bromochloroacetic-acid and Adenoma--Pleomorphic

Primary pleomorphic adenoma of the lung is an uncommon condition. We present a case of primary pulmonary pleomorphic adenoma and its immunohistologic features. The presence of immunoreactivity to both anticytokeratin and antivimentin antibodies for its epithelial components is suggestive of a primary pulmonary lesion. Its high proliferation index and its immunoreactivity to tumor regulatory gene p16(INK4A) are features that, to our knowledge, have not been reported previously. They may have a role in the frequent recurrence of these tumors many years after their apparently complete excision. Detailed genetic investigation and long-term follow-up of this rare tumor will aid in the characterization of its biologic profile.

Topics: Adenoma, Pleomorphic; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Middle Aged; Vimentin

Topics: Adenoma, Pleomorphic; Adolescent; Choristoma; Cytoplasm; Head and Neck Neoplasms; Humans; Keratins; Male; Neoplasms, Multiple Primary; Salivary Glands; Vacuoles

True malignant mixed tumor (TMMT) of salivary glands, with both carcinomatous and sarcomatous components, is exceedingly rare. We offer a case of TMMT in a 79-yr-old man, which may represent the first report example of this unusual neoplasm arising in the tongue. The carcinomatous component was mainly of solid basaloid carcinoma with focal glandular differentiation, while the sarcomatous component was composed of pleomorphic elements such as chondrosarcoma, myxosarcoma and fibrosarcoma. Carcinoma cells at the periphery of solid nests occasionally merged into these sarcomatous elements. Immunohistochemically, basaloid carcinoma cells showed positive reaction for both low molecular weight cytokeratin and S-100 protein, whereas carcinoma cells lining ductal spaces were positive for a wide spectrum of keratin and EMA. The sarcomatous elements revealed the presence of vimentin and S-100 protein. Ultrastructurally, basal lamina-like material and/or mucoid precipitates often accumulated separating the tumor cells from each other singly or into a few cell group. Some sarcomatous cells assumed the myoepithelial features, such as the presence of microfilament bundles with dense bodies and pinocytotic vesicles along the cell periphery. These findings may indicate that TMMT shares a common histogenesis with pleomorphic adenoma.

Topics: Actin Cytoskeleton; Adenoma, Pleomorphic; Aged; Carcinosarcoma; Desmosomes; Humans; Immunohistochemistry; Keratins; Male; S100 Proteins; Tongue Neoplasms; Vimentin

An unusual case of pleomorphic adenoma displaying numerous horny pearls is described. The tumour arose in the right lateral lingual border of a 33-year-old man. In many pearls the cores were organized in two separate portions with distinct structural and histochemical features. The narrow peripheral portion had a compact structure and was rich in keratin since it contained cystine and was coloured with acid dyes of intermediate molecular size. The central portion was characterized by a loose texture and its histochemical profile (affinity for acid dyes of large molecular size, weak alcianophilia, vivid binding of colloidal iron) resulted from the existence of acidic mucosubstances in the cell coating of the neoplastic keratinized cells. These observations suggest that certain similarities exist between the processes of normal keratinization and squamous metaplasia in pleomorphic adenoma.

Topics: Adenoma, Pleomorphic; Adult; Histocytochemistry; Humans; Keratins; Male; Metaplasia; Salivary Gland Neoplasms

10 pleomorphic adenomas of the human parotid gland were transplanted on several groups of nude mice. For comparative reasons, 10 other pleomorphic adenomas, a neurinoma and a chordoma and transplants of squamous cell carcinomas and of normal salivary gland tissue were also analysed. In the primary tumours and in the transplants, the presence of keratin, carcinoembryonic antigen, tissue polypeptide antigen, lactoferrin, lysozyme, immunoglobulins, secretory component, amylase, fibronectin and of several lectin-receptors (PNA, WGA, HPA, Ulex europaeus) was sought. The immunohistological observations show that many of the features of a pleomorphic adenoma are constant under the conditions of transplantation. In the transplanted tumour, the same heterogeneity as in the primary tumours can be observed. Autoradiographic studies show little labelling with 3-H thymidine, which is in good accordance with the biological behaviour of the tumour. The distribution of fibronectin shows an interesting association with myoepithelial-like cells. Our results support the hypothesis that the histogenetic origin of the pleomorphic adenoma is a cell pool of the terminal ductal segment. A differentiation towards ductal cells (with production of secretory substances) and towards myoepithelial cells (associated with large amounts of basal membrane like substances) is observed.

Topics: Adenoma, Pleomorphic; Animals; Autoradiography; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cell Division; Fibronectins; Histocytochemistry; Humans; Immunochemistry; Immunoglobulin A; Immunoglobulin A, Secretory; Immunoglobulin G; Immunoglobulin M; Keratins; Lactoferrin; Lectins; Mice; Mice, Nude; Muramidase; Neoplasm Transplantation; Salivary Gland Neoplasms; Tetradecanoylphorbol Acetate; Transplantation, Heterologous

Cutaneous myoepithelial neoplasms are a heterogenous group of neoplasms with mixed tumors typically affecting the head and myoepitheliomas showing a predilection for the extremities. Their malignant counterparts, myoepithelial carcinoma, and malignant mixed tumor are exceptionally rare in the skin, and the morphologic criteria for malignancy are only poorly defined. The aim of the present study was to characterize the clinicopathologic features of myoepithelial neoplasms presenting on acral skin. The clinical and histopathologic features of 11 tumors were recorded, and follow-up was obtained. Immunohistochemistry was performed for S100, SOX10, glial fibrillary acidic protein, keratins, epithelial membrane antigen, p63, p40, smooth muscle actin, desmin, and PLAG1. The tumors mainly affected the feet of adults (range: 26 to 78 y; median: 47 y) with a predilection for the great toe and a male predominance of 1.8:1. Most tumors (91%) displayed a lobular architecture composed of solid and nested growth of epithelioid cells with plasmacytoid features in a myxoid or angiomatous stroma. Scattered cytologic atypia and rare duct differentiation were frequently noted. Three tumors with confluent cytologic atypia, infiltrative growth, and lymphovascular invasion were classified as malignant. By immunohistochemistry, the tumors were positive for S100, SOX10, keratins AE1/AE3, CK5/6 and CK7, and PLAG1. Local recurrence and bilateral pulmonary metastasis were observed in a patient presenting with a histopathologically benign-appearing tumor. Two patients with malignant tumors experienced local recurrences, and 1 developed metastasis to soft tissue, lung, and mediastinal lymph nodes. All patients are currently alive, all but 1 with no evidence of disease after a median follow-up interval of 96 months (range: 2 to 360 mo). In conclusion, acral myoepithelial neoplasms show distinctive and reproducible histopathologic and immunohistochemical features. They are best regarded as a distinctive subset of mixed tumors with features reminiscent of their salivary gland counterparts. While most tumors pursue a benign disease course, histopathologic features appear to be a poor indicator of prognosis.

Topics: Adenoma, Pleomorphic; Adult; Aged; Biomarkers, Tumor; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Myoepithelioma; Skin Neoplasms

Mucoepidermoid carcinoma (MEC) arising in pleomorphic adenoma (PA) is an extremely rare entity. Involvement of minor salivary glands by this entity has only being described twice previously. We report on a diagnostically challenging case in an 18 year old male with a large mass in the junction of the hard and soft palates that has been present for 12 months. Both cytology and incisional biopsy were inconclusive and indicated benign mixed tumour. Upon excision of the tumour with a 5 mm clear margin, histology demonstrated PA that has been replaced by small nests and cribriform islands of high-grade MEC with 13 mm of invasion beyond the original PA capsule. The tumour was composed of mostly intermediate-type cells with up to 7 mitoses per 10 high power fields. The tumour cells were positive for cytokeratin (CAM 5.2) and S100. Due to the high-grade nature and focal positive posterior margin of the resected specimen, adjuvant radiotherapy was administered. In conclusion, this case highlights the need to consider rare entities such as mucoepidermoid carcinoma ex pleomorphic adenoma in atypical cytological and histological findings. Moreover, it underlines the need to manage lesions with unconfirmed histological diagnosis with wide excision margins to avoid having involved margins post resection.

Topics: Adenocarcinoma; Adenoma, Pleomorphic; Adolescent; Carcinoma, Mucoepidermoid; Humans; Keratins; Male; Salivary Gland Neoplasms; Salivary Glands, Minor

Myoepithelial tumors comprise a group of mesenchymal lesions that show heterogeneous histomorphological features, including dual epithelial, neural, and myoid differentiation. Cutaneous myoepithelioma is a rare neoplasm that is composed primarily of myoepithelial cells and represents one end of a histopathological spectrum of cutaneous myoepithelial neoplasms including chondroid syringoma and myoepithelial carcinoma. These tumors display a wide histopathological spectrum and immunophenotypical profile often showing epithelial and myoepithelial differentiation. In this series, we studied 35 cases of cutaneous myoepitheliomas. Our cases highlighted the broad histopathological range where most cases showed a non-infiltrative and non-encapsulated tumor exclusively located in the dermis and with no subcutaneous involvement. The majority of our cases had a solid growth pattern (syncytial pattern) and the remainder of cases had a multinodular growth pattern. The tumor cells were epithelioid in 23 cases, spindled in eight cases and there was a mixture of epithelioid and spindled cells in four cases. Mitotic figures ranged from 0 to 5 per 10 HPF. By immunohistochemistry epithelial membrane antigen (EMA) was expressed in 59% of cases S100 was positive in 88% of cases, CAM 5.2 was positive in 16% of cases, AE1/AE3 was positive in 44% of cases, p63 was positive in 17% of cases, smooth muscle actin was positive in 38% of cases, desmin was positive in 6% of cases, calponin was positive in 22% of cases, and glial fibrillary acidic protein was positive in 36% of cases. In addition, there were five cases without EMA, keratin, or p63 expression that only showed S100 expression. We describe a large series of cutaneous myoepitheliomas delineating their histomorphological spectrum and immunophenotypical profile. Awareness of some of the unusual histopathological features and the heterogeneous immunohistochemical may pose difficulties for the diagnosis.

Topics: Actins; Adenoma, Pleomorphic; Adult; Anion Exchange Protein 1, Erythrocyte; Awareness; Biomarkers; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; Carcinoma; Chloride-Bicarbonate Antiporters; Desmin; Diagnosis, Differential; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Male; Membrane Proteins; Microfilament Proteins; Mucin-1; Myoepithelioma; S100 Proteins; Skin Neoplasms

Carcinoma ex pleomorphic adenoma (Ca ex PA) is a malignant neoplasm arising from primary or recurrent benign pleomorphic adenoma. It is rare with an annual incidence rate of 0.17 tumors per million. Histopathology remains the gold standard for the diagnosis of Ca ex PA, with only a handful of cases reported on cytology. In our case a 66-year-old male presented with the right parotid mass for 5 years rapidly increasing for the last 3 months. Fine needle aspiration cytology (FNAC) smears showed malignant tumor cells in clusters along with benign myoepithelial cells in chondromyxoid background. Histopathologically, highly pleomorphic malignant epithelial cells in sheets along with foci of comedonecrosis and areas corresponding to benign pleomorphic adenoma were observed on careful scrutiny. Immunohistochemistry revealed positivity for cytokeratin (CK 7) and gross cystic disease fluid protein 15 (GCDFP-15) while CK5/6 and high molecular weight CK (34 βE12) were negative in the malignant tumor cells. So, the final impression was Ca ex PA with salivary duct carcinoma as malignant component. We hereby report this case to highlight the significance of FNAC in the diagnosis of Ca ex PA which can be easily missed on cytopathology. However, it is important to corroborate the cytological findings with clinical suspicion of malignancy as well as radiology. Diagn. Cytopathol. 2017;45:651-654. © 2017 Wiley Periodicals, Inc.

