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PubMed2001

[About the prognostic value of Her-2 gene-amplification and cell-proliferation in salivary duct carcinoma of the major salivary glands - a pilot-study].

INTRODUCTION: The salivary duct carcinoma (sdc) represents a rare variant of the group of adeno-carcinomas of the salivary glands. Histopathologically, it is marked by solid and cribriform cell nests with central necrosis, displaying distinct similarity with the ductal carcinoma of the breast, where prognosis can be correlated with Her-2 gene-amplification. Based on this histopathological similarity, the prognostic value of Her-2 gene amplification in SDC was examined in the presented pilot-study. PATIENTS AND METHODS: Four own patients with different clinical courses were examined in regard to their histopathological features, Her-2 gene-amplification and proliferation (Ki67). RESULTS: Three of the four patients died tumor related 2.4, 5.5 and 8.2 years after initial diagnosis. The remaining patient died tumor-free 6 year after diagnosis (myocardial infarct). The two patients with an early recurrent disease and distant metastasis showed a high Her-2 expression and proliferation (Ki67), compared to the other two patients. CONCLUSION: In the presented pilot-study a distinct correlation between Her2-gene-amplification, proliferation (Ki67) and clinical course could be observed. Additional analysis to evaluate this aspect seems rectified, especially under recognition of therapy decisions.

Adenocarcinoma↗
PubMed1997

Aspiration and imprint cytopathology of salivary duct carcinoma.

BACKGROUND: Salivary duct carcinoma (SDC) is a highly malignant primary epithelial neoplasm of the salivary glands. The histology of this lesion resembles that of cribriform and comedo-type intraductal carcinoma of the breast, yet the cytopathology of salivary duct carcinoma has been described in only a few instances in the past. METHODS: The authors report two cases of SDC diagnosed by fine-needle aspiration biopsy and one case imprinted after resection. The cytologic features that may permit diagnosis of this entity are described. RESULTS: Cytologic features include variably cellular smears containing loose clusters of cribriform and glandlike aggregates; monomorphic polygonal cells with round-to-oval nuclei; abundant, finely granular cytoplasm; indistinct nucleoli; and variable necrosis. CONCLUSIONS: The cytologic findings for SDC are relatively unique and may allow for its specific diagnosis on aspiration cytopathology.

Aged↗
PubMed2001

Expression of androgen receptor, epidermal growth factor receptor, and transforming growth factor alpha in salivary duct carcinoma.

BACKGROUND: Salivary duct carcinoma (SDC) is a rare, highly aggressive neoplasm that primarily affects the major salivary glands. It is a distinct clinicopathological entity characterized by its morphologic resemblance to ductal carcinoma of the breast, a high incidence of regional lymph node metastasis, and distant dissemination. Frequent expression of androgen receptor (AR) but not estrogen receptor or progesterone receptor in SDCs suggests that SDC bears a close immunophenotypic homology with prostatic carcinoma. An AR-mediated autocrine growth pathway consisting of epidermal growth factor receptor (EGFR) and its ligand, transforming growth factor alpha (TGF-alpha), has been implicated in the carcinogenesis of prostatic carcinoma. Androgens, in the presence of AR, mediate their mitogenic effects on prostatic cancer cells by up-regulating the transcriptional and translational activities of EGFR and TGF-alpha. Through an autocrine mode of action, TGF-alpha produced in the tumor cells binds to its receptor, EGFR, which is also expressed by these cells, resulting in a proliferative response. OBJECTIVE: To investigate whether a TGF-alpha/EGFR autocrine pathway is present in SDCs. DESIGN: Retrospective analysis of the expression of AR, EGFR, and TGF-alpha in 12 SDCs. SETTING: An academic medical center. RESULTS: Salivary duct carcinoma expresses AR, TGF-alpha, and EGFR in 11 (92%), 8 (67%), and 11 (92%) of 12 cases, respectively. CONCLUSION: An AR-mediated TGF-alpha/EGFR autocrine pathway may be implicated in the tumorigenesis of SDC.

