bromochloroacetic-acid and Salivary-Gland-Neoplasms

There is a lack of a comprehensive immunohistochemical (IHC) analysis of canalicular adenoma (CanAd), especially when combined with a description of the unique histologic features. Given the usual small biopsies, IHC may be useful in distinguishing CanAd from other tumors in the differential diagnosis. Retrospective. The patients included 54 females and 13 males (4.2:1), aged 43-90 years, with a mean age at presentation of 69.9 years. Clinical presentation was generally a mass (n = 61) slowly increasing in size (mean 38.5 months), affecting the upper lip (n = 46), buccal mucosa (n = 17) or palate (n = 4), involving the right (n = 29), left (n = 24) or midline (n = 9), without any major salivary gland tumors. The tumors ranged in size from 0.2 to 3 cm (mean 1.2 cm). Most tumors were multilobular or bosselated (76 %), often surrounded by a capsule. Histologically, the tumors were characterized by cystic spaces, tumor cords with beading, tubule formation, and by the presence of luminal squamous balls (n = 41). The cells were cuboidal to columnar with stippled chromatin. Mitoses were inconspicuous. A myxoid stroma (n = 64), sclerosis (n = 42), luminal hemorrhage (n = 51), and luminal microliths (calcifications) (n = 33) were characteristic. Nine (13.4 %) were multifocal. CanAd showed the following characteristic immunohistochemistry findings: CK-pan and S100 protein (strong, diffuse reaction); peripheral or luminal GFAP reaction; CK5/6 and p16 luminal squamous ball reaction; SOX10 nuclear reaction; cytoplasmic p63 reaction. CanAd are unique minor salivary gland tumors showing a distinct architecture and phenotype. They predilect to older women, with the majority multilobulated and affecting the upper lip, multifocal in 13 %; no major salivary gland tumors were identified. S100 protein, CK-pan, GFAP and SOX10 are positive, with luminal squamous balls highlighted by CK5/6 or p16.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Biopsy; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Retrospective Studies; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands; SOXE Transcription Factors

This is the first part of a 3-part comprehensive review of intraosseous carcinoma of the jaws. We have outlined 4 groups of intraosseous carcinoma of the jaws (metastatic, salivary-type, odontogenic, and primary intraosseous carcinoma), emphasizing the need for accurate diagnosis and the problems associated with changing classification systems, standardization of diagnostic criteria and nomenclature, and the accuracy of existing literature. In this first part, the features of metastatic and the very rare salivary-type carcinomas of the jaws are examined with particular emphasis on histologic and immunohistochemical characteristics, diagnostic difficulties, and uncertainties.

Topics: CA-125 Antigen; Carcinoma; Humans; Immunohistochemistry; Jaw Neoplasms; Keratins; Mandibular Diseases; Maxillary Diseases; Odontogenic Cysts; Salivary Gland Neoplasms; Transcription Factors

Hyalinizing clear cell carcinoma (HCCC) is a low-grade malignancy with infiltrative growth pattern. It affects mainly the minor salivary glands of adult women. The most frequent locations of this tumor are the palate and tongue. HCCC shows a poorly circumscribed, infiltrative, and essentially monomorphic population of clear cells with few mitoses and almost no nuclear or cellular pleomorphism. These cells form trabeculae, cords, islands, and/or nests, circumscribed by variable amounts of hyalinized fibrous bands with foci of myxohyaline stroma. S-100 protein, muscle-specific actin, smooth muscle actin, myosin, and calponin are consistently negative, which strongly indicates the absence of myoepithelial cell differentiation in this tumor. We present a case of HCCC affecting the upper vestibule in a 53-year-old man. The patient was treated by surgery and postoperative radiation and did not show recurrence or distant metastases 3 years after treatment. Discussed also are the clinical and pathologic features of this tumor along with the differential diagnosis and a literature review.

Topics: Adenocarcinoma, Clear Cell; Biopsy; Connective Tissue; Cytoplasm; Epithelial Cells; Follow-Up Studies; Humans; Hyalin; Keratins; Male; Middle Aged; Salivary Gland Neoplasms; Salivary Glands, Minor

Myoepithelial carcinoma with predominantly clear cell morphology is rare. A review of the literature identified 15 unequivocal cases, only two of which were of minor salivary gland origin. A case of minor salivary gland clear cell myoepithelial carcinoma of the retromolar region in a 70-year-old man is presented. It is important to recognize the clinicopathologic features of this unusual tumor, because of its histological similarity to several other primary and metastatic clear cell tumors and its aggressive behavior.

Topics: Aged; Carcinoma; Follow-Up Studies; Humans; Keratins; Male; Membrane Proteins; Neoplasm Invasiveness; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Serine Proteinase Inhibitors; Serpins; Vimentin

Myoepithelial carcinoma (MC), also known as malignant myoepithelioma, is a rare malignant salivary gland neoplasm with a predilection for the parotid gland. We present the clinicopathological and immunohistochemical features of 7 cases of intraoral MC in attempt to better understanding this entity.. Seven intraoral MCs were retrieved from the files of the Department of Oral Pathology, School of Stomatology, Wuhan University, during a 10-year period. Immunohistochemical markers, including cytokeratin (CK) AE1/AE3, S100, vimentin, smooth muscle actin (SMA), p63, and maspin, were used to further characterize these lesions. A review of contemporary relevant literature is also provided.. The patients were 5 women and 2 men, and the age range was 37 to 75 years (mean 57.9 years). Three cases arose in the hard palate, 2 in the retromolar region, and 1 each in the tongue and the floor of the mouth. Histologically, the tumors exhibited a solid architecture with cells arranged in nodules, nests, trabeculae, or cords. The epithelioid cell type is the most frequently encountered, followed by clear cells. The tumor-associated matrix is more prevalent hyalinized than myxoid. Immunohistochemically, CK AE1/AE3, S100, vimentin, p63, and maspin were expressed in all cases. Positivity for SMA was seen in 3 tumors. Five patients with follow-up information showed no evidence of disease after a mean follow-up of 69.6 months (range 22-108 months).. Combining the current series with 21 additional cases in the literature indicated that myoepithelial carcinoma of intraoral minor salivary glands is generally a low-grade malignant tumor with little propensity for regional or distant metastasis and low recurrence. Awareness of the clinicopathological and immunohistochemical features of intraoral MC is necessary for accurate diagnosis. Wide local excision with tumor-free margins is the treatment of choice.

Topics: Actins; Adult; Aged; Disease-Free Survival; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Myoepithelioma; Neck Dissection; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Serine Proteinase Inhibitors; Serpins; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins; Vimentin

Significant progress in the diagnosis and therapy of salivary gland diseases has been made in recent years. The new technique of diagnostic and interventional sialendoscopy has made an important contribution and is indicated in every case of obstructive sialadenitis. The number of open resections of salivary glands due to stones will clearly decrease in the future in favor of endoscopic removal. Due to recent publications on the appropriate extent of salivary gland resection in benign tumors, more and more specimens with reduced cuffs of healthy salivary gland tissue will be sent to the pathologists. Ultrasound will stay the procedure of first choice for imaging of salivary gland diseases in Germany. In combination with fine-needle aspiration cytology high sensitivity and specificity for the assessment of salivary gland tumors can be achieved. Diffusion-weighted magnetic resonance imaging (MRI) is a new imaging tool and the power of distinction of pleomorphic adenoma from malignant tumors is promising. The use of botulinum toxin for salivary glands diseases is increasing. Intraglandular injections have been shown to induce salivary gland atrophy in animal experiments. The availability of biologicals is currently yielding new aspects for the treatment of Sjögren's disease.

Topics: AIDS-Related Opportunistic Infections; Biomarkers, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Cysts; Diagnosis, Differential; Epithelium; Humans; Keratins; Lymph Nodes; Lymphoma, B-Cell, Marginal Zone; Parotid Diseases; Salivary Ducts; Salivary Gland Neoplasms; Salivary Glands; Sialadenitis; Sjogren's Syndrome

Clear cell carcinoma, not otherwise specified (CCC-NOS), is a recently described rare malignant salivary neoplasm. We report the clinicopathologic and immunohistochemical features of 4 cases. The results were then analyzed collectively with the approximate 60 cases of CCC-NOS reported in the English-language literature to define the characteristics of this unusual neoplasm. Combining our cases with those in the literature, a total of 66 cases, confirms that CCC-NOS is a low-grade malignant neoplasm with distinctive clinical and pathologic features. It arises primarily in the minor salivary glands (91% of cases), particularly in the palate or base of tongue, and usually occurs in patients >30 years of age (mean 54.2 years) with a female-to-male ratio of 1.4:1; 12.3% of patients experience local recurrences, 19.3% develop positive regional lymph nodes, 8.8% have distant metastases, and 3.5% die of the disease. Immunohistochemical study focusing on tumor differentiation was performed for our cases, and the findings support the concept that CCC-NOS is of ductal epithelial origin without myoepithelial cell participation.

Topics: Adenocarcinoma, Clear Cell; Aged; Fatal Outcome; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Salivary Gland Neoplasms; Salivary Glands, Minor

Clear cell carcinoma is a rare neoplasm that arises in salivary glands. They are more frequent in the intraoral minor salivary glands than the major salivary glands. The present case involved a 44-year-old Japanese man with a slight reddish swelling on the mandibular gingiva. Initial clinical diagnosis was squamous cell carcinoma based on this erythroplakial lesion. All tumor cells displayed the expected pattern of immunoreactivity, with positive results for pancytokeratin and high molecular weight cytokeratin. This report examined the immunohistochemical characteristics of clear cell carcinoma, minor salivary gland, and reviewed the existing literature.

Topics: Adenocarcinoma, Clear Cell; Adult; Gingival Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Salivary Gland Neoplasms; Salivary Glands, Minor

Sialadenoma papilliferum is a rare exophytic tumor of salivary gland origin, accounting for less than 1% of minor salivary gland tumors. It usually occurs in males older than 50 years as a painless papillary intraoral lesion. An 18-year-old male patient presented with an exophytic intraoral lesion present for approximately 12 years. The tumor was excised with a clinical diagnosis of infected hemangioma. However, histopathological diagnosis was consistent with sialadenoma papilliferum. The patient was followed up at regular intervals and no evidence of recurrence was noted. Our patient, aged 18 years, with tumor lasting for 12 years becomes the youngest case of intraoral sialadenoma papilliferum yet reported. This case highlights the importance of keeping sialadenoma papilliferum as a differential diagnosis of an intraoral exophytic proliferative lesion even in a young patient.

Topics: Adolescent; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Lip Neoplasms; Male; Salivary Gland Neoplasms; Salivary Glands, Minor

The aim of this study was to report an unusual case of mucoepidermoid carcinoma (MEC) in a 39-year-old woman. The tumor showed a prominent population of clear and intermediate basal cells. Clear cells rarely predominate over other cell types. Such cases are called clear cell variant of MEC. The case also revealed a variable amount of calcified material in the tumor mass. Calcifications are rare in clear cell MEC. These structures were periodic acid-Schiff positive and diastase resistant, excluding glycogen origin. Immunohistochemistry was performed, and the epidermoid component was positive for cytokeratin (CK)7, CK13, CK14, and CK19. The mucous and clear cells presented mild staining for CK7. Cytokeratins 7, 13, and 19 stained luminal cells, and intermediate cells exhibited positivity for CK7, CK14, and vimentin. The origin of the calcifications is speculated to be the result of dystrophic calcification of the amorphous eosinophilic material secreted by intermediate basal cells.

Topics: Actins; Adult; Carcinoma, Mucoepidermoid; Female; Humans; Keratins; Mouth Floor; Neoplasms, Glandular and Epithelial; Salivary Gland Neoplasms; Vimentin

Polymorphous low-grade adenocarcinoma (PLGA) and adenoid cystic carcinoma (ACC) have several overlapping histological patterns, including cribriform, tubular and solid patterns. The overlapping clinicopathological features of PLGA and ACC may result in a diagnostic pitfall. ACC has a much worse prognosis than PLGA, making differentiation important for therapeutic and prognostic purposes. Histopathological features remain the most reliable criteria to distinguish between these two tumours. Although PLGA and ACC have many features in common, PLGA is uncommon in the major salivary glands. Histopathological distinction is therefore mainly a problem in tumours of minor salivary gland origin where small biopsies often contribute to diagnostic difficulties. This paper reviews studies which have utilised several immunohistochemical markers in attempts to distinguish between PLGA and ACC, and also studies which have focussed on the two tumours individually. The potential discriminating value of immunohistochemistry between cases of PLGA and ACC still remains controversial.

Topics: Actins; Adenocarcinoma; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Adenoid Cystic; Diagnosis, Differential; Humans; Keratins; Mucin-1; Proliferating Cell Nuclear Antigen; S100 Proteins; Salivary Gland Neoplasms

We describe a case of pulmonary carcinoma with myoepithelial differentiation, analogous to basal cell adenocarcinoma of salivary glands. The patient, a 60 year-old man, smoker, presented with three peripheral nodules of the left lung. Preoperative staging was negative for metastatic disease and the patient underwent a surgical resection of the nodules. After 22 months, the patient is alive with no evidence of disease. Microscopically, the tumours were composed of atypical cells arranged in lobules, separated by basal membrane-like material. Immunohistochemically, tumour cells were positive for cytokeratin AE1/AE3, cytokeratin 14, vimentin, calponin, S-100 protein and gliofibrillary acid protein (GFAP). Electron microscopy showed features of epithelial and myoid differentiation and confirmed the myoepithelial nature of the tumour. Pulmonary tumours with myoepithelial differentiation are rare, but they have a wide and distinctive morphological spectrum.

Topics: Basement Membrane; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; Carcinoma, Basal Cell; Carcinoma, Non-Small-Cell Lung; Cell Differentiation; Epithelium; Glial Fibrillary Acidic Protein; Humans; Keratins; Lung Neoplasms; Male; Microfilament Proteins; Microscopy, Electron; Middle Aged; Myoepithelioma; Neoplasm Proteins; Organ Specificity; Remission Induction; S100 Proteins; Salivary Gland Neoplasms; Staining and Labeling; Vimentin

Primary undifferentiated carcinoma of the salivary glands is a rare, high-grade neoplasm which accounts for a very small number (1-5.5%) of malignant salivary gland tumors. The large-cell variant (LCU) is less well-characterized than the small-cell form. We report on the fine-needle aspiration (FNA) biopsy findings of 2 cases of LCU, one arising in the parotid gland, and the other in a buccal mucosa accessory salivary gland. The 2 cases were similar in composition: isolated and loosely cohesive large cells with abundant cytoplasm, and variability pleomorphic nuclei with prominent nucleoli. One case also featured multinucleated tumor giant cells and macrophage polykaryons; the latter has not previously been described in FNA biopsies of LCU. There was no evidence of squamous, myoepithelial, or widespread mucinous differentiation by morphological, cytochemical, or immunohistochemical analyses (focal rare mucin production identified on special stains in one case). The differential diagnosis is lengthy and consists of other high-grade primary salivary gland malignancies as well as metastatic lesions, including melanoma. The pattern of immunohistochemical reactivity (positive keratin, negative S-100, and HMB-45 antigens), and lack of conspicuous mucin production of significant lymphoidinfiltrate, were useful in establishing the correct diagnosis.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Biopsy, Needle; Carcinoma, Large Cell; Cell Nucleolus; Cell Nucleus; Cytoplasm; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Melanoma-Specific Antigens; Neoplasm Proteins; S100 Proteins; Salivary Gland Neoplasms

Topics: Actin Cytoskeleton; Aged; Basement Membrane; Carcinoma, Adenoid Cystic; Cytoplasmic Granules; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Microvilli; Mitochondria; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Solitary Pulmonary Nodule; Tongue Neoplasms

The light microscopic, immunohistochemical, and ultrastructural features of a case of apocrine carcinoma of the upper lip of a 54-year-old white man are described. The neoplasm had a cribriform intraductal component resembling apocrine carcinoma of the breast. The tumor had irregular borders and infiltrated skeletal muscle. The neoplastic cells had abundant eosinophilic granular cytoplasm and showed apical decapitation secretion characteristic of apocrine differentiation. The differential diagnosis is discussed with particular reference to distinction of the tumor from oncocytic carcinoma and ductal carcinoma of minor salivary gland.

Topics: Adenocarcinoma; Antibodies, Neoplasm; Apocrine Glands; Apolipoproteins; Apolipoproteins D; Carcinoembryonic Antigen; Carcinoma; Carrier Proteins; Diagnosis, Differential; Glycoproteins; Humans; Immunoenzyme Techniques; Keratins; Lip Neoplasms; Male; Membrane Transport Proteins; Middle Aged; Salivary Gland Neoplasms

The glandular odontogenic cyst (GOC) is a rare odontogenic cyst which is still controversial in regard to classification, terminology, and origin. The first Japanese case of GOC is reported. Immunohistochemical examination for expression of cytokeratins and epithelial membrane antigen by monoclonal antibodies suggested that the lining epithelium was of odontogenic origin with metaplastic mucus-laden cells. We have reviewed the literature and compared the clinicopathological findings of the reported case of GOC with those of botryoid odontogenic cysts (BOC). The anatomical location, age range, and sex of GOC cases were very similar to those of BOC. GOC appears to be a multiocular and mucoepidermoid variant of non-keratinizing odontogenic cysts, which also includes BOC. GOC should be separated from the other types of odontogenic cyst and central mucoepidermoid tumours of salivary gland origin.

Topics: Aged; Diagnosis, Differential; Epithelium; Gene Expression; Humans; Keratins; Male; Mandibular Diseases; Membrane Glycoproteins; Mucin-1; Mucins; Mucoepidermoid Tumor; Mucus; Neoplasm Proteins; Odontogenic Cysts; Salivary Gland Neoplasms

Small cell carcinomas of the major salivary glands are rare tumors, accounting for less than 1% of malignant neoplasms at these sites. To date, approximately 41 such tumors have been described. They recently have been classified into two groups, based on the ultrastructural presence or absence of intracytoplasmic neuroendocrine (NE) granules, "small cell neuroendocrine carcinoma" and "small cell ductal carcinoma". This study concerns 11 primary small cell carcinomas that had been previously studied ultrastructurally; it was undertaken to determine whether these lesions possessed a neuroendocrine phenotype, using a battery of immunohistochemical stains. Antibodies to epithelial membrane antigen (EMA), cytokeratin (CK), Leu 7, vimentin (VIM), synaptophysin (SYN), chromogranin (CHR), and neuron-specific enolase (NSE) were employed, with the avidin-biotin-peroxidase complex technique and paraffin sections. All tumors in this study expressed at least one neuroendocrine marker. In eight tumors EMA was found; CK was present in all 11 cases, seven of which demonstrated focal paranuclear staining. Leu 7 was seen in eight tumors, VIM was expressed in two cases, SYN was found in three tumors, and CHR was detected in three neoplasms. Anti-neuron-specific enolase labeled eight tumors. From the preceding data one may conclude that all small cell salivary gland carcinomas have neuroendocrine characteristics, even though dense core granules cannot be demonstrated in some of them ultrastructurally.

