Salivary Gland Pleomorphic Adenoma Research Articles

Pleomorphic Adenoma of the Sublingual Salivary Gland - A Rare Occurrence

Pleomorphic Adenoma of the Sublingual Salivary Gland - A Rare Occurrence

Pleomorphic adenoma of salivary glands: common and uncommon CT and MR imaging features.

Pleomorphic adenoma (PA) is the most common salivary gland tumor and is characterized by cytomorphological and architectural diversity. On CT and MR images, PAs are shown as well-defined lesions occasionally accompanied by characteristic lobulated contours. On T2-weighted images, typical PAs show marked hyperintensity, which reflects the abundant myxochondroid stroma, with a hypointense rim indicating the fibrous capsule. However, intratumoral signal intensity varies according to the cellular density, proportion of epithelial and stromal components, and type of stromal components. In addition, a variety of secondary histological changes, including fibrosis, lipometaplasia, ossification, cystic degeneration, and infarction, occur rarely in PAs; therefore, they are associated with difficulty in differential diagnosis from other salivary gland tumors. This review article describes the common and uncommon CT and MR imaging features of PA of the salivary glands.

HISTOPATHOLOGICAL CHARACTERISTICS OF PLEOMORPHIC ADENOMA; A RETROSPECTIVE ANALYSIS OF 120 CASES

Background: The salivary gland pleomorphic adenoma (PA) is a benign epithelial neoplasm, histologically characterized by a great diversity of morphological aspects. It is the most common neoplasm of salivary gland origin. Objective: Studying the histopathological characteristics of PA with special attention to the various morphological features of the epithelial cells and stromal components of this neoplasm. Methods: Hematoxylin and Eosin (H&E) stained tissue sections of 120 cases of PA were reviewed. The tumors were classified according to their histological subtypes as described by Seifert et al. The epithelial components were analyzed considering the type of cells and the morphological pattern. The stromal components were analyzed according to the presence of myxoid, hyaline, chondroid or calcified tissue. Results: This study revealed that most of the tumors were located in the parotid gland (44%). Myxoid or stroma-rich was the most frequent histological subtype (43%). Plasmacytoid cells were the most commonly seen epithelial component (100%), followed by cuboidal cells in (80%) of the cases. Trabecular pattern was the predominant epithelial morphological pattern (90 %), and the myxoid component was the most frequent stromal component (80%). Conclusion: PA of the salivary glands demonstrates a wide variety of cells, stromal components, and morphological characteristics. Since it is the most frequent salivary gland neoplasm that can resemble other salivary gland tumors, the knowledge about these variations is essential for a correct diagnosis. Keywords: Histopathology, pleomorphic adenoma, salivary gland neoplasms Citation: Sarkis SA, Al-Drobie BF, MajeedGH, Al-Marzooq TJM.Histopathological characteristics of pleomorphic adenoma; a retrospective analysis of 120 cases. Iraqi JMS. 2018; Vol. 16(1): 84-91. doi: 10.22578/IJMS.16.1.12

Cripto-1 is overexpressed in carcinoma ex pleomorphic adenoma of salivary gland.

Cripto-1 is a member of the epidermal growth factor-Cripto-1/FRL-1/Cryptic family. Besides being critical for early embryonic development, Cripto-1 is also associated with the development and behavior of several cancers. We analyzed the immunoexpression of Cripto-1 in normal salivary glands (NSGs), pleomorphic adenomas (PAs), and carcinoma ex pleomorphic adenomas (CaExPAs) of salivary glands. A total of 12 NSGs, 16 PAs and 12 CaExPAs underwent immunohistochemical study by the polymeric biotin-free technique. Immunopositive cells were evaluated semiquantitatively (scores 0-3). For statistical analysis, Mann-Whitney and Kruskal-Wallis tests were performed and a significance level of p ≤ 0.05 was established. Most CaExPAs (n = 10) were strong positive (score 3) for Cripto-1, and only three cases of PAs and two specimens of NSGs exhibited some expression (score 1), being statistically significant these findings (p < 0.001). No difference between the expression of this protein in tumors of major and minor salivary glands was observed. Overexpression was found mainly in cases of CaExPAs with invasive growth (n = 8) when compared to those without capsular invasion (intracapsular pattern) (p = 0.036). Patients with or without lymph node metastasis showed no difference (p = 0.294). The results revealed a significantly higher expression of Cripto-1 in CaExPA compared to PA and NSG, suggesting this protein is possibly deregulated in PA malignant transformation. Furthermore, the increased expression of this protein is associated with a more aggressive behavior (invasive growth) in salivary gland tumors.

