Primary Salivary Duct Carcinoma Research Articles

Primary salivary duct carcinoma of the lung: clinicopathological features, diagnosis and practical challenges

AimsTo investigate the clinicopathological features, molecular characteristics and diagnostic criteria of primary salivary duct carcinoma of the lung (LSDC).MethodsWe analysed the clinicopathological and molecular features of five cases of LSDC...

Primary and Secondary/ Metastatic Salivary Duct Carcinoma Presenting within the Sinonasal Tract

Traditionally, sinonasal adenocarcinomas have been subdivided into intestinal (ITAC) and non-intestinal (non-ITAC) categories. The latter encompasses salivary-type adenocarcinomas originating from the seromucinous glands of the sinonasal mucosa and non-salivary adenocarcinomas. The non-salivary adenocarcinoma category is further subdivided into low-and high-grade variants. Among salivary-type sinonasal adenocarcinomas, tumors recapitulating salivary duct carcinoma (SDC) are exceedingly rare, but some might have been lumped into the high-grade non-ITAC category. To date, only three primary SDCs originating in the sinonasal tract have been reported. We herein describe 7 cases of SDC including one previously reported case (4 primary sinonasal, 3 metastatic/ extension from parotid gland SDC). The primary tumors affected 3 males and one female aged 60 – 75. Different sites were involved by the primary tumors while the secondary tumors affected the sphenoidal (2) and the frontal + maxillary (1) sinuses. Three primary tumors were de novo high-grade SDC and one was confined to contours of a pre-existing pleomorphic adenoma. All 3 secondary tumors were SDC ex pleomorphic adenoma of the parotid with a long history of recurrences, ultimately involving the sinonasal tract. Androgen receptor was positive in 7/7 cases. Four of 6 cases were strongly HER2/neu + (either score 3 + or with verified amplification). This small case series adds to the delineation of primary sinonasal SDC highlighting that almost half of invasive SDC presenting within sinonasal tract indeed represents extension or metastasis from a parotid gland primary. There is a tendency towards overrepresentation of HER2/neu-positive cases in both categories (primary and metastatic), but this needs clarification in larger studies.

Prognostic value of PSMA, c-MET and E-cadherin in salivary duct carcinoma.

Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer. Androgen receptor (AR) (96%) and HER2 (29-46%) expression, and a high propensity for regional lymph node metastases are hallmarks of the disease. We hypothesized that c-MET, E-cadherin, PSMA tumor and PSMA neovascular expression may be prognostic factors in SDC. Expression levels of these proteins were established on tissue microarrays containing 165 primary SDC tumor specimens. Association with survival was studied with Kaplan-Meier curves, and univariable and multivariable Cox regression models. Furthermore, association with lymph node status, AR and HER2 expression, and gender was studied. We found that patients with high PSMA tumor expression showed a significantly longer overall survival (OS) (median 83 vs. 43 months, P = 0.022), a trend towards a longer DFS (median 51 vs. 22 months, P = 0.094), and significantly reduced hazard ratio for death in the univariable Cox regression model (HR 0.46, P = 0.034). In the multivariable model only a high number of tumor-positive lymph nodes and high age (>80) at diagnosis were prognostic for poor OS. High PSMA tumor expression was also significantly associated with low N-stage (P = 0.001) and expression was higher in women versus men (P = 0.029). High PSMA tumor expression and E-cadherin loss were significantly associated with strong and weak AR-expression, respectively (P = 0.033 and P = 0.007). None of the factors were significantly associated with HER2 expression. c-MET, E-cadherin, and tumor and neovascular PSMA expression are no independent prognostic factors in SDC.

Reciprocal and Autonomous Glucocorticoid and Androgen Receptor Activation in Salivary Duct Carcinoma.

To determine the expression of glucocorticoid receptor (GR) and androgen receptor (AR) in salivary duct carcinoma (SDC) and to analyze the role of these proteins in the development and management of this disease entity. We performed a phenotypic assessment of GR and AR localization and expression, and determined their association with clinicopathologic factors in 67 primary SDCs. In vitro functional and response analysis of SDC cell lines was also performed. Of the 67 primary tumors, 12 (18%) overexpressed GR protein, 30 (45%) had constitutive expression, and 25 (37%) had complete loss of expression. Reciprocal GR and AR expression was found in 32 (48%) tumors, concurrent constitutive GR and AR expression in 23 (34%), and simultaneous loss of both receptors and high GR with AR expressions were found in 12 (18%). GR overexpression was significantly associated with worse clinical outcomes. In vitro ligand-independent AR activation was observed in both male- and female-derived cell lines. GR antagonist treatment resulted in decreased cell proliferation and survival in GR-overexpressing cells, irrespective of AR status. Reciprocal GR- and AR-knockdown experiments revealed an independent interaction. Our study, for the first time, demonstrates differential GR and AR expressions, autonomous GR and AR activation, and ligand-independent AR expression and activation in SDC cells. The findings provide critical information on the roles of GR and AR steroid receptors in SDC tumorigenesis and development of biomarkers to guide targeted steroid receptor therapy trials in patients with these tumors.