Topics: Animals; Carcinoma, Small Cell; Humans; Immunohistochemistry; Keratins; Meta-Analysis as Topic; Rabbits; Salivary Gland Neoplasms; Staining and Labeling

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

The cellular characteristics of the basilar epithelium in Warthin's tumor have had limited investigation. Ultrastructural examination of basal cells in 9 Warthin's tumors reveals that in addition to numerous mitochondria these cells possess a rich complement of tonofilaments. However, in three examples there are a proportion of these tonofilament-rich cells that have a narrow band of microfilaments in the peripheral cytoplasm adjacent to the basal lamina. Frozen sections of Warthin's tumor and normal salivary glands, doubly labeled with rhodamine-phalloidin for actin and monoclonal antibody 312C8-1 for cytokeratin 14, show that normal myoepithelial cells of acini and intercalated ducts have both of these filaments, as do a proportion of basal cells in the tumor. There are distinct differences in the cytokeratin polypeptide complement between normal luminal and myoepithelial cells as well as between luminal and basal cells in Warthin's tumor. Differences occur in the cytokeratin profiles between the luminal and basal cells of Warthin's tumor and comparable cells in the normal gland; however, there continue to be some similarities in the cytokeratin polypeptides of myoepithelium and the basal cells of normal salivary ducts and the basal cells of Warthin's tumor. These findings show that basal cells in Warthin's tumor are a mixed population with some capable of differentiating as myoepithelial-like cells, and that this tumor could arise from any level of the normal salivary gland duct system.

Topics: Adenolymphoma; Antibodies, Monoclonal; Carcinoma, Basal Cell; Cytoplasmic Granules; Epithelium; Humans; Immunohistochemistry; Keratins; Microfilament Proteins; Microscopy, Fluorescence; Salivary Gland Neoplasms; Staining and Labeling

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

Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of salivary glands in children and young adults. Typically, it is composed of squamoid, mucin-producing and intermediate-types cells. However, overt keratinization is rare. To the best of our knowledge, extensive keratinization or keratin pearls in MEC has never been reported. Keratinization or keratin pearls are regard "practically never seen in low-grade MEC". Herein, we report a case of a 34-year-old woman who presented with a tumor in right parotid gland for 2 months. Microscopically, the tumor was composed of extensive squamous cells with overt keratin pearls, intermediate cells and few scattered mucous cells.

Topics: Adult; Carcinoma, Mucoepidermoid; Child; DNA-Binding Proteins; Female; Humans; In Situ Hybridization, Fluorescence; Keratins; Nuclear Proteins; Parotid Gland; Salivary Gland Neoplasms; Trans-Activators; Transcription Factors; Young Adult

Intercalated duct lesions (IDLs) are usually asymptomatic. We report a case of IDL, in which a palpable mass formed. The patient was a 45-year-old Japanese male, who noticed a mass in the left parotid region. The nodular lesion was well-circumscribed, but did not have a fibrous capsule or exhibit infiltrative growth. It contained a small cystic space and consisted of basaloid cells arranged in a cribriform pattern and inner ductal cells. It had some solid areas of nest-like proliferation displaying mild cellular atypia. Immunohistochemically, the luminal cells were positive for cytokeratin (CK)7 and epithelial membrane antigen, and the abluminal cells were positive for CK5/6, p63, and DOG1. S-100 protein-positive stromal cells were also seen. The lesion's cells were all positive for SOX10, and the nuclei of some basaloid cells were positive for β-catenin. The Ki-67 labeling index was 3.8%. The ductal cells contained diastase-digestion-resistant, Periodic acid Schiff-positive zymogen granules. Genetically, the lesion harbored a missense mutation in the CTNNB1 gene. We diagnosed the lesion as an IDL. As IDLs are usually small non-neoplastic lesions, symptomatic cases are rare. Based on its common immunohistochemical and genetic features, IDL may be a precursor of basal cell adenoma/adenocarcinoma, such as intercalated duct adenoma.

Topics: Adenocarcinoma; Adenoma; Amylases; beta Catenin; Humans; Keratins; Ki-67 Antigen; Male; Middle Aged; Mucin-1; Parotid Gland; Periodic Acid; S100 Proteins; Salivary Gland 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

The nature of the lymphoid stromal component in Warthin tumor and lymphadenoma of the parotid gland has been a controversial topic in salivary gland pathology for decades. Two theories exist: first, that these tumors arise from salivary gland inclusions within intraparotid lymph nodes; and second, that they arise within salivary gland parenchyma and induce tumor-associated lymphoid proliferation (TALP). A recent study demonstrated that low molecular weight cytokeratin is effective in distinguishing salivary gland tumors within lymph nodes from those inducing TALP via identification of extrafollicular reticulum cells, which are only found in true lymph nodes. Twenty-one Warthin tumors and 4 lymphadenomas were retrieved from the archives of the Department of Pathology at University of Texas Southwestern Medical Center. Cam5.2 immunohistochemistry was performed on each case and independently evaluated by two pathologists. Extrafollicular reticulum cells were identified by Cam5.2 immunostaining in 21 of 21 Warthin tumors (100%), and 3 of 4 lymphadenomas (75%). Extrafollicular reticulum cells were consistently localized to the perisinusoidal and paracortical areas of the lesions studied. Extrafollicular reticulum cells were identified via low molecular weight cytokeratin Cam5.2 immunohistochemistry in all of the Warthin tumors and most of the lymphadenomas evaluated. This finding strongly supports the notion that these most if not all of these tumors arise within intraparotid lymph nodes, presumably from salivary gland inclusions entrapped during embryonic development.

Topics: Adenolymphoma; Biomarkers; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Parotid Neoplasms; Salivary Gland Neoplasms

Tumor-associated lymphoid proliferation (TALP) is a well-recognized lymphocytic reaction that is commonly associated with certain salivary gland tumors. A salivary carcinoma with TALP may be confused for true lymph node involvement by that tumor, constituting a potential pitfall in tumor staging that may result in unnecessary therapeutic intervention or erroneous prognostication for patients. True lymph nodes harbor populations of extrafollicular reticulum cells (ERCs), which can be highlighted by low molecular weight cytokeratin immunohistochemistry. We sought to determine whether low molecular weight cytokeratin Cam5.2 immunostaining may be utilized to differentiate true lymph node involvement by salivary gland tumors from TALP. The surgical pathology archives of the University of Texas Southwestern Medical Center was searched for cases of salivary gland neoplasms exhibiting either TALP or true lymph node involvement. Hematoxylin and eosin-stained sections were examined. Cases were classified on the basis of a definitive lymph node capsule and subcapsular sinus, as seen on routine histologic evaluation. Low molecular weight cytokeratin Cam5.2 immunostaining was performed and evaluated on all cases. Twenty-three salivary gland carcinomas with TALP and 16 carcinomas involving a lymph node (14 carcinomas metastatic to regional lymph nodes and 2 carcinomas arising from benign lymph node inclusions) were identified. Numerous Cam5.2-positive ERCs were identified within the nodal tissue of all true lymph nodes involved by carcinoma (16 of 16 cases), while Cam5.2-positive ERCs were completely absent in all cases of salivary gland lesions with TALP (0 of 23 cases) (100% vs. 0%, p < .0001, Fisher's Exact). Utilization of low molecular weight cytokeratin Cam 5.2 immunostaining for ERCs is a highly useful tool for distinguishing true lymph node involvement by salivary gland carcinomas from TALP. This strategy may be useful in identifying genuine nodal metastasis in histologically ambiguous cases, and to avoid erroneously upstaging tumor with TALP as nodal metastasis with the resulting prognostic and therapeutic implications. Moreover, low molecular weight cytokeratin immunostaining may be useful in confirming the rare examples of salivary gland tumors arising from intranodal salivary gland inclusions.

Topics: Biomarkers; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Salivary Gland 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

The diagnosis of polymorphous low-grade adenocarcinoma (PLGA) remains difficult for general pathologists, particularly in cases of small biopsy samples. We aimed to characterize the histopathological spectrum and immunohistochemical aspects by using an accessible immunohistochemical panel of cytoskeletal proteins in limited samples of PLGA.. Forty-six patients diagnosed with PLGA in incisional biopsies were identified retrospectively. Seventy-two per cent of patients were women and 28% were men, with a mean age of 55 years. The palate was the most affected site. Grossly, the mean size of the samples was 0.8 cm and 74% of specimens were fragmented. All tumours characteristically displayed the microscopic features of architecturally diverse patterns, infiltrative areas and low-grade cytology. Neoplastic cells were diffusely positive to cytokeratin (CK) 7, vimentin and S100 protein, but only focally positive to CK14 and negative to α-smooth muscle actin (α-SMA), thus lacking myoepithelial differentiation.. Microscopic recognition of PLGA is facilitated by a characteristic combination of multiple architectural patterns of growth, infiltration of adjacent tissues and cytological aspects. These features are present even in small biopsy samples. The association of histopathological aspects with CK7, CK14, vimentin, S100 and α-SMA immunoexpression is helpful in reaching the diagnosis of doubtful cases.

Topics: Actins; Adenocarcinoma; Adult; Aged; Algorithms; Biomarkers, Tumor; Biopsy; Female; Humans; Immunohistochemistry; Keratin-14; Keratin-7; Keratins; Male; Middle Aged; Retrospective Studies; S100 Proteins; Salivary Gland Neoplasms; Vimentin

Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumour that harbours the recurrent ETV6-NTRK3 translocation. This is the first series of MASC cases identified in the historic cohort of carcinomas of salivary glands with clinical/pathological correlation and follow-up data. We reviewed 183 primary carcinomas of major and minor salivary glands resected at the Medical University of Gdańsk, Poland, between 1992 and 2012. Based on morphology and immunohistochemistry, cases suspicious for MASC were selected, and the diagnosis was confirmed by fluorescence in situ hybridization (FISH) for ETV6 rearrangement and by RT-PCR for the ETV6-NTRK3 fusion transcript. Seven carcinomas met the criteria of MASC, as they exhibited a typical appearance with solid/microcystic and papillary architecture and intraluminal secretions, and cells completely devoid of basophilic cytoplasmic zymogen granules indicative of true acinar differentiation. The only paediatric case was an unencapsulated tumour composed of macrocystic structures covered by a mostly single but, focally, double layer of cells with apocrine morphology. In all cases, the neoplastic cells revealed immunoreactivity for S100, mammaglobin, cytokeratin CK7, CK8, STAT5a and vimentin. FISH for ETV6 gene rearrangement was positive in six out of seven cases, and RT-PCR was positive in three cases. MASC is a new entity of malignant epithelial salivary gland tumours not included in the 2005 WHO Classification of Head and Neck Tumours. There is a growing body of evidence that it is not as rare as was assumed, as is also indicated by our series (3.8 %). In most cases, MASC shares some microscopic features with AciCC, adenocarcinoma/cystadenocarcinoma NOS and low-grade MEC. In rare cases, MASC with high-grade transformation may mimic the morphological appearances of high-grade salivary gland malignancies, such as salivary duct carcinoma.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; ETS Translocation Variant 6 Protein; Female; Follow-Up Studies; Gene Fusion; Gene Rearrangement; Humans; Keratins; Male; Middle Aged; Proto-Oncogene Proteins c-ets; Receptor, trkC; Repressor Proteins; Retrospective Studies; S100 Proteins; Salivary Gland Neoplasms; STAT5 Transcription Factor; Translocation, Genetic; Tumor Suppressor Proteins; Vimentin; Young Adult

To compare the expression of cytokeratins (CKs) in the solid, microcystic, follicular, and papillary-cystic subtypes of salivary gland acinic cell carcinoma (AcCC) in order to characterize the cell origin.. The expression of CK7, CK14, CK19, CK20, and alpha-smooth muscle actin (α-SMA) in 18 cases of AcCC was assessed with the use of immunohistochemical staining. Ten normal salivary glands were used as controls.. The expression of CKs in AcCCs varied according to their growth patterns. CK7 showed strong and diffuse positive staining in the microcystic, follicular, and papillary-cystic subtypes, whereas staining was weakly positive or negative in the solid subtype. CK14 expression was negative in almost all AcCCs. Expression of CK19 was observed in the microcystic, follicular, and papillary-cystic subtypes, but was minimally observed in the solid subtype. No cells positive for CK20 or α-SMA were found in any AcCCs.. We demonstrated that the microcystic, follicular and papillary-cystic subtypes of AcCC exhibit features of ductal luminal cells with expression of CK7 and CK19, suggesting their ductal origination. By contrast, the solid subtype might originate from different cells with no ductal CK expression.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Carcinoma, Acinar Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Salivary Gland Neoplasms

We report a peculiar case of canalicular adenoma of the upper lip in a 57-year-old woman, presenting as two distinct asymptomatic nodules diagnosed and treated surgically within a 2-year period.

Topics: Adenoma; Disease-Free Survival; Female; Humans; Keratins; Lip; Lip Neoplasms; Middle Aged; Neoplasms, Second Primary; Proto-Oncogene Proteins c-kit; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor

Canalicular adenoma is an uncommon benign tumour that generally arises in the minor salivary glands of individuals over 60 years old. This study illustrates a case of canalicular adenoma in a 70-year-old female, presenting as two distinct asymptomatic nodules in the upper lip. Immunohistochemistry analysis was performed. Clinical features, management, histology and immunoprofile from this case and from the literature are discussed.

Topics: Adenoma; Aged; Asymptomatic Diseases; Female; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Ki-67 Antigen; Lip Neoplasms; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Transcription Factors; Tumor Suppressor Proteins

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

Metastatic clear cell renal cell carcinoma (CCRCC) should be considered in differential diagnosis of intraoral clear cell tumors, including mucoepidermoid carcinoma (MEC).. We compared the clinical, histologic, histochemical, and immunohistochemical characteristics of 9 oral metastatic CCRCCs and 8 intraoral clear cell MECs.. Oral metastatic CCRCC affected salivary-gland containing tissues in 7 cases (78%). Microscopically, oral metastasis revealed a proliferation of neoplastic clear cells arranged in an alveolar pattern with central blood vessels, features that were not seen in any intraoral clear cell MEC. Mucicarmine staining was positive only in clear cell MEC. Immunohistochemistry showed similarities in cytokeratin expression; vimentin and CD10 were expressed in all oral metastatic CCRCCs but in only 1 clear cell MEC each.. Besides clinical history, the alveolar pattern, vessel distribution, absence of mucicarmine staining, and vimentin and CD10 immunoexpression are useful in histologic differential diagnosis of CCRCC and clear cell MEC.

Topics: Adenocarcinoma, Clear Cell; Adult; Aged; Aged, 80 and over; Carcinoma, Mucoepidermoid; Carcinoma, Renal Cell; Carmine; Cell Nucleus; Coloring Agents; Cytoplasm; Diagnosis, Differential; Female; Hemorrhage; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Male; Microvessels; Middle Aged; Mouth Neoplasms; Neprilysin; Salivary Gland Neoplasms; Vimentin

Parotid gland carcinomas are rare. Among them, the epithelial-myoepithelial carcinoma (EMC) is extremely rarely diagnosed. This case report was based on a female with a history of 17 years of recurrent EMC of the parotid and evidence of distant metastasis over a period of 2 years. During debulking procedures of her extensive facial tumour, small tumour samples were transplanted to nude mice. The tumours grew well on the mice and were characterized morphologically and immunohistochemically after explantation. Cellularity per mm(2) ranged between 3,470 and 7,410. The tumours were characterized by the typical bipolar pattern of tumour cells and broad stromal septae. All but one of 7 transplanted tumours were positive for pan-cytokeratin marker KL-1. The proliferation index in terms of MIB-1-stained nuclei increased from 2% to 20% and was correlated positively to the expression of EGFR. IGF-1R-, VEGF- and FLK1-stained cells were found in all cases. The increase in EGFR- and MIB-1-positive cells correlated with the clinical course of the patient, who showed shorter periods of tumour recurrence prior to her death. These findings in EMC transplanted to the nude mouse demonstrate the feasibility of growing EMC in vivo.

Topics: Animals; Biomarkers, Tumor; Carcinoma, Ductal; Epithelium; ErbB Receptors; Immunohistochemistry; Keratin-8; Keratins; Ki-67 Antigen; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Glandular and Epithelial; Receptors, Growth Factor; Salivary Gland Neoplasms; Tomography, X-Ray Computed

Intercalated duct lesions (IDLs) are rare, poorly understood and not well-studied lesions that have been associated with a small number of epithelial-myoepithelial carcinomas (EMC) and basal cell adenomas. To examine the nature of IDLs and their association with salivary gland tumors, we reviewed 34 lesions in 32 patients. The IDLs were stained with CK7, estrogen receptors (ER), progesterone receptors, lysozyme, S100, calponin, and CK14. The patients ranged in age from 19 to 80 years (mean 53.8) with a 1.7:1 female predominance. The majorities of IDLs were parotid lesions (82%), were small and nodular (average size 3.1 mm) and showed 3 architectural patterns: hyperplasia (20), adenoma (9), and hybrid forms (5). In 59% of cases, IDLs were seen in conjunction with another salivary gland tumor, most commonly basal cell adenoma (8 cases), followed by EMC (3 cases). One case showed a combination of intercalated duct hyperplasia and basal cell adenoma. The IDLs stained diffusely with CK7 (100%) and S100 (73%) and focally for ER (91%) and lysozyme (100%). Calponin and CK14 highlighted a thin myoepithelial cell layer around all ducts (100%). Normal intercalated ducts were also consistently positive for CK7 and lysozyme, and focally for ER, but were S100 negative. In summary, IDLs have a variety of patterns ranging from hyperplasia to adenoma with hybrid lesions and share morphologic and immunophenotypic features with normal intercalated ducts. There is an association with basal cell adenomas and EMC, which lends credence to their role as a putative precursor lesion.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; Female; Humans; Hyperplasia; Keratins; Male; Microfilament Proteins; Middle Aged; Muramidase; Neoplasms, Multiple Primary; Parotid Gland; Receptors, Steroid; S100 Proteins; Salivary Ducts; Salivary Gland Neoplasms; Submandibular Gland; Young Adult

We evaluated the medical record of patients with salivary gland neoplasms diagnosed at Timisoara City Hospital from 2002 to 2009. A study has been carried out for seven years on 204 cases of salivary gland tumors and only two cases of salivary gland lymphomas were diagnosed. The two cases were females of 71- and 49-year-old, respectively. The formalin-fixed paraffin-embedded tissue samples were cut in 4 mum thick sections and stained with Hematoxylin and Eosin. The primary monoclonal antibodies for the immunohistochemical analysis were the followings: LCA (2B11, Dako), CD20 (L26, Dako), cytokeratin (MNF116, Dako), p53 (DQ-7, Dako), and PCNA (PC-10, Dako). The histopathology and immunohistochemistry suggested in the first case a low-grade diffuse large B-cell mucosa associated lymphoid tissue lymphoma and in the second case a high-grade extranodal marginal zone B-cell lymphoma.

Topics: Aged; Antigens, CD20; Biomarkers, Tumor; Female; Humans; Immunohistochemistry; Keratins; Lymphoma, Non-Hodgkin; Middle Aged; Prognosis; Proliferating Cell Nuclear Antigen; Romania; Salivary Gland Neoplasms; Tumor Suppressor Protein p53

Epithelial-myoepithelial carcinoma (EMC) is a rare malignant salivary gland neoplasm that most commonly occurs in the parotid gland, but can also arise in the minor salivary glands. Three cases are reported of epithelial-myoepithelial carcinoma of the minor salivary glands, with the goal of better defining this entity.. All three cases showed a characteristic nodular/multinodular growth pattern and classic biphasic tubular histology. All parts of each tumor were surrounded by a myoepithelial cell rim and there was evidence of invasion.. Immunohistochemical analysis showed the tumor cells to be weakly positive for S100, cytokeratin (CK) CK5/6, CK7, CKAE-1/AE-3 and strongly positive for epithelial membrane antigen (EMA) and p63; they were focally positive for calponin and acute lymphoblastic leukemia antigen (CD10). The tumor cells were negative for vimentin, alpha-smooth muscle actin (SMA) (except one case), glial fibrillar acid protein (GFAP) and MIB1. The tumors were resected completely with wide margins and no recurrence or metastasis had occurred from 6 to 15 months after surgery.. Three cases of minor salivary gland tumors are described and the differential diagnosis underlined in relation to benign myoepithelioma. The characteristic morphological and immunohistochemical features aided diagnosis of these biphasic tumors.