Topics: Adenocarcinoma; Adenoma, Pleomorphic; Aged; Biomarkers; Biomarkers, Tumor; Biopsy, Fine-Needle; Carrier Proteins; Diagnosis, Differential; Epithelial Cells; Gene Expression; Glycoproteins; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Membrane Transport Proteins; Parotid Gland; Parotid Neoplasms; Salivary Gland Neoplasms

Pleomorphic adenoma (PA) of the breast is a rare tumour seen usually in postmenopausal women. Although PA of the salivary glands (SG) is recognized to be a benign tumour, the nature and biology of similar tumours seen in the breast remains to be defined. The aim of this study was to describe PA of the breast that was reported on core biopsy as an invasive matrix-producing metaplastic breast carcinoma (MBC).. A core biopsy from a clinically malignant retroareolar mass showed mildly atypical polygonal cells with surrounding myxoid stroma. Immunohistochemistry showed expression of basal and luminal cytokeratins, but oestrogen receptor, human epidermal growth factor receptor 2 (HER2) and myoepithelial markers were negative. The excision specimen showed similar features, but in addition the stroma showed cartilage and bone. Also it was clear that the lesion was circumscribed and merged with a sclerosed papillary lesion consistent with what has been described as mammary PA.. This lesion shows an overlap of morphology and immunophenotype with SG-PA and with MBC. The majority of mammary PAs have a benign behaviour, but local recurrence and development of carcinoma occur. We propose a new terminology of pleomorphic adenoma-like tumour of the breast to reflect the uncertain nature of these tumours and help guide management decisions.

Topics: Adenoma, Pleomorphic; Biomarkers, Tumor; Breast; Breast Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Neoplasm Recurrence, Local; Receptor, ErbB-2; Salivary Gland Neoplasms; Salivary Glands

We report a rare case of pleomorphic adenoma arising from the nasal septum. A 37-year-old woman presented with a 1-year-history of right-sided occasional epistaxis. Computed tomographic scans revealed an oval mass in the right nasal cavity. The tumor was removed endoscopically with endonasal approach. The microscopic finding showed numbers of myoepithelial cells and duct-like structures consisting of loose myxoid stroma. This lesion had histological characteristics of a pleomorphic adenoma, and this was confirmed by immunohistochemical expression of cytokeratin, S-100 protein and SMA. Her post-operative course was uneventful, and she is currently free from the disease 1.5 years after surgery.

Topics: Actins; Adenoma, Pleomorphic; Adult; Endoscopy; Epistaxis; Epithelial Cells; Female; Humans; Keratins; Nasal Septum; Nose Neoplasms; S100 Proteins

There are well known that Wnt signaling was some roles of cell differentiation at the development tissues, especially the oral and maxillofacial regions of some developmental stages. Therefore, to determine Wnt signaling in the pleomorphic adenoma tissues, we examined. The expression of Wnt1 and β-catenin as well as the distribution of various cytoskeletal proteins CK7 and CK13 was examined in 30 cases of pleomorphic adenoma by immunohistochemistry. Wnt1 was detected in almost all tumor cells. The peripheral columnar cells in squamous metaplasia and small cuboidal cells in duct-like structures were strongly positive to Wnt1. Although β-catenin was clearly localized on the cell membrane of tumor cells, nuclear translocation was observed in small cuboidal cells and in some basaloid cells. The immunofluorescent staining pattern of Wnt1 and CK7 as well as Wnt1 and CK13 was consistent with IHC results. Thus, in pleomorphic adenoma, Wnt is involved in tumor cell differentiation of peripheral columnar cells forming solid nests and small peripheral columnar cells forming duct-like structures. Moreover, among the three currently known Wnt pathways, β-catenin is the suggested pathway working during cell differentiation. Furthermore, peripheral columnar cells in solid tumor nests and in squamous metaplasia are governed by another Wnt pathway other than β-catenin. Therefore, Wnt signaling through β-catenin pathway may be involved in the 'mixed' differentiation characteristic of pleomorphic adenoma although another pathway may also be possibly working in other parts of the tumor tissue.

Topics: Adenoma, Pleomorphic; beta Catenin; Cell Differentiation; Epithelial Cells; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Wnt Signaling Pathway; Wnt1 Protein

We report a case of carcinoma ex pleomorphic adenoma of a sublingual gland in a 70-year-old man. Under a clinical diagnosis of benign salivary gland tumor, excision of the mass with the sublingual salivary gland in an en bloc fashion via an intraoral approach was performed. Histopathologically, there was a rupture of the fibrous capsule and diffuse cell-rich sheets composed of myoepithelial cells with round nuclei were also seen. Immunohistochemically, the cells that composed of cell rich sheets were positive to smooth muscle actin. Final diagnosis of myoepithelial carcinoma ex pleomorphic adenoma was made.

Topics: Adenoma, Pleomorphic; Aged; Carcinoma; Diagnosis, Differential; Glial Fibrillary Acidic Protein; Humans; Keratins; Male; Myoepithelioma; Neoplasm Invasiveness; S100 Proteins; Sublingual Gland Neoplasms

Pleomorphic adenoma is the most common neoplasm of the salivary glands and is most commonly located in the parotis followed by the submandibular glands. Its localization in the minor salivary glands is mostly reported in the palate. Few publications report pleomorphic adenoma cases located in the lip. We present a 35-year-old male patient with a pleomorphic adenoma located in the upper lip.

Topics: Actins; Adenoma; Adenoma, Pleomorphic; Adult; Biomarkers, Tumor; Diagnosis, Differential; Humans; Keratins; Lip Neoplasms; Male; Myoepithelioma; Salivary Gland Neoplasms; Salivary Glands, Minor

Pleomorphic adenoma (PA), the most common salivary gland tumor, accounts for 54 to 65% of all salivary gland neoplasias and 80% of the benign salivary gland tumors. It most frequently affects the parotid gland, followed by the submandibular and the minor salivary glands. Microscopically, mucous, sebaceous, oncocytic and squamous metaplasia, sometimes with the formation of keratin pearls, may be present, but the latter rarely results in the formation of extensive keratin-filled cysts lined by squamous epithelium. Extensive squamous metaplasia can be mistaken for malignancy, including mucoepidermoid carcinoma and squamous cell carcinoma. Here, we present an unusual case of PA with extensive squamous metaplasia and keratin cyst formations in a minor salivary gland, and discuss its microscopic features, including the immunohistochemical characteristics, and differential diagnosis of this uncommon presentation.

Topics: Adenoma, Pleomorphic; Adult; Humans; Immunohistochemistry; Keratins; Male; Metaplasia; Salivary Gland Neoplasms; Salivary Glands, Minor

Squamous cell carcinoma ex-pleomorphic adenoma (CXAP) is a malignant and rare mixed tumor. We report a new case.. A seventy-year-old woman consulted for a mass in the left hemi-face having evolved over the last 20years. The physical examination revealed a hard and large tumor invading all the palate. Computed tomography revealed a heterogeneous 8.5cm long maxillary mass. The diagnosis of CXAP was made on a biopsy. A histological study confirmed the diagnosis after surgical resection of the tumor, specifying its noninvasive character.. CXAP is generally located in the parotid gland; it is very rarely located in the palate. The degenerated epithelial component generally corresponds to an adenocarcinoma or an undifferentiated carcinoma; squamous-cell carcinoma is more rarely reported. The prognosis is excellent for the micro and noninvasive types. Surgery remains the treatment of choice.

Topics: Adenoma, Pleomorphic; Aged; Amyloid; Biopsy; Carcinoma, Squamous Cell; Cell Nucleus; Epithelial Cells; Female; Follow-Up Studies; Humans; Keratins; Neoplasms, Multiple Primary; Neprilysin; Palatal Neoplasms; Tomography, X-Ray Computed

Pleomorphic adenoma (PA) is a rare tumor of the skin that may arise from either the apocrine or the eccrine glands. Only 4 cases of PA in the auricle have been reported. We experienced the case of a 40-year-old woman who had a slowly growing, nontender auricle mass for 3 years. Under a clinical diagnosis of an epidermal inclusion cyst, we performed a total excision of the tumor with the skin and with direct closure. No recurrence was found during the 18 months of postoperative follow-up. Histologic examination confirmed a diagnosis of PA. Hematoxylin-eosin stain showed tubules that were lined with 2 layers of epithelial cells. The stroma was composed of the myxoid and chondroid matrices. Immunohistochemical staining was positive for cytokeratin, epithelial membrane antigen, and gross cystic disease fluid protein, whereas it was negative for S-100 and carcinoembryonic antigen. These findings suggested that this tumor originated from the apocrine glands. Only a few cases of PA in the auricle have been reported in the literature, 2 of which occurred in the helical rim. Recurrence is rare if there is complete resection of the tumor along with the surrounding capsule. We report herein a rare case of PA that developed in the auricle.

Topics: Adenoma, Pleomorphic; Adult; Biomarkers, Tumor; Carrier Proteins; Cyst Fluid; Diagnosis, Differential; Ear Auricle; Ear Diseases; Ear Neoplasms; Epidermal Cyst; Epithelial Cells; Female; Follow-Up Studies; Glycoproteins; Humans; Keratins; Membrane Transport Proteins; Mucin-1

Topics: Adenoma, Pleomorphic; Adult; Biomarkers, Tumor; Bone Marrow Cells; Calcinosis; Forehead; Humans; Keratins; Male; Ossification, Heterotopic; Radiography; Sweat Gland Neoplasms

The histogenetic origin of salivary gland tumours is not clear. In normal tissues smooth muscle actin (SMA) is expressed in myoepithelial cells, CK14 immunoreactivity is seen in myoepithelial and basal cells and CK10 in keratinized squamous epithelium. In this study, we examine the immunophenotypic properties of salivary gland tumours in order to obtain further insight into their histogenesis. 30 cases of salivary gland tumours (18 pleomorphic adenomas, 8 Warthin's tumours, 2 basal cell adenomas, 2 acinic cell carcinomas) were included in our study. Cytokeratin (CK) 10, CKI4, CKI7, CK18, CK 19, and smooth muscle actin (SMA) immunostains were applied to the sections. Immunoreactivities were detected and the statistical significance was evaluated by chi square test. SMA was not detected in Warthin's tumour (p < 0.0001). CK14 was found in all tumours except acinic cell carcinomas (p < 0.0001). CK10 immunoreactivity was observed in 5 Warthin's tumour. In conclusion, pleomorphic adenomas and basal cells adenomas originate from stem cells. Immunophenotypic profile of Warthin's tumour is suggestive of an embryological remnant origin.

Topics: Actins; Adenolymphoma; Adenoma; Adenoma, Pleomorphic; Carcinoma, Acinar Cell; Humans; Immunophenotyping; Keratins; Neoplasm Proteins; Organ Specificity; Protein Isoforms; Retrospective Studies; Salivary Gland Neoplasms

To characterize the cellular component in pleomorphic adenoma (PA) that undergoes malignant transformation in carcinoma ex pleomorphic adenoma (CXPA).. A panel of antibodies against cytoskeletal proteins was applied in 16 cases of CXPA: intracapsular carcinoma (five cases), minimally invasive (four cases) and frankly invasive (seven cases). The CXPAs were classified into two main groups according to their predominant cellular component as detected by the panel of antibodies: (i) carcinomas with only epithelial differentiation (75% of the cases), and (ii) carcinomas with a myoepithelial component (25%). CXPA with only epithelial differentiation showed two types of malignant areas in the part of the tumour that was confined by the PA capsule: (i) intraductal carcinoma areas characterized by ductal structures containing both benign myoepithelial cells positive for alpha-smooth muscle actin (alpha-SMA), vimentin and cytokeratin (CK)14 and proliferating atypical luminal cells reactive for CK7, CK8 and CK19, and (ii) carcinoma areas composed only of epithelial cells reactive for CK7, CK8 and CK19. In the latter, the cells presented morphological and immunohistochemical characteristics similar to those found in areas of invasive carcinoma outside the PA capsule. CXPAs with a myoepithelial component were composed mainly or exclusively of cells that expressed vimentin and alpha-SMA. In this group, ductal structures reminiscent of PA filled by malignant cells were not identified.. Most CXPAs consist only of epithelial cells that have an immunoprofile comparable to ductal luminal cells of PA. These malignant luminal cells arise in the duct-like structures as intraductal carcinoma and probably only at this early stage of development should the lesion be considered as a non-invasive carcinoma.

Topics: Actins; Adenocarcinoma; Adenoma, Pleomorphic; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Disease Progression; Female; Humans; Immunohistochemistry; Keratin-14; Keratin-7; Keratins; Male; Middle Aged; Muscle, Smooth; Vimentin

Pleomorphic adenoma of the external auditory canal is a rare disease. It is considered to derive from the ceruminous glands. The objective of this study is to familiarize the clinician with the clinical presentation and treatment of this disease. We report the case of a 58-year-old woman. Complete resection should be applied for cases in which magnetic resonanace imaging (MRI) and computerize tomography (CT) examination indicate no erosion in the bone and cartilage tissue. The patient should be seen regularly for recurrence.

