these tumors and the diverse pathological subtypes, currently available information regarding predictive and prognostic clinicopathological factors for survival is insufficient. Complete surgical excision is the primary treatment strategy for patients with salivary gland tumors, followed by radiotherapy or chemoradiotherapy in patients with malignant histology such as adenoid cystic carcinoma or salivary duct carcinoma, especially with features associated with high risk of recurrence. In advanced cases, chemotherapy may be used for systemic control, and radiotherapy, particle therapy including proton and carbon ion therapy, or concurrent chemoradiotherapy may facilitate palliation or local symptomatic control. 3
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In this study, 107 malignant salivary gland tumors, in- cluding 12 different subtypes, with the addition of 10 corresponding metastases were tested for the presence of 27 different HPV types (including all known high risk HPV types) using a multiplex bead based assay. One of the 107 malignant salivary gland tumors and its corre- sponding metastasis on the neck were positive for HPV16 DNA, and both also overexpressed p16 and therefore could be defined as being HPV positive. All other subtypes tested were HPV DNA negative. In total, only one of seven squamous cell carcinoma salivary gland tumors was HPV positive and due to the small sample size of squamous cell salivary gland tumors it was not possible to draw any reliable conclusion to whether HPV was involved in the development of this tumor type. Furthermore, all other subgroups lacked high risk HPV DNA and did not express presence of any of the other tested HPV types, suggesting that HPV does not play a major role as a causative agent in these sub- groups. The latter was shown in a more limited study by Skalova et al. .
Abstract: Malignant salivary gland neoplasms are rare, representing approximately 3% to 7% of all head and neck cancers. Contrasting from the more common mucosal head and neck cancers, which, in general, are ascribed to excessive tobacco, alcohol use, and more recently to viral infection, specific carcinogenic factors for malignant salivary gland growths have not been as clearly identified. Histologically, they represent a heterogeneous group of tumors. Forty histologic types of epithelial tumors of the salivary glands have been reported; some are exceedingly rare and may be the topic of only a few case reports. Salivary tumors can arise in the major salivary glands or in one of the minor salivary glands (predominantly mucus secreting glands), which are distributed throughout the upper aerodigestive. Most patients who develop malignant salivary gland tumors are in the sixth or seventh decade of life. FNA should be considered as part of the diagnostic evaluation but due to its varying sensitivities and specificities imaging modalities such as ultrasound, CT scans, and MRI should also be used as diagnostic adjuncts. Surgery is the primary modality for management of these tumors, nontraditional surgical approaches and instrumentation, as well as facial nerve monitoring, can be selectively utilized to try and decrease the morbidity associated with these surgical procedures. Adjuvant treatment is primarily achieved with radiation therapy. Chemotherapy continues to have a palliative role in the management of salivary gland tumors; however, research in this field is trying to identify a therapeutic role for chemotherapy in order to improve overall survival.
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We assessed the predictive ability of the MR imaging criteria based on the ADC levels (extremely low, low, intermediate, or high) for the differen- tiation between benign and malignant tumors as follows: negative pre- dictive values and positive predictive values were used to assess the per- formance of ADC maps in the differentiation of benign and malignant salivary gland tumors. The negative predictive value is the percentage of salivary gland tumors identified by ADC maps as negative for malignancy or a specific tumor pathology; these tumors were histopathologically proved to be nonmalignant or lacking the specific tumor pathology. The positive predictive value is the percentage of salivary gland tumors iden- tified by ADC maps as positive for malignancy or for the specific tumor pathology; these tumors were histopathologically proved to be malignant or to have the specific tumor pathology. We also calculated the sensitivity (true-positive results/[true-positive results ⫹ false-negative results]) and specificity (true-negative results/[true-negative results ⫹ false-positive results]). The accuracy was calculated by the following formula: (true- positive results ⫹ true-negative results)/total number of salivary gland tumors.