Topics: Aged; Aged, 80 and over; Epithelial Cells; Female; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Male; Middle Aged; Myoepithelioma; Salivary Gland Neoplasms

Mucoepidermoid carcinoma is the most common malignant salivary gland tumor, composed of several different cell types, with controversial histogenesis. The aim of this study was to assess the expression of cytokeratins in mucoepidermoid carcinoma, comparing to cytokeratin expression in normal salivary glands, in order to establish a possible correlation between tumor cells immunostaining and mucoepidermoid carcinoma histogenesis and differentiation. Eighty cases of salivary gland mucoepidermoid carcinoma were immunohistochemically examined with the use of antibodies against cytokeratins 6, 7, 8, 13, 14, 18, and 19. Cytokeratin expression varied according to the cellular type: squamous cells presented high expression of cytokeratins 6, 7, 8, 14, 18, and 19; intermediate and mucous cells of cytokeratin 7; clear and columnar cells of cytokeratins 6, 7, 8 and the latter also expressed cytokeratin 18. Cytokeratin 13 expression was low in all cell types. Cytokeratin immunoexpression in mucoepidermoid carcinoma was variable according to the cellular type; but regardless of the cellular type studied, cytokeratins 7 and 13 were, respectively, constantly high and low expressed. The immunoprofile of the normal salivary glands was variable according to the component but, in general, cytokeratin profile in mucoepidermoid carcinoma showed similarity to the immunoexpression on the excretory duct unit of normal salivary glands.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Mucoepidermoid; Child; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Salivary Gland Neoplasms; Salivary Glands, Minor; Young Adult

Salivary duct carcinoma (SDC) is an uncommon malignant tumor, characterized by aggressive behavior and poor prognosis. SDC usually arises from ductal epithelium of the major salivary glands, and it is quite infrequent elsewhere. We present a rare case of a 73-year-old man with SDC, which is possibly originated from the paranasal sinuses or the lacrimal system. Microscopic evaluation revealed that the tumor cells, with pleomorphic nuclei and abundant eosinophilic cytoplasm, formed cell nests and duct-like structure. A cribriform growth pattern was also seen. Immunohistochemical staining was positive for cytokeratins (CAM 5.2 and 34betaE12), gross cystic disease fluid protein 15 (GCDFP-15), and androgen receptor protein, while p63 and involucrin were negative. The patient already had multiple metastasis of the tumor in the lung at diagnosis, and he could not undergo definitive surgical procedures, because of severe restrictive lung disease. Although SDC in the sinonasal tract is quite rare, SDC should be in the differential diagnosis in these regions, due to its aggressive behavior and poor prognosis.

Topics: Aged; Biomarkers; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Neoplasms, Second Primary; Paranasal Sinus Neoplasms; Prognosis; Salivary Ducts; Salivary Gland Neoplasms; Tomography, X-Ray Computed

Topics: Adenocarcinoma; Aged; Carcinoma, Adenoid Cystic; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Mucin-1; Neoplasms, Multiple Primary; Salivary Gland Neoplasms

The objective of this experiment was to determine the relationship between the expression of cytokeratins (CKs) and histologic grading in MEC. Eleven cases of MEC were selected and graded as low, intermediate and high-grade tumors. The expression of CKs 7, 8, 10, 13 and 14 was assessed immunohistochemically using streptavidin-biotin complex method. The results showed that the studied CKs were expressed in most cases of MEC, independently of histologic grading. Nonetheless, low-grade tumors demonstrated intense staining of CK 7 and 8; additionally, CK 10 and 13 were more pronounced in this grade. The immunoexpression was variable according to cellular type and organization pattern of the tumor. Mucous cells were positive for CK 7 and 8; epidermoid cells were stained for CK 10, 13 and 14; CK 7, 8, 10 and 14 were observed in intermediate cells, and CK 7 was occasionally seen in clear cells. Cystic structures and duct-like elements in MEC were positive for CK 7 and 8, whereas solid nests showed positivity for all CKs. These results suggest that expression profile of these proteins does not reflect the biological behavior of MCE, however, it guides the detection of cellular types and differential diagnosis from other salivary gland tumors.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Mucoepidermoid; Child; Diagnosis, Differential; Female; Humans; Immunochemistry; Keratins; Male; Middle Aged; Neoplasm Staging; Salivary Gland Neoplasms

Salivary gland lymphoepithelial carcinomas (LECs) are associated with Epstein-Barr virus (EBV) in endemic areas, whereas sporadic cases are usually EBV negative. We have studied two EBV-associated LECs from Caucasian patients for their EBV gene expression profile and their immunophenotype. Tumour cells of case 1 showed expression of EBNA1 only, corresponding to an EBV latency type I. Tumour cells of this case expressed various basal and glandular cytokeratins. In case 2, the LEC was accompanied by a low-grade spindle cell lesion with an immunophenotype of myoepithelial cells, whereas the high-grade tumour expressed cytokeratin (Ck) 8 only. In case 2, the high-grade tumour showed an EBV lantency II pattern with expression of EBNA1, LMP1 and LMP2A (latency II). The spindle cell lesion of this case was also EBV-infected and showed low levels of EBNA1 and LMP1 expression, while LMP2A was not detectable. The detection of EBV in both components of case 2 together with immunophenotypic evidence of transition between both components supports the notion that at least some LECs arise through a low-grade myoepithelial intermediate. Expression of LMP2A may be of therapeutic interest because it may make such cases amenable to immunotherapy with EBV-specific cytotoxic T cells.

Topics: Carcinoma, Squamous Cell; Epstein-Barr Virus Infections; Epstein-Barr Virus Nuclear Antigens; Female; Gene Expression; Gene Expression Profiling; Herpesvirus 4, Human; Humans; Immunophenotyping; In Situ Hybridization; Keratins; Male; Middle Aged; Salivary Gland Neoplasms; Tumor Virus Infections; Viral Matrix Proteins; Viral Proteins

We have used a recently described model in which a ras oncogene is expressed in cytokeratin 5 (K5)-expressing cells on doxycycline administration to explore the effects of this oncogene in salivary glands of adult mice. Inducible expression of a mutated K-ras gene under the control of the K5 promoter led to the development of hyperplastic and dysplastic epithelial lesions and carcinomas, with an incidence of 100% and a minimum latency of a week. All major salivary glands were affected, as well as a set of previously undescribed buccal accessory salivary glands located on the apex of the masseter muscle, close to the oral angle. The tumors appear to arise from the cytokeratin 5-positive basal cell compartment. Myoepithelial cells participated in the hyperplasias but not in carcinomas, because the tumors are negative for smooth muscle actin. Carcinomas did not accumulate immunoreactive p53 but are positive for p63, as assayed by immunohistochemistry using an antibody against the N terminus of DeltaN p63, a splice variant of p63 that can inhibit p53 transcriptional activity. In this study, we provide evidence that the ras oncogene, targeted to a specifically sensitive cell compartment within the salivary glands, can trigger a series of event that are sufficient for full carcinogenesis.

Topics: Animals; Carcinoma; Carcinoma, Squamous Cell; Cell Proliferation; Cheek; Female; Fibroadenoma; Gene Expression Regulation, Neoplastic; Genes, ras; Keratins; Male; Mice; Mice, Transgenic; Mouth Mucosa; Promoter Regions, Genetic; Salivary Gland Neoplasms; Salivary Glands; Submandibular Gland

Topics: Actins; Adenocarcinoma, Papillary; Calcium-Binding Proteins; Calponins; Humans; Immunohistochemistry; Keratins; Male; Microfilament Proteins; Middle Aged; Muscle, Smooth; Nose Neoplasms; Paranasal Sinus Neoplasms; Salivary Gland Neoplasms

Primary lung tumors showing features of salivary gland-type neoplasms are extremely rare, and their immunohistochemical profile has been seldom studied. We report two cases of bronchial pleomorphic and mucous gland adenomas and study the expression of markers such as TTF-1 and high molecular weight keratins in these tumors. Both tumors were endobronchial. The pleomorphic adenoma also had a well-circumscribed parenchymal component, with a biphasic morphology composed of epithelial and myoepithelial cells in a background of myxoid and hyaline stroma. The mucous gland adenoma displayed papillary and dilated glandular structures. In both cases, epithelial cells showed strong and diffuse cytoplasmic staining with high molecular weight cytokeratins (cytokeratin 5/6 and keratin 903), and lacked TTF-1 expression. This immunoprofile provides useful clues for the histogenesis of pulmonary benign salivary gland-type adenomas and helps in distinguishing them from primary adenocarcinomas in small biopsy specimens.

Topics: Bronchial Neoplasms; Cytoplasm; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Salivary Gland Neoplasms

Inverted ductal papilloma (IDP) is a type of ductal papilloma arising in ducts of minor salivary glands. Very few cases, and no cases in Japan, have been reported. Reported herein is a case of IDP with a review of the literature. The patient was a 49-year-old man presenting with a lump in the right buccal mucosa of the premolar area of the mandible. The tumor was excised en bloc after a biopsy diagnosis of IDP. On the surface of the covering epithelium, an opening was seen to be filled with mucinous material. On cut surface the opening led to the tumor cavity. The major portion of the tumor parenchyma was made up of papillary proliferation of basaloid squamous cells. Some crypts, microcysts, and mucous cells were seen. There were no findings suggestive of a malignant tumor. The patient's postoperative course was uneventful and there has been no recurrence after 1 year's follow up. Immunohistochemical analysis of the present case supports the hypothesis that IDP originates from squamous metaplasia and proliferation of minor salivary gland duct cells.

Topics: Biomarkers, Tumor; Humans; Keratins; Male; Middle Aged; Mouth Mucosa; Mucin-1; Papilloma, Inverted; Salivary Ducts; Salivary Gland Neoplasms; Salivary Glands, Minor

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

Epithelial myoepithelial carcinoma (EMC) is a rare low grade malignant salivary gland neoplasm that most commonly occurs in the parotid gland but can also arise in minor salivary glands. We report a case of primary epithelial myoepithelial carcinoma of minor salivary gland in a 25 year old women who presented with swelling left cheek of one year duration and bilateral submandibular lymphadenopathy. A mass causing erosion of mandible, thyroid cartilage and masseter muscle was identified on CT scan. This was excised and histological examination revealed a mixture of ductal structures consisting of inner dark cells and outer clear cells seen in solid sheets. Immunohistochemical analysis showed the clear cells to be weakly positive for S100 and smooth muscle actin (SMA) and ductal cells to be positive for cytokeratin (CK) and epithelial membrane antigen (EMA). The characteristic morphological and immunohistochemical features aided in the diagnosis of epithelial myoepithelial carcinoma.

Topics: Actins; Adult; Carcinoma; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Mandible; Mucin-1; Myoepithelioma; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands

Salivary duct carcinomas (SDC) are high grade neoplasms morphologically reminiscent of breast ductal carcinomas. Whereas the latter are well characterized, the body of immunophenotypic and cytogenetic data on SDC is limited. We studied 23 SDC by conventional histology, immunohistology, in situ hybridization, and comparative genomic hybridization (CGH). Data were subjected to biomathematical analysis in comparison to previously characterized breast ductal carcinomas in situ and invasive ductal carcinoma cases. Most SDC stained for cytokeratins (Ck) Ck 8/18 (77 %) or Ck 5/6 (30 %), 30 % of cases expressed the androgen receptor (AR), 14 cases (63 %) expressed c-erbB2, and one case stained for prostate specific antigen. Except for two cases, Ck 8/18 and Ck 5/6 were not coexpressed. Ck 8/18 expression positively correlated with presence of c-erbB2 and AR. At variance, Ck 5/6 correlated positively with p63 and inversely with both AR and c-erbB2 expression. Ck 5/6 and p 63 co-expression was also found in a distinct population of ductal epithelial cells of normal salivary glands. CGH analysis of SDC revealed increasing numbers of alterations in correlation with advanced diseases, but no recurrent alterations. Cluster analysis of phenotypic and genotypic markers assigned both salivary and breast carcinomas to numerous clusters independent of the primary tumour site. Although undistinguishable by conventional histology, SDC are heterogeneous, comprising at least two immunophenotypically distinct subgroups of neoplasms. Cluster analysis suggests several distinct patterns of gene expression common to both primary sites explaining morphologic parallels between SDC and high grade breast cancer.

Topics: Genotype; Humans; Keratins; Phenotype; Salivary Ducts; Salivary Gland Neoplasms

The differential diagnosis of oncocytic neoplasms of salivary glands includes both primary and metastatic tumors, one of which is renal cell carcinoma. This study compared immunohistochemical staining characteristics of oncocytomas arising from salivary gland to metastatic renal cell carcinoma using a panel of markers.. Immunohistochemistry for cytokeratin 7 (CK7), cytokeratin 20 (CK20), epithelial membrane antigen (EMA), vimentin, CD10, and renal cell carcinoma marker (RCC) was performed on 10 oncocytomas and compared with ten metastatic renal cell carcinomas.. There were overlapping histologic findings in the oncocytomas and metastatic renal cell carcinomas, with oncocytomas displaying clear cell changes in 2 of 10 cases. CK7 was positive in 9 of 10 oncocytomas and CK20 in 8 of 10 (7/10 stained for both), and vimentin was only weakly positive in 4 of 10 oncocytomas. All oncocytomas were EMA positive, with membranous staining, and all were negative for CD10 and RCC. Metastatic renal cell carcinoma was strongly positive for vimentin, EMA, and CD10 in most cases. RCC and CK7 were variably positive in metastatic renal cell carcinomas (4/10), and only 1 of 10 showed weak staining with CK20.. Salivary gland oncocytomas and metastatic renal cell carcinomas share some similar histologic and immunohistochemical characteristics. CD10 and CK20 were the most useful markers to distinguish metastatic renal cell carcinoma from oncocytomas in the salivary gland, whereas RCC, EMA, CK7, and vimentin are not as useful.

Topics: Adenoma, Oxyphilic; Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Immunohistochemistry; Immunophenotyping; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Kidney Neoplasms; Male; Middle Aged; Mucin-1; Neprilysin; Salivary Gland Neoplasms; Vimentin

The differential diagnosis of salivary gland carcinoma is often difficult because of the confusing histopathological features of the different types of salivary gland carcinomas. The expression of MUC3, MUC5AC, MUC6, cytokeratin (CK)7 and CK20 was studied in 20 mucoepidermoid carcinomas (MEC), 20 adenoid cystic carcinomas (AdCC), and 11 acinic cell carcinomas (ACC). All the cases (51/51, 100%) were positive for CK7, but they were not positive for CK20. All the cases (100%) of the MEC were positive for MUC5AC, while all MEC (100%) were negative for MUC3. Only two cases (10%) were positive for MUC6. All cases (100%) of AdCC were negative for MUC3, MUC5AC and MUC6. Eight cases (73%) of ACC were positive for MUC3, but all the cases (100%) were negative for MUC5AC and MUC6. It is concluded that the positive expression of MUC5AC is very unique to MEC, and that the positive expression of MUC3 is very unique to ACC. These findings will be very useful for the differential diagnosis of the salivary gland carcinomas.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Acinar Cell; Carcinoma, Adenoid Cystic; Carcinoma, Mucoepidermoid; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Mucin 5AC; Mucin-3; Mucins; Salivary Gland Neoplasms

Five cases of mucoepidermoid carcinoma (MEC) of the breast are reported. All patients were women ranging in age from 29 years to 80 years. As histological grading is one of the most important prognostic factors in breast invasive carcinomas, MEC was graded using the Auclair et al. [1] grading system specific for MEC of salivary glands and the Elston and Ellis [4] grading method, a widely employed grading system in breast cancer. It was found that the two different grading systems appear to be interchangeable in assessing the grade of MEC of the breast. Accordingly, three cases were regarded low grade (G. 1), one intermediate (G. 2) and one high grade (G. 3). The cases were studied with immunohistochemistry and were found to have the same keratin pattern shown by their salivary gland counterpart. It was found that there are more similarities than differences between MEC of the breast and of salivary glands.

Topics: Actins; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Calcium-Binding Proteins; Calponins; Carcinoma, Mucoepidermoid; Cell Nucleus; Chromatin; Cytoplasm; DNA-Binding Proteins; Female; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Microfilament Proteins; Middle Aged; Periodic Acid-Schiff Reaction; Phosphoproteins; Prognosis; Salivary Gland Neoplasms; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

On the basis of the heterogeneity of cytokeratins 7 and 20 expression in malignant epithelial tumors, the cytokeratin 7/20 immunophenotype has served as a useful diagnostic tool for discrimination of primary and/or metastatic carcinomas of unknown origin. However, the expression pattern of these cytokeratins in malignant salivary gland tumors has not been thoroughly studied. Our study material was composed of 84 malignant tumors of primary major or minor salivary gland origin. Nine histologic types of carcinoma were represented, including mucoepidermoid (26 cases), adenoid cystic (25), polymorphous low grade (11), salivary duct (8), acinic cell (4), ex mixed tumor (3), not otherwise specified (3), clear cell (2), and basal cell (2). In all, 13 cases of primary skin or mucosal squamous cell carcinoma with secondary salivary gland involvement were also examined. Immunoreactivity for cytokeratin 7 was evident in all malignant salivary gland tumors; the staining pattern was diffuse and strong in 62 cases, and focal and strong in 22 cases. In contrast, 78 cases were negative for cytokeratin 20, whereas only six cases (two mucoepidermoid, one adenoid cystic, and three salivary duct) displayed focal weak positivity. Overall, 92.9% of malignant salivary gland tumors were characterized by a cytokeratin 7 positive/20 negative immunoprofile, the remaining 7.1% of cases being positive for both cytokeratins. The latter phenotype was more common in salivary duct carcinomas (P< or =0.05). On the other hand, most squamous cell carcinomas (69%) were negative for both cytokeratins, while the remaining cases (31%) were negative for cytokeratin 20 and focally weakly positive for cytokeratin 7. We suggest that assessment of cytokeratin 7/20 immunoprofile may facilitate the differential diagnosis of (a) primary malignant salivary gland tumors from metastatic tumors, (b) metastatic salivary gland tumors, (c) primary salivary gland tumors, especially mucoepidermoid carcinomas, from squamous cell carcinomas, and (d) salivary duct carcinomas from other malignant salivary gland tumors.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Child; Child, Preschool; Female; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Salivary Gland Neoplasms

Myoepithelial cell carcinoma (MCC) of the salivary gland is a rare entity. Here, we describe the karyotype of MCC. The patient was a 53-year-old man, with a rapidly growing lesion of the palate. Despite complete surgical excision, radio- and chemotherapy, the lesion rapidly harboured local and distant metastases leading to the death of the patient, 4 months after the diagnosis. On histological and ultrastructural examination, the primary tumour and the related metastases were composed of oval and spindle cells, with features of myoepithelial cell differentiation reported in the literature. Cytogenetic analysis showed a composite karyotype in the primary tumour: 45-46,XY, +3[cp3]/ 44-45,XY, -17[cp4]/ 46,XY[5]. The lymph-node metastasis was near-triploid and showed a complex karyotype. Our cytogenetic data differ from those described in benign or slowly growing salivary gland tumours showing myoepithelial cell differentiation. It is suggested that highly aggressive tumours might follow a different pathway of malignant transformation.

