Histogenesis Of Salivary Gland Tumors Research Articles

Comparison of Diagnostic Reliability of p63 and Smooth Muscle Actin in Salivary Gland Neoplasms.

Salivary gland neoplasms pose considerable diagnostic difficulty owing to their diverse histological features in individual lesions and the presence of a number of types and variants & similar histological features with other tumor entities. Myoepithelial and basal cells play a significant role in the pathogenesis of salivary gland neoplasm. p63 and smooth muscle actin are more reliable markers for identifying these cells and not studied much comparing their reliability in the diagnosis of salivary gland neoplasms. Hence, the aim of this study is to evaluate and compare the diagnostic reliability of immunohistochemical markers such as p63 and smooth muscle actin (SMA) in the diagnosis of various benign and malignant salivary gland neoplasms. The study comprises of 18 samples categorized into two groups: Group I comprised 9 cases, of which 4 cases were Pleomorphic adenoma, 2 cases were Myoepithelioma, 2 cases of Basal cell adenoma and 1 case was Warthin's tumor; and Group II consisted of 9cases, of which 3 was Mucoepidermoid carcinoma, 1 cases were Myoepithelial carcinoma and 5 cases were Adenoid cystic carcinoma. The selected cases were subjected to immunohistochemistry (IHC) procedure to assess the expression pattern of p63 and smooth muscle actin. The obtained data was analysed statistically by using Mann-Whitney test. In SMA, strong positivity for epithelial and connective tissue components of benign salivary neoplasm is about 22.2%respectively. In malignant salivary neoplasm, SMA was strongly positive for the epithelial and connective tissue component of about 77.7% and 88.8% cases respectively. The difference in the connective tissue components was found to be statistically significant (U = 24, P = 0.032). P63 was strongly positive for the epithelial and connective tissue component of benign salivary neoplasm of about 33.3% and 11.1% cases respectively.In malignant salivary neoplasm, p63 was strongly positive for the epithelial component of about 66.6% cases and connective tissue is completely negative. Alpha-SMA can be utilized as reliable IHC markers for salivary gland neoplasms due to its diagnostic importance in tumors with myoepithelial origin indicative of the histogenesis of salivary gland tumors and even p63 can be used as specific markers for differentiation of malignant salivary gland tumors.

PLAG1 enhances the stemness profiles of acinar cells in normal human salivary glands in a cell type-specific manner

ObjectivesDetails of the histogenesis of salivary gland tumors are largely unknown. The oncogenic role of PLAG1 in the salivary gland has been demonstrated in vivo. Herein, we demonstrate PLAG1 roles in the acinar and ductal cells of normal human salivary glands to clarify the early events that occur during the histogenesis of salivary gland tumors. MethodsNormal salivary gland cells with acinar and ductal phenotypes were transfected with PLAG1 plasmid DNA. Subsequently, PLAG1 overexpressed and mock cells were examined by cell proliferation, transwell migration, and salisphere formation assays. Differentiation and salivary and pluripotent stem cell marker expression levels were evaluated by quantitative reverse transcription-polymerase chain reaction and immunofluorescence. Alterations in transcriptional expressions were investigated via cap analysis of gene expression with gene-enrichment and functional annotation analysis. ResultsPLAG1 promoted cell proliferation and transwell migration in the acinar and ductal cells, and markedly enhanced the stemness profiles and luminal cell-like profiles in acinar cells; the stemness profiles were partially increased in the ductal cells. ConclusionPLAG1 enhanced the stemness profiles in the acinar cells of normal human salivary glands in a cell type-specific manner. Thus, it may be involved in salivary gland tumorigenesis by increasing the stemness character of the normal salivary gland cells.

Elucidation of histogenesis of salivary gland tumors

Elucidation of histogenesis of salivary gland tumors

Utility of smooth muscle actin and CD117 as reliable markers in the diagnosis of salivary gland neoplasms.

Objective:The aim of this study is to analyze the utility of immunohistochemical markers such as CD117 and smooth muscle actin (SMA) in the diagnosis of various benign and malignant salivary gland neoplasms.Materials and Methods:The study comprises 17 samples categorized into three groups: Group I consisted of 5 histopathologically normal salivary gland tissue; Group II comprised 7 cases, of which 3 cases were pleomorphic adenoma, 3 cases were myoepithelioma and 1 case was Warthin's tumor; and Group III consisted of 5 cases, of which 1 was mucoepidermoid carcinoma and 4 cases were adenoid cystic carcinoma. The selected cases were subjected to immunohistochemistry (IHC) procedure to assess the expression pattern of CD117 and SMA.Results:In SMA, 85.8% showed severe-to-moderate intense expression among the tumor cells in benign salivary gland tumor. All the 5 malignant tumors showed the expression of SMA and 3 cases demonstrated severe expression among the tumor cells. An intense expression pattern of SMA was observed in both benign and malignant neoplasms in the periphery and stromal components of the tumor. Only two cases were positive for CD117, and connective tissue components were completely negative in both malignant and benign salivary gland neoplasms.Conclusion:Alpha-SMA can be utilized as reliable IHC markers for salivary gland neoplasms due to its diagnostic importance in tumors with myoepithelial origin indicative of the histogenesis of salivary gland tumors.

