Salivary Gland Pleomorphic Adenoma Research Articles

Immunohistochemical Evaluation of Epidermal Growth Factor Receptor (EGFR), MMP-2 and Heparanase in Pleomorphic Adenoma of Salivary Glands

Background: Salivary gland tumors are morphologically and clinically diverse group of neoplasms .The most common benign tumor is the pleomorphic adenoma, it contains the epithelial, myoepithelial and mesenchymal component, with variable morphological patterns. Epidermal growth factor receptor (EGFR) is a 170 KD glycoprotein which has a tyrosine kinase activity. It is found at abnormally high levels on the surface of many types of cells, so these cells may divide excessively in the presence of epidermal growth factor.MMP-2 is a widely studied matrix metalloproteinase which participates in extracellular matrix (ECM) degradation, having a wide range of substrates and able to degrade type I, IV, V, VII and X collagens, laminin, elastin, fibronectin and proteoglycans. Heparanase (HPA) is an endo-β-D-glucuronidase that has the activity of cleaving heparan sulfate (HS) side chains of heparan sulfate proteoglycans (HSPGs), the major proteoglycans of the extracellular matrix (ECM) and basement membrane (BM) which play a key role in preventing tumor cells invasion and metastasis. Aims of the study: This study aimed to evaluate the expression of EGFR, MMP-2 and heparanase in pleomorphic adenoma of salivary glands and to correlate the expression of the aforementioned biomarkers with the clinical parameters, histological subtypes and components, and with each other as well. Materials and methods: Twenty five paraffin blocks of pleomorphic adenoma were included in this study. Sections immunohistochemically stained with anti EGFR, anti MMP-2 and anti heparanase monoclonal antibodies (Mabs). Results: Positive EGFR, MMP-2 and hepranase immunohistochemical expression was found in 22 (88%), 14(56%) and 21 (84%) of the studied cases respectively. Statistically non- significant correlation was found among the aforementioned markers with each other, and between the markers and any of the clinical parameters and histological classifications, except a statistically highly significant negative correlation revealed regarding EGFR expression with the squamous cells of epithelial component (p =0.001) and a highly significant positive correlation found regarding MMP-2 expression with the chondroid stromal component (0.003). Conclusions: Histological variation of pleomorphic adenoma has no influence on its biological behavior concerning EGFR, MMP-2 and heparanase expression. The immunoscores reorded in this study are expected to contribute to a better understanding of the biological behavior of PA.

An unusual pleomorphic adenoma

Pleomorphic adenoma is the most common neoplasm in major and minor salivary glands. It constitutes approximately 90% of all benign salivary gland lesions and the parotid is the most affected location. When the minor salivary glands are affected, it mostly occurs at the junction of the hard and soft palates. The diagnosis is complex because of the great histological variety and biological behavior of this tumor, a histopathological examination being essential. The recommended treatment is surgical excision. For lesions located superficially in the parotid gland, superficial parotidectomy - identifying and preserving the facial nerve - is necessary. Lesions in the palate or gums sometimes demand a margin of safety, being excised below the periosteum, including the overlying mucosa. With correct surgical removal, the prognosis is excellent. The aim of this study is to report a case of an unusual minor salivary gland pleomorphic adenoma in the hard palate, describing the most important aspects of this pathology.

Diagnostic Utility of PLAG1 Immunohistochemical Determination in Salivary Gland Tumors

PLAG1 (pleomorphic adenoma gene 1) is a proto-oncogene whose overexpression is a crucial oncogenic event in salivary gland pleomorphic adenomas (PA), and in carcinoma ex-PA. The aim of the present study is to evaluate the sensitivity and the specificity of PLAG1 as a marker in the differential diagnosis of salivary gland benign and malignant tumors. We examined 101 cases, including 36 PAs, 8 myoepitheliomas, 3 basal cell adenomas, and 1 canalicular adenoma among benign tumors; 16 mucoepidermoid carcinomas, 10 adenoid cystic carcinomas, 8 acinic cell carcinomas, 8 polymorphous low-grade adenocarcinomas, 7 salivary duct carcinoma, and 4 epithelial-myoepithelial carcinoma among malignant tumors. PLAG1 was diffusely positive in 94.4% of PAs and in all myoepitheliomas, although with a lower staining intensity. Among malignant tumors, 2 (25%) polymorphous low-grade adenocarcinomas and 1 salivary duct carcinoma ex-PA were positive. In conclusion, PLAG1 is a marker with good specificity for PA and could be a useful diagnostic adjunct in the diagnosis of salivary gland tumors. In particular, this marker is negative in the most common salivary carcinomas, including adenoid cystic carcinoma, mucoepidermoid carcinoma, and acinic cell carcinoma. However, some mimickers of PA, like polymorphous low-grade adenocarcinoma, may show occasional positivity for PLAG1, thus limiting its diagnostic use. In addition, carcinoma ex-PA shows consistent positivity, and therefore should be considered as a diagnostic possibility in case of a malignant tumor with PLAG1 expression.

