organization, and cytologic modifications of the chondromyxoid regions. Neoplastically modified myoepithelial cells are also generally accepted to be a significant component of salivary gland tumors such as epithelial-myoepithelial carcinoma, certain adenocarcinomas, and, of course, myoepitheliomas. The range of myoepithelial cell alterations can be appreciated via ultrastructural assessment of the above four classes of salivary gland tumors. An electron microscopic survey of monomorphic adenomas, adenoid cystic carcinomas, and mucoepidermoid carcinomas reveals some having a tumor cell component with structural modifications and localization similar to the modified myoepithelial cells in pleomorphic adenomas and the adenocarcinomas noted above. Such ultrastructural findings have important implications for clarifying diagnostic problems, for understanding histogenetic relationships, and for improving the classification of salivary gland tumors.     

Myoepithelial cells in salivary gland tumors--revisited

It is an interesting parallel that the myoepithelial cell with its hybrid epithelial and mesenchymal structural and functional phenotype has a dual role in such salivary gland tumors as pleomorphic adenoma. This cell is responsible for considerable proportions of the epithelial component of this tumor, including squamous metaplasia, and is also the agent principally involved in the synthesis, organization, and cytologic modifications of the chondromyxoid regions. Neoplastically modified myoepithelial cells are also generally accepted to be a significant component of salivary gland tumors such as epithelial-myoepithelial carcinoma, certain adenocarcinomas, and, of course, myoepitheliomas. The range of myoepithelial cell alterations can be appreciated via ultrastructural assessment of the above four classes of salivary gland tumors. An electron microscopic survey of monomorphic adenomas, adenoid cystic carcinomas, and mucoepidermoid carcinomas reveals some having a tumor cell component with structural modifications and localization similar to the modified myoepithelial cells in pleomorphic adenomas and the adenocarcinomas noted above. Such ultrastructural findings have important implications for clarifying diagnostic problems, for understanding histogenetic relationships, and for improving the classification of salivary gland tumors.     

Myoepithelial Cells: Their Origin and Function in Breast Morphogenesis and Neoplasia

The human breast epithelium is a branching ductal system composed of an inner layer of polarized luminal epithelial cells and an outer layer of myoepithelial cells that terminate in distally located terminal duct lobular units (TDLUs). While the luminal epithelial cell has received the most attention as the functionally active milk-producing cell and as the most likely target cell for carcinogenesis, attention on myoepithelial cells has begun to evolve with the recognition that these cells play an active part in branching morphogenesis and tumor suppression. A major question that has been the subject of investigation pertains to how the luminal epithelial and myoepithelial lineages are related and precisely how they arise from a common putative stem cell population within the breast. Equally important is the question of how heterotypic signaling occurs between luminal epithelial and surrounding myoepithelial cells in normal breast morphogenesis and neoplasia. In this review we discuss data from our laboratories and from others regarding the cellular origin of human myoepithelial cells, their function in maintaining tissue polarity in the normal breast, and their role during neoplasia.     

Desmoplasia in Different Degrees of Invasion of Carcinoma Ex-Pleomorphic Adenoma

Stroma desmoplasia was studied by immunohistochemistry for α-smooth muscle actin (α-SMA) in 17 instances of carcinoma ex-pleomorphic adenoma (CXPA) classified according to the presence of epithelial and myoepithelial cells and the degree of invasion: intracapsular, minimally and frankly invasive carcinoma. In “resident” pleomorphic adenoma, no desmoplasia was detected. In invasive areas of the intracapsular type of CXPA with only an epithelial component, desmoplasia started to be revealed by the presence of myofibroblasts close to the capsule. In the minimally invasive type, myofibroblasts were seen in the septum between islands of malignant cells and in focal peripheral areas of the tumor interpreted as the actual front of invasion. In the frankly invasive type of CXPA showing large blocks of cells, intense desmoplasia was seen, also separating the tumor cells from the neighboring normal tissue. In tumors with cords and/or small nests of cells, desmoplasia was very slight. In the invasive type of CXPA with a myoepithelial component, α-SMA expression was seen in the septum between the islands of cells. The expression was less intense and not present in all areas of the stroma. In CXPA with epithelial and myoepithelial cells, myofibroblasts were rarely seen in the septum separating sheets of cells. Thus, we may deduce that the presence of desmoplasia parallels the capacity of invasion of CXPA by epithelial cells, being minimum in the intracapsular and minimally invasive type of CXPA and increasing as the tumor becomes frankly invasive. Furthermore, we may also conclude that in CXPA with a myoepithelial component, desmoplasia is very rare.     