Assessment of CTNNB1 gene mutations and β-catenin immunoexpression in salivary gland pleomorphic adenomas and adenoid cystic carcinomas.

β-Catenin exerts multiple functions in several neoplasms, playing a major role in cell signaling and tumor progression. This study analyzed possible CTNNB1 mutations in salivary gland pleomorphic adenomas (PAs) and adenoid cystic carcinomas (ACCs), and determined possible differences in β-catenin immunoexpression in relation to these mutations, as well as histopathological aspects of these tumors. Twenty-four PAs (15 cell-rich and 9 cell-poor tumors) and 24 ACCs (10 tubular, 8 cribriform, and 6 solid tumors) were selected for the analysis of β-catenin distribution and cellular localization. Furthermore, β-catenin expression was evaluated using the H-score scoring system. Mutations in CTNNB1 exon 3 were investigated by the single-strand conformational polymorphism test. Diffuse β-catenin expression was more frequently observed in ACCs compared to PAs (P = 0.008). No significant difference in β-catenin cellular localization was observed between these tumors (P = 0.098). Comparisons between PA and ACC cases revealed a higher median H-score in the latter (P = 0.036). Cell-rich PAs exhibited a trend for higher H-score than cell-poor tumors (P = 0.060), whereas lower H-scores were observed in cribriform ACCs when compared to tubular and solid ACCs (P = 0.042). Mutations in CTNNB1 were observed in 6 PAs and 7 ACCs, with no significant difference in H-scores for β-catenin according to mutation status (P = 0.135). β-Catenin is important in the pathogenesis of salivary gland PAs and ACCs. In addition, CTNNB1 exon 3 mutations do not seem to significantly influence β-catenin cytoplasmic/membranous expression or nuclear translocation in these tumors.

Institutional protocol and retrospective analysis of 23 cases of palatal pleomorphic adenoma at a Nigerian tertiary hospital

Background: Pleomorphic adenoma (PA) of the minor salivary gland is the most common benign tumour of the minor salivary glands as majority of the tumours of the minor salivary gland are malignant. The most common site of occurrence of PA of the minor salivary gland is the palate. The major challenges in the surgical management of these cases include management of associated primary haemorrhage and prevention of recurrence. This study documents the experiences gained from management of 23 cases at a Nigerian tertiary hospital. Methods: A retrospective review of patients who had surgical excision of histologically diagnosed PA of the palate was conducted amongst patients attending maxillofacial outpatient clinic over a 5-year period (January 2012–December 2016). The information retrieved from the patients' case files included the sociodemographics as well as clinical characteristics. The data were analysed using the Statistical package for the Social Sciences (SPSS) software version 15.0 (SPSS Inc., Chicago, IL, USA). Results: A total of 23 cases of PA were operated in 23 patients. Fourteen of these were female, while 9 were male, giving a gender ratio of 1:1.5 (m:f). Ages of the patients ranged from 19 to 51 years, with a mean age (standard deviation) at 33 (7.1) years. Clinical symptoms varied from painless asymptomatic palatal swelling to complaints of mild discomfort. The sizes of the lesions ranged from 2 cm to 10 cm in the widest diameter (mean 4.6 ± 3.2 cm). The duration of hospital stay ranged from 7 days to 14 days (mean 5 ± 4.1 days) which was counted from the date of admission to the date of discharge. Surgical treatment in all cases was excision with a margin of grossly intact tissue as well as overlying mucosa. Conclusion: PA of minor salivary glands of the palate can be complicated by an eventful primary haemorrhage and tumour recurrence. Ligation of related vasculature and complete surgical excision will guarantee cure and uneventful surgery.