Pleomorphic adenoma of oral minor salivary glands: An investigation of its neoplastic potential based on apoptosis, mucosecretory activity and cellular proliferation

ObjectiveThe aim of this study was to investigate the neoplastic potential of the PA of minor oral salivary glands measured by apoptosis (Bcl-2, Bax and p53), mucosecretory activity (MUC1), and cellular proliferation (Ki-67). DesignThirty-one cases of PA of the oral cavity and four controls (C) taken from normal oral minor salivary glands were analyzed using the immunohistochemistry technique. The proteins were detected utilizing a semi-quantitative method (scores) as follows: (−) negative ≤5%, (+) low 6–25%, (++) moderate 26–50% and (+++) high >50% of positive tumour cells. The apoptotic indices were evaluated by the ratio Bcl-2/Bax. Non-parametric comparison and correlation tests were used for analysis. ResultsThe data showed high staining of anti-apoptotic protein Bcl-2 in both groups (PA=57.9%; C=67.7%) and a significantly lower expression of pro-apoptotic protein Bax (PA=22.7%; C=97.7%) and MUC1 (PA=14%; C=82.3%) in PA than in C (p<0.001). On the other hand, a similar expression of Ki-67 and p53 proteins (≤5%) was seen in both PA and C. In PA, only 2/31 cases showed the ratio Bcl-2/Bax<1.There was no difference in cellular expression with regard to clinical variables or clinical outcome (p>0.05). ConclusionThe neoplastic potential of PA could be associated with an imbalance in apoptotic processes and a lower index of cellular proliferation. Mucosecretory activity does not play a significant role in primary PA.

Lacrimal Gland Pleomorphic Adenoma and Carcinoma ex Pleomorphic Adenoma

To study genetic alterations in lacrimal gland pleomorphic adenoma (PA) and carcinoma ex pleomorphic adenoma (Ca-ex-PA) with focus on copy number changes and expression patterns of the translocation target genes PLAG1, HMGA2, and CRTC1-MAML2 in relation to clinical data. Experimental study. A total of 36 tumors from 32 patients with lacrimal gland PA or Ca-ex-PA were included in the study. Genome wide, high-resolution array-based comparative genomic hybridization (arrayCGH) and immunohistochemistry were used to study the genomic profiles and expression patterns of the translocation targets PLAG1, HMGA2, and CRTC1-MAML2. Copy number alterations (gains/losses) and protein expression of PLAG1, HMGA2, and CRTC1-MAML2. Genome-wide arrayCGH analysis revealed normal genomic profiles in 10 of 17 PA samples. The average number of genomic imbalances per tumor was 3.25 (range, 1-7) in primary and recurrent PAs with alterations compared with 7.7 (range, 4-12) in Ca-ex-PAs. Five recurrent copy number alterations were identified in PAs, including losses of 1pter-p31.3, 6q22.1-q24.3, 8q24.22-q24.3, and 13q21.31-q21.33, and gain of 9p23-p22.3. Gain of 9p23-p22.3 also was seen in a Ca-ex-PA. In Ca-ex-PA, gain of 22q12.3-qter was the only recurrent alteration. Detailed analysis of the array data identified NFIB and PDGFB as the 2 major candidate target oncogenes that may be activated as a result of copy number gains involving 9p and 22q. Both genes have been implicated in the pathogenesis of PA and other types of salivary gland tumors. Immunohistochemical analysis revealed frequent overexpression of the translocation target gene PLAG1 in PAs and in 1 Ca-ex-PA. In contrast, overexpression of HMGA2 was observed in only a small subset of PAs. The CRTC1-MAML2 fusion oncoprotein was overexpressed in 2 mucoepidermoid Ca-ex-PAs. Lacrimal and salivary gland PAs and Ca-ex-PAs have similar genomic profiles and frequently overexpress the PLAG1 oncoprotein. Copy number gains involving 9p23-p22.3 (NFIB) and 22q12-qter (PDGFB) may be of importance for disease progression in a subset of lacrimal gland PAs.