SOX10 is a novel marker of acinus and intercalated duct differentiation in salivary gland tumors: a clue to the histogenesis for tumor diagnosis

Salivary gland tumors are relatively rare and morphologically diverse and heterogeneous tumors; therefore, histogenesis-based tumor markers are sorely needed to aid in diagnosing and determining the cell type of origin. SRY-related HMG-box 10 (SOX10) protein is a transcription factor known to be crucial in the specification of the neural crest and maintenance of Schwann cells and melanocytes. In addition, positive expression has also been implicated in the major salivary gland. Here, we examined SOX10 expression in various salivary gland tumors to correlate this expression with myoepithelial markers. Overall, 76 malignant and 14 benign tumors were examined. SOX10 expression clearly delineated two distinct subtypes of human salivary gland tumors; acinic cell carcinomas, adenoid cystic carcinomas, epithelial-myoepithelial carcinomas, myoepithelial carcinomas, and pleomorphic adenomas, including the pleomorphic adenoma component of carcinoma, were SOX10 positive, while salivary duct carcinomas, mucoepidermoid carcinomas, an oncocytic carcinoma, Oncocytomas, and Warthin tumors were SOX10 negative. Also, SOX10 was expressed in solid-type or non-specific morphology salivary gland tumors, but was not expressed in poorly differentiated squamous cell carcinomas. In normal human salivary gland tissue, SOX10 expression was specific to the nuclei of acini and both luminal and abluminal cells of intercalated ducts but not in other sites. Moreover, the murine model suggested that SOX10 continued to be expressed from the developmental stage to adulthood in the acinar and both luminal and abluminal intercalated ducts in the major salivary gland. Thus, SOX10 is a novel marker for diagnosing and understanding the histogenesis of salivary gland tumors.

Histogenesis of salivary gland neoplasms

Salivary gland tumors are one of the most complex and relatively rare group of lesions encountered in oral pathology practice. Their complexity is attributed to heterogeneity of the cells of origin of these lesions. The problem is compounded by the ability of these cells to differentiate and modify into various morphological subtypes resulting in a myraid of histomorphological patterns. This also leads to a frequent overlap of microscopic features among various neoplasms and sometimes even between benign and malignant lesions causing significant diagnostic dilemma which sometimes may even not be resolved by immunohistochemical studies. Despite this the knowledge of histogenesis and morhogenetic concepts of salivary gland tumorigenesis greatly helps the pathologist in classifying these lesions as well as determining the prognosis. It will also help in development of newer strategies for differentiating these lesions and making an early diagnosis. The present article is aimed at reviewing and summarizing the current concepts regarding the histogenesis of salivary gland tumors and their relevance to routine diagnosis and classification of these lesions.

A study of HER-2/neu expression and silver binding nucleolar organizer regions (Ag NORs) in perilesional normal salivary gland tissue

Salivary gland neoplasms comprise phenotypically and biologically diverse lesions of uncertain histogenesis. The present study was carried out to assess the immunohistochemical expression of HER-2/neu protein and of silver binding nucleolar organizer regions in normal salivary tissue. Twenty paraffin blocks of salivary tumors containing surrounding normal salivary tissue were used in the study. One section was processed to investigate HER-2/neu protein expression and another section was stained to assess the mean Ag NOR counts in normal salivary tissue. Only two cases of the studied normal salivary tissue showed HER-2/neu expression (10%), which was expressed only in ductal cells with 4.2±2.1 mean number of reactive cells per five high power fields (HPFs). Statistically significant (P=0.01) higher mean Ag NOR counts in ductal (2±0.83) than in acinar cells (1.2±0.01) of normal salivary tissue were found. It was concluded from the data of the present study that ductal cells of normal salivary tissue are a proliferative pool and an oncogenic target which plays an important role in the histogenesis of salivary gland tumors.

