In conclusion, our 117 patients with salivarygland malignancies harbored 354 alterations (median = 3 per patient), 240 of which were distinct aberrations. The most common aberrations in patients with salivarygland tumors were in the TP53 gene, followed by alterations in the cyclin pathway and the PI3K pathway (PIK3CA, PIK3R1, PTEN or AKT) (Table 1 and Figure 1A). Interestingly, in multivariate analysis, there was a significant independent association between alterations in the TP53 and ERBB2 genes (p = 0.01) (Table 2), cyclin pathway and the MDM2 gene (p = 0.03) (Table 3), and between HRAS and the PI3K pathway (p = 0.0001) (Table 4), suggesting that dual targeting with cognate inhibitors may be necessary to overcome resistance. The vast majority of patients (91.5%) had at least one aberration that was potentially targetable by an FDA-approved drug or an investigational agent in a clinical trial. Indeed, of the 240 distinct aberrations, 155 (64.6%) were potentially actionable. These observations suggest that matching patients with appropriately targeted agents is feasible and warrants study. However, only 10 of 117 patients (8.5%) had a molecular portfolio identical to at least one other patient. The latter results are similar to those that we reported in metastatic breast cancer, where we recently described 131 distinct aberrations in 57 patients with no two patients having the same molecular portfolio [49–51]. Taken together, these observations suggest that customized combination therapy may have the potential to provide significant benefit for these patients.
This has been used synonymously with carcinoma ex pleomorphic adenoma (carcinoma arising from a mixed tumour). The true malignant pleomorphic ad- enoma is very rare and presents in two forms: the first is the benign pleomorphic adenoma which inexplicably metastasizes and the second is the carcinoma which develops after a number of years in a previously benign tumour. The carcinoma arising in a mixed cell tumour is commoner and represents 1-6% of mixed cell lesions. It is commonest in the parotid gland, then the submandibular gland followed by the monor salivary glands of the palate, lip, paranasal sinuses, na- sopharynx and tonsil. The original mass will usually have been present for 5-15 years and even when malignancy supervenes the tumour may remain grossly en- capsulated. It has the worst prognosis of any salivarygland malignancy. There is an accelerated recurrence rate and a high incidence of metastases (30-70%). Most series report a 5 year survival rate of less than 40%.
There are two other Drosophila members of the RYK subfamily, doughnut on 2 (dnt) and Derailed 2 (Drl-2), that might participate in Wnt5 signaling. DNT can partially rescue a muscle attachment defect of drl mutant embryos, suggesting that DNT and DRL may have significant overlapping biochemical activities (Oates et al., 1998). Drl-2, like drl, has been implicated in axon guidance (S. Yoshikawa and J. B. Thomas, personal communication). Since drl- null mutations caused only a partially penetrant salivarygland phenotype, we tested whether the other two Drosophila RYKs might be acting redundantly with drl. By themselves, both dnt and Drl-2 mutant embryos showed qualitatively similar phenotypes to those of drl mutants, but with significantly lower penetrance (Fig. 4B,C,E). We also discovered dominant genetic interactions between mutations in drl and Drl-2, suggesting that these two genes might be acting in the same process (Fig. 4D,E). As embryos lacking both drl and Drl-2 did not show an enhancement over either of the single mutants with regard to salivarygland migration, it remains unclear whether these genes act redundantly in salivarygland positioning.
Fine needle aspiration cytology is a simple and reliable method for obtaining diagnosis of a salivarygland neoplasm. Eneroth et al first reported FNAC of a salivarygland tumour..(1967). The sensitivity and specificity of FNAC for salivarygland tumours reported in literature range from a high of 99% sensitivity and 100% specificity ( Bhatia et al..) to a low of 90%sensitivity and 75% specificity(Cohen et al..) in general, however, recent series document a trend toward a higher degree of sensitivity and specificity. A higher degree of accuracy has been reported for benign tumours. Mucoepidermoid carcinomas appear to be the most difficult to diagnose by FNAC. To improve the diagnostic accuracy of FNAC, special immunohistochemical stains such as glial fibrillary acidic protein for pleomorphic adenomas and silver staining of nucleolar organizer regions have been used. this investigation is essentially free of complications, though there are reports of hemorrhage and necrosis of the tumour following aspiration in case of Warthin’s tumour and lymphoma, the occurrence of which is extremely rare. And many specific reports have alleviated the concerns over needle track seeding.