Pleomorphic Adenoma in Retromolar Area: A Rare Case Report and Review of Literature

Pleomorphic adenomas are benign salivary gland tumors which represent about 3-10% of the neoplasms of head & neck region. They are the most common tumors comprising 50% of major & minor salivary gland tumors. The Palate is considered the most common (65%) and retromolar area uncommon (2.5%) intra oral site. A case of retromolar swelling diagnosed as pleomorphic adenoma of minor salivary glands is presented with review of literature of minor salivary gland tumors & pleomorphic adenoma.

Epithelial and stromal patterns of pleomorphic adenoma of minor salivary glands: A histopathological and histochemical study.

Background:Pleomorphic adenoma (PA) accounts for 45–74% of all the salivary gland neoplasms, of which 40–70% are present in minor salivary glands. Studies have depicted variations in histological typing and classification of these tumors. Its pleomorphism is attributed to the cytological differentiations of the epithelial components and the diverse stromal components. Biochemical investigations of saliva have revealed “mucins” to be its main component. Mucins reflect in their composition, the functional state of the mucosa, both in health and disease. Many reviews on histochemical classification and identification have been put forward to explain the intricacies of mucins; however, no attempts have been made to classify salivary gland tumors based on their mucin profiles and assess its prognostic significance. Thus, this study was executed to analyze the clinical, histopathological and histochemical behavior of PA of minor salivary glands and decipher a correlation.Materials and Methods:Twenty-six diagnosed cases of PA of minor salivary glands and five controls of normal minor salivary glands of the hard palate were included in the study. Blocks were retrieved, sectioned and stained with hematoxylin and eosin (H and E) stain as well as combined Alcian blue (AB)-periodic acid-Schiff (PAS) stains.Results:The stained slides revealed an array of epithelial and stromal patterns and varying heterogeneity of mucin expression of normal and neoplastic minor salivary glands.Conclusion:The study elucidated the role of mucins in tumorigenesis and its prognostic implications.

Pleomorphic Adenoma of Palate- A Case Report with CT and CBCT Features

Pleomorphic adenoma (PA) can be defined as a benign mixed tumor composed of epithelial and myoepithelial cells arranged with wide cytomorphologic and architectural diversity and morphological patterns, demarcated from surrounding tissues by fibrous capsule. PA is one of the salivary gland tumors affecting both major and minor salivary glands. Parotid gland is the most commonly affected of the major group, and palate is the most common site of the minor salivary glands affected. The tumor has 3 components: an epithelial cell component; a myoepithelial cell component; and a mesenchymal component. The identification of these 3 components, which may vary quantitatively from one tumor to another, is essential to the recognition of pleomorphic adenoma. The tumor is also known as a benign mixed tumor. When these lesions affects the minor salivary glands on palate and if there is any involvement of the surrounding structures like maxillary antrum and nasal floor, then pre-operative imaging of these lesions is mandatory by 3-dimensional imaging modalities like CT or CBCT to evaluate the exact depth and the dimensions of the lesion. Following case of pleomorphic adenoma of palatal salivary glands which was evaluated with CT as well as CBCT pre- operatively.