The second most common aberrations involved the cyclin pathway (CCND1, CDK4/6 or CDKN2A/B), which was abnormal in 26.5% of patients (31/117) with salivary gland tumors. Aberrations in the cyclin D-cyclin-dependent kinase pathway that regulates the cell cycle restriction point is a common feature of human cancer, contributing to tumor proliferation, genomic instability and chromosomal instability [31–33]. This pathway can be altered through multiple mechanisms including increased signaling through CDK4 and CDK6 amplification, overexpression of cyclin D1, and loss of inhibitors including CDKN2A (p16) and/or CDKN2B (p15) [34–37]. Mutation or loss of RB1 (Rb; retinoblastoma) also alters this pathway, but renders tumors resistant to CDK inhibitors. Only three patients in our series had RB1 mutations. According to Etges et al , malignant salivary gland tumors expressed the cyclin pathway differently from normal salivary gland when assessed by immunohistochemistry. They reported that expression of cyclin D1, CDK4 and CDKN2A were significantly higher in malignant salivary gland tumors (including adenoid cystic carcinoma and mucoepidermoid carcinoma) when compared to normal salivary gland. Meanwhile protein expression level of Rb was lower in malignant salivary gland tumors when compared to normal salivary gland . Although it is unclear why CDKN2A protein expression was higher in malignant salivary gland tumors in this study, it is possible that the cyclin pathway is involved in tumorigenesis of salivary gland cancers. Regarding therapeutic implications, the cyclin pathway is possibly targetable with CDK4/6 inhibitors such as with palbociclib  and further investigation is warranted. Of interest, MDM2 amplifications were more likely to be associated with abnormalities in the cyclin pathway (6/10 [60.0%] versus 25/107 [23.4%]; p = 0.03 after multivariate analysis) (Table 3). Similarly, Moller et al reported that five out of seven patients with diffuse large B cell lymphomas had co-aberrations in MDM2 (amplification) and CDKN2A (deletion), when assessed by immunohistochemistry and polymerase chain reaction respectively . Since MDM2 is negatively regulated by CDKN2A, MDM2 amplification and aberrations in the
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The PP and D values were much overlapped among different types of head and neck tumors as shown in Fig 6. However, these values may be useful in differentiating among some types of head and neck tumors, for example between benign and malignant salivary gland tumors. In addition, this simplified technique for simultaneously assessing perfusion and diffusion characteristics is easy to use and fast. Therefore, a combined use of PP and D values obtained with DWI could be an adjunct to conventional MR im- aging for preoperatively diagnosing different types of head and neck tumors.
expression of this potential tumor marker in salivary gland tumors. The available data, however, suggest that there may be a connection between the behavior of sal- ivary gland tumors and EZH2 expression as well [9, 10]. The purpose of our study is to examine EZH2 expres- sion in a variety of benign and malignant salivary gland tumors, and to investigate if it provides any useful infor- mation for their recognition. All 40 benign salivary gland tumors investigated were negative for EZH2, while 52 of the 54 malignant tumors proved to be positive. Based on this observation EZH2 immunohistochemistry might provide valuable information for the histological examin- ation of salivary gland tumors.
Although there is limited information in the literature re- garding the cytology of parotid SFTs, most reported cases are histologically fibrous and show spindle cell cytomorphol- ogy, suggesting a spindle cell neoplasm [5, 13, 17]. However, the combination of myxofibrillarystroma and atypical basa- loid cell morphology (as seen in our case, Fig. 1c,d)has not been described in the literature, which could be a potential diagnostic pitfall due to the morphological overlap with epi- thelial neoplasms of the parotid gland on FNA. A broad dif- ferential diagnosis of cellular basaloid neoplasm should be considered, including cellular pleomorphic adenoma, carcin- oma ex pleomorphic adenoma, epithelial-myoepithelial car- cinoma, and basal cell adenoma/adenocarcinoma. As in our case, the clinical finding of a parotid gland neoplasm, ab- sence of spindle cells, and the sampling of dedifferentiated/ epithelioid area, lead to the diagnosis of SUMP. Neverthe- less, in general practice, as long as a diagnosis of “neoplasm” is used, appropriate surgical management will be imple- mented regardless of whether a diagnosis of primary salivary gland epithelial neoplasm or mesenchymal neoplasm is ren- dered . Moreover, the cell block could be key to identify- ing the HPC-like pattern and can be a source for the application of immunohistochemical stains [19, 20].