Pleomorphic Adenoma of Buccal Minor Salivary Gland: A Case Report

Salivary gland tumors are relatively uncommon tumors, accounting approximately 3-10% of head and neck neoplasm. Most of them are benign and pleomorphic adenoma is the commonest among them that involves both major (90%) and minor (10%) salivary glands. The most predominant site of pleomorphic adenoma is palate; however, it may occur in any part of oral cavity like lip, floor of mouth, tongue, tonsil, pharynx, retromolar area and nasal cavity. Mucosa of cheek (4%) is an extremely rare site. A case of 25 years young male is reported here possessing pleomorphic adenoma of buccal minor salivary gland that was presented to us with a mobile swelling over right cheek that found to be pleomorphic adenoma of buccal minor salivary gland after histopathological examination. Surgical excision was done by intra oral approach with adequate margins. Patient had an uneventful postoperative course and discharged same day on oral antibiotics.

Pleomorphic Adenoma of Salivary Glands:

Pleomorphic Adenoma of Salivary Glands:

Pleomorphic adenoma of the soft palate: A case report with literature review

Pleomorphic adenoma is a benign mixed salivary gland tumor and consists of a combination of epithelial and mesenchymal elements. The parotid and other major salivary glands are the common locations for it. Pleomorphic adenoma less frequently originates from minor salivary glands with a malignant potential in most of the cases. The present case is a pleomorphic adenoma of the minor salivary gland of soft palate in a 72-year-old male, and the tumor is large, well circumscribed, firm but still benign in nature and needs reporting.

Metastasising Pleomorphic Adenoma: A rare case report of a pleomorphic salivary adenoma with synchronous cervical lymph node metastases

Introduction: Metastatic Pleomorphic Adenoma (MPA) is a rare and controversial salivary gland neoplasm. Classified as a low-grade malignancy, benign histological features exist discordantly alongside their biological behaviour. An enigma; a benign tumour capable of distant metastases. Since 1942, there have been approximately 62 reported cases, though diagnosis is controversial considering their rarity and confounding histological interpretation. Pathogenesis is hypothesised to occur haematogenously through incomplete resection of primary PSAs or surgical disruption, aspiration of seeded tumour cells, or a lymphatic metastatic route. This is the first known case in the English-literature of an untreated minor salivary gland pleomorphic adenoma metastasising to a cervical node, demonstrating support for lymphatic dissemination.

Perfusion MR imaging detection of carcinoma arising from preexisting salivary gland pleomorphic adenoma by computer-assisted analysis of time-signal intensity maps.

Tumor perfusion can be evaluated by analyzing the time-signal intensity curve (TIC) after dynamic contrast-enhanced (DCE) MR imaging. Accordingly, TIC profiles are characteristic of some benign and malignant salivary gland tumors. A carcinoma ex pleomorphic adenoma (CXPA) arises from a long-standing pleomorphic adenoma (PA) and has a distinctive prognostic risk depending on the tumor growth potential such as invasion beyond the preexisting capsule. Differentiating CXPA from PA can be very challenging. In this study, we have attempted to discriminate CXPA from PA based on a two-dimensional TIC mapping algorithm. TIC mapping analysis was performed on 8 patients with CXPA and 20 patients with PA after dynamic contrast-enhanced (DCE) MR imaging using a 1.5-T MR system. The TIC profiles obtained were automatically categorized into 5 types based on the enhancement ratio, maximum time, and washout ratio (Type 1 TIC with flat profile, Type 2 TIC with slow uptake, Type 3 TIC with rapid uptake and a low washout ratio, Type 4 TIC with rapid uptake and a high washout ratio, and Type 5 TIC not otherwise specific). The percentage tumor areas with each of the 5 TIC types were compared between CXPAs and PAs. Stepwise differentiation and cluster analysis using multiple TIC cut-off thresholds distinguished CXPAs from PAs with 75% sensitivity, 95% specificity, 86% accuracy, and 86% positive and 90% negative predictive values, when tumors with ≤1.1% Type 1 and ≥15% Type 4, or those with ≤1.1% Type 1, ≥78.1% Type 2, ≥16.1% Type 3, and <15% Type 4, or those with >1.1% Type 1, ≥78.1% Type 2, and ≥16.1% Type 3 areas were diagnosed as CXPAs. The overall TIC profiles predicted some aggressive CXPA growth patterns. These results suggest that stepwise differentiation based on TIC mapping is helpful in differentiating CXPAs from PAs.