Hyaline Cells in Salivary Gland Tumours Med J Malaysia Vol 41 No 3 September 1986 HYALINE CELLS IN SALIVARY GLAND TUMOURS K H NG C H SIAR SUMMARY The morphology, incidence and distribution of hyaline[.]
Abstract: A fully developed tumor is the first manifestation of a typical salivarygland neoplasm. Identification of precursor lesions and the accompanying clinical findings may improve our understanding of these tumors. The frequency of possible precursor lesions of salivarygland tumors have not been systematically investigated to date. In this study, slides of 661 cases from three pathology laboratories in Ankara, Turkey were reviewed to search for possible precursor lesions. Salivarygland parenchymal changes adjacent to a variety of salivarygland disorders such as metaplastic changes, ductal epithelial hyperplasia, adenomatoid ductal hyperplasia, adenomatoid oxyphilic hyperplasia, adenomatoid hyperplasia of the minor salivary glands, myoepithelial sialadenitis and dysplasia were screened histologically as potentially precursor lesions. Nuclear protein Ki-67 and cellular tumor antigen p53 were also analyzed immunohistochemically in selected cases. Approximately 16% of the cases in this series contained various types of pathologic hyperplasia. Only a minority of these lesions were originally reported, so most of the findings in this study were not part of the original histology reports. The majority of these parenchymal changes were seen in parotids. Adenomatoid ductal hyperplasia was the most frequent possible precursor lesion, and it was found most frequently around pleomorphic adenomas. Although the biological significance of most of the lesions described in this report still remains to be understood completely, efforts to define and detect possible preneo- plastic lesions should be intensified. We believe that detection and eradication of the precursors is the best way of decreasing the overall morbidity caused by salivarygland tumors.
Limitations of this study included a limited number of available cases of each tumor type and missing of some tumor types such as Acinic cell carcinomas due to its relatively infrequent occurrence. Hence we recommend further studies for studying the immnunohistochemical expression of p63 and CK-14 in other types of salivarygland tumors not encountered in the present study.
Pathology, Nanjing Stomatological Hospital, Medical School of Nanjing University (China), including 98 cases of ACC and 68 cases of non- ACC neoplasms (20 cases of basal cell adeno- ma, 12 cases of pleomorphic adenoma, 11 cases of myoepithelioma, 10 cases of Warthin tumor, 6 cases of oncocytoma and 9 cases of basal cell carcinoma). All the cases were pri- mary tumors resected for the first time. None of them was treated with radiotherapy, chemo- therapy or immunotherapy pre- or post-opera- tively. The 20 wax blocks of salivarygland tis- sue adjacent to ACC and 5 wax blocks of salivarygland tissue of non-neoplastic lesions (including submandibular gland calculus and inflammation) were selected as controls. According to the 2005 WHO histological classi-
MSCs to differentiate into salivary epithelial cells and re- store function to the salivarygland of mice exposed to head and neck irradiation. Salivary flow rate significantly increased at 8 and 24 weeks post-radiation in MSC- treated mice compared with untreated controls: at 8 weeks it was 2-fold higher, and had increased to a level compar- able to that of normal mice. Compared to untreated con- trols, MSC-treated mice displayed significantly reduced cell apoptosis, a 2.5-fold increase in blood vessel percent, a significantly increased number of proliferative salivary epithelial cells, and significantly higher regeneration of ac- inar cells . Moreover, transplanted MSC differentiation into salivary epithelial cells was observed. These results in- dicate that MSCs have vasculogeneic and paracrine effects that increase acinar cell proliferation and inhibit cell apop- tosis, as well as the capacity to directly differentiate into salivary epithelial cells. Thus, MSCs can restore gland function and regenerate radiation-damaged salivary tissue. Lin et al.  studied the therapeutic potential of MSCs for salivarygland regeneration both in vitro and in vivo. After 3 weeks of co-culture (MSCs and acinar cells), about half of the MSCs had differentiated into acinar-like cells, demonstrating MSC differentiation capacity in vitro. Both MSCs and differentiated acinar-like cells significantly in- creased saliva production, salivarygland weight, and body weight when transplanted into radiation-treated mice; these systemic and local effects indicate salivarygland re- generation. Moreover, after 43 days, transplanted MSCs were found to be integrated into the salivarygland and transdifferentiated into acinar-like cells. Therefore, trans- plantation of either MSCs or differentiated acinar-like cells may aid regeneration and restore functional salivary glands.