2. RADIATION: An association between high dose radiation and salivary gland cancer is seen in studies of atomic bomb survivors. Iodine 131 used to treat thyroid disease also concentrated in salivary glands and increases the risk of salivary tumors. 26. The risk of malignant salivary tumors is increased in patients of childhood cancer in head and neck region, treated by a combination of chemotherapy and radiotherapy. 27 Recent study of a population shows a higher frequency of benign parotid tumors, in a population of higher than average mobile telephone users 28 .
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Conclusion: Based on these results, we concluded that although the accuracy of PLGA diagnoses has improved, they remain a challenge for pathologists. To facilitate PLGA diagnoses, we have therefore made some suggestions for pathologists regarding tumors composed of single-layer strands of cells that form all of the histological patterns present in the tumor, consistency of the cytological appearance and uniformly positive CK7, vimentin and S100 immunohistochemistry, which indicate a single PLGA phenotype.
Salivary gland tumors, includ- ing malignancy, represent a he- terogeneous group of patholo- gy, so it is difficult to under- stand their molecular patho- genesis and genetic altera- tions. As is well known, PA is the most common benign tu- mor of the parotid gland, and the World Health Organization classification reported that 3-4% of all pleomorphic adenomas become malig- nant . Carcinoma ex-pleomorphic adenoma (CXPA) is defined as a carcinoma arising from a primary or recurrent PA [8, 32]. Unlike PA, Warthin’s tumor presents less than a 1% risk of malignant transformation . We collected 32 surgically treated salivary tumors and analyzed their clinicopathologic and molecular biologic Figure 2. Scatter plot of telomere length (A), PIK3CA amplification (B), and
the other less frequently identified symptoms. The involvement of non-oral sites is rare and has included only the nasal cavity (1%) and the nasopharynx (0.5%) 4.This mainly occurs in the fifth through eight decades of life, with a mean age of 59 years. The female to male ratio is about 2:1.This mostly affects the minor salivary glands located mainly in the palate, lips, buccal mucosa, retromolar mucosa, and floor of mouth, tongue, parotid and rarely the submandibular gland. A wide range size has been noted, but most are between 1 and 4 cm in diameter. It has a slow growth rate which is evidenced by the long duration, from many months to years, before diagnosis and treatment planning. Metastasis to the local nodes only accounts to 10%.The definitive diagnosis only comes after the histopathologic examination.In this article, we report a case of PLGA to discuss and review its clinical and histopathologic features.
Histopathologic diagnosis requires presence of a be- nign mixed component adjacent to a malignant compo- nent and foci of apparent transition between benign and malignant areas may be demonstrated. This may also be challenging, as the residual mixed tumor component may be small and overlooked. In fact, up to 100 cuts may be necessary to find a small mixed tumor within a salivary gland carcinoma . The malignant component may even completely replace the benign component; in such cases the diagnosis is inferred from the presence of hya- line scarring, highly characteristic of degenerated PA . Furthermore, the malignant component may be difficult to classify , providing an additional challenge for pathologic diagnosis.
In conclusion, the present studyis a single institution experience that shows salivary gland tumors to be found mainly in minor salivary glands with slight male predominance.Pleomorphic adenoma and mucoepidemoid carcinoma were the most frequent benign and malignant tumors respectively. The palate was the most affected site by benign and malignant tumors. The benign SGTs peaked at the second decade of life while the malignant tumors were more frequent in 5 th decade
These are group of malignant salivary gland tumor in which the neoplastic cells demonstrates serous acinar cell differentiation. Spiro RH (1986) loc.cit had found an incidence of 10% of the primary malignant tumors. In our study, the incidences are slightly higher to around 23% and this could be due to the smaller sample size of lesions. All the 3 cases of acinic cell carcinoma occurred in the parotid region akin to the observations of Spiro RH loc.cit (1986) who found more there 80% of these tumors occur in parotids. It is a female predominant tumor and the mean age is 44 years. In our study it was more common in women and we had a single case presenting in a male patient. The mean age of the patients in our study was 51. It was a slow growing mass and one of our case experienced facial muscle weakness. Ellis GL and Corio RL (1983) have reported a facial muscle weakness in 5-10% of their patients.