Topics: Adenoma, Pleomorphic; Audiometry, Pure-Tone; Chondrocytes; Ear Neoplasms; Ear, External; Female; Hearing Disorders; Humans; Immunohistochemistry; Keratins; Magnetic Resonance Imaging; Middle Aged; S100 Proteins; Severity of Illness Index; Tomography, X-Ray Computed

Topics: Actins; Adenoma, Pleomorphic; Diagnosis, Differential; Glial Fibrillary Acidic Protein; Humans; Infant; Keratins; Male; Nasal Cavity; Neoplasm Recurrence, Local; Nose Neoplasms; Reoperation; Vimentin

We report a rare case of pleomorphic adenoma arising from the nasal septum. A 32-year-old woman presented with a 3-week-history of left-sided nasal obstruction. Computed tomographic scans revealed an oval mass, measuring about 30 mm in its greatest dimension, in the left anterior nasal cavity. The tumor arose from the anterior part of the nasal septum, and was removed endoscopically with endonasal approach. The microscopic finding showed a lobular and duct-like structures consisting of a loose chondromyxoid stroma. This lesion had histological characteristics of a pleomorphic adenoma, and this was confirmed by immunohistochemical expression of cytokeratin and S-100 protein. Her post-operative course was uneventful, and she is currently free from the disease 8 months after surgery. Diagnosis, clinical behavior and treatment of pleomorphic adenoma of the nasal septum are reviewed from perusal of the literature.

Topics: Adenoma, Pleomorphic; Adult; Female; Humans; Immunohistochemistry; Keratins; Nasal Septum; Nose Neoplasms; Tomography, X-Ray Computed

To determine the cellular origin of plasmacytoid cells in salivary gland adenomas, immunohistochemistry was performed on sections from 12 pleomorphic adenomas rich in these cells. In normal salivary glands included in these sections, the myoepithelial cells (MECs) expressed alpha-smooth muscle actin (alphaSMA) and smooth muscle myosin heavy chain (SMMHC), whereas the duct luminal cells expressed keratins 19, 18 and 8. Some of the salivary duct basal cells expressed these keratins, and the acinar cells expressed keratins 18 and 8. The expression profile was similar in rat salivary glands not only after but also during development. The immature MECs never expressed the keratins nor did the immature duct cells express alphaSMA. In seven cases, up to 60% of the plasmacytoid cells expressed keratin 19. In three of these cases, about 10% of the plasmacytoid cells expressed keratin 18. No plasmacytoid cells expressed alphaSMA, SMMHC or keratin 8. These results indicate that plasmacytoid cells originate from luminal cells and not from MECs. Furthermore, in addition to the luminal tumor cells, the non-luminal cells could express keratins 19, 18 and 8. Therefore, it is necessary to re-evaluate the prevailing notion that non-luminal cells are modified MECs. Keratin 14, basic calponin, vimentin and p63 were bi-specific for the MECs and the duct cells. Therefore, expression of these proteins by significant numbers of the non-luminal tumor cells and the plasmacytoid cells never denied the above notion.

Topics: Adenoma, Pleomorphic; Adult; Aged; Animals; Biomarkers, Tumor; Cell Lineage; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Rats; Salivary Gland Neoplasms; Salivary Glands

Intranasal pleomorphic adenoma is a rare neoplasm, and thus only one case report addressed immunohistochemical findings of this neoplasm. To define immunohistochemical features of intranasal pleomorphic adenoma, we studied three cases of the pleomorphic adenoma developed from the nasal septum. Subsequently, immunohistochemical reactivities of the tumor cells for various cytokeratins, glial fibrillary acidic protein (GFAP), S100 protein, alpha-smooth muscle actin (SMA), and vimentin were similar to those of pleomorphic adenoma of the parotid gland. The tumors examined in this study had different histological components, such as predominance of myxoid area, solid area, or tubuloductal structure, but immunoreactivity of both epithelial and myoepithelial tumor cells were the same in the tumors. Therefore, immunoreactivity of the tumor cells were the same among the intranasal pleomorphic adenoma having various histological components.

Topics: Actins; Adenoma, Pleomorphic; Adult; Aged; Biomarkers, Tumor; Female; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Keratins; Male; Nasal Cavity; Nasal Obstruction; Nose Neoplasms; S100 Proteins; Vimentin

Topics: Actins; Adenoma, Pleomorphic; Adipose Tissue; Aged; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Muscle, Smooth; Parotid Neoplasms; S100 Proteins

Our recent study of developing myoepithelial cells (MECs) in rat salivary glands demonstrated that developing MECs begin to express alpha-smooth muscle actin (alphaSMA) first and, thereafter, keratin 14. Therefore, it is unlikely that duct basal cells expressing keratin 14 alone are immature or undifferentiated MECs. In this study we carried out immunohistochemistry of pleomorphic adenomas and adenoid cystic carcinomas including normal salivary glands using monoclonal antibodies to keratin 14, smooth muscle proteins and keratin 19. The smooth muscle proteins examined included alphaSMA, h-caldesmon and h1-calponin; h1-calponin was observed in keratinocytes and nerve fibers, indicating that the protein is not specific to smooth muscle, whereas alphaSMA and h-caldesmon turned out to be highly specific markers for smooth muscle cells in normal tissues. In normal glands, MECs were positive for both keratin 14 and smooth muscle proteins (alphaSMA and h-caldesmon). Non-MEC cells were essentially devoid of smooth muscle proteins. Non-MEC duct basal cells expressed keratin 14 with or without keratin 19, and luminal cells keratin 19 with or without keratin 14. This suggests that the keratin 14-positive, smooth muscle proteins-negative duct basal cells are luminal cell progenitors. Luminal cells in tubular structures of both tumors were positive for keratin 19 with or without keratin 14. Nonluminal peripheral cells of pleomorphic adenomas were mostly positive for keratin 14, and a small fraction of them expressed smooth muscle proteins. Conversely, peripheral cells of adenoid cystic carcinomas were mostly positive for smooth muscle proteins, and some of them expressed keratin 14. These results strongly suggest (1) that the luminal cell progenitors transform into major constituents of pleomorphic adenoma cells with keratin 14 but not smooth muscle proteins, and (2) that the peripheral cells of adenoid cystic carcinoma are derived from undifferentiated MECs. Solid structures of pleomorphic adenomas were formed by proliferation of the peripheral cells. MECs were observed only occasionally in the periphery. Solid and cribriform structures of adenoid cystic carcinomas were formed by proliferation of the luminal cells. MECs were observed in the periphery and around the pseudocyst.

Topics: Actins; Adenoma, Pleomorphic; Adult; Aged; Antibodies, Monoclonal; Calcium-Binding Proteins; Calmodulin-Binding Proteins; Calponins; Carcinoma, Adenoid Cystic; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratin-14; Keratins; Male; Microfilament Proteins; Middle Aged; Muscle, Smooth; Salivary Gland Neoplasms

A panel of antibodies composed of the cytokeratins (CKs), vimentin, and actin was applied to 114 minor salivary gland tumors to evaluate its diagnostic value. The results revealed that luminal cells of intercalated duct-like structures, such as those seen in pleomorphic adenoma, basal cell adenoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma, expressed CKs 7, 8, 14, and 19. The outer cells of these structures exhibited vimentin or vimentin plus muscle-specific actin, but rarely CK14, which is seen particularly in pleomorphic adenoma, in the tubular type of basal cell adenoma, and seldom in the tubular type of adenoid cystic carcinoma. Modified myoepithelial cells of pleomorphic adenoma and myoepithelioma exhibited a variable immunoprofile. CKs 7 and 8 were also observed in acinar cell adenocarcinoma and polymorphous low-grade adenocarcinoma with vimentin in the latter. CK13 was expressed only by canalicular adenoma and mucoepidermoid carcinoma cells. This study showed that the panel of antibodies employed is effective in distinguishing among salivary gland tumors.

Topics: Actins; Adenocarcinoma; Adenoma; Adenoma, Pleomorphic; Carcinoma; Carcinoma, Acinar Cell; Carcinoma, Adenoid Cystic; Carcinoma, Mucoepidermoid; Immunohistochemistry; Keratins; Myoepithelioma; Salivary Gland Neoplasms; Vimentin

To observe immunohistochemical expression of S-100A1, S-100A2, S-100A4, S-100A6, S-100B, K8.12, KL1, Vimentin, GFAP and NSE in pleomorphic adenoma of salivary gland, and to evaluate the differential localization of S-100 proteins and biological behaviour of neoplastic myoepithelial cells.. 23 cases of normal salivary gland and 60 cases of pleomorphic adenoma were embedded, in paraffin and were routinely diagnosed on the basis of hematoxylin and eosin-stained sections. Serial sections at 4 microns from the paraffin embedded blocks were used for the immunohistochemical studies.. Normal salivary glands had positive immunoreactivity for S-100A families, K8.12 and KL1 in the ductal cells, while S100B, GFAP and NSE were observed in peripheral nerve fibers innervating the gland. In pleomorphic adenomas, luminal tumor cells in duct-like structures had positive immunoreactivity for S-100A subfamilies and keratin. Nonluminal tumor cells had positive immunoreactivity for S-100B, as well as Vimentin, keratins detected by monoclonal K8.12 and KL1, GFAP and NSE.. These findings may suggest that the neoplastic myoepithelial cells contain Ca2+ binding proteins which may have a role in the regulation of calcium ions or calcium signaling mechanisms in the modulation of extracellular matrix deposition in pleomorphic adenoma which may in turn affect the extracellular matrix synthesis as well as histomorphology of the tumor.

Topics: Adenoma, Pleomorphic; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Phosphopyruvate Hydratase; Protein Isoforms; S100 Proteins; Salivary Gland Neoplasms; Vimentin

Salivary gland rests occur in the posterior lobe of the pituitary gland near or often communicating with the Rathke's cleft or its cystic subdivisions, and are usually incidental autopsy findings. They are attributed to the oropharyngeal development of the Rathke's pouch and may rarely give rise to salivary gland-like tumors in the sella. We present a pleomorphic adenoma, a rare tumor of the sellar region, that has not been previously recognized in association with Rathke's cleft cyst. It occurred in a 44-year-old man who presented with hypopituitarism and reduced vision. Magnetic resonance imaging showed a sellar mass with suprasellar extension which was totally removed. It consisted of segments of a cyst wall lined by focally ciliated columnar of cuboid epithelium containing goblet cells. An eosinophilic granular material with cholesterol clefts represented the contents of the cyst. Within its wall there was a tumor with ductal structures and non-ductal varied cellular components including hypercellular areas of spindle and ovoid cells forming interlacing fascicles. Individual cells appeared to float in abundant mucinous material. The appearances were those of a salivary gland pleomorphic adenoma arising within the wall of a Rathke's cleft cyst. The myoepithelial nature of non-ductal tumor cells was confirmed with immunocytochemistry. The existence of seromucous glands communicating with the Rathke's cleft remnants, explains the concomitant occurrence of the tumor and the cyst. This rare neoplasm from salivary gland rest should be considered in the differential diagnosis of unusual sellar and suprasellar tumors.

Topics: Actins; Adenoma, Pleomorphic; Adult; Biomarkers; Brazil; Central Nervous System Cysts; Diagnosis, Differential; Glial Fibrillary Acidic Protein; Humans; Hypopituitarism; Immunohistochemistry; Keratins; Magnetic Resonance Imaging; Male; Mucin-1; Neoplasms, Second Primary; S100 Proteins; Salivary Gland Neoplasms; Vision Disorders

The morphogenesis of salivary gland pleomorphic adenoma was examined in vitro using three-dimensional (3-D) collagen gel culture. Pleomorphic adenoma cells were isolated from three parotid gland tumours and cultured as monolayers, after which they were subcultured in floating-collagen gel sandwiches. Cells cultured in both conditions were immunohistochemically characterized and compared using antibodies against various proteins representative of each histological component of salivary glands. Monolayers had myoepithelial characteristics, being positive for vimentin and alpha-smooth muscle actin. In collagen gels, however, the cells assembled in epithelial nests, showing an architecture similar to that of pleomorphic adenoma. The nests were composed of duct-lining epithelial cells that were positive for epithelial markers, surrounded by myoepithelial cells. Collagen gel culture induces multidirectional differentiation of adenoma cells, suggesting that pleomorphic adenomas originate from stem or reserve cells.