Upper Lip Pleomorphic Adenoma: Comparison of Reported Cases between 1990 and 2012

Introduction: Pleomorphic adenoma of the upper lip is a rare entity and its diagnosis requires a high index of suspicion. The aim of this study was to review the reported cases of adenoma (PA) of the upper lip. Methods: This study was performed on the basis of the clinical features of 10 well-documented reported cases of the upper lip adenomas from 1990 to 2012 which have been indexed in the PubMed. The search strategy based on MeSH keywords included salivary gland tumor, salivary gland cancer, pleomorphic adenoma, and mixed tumor. In the clinical records the following data have been considered: Age, sex, clinical view, complaint time, site, size, texture, pathological view, treatment, recurrence rate, symptom and follow-up period. Results: Of the 11 reported cases of PA, 7 (63.7%) were female and 4 (36.3%) were male, with age ranging from 12 to 65 years. 50% of the patients were between 35 and 55 years of age. Only 3 (27.2%) of cases were younger than 20. The main clinical presentation of lesion in all cases was a submucosal nodule. There was a large interval between the first symptoms and diagnosis. The size of the lesions were between 1 and 3 cm. Involvement of the right half of the upper lip was more common than the left side. 63.6% of the lesions showed a firm consistency and bone formation was seen in one (9.09%) case. The follow-up period ranged from 5 to 48 months. There was no evidence of recurrence in any of the reported cases. Conclusion: Although rare, adenoma should be considered as a differential diagnosis for the swellings in the upper lip. PA has a potential for malignant transformation. Therefore this entity should be evaluated carefully by all clinicians.

The Increased P16 and Cyclin D1 Expression in Recurrence of Salivary Gland Pleomorphic Adenoma

The Increased P16 and Cyclin D1 Expression in Recurrence of Salivary Gland Pleomorphic Adenoma

CRTC1-MAML2 and CRTC3-MAML2 Fusions Were Not Detected in Metaplastic Warthin Tumor and Metaplastic Pleomorphic Adenoma of Salivary Glands

The recurrent translocations t(11;19) and t(11;15) resulting in CRTC1-MAML2 or CRTC3-MAML2 fusion oncogenes, respectively, are identified in a large proportion of mucoepidermoid carcinomas (MECs) of the salivary gland and have impact on prognosis. However, there are conflicting data on the specificity of this translocation, in particular, on its putative occurrence in Warthin tumor (WT) of the parotid gland as reported in few previous cases. It was speculated that extensive squamous metaplasia could explain the presence of t(11;19) translocation in a subset of WTs. We evaluated 76 salivary gland tumors, including 16 cases of metaplastic WT and 8 cases of pleomorphic adenoma (PA) with squamous and/or mucinous metaplasia, extensive enough morphologically to mimic MEC. Detection of CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts and MAML2 gene break was performed using nested reverse transcription-polymerase chain reaction and fluorescence in situ hybridization (FISH), respectively. None of 16 analyzed metaplastic WTs showed positivity for fusion transcripts CRTC1-MAML2 or CRTC3-MAML2, and none showed rearrangement of the MAML2 gene by FISH. Similarly, we did not detect these transcripts or break of MAML2 gene in any case of PA with extensive squamous/mucinous metaplasia. For comparison, 40 cases of low-grade MEC were also evaluated. CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts were detected in 17 and 5 cases, respectively. The FISH method using break-apart probe demonstrated the MAML2 gene rearrangement in 25 cases of low-grade MEC. In contrast to low-grade MEC, neither metaplastic WTs nor metaplastic PAs harbored translocations t(11;19) and anticipated t(11;15) resulting in CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts, respectively, and/or MAML2 gene rearrangement.

Pleomorphic adenoma of hard palate: A report of four cases

Introduction: Pleomorphic adenoma is the most common tumor of the salivary gland. The tumor most commonly arises in the parotid or submandibular salivary glands. Infrequently, it arises from minor salivary glands. Minor salivary gland tumors are mostly malignant. Case Report: We report four cases of pleomorphic adenoma of hard palate. All four cases range from 30–45 years. All were benign. Conclusion: Pleomorphic adenoma of minor salivary gland of hard palate is a rare benign tumor. Benign tumors at this site are more common then malignant ones. Complete evalutation of patients and complete removal of the tumor must be ensured so that tumor does not recur.

RARE CASE OF MULTIFOCAL EPITHELIAL HYPERPLASIA OF ORAL MUCOSA.