Adult↗
PubMed2002

Patch-clamp studies on epithelial sodium channels in salivary duct cells.

Mouse mandibular salivary duct cells contain an amiloride-sensitive Na+ current and express all three subunits of the epithelial Na+ channel, ENaC. This amiloride-sensitive Na+ current is subject to feedback regulation by intracellular Na+ and we have previously demonstrated that this regulation is mediated by an ubiquitin-protein ligase, which we identified as Nedd4. The evidence supporting this identification is as follows: (1) antibodies raised against murine Nedd4 block Na+ feedback inhibition; (2) a mutant of murine Nedd4 containing the WW domains but no HECT domain (ubiquitin-protein ligase) blocks Na+ feedback inhibition; and (3) Nedd4 is expressed in mouse mandibular salivary duct cells. In the present studies, we have used whole-cell patch-clamp methods to further investigate the mechanisms by which ubiquitin-protein ligases regulate the amiloride-sensitive Na+ conductance in mouse salivary duct cells. In particular, we have examined the possibility that the ubiquitin-protein ligase, KIAA0439, which is closely related to Nedd4, may mediate Na+ feedback control of amiloride-sensitive Na+ channels. Furthermore, we have attempted to define the mechanism by which ubiquitin-protein ligases inhibit Na+ channels. We have found that KIAA0439 is expressed in mouse mandibular ducts and interacts with the PY motifs of the alpha-, beta-, and gamma-subunits of ENaC in vitro. Furthermore, in whole-cell patch-clamp studies, a glutathione-S-transferase (GST)-fusion protein containing the WW motifs of human KIAA0439 was able to inhibit feedback regulation of the amiloride-sensitive Na+ current by intracellular Na+. We also examined whether GST-fusion proteins containing the C-termini of the alpha-, beta-, and gamma-subunits of ENaC are able to interrupt Na+ feedback regulation of the amiloride-sensitive Na+ current. We found that the C-termini of the beta- and gamma-subunits were able to do so, whereas the C-terminus of the alpha-subunit was not. We conclude that KIAA0439 is, together with Nedd4, a potential mediator of the control of epithelial Na+ channels in salivary duct cells by intracellular Na+. We further conclude that ubiquitin-protein ligases interact with the Na+ channels through the C-termini of the beta- and gamma-subunits of the Na+ channels.

Amiloride↗
PubMed1988

Salivary duct carcinoma in major and minor salivary glands. A clinicopathological analysis of four cases.

Salivary duct carcinomas are an uncommon but distinct group of highly malignant salivary gland tumours. We report the clinical course, pathological findings and surgical treatment of this tumour in 4 patients. In one patient an intraductal tumour developed in a minor salivary gland, while in the other three patients, a major salivary gland was involved by an infiltrating salivary duct carcinoma. We point out the highly aggressive biological behaviour of the tumour when occurring in the major salivary glands, in contrast to the benign course of the intraductal carcinoma in the minor salivary gland.

Adenocarcinoma, Papillary↗
PubMed2003

Expression of peroxisome proliferator-activated receptor gamma in salivary duct carcinoma: immunohistochemical analysis of 15 cases.