Apurinic/apyrimidinic endonuclease 1 (APE1) is overexpressed in malignant transformation of salivary gland pleomorphic adenoma.

DNA repair systems play a critical role in protecting the human genome against cumulative damage. The apurinic/apyrimidinic endonuclease 1 is a protein involved in DNA base excision repair and its expression still needs to be investigated in salivary gland tumors. The objective of this study is to analyze the immunoexpression of apurinic/apyrimidinic endonuclease 1 in pleomorphic adenomas and carcinomas ex pleomorphic adenomas of the salivary glands. A total of 33 pleomorphic adenomas and 16 carcinomas ex pleomorphic adenomas of the salivary glands underwent immunohistochemical study by the polymeric biotin-free technique. Immunopositive cells were analyzed quantitatively. For statistical analysis, Mann-Whitney test was performed and a significance level was set at p≤0.05. All analyzed tumors (n=49) were positive for apurinic/apyrimidinic endonuclease 1. However, there was a higher median expression in carcinomas ex pleomorphic adenomas (p<0.001). There was no difference between this protein immunoexpression and tumors of major or minor salivary gland. Overexpression was found mainly in cases of carcinomas ex pleomorphic adenomas with lymph node metastasis (p=0.002) and invasive growth (p=0.003), when compared to cases without metastasis and without capsular invasion (intracapsular pattern). Our findings revealed that apurinic/apyrimidinic endonuclease 1 is downregulated in pleomorphic adenomas and overexpressed in carcinomas ex pleomorphic adenomas, suggesting that this protein is possibly deregulated in pleomorphic adenoma malignant transformation. Furthermore, the increased expression of this protein is associated with a more aggressive behavior in carcinomas ex pleomorphic adenomas, which suggests that this protein may represent a prognostic biomarker in the studied salivary gland tumors.

Submandibular salivary gland tumors: Clinical course and outcome of a 20-year multicenter study.

The purpose of this retrospective chart review study was to review the nature and clinical course of benign and malignant submandibular gland tumors at 2 major university-affiliated tertiary medical centers. All patients who underwent submandibular salivary gland excision between 1990 and 2010 were included. Clinical and disease-related data were collected from the medical charts. One hundred ninety-three patients were identified, of whom 108 (56%) had non-neoplastic disorders (sialolithiasis and sialadenitis). The remaining 85 patients (44%) had a submandibular salivary gland tumor. The most common benign neoplasm was pleomorphic adenoma (53 patients). Twenty tumors (24%) were malignant: adenoid cystic carcinoma in 11 patients, mucoepidermoid carcinoma in 6 patients, and adenocarcinoma in 3 patients. Recurrence was noted in 7 patients with submandibular gland malignancy and in 2 patients with pleomorphic adenoma. The 5-year disease-free survival rate was 63%. Tumors of the submandibular gland are infrequently malignant. Recurrent submandibular salivary gland pleomorphic adenoma is rare compared with recurrences in the parotid gland.