Introduction: Multifocal papilloma virus epithelial hyperplasia (MPVEH) is a rare disease of the oral mucosa associated with the human papilloma viruses (HPV) 13 and 32. It occurs at any age, but children have the highest incidence. Purpose: To present a case of oral multifocal papilloma virus epithelial hyperplasia with palatal tumour and multiple metachronic primary cancers. Material and methods: The medical history shows a 60 years female patient with complaints of asymptomatic mass on the palatal mucosa, with a two years’ development. The patient has been treated surgically for previous thyroid cancer, endometrial cancer and cancer of the mammary gland. An incisional biopsy has been performed in her left buccal mucosa 10 years ago and histopathological examination confirmed the diagnosis of MPVEH. The palatal tumour was removed surgically by electroexcision and the histological result was pleomorphic adenoma of a small palatal salivary gland. Conclusion: Papillomatosis is considered as a benign neoplasm with an unpredictable course and with a low probability of malignancy.We report of an unusual case of MPVEH persistent for more than 30 years without regression and with significant impact on a patient‘s quality of life.

Pleomorphic adenoma of the minor salivary gland of the cheek

Pleomorphic adenoma is the most common tumour of the salivary gland. While the majority arises from the parotid gland, only a small percentage arises from the minor salivary glands. The cheek, however, is a rarely affected site with respect to pleomorphic adenomas of the minor salivary glands. Herein, we report a case of pleomorphic adenoma of the cheek, which presented with intraoral swelling, and conclude that complete surgical excision can be a curative treatment for this benign tumour.

Immunohistochemical Analysis of E-Cadherin Expression in Pleomorphic Adenoma and Mucoepidermoid Carcinoma of Salivary Glands

Objective: E-cadherin is a classic cadherin that plays a key role in epithelial cell adhesion. This protein is being referred to as the suppressor of proliferation and invasion. Limited studies have investigated E-cadherin expression in salivary gland neoplasms. This study sought to assess the expression of E-cadherin and its possible role in progression and invasion of salivary gland neoplasms. Methods: In this retrospective cross-sectional study, 15 samples of pleomorphic adenoma (PA) and 9 samples of mucoepidermoid carcinoma (MEC) were immunohistochemically stained for evaluation of E-cadherin expression. Degree of staining was calculated as the percentage of positively stained cell membranes out of a minimum of 1000 neoplastic cells. Results: In normal salivary gland specimens, intense membrane staining was observed around the acinar mucous and serous cells as well as the ductal cells. Myoepithelial cells were negative. In PA, intense staining was noted along the membrane of attached cells forming the ducts, islands, cellular cords and cellular sheets but the stromal myoepithelial cells were negative. In MEC, epidermoid and intermediate cells showed intense membrane staining. Mucous cells also showed membrane staining. After statistical analysis, the percentage of positive cells was found to be 82.56±11.66 and 67.4±7.24 in MEC and PA, respectively. This difference was not statistically significant (P>0.05). Conclusion: E-cadherin expression was not a suitable marker for differentiation of PA from MEC. It was only correlated with cell phenotype.

Pleomorphic adenoma of the major salivary glands: Diagnostic utility of FNAB and MRI

Pleomorphic adenoma (PA) is the most common, benign tumor of the major salivary glands. Surgical resection is the treatment of choice. Initial preoperative workup of major salivary gland neoplasms often includes fine needle aspiration biopsy (FNAB) and magnetic resonance imaging (MRI) of the head and neck. Our objective was to assess the positive predictive value of FNAB and MRI in the evaluation of PA arising from within the major salivary glands. Retrospective chart review. All patients with a FNAB diagnosis of PA of the major salivary glands and who underwent surgical excision at our institution from 2001 to 2011 were identified. FNAB slides from these cases were reviewed by a cytopathologist for findings suggestive of PA: fibrillary stroma, mesenchymal elements, plasmacytoid myoepithelial cells, epithelial cells forming ducts or tubules, and the absence of nuclear atypia. For those patients with a preoperative MRI, the MRI studies were reviewed by a neuroradiologist for findings suggestive of PA, including homogenous T2 hyperintensity, well-circumscribed borders, and solid contrast enhancement. Positive predictive value (PPV) of these specific FNAB and MRI findings were calculated using chi-squared testing. One hundred forty-six patients met inclusion criteria, and 68 had preoperative MRI. PPV of a FNAB diagnosis of PA was 97.8%. Characteristic features of PA on FNAB (fibrillary stroma, mesenchymal elements, plasmacytoid myoepithelial cells, epithelial cells forming ducts or tubules, and the absence of nuclear atypia) and MRI (homogenous T2 hyperintensity, well-circumscribed borders, and solid contrast enhancement) all demonstrated PPVs of 95% or greater in patients with FNA diagnosis of PA. PPV of a FNAB diagnosis of PA in the major salivary glands is high. Among patients with a FNAB diagnosis of PA, specific MRI characteristics also have a high PPV. The diagnostic accuracy of these studies in combination allows for the confident preoperative diagnosis of PA.