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stellate cells respectively whereas 12 cases had prominent or scattered chondroid areas. The authors have shown that over 50% of cells showed positive reaction to GFAP in 66% of PA, and the remaining 33% of the cases exhibited less than 50% of positive cells. In PLGA, though 73% of cases failed to react with GFAP, remaining 23% cases had faint and spotty staining that was mainly confined to the less numerous medium-sized polygonal cells rather than the ovoid cells that comprise the bulk of the lesion. The authors stated that minor gland lesions differ from major gland lesions in that they are more often cellular, lacking a prominent fibrous capsule, and containing scant or absent myxoid and chondroid material and hence, the use of GFAP should be considered for differentiation of PLGA versus PA when there was overlapping architectural, background, and cellular features in the neoplasm of minor salivary glands.
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According to the ROC curve, and comprehensive ana- lysis of AUC, sensitivity, and speci ﬁ city, it could be con- cluded that energy and energy-mean were the ideal texture parameter or joint diagnostic model to identify parotid PA and malignant epithelial tumors because of their good diagnosis ef ﬁ ciency, with the AUC of 0.887 and 0.888, respectively. The sensitivity of energy was the highest (0.970), and the speci ﬁ city of energy-correlation was the highest (0.970).The energy represents the stability of the lesion texture gray scale change and re ﬂ ects the gray scale distribution uniformity and texture thickness. The higher the energy is, the more regular and stable the current texture change becomes. In this study, the energy of par- otid epithelial malignancy was statistically higher than that of PA. This may be closely related to the histopathological characteristics of PA, such as complicated histological structure and diverse cell types, including glandular epithelium, myoepithelium, mucus, mucoid tissue, and chondroid tissue.
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Out of 200 patients, there were 170 males and 30 females. Mean age of male and female patients was 40.27±15.04 and 40.12±12.15 years respectively. Youngest patient age was 10 years for male and 15 years for female, but the eldest patient age was same for both the genders i.e. 80 years. Based on MRI imaging characteristics 125 patients were labelled as having benign and 75 as having malignant tumours (Figure 1), while histopathological indings diagnosed 121 parotid tumours as benign and 79 as malignant tumours (Figure 2). On both the modalities i.e. on MRI and Histopathology, 113 patients were diagnosed as benign and 67 patients as having malignant parotid gland tumours (Image 1). Total of 20 patients had contradictory results, out of them 12 patients were diagnosed as benign on MRI but they were malignant on histopathology. Similarly 8 patients were diagnosed as having malignant tumour on MRI but on histopathology they were found to be having benign features (Table 1). Sensitivity, speci icity, positive and negative predictive value of MRI was 90.4%, 89.33%, 93.39% and 84.41% respectively. The overall diagnostic accuracy of MRI was found to be 90% while taking results of histopathology as a gold standard.
must also consider salivary gland tumors and odontogenic tumors. Positive immune reactions of the neoplastic cells with cytokeratin, EMA, vimentin, and CD10 contribute to the histomorphological diagnosis of RCC. Because the lesion discussed here was localized in the head and neck region, the diﬀerential diagnosis considered salivary gland tumors, such as mucoepidermoid carcinomas and acinic cell carcinomas, malignant melanomas, and skin appendage tumors. Because the tumor had histomorphological and immunohistochemical features typical of RCC, other lesions were excluded and the case was diagnosed as metastatic RCC [12–19].
lesions from the salivary gland first should always be ruled out. The differential diagnosis in the present case included myoepithelioma, leiomyoma/leiomyosarcoma, mucoepidermoid carcinoma and clear cell tumor of the lung. Separation of myoepithelial carcinoma from myoepithelioma is primarily based on cellular abnormalities, infiltrative growth, mitotic fig- ures and necrosis. Regarding the immunoreac- tivity of the tumor for CK and p63, which is the most useful marker to help discriminate myo- epithelial tumors from other mesenchymal tumors, like leiomyoma/leiomyosarcoma or clear cell tumor of the lung. But mucoepider- moid carcinoma is usually composed of epider- moid cells, mucous cells and intermediate cells.