Salivary duct carcinoma is a rare but highly aggressive tumor of the salivary glands that has poor prognosis. There is no effective cure for this tumor. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor family with diverse biological functions that include mediation of adipocyte differentiation, regulation of the monocyte-macrophage anti-inflammatory activity, and inhibition of tumor cell proliferation. Natural (prostaglandin J2, PG-J2) and synthetic (thiazolinediones) PPARgamma ligands with anti-proliferative agonist activity have been identified. The expression of PPARgamma has been demonstrated in human colorectal, pancreas, breast, and prostate cancers but has never been explored in salivary duct carcinoma. The aim of our study was to investigate the expression patterns of PPARgamma in salivary duct carcinoma, a finding that may provide a mechanism for treating patients with this highly aggressive tumor. Archival formalin-fixed tissues from 15 salivary duct carcinoma cases were analyzed for PPARgamma expression by an immunohistochemical staining method using a monoclonal antibody against the PPARgamma. The tissue sections were subjected to antigen retrieval by a steam heat method. All the cases of salivary duct carcinoma originated from the parotid gland. Immunohistochemistry analyses showed positive expression of PPARgamma in 12 (80%) cases, whereas 3 (20%) were negative. Of the positive cases, 9 (75%), 2 (17%) and 1 (8%) showed strong, moderate, and weak staining, respectively. All staining was cytoplasmic. Nuclear staining was not observed. We conclude that PPARgamma is frequently (80%) expressed in salivary duct carcinoma, often at high levels, and is topographically located in the cytoplasm. The high-level expression of PPARgamma may provide a potential molecular target for the treatment of salivary duct carcinoma using agonist ligands.

Adult↗
PubMed1993

Salivary duct carcinoma.

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

Adenoma, Pleomorphic↗
PubMed1998

Neuropeptide TPep action on salivary duct ciliary beating rate in the nudibranch mollusc Tritonia diomedea.

Recently, in the marine mollusc Tritonia, a family of three peptides (TPep-NLS, -PLS, -PAR) from identified pedal ganglion neurons has been characterized and shown to regulate ciliary beat frequency in epithelia and isolated cells of the molluscan foot. In this study, using an antiserum raised against TPep-NLS, immunofluorescent labelling was observed in specific nerve cell bodies and axons in the buccal ganglia of Tritonia, as well as in axons leading to and innervating the salivary ducts, salivary glands, oesophagus and foregut. This pattern of innervation suggests that buccal ganglion neurons containing TPep control the beating rate of ciliated cells in feeding organs. Accordingly, TPeps were introduced to isolated ciliated salivary ducts. It was found that TPeps and serotonin increased the ciliary beat frequency of cells of the salivary duct similarly; other peptides (such as APep from Aplysia) had no such effect. Threshold sensitivity both for TPeps and serotonin was approximately 10(-8) M, with maximal response occurring above 10(-5) M. Taken together, these structural and physiological results suggest that TPep-like peptides are present in the salivary and other feeding organs of Tritonia and are involved in the regulation of salivary transport.

Animals↗
PubMedDate not supplied

Salivary duct carcinoma of the palate.

Salivary duct carcinoma is a rare high-grade neoplasm that more frequently affects the parotid gland. Though neoplasms of this type are infrequent in minor salivary glands, they are less aggressive and may lead to early diagnosis before distant metastases could occur. Salivary duct carcinoma is also the most frequent epithelial component of carcinosarcoma. The present article reports a case of SDC of the palate in a 26-year-old male and discusses SDC as a malignant epithelial component in carcinosarcoma.

Adenoma↗
PubMed1998

Surgery of the salivary ducts.

Successful surgery of the salivary ducts relies on an understanding of the surrounding anatomy and the delicate dissection of tissues in order to reduce morbidity. Trauma to the ducts should be assessed when lacerations or wounds encroach on their paths. Early diagnosis and treatment will reduce the complications of stricture and fistula formation from these injuries. Sialoliths can be located in several places along the length of the salivary ducts. The correct diagnosis and positioning of the stone in the duct is important in establishing the appropriate surgical approach. Imaging using plain films, ultrasonography, and endoscopy can be very valuable, with sialography and CT scans helpful in cases of radiolucent stones, glandular atrophy, or suspected tumor. As the condition becomes more chronic, resulting in glandular atrophy, excision of the diseased gland is often indicated. Treatment of excessive salivary flow in patients with cerebral palsy can be managed by a combination of ductal repositioning and glandular excision. Redirection of both the parotid and submandibular glands can be accomplished, either to reroute excess salivary flow or salvage the duct in cases of lesion excision.

Humans↗
PubMed2003

Expression of HER-2/neu gene and protein in salivary duct carcinomas of parotid gland as revealed by fluorescence in-situ hybridization and immunohistochemistry.