Salivary gland-type tumors with myoepithelial differentiation arising in pulmonary hamartoma: report of 2 cases of a hitherto unrecognized association

Reported is a hitherto unrecognized association of pulmonary hamartomas with salivary gland-type tumors showing myoepithelial differentiation, namely, a case of myoepithelioma arising in a otherwise classic hamartoma with cartilage predominance, and a case of malignant mixed tumor arising in a predominantly fibrous hamartoma resembling müllerian adenofibroma. The tumors occurred in middle-aged female patients of 35 and 44 years, respectively, and presented as 7 cm (treated with lobectomy) and 13 cm (treated with pneumonectomy) masses of the right upper lobe showing a short clinical history of cough, dyspnea, and wheezing. Both lesions did not present regional lymph node metastases after mediastinal lymphadenectomy. The myoepithelioma patient was well with no signs of recurrent disease at 6-month clinical control, but she was then lost to follow-up; the malignant mixed tumor patient is alive and well after 6 months since operation. Both tumors presented with morphologic and immunohistochemical features of myoepithelial cells, and we interpret them as being derived from a myoepithelial-like stromal cell population found within the hamartomatous areas, which is also consistently detected in classic pulmonary hamartoma. The lack of individual cell necrosis, mitotic activity, cell atypia, and pulmonary parenchyma infiltration supported a diagnosis of benign or unproven malignant potential tumor for the myoepithelioma, whereas the reverse held true for the other tumor in which the diagnosis of malignant mixed tumor of the lung was rendered. Their main importance of recognizing this association lies in separating these tumors histologically from other monophasic or biphasic tumors, either primary or secondary, such as pulmonary sarcomatoid carcinomas or true sarcomas, and metastatic salivary gland tumors, spindle cell carcinomas, melanomas, and soft tissue and visceral sarcomas.     

Lysozyme Expression Can be Useful to Distinguish Mammary Analog Secretory Carcinoma from Acinic Cell Carcinoma of Salivary Glands

Lysozyme is an enzymatic marker of acinar and intercalated duct cells of normal salivary glands. The aim of this study was to verify whether lysozyme expression could be useful to distinguish acinic cell carcinoma (ACC) from its main mimic, mammary analog secretory carcinoma (MASC). For comparison, DOG1 expression was analyzed as well. Seventeen cases of ACC, 15 MASC, and 125 other salivary tumors were studied. Lysozyme expression was found in tumor cells as well as in secreted material of MASC (86.6 % of cases) and in ductal cells of epithelial–myoepithelial carcinoma (EMC-53.8 %), pleomorphic adenoma (PA-29.1 %) and polymorphous low-grade adenocarcinoma (PLGA-23.8 %). However, in ACC, lysozyme was not expressed. Three patterns of DOG1 staining were seen: apical–luminal, cytoplasmic, and mixed cytoplasmic/membranous. The apical–luminal pattern was detected in ductal cells of ACC (58.8 % of cases), EMC (38.4 %), adenoid-cystic carcinoma (AdCC-35.3 %), PA (8.3 %), and PLGA (4.8 %). These tumors also showed mixed membranous/cytoplasmic staining for DOG1. MASC, mucoepidermoid, and salivary duct carcinomas exhibited only DOG1 cytoplasmic staining. In conclusion, lysozyme cannot be used as a marker of acinar differentiation in salivary tumors. However, lysozyme expression can be helpful to distinguish MASC from ACC due to its high frequency in the former and absence in ACC. It is likely that in MASC, lysozyme expression may reflect a lactational-like secretory differentiation since lysozyme belongs to breast milk proteins. Regarding DOG1 expression, the apical–luminal pattern is related to acinar and intercalated duct differentiation whereas the cytoplasmic staining does not seem to be associated with a specific cellular phenotype.     

Polymorphous Low Grade Adenocarcinoma has a Consistent p63+/p40? Immunophenotype that Helps Distinguish it from Adenoid Cystic Carcinoma and Cellular Pleomorphic Adenoma

Polymorphous low grade adenocarcinoma (PLGA) is a tumor of minor salivary glands that exhibits considerable morphologic overlap with adenoid cystic carcinoma and cellular pleomorphic adenoma, especially in small biopsy specimens. Unlike these other tumor types. PLGAs do not harbor a myoepithelial component, yet their frequent positivity for p63 diminishes the usefulness of this particular myoepithelial marker as a discriminating immunostain. p40 is an antibody that recognizes ΔNp63, a p63 isoform that is more specific for true myoepithelial differentiation. As such, p40 immunostaining could help distinguish PLGAs from adenoid cystic carcinomas and pleomorphic adenomas. In this study, p63 and p40 immunohistochemistry was performed on paraffin embedded, formalin fixed tissue from 11 PLGAs, 101 adenoid cystic carcinomas, and 31 pleomorphic adenomas. All 11 PLGAs (100 %) were positive for p63 but completely negative for p40. Among adenoid cystic carcinomas, 91 of 101 (90 %) were positive for p63 and 90/101 (89 %) were positive for p40. The single discordant p63+/p40− adenoid cystic carcinoma exhibited solid architecture and high grade features not typically seen in PLGA. Among pleomorphic adenomas, 21/31 (68 %) were positive for p63 and 13/31 (42 %) were positive for p40. For the pleomorphic adenomas, the discordant p63+/p40− staining pattern was seen only in the overtly mesenchymal chondromyxoid stroma. The cellular epithelial component of the pleomorphic adenomas demonstrated concordant p63+/p40+ or p63−/p40− immunophenotypes. PLGA consistently exhibits a p63+/p40− immunophenotype that can help distinguish it from adenoid cystic carcinoma and cellular pleomorphic adenoma, tumors that characteristically demonstrate concordant p63 and p40 immunostaining patterns. A p63/p40 immunohistochemical panel can provide a valuable tool for making the distinction between these morphologically similar but clinically divergent entities.     