Juvenile Pleomorphic adenoma: A case report

Pleomorphic adenoma is a benign salivary gland tumor that represents less than 5% of benign tumors in childhood. World literature suggests salivary gland tumors account for less than 3% of the head and neck tumors and benign Pleomorphic adenoma of minor salivary glands arising de novo is very rare. Here we report a case of Pleomorphic adenoma of minor salivary glands occurring on the palate of 12-year-old female.Salivary glands may present with a diverse range of lesions presenting a challenge to even the most experienced clinician and pathologist. Resection with surrounding dispensable normal tissues is the key to successful treatment of such tumors.

CD24 and CD44 in salivary gland pleomorphic adenoma and in human salivary gland morphogenesis: differential markers of glandular structure or stem cell indicators?

Salivary gland neoplasms originate from salivary gland compartments, to which they are histologically related. Pleomorphic adenoma (PA) is a benign salivary gland neoplasm that comprises epithelial and myoepithelial cells and a complex stroma, whose structure, architecture and origin (from intercalated ducts) suggest stem cell participation. We compared the expression of CD24 and CD44 in PA and in developing human salivary glands to investigate whether these markers can be considered as cancer stem cell markers. One hundred and one cases of PA and salivary gland specimens from 20 human fetuses were examined by immunohistochemistry and real-time reverse transcription polymerase chain reaction (RT-PCR). All PAs were positive for CD24 and CD44 by immunohistochemistry: neoplastic luminal structures were positive for CD24; modified myoepithelial cells were positive for CD44. In fetal salivary glands, these markers were restricted to the intercalated duct region. Real-time RT-PCR assays detected increased expression of CD44, but not CD24, in PA specimens in comparison with normal salivary gland controls. PA and stem cells share the expression of CD24 and CD44; their value as markers of neoplastic cell multipotency and the implications of their expression for tumour behaviour are yet to be determined.

Pleomorphic adenoma of minor salivary gland: a case report

World literature suggests salivary gland tumors account for less than 3% of the head and neck tumors and benign pleomorphic adenoma of minor salivary glands arising de novo is very rare. Objective, case report and conclusion: A case of pleomorphic adenoma of minor salivary glands in the buccal mucosa in a 55 year-old female is discussed. It includes review of literature, clinical features, histopathology, radiological findings and treatment of the tumor, with emphasis on diagnosis. The salivary glands may present with a diverse range of lesions presenting a challenge to even the most experienced clinician and pathologist. Resection with surrounding dispensable normal tissues is the key to successful treatment of such tumors.

Immunohistochemical expression of metallothionein in pleomorphic adenoma of minor salivary glands: A role in the control of apoptosis?

Pleomorphic adenoma is the most common benign neoplasm of both the major and minor salivary glands. The histological features are diverse and are characterized by the involvement of epithelial–myoepithelial structures. Metallothionein is a cysteine-rich protein present in myoepithelial cells of several benign and malignant neoplasms. The function of metallothionein is associated with DNA protection, oxidative stress and apoptosis. The purpose of this study was to evaluate the expression of metallothionein in pleomorphic adenoma of the minor salivary glands. Additionally, we investigated the association of the clinicopathological features of the lesions with metallothionein, specifically its association with Bcl-2, in an attempt to evaluate the role of metallothionein in the control of apoptosis. Thirty-five cases of pleomorphic adenoma were selected and immunohistochemistry was performed for metallothionein and Bcl-2 proteins. The proteins were quantified by the Quickscore method. The samples showed epidemiological characteristics similar to those described in the literature. We did not find an association between the clinicopathological characteristics of pleomorphic adenomas and the proteins studied, but an association between metallothionein and Bcl-2 was demonstrated. The results suggest that metallothionein may have a role in the control of apoptosis in pleomorphic adenoma.