Topics: Calcium-Binding Proteins; Calponins; Cell Differentiation; Chromosomes, Human, Pair 17; Cytogenetic Analysis; DNA-Binding Proteins; Fatal Outcome; Genes, Tumor Suppressor; Humans; Karyotyping; Keratins; Lymphatic Metastasis; Male; Microfilament Proteins; Middle Aged; Monosomy; Myoepithelioma; Neoplasm Metastasis; Palate, Hard; Phosphoproteins; Salivary Gland Neoplasms; Trans-Activators; Transcription Factors; Tumor Suppressor Protein p53; Tumor Suppressor Proteins

Central mucoepidermoid carcinoma (MEC) is an entity whose origin is still controversial. Glandular odontogenic cyst (GOC) is a recently described lesion whose relationship to low-grade central MEC has been reported in the literature. Our aim was to assess the cytokeratin (CK) profile of central MEC and GOC, and compare the results with CK expression in salivary gland MEC and odontogenic cysts and tumors. Eighty-five cases, including 6 central MECs, 23 salivary gland MECs, 10 GOCs, 34 odontogenic cysts and 12 ameloblastomas, were studied through immunohistochemistry using eleven monoclonal anti-CK antibodies. All central MECs expressed CKs 5, 7, 8, 14, and 18 and all GOCs expressed CKs 5, 7, 8, 13, 14, and 19. Comparing CK expression from GOC and central MEC we found differences in CKs 18 (30% vs 100%) and 19 (100% vs 50%). Central MEC and GOC are probably distinct entities with CK profiles similar to lesions of glandular and odontogenic origins, respectively, and expression of CKs 18 and 19 could be useful in their differential diagnosis.

Topics: Adult; Aged; Carcinoma, Mucoepidermoid; Female; Humans; Immunohistochemistry; Jaw Diseases; Keratins; Male; Mandibular Diseases; Maxillary Diseases; Middle Aged; Odontogenic Cysts; Salivary Gland Neoplasms

The tissue organization of the salivary gland is complex, and a large number of salivary gland tumor entities with a broad morphologic spectrum are listed, creating tumor classification schema for the salivary glands that are difficult to understand. In the present study, we attempted to examine how the anatomical components of the salivary gland are associated with morphological subtypes of tumors. We selected a panel of 12 molecules, which labeled one or some of the components, with all of the markers covering every component of the salivary glands. Using tissue microarray, expression profiles of these molecules were examined in four representative spots from each of 88 salivary gland tumors. The resulting large data matrix was analyzed using principle component analysis (PCA). We considered the first three eigenvectors to be significant; as the eigenvalues were more than 1.0 and the cumulative proportion achieved was 67%. Comparison with expression patterns in normal tissue suggested that the three components represented myoepithelial differentiation, and luminal and basal cell phenotypes. Then, we compared the PCA results with individual morphologic subtypes. Individual subtypes were clustered among the three dimensions of the components. This implies that salivary gland tumors may be well characterized by using only three components.

Topics: 14-3-3 Proteins; Actins; Biomarkers, Tumor; Calcium-Binding Proteins; Calmodulin-Binding Proteins; Calponins; DNA-Binding Proteins; Exonucleases; Exoribonucleases; Genes, Tumor Suppressor; Glycoproteins; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratins; Microfilament Proteins; Muscle, Smooth; Neoplasm Proteins; Neprilysin; Phosphoproteins; Principal Component Analysis; Proteins; Salivary Gland Neoplasms; Serpins; Tissue Embedding; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

The canalicular adenoma is an uncommon, benign salivary gland tumour that most frequently occurs in the upper lip. Although the incidence of multifocal epithelial tumours of the minor salivary is very low, canalicular adenoma sometimes present as a multifocal lesion. We present a case of multifocal canalicular adenomas of upper lip in a woman aged 68 years and discuss their features, emphasising diagnosis, clinical behaviour, treatment, histological and immunohistochemical aspects.

Topics: Adenoma; Aged; Biopsy, Fine-Needle; Disease-Free Survival; Female; Humans; Immunohistochemistry; Keratins; Lip; Salivary Gland Neoplasms; Salivary Glands, Minor

Sialadenoma papilliferum (SP) is a rare benign tumour of salivary gland origin, which has been included among the ductal papillomas in the latest classification of tumours by the World Health Organisation. Two SP from the minor salivary gland of the palate of middle age patients were presented and studied by immunohistochemical. Our results showed presence of cytokeratins (CKs) 13, 14, 7, 8, 19 and absence of vimentin and smooth muscle actin. This immunoprofile is similar to the excretory duct of salivary gland.

Topics: Adenoma; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Palatal Neoplasms; Palate, Hard; Palate, Soft; Salivary Gland Neoplasms; Salivary Glands, Minor

Acinic cell carcinoma (ACC) is an uncommon low-grade malignancy of the salivary glands. Most cases occur in the major salivary gland, but a few cases affecting the minor salivary gland have also been described. Although various growth patterns have been reported in the literature, a few cases have been diagnosed as ACC with follicular pattern. We present a rare case of ACC with follicular pattern of the soft palate in a 60-year-old man. The occurrence of ACC in this area is extremely rare, and its striking thyroid-like appearance may cause confusion in the differential diagnosis.

Topics: Carcinoma, Acinar Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Palate, Soft; Salivary Gland Neoplasms; Vimentin

Intra-oral lipoma is a well-known entity, but lipomatous tumors including salivary gland tissue containing clustered or peripherally located ducts and acinar cells are uncommon. They are a newly recognized entity of salivary gland lipoma, designated sialolipoma. We describe a case of sialolipoma arising in the floor of the mouth presenting with apparently normal salivary gland tissue, as demonstrated by both histologic and immunohistochemical findings, in a 67-year-old female. Complete surgical removal of the tumor with preservation of the sublingual gland was implemented after a careful examination confirming that the lesion did not originate from the sublingual gland.

Topics: Actins; Aged; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lipoma; Mouth Floor; Mucin-1; Muscle, Smooth; S100 Proteins; Salivary Gland Neoplasms

Topics: Aged; Aneuploidy; Biopsy; Carcinoma; Diagnosis, Differential; Diploidy; Female; Flow Cytometry; Humans; Keratins; Male; Middle Aged; Palatal Neoplasms; S100 Proteins; Salivary Ducts; Salivary Gland Neoplasms; Salivary Glands, Minor

Immunohistochemistry is an important tool when dealing with salivary gland neoplasms. Canalicular adenoma and polymorphous low-grade adenocarcinoma may share some histologic characteristics that can cause difficulties in their separation. In the present study, cases of polymorphous low-grade adenocarcinoma and canalicular adenoma were submitted to a panel of antibodies to evaluate the differences in their immunoprofiles. The results obtained showed that, while vimentin is only expressed by polymorphous low-grade adenocarcinoma, CK7 and CK8 are present in both neoplasms. Therefore, vimentin is the best marker to differentiate between these tumors.

Topics: Adenocarcinoma; Adenoma; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratin-7; Keratins; Salivary Gland Neoplasms; Salivary Glands, Minor; Vimentin

Basal cell adenoma is an uncommon epithelial neoplasm of the salivary gland most commonly arising in the parotid glands. We report a case of basal cell adenoma of the minor salivary gland presenting as a slowly progressing, large parapharyngeal mass. Histopathology revealed a well-encapsulated mass with characteristic histomorphology. Immunohistochemistry showed selective positivity for pancytokeratin, S-100, and smooth muscle actin in the tumor which highlighted the participation of myoepithelial cells in histogenesis. In addition, positivity was noted for carcinoembryonic antigen and vimentin. Ultrastructural analysis showed characteristic features including reduplicated basal laminae around the tumor cells, presence of intermediary filaments, and rough endoplasmic reticulum in the cytoplasm. There are no reports of basal cell adenoma presenting as a parapharyngeal mass lesion in the available English literature. This case highlights the rarity of this tumor with regard to its site of origin, possibly from a minor salivary gland.

Topics: Actins; Adenoma; Biomarkers, Tumor; Cytoplasmic Structures; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Neck; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Tomography, X-Ray Computed; Treatment Outcome

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

To investigate the clinicopathological features of mucinous adenocarcinoma of salivary glands.. The clinical manifestations and histopathological characteristics of 6 cases of mucinous adenocarcinoma of salivary gland were studied by retrospective and routine histopathology and immunohistochemistry.. Four mucinous adenocarcinoma occurred in palate and 2 in mouth floor. Average age of patients was 60 years (48 - 70) and males were affected more often than females (4:2). Pathologically, the tumor grew with infiltration of surrounding tissues. The tumor consisted of unitary mucinous cells and mucin pool was obvious. The cell pleomorphism and nuclear mitosis were often seen. Some tumors showed acinus-like structure. Tumor cells often formed incomplete duct-like structure and small clusters floating in mucinous pool. There were intracellular mucin and signet ring cells in the tumor. Tumor cells showed positive reaction to PAS, Alcin blue, and some cytokeratin staining.. Mucinous adenocarcinoma of salivary gland is a rare malignant tumor which mainly affects palate and mouth floor of older patients. The tumor may originate from acinic cell of mucous acinus or multi-potential cell of salivary gland.

Topics: Adenocarcinoma, Mucinous; Aged; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Salivary Gland Neoplasms

A correct histologic differential diagnosis between salivary acinic cell carcinoma (ACC) and adenocarcinoma not otherwise specified (AC-NOS) is highly relevant because of the strikingly different biologic behavior and related therapeutical strategies. The distinction between both tumor types can be difficult because of an enormous variation in histologic appearance, with either type showing partially overlapping morphologic features. Owing to a lack of approved markers, the expression of PAS-staining, alpha-Amylase, alpha-1 Anti-trypsin, cytokeratin (CK)-subtypes 7/18 and Ki-67 was evaluated in 16 cases of ACC and 16 cases of AC-NOS. CK 7 is identified as the most reliable marker with strong positivity in AC-NOS, and complete or preponderant negativity in ACC. The characteristic membranous staining pattern of CK 18 in ACC, in contrast to a diffuse cytoplasmic pattern in AC-NOS, proved to be an additional valuable criterion. PAS and alpha-Amylase are only of little value when ACC is diagnosed, as many cases are only faintly positive or completely negative. The proliferation index (Ki-67) proved to be significantly higher in AC-NOS; however, the diagnostic usefulness is limited by a relevant overlap. In conclusion, we recommend CK 7 and 18 as the most valuable markers in cases with difficult differential diagnosis between ACC and AC-NOS.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Acinar Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Middle Aged; Salivary Gland Neoplasms

The purpose of this study was to evaluate the biological mechanisms of docetaxel (TXT) on salivary gland carcinoma.. The effects of TXT on a spontaneous murine salivary carcinoma were determined. Proliferation, cell cycle regulation, connexin43 expression, gap-junctional intercellular communication, apoptosis, and Fas receptor (FasR) expression were measured.. We characterized a spontaneous mouse salivary gland carcinoma (SGC1). SGC1 is a poorly differentiated carcinoma that originated from the parotid gland of a BALB/c mouse. SGC1 cells were cultured and found to be immortal past 30 passages. Initially, cells formed tumor nodules in severe combined immunodeficient (SCID) mice. Afterward, SGC1 cells that were subcultured from SCID tumors readily formed colonies in soft agar and were highly tumorigenic in SCID mice and immune-competent BALB/c hosts. Dose response for TXT with respect to growth suppression, G(2)-M cell cycle arrest, and apoptosis was found. Induction of apoptosis by TXT coincided with an increase in cell surface FasR expression. Up-regulation of FasR with lower doses of TXT rendered cells susceptible to FasR agonist antibody-mediated apoptosis. In the absence of TXT, anti-FasR antibodies were completely without effect, suggesting that TXT is critical for priming apoptosis mediated through the Fas pathway. In addition, gap-junctional intercellular communication was augmented by TXT in SGC1 cells concomitant with increased connexin43 expression and membrane localization.. We have identified several novel targets of TXT that contribute to its antitumor activity in poorly differentiated salivary gland carcinoma. These results suggest that TXT may be appropriate for additional in vivo studies and clinical trials in patients with salivary cancers.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Blotting, Western; Cell Communication; Cell Cycle; Cell Division; Connexin 43; Docetaxel; fas Receptor; Female; Flow Cytometry; Fluorescent Antibody Technique; Gap Junctions; Immunoenzyme Techniques; Keratins; Mice; Mice, Inbred BALB C; Mice, SCID; Paclitaxel; Precipitin Tests; Proliferating Cell Nuclear Antigen; S100 Proteins; Salivary Gland Neoplasms; Taxoids; Tumor Cells, Cultured

The purpose of the present study is to determine the presence and distribution of epithelial and myoepithelial cells in mucoepidermoid carcinoma (MEC) of salivary glands and to compare them with normal salivary gland tissue and other primary carcinomas. This is in order to establish novel diagnostic criteria and to better understand MEC histogenesis. Formalin-fixed paraffin-embedded tissues from ten well-differentiated MECs, three adenoid cystic carcinomas (ACC), four acinic cell carcinomas (AC), and three epithelial-myoepithelial carcinomas (EMCC) of salivary glands were studied with immunohistochemistry using antibodies that recognise antigens indicative of epithelial and myoepithelial cell differentiation. An anti-mitochondrial antibody was also employed. Normal salivary tissue was present for comparative study in non-tumorous areas of the same section from 12 cases. MEC contained numerous keratin-positive cells. Anti mitochondrial antibody was diffusely positive in all ten of these tumours. Smooth muscle actin, h-caldesmon, and smooth muscle heavy chain myosin, which are indicative of myoepithelial cell differentiation, were negative. Rare cells in only one case were stained by calponin. Cytokeratin 14 (CK14) and anti mitochondrial antibody stained cells located mainly at the periphery of neoplastic nests and cystic spaces, while CK7 was mainly present in cells bordering gland lumina (zoning pattern). The immunohistochemical cell profile was similar to that seen in striated normal ducts. All others tumours studied showed a different immunohistochemical pattern, mostly consisting of a lack of mitochondrion-rich cells and the presence of myoepithelial cells in ACC and EMCC. Immunoreactivity in MEC for CK7, CK14 and mitochondrial antibodies appears as a peculiar pattern of staining, different from that of other salivary gland tumors; this seems helpful for diagnostic purposes. In addition, a differentiation of the "striated duct phenotype" is suggested.

Topics: Actins; Autoantigens; Calcium-Binding Proteins; Calmodulin-Binding Proteins; Calponins; Carcinoma, Mucoepidermoid; Humans; Immunohistochemistry; Keratins; Microfilament Proteins; Mitochondria; Myosins; Salivary Gland Neoplasms

Topics: Aged; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Lipoma; Male; Parotid Gland; Salivary Gland Neoplasms; Vimentin

Basal cell adenoma is a benign epithelial neoplasm with a uniform histologic appearance dominated by basaloid cells. Those cells may be distributed in various arrangements as solid, trabecular, tubular and membranous. Canalicular adenoma is also a benign neoplasm composed by columnar cells arranged in branching and interconnecting cords of single or double cell thick rows. There is some disagreement among investigators about whether canalicular adenoma should be included within the basal cell adenoma histologic spectrum. In the present study we compared the expression of cytokeratins (CK), vimentin and muscle-specific actin, utilizing immunohistochemical technique, in three cases diagnosed as basal cell adenomas predominantly of the solid type, and three cases of canalicular adenomas. The results obtained showed a distinct immunoprofile for both neoplasms. Solid areas of basal cell adenomas did not stain for any of the tested antibodies; only when there was tubular differentiation, those structures expressed CKs 7, 8, 14, and 19 in luminal cells and vimentin in non-luminal cells. On the other hand, canalicular adenomas strongly expressed CKs 7 and 13. The panel of antibodies utilized supports the separation of the two entities.

Topics: Actins; Adenocarcinoma; Adenoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Neoplasm Proteins; Salivary Gland Neoplasms; Vimentin

Salivary duct carcinoma is an uncommon malignant salivary gland tumor that occurs predominantly in the parotid gland. Oral involvement is extremely rare, with few cases having been reported in the literature. The tumor is characterized by an aggressive behavior and has a poor prognosis. We describe a case of salivary duct carcinoma arising in the hard palate of a 63-year-old man. Immunohistochemical analysis revealed that tumor cells tested positive for cytokeratin, epithelial membrane antigen, proliferating cell nuclear antigen, Ki67, p53, laminin, and collagen IV. Despite radical surgical resection, bilateral neck dissection, and postoperative radiotherapy, liver metastases developed, and the patient subsequently died of his disease.

Topics: Carcinoma; Collagen; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Laminin; Liver Neoplasms; Male; Middle Aged; Mucin-1; Palatal Neoplasms; Prognosis; Proliferating Cell Nuclear Antigen; Radiotherapy, Adjuvant; Salivary Ducts; Salivary Gland Neoplasms; Salivary Glands, Minor; Tumor Suppressor Protein p53

Pathologic factors of predictive value for carcinoma ex pleomorphic adenoma (CXPA), an aggressive salivary gland malignancy, are poorly defined. Because residual mixed tumor may be relatively inconspicuous and various carcinoma subtypes are encountered, misdiagnosis is common. To describe the pathologic features and identify potential prognostic factors, we retrospectively examined 73 cases of CXPA of the major salivary glands treated at Mayo Clinic. Paraffin section immunostaining for keratins (AE1/AE3, CK7, CK20), epithelial membrane antigen, carcinoembryonic antigen, vimentin, actin, S-100 protein, glial fibrillary acidic protein, and p53 and c-erbB-2 oncoproteins was performed in 69 cases. DNA content and proliferation indices were determined by digital image analysis of Feulgen- and MIB-I-stained sections, retrospectively. Survival was calculated by the Kaplan-Meier method, and prognostic variables were analyzed with the log-rank test. The carcinoma component was predominant in 82% of tumors. Adenocarcinoma not otherwise specified (31 cases) and salivary duct carcinoma (24 cases) were the most frequent histologic subtypes. Sixty-two tumors were high grade (Broders 3 or 4). Residual mixed tumor was extensively hyalinized in 54 cases. Pathologic features significantly associated with overall survival included pathologic stage (P =.009), tumor size (P =.012), grade (P =.005), proportion of carcinoma (P =.004), extent of invasion (P =.002), and proliferation index of carcinoma (P =.03). Of 4 patients with intracapsular (noninvasive) carcinoma, none had an adverse outcome. The immunohistochemical profile of CXPA included positive staining reactions in the malignant component for AE1/AE3 in 97% of cases, CK7 in 94%, epithelial membrane antigen in 86%, carcinoembryonic antigen in 75%, vimentin in 52%, and S-100 protein in 29%. Expression of p53 and c-erbB-2 oncoproteins was detected in 41% and 30% of the carcinomas, respectively, but neither was associated with decreased survival. High-grade salivary adenocarcinoma that is difficult to classify should raise the suspicion of possible CXPA. Intracapsular carcinoma has a benign clinical course. Significant prognostic factors in CXPA include tumor stage, grade, proportion of carcinoma, extent of invasion, and proliferation index.

