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Immunohistochemical expression of cytokeratins 7 and 20 in malignant salivary gland tumors.

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.

Adenocarcinoma↗

Expression of neurofilaments in a neoplastic human salivary intercalated duct cell line or its derivatives and effect of nerve growth factor on the cellular proliferation and phenotype.

A neoplastic salivary cell line with an ultrastructure similar to that of an intercalated duct cell of the salivary gland, established from a human submandibular salivary gland, has been used in our laboratory as a model for studying mechanisms regulating cytodifferentiation in salivary glands. The expression of neurofilaments (Mr 200,000, 160,000, and 68,000) in the neoplastic human salivary intercalated duct cell line and its derivatives was found by the immunofluorescence staining technique, immunoblotting, or immunoelectron microscopy. In addition, these cells stained with Bodian impregnation and expressed specific antigens such as tubulin alpha and beta chain, HNK-1 antigen, and laminin. When these cells were cultured in the presence of nerve growth factor, only the cells with a myoepithelial cell phenotype formed the long cytoplasmic processes which were densely packed with ample microfibrils in addition to microtubule bundles, and they exhibited marked suppression of anchorage-independent and anchorage-dependent growths. These findings indicate that the characteristics of neoplastic human salivary intercalated duct cell line and its derivatives are similar to those of neuronal cells.

Biomarkers↗

The myoepithelial immunophenotype in 135 benign and malignant salivary gland tumors other than pleomorphic adenoma.

BACKGROUND: We have previously studied the immunoreactivity of 3 novel smooth muscle-specific proteins, alpha-smooth muscle actin, smooth muscle myosin heavy chains, and calponin, to assess myoepithelial differentiation in pleomorphic adenomas. OBJECTIVE: To further expand our knowledge of myoepithelial differentiation in other benign and malignant salivary gland tumors. DESIGN: Formalin-fixed paraffin sections of 135 salivary gland tumors with associated normal glands were stained with monoclonal antibodies using the avidin-biotin complex immunoperoxidase method and enzymatic and microwave heat-induced epitope retrieval. RESULTS: In adenoid cystic carcinomas and epithelial-myoepithelial carcinomas, all 3 markers exclusively highlighted the myoepithelial cell components and the epithelial cells were entirely negative. No immunostaining was detected in canalicular adenomas, oncocytomas, Warthin tumors, acinic cell carcinomas, mucoepidermoid carcinomas, squamous cell carcinomas, and polymorphous low-grade adenocarcinomas. Salivary duct carcinomas and adenocarcinomas, not otherwise specified had a distinctive pattern of uniform periductal staining of reactive myofibroblastic cells, and in salivary duct carcinomas some ducts retained a peripheral immunoreactive myoepithelial cell layer. CONCLUSION: Immunoreactivity for these 3 smooth muscle-specific proteins confirms the known neoplastic myoepithelial component of adenoid cystic carcinomas and epithelial-myoepithelial carcinomas. The consistently positive staining pattern in adenoid cystic carcinomas may be diagnostically useful in discriminating histologically similar but consistently negative polymorphous low-grade adenocarcinomas. Periductal linear staining in adenocarcinoma, not otherwise specified and salivary duct carcinomas is distinctive and appears to represent a tight cuff of myofibroblasts associated with the infiltrating glands.

Actins↗

Application of magnetic resonance virtual endoscopy as a presurgical procedure before sialoendoscopy.