Topics: Actins; Adenoma, Pleomorphic; alpha-Amylases; Collagen; Gels; Humans; Immunohistochemistry; Keratins; Male; Salivary Gland Neoplasms; Tumor Cells, Cultured

An immunohistochemical analysis of 8 cases of the apocrine type of cutaneous mixed tumor is reported. Histologically, 7 cases of the tumor were suggested to have follicular and/or sebaceous differentiation. Carcinoembryonic antigen (CEA), epithelial membrane antigen and gross cystic disease fluid protein-15 were present in the inner surface and/or in the luminal cell bodies of the tubular structures. CEA and non-specific cross-reacting antigen were also detected in the keratinous cysts. Positive reactions for S-100 protein and vimentin were observed in the solid nests, the outer layer of the tubular structures and some stromal cells. However, smooth muscle actin was only focally expressed in the outer cells of the tubular nests in one case. Involucrin was positive in the inner layers of the keratinous cysts. Various staining patterns were observed in the keratin immunohistochemistry. The solid nests showed heterogeneous expressions of CK1/5/10/14, CK7, CK10/11, CK14, CK8/18 and CK19. The inner cells of the tubular structures were constantly positive for CK7, CK8/18 and CK19, and heterogeneously for CK1/5/10/14, CK10/11 and CK14. The outer cells were heterogeneously positive for CK1/5/10/14 and CK14. The keratinous cysts showed positive reactions for CK1/5/10/14 throughout the whole cell layers, and for CK14 in the basal layer. The inner layers in some keratinous cysts expressed CK6, CK10/11 and CK17, but only CK10 in others. CK13 was positively stained in the transitional portion between the matricial structure and the column of shadow cells in the cyst wall in only one case. When compared with the immunohistochemistry of the normal skin, the apocrine type of cutaneous mixed tumor can show various immunophenotypical patterns similar to those of entire structures of hair follicles, sebaceous glands and all components of apocrine glands, that is to say, the folliculosebaceous-apocrine unit.

Topics: Adenoma, Pleomorphic; Adipocytes; Adult; Aged; Aged, 80 and over; Apocrine Glands; Biomarkers, Tumor; Cell Differentiation; Epidermis; Female; Hair Follicle; Humans; Immunohistochemistry; Keratins; Male; Melanocytes; Middle Aged; Sebaceous Glands; Skin Neoplasms; Stromal Cells; Sweat Gland Neoplasms

This case report describes a unique palatal tumor with features of a dermal neoplasm. Microscopically, the lesion appeared similar to a trichoepithelioma and trichoadenoma.. Light microscopic and immunohistochemical studies were performed to arrive at the final diagnosis.. The lesion arose from the surface epithelium and had features of a dermal tumor.. The case report describes a unique benign palatal neoplasm.

Topics: Adenoma, Pleomorphic; Adult; Diagnosis, Differential; Epithelial Cells; Epithelium; Female; Humans; Hyalin; Immunohistochemistry; Keratins; Keratosis; Mouth Mucosa; Neoplasms, Basal Cell; Palatal Neoplasms; Palate, Soft; Skin

An immunohistochemical study of nine cases of chondroid syringomas/mixed tumors of the skin was performed to elucidate the nature of the so-called neoplastic myoepithelial cells (NMEC) in tumor tissues. These nine tumors contained NMEC of considerable variability in number from one tumor to another. These NMEC were classified into three types: (i) hyaline cells (plasmacytoid cells); (ii) spindle NMEC; and (iii) polyhedral cells. They showed different immunostaining patterns, as the following describes. Cytokeratin 14 was positive in most of the spindle NMEC and a large number of the polyhedral cells, and in a small number of the hyaline cells. Concerning low molecular weight cytokeratins, most of the hyaline cells showed immunoreactivity, whereas they were negative in many of the spindle NMEC and were expressed only in a small number of the polyhedral cells. alpha-Smooth muscle actin and muscle-specific actin were positive in the spindle NMEC but negative in any of the hyaline cells and polyhedral cells. These findings strongly indicate that the hyaline cells and the spindle NMEC are of the simple epithelial and myoepithelial types, respectively. The findings also suggest that the polyhedral cells show differentiation toward basal cells of the sweat gland dermal ducts or myoepithelial cells.

Topics: Adenoma, Pleomorphic; Adult; Aged; Biomarkers; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Myoepithelioma; Sweat Gland Neoplasms

Juvenile pleomorphic adenoma of the parotid gland represents an extremely rare tumour entity and is comparable to congenital tumours of the salivary glands concerning its embryonal structure. The clinical detection of the tumour in a 7-year-old girl does not exclude that the tumour had developed either earlier or immediately after the birth. The high cellularity and the evidence of primitive epithelial and myoepithelial cellular structures do not justify its classification as a malignant tumour. However the presence of embryonal tissue structures associated with the end of the third month of embryogenesis is characterized by more solid cell formations in partly verticulate arrangement. The absence of further differentiation into lobular structures and differentiated duct or acinic cell formations may be due to cell arrest. Differential diagnosis of juvenile pleomorphic adenoma must distinguished it from other congenital salivary gland tumours (e.g. congenital basal cell adenoma, hybrid basal cell adenoma-adenoid cystic carcinoma, sialoblastoma, salivary gland anlage tumour.

Topics: Adenoma, Pleomorphic; Biomarkers, Tumor; Cell Transformation, Neoplastic; Child; Diagnosis, Differential; Epithelium; Female; Humans; Keratins; Neoplasms, Germ Cell and Embryonal; Parotid Gland; Parotid Neoplasms

Clinical, histological and immunohistochemical data on 71 parotid gland tumors were analyzed. Benign neoplasms accounted for 71.8% of the case material and malignant tumors 22.6%. Chronic parotitis occurred in 5.6% of the total case number. Pleomorphic adenomas and mucoepidermoid carcinomas were the most frequently occurring benign and malignant neoplasms. Pleomorphic adenomas stained positive for S-100 protein, tenascin, smooth muscle actin, synaptophysin and chromogranin A. This immunohistochemical, histological and clinical analysis was believed to be of potential assistance in the diagnosis, treatment and prognosis of parotid gland tumors.

Topics: Actins; Adenoma, Pleomorphic; Antigens, Neoplasm; Carcinoma, Mucoepidermoid; Chromogranin A; Chromogranins; Chronic Disease; Desmin; Glycoproteins; Humans; Immunoglobulin A, Secretory; Immunohistochemistry; Keratins; Parotid Neoplasms; Parotitis; Prognosis; S100 Proteins; Secretory Component; Synaptophysin; Tenascin; Tumor Suppressor Protein p53

A 58-year-old Japanese male presented with a cutaneous mixed tumor containing ossification and hair matrix differentiation on the left side of the chin. Histologically, the tumor consisted almost exclusively of apocrine-type epithelial ductal structures and chondroid stroma. Strands and aggregation of basaloid cells which contained keratinous cystic structures with a column of shadow cells arising from basophilic basaloid cells, sebaceous duct-like structures, and ossification in the stroma were also evident. These findings suggest that cutaneous mixed tumors with ossification and hair matrix differentiation are related to both the whole hair follicle and the sweat apparatus.

Topics: Adenoma, Pleomorphic; Apocrine Glands; Cell Differentiation; Chin; Epithelium; Facial Neoplasms; Hair; Hair Follicle; Humans; Keratins; Male; Middle Aged; Ossification, Heterotopic; Sebaceous Glands; Skin Neoplasms

To investigate the histogenesis of mixed tumor of the skin, apocrine type, the immunophenotypes of 10 cases were examined using 19 different monoclonal anti-keratin antibodies and antibodies against carcinoembryonic antigen (CEA) and involucrin. By using light microscopy, four epithelial elements in this tumor were characterized: tubular branching structures with lumina lined by cuboidal epithelium and those with lumina lined by columnar epithelium, keratinous cysts, and solid aggregates of epithelial cells. The immunohistochemical patterns of cytokeratin expression suggested that cuboidal and columnar cells differentiated, respectively, toward the ductal and secretory cells of apocrine glands, whereas keratinous cysts revealed follicular infundibular differentiation. Furthermore, CEA expression, a marker for sweat-gland differentiation, was present not only on tubules' luminal surfaces but also on the inner surfaces of keratinous cysts. The simultaneous coexpression of CEA and cytokeratins specific for follicular infundibulum in the keratinous cysts, although perplexing, suggested that keratinous cysts may contain some cells differentiating toward the intrafollicular portion of apocrine ducts that enter infundibulae rather than eccrine ducts that have no infundibular association. We conclude that apocrine type of mixed tumors of the skin demonstrate differentiation toward all components of apocrine units.

Topics: Adenoma, Pleomorphic; Apocrine Glands; Carcinoembryonic Antigen; Cell Differentiation; Cell Lineage; Cysts; Eccrine Glands; Epithelial Cells; Epithelium; Gene Expression Regulation, Neoplastic; Hair Follicle; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Middle Aged; Protein Precursors; Skin Neoplasms; Sweat Glands

In view of the different terminology for salivary gland tumours with giant cells, eleven cases were analysed by histopathology and immunocytochemistry. Four cases (three pleomorphic adenomas, one carcinosarcoma in a pleomorphic adenoma) were classified as having a foreign-body giant cell reaction, and five cases (two mucoepidermoid carcinomas, one acinic cell carcinoma, two carcinomas in pleomorphic adenomas) as having a sarcomatoid osteoclast-like giant cell reaction. In two further cases a giant cell tumour and a giant cell granuloma were associated with carcinomas in pleomorphic adenomas. All giant cells showed characteristic expression of CD68 as a typical marker for histiocytes and macrophages with their origin in mononuclear haematopoetic stem cells. There was no evidence for an epithelial origin of the giant cells because all those examined had a negative reaction to cytokeratin. Foreign-body cells were characterized by cytoplasmic vacuoles and irregularly dispersed nuclei. They showed a focally circumscribed reaction mostly outside the connective tissue pseudocapsule of the tumours. The sarcomatoid osteoclast-like giant cell reactions in carcinomas were distinctly intermingled with the carcinomatous patterns. In contrast, the associated osteoclast-like giant cell tumour was distinctly separate from the salivary gland tumour tissue and was composed of numerous larger osteoclast-like giant cells with a greater number of nuclei (more than 20); these giant cells were uniformly distributed throughout the tumour tissue. The giant cell granuloma was also separate from the carcinoma and was composed of nests of smaller, more irregularly distributed giant cells.

Topics: Adenoma, Pleomorphic; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Carcinoma; Carcinoma, Acinar Cell; Carcinoma, Mucoepidermoid; Carcinosarcoma; Cell Lineage; Cell Nucleus; Connective Tissue; Epithelial Cells; Foreign-Body Reaction; Giant Cell Tumors; Giant Cells; Giant Cells, Foreign-Body; Granuloma, Giant Cell; Hematopoietic Stem Cells; Histiocytes; Humans; Immunohistochemistry; Keratins; Macrophages; Neoplasms, Multiple Primary; Osteoclasts; Salivary Gland Neoplasms; Sarcoma; Vacuoles

Twenty-four salivary gland tumours (six pleomorphic adenomas, two myoepitheliomas, five basal cell adenomas, six adenoid cystic carcinomas and five polymorphous low grade adenocarcinomas) were investigated by an immunocytochemical technique using monoclonal antibodies against cytokeratins (CKs) 7, 8, 10, 13, 14, 18 and 19. The luminal cells of ductal structures of the tumours reacted with all the CKs studied except for CK 13 and CK 10 and sometimes CK 14, showing an immunoprofile comparable to that of the intercalated segment of a normal salivary gland. The outer cells of the ducts rarely stained with CK 14, confirming that full differentiation of the myoepithelial cells is seldom achieved in tumours. Considerations were made regarding the intriguing expression of CK 14, the heterogeneous expression of CKs in the modified myoepithelial cells and the immunoprofile of the polymorphous low-grade adenocarcinoma.

Topics: Adenocarcinoma; Adenoma; Adenoma, Pleomorphic; Antibodies, Monoclonal; Biomarkers, Tumor; Humans; Keratins; Myoepithelioma; Neoplasm Proteins; Salivary Gland Neoplasms

Benign cutaneous adnexal tumors displaying divergent differentiation are rare, with very few well-documented cases reported in the literature. We describe eight cases of benign adnexal tumors showing a variable combination of eccrine, apocrine, and folliculosebaceous differentiation. Clinically, all tumors presented as solitary, slowly enlarging dermal or subcutaneous nodules located in the head and neck and the extremities. Histologically, they were characterized by well-circumscribed, unencapsulated nodules composed of a lobular proliferation of epithelial cells displaying a spectrum of trichogenic, sebaceous, apocrine, and eccrine differentiation. The histological spectrum included lobules and trabeculae of basaloid cells with glandular and ductal elements, well-formed folliculosebaceous units, primitive follicles, and foci of tricholemmal keratinization. Immunohistochemical evaluation in four cases showed similar cytokeratin, carcinoembryonic antigen, and epithelial membrane antigen staining profiles as those reported for sweat gland adenomas; in addition, focal S-100 protein positivity and GCDFP-15 positivity could also be demonstrated, suggesting eccrine-apocrine differentiation. The tumors were most frequently confused histologically with other adnexal neoplasms, including sebaceoma, sebaceous adenoma, basal cell carcinoma, chondroid syringoma, and trichoepithelioma. The present series highlights the capability.