Topics: Actins; Adenocarcinoma; Adenoma; Adult; Aged; Carcinoembryonic Antigen; Cell Division; DNA, Neoplasm; Female; Glial Fibrillary Acidic Protein; Humans; Keratins; Male; Middle Aged; Mucin-1; Neoplasm Invasiveness; Prognosis; Receptor, ErbB-2; Retrospective Studies; S100 Proteins; Salivary Ducts; Salivary Gland Neoplasms; Survival Rate; Tumor Suppressor Protein p53; Vimentin

Cribriform areas are common features of both adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma. Both are malignant salivary gland tumors that share similar histologic patterns, but with marked distinct clinical behavior. This study was undertaken to improve the accuracy of the histopathology diagnostic process, using an immunohistochemical panel to differentiate adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma, with special concern to the common cribriform areas shared by these tumors. Three-microm serial sections of these tumors were submitted to the streptavidin-biotin peroxidase immunotechnique against the monoclonal antibodies anticytokeratins 7, 8, 14 and 19, and anti-integrins beta1, beta3, and beta4. In the neoplastic lobules of adenoid cystic carcinoma cribriform type, the spaces were mainly surrounded by cells negative for the cytokeratins and integrins studied. In the solid type of adenoid cystic carcinoma, the microcystic areas were caused by spaces lined by neoplastic luminal cells positive for cytokeratins and presenting integrins concentrated in the apical pole of these cells. The cribriform areas of polymorphous low-grade adenocarcinoma were composed of cords of luminal cells, positive for cytokeratins and showing integrins disposed in a bipolar pattern. We concluded that cribriform areas of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma are histologically similar, although not identical. Indeed, their cellular composition is distinct and can be distinguishable from one another by the proteins of the cytoskeleton, by the integrins, or both.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Adenoid Cystic; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Integrins; Keratins; Salivary Gland Neoplasms

Topics: Adult; Biopsy, Needle; Carcinoma, Squamous Cell; Female; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immunoenzyme Techniques; In Situ Hybridization; Keratins; Ribosomal Proteins; RNA-Binding Proteins; RNA, Viral; Salivary Gland Neoplasms

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

The aims of this study were to ascertain the incidence of intercalated duct hyperplasia in association with cases of epithelial-myoepithelial carcinoma (EMC), and to explore a possible relationship between them and hybrid carcinomas of salivary glands.. Seven cases of EMC with sufficient surrounding non-tumour parotid were examined. Three cases contained foci of intercalated duct hyperplasia adjacent to the tumour. One of the cases was a hybrid tumour composed of EMC and mucoepidermoid carcinoma. The hyperplastic intercalated ducts formed multiple foci within the salivary parenchyma and were composed of bland, uniform ducts. Cytological atypia was not identified.. Intercalated duct hyperplasia may be a precursor lesion to EMC. Furthermore, it may also explain why EMC is frequently associated with other salivary gland carcinomas, so-called hybrid tumours, as well as sharing histological features with adenoid cystic carcinoma. Recognition of the latter is of particular importance because adenoid cystic carcinoma carries a poor prognosis.

Topics: Actins; Biomarkers; Carcinoma; Humans; Hyperplasia; Immunohistochemistry; Keratins; Muscles; Neoplasms, Multiple Primary; S100 Proteins; Salivary Ducts; 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

We report a unique case of a salivary gland type of "hybrid carcinoma" arising within a Bartholin's gland adenoma. The tumor was characterized by large areas of an epithelial-myoepithelial carcinoma similar to that of the salivary gland with a peripheral infiltrative pattern of an adenoid cystic carcinoma (ACC).

Topics: Adenoma; Bartholin's Glands; Biopsy; Carcinoma, Adenoid Cystic; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Middle Aged; Neoplasms, Multiple Primary; S100 Proteins; Salivary Gland Neoplasms; Vulvar Neoplasms

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

Salivary duct carcinoma is rare. We describe a 56-year-old man who developed salivary duct carcinoma in the mandible 10 years after removal of the right second and third molars. The tumour originated in the retromolar gland or the ectopic minor salivary gland in the mandible. The panoramic radiograph showed a radiolucent, poorly circumscribed area about 40 x 30 mm in size and distal to the lower right first molar. This tooth, together with all neoplastic tissue, was removed, and histopathological examination showed it to be a salivary duct carcinoma in the mandible. On immunohistochemical staining, keratin antibodies stained the ductal structure, 1A4 antibody stained myoepithelial cells, but S-100 protein and vimentin were not seen. The patient was well and with no sign with recurrence 6 years postoperatively.

Topics: Actins; Carcinoma; Choristoma; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Mandibular Diseases; Middle Aged; Molar; Radiography, Panoramic; S100 Proteins; Salivary Ducts; Salivary Gland Neoplasms; Vimentin

The purpose of this study was to examine the ultrastructural and immunohistochemical characteristics of basal cell adenocarcinoma.. Three cases of basal cell adenocarcinoma of the salivary glands were studied by means of light microscopy, electron microscopy, and immunohistochemistry.. Some of the architectural tumor patterns encountered were solid, some were trabecular, and some were mixed. Ultrastructurally, solid areas were composed of nonluminal cells, some of which contained tonofilaments and well-formed desmosomes; tubulo-trabecular areas differentiated into both luminal and nonluminal cells. Both growth patterns were associated with the formation of excess basal lamina, marginally and between nonluminal cells. Myofilaments were infrequent in nonluminal cells of solid or trabecular areas. Cytokeratin (AE1/AE3) stained all 3 tumors, more peripherally in the solid pattern and usually centrally in the trabecular areas; vimentin stained all 3 tumors diffusely; smooth muscle actin (IA4) stained all 3 tumors but was mainly confined to peripheral tumor cells in both the solid and the trabecular growth patterns; epithelial membrane antigen and carcinoembryonic antigen stained 1 of the 3 tumors, predominantly in the luminal cells; p53 oncoprotein was focally positive in 2 of the 3 tumors; Ki-67 stained less than 5% of the tumor cells in all cases; and c-erb-B2 was uniformly negative in all cases. Staining patterns of cytokeratin and actin varied with the architecture of the tumor.. Neither ultrastructural characteristics nor immunohistochemistry findings appear to distinguish basal cell adenocarcinoma from basal cell adenoma.

Topics: Actins; Adenocarcinoma; Antigens, Neoplasm; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; S100 Proteins; Salivary Gland Neoplasms; Vimentin

In order to characterize the cellular component of the polymorphous low-grade adenocarcinoma (PLGA) of the salivary gland, a morphological and immunohistochemical study was carried out. Thirty cases of PLGA were studied by light microscopy and immunohistochemistry and five cases by transmission electron microscopy (TEM). The expression of cytokeratins (CKs) 7,8,10,13,14,18,19, vimentin and muscle-specific actin (MSA) was investigated through the streptavidin-biotin method. The majority of tumor cells stained for vimentin, CKs 8, 18 and 7. CK 14 was positive in most cells of the papillary and trabecular sub-types. Although the expression of CKs 8,18 and 14 varied among the tumors sub-types, a straight relationship between each histologic pattern and the CK expression could not be delineated. MSA was reactive in only three tumors while CKs 10 and 13 were not detected in any tumor studied. The absence of MSA and the expression of CKs 8,18 and 7, in most of the tumor cells, lead to the hypothesis that myoepithelial cells are not the major cellular component of the PLGA. TEM revealed cells exhibiting microvilli and variable amounts of secretory granules, some of them suggesting an excretory activity. The presence of CKs 8,18 and 7, added to the secretory granules, indicates that PLGA originates from cells located at the acinar-intercalated duct junction.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biotin; Cytoplasmic Granules; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Microvilli; Middle Aged; Neoplasm Proteins; Salivary Gland Neoplasms; Streptavidin; Vimentin

Myoepithelioma, a rare benign salivary gland neoplasm, is a tumor composed entirely of myoepithelial cells. Unlike pleomorphic adenoma, these tumors lack any ductal epithelial differentiation, and manifest a minor stromal element. Previous cytogenetic and molecular genetic studies have mainly investigated pleomorphic adenomas and reported recurring specific chromosomal alterations at 8q12 and 12q13-q15 regions. The cell origin of these alterations, however, remains speculative. We report the cytogenetic analysis of a parotid myoepithelioma and discuss the putative origin for the cells with cytogenetic alterations. Our analysis shows 12q12 involved in a translocation with a previously unreported partner (1q), and nonrandom del(9)(q22.1q22.3) and del(13)(q12q22). Our results indicate that the myoepithelial cell is the source of those cells with chromosomal alterations, and that myoepithelioma shares 12q alterations reported in a subset of pleomorphic adenomas.

Topics: Actins; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 9; Desmin; Flow Cytometry; Humans; Immunohistochemistry; Karyotyping; Keratins; Male; Middle Aged; Myoepithelioma; Salivary Gland Neoplasms; Translocation, Genetic

Carcinomas of salivary gland ducts are described in five cats. The typical histological pattern was the formation of large cell aggregates resembling dilated ducts, often with central necrosis and a looping pattern. All tumours were labelled with antibody to cytokeratins (CKs) 5, 6, 8, 14, 17 and 19. Labelling of tumour cells with CK14 suggested basal cell differentiation. All tumours stained with Jack bean (Canavalia ensiformis) agglutinin (Con A); this is a feature of normal salivary gland ducts but is seen in other salivary gland tumours. Staining of tumour cells at the luminal surface of ductal structures with wheat germ (Triticum vulgaris) agglutinin (WGA) in the cat tumours was similar to that seen in ducts of normal cat salivary glands but occurs in other cat tumours. Other immunohistochemical staining results were unremarkable. 1999 Harcourt Publishers Ltd.

Topics: Adenocarcinoma; Animals; Biomarkers, Tumor; Cat Diseases; Cats; Female; Immunoenzyme Techniques; Keratins; Male; Salivary Ducts; Salivary Gland Neoplasms

Uncertainty about the factors influencing phenotypes in salivary canalicular adenoma prompted the present investigation.. Specimens of canalicular adenoma from 15 patients were examined with the use of histology, histochemistry for protein, mucosubstances and pigments, nerve staining and immunocytochemistry for cytoskeleton components. The tumours consisted largely of simple cells lining tubules that were occasionally cystic or branching and budding, and were set in loose, vascular and often haemorrhagic stroma. Other phenotypes recognized were mucous cells, apocrine-like cells, pigmented cells, microliths and stromal macrophages, detected in 26.6%, 20%, 33.3%, 20% and 53. 3% of the patients, respectively. Simple cells showed moderate levels of -SH groups and strong immunoreactivity for 'simple' epithelial phenotype cytokeratin. The simple cells lining cystic tubules showed additional immunoreactivity for 'stratified' epithelial phenotype cytokeratin, possibly an adaptation to mechanical pressure. Lumina showed variable levels of neutral and carboxylated glycoproteins, and chondroitin sulphate. Stroma showed high levels of chondroitin sulphate and hyaluronic acid. Mucous cells showed high levels of -SS- groups and nonsulphated glycoproteins. Apocrine-like cells contained lipofuscin. Pigmented cells contained haemosiderin, possibly a consequence of localized iron overload. Microliths contained mucosubstances. Macrophages often contained lipofuscin. No nerves were found in relation to the tumours.. The results suggest that, contrary to popular belief, phenotypes in canalicular adenoma do not reflect histogenetic concepts but rather may derive from the interplay between an altered secretory product, consisting of glycosaminoglycan and an immature form of glycoprotein, the lack of neuro-effector relationships and the different microenvironments throughout the tumour.

Topics: Adenoma; Aged; Aged, 80 and over; Calcium; Female; Glycoproteins; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Nerve Fibers; Phenotype; Salivary Gland Neoplasms; Salivary Glands, Minor

Clear cell adenocarcinoma of salivary glands (CCASG) is a relatively rare tumor, composed entirely of clear cells of putative ductal origin. It bears striking morphologic similarities to renal cell carcinoma (RCC) of clear cell type on hematoxylin and eosin stains. Differentiation between CCASG and metastatic RCC to the salivary glands has been considered problematic or even impossible on morphologic grounds. We examined three cases of CCASG and 12 cases of RCC (6 primary and 6 metastatic) by hematoxylin and eosin staining, immunohistochemistry, and electron microscopy. Two distinctive immunohistochemical and ultrastructural patterns emerged from this analysis. CCASG showed positivity for high molecular weight cytokeratin and carcinoembryonic antigen and ultrastructurally showed prominent squamoid differentiation, glycogen pools, and absence of lipid. In contrast, RCC was characterized by positivity for vimentin and complete absence of staining for high molecular weight cytokeratin and carcinoembryonic antigen. On ultrastructural studies, RCC lacked any squamoid differentiation, and the tumor cells contained abundant cytoplasmic lipid in addition to glycogen. Thus, based on the consistent differences on the immunohistochemical staining patterns and their characteristic subcellular morphology, CCASG and RCC can be distinguished on pathologic evaluation. The different direction of differentiation of the cells in CCASG and RCC (i.e., ductal in the former and renal tubular and mesodermal in the latter) results in their distinctive immunophenotypical and ultrastructural features.

Topics: Adenocarcinoma, Clear Cell; Adult; Aged; Carcinoembryonic Antigen; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Glycogen; Humans; Immunoenzyme Techniques; Keratins; Kidney Neoplasms; Lipids; Male; Middle Aged; Salivary Gland Neoplasms; Vimentin

The diagnosis of polymorphous low-grade adenocarcinoma (PLGA) of salivary glands remains difficult for general surgical pathologists. In an effort to understand the morphological heterogeneity of these neoplasms and facilitate their recognition we reviewed the architectural patterns, cell differentiation and immunohistochemical features of 17 case of PLGA.. There were 11 females and six males with a mean age of 58 years. Twelve tumours were located in the palate, two in the posterior third of the tongue, and one each in the upper lip, buccal mucosa and retromolar triangle. Two patients presented with neck metastases. The mean tumour size was 20 mm (range 6-50 mm). The tumour cells were arranged in five architectural patterns: tubules and small duct-like structures; cords and trabeculae; solid nests; cribriform areas and papillae. Twelve (71%) cases were composed of a combination of tubules and small duct-like structures, cords and trabeculae, and solid nests. Cribriform areas with pseudoluminal spaces were seen in six (35%) cases. A focal papillary pattern was evident in three cases and constituted 40% of the tumour in one. Perineural invasion was seen in 13 cases (76%). All cases studied were positive for CAM5.2, 34BE12, vimentin and S100 protein and showed overexpression of bcl-2 protein. Rb protein was present in 13 cases whereas p53 expression was absent in all cases. The average proliferation index (PI) was 7% (range 1-17%). Three patients developed local recurrences with cervical lymph node metastases but no patient died as result of tumour. No morphological features were found to be prognostic for the development of local recurrences or lymph nodes metastases.. PLGA is a distinctive neoplasm of salivary glands formed by luminal and nonluminal tumour cells with limited patterns of architectural differentiation. The relative proportion of these cells seems to play a significant role in the morphogenesis of these tumours. The overexpression of the bcl-2 protein and the low PI suggest that inhibition of programmed cell death may be involved in the oncogenesis of PLGA.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Cell Differentiation; Cyclin D1; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Retinoblastoma Protein; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor

The expression of cytokeratins (CKs) 7,8,10,13,14,18,19, vimentin and muscle-specific actin (MSA) was investigated in 17 mucoepidermoid carcinomas (MEC) by the streptavidin-biotin technique. The results revealed that CKs 7, 8 and 18 were positive for intermediate, luminal columnar and mucous cells. For epidermoid cells, the expression was heterogeneous and discrete. The reaction with CK19 was similar to that seen for the above CKs, except for the fact that mucous cells were negative. CK 14 was preferentially expressed in the intermediate cells localised in basal, parabasal and epidermoid cells. CK13 was localised in intermediate, epidermoid and luminal columnar cells. In stratified epithelium, CK13 was expressed in intermediate cells and negative in basal cells. These findings were more expressive in cystic areas of the tumours. CK10 was negative for all the cases studied. MSA was positive only in stromal elements, and only two cases of CME were heterogeneously positive for vimentin. The result obtained showed that the immunoprofile of MEC, for the studied antigens, is similar to that exhibited by the excretory duct of normal salivary glands.

Topics: Actins; Carcinoma, Mucoepidermoid; Cell Differentiation; Cytoskeletal Proteins; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Proteins; Salivary Gland Neoplasms; Vimentin

An extremely rare case of epithelial-myoepithelial carcinoma (EMC) of a lobar bronchus in a 47-year-old female is reported. Grossly, the tumor formed a polypoid mass obstructing the bronchial lumen. Microscopically, it was composed of two cellular types--epithelial cells with eosinophilic cytoplasm and clear myoepithelial cells. Numerous tubules formed by an inner epithelial and outer myoepithelial layer were found. Focally, the tumor showed solid growth of clear cells. Prominent hyalinization of the stroma was found. The nature of the cells was confirmed by positive expression of cytokeratins and epithelial membrane antigen in epithelial cells and vimentin and smooth muscle actin in myoepithelial cells. Differential diagnosis of EMC includes a broad spectrum of salivary gland-type tumors. Furthermore, metastases of clear cell carcinoma of the kidney or thyroid, clear cell ("sugar") tumor of the lung, glandular form of carcinoid, bronchioalveolar adenocarcinoma with myoepithelial cells and pulmonary adenosquamous carcinoma with amyloid-like stroma must be distinguished from EMC. The tumor has neither recurred nor metastasised, a fact supporting the current opinion, that EMC is a tumor of low grade malignancy.

Topics: Actins; Adenocarcinoma; Bronchial Neoplasms; Carcinoma; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Kidney Neoplasms; Lung Neoplasms; Middle Aged; Salivary Gland Neoplasms; Thyroid Neoplasms

Malignant myoepithelioma (MME) of the salivary gland, also known as myoepithelial carcinoma, is rare and its biologic behavior has not been clarified fully.. Ten cases of MME were analyzed for their clinicopathologic features and immunohistochemical characteristics, focusing on prognostic factors and tumor differentiation. In addition, six cases of benign myoepithelioma (BME) also were examined for comparison.. The ten patients with MME (3 men and 7 women) ranged in age from 48-81 years (mean, 61.9 years). Seven cases of MME arose in the parotid salivary gland, two in the submandibular salivary gland, and one in minor salivary glands of the soft palate. In the current series, the incidence of MME was 0.45% among 1945 cases of major salivary gland tumors. Seven cases of MME developed from a benign preexisting tumor (six in pleomorphic adenoma and one in BME). Four of nine patients with MME died of the disease and two patients developed a recurrence. It was shown that MMEs were comprised of one cell type or a combination of two cell populations; these included, in order of incidence, epithelioid, spindle, and plasmacytoid cells. Patients with MME with marked cellular pleomorphism and perineural invasion had a poor prognosis. Immunohistochemically, putative myoepithelial markers such as muscle actins, cytokeratin 14, vimentin, and calponin, and S-100 protein were expressed highly in MME. High and low molecular weight cytokeratins and epithelial membrane antigen also frequently were positive in MME. p53 expression was observed in five MME cases, four of which either recurred or were fatal. Cellular proliferative activity assessed by mitotic count and the Ki-67 labeling index was significantly higher in MME cases than in BME cases. In limited cases, such cellular proliferative activity was shown to have prognostic value. Ultrastructurally, the tumor cells displayed certain myoepithelial characteristics.. MME is a rare salivary gland tumor showing clinicopathologic diversity and presenting with various stages of myoepithelial differentiation. Histologic aggressiveness, marked cellular pleomorphism, p53 expression, and high cell proliferative activity were found to be correlated with a poor clinical outcome.