OBJECTIVES: The objectives of this study were to investigate the feasibility of clinical application of magnetic resonance (MR) virtual endoscopy as a presurgical procedure before sialoendoscopy and to evaluate its value in the diagnosis of obstructive salivary gland diseases and preoperative visualization of endoluminal views. STUDY DESIGN: This study presents our initial experience to use MR virtual endoscopy for the presurgical visualization of salivary duct lumen and ductal pathologies in comparison to the sialoendoscopy findings in a feasibility study. METHODS: Six consecutive patients with suspected obstructive salivary gland diseases underwent MR sialography with a three-dimensional fast imaging using steady-state acquisition. The three-dimensional MR data were transferred to an independent workstation and were postprocessed with navigator software to generate three-dimensional reconstruction and virtual endoscopic images. The fly-through mode was used to imitate the sialoendoscopic exploratory procedure. Then the patients underwent sialoendoscopy and the endoscopic findings were compared with the preoperative virtual endoscopic images. RESULTS: The MR data acquisition and postprocessing protocol were feasible. The virtual endoscopy created clear endoluminal views of salivary duct and the ductal pathologies. The diagnoses were all confirmed by surgical sialoendoscopy. The virtual endoscopic images showed close resemblance to the sialoendoscopic findings. CONCLUSIONS: MR virtual endoscopy is an effective and noninvasive diagnostic method for evaluating the endoluminal anatomy and pathologies of the salivary duct. The clinical application of MR virtual endoscopy as a presurgical procedure before sialoendoscopy is a valuable and promising approach, which can provide surgeons useful morphologic and pathologic information.

Adult↗

Parotid duct laceration repair in two horses.

Repair of parotid duct lacerations in 2 horses is described using intraluminal silastic tubing as a stent. The duct was lacerated traumatically at the facial vessel notch (incisura vasorum facialium) in the 1st horse, and iatrogenically after removal of an intraluminal sialolith after development of infection within the duct in the 2nd horse. In both cases, a silastic tube was passed retrograde into the duct via the salivary papilla, past the wound until the end lay rostroventral to the parotid salivary gland. The severed salivary ducts and the wounds were sutured. The external portion of the silastic tube was sutured to the skin and the tube left in place. Recovery in the 1st case was uneventful. In the 2nd case a salivary duct/cutaneous fistula formed at a wound distant from the sutured wound, which healed spontaneously. This technique differs from a similar described technique in that the stent tube exits the oral cavity and is attached to the outer skin surface.

Animals↗

Extramammary Paget's disease of the oral mucosa with in situ carcinoma of minor salivary gland ducts.

This paper describes a case of oral extramammary Paget's disease associated with widespread in situ carcinoma of minor salivary gland ducts and invasive, poorly differentiated carcinoma. Clinically, the case was characterized by unusually extensive and rapidly spreading erythroplakia of the oral mucosa, accompanied by a relatively small invasive salivary gland carcinoma. Despite the similarities of breast and salivary tissue, oral extramammary Paget's disease appears to be extremely rare.

Aged↗

Cystic lesion of the parotid gland with squamous metaplasia mistaken for squamous cell carcinoma. A case report.

BACKGROUND: The diverse range of diseases that affect the salivary glands may lead to problems and pitfalls in cyto-diagnosis. While false negative diagnosis of cystic salivary gland tumors is well known, false positive cytodiagnosis in nonneoplastic salivary cysts is less well documented. CASE: An 85-year-old female presented with a painless left parotid gland swelling of three months' duration. Fine needle aspiration cytology yielded fluid, smears of which showed keratinizing squamous cells with nuclear atypia leading to a cytologic diagnosis of cystic squamous cell carcinoma. A total radical parotidectomy followed. Histopathologic study showed cystic dilatation of many of the salivary ducts, which were lined with metaplastic squamous epithelium that showed atypia. There was no evidence of squamous cell carcinoma. CONCLUSION: Squamous metaplasia is known to occur in benign salivary gland lesions, such as pleomorphic adenoma and Warthin's tumors, as well as in salivary duct cysts and necrotizing sialometaplasia. However, atypical squamous metaplasia of salivary duct cysts mimicking squamous cell carcinoma on cytology is unusual.

Aged↗

Effect of intestinal microflora on 2,2'-dimethyl-4-aminobiphenyl-induced carcinogenesis in F344 rats.