Topics: Adenoma; Adenoma, Pleomorphic; Adenoma, Sweat Gland; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Apocrine Glands; Apolipoproteins; Apolipoproteins D; Carcinoembryonic Antigen; Carcinoma, Basal Cell; Carrier Proteins; Eccrine Glands; Epithelium; Female; Glycoproteins; Hair Follicle; Humans; Immunohistochemistry; Keratins; Male; Membrane Transport Proteins; Middle Aged; Mucin-1; Neoplasm Proteins; Neoplasms, Basal Cell; S100 Proteins; Sebaceous Gland Neoplasms; Sweat Gland Neoplasms

We report a case of hyaline cell-rich chondroid syringoma arising in the skin on the left side of the neck. The tumor was composed exclusively of hyaline cells arranged in a predominantly thick trabecular pattern. Ductal structures of various sizes in the tumor were composed of eosinophilic cuboidal cells showing transition to hyaline cells. Immunohistochemically, the hyaline cells were positive for cytokeratin, S-100, and vimentin, although the best marker for myoepithelial differentiation, alpha-smooth muscle actin, was negative. As is the case with plasmacytoid monomorphic adenomas of the salivary gland and some reported cases of hyaline cell-rich chondroid syringoma, hyaline cells in the present tumor similarly lacked any evidence of myoepithelial differentiation. These immunohistochemical findings reveal that the hyaline cells in the present tumor were epithelial.

Topics: Adenoma, Pleomorphic; Cell Differentiation; Epithelium; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Sweat Gland Neoplasms; Vimentin

Previous morphologic and histochemical studies have documented extracellular elastin and elastic fibers within the matrix of pleomorphic adenomas of the salivary glands. By morphologic criteria, the elastin appeared to be synthesized by the tumor rather than being a consequence of stroma produced in response to the tumor cells. To examine this issue, nine pleomorphic adenomas were studied by immunohistochemistry and in situ hybridization with tropoelastin-specific antibodies and complementary DNAs. Corroborating the previous morphologic studies, immunohistochemistry demonstrated abundant extracellular elastin within the matrix of pleomorphic adenomas. Additionally, both immunohistochemistry and in situ hybridization demonstrated continued synthesis of tropoelastin by the neoplastic cells. Tropoelastin production was seen in neoplastic cells with all morphologies.

Topics: Adenoma, Pleomorphic; Adult; Aged; Aged, 80 and over; Antibodies; DNA, Complementary; Elastin; Extracellular Matrix; Female; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Male; Middle Aged; Parotid Neoplasms; S100 Proteins; Tropoelastin

A case of so-called mixed tumor of the skin arising on the wrist was reported. Immunohistochemical staining of keratins of several molecular weights (AE1/AE3, RCK102, NCL-5D3 and 35 beta H11), carcinoembryonic antigen (CEA), S-100 protein, and desmin was performed. AE1/AE3 and RCK102 were positive in all the tumor cells; CEA, NCL-5D3 and 35 beta H11 were positive mainly in luminal cells of the tubuloalveolar structures. S-100 protein was positive in peripheral cells of the tubular lumina and in scattered cells in the mucous stroma. Desmin was negative in all the tumor cells. Immunohistochemical findings lent further support to the hypothesis that so-called mixed tumor of the skin differentiates into the secretory and ductal portions of the sweat gland.

Topics: Adenoma, Pleomorphic; Carcinoembryonic Antigen; Desmin; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; S100 Proteins; Skin Neoplasms

Markers for normal salivary gland myoepithelium were used to determine the extent of their expression in the neoplastic myoepithelial (nonluminal) cells of pleomorphic adenomas and then in the tumor cells in myoepitheliomas and to gather information necessary to establish diagnostic criteria, especially muscle actin expression, for myoepitheliomas.. Methanol/acetic acid-fixed and paraffin-embedded tissue was used to immunohistochemically study expression of intermediate and smooth-muscle actin filaments in nonluminal cells in 14 pleomorphic adenomas and to compare this to their expression in five myoepitheliomas.. In routine histologic sections, the morphologic variants of nonluminal tumor cells--spindle, stellate, polygonal, angular, and plasmacytoid--in pleomorphic adenoma mirror the spectrum of tumor cells in myoepitheliomas. Immunocytochemical similarities are also apparent. Two specific markers for myoepithelial cells in the normal salivary gland, muscle-specific actin and cytokeratin 14, were both variably, independently, and never uniformly expressed in nonluminal cells of pleomorphic adenoma and tumor cells in myoepitheliomas regardless of their morphology. Cytokeratin 14 in addition labels basal cells of excretory ducts. Both muscle-specific actin and cytokeratin 14 preferentially localized to single layers of periductal cells in pleomorphic adenomas, angular, polygonal, and plasmacytoid cells preferentially expressed cytokeratin 14. Similar patterns were noted in the three myoepitheliomas with reasonable expression of the two markers. Only isolated single cells or small groups of plasmacytoid cells in four pleomorphic adenomas with a significant component of these cells and the two plasmacytoid myoepitheliomas immunostained for muscle-specific actin and cytokeratin 14. In both tumor types, vimentin was nearly uniformly expressed in nonluminal tumor cells of all morphologic types, including plasmacytoid cells.. The range and transition of morphology of nonluminal cells in pleomorphic adenomas is reflected in myoepitheliomas. Incomplete or absent expression of the myoepithelial/basal cell markers, muscle-specific actin, and cytokeratin 14, and the general expression of vimentin is common to both tumors. Because these findings apply to the majority of plasmacytoid cells in pleomorphic adenomas, tumor cells with a similar morphology and immunoprofile are to be expected in myoepitheliomas; the term plasmacytoid myoepitheliomas is thus appropriate regardless of the presence or absence of muscle-specific actin.

Topics: Actins; Adenoma, Pleomorphic; Biomarkers, Tumor; Cytoskeletal Proteins; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Keratins; Myoepithelioma; Neoplasm Proteins; Parotid Gland; Parotid Neoplasms; Salivary Gland Neoplasms; Vimentin

Primary lung tumors showing features of salivary gland-type neoplasms are extremely rare.. Eight patients with primary lung neoplasms showing light microscopic and immunohistochemical features of salivary gland-type mixed tumors were studied.. The patients were six women and two men, ages 35-69 years (mean, 52.5 years). The tumors ranged from 2 to 16 cm in greatest diameter. In two patients the lesions presented as polypoid endobronchial lesions obstructing the lumen; in another two patients the lesions were found in close proximity or in continuity with a bronchus; in three patients, the lesions presented as peripheral parenchymatous nodules unrelated to a bronchus; and in one patient, the relationship to the bronchus could not be determined. Histologically, the lesions were biphasic, showing admixtures in varying proportions of epithelial elements containing a predominant myoepithelial cell population with a stromal component containing an abundant myxoid or focally chondroid matrix. Immunohistochemical studies showed strong positivity of the cells in the epithelial component with low molecular weight keratins (CAM 5.2), and to a lesser extent with broad spectrum keratin, actin, and vimentin antibodies. The cells also showed variable reactivity in the epithelial and nonepithelial elements with S-100 protein and glial fibrillary acidic protein. Six tumors were grossly and histologically benign; in two patients, the tumors were larger, locally invasive, and showed more atypical histologic features. All patients were treated with surgical excision. On follow-up, of the six patients with histologically benign-appearing tumors, one was alive and well 6 years after surgery; another died 4 years after surgery of a second unrelated malignancy; one died during the immediate postoperative period of myocardial infarction; and three have been lost to follow-up. In the two patients with histologically atypical lesions, the tumors recurred and metastasized after 2 and 3 years, respectively, with one of them leading to death caused by widespread metastases and superior vena cava syndrome.. Review of the literature and the findings in the current series indicate that salivary gland-type mixed tumors of the lung may present with a spectrum of histologic features and clinical behavior, ranging from benign to frankly malignant, similar to that observed for their salivary gland counterparts. Size of the lesion at the time of presentation, extent of local infiltration, and degree of mitotic activity appear to be the most reliable prognostic features of these tumors.

Topics: Actins; Adenoma, Pleomorphic; Adult; Aged; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Middle Aged; Mixed Tumor, Malignant; S100 Proteins; Vimentin

A mixed tumor with apocrine differentiation seen in the external auditory canal of a 39 year old male is reported. The well demarcated polypoid tumor showed proliferation of elongated gland-like or duct-like structures lined by two rows of epithelial cells, occasionally accompanied by foci of keratinization. There were fat cells in the myxoid stroma, in which no chondroid elements were seen. This neoplasm is considered to have arisen from the ceruminous gland, the modified apocrine gland of the skin.

Topics: Actins; Adenoma, Pleomorphic; Adult; Apocrine Glands; Ear Canal; Ear Neoplasms; Histocytochemistry; Humans; Keratins; Male

Clear cell carcinoma of salivary gland is a rare neoplasm. We report a third case of clear cell carcinoma arising in a pleomorphic adenoma and also in an extraparotid location. We document the immunohistochemical profile of the tumour including reactivity with a marker for the c-erbB-2 oncoprotein and suggest a myoepithelial origin for these lesions. The presence of a tetraploid stemline may account for the rapid tumour progression in this case.

Topics: Adenocarcinoma, Clear Cell; Adenoma, Pleomorphic; Biomarkers, Tumor; DNA, Neoplasm; ErbB Receptors; Female; Humans; Keratins; Middle Aged; Proto-Oncogene Proteins; Receptor, ErbB-2; S100 Proteins; Submandibular Gland Neoplasms; Vimentin

The localization of bone morphogenetic protein (BMP)-1, -2, -3 and transforming growth factor (TGF)-beta in normal salivary gland and pleomorphic adenoma of the salivary gland has been examined immunocytochemically. Tumor cells with BMP immunostaining in pleomorphic adenoma were associated with some solid cellular and tubuloglandular patterns, and with stellate cells in the myxoid area. In addition, in the chondroid area of three pleomorphic adenomas, chondrocyte-like cells were positive for BMPs. It is speculated that BMPs secreted by the tumor cells play a role in the formation of the chondroid component in pleomorphic adenoma by inducing some tumor cells, probably neoplastic myoepithelial cells, to differentiate to chondrocytes by metaplastic change. No tumor cells specifically immunostained with TGF-beta were found. TGF-beta was positive in fibrous and hyalinized stroma. In the submandibular gland, only anti-BMP-1 antibody specifically reacted to apical portions of degenerated serous acinar cells.

Topics: Adenoma, Pleomorphic; Animals; Bone Morphogenetic Proteins; Collagen; Humans; Immunohistochemistry; Keratins; Neoplasm Proteins; Protein Biosynthesis; Proteins; Rabbits; Salivary Gland Neoplasms

"Collagenous spherulosis" is the term used to describe striking concentric and radiating formations of collagen in tumors. It was originally used for these formations in epithelial tumors of the breast and subsequently in tumors of salivary glands. Recently, the histologic, immunohistochemical, and ultrastructural features were described in a chondroid syringoma. We report a case of collagenous spherulosis in a schwannoma. Routine histologic sections showed a circumscribed tumor in which the predominant feature was radiating fibrillar structures that tended to compress the cellular component of the tumor. Immunohistochemical studies showed that the cells were positive for glial fibrillary acidic protein (GFAP) and S-100 protein but negative for keratin. EMA showed a positive reaction in a thin band of cells around the periphery of the tumor consistent with perineurial cells. Type IV collagen stained around the periphery of the collagen formations. Electron microscopy revealed that the material was consistent with collagen. Our findings were essentially identical to those reported in the chondroid syringoma. This case confirms the findings of the previous study and shows that these unusual formations are not confined to tumors of epithelial origin. Because the architecture of the tumor is distorted, special stains may be required for correct diagnosis.