Salivary gland pleomorphic adenoma in the Netherlands: A nationwide observational study of primary tumor incidence, malignant transformation, recurrence, and risk factors for recurrence

IntroductionWhereas salivary gland pleomorphic adenoma (SGPA) is the most common type of salivary gland tumor, little is known about its epidemiology because national cancer registries do not register this disease. ObjectivesTo establish SGPA incidence trends, rates of secondary malignant transformation and recurrence and associated factors in the Netherlands. Materials and methodsData on incidence, epidemiology, secondary malignant transformation and recurrence were retrieved from the Dutch pathology registry (PALGA) for the years 1992, 1997, 2002, 2007, and 2012. Multivariate analysis was performed to discover the risk factors for recurrence. Results3506 cases of SGPA were recorded implying an overall European standardized rate of 4.2–4.9 per 100,000 person-years. Our figures showed a female preponderance (1:1.43) with an annual 1% rise in female incidence (95% confidence interval [CI]: 0.2–1.8) and a bimodal age distribution in women (p<0.0001). The overall 20-year recurrence rate was 6.7%, and median time to first recurrence was 7years.Positive and uncertain resection margins and younger age at diagnosis were risk factors for recurrence, with odds ratios (ORs) of 4.62 (95%CI 2.84–7.51), 4.08 (95%CI 2.24–7.43), and 0.42 (95%CI 0.29–0.63) respectively. Tumor locations in the minor salivary glands had lower odds of recurrence than tumors in the parotid (OR 0.24; 95% CI: 0.07–0.77; p<0.016). Malignant transformation occurred in 0.15% of SGPAs (3.2% of recurrences). ConclusionThis first nationwide study clearly showed sex differences in SGPA epidemiology, possibly suggesting some underlying hormonal mechanism. Long-term recurrence risks were low, and secondary malignant transformation risks were very low.

Pleomorphic adenoma in the cheek a rare finding

Pleomorphic adenoma, also known as the benign mixed tumor is the most common tumor of salivary gland origin, accounting for about 60% of all salivary tumors. Up to 80% of tumors which occur in the parotid gland only, 10% in the submandibular glands, and the rest in the minor salivary glands. The pleomorphic adenoma comprises of the majority of both major and minor salivary gland tumors accounting for 3%–10% of neoplasms of head and neck region. The most common sites of pleomorphic adenoma of the minor salivary glands are the palate, followed by lips and then cheeks. These minor salivary gland pleomorphic adenomas require diagnosis based on clinical features and incisional biopsy should be avoided. These are managed by wide surgical excision. The recurrence of this tumor is a well-known factor, and inadequate initial surgical procedure is the most common cause of recurrence. Carcinoma arising from pleomorphic adenoma accounts for about 3% of salivary tumors. We are reporting a case of pleomorphic adenoma of minor salivary glands around the upper right buccal vestibule in a 36-year-old female.

An unusual presentation of mixed tumor of salivary gland

Pleomorphic adenoma 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 hard palate is the most common site of the minor salivary glands affected. Pleomorphic adenoma is a benign mixed tumor of the salivary glands that has elements of both epithelial and mesenchymal tissues. We report a case of pleomorphic adenoma of minor salivary glands in the soft palate. Incisional biopsy revealed features of pleomorphic adenoma.

Diffusion-weighted MRI for differentiation between sialadenitis and pleomorphic adenoma.

The aim of this study was to compare apparent diffusion coefficient (ADC) values from diffusion-weighted MRI (DWI) among normal salivary glands, cases with sialadenitis and cases with pleomorphic adenoma of major salivary glands. 22 patients (totalling 44 major salivary glands) diagnosed with either unilateral sialadenitis (on either parotid or submandibular gland) or parotid gland pleomorphic adenoma were selected. Contralateral non-affected glands (normal) were also analyzed. DW images were achieved using a spin-echo pulse sequence with a 1.5-T MRI device. Mean ADC values were compared among the three groups analyzed (contralateral normal glands, sialadenitis and pleomorphic adenoma). The mean ADC values were significantly higher in cases of parotid sialadenitis (p = 0.001), but not in cases of submandibular sialadenitis (p = 0.466), as compared with the contralateral non-affected glands. Cases of pleomorphic adenoma presented the highest ADC values of the study. In addition, one-way ANOVA test revealed a significant difference among the three groups of parotid glands analyzed. Within the limitations of this study, the present results suggest that DWI allows for differentiation between parotid sialadenitis and pleomorphic adenoma.