The pathology of head and neck tumors: Salivary glands,part 3

The term adenoma is applied to a rather wide variety of histopathologic entities in the salivary glands. These include tumors derived from the ductal epithelium and/or from myoepithelial cells and other salivarygland elements, such as the sebaceous glands. Within the categories of mixed tumor (pleomorphic adenoma), monomorphic adenoma, clear-cell tumor, and sebaceous lesions, there are also several subtypes, each of which lends further credence to the germinative potential of the salivary tissues. Presented in this report is a clinicopathologic and histogenetic analysis of these lesions. Specifically discussed are mixed tumor, monomorphic adenoma, carcinoma ex-pleomorphic adenoma, clear-cell tumor, sebaceous lymphadenoma, and sebaceous carcinoma.     

Carcinoma ex Pleomorphic Adenoma of the Nasal Cavity

Background  

Carcinoma ex pleomorphic adenoma (CXPA) is a malignant epithelial neoplasm arising in a benign mixed tumor (i.e., pleomorphic adenoma or PA); it accounts for approximately 3–4% of all salivary gland neoplasms. CXPA is exceedingly rare in the nasal cavity, with only three cases previously documented.     

Do Myoepithelial Cells Hold the Key for Breast Tumor Progression?

Mammary myoepithelial cells have been a neglected facet of breast cancer biology, largely ignored since they have been considered to be less important for tumorigenesis than luminal epithelial cells from which most of breast carcinomas are thought to arise. In recent years as our knowledge of stem cell biology and the cellular microenvironment has been increasing, myoepithelial cells are slowly starting to gain more attention. Emerging data raise the hypothesis whether myoepithelial cells play a key role in breast tumor progression by regulating the in situ to invasive carcinoma transition and that myoepithelial cells are part of the mammary stem cell niche. Paracrine interactions between myoepithelial and luminal epithelial cells are known to be important for regulation of cell cycle progression, establishing epithelial cell polarity, and inhibiting cell migration and invasion. Based on these functions, normal mammary myoepithelial cells have been called “natural tumor suppressors.” However, during tumor progression myoepithelial cells seem to loose these properties, and eventually this cell population diminishes as tumors become invasive. Better understanding of myoepithelial cell function and their role in tumor progression may lead to their exploitation for cancer therapeutic and preventative measures.     

Characterization of epimyoepithelial islands in benign lymphoepithelial lesions of major salivary gland: an immunohistochemical and ultrastructural study

Knowledge of the processes leading to the development of epimyoepithelial islands bears on histogenetic and morphogentic processes in salivary gland tumors. Immunohistochemical and ultrastructural investigations of the cellular composition of epimyoepithelial islands were carried out on three examples of benign lymphoepithelial lesions with varying histologic features. The monoclonal anti-keratin antibody 312C8-1, which specifically decorates myoepithelial cells of the normal salivary gland, also stains the myoepithelial cells surrounding residual acini and intercalated ducts in benign lymphoepithelial lesions and the cell population of epimyoepithelial islands, with the exception of persisting luminal epithelial cells. Ultrastructurally, the myoepithelial cells of involuting acini and ducts and the modified myoepithelial cells of epimyoepithelial islands, identified in both locations by the monoclonal antibody 312C8-1, show an increasing complement of tonofilament bundles. In addition, persisting lumens (often distended with lymphocytes) and definite luminal epithelial cells can be seen in electron micrographs of some epimyoepithelial islands. The designation for this characteristic epithelial feature of benign lymphoepithelial lesions is therefore appropriate.     

Pleomorphic adenoma with extensive lipometaplasia: report of three cases

We report a series of three cases of pleomorphic adenoma with extensive lipometaplasia, a recently described subtype of pleomorphic adenoma of salivary gland origin. Two patients were female and one male, ranging in age from 30 to 45 years. Two occurred in the minor salivary glands of the lip and palate, respectively, and one in the parotid. Typical histologic findings are presented. In addition, one case consists of a proliferation of spindle cells with an interesting combination of mature adipose tissue, hyaline cartilage, and bone in the absence of ductal structures. The differential diagnosis, as it pertains to other fat-containing tumors (such as lipoadenoma, spindle cell lipoma, interstitial lipomatosis, and benign mesenchymoma), is discussed. It is likely that the ability of myoepithelial cells to undergo various metaplasias is the cause of the unusual histologic appearances of this tumor.