Adenomatous ductal proliferation of the salivary gland

Objective: The objective of this study is to report a series of patients with adenomatous ductal proliferation of the salivary gland and to investigate the nature and histogenesis of this process. Study Design: The histologic and immunohistochemical studies of 13 patients with adenomatous ductal proliferation of the salivary gland were performed. Results: Ten cases coexisted with other diseases, such as salivary gland tumor or chronic parotitis. Most of the lesions were limited to 1 or 2 lobules and showed prominent ductal proliferation with some acinar cell complexes. The proliferative ducts had a compact growth pattern with little stroma. Dedifferentiation of acinar cells, identified by the loss of their secretory granules and appearing similar to intercalated duct epithelium, was seen in the early stages of adenomatous ductal proliferation. Conclusion: Acinar cells play a role in the histogenesis of salivary gland tumors because acinar cells clearly participate in the formation of the proliferative ducts. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:215-21)

Histogenesis and development of membranous basal cell adenoma

The histogenesis of salivary gland tumors remains controversial. A histologic and immunohistochemical study was carried out on 12 cases of membranous basal cell adenoma in the salivary glands to investigate its histogenesis and development. In 4 cases, multiple focal proliferations of striated ducts in the surrounding salivary gland, which were conspicuous, allowed tracing of the development of the tumors from their origin. The earliest changes were characterized by hyperplasia of the basal cells of striated ducts. Continuous ductal proliferation led to the formation of microadenomas. The observations suggest that proliferating basal cells of striated ducts apparently participate in and play a main role in the histogenesis of some membranous basal cell adenomas of the salivary glands.

Primary Epithelial Tumors of Salivary Glands.Histomorphological and Immunohistochemical Implications.

The predominant amount of research dealing with salivary gland tumors has been the histogenesis of different epithelial tumors and supplementally immunohistochemical and ultrastructural assessments. Salivary gland tumors, both benign and malignant, showed most heterogeneity of histopathology and histochemistry that considered biological roles of epithelial-mesenchymal interactions as biosynthesis of extracellular matrix proteins. Many primary salivary gland tumors histologically consist of most epithelial structures associated with modified or neoplastic myoepithelial cells which have been recognized to be complex properties of epithelial, mesenchymal and other structural components, although normal myoepithelial cells showed more simple properties. Recently, modified or neoplastic myoepithelial cells in salivary gland tumors were not shown to originate from myoepithelial cells and were possible ductal cells in origin. However those uncomprehensive or non-distinct properties of histogenetic concepts in human salivary gland tumors can not be instead of animal studies. Moreover rodent submandibular glands have shown specific structures as granular convoluted tubules which are the source of growth factors or biologically active peptides, and human specimens may have a possibility to synthesize or produce growth factors. Thus the present review deals with critical evidence or possible identification of specific target subjects during histogenesis of salivary gland tumors, as well as different histologic types of tumor lesions without common classification. With the continued interest of salivary gland research under pathologic implication, unique systems for identification or molecular manipulations of salivary gland tumors may provide new opportunities in the health sciences.

An unusual parotid tumor with histogenetic implications for salivary gland neoplasms

This case report describes an unusual parotid salivary gland tumor in which major proliferating elements arise in relation to well-differentiated, branching ducts. Both light and electron microscopic examination indicates that these ducts are formed by two distinct cell layers, an inner row of luminal epithelial cells and an outer layer of modified myoepithelial cells. It is from this outer layer of cells that discrete clusters of uniform basaloid cells develop. Although the majority of basaloid nests were relatively compact, a few showed a small number of clear, slightly widened, intercellular spaces which, ultrastructurally, were lined with basal lamina. Particularly in one area of the lesion, clusters of basaloid cells showed increasing numbers and sizes of these intercellular spaces with the gradual formation of an adenoid cystic pattern of differentiation. Even in this situation, however, luminal epithelial cells forming ducts could still be identified. The bidirectional cellular differentiation, the origin of basaloid clusters in relation to modified myoepithelial cells, and the mode of development of intercellular spaces resulting in an adenoid cystic pattern all have important implications for the histogenesis of salivary gland tumors.

Histogenesis of Salivary Gland Neoplasms

In an attempt to explain the histogenesis of salivary gland tumors, a bicellular theory of origin has been presented. This theory is supported by indirect evidence from light and electron microscopy. Two cells, the excretory duct reserve cell and the intercalated duct reserve cell, are presented as the hypothetical cells of origin for salivary gland neoplasms. It is argued that the excretory duct reserve cell gives rise to squamous cell carcinomas and mucoepidermoid carcinomas, and that the intercalated duct reserve cell gives rise to all others. It It is also shown that myoepithelial cells are responsible in part for the wide histologic variation of these neoplasms.