AIMS: Salivary duct carcinoma is a highly malignant salivary gland tumour with aggressive clinical behaviour, characterized by histological resemblance to invasive ductal carcinoma of the breast. Amplification of HER-2/neu oncogene and over-expression of its gene product have both prognostic and therapeutic implications in breast cancer. Recent report on salivary duct carcinomas for HER-2/neu using immunohistochemistry (IHC) has shown over-expression in most cases. However, correlation between IHC and molecular genetic analysis of HER-2/neu in salivary duct carcinoma has not yet been performed. METHODS AND RESULTS: We have now evaluated 11 cases of salivary duct carcinomas for HER-2/neu status using IHC and fluorescent in-situ hybridization (FISH). To our knowledge, this is the first molecular genetic analysis of HER-2/neu in salivary duct carcinoma. CONCLUSIONS: In immunohistochemistry, over-expression of HER-2/neu protein was identified as distinct membrane staining in most carcinoma cells in all our salivary duct carcinoma cases, while only four cases revealed an amplification of HER-2/neu gene by means of FISH analysis. Both amplified and non-amplified salivary duct carcinomas with strong immunohistochemical staining for HER-2/neu protein were associated with poor clinical outcome for the patients. Apparently, HER-2/neu protein over-expression could also be controlled by mechanisms other than gene amplification. In the group of salivary gland tumours other than salivary duct carcinoma, strong over-expression was detected only in three cases of carcinoma ex pleomorphic adenoma. Thus, over-expression of HER-2/neu protein is also a useful marker of malignant transformation in pleomorphic adenomas.

Adult↗
PubMed2003

Mucin-rich variant of salivary duct carcinoma: a clinicopathologic and immunohistochemical study of four cases.

Salivary duct carcinoma is a relatively uncommon aggressive neoplasm, typically found in the parotid glands of older men. The histologic appearance is that of an in situ and invasive high-grade adenocarcinoma, and it closely resembles ductal carcinoma of the breast. Several variants of the latter are very well known, but only papillary, sarcomatoid, and low-grade subtypes have so far been reported in salivary duct carcinoma. This study describes the clinicopathologic and immunohistochemical findings in four examples of an additional previously undescribed variant, rich in mucin. Each tumor showed areas of typical salivary duct carcinoma, but in addition there were lakes of epithelial mucin-containing malignant cells, i.e., mucinous (colloid) carcinoma. All four tumors expressed androgen receptors, cytokeratins, epithelial membrane antigen, gross cystic disease fluid protein-15, and carcinoembryonic antigen, but S-100 protein, other myoepithelial markers, and estrogen and progesterone receptors were negative. The mucin antigen profile showed positivity for MUC2, MUC5B, and MUC6 in all cases but only rare staining with MUC5AC and MUC7. Strong immunohistochemical overexpression of HER2/neu was demonstrated in one tumor, together with amplification by fluorescence in situ hybridization; another case was weakly positive with just one antiserum, but the remaining two tumors were completely negative. Small quantities of mucin have often been described in salivary duct carcinoma but not large extracellular mucinous lakes, which though prominent in the present series, were not as extensive as in mucinous adenocarcinoma. The relatively poor clinical outcome of the patients in our study mirrored that seen in usual-type salivary duct carcinoma and emphasizes the importance of differentiating mucin-rich salivary duct carcinoma from pure mucinous (colloid) adenocarcinoma, a tumor not fully defined, but possibly with a better prognosis.

Adenocarcinoma, Mucinous↗
PubMed1997

Submandibular gland duct endoscopy. Diagnostic value for salivary duct disorders in comparison to conventional radiography, sialography, and ultrasonography.