Topics: Adenoma, Pleomorphic; Adult; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; CD57 Antigens; Cell Nucleus; Collagen; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Mucins; Neoplasm Proteins; Neurilemmoma; Phosphopyruvate Hydratase; S100 Proteins; Skin Neoplasms; Staining and Labeling

Control of keratin (K) gene expression may be important for cell differentiation in complex epithelia such as salivary gland. To investigate differences in distribution between keratin mRNAs and their respective proteins, a combined in situ hybridization (ISH) and immunohistochemical study was undertaken on nine normal salivary glands and seven pleomorphic adenomas. ISH employed riboprobes to K7, K8, K14, K18, and K19. Immunohistochemistry was performed on adjacent sections using monoclonal antibodies (MAbs) to the same keratins. Normal luminal cells showed abundant hybridization with probes for K7, K8, K18, and K19. Keratin 14 mRNA was present in basal and myoepithelial cells at a low level of expression. Proteins of their keratins were strongly stained. Neoplastic cells showed variable expression of mRNA and protein for K7, K8, K18, and K19. There was a high level of K14 mRNA but variable protein. The findings provide evidence that expression of these keratins in normal salivary epithelia is regulated transcriptionally and that in neoplasia this system is in considerable disarray.

Topics: Adenoma, Pleomorphic; Epithelium; Gene Expression Regulation, Neoplastic; Humans; In Situ Hybridization; Keratins; RNA Probes; RNA, Messenger; Salivary Gland Neoplasms; Salivary Glands

Salivary duct carcinoma (SDC) is a distinctive salivary gland neoplasm morphologically characterized by intraductal and infiltrating components. Most tumors occur in the major salivary glands and demonstrate a propensity for invasive growth with early regional and distant metastases. Therefore, SDC is regarded as a high-grade malignancy in the current classification of salivary gland neoplasms.. In an effort to identify clinically relevant prognostic features, we studied the clinicopathologic and immunohistochemical findings in 15 SDC, with ultrastructural evaluation of three tumors.. Thirteen SDC occurred in the parotid gland, one in the Stensens duct, and one in the palate. Twelve patients were men (ratio of men to women = 4:1). Patients ranged in age from 39 to 81 years (mean = 59 years). Tumor size varied from 1.2 to 6.5 cm (mean = 3.1 cm). An intraductal component was identified in 10 of 14 primary SDC that made up 10% to 95% of the tumor. In three SDC a preexisting pleomorphic adenoma was identified. Immunohistochemical and electron microscopic evaluation showed the SDC to be composed entirely of ductal cells, and one tumor exhibited features of striated duct differentiation.. SDC show a broader clinicopathologic spectrum than previously described. The tumor may arise in a pleomorphic adenoma. The proportion of intraductal and extraductal growth is variable and of prognostic significance. Although the majority of SDC behave in a high-grade fashion, those with a predominant intraductal component of greater than 90% (PID-SDC) and minimally invasive (< 8 mm) SDC in pleomorphic adenoma appear to have a more favorable prognosis.

Topics: Adenoma, Pleomorphic; Adult; Aged; Aged, 80 and over; Carcinoma, Intraductal, Noninfiltrating; Cell Membrane; Cell Nucleus; Cytoplasm; Epithelium; Female; Humans; Hyalin; Hyperplasia; Keratins; Male; Middle Aged; Mitochondria; Neoplasm Invasiveness; Neoplasms, Multiple Primary; Palatal Neoplasms; Parotid Neoplasms

Immunohistological expressions of the cytokeratin (CK) subclass, vimentin, glial fibral antigen protein (GFAP), alpha-smooth muscle actin, and S-100 protein were investigated in pleomorphic adenoma of the parotid gland. In addition, the correlation between immunohistological findings in the normal parotid gland and those in pleomorphic adenoma was examined. Vimentin, S-100 protein, and GFAP, which were not detected in the normal parotid gland, were observed in pleomorphic adenoma. Only CK-1, which was not detected in the normal parotid gland, was expressed intensely in squamous metaplastic lesions of pleomorphic adenoma. All other CK detected in pleomorphic adenoma were also expressed in the normal parotid gland. Therefore, the expression of vimentin, S-100 protein, GFAP, and CK-1 in pleomorphic adenoma is related to oncogenesis. Since most types of CK expression were observed in solid pleomorphic adenoma lesions and all types of CK expression detected in other lesions were included, cellular differentiation between solid and nonsolid lesions was elucidated. According to the pattern of CK subclass expression, the following sequence of differentiation was suggested; solid lesion-->myxoid lesion-->chondroid lesion, solid lesion-->tubular lesion, solid lesion-->myoepithelioid lesion, and solid lesion-->squamous metaplastic lesion. In normal parotid glands, satellite cells around the ductal cells showed all types of CK subclass expression detected in myoepithelial cells, acinus cells, and ductal cells. Since the types and patterns of CK expression in solid lesions of pleomorphic adenoma are the same as those in satellite cells in the normal parotid gland, pleomorphic adenoma seems to originate from satellite cells. If satellite cells in the normal parotid gland are considered to be so-called reserve cells in the bicellular theory, the origin and cellular differentiation of pleomorphic adenoma can be explained in relation to CK subclass expression.

Topics: Actins; Adenoma, Pleomorphic; Cell Differentiation; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Parotid Gland; Parotid Neoplasms; S100 Proteins; Vimentin

An unusual coexpression of glial fibrillary acid protein (GFAP), keratin and vimentin occurs in pleomorphic adenoma of salivary gland. We designed this study to see if coexpression of the markers was also present in monomorphic adenoma of the salivary gland and whether monomorphic adenoma could be distinguished from other salivary gland tumours by marker studies. Immunocytochemical markers were used on fine needle aspiration samples from four cases of monomorphic adenoma, two cases of oncocytic adenoma, three cases of adenoid cystic carcinoma and four cases of pleomorphic adenoma. While positivity for cytokeratin, vimentin and S-100 was consistently found in all cases of monomorphic adenoma, only cytokeratin was expressed in adenoid cystic carcinoma. In pleomorphic adenoma, GFAP, cytokeratin and vimentin were coexpressed while in cases of oncocytic adenoma none of the markers was localized. Thus, it appears that by using a combination of GFAP, cytokeratin, vimentin and S-100 a distinction between these neoplasms may be possible. However, a larger study is needed to establish the usefulness of this approach.

Topics: Adenoma; Adenoma, Pleomorphic; Biomarkers, Tumor; Diagnosis, Differential; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; S100 Proteins; Salivary Gland Neoplasms; Vimentin

Among salivary gland neoplasms are a group of rare tumors that are histologically identical to benign mixed tumors that inexplicably metastasize; they have been called metastasizing mixed tumor (MZMT) of salivary glands. We report the clinicopathologic features and flow cytometric findings for 11 cases of MZMT. At the time of discovery of metastatic disease, the patients, six women and five men, ranged in age from 20 to 83 years. Primary sites of involvement included the parotid gland (eight cases), submandibular gland (two cases), and the nasal septum (one case). With one exception, all the patients had at least a single recurrences of their primary mixed tumor, but two or more recurrences were the norm before development of metastatic foci. The metastases were discovered from six to 52 years following the occurrence of the primary tumor. Metastatic deposits were identified in bone, lung, regional lymph nodes, skin, kidney, retroperitoneum, oral cavity, pharynx, calvarium, and central nervous system. The metastases either occurred simultaneously with an episode of recurrent mixed tumor (n = 5) or from 5 to 29 years after a recurrence (n = 6). The treatment of the primary, recurrent, and metastatic neoplasms was surgical excision. Follow-up, ranging from 8 months to 16 years following the diagnosis of MZMT, revealed seven patients to be alive without disease (64%) and two dead of causes unrelated to metastatic disease (18%). Two patients (18%) died as a direct result of metastatic tumor at 3 and 2 years after metastasis of their mixed tumors. Flow cytometric analysis revealed a diploid DNA cell population in the primary and/or metastatic tumors in nine cases. Aneuploid DNA cell content was identified in two of the cases. DNA ploidy levels and cell proliferation rates were compared with those of conventional benign mixed tumors and also with malignant mixed tumors. Retrospective analysis of histologic parameters (mitotic rate, cellular pleomorphism, infiltrative growth, vascular or lymphatic invasion) and flow cytometric analysis failed to identify criteria to predict the development of metastasis in these neoplasms.

Topics: Actins; Adenoma, Pleomorphic; Adolescent; Adult; Aged; Aged, 80 and over; Child; DNA, Neoplasm; Female; Flow Cytometry; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Recurrence; Retrospective Studies; S100 Proteins; Salivary Gland Neoplasms; Vimentin

The distribution of immunostaining in normal major salivary gland and in 12 pleomorphic adenomas was studied using monospecific monoclonal antibodies to a number of cytokeratins, including cytokeratin 14, to smooth muscle actin and vimentin. A number of these antibodies enabled a distinction to be made between structural components of the normal gland, and to relate this to the different structures of pleomorphic adenomas. In the normal gland, the luminal duct cells expressed cytokeratins 7, 8, 18 and 19. Three antibodies were of particular value for the characterization of normal myoepithelial and basal cells; while the antibody to smooth muscle actin and the cytokeratin antibody Ks8.12 mutually exclusively stained the myoepithelial (basket) cells and the basal duct (light) cells, respectively, the recently established monospecific antibodies to cytokeratin 14 showed specific immunostaining with both cell types. These three antibodies left luminal cells virtually unstained. Ck 13 was found occasionally in single luminal excretory duct cells. Antibodies to cytokeratins 1/2, 10 and 10/11 did not show any staining in the normal gland. In the pleomorphic adenomas, the staining pattern of the two-layered tubular formation resembled that of the normal gland ducts: tumour luminal cells showed the characteristic, although more irregular, expression of cytokeratins 7, 8, 18 and 19; the outer cells resembled normal ductal basal cells with their anti-cytokeratin 14/Ks8.12-epitope staining and in that they virtually lacked staining for smooth muscle actin. Trabecular formations and cells in myxoid areas were reactive with Ks8.12 and for cytokeratin 14, occasionally also for cytokeratins 7, 18 and 19. Epidermoid cell islets expressed mainly cytokeratin 14 and inconsistently the squamous epithelial cytokeratin 13 and the epidermal cytokeratin 10/11. Vimentin was found in cells of myxoid areas. The results support the postulate that some of the normal duct basal cells act as reserve cells and can give rise to tumour formation with a primitive myxoid or trabecular pattern and a more differentiated tubular or epidermoid configuration.

Topics: Actins; Adenoma, Pleomorphic; Antibodies, Monoclonal; Biomarkers, Tumor; Epithelial Cells; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Parotid Gland; Parotid Neoplasms; Reference Values; Salivary Gland Neoplasms; Submandibular Gland; Vimentin

Histogenesis of pleomorphic adenomas was investigated by histological and electron microscopical methods. Histochemically alkaline phosphatase activity was revealed in transformed cells. Positive immunohistochemical reaction was shown in cells of pleomorphic adenomas with polyclonal antibodies against the smooth muscle myosin, human carbonic anhydrase III and monoclonal antibodies to cytokeratins N8, N17, N18, vimentin (clone NT-30) and to membrane epithelial antigen. It is concluded that these tumours are of the epithelial nature.

Topics: Adenoma, Pleomorphic; Alkaline Phosphatase; Antigens, Neoplasm; Epithelium; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Salivary Gland Neoplasms; Vimentin

In an attempt to determine if both pleomorphic adenomas and adenoid cystic carcinomas are derived from myoepithelial cells, 23 pleomorphic adenomas, 22 adenoid cystic carcinomas, and 17 normal salivary glands were examined immunohistochemically by using monoclonal antibodies directed against actin (HUC1-1, 1A4), keratin (AE-1, 34 beta E 12), and vimentin (V9). In normal salivary glands, the myoepithelial cells demonstrated a positive reaction to the monoclonal antibodies against actin and only rarely reacted with those against vimentin. No reaction to those against keratin was noted. In pleomorphic adenomas, cells that histologically resembled myoepithelial cells displayed a positive reaction to HUC1-1 in 60.9% and to 1A4 in 65.2%. In adenoid cystic carcinoma, 59.1% of cases demonstrated a positive reaction to both HUC1-1 and 1A4. These results supported the hypothesis that the majority of pleomorphic adenomas and adenoid cystic carcinomas arise from cells of myoepithelial origin.