Topics: Actins; Aged; Aged, 80 and over; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Microfilament Proteins; Middle Aged; Myoepithelioma; Myosins; Parotid Neoplasms; S100 Proteins; Salivary Gland Neoplasms; Submandibular Gland Neoplasms; Tumor Suppressor Protein p53; Vimentin

The cytologic features in fine-needle aspirates from a rare benign nasopharyngeal salivary gland anlage tumor in a newborn boy are described and commented on, regarding therapeutically important differential diagnoses.

Topics: Biomarkers; Biopsy, Needle; Humans; Immunohistochemistry; Infant, Newborn; Keratins; Male; Nasopharyngeal Neoplasms; Salivary Gland Neoplasms

A case of heterotopic salivary gland adenocarcinoma (HSGA) in the right cervical region is presented. The carcinoma cells were positive for alpha-amylase, carcinoembryonic antigen, epithelial membrane antigen, cytokeratin as well as for expression of human salivary alpha-amylase messenger ribonucleic acid. The possibility of HSGA should be considered when an adenocarcinoma producing human salivary alpha-amylase is diagnosed away from sites where major and minor salivary glands normally are found.

Topics: Adenocarcinoma; Aged; alpha-Amylases; Carcinoembryonic Antigen; Choristoma; Diagnosis, Differential; Fatal Outcome; Head and Neck Neoplasms; Humans; Keratins; Male; Mucin-1; Neck; Neoplasms, Unknown Primary; RNA, Messenger; Salivary Gland Neoplasms; Salivary Glands

This unusual case is that of a middle-aged man exhibiting a tumor diathesis including a basal cell adenocarcinoma with features of adenoid cystic carcinoma arising in minor salivary gland of lip in association with multiple primary malignant cylindromas of skin. The labial lesion showed invasive tubules, solid epithelial sheets and cribriform structures. It did not exhibit PAS positive juxta-tubular basement membrane material. The skin lesions all showed features of a highly infiltrative cylindromatous carcinoma with two cell types, peripheral palisading and prominent PAS positive juxta-tubular basement membrane material. Immunocytochemical studies of the lip lesion and one of the skin lesions showed similarities, including positive staining for high and low molecular weight keratins and S-100 with negative staining for CEA. The precious descriptions of tumor diatheses involving dermal cylindromas and dermal analogue tumors of salivary glands and the distinctions with the present study are noted. If benign and even malignant cylindromas were described in the literature to be associated with basal cell adenocarcinoma of the major salivary glands, our case is unique by its association with this rare malignant tumor in a minor salivary gland.

Topics: Adenocarcinoma; Adult; Carcinoma, Adenoid Cystic; Disease Susceptibility; Humans; Keratins; Lip; Male; S100 Proteins; Salivary Gland Neoplasms; Scalp; Skin Neoplasms

Acinic cell carcinoma (ACC) is a rare salivary gland tumour, making up 4% of all minor salivary gland tumors. Typically, it is composed of acinic cells although transitional and duct-like cells are also identified. In the present study, a panel of antibodies was applied to eight minor salivary gland ACCs. Antibodies tested were: cytokeratins 7, 8, 13, 14, 18, 19, vimentin and actin (HHF35). Immunohistochemical staining revealed that cytokeratin 8, among the tested antibodies, was the more specific to neoplastic cells with a pattern of distribution quite variable and peculiar. This staining may be useful in the recognition of neoplastic acinic cells.

Topics: Adult; Biomarkers, Tumor; Carcinoma, Acinar Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Salivary Gland Neoplasms; Salivary Glands, Minor

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

To their knowledge, the authors report the first recognized case of ductal adenocarcinoma of the lacrimal gland (histologic equivalent of salivary duct carcinoma). Primary adenocarcinoma of the lacrimal gland is rare and has been described generically. In contrast, primary adenocarcinomas of the major and minor salivary glands are much more common and have been classified into histopathologic subtypes that have different clinical characteristics and outcomes.. A 68-year-old man presented with a 6-month history of a painless mass in the right upper outer eyelid. The authors describe the clinical, radiologic, and histopathologic features of this case and review the lacrimal gland literature.. A modified en bloc orbitectomy was performed, and postoperative radiotherapy was administered. The patient was alive and well without evidence of tumor recurrence 10 months after surgery.. The World Health Organization classification of salivary adenocarcinomas (1991) provides a framework for further insight into the presentation and biologic behavior of the less common lacrimal carcinomas.

Topics: Aged; Carcinoma, Ductal, Breast; Humans; Immunoenzyme Techniques; Keratins; Lacrimal Apparatus Diseases; Male; Orbit; Radiotherapy, Adjuvant; Salivary Ducts; Salivary Gland Neoplasms; Tomography, X-Ray Computed

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

Myoepitheliomas of the salivary glands remain a controversial entity. To contribute to the knowledge of this entity, 16 myoepithelial tumors of the salivary glands were studied: 12 benign myoepitheliomas (BME) and 4 malignant myoepitheliomas (MME). The clinical and the histologic findings of each case were studied Immunohistochemistry and flow-cytometry analysis were performed from the paraffin-embedded material in 15 cases. An electron-microscopy study was performed in 8 cases. The myoepithelial tumors affected patients of both sexes equally. The mean age of the patients with BME was 54 years, and the mean age of patients with MME was 62 years. Eight cases of BME originated in the parotid gland and 4 cases originated in the minor salivary glands. All the MME developed from a benign preexistent tumor: two developed from a pleomorphic adenoma in the parotid gland, and the other two MME developed in the minor salivary gland from a BME. The myoepithelial tumors were composed of epithelioid, plasmacytoid, spindle, or clear cell types, and they showed a solid or a myxoid pattern of growth. Immunohistochemical studies revealed marked and diffuse positivity to cytokeratins, vimentin, and S-100 protein in all cases. Glial fibrillary acidic protein was positive in 8 cases (53%), and muscle-specific actin and smooth-muscle actin were positive in only 3 cases (20%); they were all cases of BME. Desmin was negative in all tumors. Ultrastructural studies showed the presence of basal membrane, tight junctions, intermediate filaments, and microvilli as well as actin-like filaments lacking focal densities in all cases. But actin-like filaments with focal densities were not identified. Flow cytometry determined that all BME were diploid with a mean proliferative index of 7.73%. Two of the MME were diploid and the other two MME were aneuploid. The mean proliferative index of MME was 11.93%. In conclusion, BME and MME originated in major and minor salivary glands can display different histologic patterns and cellular features. Some immunohistochemical and ultrastructural characteristics have been found in all these neoplasms, which supports the idea that myoepitheliomas are composed by neoplastic modified myoepithelial cells, not fully differentiated. These techniques can be useful for the diagnosis of these tumors.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Desmin; DNA, Neoplasm; Female; Flow Cytometry; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Maxillary Neoplasms; Microscopy, Electron; Middle Aged; Myoepithelioma; Parotid Neoplasms; Ploidies; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands; Salivary Glands, Minor; Vimentin

Sialadenoma papilliferum (SP) is a rare, benign, salivary gland tumor which most commonly arises in the palate. It has a typical biphasic gross and microscopic appearance which distinguishes this tumor from other papillary-like tumors of the oral cavity. This study reports the clinico-pathologic features of 5 new cases and analyzes the morphologic and immunophenotypic features of their cell components. Adluminal epithelial cells of duct-like structures appeared immunoreactive to cytokeratin 19 and to S-100 protein antibodies; two subsets of basally-located cells were identified by means of immunohistochemistry. One cell subset expressed cytokeratin 14, S-100 protein, GFAP, vimentin and smooth muscle actin immunoreactivity; this antigenic profile is consistent with myoepithelial differentiation. The second subset of basal cells expressed cytokeratins 13 and 14 reactivity but it was negative to all other antibodies. Anti-CD 1a and anti-S-100 protein antibodies revealed distinct cells with dendritic processes which resembled Langerhans cells. The extralobular location of SP, the continuity between neoplastic duct-like structures and the surface epithelium along with the presence, within the excretory ducts adjacent to the tumour, of lesions which possibly precede the development of SP give further strength to the hypothesis of an origin from the excretory ducts of this tumor. Langerhans cells seem to be present in sialadenoma papilliferum but their role in this tumor is still unclear.

Topics: Actins; Adenoma; Adult; Antigens, Neoplasm; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Palate; S100 Proteins; Salivary Ducts; Salivary Gland Neoplasms; Salivary Glands, Minor; Vimentin

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

Ultrastructural features and cytokeratin expression of inverted ductal papillomas of minor salivary gland origin were studied. Under the electron microscope, an increased number of desmosomes and mucus-like granules in some cells were the most striking features. Immunohistochemical study revealed that tumor cells displayed strongly positive reactions with cytokeratins 13 and 14, and less strong reactions with cytokeratins 7, 8, 18 and 5D3. These results support the hypothesis that an inverted ductal papilloma can be derived from the proximal portion of a salivary gland excretory duct.

Topics: Adult; Cell Membrane; Connective Tissue; Cytoplasmic Granules; Desmosomes; Endoplasmic Reticulum, Rough; Epithelium; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Mucus; Papilloma, Inverted; Salivary Ducts; Salivary Gland Neoplasms; Salivary Glands, Minor

A primary bronchial tumor with a histological pattern similar to that of epithelial-myoepithelial tumor of the salivary gland is reported in a 55-year-old woman. The tumor was well delimited, although not encapsulated, and showed a polypoid growth. The tumor was composed of two types of neoplastic cells: epithelial cells displaying tubules and myoepithelial cells that either formed compact masses or surrounded the tubular formations. Immunohistochemical study confirmed positive immunoreaction to both high- and low-molecular-weight cytokeratins in the epithelial cells and positive immunoreaction to vimentin, S-100 protein, and myosin in the myoepithelial cells.

Topics: Bronchial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Myoepithelioma; Myosins; Neoplasms, Glandular and Epithelial; S100 Proteins; Salivary 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

Canalicular adenoma is a newly recognized salivary gland adenoma that may be confused with malignant salivary gland tumors. To better characterize this neoplasm, six examples were investigated with a panel of immunohistochemistry antibodies including anti-keratin (AE1/AE3), anti-epithelial membrane antigen, anti-carcinoembryonic antigen, anti-vimentin, anti-S-100, anti-muscle specific actin, and anti-glial fibrillary acid protein. All canalicular adenomas stained in a similar fashion showing positive staining with anti-keratin, anti-vimentin, and anti-S-100 (6 of 6 cases each). Rare focal staining with anti-epithelial membrane antigen and anti-glial fibrillary acid protein was noted (1 of 6 cases each). This immunohistochemistry staining pattern was compared with those of ameloblastoma, polymorphous low-grade adenocarcinoma, and adenoid cystic carcinoma. Immunohistochemistry may be useful in the distinction of canalicular adenoma from other salivary gland tumors.

Topics: Actins; Aged; Ameloblastoma; Antibodies, Monoclonal; Carcinoembryonic Antigen; Carcinoma, Adenoid Cystic; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Diagnosis, Differential; Female; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Keratins; Lip Neoplasms; Male; Membrane Glycoproteins; Middle Aged; Mouth Mucosa; Mucin-1; Mucins; Neoplasm Proteins; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Vimentin

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

A case of intraductal papilloma occurring in the anterior lingual salivary gland (Blandin-Nuhn's gland) of a 58-year-old woman is presented. This location has not been reported previously. The results of histologic and immunohistochemical studies point to an epithelial origin of excretory salivary gland ducts and also demonstrate the secretory potential of the tumor cells.

Topics: Antigens, Neoplasm; Female; Humans; Immunohistochemistry; Keratins; Lactoferrin; Membrane Glycoproteins; Middle Aged; Mucin-1; Papilloma; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Tongue Neoplasms

Topics: Adenocarcinoma, Mucinous; Aged; Aged, 80 and over; Biomarkers, Tumor; Female; Humans; Immunoenzyme Techniques; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Neoplasm Recurrence, Local; Nuclear Proteins; Proliferating Cell Nuclear Antigen; Salivary Gland Neoplasms; Salivary Glands, Minor; 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

Topics: Carcinoma; Diagnosis, Differential; Female; Glycogen; Humans; Immunohistochemistry; Keratins; Mandibular Neoplasms; Middle Aged; Salivary Gland Neoplasms; Salivary Glands, Minor

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

Among adenoid cystic carcinomas of salivary glands (ACCs), the solid basaloid type has a poor prognosis similar to that of undifferentiated adenocarcinomas. We studied 24 cases in immunohistochemistry using antibodies reactive with keratins of various molecular weights, vimentin, S-100 protein, and its A and B subunits. Our findings were correlated with the histological pattern and with the variable degree of differentiation of these carcinomas. In comparison with other types of ACC, intermediate filament proteins in this group were weakly expressed. The co-expression of cytokeratin and vimentin was noted in some cases. Additional features noted were the presence of cribriform cavities associated with solid lobules and areas of necrosis giving a comedocarcinomatous pattern. In these two variants, cells characterized by the dual expression of cytokeratin and S-100 protein were seen. In the highly malignant anaplastic variety, only a few cells were weakly positive with antisera to cytokeratin and vimentin. This group shows similarities to undifferentiated adenocarcinomas of salivary glands. Such similarities could be explained by the common origin of these tumours from intercalated ducts.

Topics: Carcinoma, Transitional Cell; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Male; S100 Proteins; Salivary Gland Neoplasms; Vimentin

Because the data on the antigenic phenotype of mucoepidermoid carcinoma (MEC) are incomplete and somewhat disparate, 45 MECs were evaluated immunohistochemically for low- and high-molecular-weight keratins, vimentin, glial fibrillary acidic protein, smooth muscle actin, and S-100 protein. Tumors stained uniformly for keratins and, on occasion, focally for vimentin. Tumors were nonreactive with antibodies to glial fibrillary acidic protein and, with few exceptions, to muscle-specific actins and S-100 protein. Clear cell and papillary histologic variants were seen as potential diagnostic pitfalls. If used with hematoxylin-and-eosin-stained sections, limited potential is seen for this antibody panel in surgical pathology. Myoepithelial cell-associated antigens are expressed to a very limited extent in MECs.

Topics: Actins; Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma; Child, Preschool; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Vimentin

Among a series of 76 adenoid cystic carcinomas (ACC), 51 cases with cibriform or trabecular patterns were selected for an immunohistochemical study. These tumors were composed of three types of cells: basaloid, myoepithelial and ductal luminal acinous or tubular cells with a variable amount of each cell type from one case to another. Monoclonal antibodies (MoAb) against keratins (PKK1, KL1, K8.12, K8.13, K4.62 anti-cytokeratins antibodies) and against vimentin were used. Tubular cells were characteristically marked by anti-cytokeratins MoAb, but with a great heterogeneity of keratin distribution. In myoepithelial cells, keratin was absent or slightly positive and vimentin was present, with co-expression of the two types of filaments in some cells. Like myoepithelial cells, basaloid cells were positive to anti-vimentin antibody and negative or slightly positive to anti-keratin antibodies, with sometimes a co-expression of vimentin and keratin filaments in the same cell. Histogenesis of adenoid cystic carcinomas was discussed. Progenitor intercalated duct reserve cells may change into ductal luminal and myoepithelial tumor cells. Otherwise, basaloid cells, arising also from intercalated duct reserve cells, are able to acquire some secretory organites.

Topics: Antibodies, Monoclonal; Carcinoma, Adenoid Cystic; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Salivary Gland Neoplasms; Vimentin

We performed an immunohistochemical study that compared a primary adenoid cystic carcinoma (ACC) of the skin with two salivary gland ACC. All three tumors stained positively and in identical fashion for epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), broad-spectrum keratins, and low-molecular-weight keratins. Both EMA and CEA were localized to the luminal surfaces and the secreted contents of the tubular structures and the ductlike structures of the cribriform formations. The staining reactions for both types of keratin were more intense in the cells lining the tubular structures and the ductlike structures of the cribriform formations. One of the two salivary ACCs stained positively for S-100 protein; the other was positive for vimentin. The cutaneous ACC was negative for both antigens. Leu-7 antigen was not detected in either type of ACC. These results show that primary cutaneous ACC and salivary ACC have similar immunohistochemical staining patterns for a number of antigens. We believe this similarity is due to the fact that these antigens are shared by the sweat glands and salivary glands, which are considered to be the respective sites of origin for these two types of tumors.

Topics: Adult; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma, Adenoid Cystic; Female; Humans; Immunoenzyme Techniques; Keratins; Killer Cells, Natural; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; S100 Proteins; Salivary Gland Neoplasms; Skin Neoplasms; Staining and Labeling; 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

Sixteen polymorphous low-grade adenocarcinomas were reviewed and compared with 17 adenoid cystic carcinomas and with 21 other histologically similar minor salivary gland neoplasms. The polymorphous low-grade adenocarcinomas were for the most part distinctive in their microscopic appearance. Typically they exhibited infiltrative growth by small uniform cells in single-layered ducts. A syncytium of tumor cells was also characteristic, although solid and cribriform patterns were seen, making definitive diagnosis difficult with some tumors. Immunohistochemical staining for S-100 protein, glial fibrillary acidic protein, actin, vimentin, and keratins resulted in relatively distinctive antigenic profiles for the tumors studied. Of significance was strong S-100 protein and weak actin staining of polymorphous low-grade adenocarcinomas, moderate actin staining of adenoid cystic carcinomas, moderate glial fibrillary acidic protein staining of monomorphic adenomas and pleomorphic adenomas, and nonreactivity of monomorphic adenomas for vimentin. It is believed that the immunoprofiles could be useful in the microscopic diagnosis of salivary gland tumors. The identification of antigens found normally in myoepithelial and epithelial cells supports the concept that these tumors are derived from pluripotential reserve cells.

Topics: Actins; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma, Adenoid Cystic; Female; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Male; Middle Aged; Molecular Weight; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; 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

Three cases of monophasic glycogen-rich clear cell tumors of palatal gland origin were examined immunohistochemically and ultrastructurally in attempts to characterize their cellular composition. Despite their histologic resemblances, the clear cells from each case showed different immunohistochemical features. In case 1 the extensive positivity for vimentin and S-100 protein, in addition to the focal expression of actin and glial fibrillary acidic protein, strongly suggested that the clear cells were myoepithelial in nature. In contrast, the clear cells from case 2 exhibited both keratin and epithelial membrane antigen positivity, as well as ultrastructural features that suggested that they were glandular epithelial in nature. In case 3 no special markers except for keratin could be detected, indicating the less differentiated nature of the clear cells. These results show the heterogeneity of the clear cell tumor group of minor salivary glands.