Pleomorphic adenoma and adenoid cystic carcinoma of salivary glands: E-cadherin immunoexpression and analysis of the CDH1 -160C/A polymorphism

ObjectiveDespite their similar cellular origin, pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC) present distinct behaviors. This study aimed to analyze the immunoexpression of E-cadherin in PA and ACC of salivary glands, and to investigate differences in its expression in relation to E-cadherin gene (CDH1) -160C/A polymorphism. DesignTwenty-four PA (15 cell-rich and 9 cell-poor tumors) and 24 ACC (10 tubular, 8 cribriform and 6 solid tumors) were selected for the analysis of pattern of distribution, and cellular localization of E-cadherin. In addition, E-cadherin expression was evaluated using the H-score scoring system. The CDH1 -160C/A polymorphism was investigated by PCR-RFLP. ResultsNo significant differences in pattern of distribution (p=0.181) and cellular localization (p=0.192) of E-cadherin were observed between PA and ACC. Comparison of PA and ACC cases revealed a higher median H-score in the latter (p=0.036). Cell-rich PA presented a higher H-score than cell-poor tumors (p=0.013), whereas no significant differences in E-cadherin expression were observed between ACC subtypes (p=0.254). The heterozygous genotype of the CDH1 -160C/A polymorphism was detected in only one PA and one ACC. H-scores for tumors carrying the polymorphism were below the lower quartile of their respective groups. ConclusionsThe results suggest that E-cadherin expression in PA and ACC is mainly related to cellular composition (epithelial cells versus myoepithelial cells) and degree of differentiation of myoepithelial cells in these tumors. The CDH1 -160C/A polymorphism does not seem to significantly influence the expression of E-cadherin in PA and ACC of salivary glands.

Pleomorphic adenomas of the salivary glands: retrospective multicentric study of 130 cases with emphasis on histopathological features.

Pleomorphic adenoma (PA) is the most frequent benign epithelial lesion of salivary gland origin, showing great histopathological diversity. The aim of this study was to perform a retrospective analysis, with emphasis on histopathologic features of PA of salivary glands. Clinical and histopathologic characteristics of 130 cases of minor and major salivary glands PAs from three Brazilian reference centers were studied. Higher frequency of PAs was observed in female (55.4%) subjects, with mean age of 49.7years. The most common affected site was palate (64.5%) for the PAs of minor salivary glands and parotid for cases affecting major glands (86.2%). Microscopically, most cases were classified as classic PAs (50%). Incomplete capsule was observed in 36.2% of the cases, while 47.2% showed capsular infiltration. Rounded (66.9%), angular (49.2%), oval (46.2%) and plasmacytoid (39.2%) cells were widely observed, as well as fibrous (73.8%) and myxoid (69.2%) stroma, squamous metaplasia (25.4%) and cystic degeneration (43.1%). Crystalloids (3.1%), increased mitotic activity (5.4%) and vascular invasion (2.3%) were rarely observed. PAs arising in minor salivary glands were associated with incomplete capsules, spindle, oval, angular, plasmacytoid and pleomorphic cells, fibrous and hyaline stroma, cystic degeneration, squamous metaplasia and pleomorphism (p<0.05). No association between capsular features and histological subtype was noted (p≥0.05). These results confirm the findings of previous studies regarding major clinicopathological features of pleomorphic adenomas; and highlighted some important morphologic characteristics like the capsule, vascular invasion, pleomorphism and increased mitotic activity, which can reflect the biological behavior of these tumors.

True Malignant Mixed Tumor of Submandibular Salivary Gland – A Case Report

Malignant mixed tumors of salivary gland are extremely rare tumors defined by the presence of malignant epithelial and mesenchymal components together. We report here a case of carcinosarcoma arising from a recurrent pleomorphic adenoma of submandibular salivary gland in a 36 year old woman. Histology showed a monomorphic picture dominated by malignant mesenchymal component with mixed nature proven by immuno histochemical analysis. We reviewed literature and discuss the theories on tumurogeneis, role of immunohistochemistry in diagnosis and clinicopathological features of this rare entity. Keywords: Carcinosarcoma, Immunohistochemistry (IHC), Malignant mixed tumors, Submandibular salivary gland