Topics: Actins; Adenoma, Pleomorphic; Antibodies, Monoclonal; Carcinoma, Adenoid Cystic; Humans; Immunoenzyme Techniques; Keratins; Muscle, Smooth, Vascular; Salivary Gland Neoplasms; Vimentin

Immunohistochemical staining for S-100 protein and the intermediate filaments keratin and vimentin, was made in 41 salivary adenomas. In pleomorphic adenomas, great heterogeneity in the staining, as well as multiple and co-expressions of these proteins were found in the outer tumor cells of tubulo-ductal structures and modified myoepithelial cells, but not in the luminal tumor cells. All the outer tumor cells stained for S-100 protein, 97% for K8.12 keratin and 85% for vimentin. Of these cells, 29% showed multiple expression of K8.12 keratin, vimentin, and S-100 protein, and 17% showed co-expression of K8.12 and S-100 protein. Modified and neoplastic myoepithelial cells showed similar expressions of these proteins to those of outer tumor cells; myoepithelioma cells displayed the most complicated pattern, being positive for KL1, PKK1, and K8.12 keratins, vimentin and S-100 protein. In luminal tumor cells there was a heterogeneous expression of KL1 and PKK1 in 82%, and of KL1, PKK1, and K8.12 in only 14.7%. Based on the immunohistochemical findings obtained with different monoclonal antibodies in pleomorphic salivary adenomas, outer tumor cells may be derived from ductal basal cells and luminal tumor cells from intercalated duct cells.

Topics: Adenoma, Pleomorphic; Antibodies, Monoclonal; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands; Vimentin

The neoplastic cells present in a sialadenoma pappiliferum were found by immunoperoxidase method and immunofluorescent staining technique to co-express 3 different types of intermediate-sized filaments (IFs) defined by monoclonal antibodies to cytokeratin, vimentin and desmin. When other salivary gland tumors such as 18 pleomorphic adenomas, 15 adenolymphomas, 2 oxyphilic adenomas, 7 mucoepidermoid tumors, 5 acinic cell tumors, 8 adenoid cystic carcinomas and 6 adenocarcinomas were examined immunohistochemically for the expression of IFs, no tumors with all 3 types of IFs observed in sialadenoma papilliferum were found.

Topics: Adenocarcinoma; Adenolymphoma; Adenoma, Pleomorphic; Carcinoma; Carcinoma, Adenoid Cystic; Desmin; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Papilloma; Salivary Gland Neoplasms; Vimentin

Ten malignant myoepithelial tumors of the salivary glands and one of lacrimal gland origin were studied by light, electron microscopy and immunocytochemistry. The light microscopic appearance of the tumors varied from primarily spindle cell neoplasms (two cases), to others with predominantly epithelial components (four cases) and mixed varieties (five cases). Therefore, they can be confused with other epithelial and mesenchymal neoplasms. The electron microscopic spectrum varied from tumors with widespread and typical myoepithelial differentiation (i.e. myofilament bundles at the cell periphery, attachment plaques and intercellular junctions) to some with diffusely distributed filaments, without associated spindle densities but with attachment plaques, and others with evidence of duct formation and containing scattered cells showing intracytoplasmic tonofilaments. Often the tumors revealed mixed ultrastructural features; the relative numbers of the different cellular components was variable. The eleven neoplasms were S-100 protein, actin and keratin positive, either focally or diffusely, with varying degrees of intensity. Ten of the eleven tumors were positive for vimentin and nine of ten tested expressed carcinoembryonic antigen. Only two of nine were focally positive for glial fibrillary acidic protein. The study emphasizes the variable light microscopic appearances of these neoplasms and their immunocytochemical and ultrastructural spectrum. Accurate determination of myoepithelial differentiation sometimes requires careful evaluation of the light, ultrastructural and immunocytochemical findings. If all three diagnostic modalities are not utilized, it is likely that some of these neoplasms will be improperly classified.

Topics: Actin Cytoskeleton; Actins; Adenoma, Pleomorphic; Adult; Aged; Carcinoembryonic Antigen; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Lacrimal Apparatus; Lacrimal Apparatus Diseases; Male; Microscopy, Electron; Middle Aged; Myoepithelioma; Neoplasms, Germ Cell and Embryonal; S100 Proteins; Salivary Gland Neoplasms; Vimentin

13 cases of salivary glands and 30 of salivary gland tumors were studied by ABC method with 6 monoclonal antibodies to intermediate filaments and one to microfilament. The results showed that the distribution of intermediate filaments in salivary glands had their regularity. According to the reaction to the antibodies, these tumors could be divided into 3 groups and 3 subgroups. The findings also suggested that in the salivary gland tissue the epithelial cells which mainly contained the 54 Kd keratin and the epithelial cells which mainly contained 57/66 Kd keratin were the origin of the salivary gland tumors. The actin-positive myoepithelial cells might play a role in some tumor formation.

Topics: Actins; Adenoma, Pleomorphic; Antibodies, Monoclonal; Carcinoma; Carcinoma, Adenoid Cystic; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Parotid Gland; Salivary Gland Neoplasms; Salivary Glands

A case of pleomorphic adenoma in the upper lip is reported. A 61-year-old male had a tumor at the left side of the upper lip for 8 years. The tumor was surgically excised without recurrence. Histopathologically, the tumor was a typical pleomorphic adenoma with keratinization and glandular differentiation of tumor cells and fibroblastic, mucinous, hyalinized, and cartilagenous stroma.

Topics: Adenoma, Pleomorphic; Cell Differentiation; Cell Division; Humans; Keratins; Lip Neoplasms; Male; Middle Aged

In a series of 570 pleomorphic adenomas of main and accessory salivary glands, we found 48 recurrences (8.04%). These recurrences occurred between several months and 19 years after surgical treatment. They were more frequently noted in parotid tumors. Comparatively to a control series, in recurrent tumors myxoid structures were more frequent than epithelial structures, as demonstrated by immuno-markings (anti-protein S 100 and anti-vimentin sera). Besides, in these tumors, extracapsular myxoid expansions were commonly seen. The proliferative potential of myoepithelial cells which are the main cellular component of myxoid areas, is thus suggested as a mainly factor of recurrence of pleomorphic adenomas.

Topics: Adenoma, Pleomorphic; Carcinoembryonic Antigen; Humans; Immunohistochemistry; Keratins; Myxoma; Neoplasm Recurrence, Local; S100 Proteins; Salivary Gland Neoplasms; Vimentin

The coexpression of keratin and vimentin is described in 45 pleomorphic adenomas using an immunoperoxidase MAb method. Histopathologically, the outer layer of tubuloductal structures and peripheral tumor cells in solid masses, including modified or neoplastic myoepithelial cells, showed positive staining with monoclonal keratin antibody K8.12 and vimentin. This staining was found in the ratio of 10/26 (38.5%) in tubuloductal structures, 2/7 (28.6%) in peripheral tumor cells and 8/12 (66.7%) in modified myoepithelial cells. Concomitant staining of other keratin antibodies (PKK1, KL1) and vimentin did not exist. In addition, the ductal basal cells of normal salivary glands showed positive K8.12 labelling. The histogenesis of pleomorphic adenoma is discussed in relation to the differentiation of either ductal basal cells or ductal luminal cells from a single stem cell origin or the direct transformation of ductal basal cells to outer tumor cells and/or modified myoepithelial cells, both coexpressing K8.12 and vimentin.

Topics: Adenoma, Pleomorphic; Antibodies; Antibodies, Monoclonal; Connective Tissue; Epithelium; Humans; Immunohistochemistry; Keratins; Microtubules; Salivary Gland Neoplasms; Staining and Labeling; Vimentin

In the normal salivary gland, the monoclonal antibody to keratin 8 immuno-morphologically identifies the epithelium that covers acini and ducts. The monoclonal antibodies to keratin 17 and vimentin detect normal myoepithelium. The two keratins are found both in the epithelioid and mesenchyma-like components of pleomorphic adenoma, suggesting a single epithelial nature of this tumor. In all the morphological components of the pleomorphic adenoma, there are cells that combine protein expression of intermediate filaments normally labelling different cell subpopulations. This fact provides support for the hypothesis that the pleomorphic adenoma originates from bipotent precursor cells. A particular phenotype of pleomorphic adenoma elements is realized under the control of the local density of cells and microenvironment, as a result of which the cells expressing vimentin predominate in the mesenchymal component, keratin 8 in the epithelial tubular one.

Topics: Adenoma, Pleomorphic; Antibodies, Monoclonal; Epithelium; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Phenotype; Salivary Gland Neoplasms; Salivary Glands; Vimentin

The purpose of this immunohistochemical study was to know the degree and direction of differentiation, the mechanism of mesenchymal appearance, and histogenesis in pleomorphic adenomas which were obtained from surgical removed specimens. All specimens were fixed in 10% neutral phosphoate buffered formalin, and embedded in paraffin. Sections were steined with the avidin-biotin peroxidase complex method for keratin, vimentin, desmin and S-100 protein, the peroxidase-antiperoxidase method for lysozyme, and the direct immunoperoxidase method for IgA and secretory component. Normal salivary glands were employed as controls. 1. Solid portion of pleomorphic adenomas were consisted of the focal hypline cells and scattered the duct cell-like cells. The hyaline cells were positive for vimentin and S-100 protein, and the duct cell-like cells were positive for keratin. But one case was found the bundles of spindle-shaped cells which was similar to myoepithelial cells were positive for actin and another case was consisted of the focal duct cell-like cells were observed. 2. In the tubular portion, the duct-like structures were classified into three types. One type was mono-layered structure, another type was double-layered structure and the other type is duct-like structure in the solid portion. Any inner layer of the duct-like structure were positive for keratin. 3. Double-layered duct-like structures were most common type. Among the double-layered structures, hyaline cells mostly made up the outer layered structures. At times, the spindleshaped cells of the outer layer were found. This structures were similar to intercalated portion of normal salivary glands. In one case, inner and outer layer was consisted of keratin positive cells, but outer layer was steined for keratin stronger than inner. This structure was similar to excretory duct of normal salivary glands. 4. IgA and sc were seen at inner cells and in luminal accumulation of the duct-like structures. 5. In the myxoid regions, stellate cells or spindle cells were positive for vimentin, S-100 protein and partial positive for desmin. In the chondroid regions, chondrocyte-like cells were positive for vimentin and S-100 protein. These results seemed to suggest that pleomorphic adenomas were composed of duct cell-like cells and hyaline cells. Duct cell-like cells consisted of the duct-like structure in order to transport secretion which was similar to the duct of normal salivary glands.(ABSTRACT TRUNCATED AT 250 WO

Topics: Adenoma, Pleomorphic; Desmin; Humans; Immunoenzyme Techniques; Keratins; Parotid Neoplasms; S100 Proteins; Vimentin

Variant expressions of modified myoepithelial cells in salivary pleomorphic adenomas are described as determined by immunohistochemical techniques which visualized the distributions of S-100 protein, intermediate-sized filament proteins (keratin, vimentin, and desmin), and contractile proteins (myosin and actin), as well as lysozyme and lactoferrin. Immunohistochemical staining patterns of S-100 protein were basically used to classify modified myoepithelial cells, along with histologic criteria. Histochemical modifications of myoepithelial cells in pleomorphic adenoma of salivary glands could be divided into a) reactive, b) transformed, and c) neoplastic myoepithelial cells. Reactive myoepithelial cells were stromal-like cells which displayed an intense S-100 protein reaction. Transformed myoepithelial cells were negative or slightly positive for S-100 protein; they were located in the outer zone of tubular or duct-like structures and were spindle-shaped. The inner round cells of tubular and ductal structures, which could be ductal origin, gave intense keratin staining, as well as marked reactions for lysozyme and lactoferrin. Neoplastic myoepithelial cells were plasmatoid or fibrous types of cells and contained abundant S-100 protein and vimentin. These cells were termed "myoepithelioma" as in classical diagnosis.

Topics: Actins; Adenoma, Pleomorphic; Desmin; Humans; Keratins; Myoepithelioma; Myosins; S100 Proteins; Salivary Gland Neoplasms; Vimentin

Two malignant mixed tumours, in which both carcinomatous and sarcomatous features were present, are described. They arose in the palate in patients who had undergone surgery and irradiation for a pleomorphic adenoma at the same site 30 and 36 years previously. The histological differential diagnoses of recurrent benign pleomorphic adenoma, pleomorphic adenoma resembling mesenchymal tumour, and carcinoma in (ex) pleomorphic adenoma are discussed. On the basis of their positive reaction for keratin with specific monoclonal antibodies it is suggested that the myoepithelial cells are of epithelial origin. Immunohistochemical studies together with the histological appearance of the neoplasms indicate that the carcinomatous as well as the sarcomatous elements were derived from modified myoepithelial tumour cells. Irradiation may have been responsible for inducing a true malignant mixed tumour as distinct from the more common malignancy which may arise in pleomorphic adenoma, this being a simple carcinoma.