Topics: Actins; Adult; Antigens, Neoplasm; Female; Humans; Immunohistochemistry; Keratins; Laminin; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Palate; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Vimentin

Histologic diversity is intrinsic to salivary gland tumors, but it is a particular feature of polymorphous low-grade adenocarcinoma as denoted by the terminology. Application of immunohistochemistry and electron microscopy to three examples allowed the study of some aspects of tumor cell differentiation in this minor salivary gland lesion. In one case where the tumor cells were cytologically of one type, immunohistochemistry clearly identified both luminal and nonluminal tumor cells, but the latter showed no evidence of myoepithelial cell differentiation. A second case revealed differentiation only of luminal-type tumor cells, while a third example was largely differentiated as myoepithelial cells but again immunohistochemistry confirmed focal formation of duct-like structures by luminal epithelium. These cases show a considerable range of tumor cell heterogeneity as well as variations in their organization. This variation in differentiation characteristics underlies the histology of polymorphous low-grade adenocarcinomas, and likely occurs in other salivary gland tumors. To establish specific and reliable diagnostic criteria for such tumors requires awareness of this neoplastic process. The limited malignant potential and excellent survival of patients with polymorphous low-grade adenocarcinoma is apparently little affected by patterns of differentiation in this particular neoplasm.

Topics: Actins; Adenocarcinoma; Aged; Aged, 80 and over; Cell Differentiation; Cell Transformation, Neoplastic; Female; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Male; Microscopy, Electron; Neoplasm Invasiveness; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; 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

Salivary duct carcinoma (cribriform salivary carcinoma of the excretory ducts [CSCED]) is an uncommon malignant tumor which occurs predominantly in men (83% in this series; mean age, 61 years) and most often in the parotid gland (92% in this series). The outcome is unfavorable for most patients; of 11 of 12 patients with follow-up, 45% had local recurrence, 54% had distant metastasis, and 45% were dead of disease within 10 years of diagnosis (mean, 3 years). Metastases to lymph nodes were common (72%). Immunohistochemical studies on paraffin-embedded tissue revealed that most tumors reacted with antibodies known to mark adenocarcinoma: B72.3 (11 of 11) and Lewis Y (ten of ten). High and low molecular weight cytokeratins were present in most tumors (nine of ten and seven of nine cases, respectively), supporting the concept that these adenocarcinomas were of ductal origin. Parotid ducts adjacent to CSCED expressed B72.3 in six of nine cases studied, but parotid ducts from normal tissue (adjacent to benign mixed tumors or enlarged periparotid lymph nodes) rarely expressed this marker (one of 17 cases). The detection of B72.3 diffusely in parotid ducts, especially those with atypia, may imply the presence of malignant tumor nearby, which could be useful in evaluating limited tissue from the parotid. However, further studies are necessary to confirm the significance of this finding.

Topics: Carcinoma, Intraductal, Noninfiltrating; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Molecular Weight; Neoplasm Recurrence, Local; Parotid Neoplasms; Salivary Gland Neoplasms; Submandibular Gland Neoplasms

Topics: Animals; Carcinoma; Dog Diseases; Dogs; Female; Immunoenzyme Techniques; Keratins; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands; Salivary Glands, Minor; Tongue Neoplasms

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

Fifty-eight salivary gland pleomorphic adenomas and 5 normal salivary glands were studied immunohistochemically with respect to intermediate filaments (keratin, desmin, and vimentin), actin and S-100 protein to observe the cellular differentiation of these tumor cells. Normal myoepithelial cells showed positive immunostaining for actin, vimentin and S-100 protein. Pleomorphic adenomas expressed keratin, vimentin and S-100 protein to various degrees, but only a few tumor cells of pleomorphic adenoma revealed actin. The results indicate that the tumor cells of pleomorphic adenoma show a bipolar differentiation capability of both epithelial and mesenchymal origins, although normal myoepithelial cells show only mesenchymal characteristics. The findings also support previous reports using light and electron microscopy, and also contribute to more precise diagnosis and a better understanding of the histogenesis of this tumor.

Topics: Actins; Adenoma; Desmin; Humans; Immunohistochemistry; Keratins; S100 Proteins; Salivary Gland Neoplasms; Staining and Labeling; Vimentin

An immunohistochemical study of keratin was performed in forty-five cases of adenoid cystic carcinoma of salivary gland, the results were as follows: keratin was distributed in the duct system of normal salivary gland, but the acini were negative. The distribution of keratin were varied in different patterns of adenoid cystic carcinoma. The amount of synthesis of keratin was many in tubular type of high differentiated carcinoma, but, in basaloid solid type of low differentiated carcinoma, the synthesis of keratin was less; the content of keratin in cribriform and trabecular type was between the tubular type and basaloid solid type, and the former had more keratin than the latter.

Topics: Carcinoma, Adenoid Cystic; Female; Humans; Immunohistochemistry; Keratins; Male; Prognosis; Salivary Gland Neoplasms

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

Two cases of carcinoma of the minor salivary glands are presented in which most cells had clear cytoplasm. Both patients had clinical histories in excess of 10 years and, in the one case with adequate follow-up, no recurrence had occurred after a further 11 years. Both tumours were locally invasive. The clear cells contained small amounts of glycogen, but no intracytoplasmic mucin. Immunohistochemical and ultrastructural studies showed epithelial features, with no evidence of myoepithelial differentiation. These tumours were very similar to the small number of previously reported cases, which were all considered to be low-grade carcinomas. Amongst the differential diagnoses, the most important is metastatic clear cell carcinoma of the kidney and this can only be confidently excluded clinically or by the use of imaging techniques. In summary, we consider intraoral clear cell carcinoma to be a distinct tumour of low malignant potential.

Topics: Adenocarcinoma; Aged; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Salivary Gland Neoplasms

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

Two cases of polymorphous low-grade adenocarcinoma of the papillary type, from minor salivary glands were studied by light microscopy and immunohistochemistry. One case exhibited a predominance of the papillary pattern, whereas the other presented the following patterns of histological appearance: papillary, solid, pseudocystic and tubular. Utilizing the peroxidase-antiperoxidase (PAP) method, the intermediate filament vimentin, keratin and S100 protein were observed in tumor cells. The immunohistochemical analysis revealed two types of neoplastic cells: myoepithelial and luminal.

Topics: Adenocarcinoma, Papillary; Adult; Female; Humans; Immunohistochemistry; Keratins; Male; Neoplasm Proteins; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Vimentin

Archival paraffin sections from normal salivary gland tissue and salivary gland neoplasms were stained by immunoperoxidase technique with a well characterized cytokeratin antibody (PKK1). In normal parotid tissue, myoepithelial cells and peripheral cells of larger ducts were selectively stained. In pleomorphic adenomas, most cells were stained, the staining being somewhat stronger towards the duct lumina. In basal cell adenomas, only cells adjacent to the duct lumina were stained where a differentiation of cells into peripheral and ductal was seen. In adenolymphomas basal cells were stained, and in oncocytomas small elongated cells reacted with the PKK1 antibody. Only a few duct cells in an acinic cell carcinoma were reactive and in mucoepidermoid carcinoma, peripheral epidermoid cells were strongly stained. In adenoid cystic carcinoma, mostly duct cells were stained whereas the peripheral ones remained unstained. Although the intermediate filament protein expression is very stable during tumorigenesis, the staining with the presently used monoclonal antibody in salivary gland neoplasms differed markedly from what could be expected according to current views on the participation of this cell type. This supports our view that cells in tumors should be characterized on the basis of their staining, i.e. state of differentiation and not on their presumed histogenesis.

Topics: Adenoma; Antibodies, Monoclonal; Carcinoma; Humans; Immunoenzyme Techniques; Keratins; Salivary Gland Neoplasms

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

The purpose of the present investigation was to study the histogenesis of the mucoepidermoid carcinoma of the salivary glands. Eleven cases of mucoepidermoid carcinoma of the minor salivary glands and five of the major glands were extensively studied employing immunohistochemical and fluorescent microscopic techniques. Both the intermediate cells and the duct cells showed a rather similar pattern of reactivity for vimentin, actin and EMA. Also, the intermediate cells and the myoepithelial cells showed a similar reaction pattern for keratin and UGA-1. The intermediate, myoepithelial and duct cells shared a similar reaction pattern for desmin, myosin, CEA, and S-100 protein. However, the rest of the tumor markers studied (AFP, PNA and WGA) were found to be non contributary. We also found that the intermediate and to some extent the epidermoid tumor cells showed a positive reaction with Azophloxine GA, which is a selective stain for myoepithelial cells in the normal glands. Based on these findings, the duct cells, the myoepithelial cell in the normal glands and the intermediate cells of the mucoepidermoid carcinoma share certain similar characteristics. The intermediate cells may actually be a mixed population, some having characteristics of the myopithelial cells and others of duct cells. These findings are relevant to the possible role of the intermediate cell in the histogenesis of the mucoepidermoid carcinoma.

Topics: Actins; Antigens, Neoplasm; Antigens, Surface; Azo Compounds; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Coloring Agents; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Microscopy, Fluorescence; Naphthalenesulfonates; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands, Minor; Staining and Labeling; Vimentin

The presence of intermediate filament proteins (IFP) in normal salivary gland tissue and investigated by immunohistochemical techniques on frozen sections. Cytokeratins (CKs) were seen in almost all normal epithelial cells. In the parotid gland and in palatal gland tissue, a co-expression of cytokeratin and glial fibrillary acidic protein (GFAP) was seen in some myoepithelial cells, but this was not apparent in the submandibular gland. In some pleomorphic adenomas, carcinomas in pleomorphic adenomas, one mucoepidermoid carcinoma, one mucus-producing adenopapillary carcinoma and one adenoid cystic carcinoma, cells expressing three different IFP classes were found (CKs, vimentin, GFAP). These cells were most often situated peripherally in the tumour cords or ducts. The cytokeratin pattern in these cells, as revealed by mAbs PKK1-3, was similar to that in normal myoepithelial cells. Furthermore, reactivity for a fourth class of IFP, desmin, could be seen in this cell type in two carcinomas in pleomorphic adenomas, and also in a few cells in a pleomorphic adenoma and an adenoid cystic carcinoma. Thus the pattern of IFP expression in salivary gland neoplasms, is very complex, and cannot always be related to the normal tissue.

Topics: Antibodies, Monoclonal; Desmin; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Parotid Gland; Salivary Gland Neoplasms; Salivary Glands; Submandibular Gland

Immunohistochemical expressions of keratin polypeptides detected by monoclonal antibodies were described in tumor cells of adenolymphoma, and the possibility of intercalated duct and ductal basal cells in the salivary glands being the progenitors was discussed. Basal cells in the tumor showed positive staining for keratin nos. 8, 13, 16, 18 and 19 detecting for monoclonal keratin antibodies (PKK 1, K 4.62, K 8.12, K 8.13), columnar tumor cells displayed strongly positive reactions with RPN 1164 and K4.62 suggesting keratin nos. 8 and 19. Great heterogeneity of distribution for keratin polypeptides was displayed by epithelial cells of adenolymphoma. Intercalated duct cells of normal salivary glands reacted with RPN 1164, RPN 1165, K 4.62 and K 8.13 monoclonal antibodies, which indicates the presence of keratins 8 and 19; and ductal basal cells reacted with PKK 1, K 4.62 and K 8.12, suggesting nos. 8, 13, 16, 18 and 19 keratins. Distribution of involucrin was variable in tumor epithelium of adenolymphoma, and was negative in the normal gland. The immunohistochemical distribution of keratin types between basal tumor cells of adenolymphoma and ductal basal cells of the normal salivary gland was compared.

Topics: Adenolymphoma; Antibodies, Monoclonal; Epithelium; Humans; Immunohistochemistry; Keratins; Paraffin; Salivary Gland Neoplasms; Salivary Glands

Twelve cases of monomorphic adenoma of the salivary glands were histologically reclassified and their immunohistochemical reactivity for S-100 and cytokeratin was correlated. All patients underwent a benign clinical course. Individual tumors were well encapsulated and frequently showed a focal cystic change. Histologically, 9 cases were of the epithelial basaloid cell type and 3 cases were of the myoepithelioma variant. About one half of the epithelial type featured a mixture of trabecular and tubular patterns. The immunoreactivity to S-100 and cytokeratin varied. All basaloid cell adenomas were positive for cytokeratin, while S-100 positivity was found mostly in the stroma along with the varied reaction and intensity in the epithelial nests. In myoepitheliomas, cytokeratin was totally negative and S-100 was positive in 2 of 3 cases. The above findings suggest that the degree of participation of myoepithelial cells determines the phenotypic expression of monomorphic adenomas, and supports the hypothesis that the basaloid cell and myoepithelial types may be located on extreme ends of the same tumor spectrum with a wide range of pleomorphic adenoma in-between.

Topics: Adenoma; Adult; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Salivary Gland Neoplasms

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

Warthin's tumor (adenolymphoma) is a monomorphous adenoma of the salivary glands well characterized histologically. Its clinical evolution is almost invariably benign, the malignant change being extremely unusual. We present the case of a 67 year-old man with a right retromandibular tumor which has evolved over a two year period, with peripheral involvement of V, VI and VII cranial nerves on the same side, and direct invasion of intracranial structures. The biopsy revealed a classic adenolymphoma which shows foci of well differentiated adenocarcinoma. Transitional areas between benign and malignant epithelium were evident. In addition, histological findings support the hypothesis of the origin of adenolymphoma from epithelial ducts trapped in the regional lymphatic tissue.

Topics: Adenocarcinoma; Adenolymphoma; Aged; Carcinoembryonic Antigen; Humans; Immunoenzyme Techniques; Keratins; Male; Salivary Gland Neoplasms; Thyroglobulin

An immunohistochemical study of 34 pleomorphic adenomas of the major salivary glands demonstrated phenotypic differences among the various morphologic regions in these tumors. The phenotypes expressed were comparable to those of normal salivary gland cells. In the normal glands, myoepithelial cells were immunoreactive for glial fibrillary acidic protein (GFAP), S-100 protein, and keratin; acinic cells exhibited strong, predominantly nuclear S-100 staining and weaker keratin staining; intercalated ducts had both cytoplasmic and nuclear S-100 positivity; and several epithelial antigens were observed throughout the ductal system. In the tumors, the presence of classic epithelial markers (including carcinoembryonic antigen, epithelial membrane antigen, secretory component, and keratin) in the luminal cells of ducts and the intense immunoreactivity with GFAP (with weaker keratin and S-100 staining) in periductal and stromal cells indicated distinct epithelial and myoepithelial differentiation. Solid epithelioid areas consisted phenotypically of intercalated duct/acinic cells and/or myoepithelial cells, the former exhibiting predominant nuclear S-100 positivity. The presence of GFAP-like immunoreactivity in normal myoepithelial cells strongly supports the extensive involvement of this cell in pleomorphic adenomas. The spectrum of phenotypes expressed adds weight to existing evidence for pleomorphism rather than a mixed origin of this tumor. The combination of keratin, S-100, and GFAP immunostaining is particularly useful in identifying the component cells in pleomorphic adenomas of the salivary glands.

Topics: Adenoma; Antigens, Neoplasm; Carcinoembryonic Antigen; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Phosphopyruvate Hydratase; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands

Adenoid cystic carcinoma is a specific variant of adenocarcinoma with a characteristic cribriform appearance. The tumor may arise from salivary glands and various other sites, but the origin and cellular composition of this unique neoplasm have been controversial. A potential use of immunohistochemistry is to provide additional information on the origin of various cellular components of tumors by comparing them with corresponding normal tissues. Immunohistochemical distributions of carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), keratin, low molecular weight keratin (54 kd), S100 protein, muscle-specific actin, laminin, and type IV collagen were evaluated in 20 adenoid cystic carcinomas arising in major and minor salivary glands. Anti-CEA, anti-EMA, anti-keratin, and anti-S100 antibodies strongly stained cells lining true lumina. Muscle-specific actin, a marker for myoepithelial cells, was found in lining cells of pseudocysts, in tumor cells proper, and in nonluminal cells with a tubular growth pattern. A monoclonal antibody against 54 kd keratin stained almost all cells in the neoplasms. In pseudocysts, replicated basal lamina reacted with antisera to laminin and to type IV collagen. The present study demonstrates that there are at least two populations of tumor cells in adenoid cystic carcinoma: luminal cells that express CEA and EMA, thus indicating their ductal character, and nonluminal cells that express muscle-specific actin characteristic of myoepithelium.

Topics: Adult; Aged; Carcinoembryonic Antigen; Carcinoma, Adenoid Cystic; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands; Staining and Labeling

The expression and distribution of cytokeratins and vimentin in fifteen malignant salivary neoplasms were examined by immunocytochemical techniques using, five monoclonal antibodies (mAbs) against different epitopes of Cytokeratins (CKs) (mAbs PKK1, PKK2, and PKK3, identifying CKs 8, 18 and 19, CKs 7, 17 and 19, and CK 18, respectively) and Vimentin (mAbs V9 and V24). Antibody PKK1 gave strong reactions in all neoplasms showing the similarity of these tumours to other digestive system adenocarcinomas. Three general staining patterns of the neoplasms were recognized with respect to the reactivity of mAbs PKK2, PKK3, and V9. Mucoepidermoid cancer, salivary duct carcinoma and a clear cell carcinoma had a higher relative content of CKs 7, 17 and 19 than of CK 18. Adenoid cystic carcinoma showed the same CK pattern but in the periphery of the tumour cords vimentin was readily detected. In two acinic cell carcinomas, the relative content of CK 18 was higher than that of CKs 7, 17 and 19. Furthermore vimentin was expressed in the tumour cells. However, one mucoepidermoid carcinoma showed vimentin expression and two acinic cell carcinomas were vimentin negative and more reactive for PKK2 than PKK3. Pecularities in CK expression were seen: squamous areas of mucoepidermoid carcinomas were stained by mAb PKK3 although CK 18 is not present in normal squamous epithelia or in squamous cell carcinomas of tongue and skin. In conclusion, the different salivary neoplasms can be distinguished on basis of IFP content. Such a differentiation fits with current theories of histogenesis, i.e. vimentin is seen in tumours presumed to arise from intercalated duct reserve cells, whilst the vimentin negative neoplasms would be expected to arise in excretory duct reserve cells.

Topics: Adenocarcinoma; Adolescent; Aged; Antibodies, Monoclonal; Carcinoma; Carcinoma, Adenoid Cystic; Female; Humans; Keratins; Male; Middle Aged; Salivary Gland Neoplasms; Vimentin

An immunohistochemical study on keratin, vimentin, and myosin was performed in 117 specimens of human salivary gland under normal and several neoplastic conditions. In normal glands, positive immunostaining for keratin was observed in the inner cells of all ductal systems, whereas myosin and vimentin were the cytoskeletal components of myoepithelial cells. In pleomorphic adenoma, the inner cells showing a tubular pattern demonstrated positive immunostaining for keratin, and the outer cells as well as the neoplastic cells with a solid and myxoid pattern exhibited positive immunostaining for all antibodies. Monomorphic tubular and trabecular adenoma, and adenolymphoma showed positive immunostaining for keratin, although one case of tubular adenoma exhibited positive immunostaining for all antibodies. Squamous cell carcinoma, adenosquamous carcinoma, and mucoepidermoid tumor showed positive immunostaining only for keratin, but one case of adenocarcinoma, two cases of adenoid cystic carcinoma, and clear cell tumor disclosed positive immunostaining for keratin and vimentin.