The effect of intestinal microflora on colon and breast carcinogenesis induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB) was studied with the use of germfree and conventional F344 rats of both sexes. At 7 weeks of age, all animals except controls were given 20 weekly sc injections of DMAB in corn oil (100 mg/kg body wt/wk). Male animals were autopsied 15 weeks after the last injection, whereas female animals were autopsied 10 weeks after the last injection. Tumors were induced in the colons, duodena, breasts, ear ducts, salivary glands, and skin of conventional rats, and in the colons, breasts, ear ducts, salivary glands, and skin of germfree rats. No consistent difference was found in the incidence of tumors in the ear ducts, salivary glands, and skin between the germfree and conventional rats. None of the germfree rats showed duodenal tumors, whereas 13% of the female and 53% of the male conventional rats developed duodenal tumors. The incidence of intestinal tumors was lower in the germfree rats than in conventional animals. The mammary tumor incidence was lower in germfree female rats than in the conventional female rats than in the conventional females. DMAB induced fewer intestinal and breast tumors in germfree rats than in conventional rats.

Adenocarcinoma↗

Salivary terminal duct carcinoma.

We report two cases of terminal duct carcinoma of the minor salivary glands. The histological features, biological behaviour, treatment and the long-term management are described.

Adenocarcinoma↗

Characteristics of salivary diffuse infiltrative lymphocytosis syndrome in West Africa.

OBJECTIVE: To determine the prevalence of diffuse infiltrative lymphocytosis syndrome (DILS) in the minor salivary glands of 30 African Cameroonian adults with the acquired immunodeficiency syndrome (AIDS). DESIGN: Salivary gland tissue was analyzed using a modified classification system that was developed to aid the diagnosis of Sjögren syndrome. The advantages and disadvantages of this approach are discussed. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded, hematoxylin-eosin-stained biopsy sections were prepared for 30 patients with AIDS, 26 healthy individuals who declined human immunodeficiency virus (HIV) testing, and 4 seronegative healthy controls. Tissues were immunostained for CD4/CD8+ lymphocytes and cytomegalovirus (CMV), and transmission electron microscopy was performed to locate viral particles. Patients were tested for HIV-1 and HIV-2 by the HIV/Chek System 3 or CAMSTIX-HIV-1 and HIV-2 assay. RESULTS: Severe salivary ductal atypia (96%) was the feature most strongly associated with AIDS, and the lymphocytic focus score was the second histologic feature most strongly correlated with AIDS. Forty-eight percent of patients with HIV-1 infection had more than 1 lymphocytic focus in a minor salivary gland. These lymphocytes were primarily CD8+. We report, to the best of our knowledge, the first case of multinucleated salivary duct epithelial cells in minor salivary glands also containing enveloped virus particles. All cases were negative for CMV. CONCLUSIONS: The prevalence of DILS in West Africans with AIDS appears higher than the prevalence reported in whites from the United States and Europe and in blacks from the United States, a group that has been reported to have a greater incidence of DILS than whites. This discrepancy may be related to differences in patient selection criteria. The determination of lymphocytic focus score, as used in the diagnosis of Sjögren syndrome, with the adjunct of ductal atypia is useful for assessing DILS. The impact of patient selection, drug therapy, and parasites on salivary gland pathology is discussed.

Adult↗

Are myoepithelial cells responsible for the widespread expression of inducible nitric oxide synthase in pleomorphic adenoma? An immunohistochemical study.

Many of the actions of nitric oxide (NO) are still poorly understood. Recently, it has been shown that the inducible isoform of the enzyme nitric oxide synthase, iNOS, is expressed in both salivary ducts and pleomorphic adenoma. The current immunohistochemistry study determined whether or not this distribution correlated with smooth muscle actin (SMA) expression, thereby suggesting the expression by myoepithelial cells in both sites. Twenty cases of histologically confirmed pleomorphic adenoma, the sections of which contained adjacent normal salivary gland tissue, were stained for iNOS and smooth muscle actin (clone 1A4). The salivary ducts of all cases were stained intensely by both antibodies, with smooth muscle actin staining also being noted around acini in the normal gland parenchyma. Moderate or heavy staining for iNOS was found in all specimens of pleomorphic adenoma, with smooth muscle actin being distributed in a similar manner in 19 cases. Smooth muscle actin, but not iNOS, was also noted in blood vessels of both normal glands and tumours. The correlation between iNOS and SMA in pleomorphic adenoma was significant (P<0.001). The presence of iNOS in normal salivary ducts and pleomorphic adenoma is most likely due to expression by myoepithelial cells.