Topics: Adenoma, Pleomorphic; Adult; Aged; Antigens, Neoplasm; Carcinoma, Intraductal, Noninfiltrating; Chondrosarcoma; Female; Humans; Keratins; Middle Aged; Neoplasms, Radiation-Induced; Palatal Neoplasms; Salivary Gland Neoplasms

Monoclonal antibodies to keratins (KL1 and PKK1) were tested on paraffin sections in forty cases of pleomorphic adenoma from salivary glands. Squamous cells in the epidermis were positive for KL1, except for the basal cells, which were positive for PKK1. In normal salivary glands, ductal cells were positive for KL1 and PKK1 keratins, whereas KL1 staining of the large excretory ducts was weaker than that of PKK1. Myoepithelial cells were positive only for KL1. In pleomorphic adenoma, the following reactions were noted: a positive staining for KL1 and PKK1 was present in the inner layer of cells within tubular and ductlike structures, a markedly positive staining for KL1 was present in squamous metaplastic cells, and a negative staining reaction with KL1 and PKK1 in spindle-shaped tumor cells was observed within the outer layer. Spindle-shaped or fibroblast-like cells in the stroma, probably myoepithelial in origin, showed an irregular staining expression for KL1 and PKK1.

Topics: Adenoma, Pleomorphic; Antibodies, Monoclonal; Humans; Keratins; Mouth Mucosa; Salivary Gland Neoplasms; Salivary Glands; Skin

Intermediate filaments are composed of 5 groups which follow the classic histogenetic division of tissue. The application of antibodies against the 5 groups for the analysis of salivary gland tumours reveals the presence of keratin in normal and neoplastic epithelial tissue. All carcinomas e.g. adenocarcinomas, acinic cell tumours, mucoepidermoid tumours and squamous cell carcinomas were positive for keratin. Vimentin was regularly found in the cells of the stroma. A special distribution pattern of intermediate filaments was found in pleomorphic adenomas and in adenoid cystic carcinomas. These tumours display the presence of two systems, keratin and vimentin filaments. The application of antibodies against intermediate filaments is useful for differential diagnosis of salivary gland tumours and for histogenetic analysis of special tumour groups.

Topics: Adenocarcinoma; Adenolymphoma; Adenoma, Pleomorphic; Antibodies; Carcinoma, Adenoid Cystic; Carcinoma, Squamous Cell; Cytoskeleton; Humans; Intermediate Filaments; Keratins; Salivary Gland Neoplasms; Vimentin

We describe two novel monoclonal antibodies specific for glial filament protein (GFP), i.e., GF12.23 and GF12.24 (both IgG2a]. These cross-react over a broad range of species with epitopes located in the alpha-helical rod domain typical of all intermediate filament (IF) proteins. These monoclonal antibodies were used, in conjunction with other monoclonal GFP antibodies, rabbit antiserum to GFP, and various antibodies to other cytoskeletal proteins, to examine the occurrence of GFP in cells outside of the central nervous system of rodents, cows, and humans. We detected some scattered GFP-containing cells in the neural sheaths in some species but not in others, and we obtained different results when comparing the rabbit antisera with the monoclonal GFP antibodies. In the enteric glia of rats, we observed GFP-positive cells with all of the antibodies used, whereas in human intestine, the various monoclonal antibodies showed no reaction with any intestinal cells. Similarly, no GFP was detected in surface cells of the lens of cows and rats using any of the GFP antibodies, whereas some reaction was seen in murine lens tissue. We were also unable to detect GFP-positive cells in human, bovine, or rat liver with any of the monoclonal antibodies, which is in contrast to the reactivity of the rabbit GFP antisera with some stellate perisinusoidal cells of rat but not bovine or human liver. The possible reasons for the discrepancies between the different species and the different antibody preparations used are discussed. In addition, using double-label immunofluorescence microscopy, we showed that normal human parotid glands contain a certain type of epithelial cell that co-expresses cytokeratins and desmosomal proteins with GFP. The histological distribution of these GFP-positive cells suggests that they represent a subset of the myoepithelial cells present in this tissue. Cells co-expressing cytokeratins and GFP - in some cases, apparently together with vimentin as the third IF protein present - were also identified in tumors derived from this salivary-gland epithelium, i.e., pleomorphic adenomas, in which GFP-positive cells were relatively frequent in the myxoid and chondroid components, thus confirming the work of other investigators. Possible implications for the concept of histogenesis of these tumor cells are discussed, as are possible mechanisms resulting in the co-expression of IF proteins.

Topics: Adenoma; Adenoma, Pleomorphic; Animals; Antibodies, Monoclonal; Cattle; Cross Reactions; Epithelium; Epitopes; Eye; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Guinea Pigs; Humans; Keratins; Microscopy, Fluorescence; Myelin Sheath; Rats; Salivary Glands; Species Specificity; Vimentin

An immunocytochemical study was carried out on normal salivary gland tissue and ten salivary gland pleomorphic adenomas. Antibodies to myosin were used to stain myoepithelial cells. Duct cells were stained using an antibody to total keratin and a subpopulation of basal duct cells with an antibody to 45/46K keratins. Basement membranes were stained with anti-type IV collagen. The results demonstrated that myoepithelial cells are relatively rare in the majority of pleomorphic adenomas and that many of the cells which have been classically described as myoepithelial in routine histological preparations do not clearly show this type of differentiation. However, the tumors presented a spectrum of differentiation patterns from those that were mainly ductal to the rare tumour which was largely myoepithelial. It is further suggested that the 45/46K keratin antibody is capable of identifying a subpopulation of cells which could possibly be important in the histogenesis of this tumour.

Topics: Adenoma, Pleomorphic; Antibodies; Collagen; Epithelium; Humans; Keratins; Myosins; Salivary Gland Neoplasms; Salivary Glands

Antisera of several secretory products of the salivary gland were used to investigate the histogenesis of acinic cell tumors and mixed salivary gland tumors for comparison. Amylase, lactoferrin, secretory piece, and proline-rich protein (PRP) immunoreactivity was detected in the majority of acinic cell tumors; staining was focal, except for PRP, which was diffuse. Lysozyme immunoreactivity was rare. There was discordance for immunoreactivity with several antisera in identifiable tumor lobules of half of the neoplasms. An antikeratin serum outlined microcystic and follicular areas but rarely solid foci. These findings support the contention that acinic cell tumors derive from a tubular type stem cell. Lactoferrin and secretory piece immunoreactivity was not common in mixed tumors and was confined to scattered ductal cells and luminal contents. Rare small foci of amylase and PRP immunoreactivity were found in two mixed tumors only.

Topics: Adenoma, Pleomorphic; Adolescent; Adult; Aged; Amylases; Carcinoma; Female; Humans; Immunochemistry; Keratins; Lactoferrin; Male; Middle Aged; Muramidase; Peptides; Proline-Rich Protein Domains; Salivary Gland Neoplasms; Staining and Labeling

Thirteen cases of pleomorphic adenoma were studied by both immunohistochemical and other histochemical methods. The exocrine cells and myoepithelial cells appear to produce similar cell products as their normal salivary gland counterparts. Keratin was found in both exocrine cells and myoepithelial cells. CEA, secretory component, and lactoferrin were detected only in the tumor exocrine cells with adenoid differentiation. S-100 protein, ferritin, fibronectin, laminin and elastin were detected only in the myoepithelial cells. The residual sugars glucosyl, mannosyl, galactosyl and fucosyl were identified in both cell types, in variably detectable amounts.

Topics: Adenoma, Pleomorphic; Adult; Aged; Carcinoembryonic Antigen; Female; Ferritins; Fibronectins; Humans; Immunoenzyme Techniques; Keratins; Laminin; Male; Middle Aged; Retrospective Studies; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands; Salivary Glands, Minor

Normal salivary glands and 55 salivary gland tumors were examined by immunostaining (immunoperoxidase [IMP] and immunofluorescence [IMF]) to identify myoepithelial cells (MCs) and speculate on their role in the histogenesis of the tumors. The classic (C) MCs of normal salivary glands stained by IMP with antibodies to cytokeratin and S100 protein and stained by IMF with the same antibodies and with antibodies to vimentin and actin. Modified (M) MCs of pleomorphic adenomas stained positively by IMP and IMF with all of the preceding antibodies. In many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas, variable numbers of CMCs and MMCs stained positively by IMP with anti-cytokeratin and anti-S100 protein antibodies. No MCs were detected in adenolymphomas or acinic cell carcinomas. We believe that MCs play a major role in the histogenesis of pleomorphic adenomas and may also be important in many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas.

Topics: Actins; Adenolymphoma; Adenoma; Adenoma, Pleomorphic; Carcinoma; Carcinoma, Adenoid Cystic; Epithelial Cells; Epithelium; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Membrane Proteins; Mucin-1; Muscle, Smooth; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands; Vimentin

Surgical specimens of the salivary gland tumor were studied by immunohistochemical techniques using the anti-keratin antibody and the anti-myosin antibody. In the normal tissue, keratin was localized predominantly in the duct epithelial cells and myosin in the myoepithelial cells. According to the immunohistochemical staining patterns, the tumors were able to be divided into two groups: one group consisted of pleomorphic adenoma, adenoid cystic carcinoma, and adenocarcinoma which showed a mixture of keratin- and myosin-positive cells, respectively, mimicking the structures of the intercalated duct; the other comprised monomorphic adenoma and mucoepidermoid tumor which disclosed keratin-positive cells predominantly, resembling the constituent of the excretory duct. These results were mostly consistent with the "bicellular theory" that the salivary tumors generate from the intercalated duct reserve cells and the excretory duct reserve cells.

Topics: Adenocarcinoma; Adenolymphoma; Adenoma, Pleomorphic; Carcinoma; Carcinoma, Adenoid Cystic; Humans; Immunoenzyme Techniques; Keratins; Myosins; Salivary Gland Neoplasms; Salivary Glands

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.

Topics: Actins; Adenoma, Pleomorphic; Adult; Aged; Antibodies, Monoclonal; Epithelium; Female; Humans; Immunoenzyme Techniques; Immunologic Techniques; Intermediate Filament Proteins; Keratins; Male; Microscopy, Electron; Microscopy, Fluorescence; Middle Aged; Parotid Gland; Parotid Neoplasms; Protein Precursors; S100 Proteins; Salivary Gland Neoplasms; Submandibular Gland; Submandibular Gland Neoplasms; Vimentin

Antibodies to human and bovine epidermal prekeratin and antibodies to mouse liver cytokeratin component D (Mr 49 000) have been applied in indirect immunofluorescence microscopy on sections of human tumors of mammary gland and liver. In non-neoplastic mammary gland all epithelial cells were stained with these antibodies. In pre-invasive and invasive ductal and lobular carcinomas a cell population was observed which was not significantly stained with antibodies to epidermal prekeratin but did strongly react with antibodies to liver cytokeratin D. In the liver, the antibodies to epidermal prekeratin as well as those directed against liver cytokeratin D strongly decorated bile duct epithelia. In contrast, significant staining of the hepatocytes was only achieved with antibodies to liver cytokeratin D. This different staining reaction was maintained in liver tumors of hepatocellular and cholangiocellular origin. Antibodies to vimentin stained mesenchymal cells and tumors of mesenchymal derivation but reacted not significantly with any of the epithelial and carcinoma cells examined. The difference is of practical importance for the discrimination between anaplastic carcinomas and sarcomas of unknown origin. Cytokeratin could also be detected by antibody staining using the peroxidase-antiperoxidase (PAP) technique in formaldehyde-fixed and paraffin-embedded material of skin, gastrointestinal, respiratory, urinary and genital tract as well as various glands, liver and kidney. Examples of positive reactions were shown in a squamous cell carcinoma, a basalioma and a pleomorphic adenoma of the parotis. It is concluded that the immunohistochemical analysis of intermediate filament proteins has diagnostic potential in clinical pathology and may help to elucidate histogenesis and differentiation of tumors and possibly also prognosis of tumor growth. It is further suggested to use antibodies recognizing different subsets of proteins of the cytokeratin family in order to distinguish between different types of carcinomas.

Topics: Adenoma, Pleomorphic; Breast Neoplasms; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Liver Neoplasms; Parotid Neoplasms; Protein Precursors; Sarcoma; Skin Neoplasms

Topics: Actins; Adenoma, Pleomorphic; Cytoskeleton; Humans; Immunoenzyme Techniques; Keratins; Microscopy, Electron; Parotid Neoplasms