Topics: Adenoma; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Myosins; Salivary Gland Neoplasms; Salivary Glands; Vimentin

Retinoic acid has marked effects on the growth, morphological features, and biological markers of a neoplastic human salivary intercalated duct cell clone in culture, whereas the cell clone was not affected by other retinoids such as retinol and retinal. A cell clone with ultrastructure and biological markers specific to the intercalated duct cells of human salivary glands was cultivated in the presence of retinoic acid. Major alterations, such as expression of tonofilaments, Mr 68,000 cytokeratin, and involucrin, were observed in those cells with a phenotype similar to that of keratinizing squamous cells. In addition, the coexpression of Mr 68,000 cytokeratin and carcinoembryonic antigen in these altered cells was found. Both the anchorage-independent and anchorage-dependent growths were markedly suppressed in the presence of retinoic acid. After the removal of retinoic acid from the culture, the treated cells returned rapidly to the phenotype of the untreated cells. These findings indicate that reversible differentiation into the keratinizing squamous cells of a neoplastic human salivary intercalated duct cell clone occurs in growth medium containing retinoic acid.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoembryonic Antigen; Cell Line; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Keratins; Microscopy, Electron; Molecular Weight; Salivary Gland Neoplasms; Tretinoin

Immunohistochemical expression of 8 cases of mucoepidermoid carcinomas (G-I, 3 cases; G-II, 2 cases; and G-III, 3 cases) revealed marked heterogeneity of the proteins examined. Immunohistochemically detectable keratins (TK, KL1, and PKK1) were distributed in epidermoid cells, but were absent in mucous secreting cells. Strongly positive deposits of keratin proteins were detected in squamoid tumor cells in the G-I tumors. The tumor cells displayed positive staining for S-100 alpha, but did not stain with polyclonal S-100 antiserum or with monoclonal S-100 beta. The cells showing highest reactivity for S-100 protein were scattered in neoplastic foci and were probably Langerhans cells. Lactoferrin and lysozyme reactions were generally negative in tumor foci; but a positive reaction for lactoferrin was found in luminal tumor cells although rarely, and lysozyme staining was occasionally noted in histiocytes in the stroma. Amylase activity was usually absent in the tumor cells, with the exception of one case in which it was confined to the tumor cells. Mucoepidermoid carcinomas of various grades indicated marked heterogeneity in terms of various immunohistochemically detectable proteins.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amylases; Carcinoma; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Lactoferrin; Lactoglobulins; Male; Middle Aged; Muramidase; Periodic Acid-Schiff Reaction; S100 Proteins; Salivary Gland Neoplasms; Staining and Labeling

Topics: Adenoma; Carcinoma; Cytoskeleton; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Salivary Gland Neoplasms; Vimentin

The light microscopic, electron microscopic and immunohistochemical features of a small cell undifferentiated carcinoma of the minor salivary gland are presented. The tumor was composed predominantly of undifferentiated small cells with focally admixed neuroendocrine, exocrine and squamous cells, occasionally arranged in an organoid manner. The presence of vasoactive intestinal polypeptide in the tumor was found immunohistochemically. In addition, the tumor cells stained with Grimelius' impregnation. Immunohistochemically the tumor contained cells that reacted positively with the antibodies to carcinoembryonic antigen, 66K keratin polypeptide, or human salivary amylase. These findings indicate that a small cell undifferentiated carcinoma of the minor salivary gland, reported here, exhibits focally multidirectional differentiation as well as neuroendocrine cell derivation.

Topics: Amylases; Carcinoembryonic Antigen; Carcinoma, Small Cell; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Microscopy, Electron; Middle Aged; Salivary Gland Neoplasms; Salivary Glands; Salivary Glands, Minor; Vasoactive Intestinal Peptide

To investigate the cellular differentiation of adenoid cystic carcinomas (ACC), a comparative immunohistochemical study of 12 normal salivary glands and eight specimens of ACC was performed. Antibodies were used against S100 protein (S), keratins (K) of various molecular weights, vimentin (V), muscle-specific actin (A), epithelial-membrane antigen, human milk fat globules, and collagen type IV. A panel of four of these antibodies (SKVA) was identified as the most helpful in characterizing cells in normal salivary glands and ACC. The immunophenotypes depended on the histologic patterns of ACC. Cells in morphologically recognizable duct structures in the cribriform and trabecular areas expressed a phenotype similar to that of the intercalated duct. Cell layers around pseudocysts and occasional cellular islands had an immunophenotype suggesting myoepithelial-cell differentiation. The most clear cut epithelial/myoepithelial bilaminar differentiation was present in areas with a trabecular pattern, in which the layers facing the stroma and the central ductal elements had SKVA phenotypes of myoepithelial and ductal differentiation, respectively. In areas with a reticular pattern, most of the cells showed ductal differentiation. Many of the cells in the cribriform and basaloid regions were immunophenotypically undifferentiated. These results indicate that ACC consists of undifferentiated cells and of cells that are differentiating toward ducts, predominantly intercalated ducts, and toward myoepithelium. These findings support previous observations by electron microscope.

Topics: Actins; Antibodies; Breast Neoplasms; Bronchial Neoplasms; Carcinoma, Adenoid Cystic; Cell Differentiation; Collagen; Histocytochemistry; Keratins; Lymphatic Metastasis; Membrane Proteins; Molecular Weight; Mucin-1; Phenotype; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands; Skin Neoplasms; Submandibular Gland Neoplasms; 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

A clonal neoplastic epithelial duct cell (HSGc) of human salivary gland origin has a fine structure similar to the intercalated duct cell and the capacity to express secretory component and lactoferrin. HSGc cells tend to form an occasional glandular arrangement in vitro and in vivo, and transplantation of cells into nude mice resulted in production of adenocarcinoma. By repeated single cell cloning, different types of clones could be isolated from HSGc. Cuboidal clones resemble the parent cell, but fail to form the glandular arrangement or express lactoferrin, suggesting a less differentiated type. Elongated clones have a fine structure similar to myoepithelial cells and carry myoepithelial markers such as S100 protein, actin, and myosin which are not detected in the HSGc and its cuboidal clones. These myoepithelial-like clones are able to express secretory component, lactoferrin, and lysozyme and to produce glycosaminoglycans, suggesting that they are a functionally active form of the neoplastic cell but different from the normal myoepithelial cell. Judging from their growth properties in vitro and in vivo, the myoepithelial-like clones are less malignant than HSGc or its cuboidal clones. Of four elongated clones, two did not produce tumors in athymic mice, while all of the cuboidal clones were tumorigenic. These findings suggest a possible conversion of the neoplastic duct cell to myoepithelial-like variants with low malignancy.

Topics: Actins; Adenocarcinoma; Antigens; Carcinoma; Cell Cycle; Cell Line; Cell Separation; Clone Cells; Epithelium; Fluorescent Antibody Technique; Humans; Keratins; Lactoferrin; Microscopy, Electron; Muramidase; Myosins; S100 Proteins; Salivary Gland Neoplasms; Secretory Component

An immunohistochemical survey of the distribution of keratin was studied in chemically induced carcinomas of the submandibular glands of mice. Initial signs of premalignant changes were degranulation of granular convoluted tubule cells and deposition of keratin protein in small limited areas of the degranulated cells. There was a gradual increase in the area showing keratin staining in altered tubule cells. Duct-like and cystic structures stained intensely for keratin, as did squamous metaplastic epithelial cells. Induced carcinomas were variably keratinized. Basal layers of cells of squamous-cell carcinomas displayed weak keratin staining, and spinous tumor cells and parakeratotic tumor cells showed somewhat increased levels of keratin staining. Some desquamated keratotic tumor cells stained intensely for keratin. Just as the localization of epidermal and nerve growth factors and lectin-binding histochemistry have been used in studying tumorigenesis in the mouse submandibular gland, immunohistochemically detected keratin proved to be a useful marker of tumor cells of ductal segment origin.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Epithelium; Histocytochemistry; Immunoenzyme Techniques; Keratins; Male; Metaplasia; Mice; Mice, Inbred Strains; Precancerous Conditions; Salivary Gland Neoplasms; Submandibular Gland; Submandibular Gland Neoplasms

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

One case of myoepithelioma was studied by immunohistochemical and histochemical methods to identify the cell products of this tumor. The myoepithelioma had two cell types: plasmacytoid cells and spindle cells. The tumor myoepithelial cells produced the same cell products as did the normal myoepithelial cells but in variable amounts, possibly related to stages of differentiation. As no exocrine cell products could be identified in this neoplasm, it is considered a "true" myoepithelioma.

Topics: Fibronectins; Humans; Keratins; Laminin; Male; Middle Aged; Myoepithelioma; S100 Proteins; Salivary Gland Neoplasms; Salivary Glands; Salivary Glands, Minor; Salivary Proteins and Peptides

Myoepithelial and basal cells were identified by a monoclonal antibody raised against keratin. This antibody (CK B1) which detects myoepithelial cells in normal salivary glands, labels spindle shaped and polygonal cells in pleomorphic adenomas. Most cells in adenoid cystic carcinomas and some basal cells in adenolymphomas were also positive for this antibody. The oncocytic epithelium of adenolymphoma was negative. An inverse reaction was seen with an antibody against cytokeratin 18. The antibody CK B1 seems to be of interest for the detection of myoepithelial/basal cells in salivary glands and salivary gland tumours.

Topics: Adenolymphoma; Adenoma; Antibodies, Monoclonal; Carcinoma, Adenoid Cystic; Humans; Keratins; Salivary Gland Neoplasms

The adenocarcinoma cell line HSG from human salivary gland, which proliferates in vitro or in nude mice, was examined by the immunoperoxidase method for the expression of three different types of intermediate-sized filaments (IFs) and of specific antigens such as carcinoembryonic antigen, S-100 protein, secretory component, lactoferrin, myosin, tropomyosin, and actin. The cultured HSG cells were found to express three different types of IFs defined by antibodies to keratin, vimentin, and desmin. In HSG cells proliferating in vitro at 34 degrees C and 37 degrees C but not at 39 degrees C, the expression of tropomyosin and carcinoembryonic antigen was observed, although myosin and S-100 protein were not detected. The expressions of actin, lactoferrin, and secretory component were restricted to cultured HSG cells at 39 degrees C and 37 degrees C, respectively. Transplantation of HSG cells into nude mice resulted in the establishment of a nude mouse system with malignant characteristics such as invasion and metastasis. The expression of IFs in the primary tumors was restricted to keratin and desmin IFs, whereas coexpression of keratin, vimentin, and desmin IFs was observed in some neoplastic cells present in the metastatic tumors in regional lymph nodes and lung. In addition, expression of actin, myosin, tropomyosin, and S-100 protein was found in the metastatic tumors, whereas myosin and S-100 protein were not detected in the primary tumors. Moreover, the metastatic tumors were almost occupied by the neoplastic cells with oncocytic changes, although oncocytic change was not found in the cultured HSG cells and their primary tumors.

Topics: Adenocarcinoma; Animals; Antigens, Neoplasm; Carcinoembryonic Antigen; Cell Line; Cytoskeleton; Desmin; Female; Humans; Keratins; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; S100 Proteins; Salivary Gland Neoplasms; Secretory Component; Transplantation, Heterologous; 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

In oral dysplasias and squamous cell carcinomas, relationships exist between the presence of keratin filaments and cell differentiation. The keratinized areas of high differentiated carcinomas are carcinoembryonic antigen (CEA) positive. The labeling of the higher molecular keratins is similar to the distribution of lectin receptors so that lectins represent membrane-oriented markers of differentiation. In dysplasias a gradual loss of blood group substances A and B can be observed. Squamous cell carcinomas possess no substances A or B. H antigen as precursor of A and B is increased in preneoplasias and absent in carcinomas. In oral papillomas, leukoplakias, and carcinomas virogen koilocytotic cell changes, papilloma viruses and viral antibodies can be demonstrated. In salivary gland tumors a distinct pattern of distribution for keratin, vimentin, CEA, tissue polypeptide antigen (TPA), metalloproteins, and enzymes can be observed. The cellular stromal reaction (lymphocytes, Langerhans cells, and so forth) can be defined more exactly by monoclonal antibodies.

Topics: Antigens, Viral; Blood Group Antigens; Carcinoembryonic Antigen; Cell Differentiation; Histocytochemistry; Humans; Intermediate Filament Proteins; Keratins; Lactoferrin; Mouth Neoplasms; Peptides; Receptors, Mitogen; Salivary Gland Neoplasms; Tissue Polypeptide Antigen

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

Squamous metaplasia is not an uncommon feature of a number of salivary gland lesions. Arterial ligation of rat submandibular and sublingual salivary glands was used for study of the processes and cell types involved in the development of the squamous metaplasia that occurs in ischemic and infarcted portions of gland parenchyma 6 to 8 days following vessel ligation. Light and electron micrographs show that the principal portion of salivary gland tissue undergoing squamous metaplasia is the acinar-intercalated duct cell complex. Early stages of this process involve a gradual dedifferentiation of acinar cells and hyperplasia of acinar, duct luminal cells, and myoepithelium. Subsequently, both luminal and myoepithelial cells have increasing accumulation of tonofilaments and formation of desmosomes, and centrally located cells may undergo keratinization. Immunohistochemical staining of ischemic salivary gland tissue with developing squamous metaplasia was performed with the use of rabbit antisera to human epidermal and Mallory body cytokeratins. The two antisera gave complementary patterns in normal acini and ducts, with antibody to epidermal cytokeratin (ECK) staining only myoepithelial cells and antibody to Mallory body cytokeratin (MBCK) staining mainly luminal epithelial cells. In early phases of squamous metaplasia (6 days after ligation), antibody to ECK stained central and peripheral (myoepithelial) cells, but by 8 days after ligation only central cells were stained. At 6 days after ligation, a proportion of central cells in squamoid clusters stained with antibody to MBCK, and myoepithelial cells were unstained. By 8 days after arterial ligation, cell clusters exhibiting squamous metaplasia were completely unstained with antibody to MBCK, despite the presence ultrastructurally of numerous tonofilament bundles in both types of cells forming these clusters. The propensity for squamous alteration of acinar-intercalated duct complexes has important connotations for salivary gland tumors such as pleomorphic adenoma and mucoepidermoid carcinoma.

Topics: Animals; Humans; Immunoenzyme Techniques; Keratins; Metaplasia; Mice; Rats; Rats, Inbred Strains; Salivary Gland Neoplasms; Salivary Glands; Submandibular Gland

The immunohistochemical distribution of keratin is reported in experimental carcinogenesis in the mouse submandibular gland (SMG). The initial changes included degranulation of granular convoluted tubule (GCT) cells and the appearance of keratin in the degranulated cells. There was a gradual increase in the area showing keratin staining in the altered tubule cells. Duct-like and cystic structures exhibited an intense keratin staining of their lining epithelium. The squamous cell carcinomas induced varying degrees of keratinization and positive immunohistochemical keratin staining. The latter technique provided a useful marker for distinguishing tumor cells of segmental duct origin in the salivary gland.

Topics: Animals; Carcinoma, Squamous Cell; Histocytochemistry; Keratins; Male; Mice; Precancerous Conditions; Salivary Gland Neoplasms; Submandibular Gland Neoplasms

Peroxidase-conjugated lectins were used for the histochemical detection of carbohydrates in experimental carcinomas of mouse submandibular glands. Induced carcinomas, 43 lesions from 25 cases, were examined histochemically with galactose-binding lectins (PNA and RCA-1), N-acetyl-galactosamine-binding lectins (DBA and SBA), a fucose-binding lectin (UEA-1), and a N-acetyl-glucosamine-binding lectin (WGA). In non- or slightly keratinized squamous-cell carcinomas, the lectin binding of PNA, RCA-1, DBA, SBA, and WGA was weak in tumor epithelia, and UEA-1 binding was slight. In highly keratinized squamous-cell carcinomas, lectin binding was increased in tumor epithelia, but no reaction was noted in completely keratinized regions. Desquamated materials in lumens of tumors gave an intense stain with lectins. Stromal connective tissue, including collagen fibers and basement membranes stained intensely. Lectin binding to submandibular carcinomas was different from binding to granular convoluted tubules and the striated ducts of the normal submandibular gland.

Topics: Amino Sugars; Animals; Carcinoma, Squamous Cell; Cytoplasm; Epithelium; Keratins; Lectins; Mice; Precancerous Conditions; Receptors, Mitogen; Salivary Gland Neoplasms; Staining and Labeling; Submandibular Gland Neoplasms

Six cases of adenoid cystic carcinoma of salivary glands have been examined with antibodies specific for either keratin or vimentin. Tumor cells in all six cases showed coexpression of keratin and vimentin.

Topics: Adult; Carcinoma, Adenoid Cystic; Cytoskeleton; Female; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Male; Microscopy, Fluorescence; Middle Aged; Salivary Gland Neoplasms; 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 against different fractions of keratins can be helpful in various fields of special pathology. Antibodies against "small" and "large" keratins permit to evaluate epithelial maturation in skin and oral mucosa. In addition, disturbances of keratinization during inflammatory processes and malignant transformation can be analyzed. The main application of antibodies against the entire fractions of keratins is the detection of the epithelial nature of a neoplasm. By this tool, particular problems in surgical pathology concerning differential diagnosis can be handled in an easier way. Among the different tissues and their neoplasms, examples of the analysis of thymus tumours and salivary gland tumours are presented. Immunoreactivity with keratin antibodies depends crucially on tissue processing. In the normal diagnostic procedure, good results are regularly obtained if cryostat or Bouin-fixed paraffin-embedded sections are used.

Topics: Adenoma; Carcinoma in Situ; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cytoskeleton; Humans; Keratins; Mouth Mucosa; Mouth Neoplasms; Parakeratosis; Salivary Gland Neoplasms; Salivary Glands; Skin; Skin Neoplasms; Thymus Gland; Thymus Neoplasms

The intermediate-sized filaments can be divided into several groups which are characteristic of different types of tissues (e.g.: epithelial, mesenchymal, muscle, astrocytic and neural origin). Antibodies specific for some of these filament types have been used to analyse a group of salivary gland tumours. Prekeratin-positive cells were seen in the normal gland, cystadenolymphomas, mucoepidermoid tumours, and squamous cell carcinomas which are all tumours of epithelial origin. The pleomorphic adenomas showed the presence of some cells which appeared to contain both prekeratin and vimentin. The results are discussed with respect to their histogenetic implications.

Topics: Adenoma; Carcinoma; Carcinoma, Squamous Cell; Cytoskeleton; Desmin; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Protein Precursors; Salivary Gland Neoplasms; Salivary Glands; Vimentin

Rabbit antisera to human 40-63 000 MW epidermal keratin, one batch with restricted distribution of reactivity from an initial (aK1) and one with "broad spectrum" distribution of reactivity from a late bleeding (aK), and to "luminal epithelial antigen" (aLEA) were applied to formalin fixed paraffin embedded sections of human normal and neoplastic mammary and salivary glands using an indirect immunoperoxidase method. aK1 reacted with myoepithelial cells, aLEA with luminal epithelial cells and aK with both cell types in normal mammary and salivary gland. In breast carcinomas the majority of intraluminal and infiltrating carcinoma cells reacted with aLEA but not with aK1 which reacted only with surrounding myoepithelial cells. aK reacted with both myoepithelial cells and with intraluminal and infiltrating tumour cells. In the salivary gland adenomas the majority of cells reacted with aK, and those cells arranged in a tubular fashion reacted with aLEA.

Topics: Adenoma; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Cytoskeleton; Epithelium; Female; Humans; Immunoenzyme Techniques; Keratins; Parotid Neoplasms; Salivary Gland Neoplasms