The purpose of this study is to evaluate the usefulness of endoscopy as a procedure for the diagnosis of submandibular gland duct disorders. Endoscopy of the submandibular glands was performed on 12 patients with symptoms of obstructive sialoadenitis to identify the cause of obstruction. The endoscopic findings were then compared to those of diagnostic procedures such as conventional radiography, sialography, and ultrasonography. Six normal subjects also underwent endoscopy to better understand the normal findings of the duct system. Endoscopy demonstrated salivary gland calculus in 5 of 12 patients, which was revealed as filling defects on sialograms and as strongly echogenic structures on ultrasonograms in 4 of the patients. Endoscopy revealed secretion plugs, secretion plaques, and/or stenosis, which could not be seen by any other diagnostic procedures in 5 patients, as the cause of recurrent swelling in all 7 patients not demonstrating sialolith. Abnormal findings of the duct wall such as vasodilatation, fibrosis, edema, or erythema were seen in four patients, three of whom exhibited dilatation of the duct system on sialograms. In four patients, a decreasing internal echo level of the gland was seen on ultrasonograms. Our initial results for submandibular gland duct endoscopy thus appear to be promising.

Adult↗
PubMed2001

Intraoral salivary duct carcinoma: case report with immunohistochemical observations.

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.

Carcinoma↗
PubMed2005

Sarcomatoid salivary duct carcinoma.

The so-called sarcomatoid salivary duct carcinoma (SSDC) is one of the variants of salivary duct carcinoma (SDC). This neoplasm is characterized by the presence of both a carcinomatous and a sarcomatoid tumor component. The histology and nomenclature of such neoplasms has been a matter of debate for many years. The histologic, immunohistochemical, and electron microscopic findings including those of 4 previously described cases of SSDC are defined and the different attitudes concerning their etiology will be discussed. In addition, the fine-needle aspiration biopsy of such a case is presented for the first time. In analogy to typical SDC there seems to be a predilection for elderly men and a location in major salivary glands. The resected SSDC tumors measured between 1.5 and 3.5 cm. Histologically, each case was a composite of SDC and sarcomatoid carcinoma. Immunohistochemical positivity for epithelial membrane antigen (EMA) and cytokeratins (AE1/AE3, CAM 5.2) was shown in the sarcomatoid tumor component. The important cytomorphologic feature of SSDC is the presence of cohesive clusters and flat sheets of cells with a cribriform pattern, in combination with an atypical spindle cell component. The use of the term SSDC seems more appropriate than the term carcinosarcoma , as the immunohistochemical, electron microscopic, and recent molecular findings in this and other biphasic neoplasms imply a monoclonal origin.

Adult↗
PubMed1991

Salivary duct adenocarcinoma.

Six cases of salivary duct adenocarcinoma are presented. All had a history of a rapidly enlarging mass in the parotid gland with involvement of the facial nerve. The histopathological appearance was distinctive, each case showing an invasive tumour resembling ductal carcinoma of the breast, often with areas of comedo necrosis. Five patients died within 26 months, and the one long-term survivor (68 months) has widespread metastatic disease. These findings are similar to cases which have previously been described, but the tumour has not been widely reported, particularly in Britain. We feel that salivary duct adenocarcinoma is a distinct clinicopathological entity and, as its histological appearance is usually unmistakable, we believe it deserves wider recognition.

Adenocarcinoma↗
PubMed1995

Salivary duct carcinoma.

Twelve cases of salivary duct carcinoma were examined clinically, pathologically and by flow cytometry to quantify their histological features as well as attempt to identify factors predictive of patient outcome. All of the tumours arose in the parotid gland. Eight of the twelve patients were male. Four patients died of disease (median survival 12.5 months); three are alive with disease; and five are alive with no evidence of disease (mean follow-up of 50 months). Two tumours arose in a pre-existing pleomorphic adenoma. Positive lymph nodes were present in eight of ten patients sampled; patients with two or more positive lymph nodes tended to die of their disease or be alive with metastases. Comedo necrosis, perineural invasion and vascular invasion were common findings by light microscopy. Ten of the twelve tumours were aneuploid. Neither clinical stage, tumour size, aneuploidy nor histological features correlated with patient outcome. This study confirms the aggressive nature of salivary duct carcinoma.

Adenocarcinoma↗