Actins↗

Induction of cells with acinar cell phenotype including presence of intracellular amylase. Treatment with 12-O-tetradecanoyl-phorbol-13-acetate in a neoplastic human salivary intercalated duct cell line grown in athymic nude mice.

The adenocarcinoma produced by transplantation into nude mice of a neoplastic human salivary intercalated duct cell line was treated with 0.1 ml of minimal essential medium (MEM) containing 12-O-tetradecanoyl-phorbol-13-acetate (TPA) at a final concentration of 10(-7) mol/l daily for 28 days and examined morphologically and immunohistochemically. The TPA treatment resulted in an enhancement of tumor growth. In addition, tumor cells containing secretory granules positively reactive to antiamylase serum were observed in the treated tumors, but not in untreated controls. These findings lead us to suggest that neoplastic intercalated duct cells treated with TPA can be induced to differentiate into acinar cells in heterotransplanted athymic nude mice.

Adenocarcinoma↗

Identification of functional receptors for vasoactive intestinal peptide and neurotensin in the human submandibular gland duct cell line, HSG-PA.

The HSG-PA human submandibular gland adenocarcinoma cell line has attracted attention recently as a potentially useful cell culture model for studies of salivary duct cell function and regulation. These cells possess a variety of morphological and biochemical markers found in salivary duct cells. Recently, muscarinic cholinergic receptors coupled to inositol intracellular Ca2+ mobilization (He et al., Eur. J. Physiol., 413 (1989) 505-510) and K+ fluxes (Ship et al., Am. J. Physiol., 259 (1990) C340-C348) have been identified in HSG-PA cells. In this study, we report the presence in these cells of functional receptors for two neuropeptides, vasoactive intestinal peptide (VIP) and neurotensin. Receptors for both peptides were labeled in intact cell radioligand binding studies and exhibited pharmacological profiles similar to receptors found in other tissues. There was close agreement between binding Ki values and the ED50 values for stimulation of second messenger production and modulation of K+ efflux, with all values between 1 and 5 nM. Whereas neurotensin stimulated K+ efflux dramatically, VIP alone had no effect but enhanced the response to neurotensin. These studies thus represent the initial documentation of functional receptors for VIP and neurotensin in a cell line of salivary duct cell origin.

Adenocarcinoma↗

[Insulin-like substance in the submaxillary glands of mice normally and in alloxan diabetes].

The content of an insulin-like substance, revealed in the submaxillary glands of mice by means of the radioimmunological method proved to decrease in alloxan diabetes, still remaining higher than in the blood serum of the same animals. Cells of the granular portions of the salivary ducts underwent some ultrastructural changes in this disease. The exogenous 125I-insulin was capable of being included into the cells of the salivary ducts. The percentage of labeled cells in these portions considerably exceeded such in acini of the submaxillary and the pancreatic ducts, and also in the islar cells. Incorporation of 125I-insulin into the salivary ducts proved to diminish in alloxan diabetes.

Animals↗

Granulomatous inflammation of minor salivary gland ducts: a new oral manifestation of Crohn's disease.

Multiple sublingual cystic masses developed in a 27-year-old man with active intestinal Crohn's disease during prednisone therapy. Surgical excision revealed noncaseating granulomatous inflammation involving the walls of minor salivary gland ducts. In some areas, this ductal lesion was associated with rupture and mucocele formation. Three weeks after excision of the salivary gland tissue, the patient experienced an exacerbation of his intestinal disease, accompanied by a recurrent lesion on the floor of his mouth and aphthous ulcerations of the buccal mucosa. The oral lesions and intestinal symptoms resolved only after azathioprine therapy. This salivary gland lesion represents a previously undescribed oral manifestation of Crohn's disease.

Adult↗