Clinicopathological analysis of 40 cases of salivary duct carcinoma

Objective: To investigate the clinical manifestations and pathological changes of salivary duct carcinoma (SDC) and the relationship between them, so as to provide reference for the diagnosis of SDC. Methods: In this retrospective analysis 40 cases of SDC diagnosed from January 2012 to August 2018 in the Department of Pathology of the First Affiliated Hospital of Zhengzhou University were enrolled and the clinical and pathological characteristics were analyzed, 29 were male and 11 were female, the ratio of male to female was 2.64∶1, the median age was 59.0 years, the average course of disease was 3.5 years. The reported cases of SDC were reviewed and compared with patients of this study. Results: Among the 40 patients, 24 cases occurred in parotid gland, 9 cases in submandibular gland and 7 cases in small salivary glands; 24 cases had cancer cell infiltration and invasion of adjacent tissues, 11 cases had lymph node metastasis and 9 cases had distant metastasis at the time of diagnosis. Pathological results showed that 27 cases belonged to primary salivary duct carcinoma, 13 cases belonged to malignant transformation of pleomorphic adenoma; 10 cases invaded local nerve, 22 cases invaded glandular lobules and ducts. Immunohistochemical results showed that 33 cases were positive for androgen receptor, 27 cases were positive for cytokeratin-7, 22 cases were positive for human epidermal growth factor receptor-2, 8 cases were positive for gross cyst disease fluid protein 15. The proliferation index of nuclear antigen Ki-67 ranged from 10% to 90%. Among them 18 cases were over 50% and 22 cases were below 50%. Conclusions: Salivary duct carcinoma is a rare and highly malignant tumor of the salivary gland. Accurate pathological diagnosis is helpful to inhibit the early local recurrence, distant metastasis and improve survival rate of salivary duct carcinoma.

Establishment and genomic characterization of primary salivary duct carcinoma cell line

ObjectivesTo develop and characterize in vitro salivary duct carcinoma as a surrogate for functional studies. Materials and methodsCells were dispersed from tumor tissue fragments under sterile conditions in RPMI media. Disassociated cells were cultivated, immortalized with hTERT and propagated for more than 100 passages. Morphologic, linage, cytogenetic and genomic analyses were performed on different passages of cell line and primary tumor. Soft agar growth was performed. ResultsAnalysis of cytomorphologic features, growth characteristics and lineage specific markers expression confirmed the epithelial derivation and the neoplastic nature of the cell line. DNA STRs analysis showed identical match of both cell line and primary tumor. Cultivated cells expressed Androgen Receptor (AR), PTEN, and EFGR proteins and the AR-V7 isoform transcript. Comparative exome-sequencing identified common mutated genes in both cell line and primary tumor. In-vitro colony formation of late passages is established. ConclusionWe report the development of the first human salivary duct carcinoma cell line (MDA-SDC-04) that retains critical biological and genomic features of the donor tumor.

The use of immunohistochemistry in the diagnosis of primary salivary duct carcinoma: three case reports

Sir,Salivary duct carcinomas (SDCs) are an uncommon group of malignant salivary gland tumours characterised by ductal formations and central necrosis, histologically resembling high grade ductal ca...

Salivary Duct Carcinoma of the Larynx: Report of a Rare Case

Salivary duct carcinomas are primarily high-grade, aggressive malignancies that affect men in the fifth and sixth decades of life. These tumors are usually found in the major salivary glands; rarely do they originate in the minor salivary glands. The distinctive feature of these neoplasms is their remarkable histologic resemblance to infiltrating ductal carcinomas of the mammary gland; both types of tumor feature epithelial and myoepithelial cells arrayed in solid, papillary, and cribriform patterns. To the best of our knowledge, only one case of a primary salivary duct carcinoma of the larynx has been previously reported. In this article, we describe a new case, and we review the literature on salivary duct carcinomas.

Cytologic characteristics and histomorphologic correlations of 21 salivary duct carcinomas.

Fine-needle samplings (FNS) of 21 salivary duct carcinomas, histologically correlated, including 19 primaries, one local recurrence, and one lymph node metastasis from 19 patients, are reported. Cytologic diagnosis of high-grade adenocarcinoma was established in 15 (71%). Five (24%) cases were misclassified as high-grade mucoepidermoid carcinomas and one (5%) as squamous-cell carcinoma. The histologic evaluation in all cases showed cytomorphologic features resembling mammary duct carcinoma with marked cytonuclear atypia and occasional oncocytic appearance. Our cytohistologic correlations indicate that irregular clusters of high-grade adenocarcinoma cells with necrotic background and oncocytic features suggest a cytologic diagnosis of either primary salivary duct carcinoma or metastatic mammary carcinoma.

Cytologic characteristics and histomorphologic correlations of 21 salivary duct carcinomas

Fine-needle samplings (FNS) of 21 salivary duct carcinomas, histologically correlated, including 19 primaries, one local recurrence, and one lymph node metastasis from 19 patients, are reported. Cytologic diagnosis of high-grade adenocarcinoma was established in 15 (71%). Five (24%) cases were misclassified as high-grade mucoepidermoid carcinomas and one (5%) as squamous-cell carcinoma. The histologic evaluation in all cases showed cytomorphologic features resembling mammary duct carcinoma with marked cytonuclear atypia and occasional oncocytic appearance. Our cytohistologic correlations indicate that irregular clusters of high-grade adenocarcinoma cells with necrotic background and oncocytic features suggest a cytologic diagnosis of either primary salivary duct carcinoma or metastatic mammary carcinoma. Diagn. Cytopathol. 1998;19:333–337. © 1998 Wiley-Liss, Inc.

Salivary duct carcinoma.

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