The material of this study consisted of 53 formalin-fixed, paraffin-embedded specimens of malignant salivarygland neoplasms, all collected from the archives of the General Pathology Department, Faculty of Medicine, Ain Shams University and National Cancer Institute, Cairo University. Fifteen cases of mucoepidermoid carcinoma (MEC), 10 of which were diagnosed as high grade and the other 5 cases as low grade, 14 cases of adenoid cystic carcinoma (ADCC), 5 cases of salivary duct carcinoma (SDC), 3 cases of epi-myoepithelial carcinoma (EMC), 5 cases of malig- nant pleomorphic adenoma (MPA), 6 cases of polymor- phous low-grade adenocarcinoma (PLGA) and 5 cases of acinic cell carcinoma (ACC). Clinical information about lymph node metastasis was obtained from patients ’ medi- cal records (summary of cases is displayed in table 1). For all specimens five micrometer thick sections were pre- pared and stained with hematoxylin and eosin to confirm the diagnosis.
The levels of IgG antibodies produced against protein fractions of tick salivarygland extract injected to immunized cattle were monitored by ELISA according to the protocol described by Harlow (Harlow and Lane, 1988). Briefly, ELISA plates (Greiner) were coated with 5 µg per well of antigen in 20 mM carbonate buffer (pH= 9.6) by incu- bation overnight at 4 ºC. They were washed three times and incubated for 1 h at 37 ºC with 1% bovine serum albumin (HAB-tech) in PBS. Then, test sera diluted 1:200 in PBS, were incubated for 1 h at 37 ºC. After this time, the plates were washed three times and 100 µl of 1:2000 sheep anti –bovine IgG conjugated with peroxidase were added to the individual wells. After incubation at 37 ºC for 1 h the plates were washed. The color developed with 2, 2`, Azino-bis 3-ethyl Benz- Thiazoline-6-Sulfonic acid (ABTS) as substrate. The optical density (OD) was de- termined at 405 nm (AWARENESS- STAT FAX 2100). Sera from immunized and con- trol cattle were collected from week 0 (be- fore the first injection) until week 18 and results were compared in two groups.
Salivarygland 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
From this study it was concluded that fine needle aspiration cytology is an excellent first line of investigation for the diagnosis of various salivarygland lesions. Its a safe, reliable, convenient, economically effective and accurate method of diagnosis.It has a high degree of diagnostic yield and sensitivity and thereby obviating the need for open biopsy.
sensitivity (90%), but it has relatively low specificity (around 60%), with respect to its ability to distinguish between benign and malignant tumors of the salivarygland . Magnetic resonance imaging (MRI) provides better soft tissue detail that CT and can help evaluate the relationship of the tumors with vascular structures. MRI findings of salivarygland tumors have been depicted in a number of reports [129-131]. It has been stated that the findings of low signal intensity and irregular tumor margins on T2-weighted MRI images indicate malignancy [129, 130]. Nevertheless, the reported sensitivities and specificities of these findings have been low and significantly overlapping [131, 132]. MRI is better to CT in terms of sensitivity (nearly 100%) and specificity (80%), in distinguishing benign from malignant tumors . 18F- FDG PET/CT (PET/CT) has been reported to be more accurate than CT or MRI for the detection of malignant tumors, whereas the glucose uptake levels show a good correlation with the histologic grading for head and neck cancer . PET/CT shows low accuracy for discriminating between benign and malignant tumors, as benign tumors such as pleomorphic adenoma and Warthin’s tumors also have high glucose uptake values [135, 136]. PET/CT provides more precise diagnostic information for the assessment of high-grade salivarygland malignancies than does CT and it has a major impact on making treatment decisions for patients with a high-grade salivary malignancy.
Results. A male neonate presented with complaints of nasal obstruction and feeding difficulties. A common diagnostic approach to neonatal nasal obstruction was performed, resulting in an unexpected and potentially life-threatening, albeit curative, result. Cannulation of the nasal cavity to rule out choanal atresia resulted in a burst of bleeding from the nose and mouth. A finger sweep of the oropharynx produced a dislodged mass lesion. Pathology revealed a salivarygland anlage tumor of the nasopharynx.
Indeed, the first vaccines administered were all live . In an effort to explore distal immune responses follow- ing SG inoculation, one study investigated tissue viral ti- ters, tissue pathology, and antibody responses. The inoculum consisted of either murine cytomegalovirus (MCMV) or the less virulent tissue-culture-derived MCMV (tcMCMV) delivered through various routes, in- cluding injecting into the salivarygland through a small incision (intraglandular) . While systemic IgG and IgM observed in response to intraglandular and intraperi- toneal inoculation were similar, of all the routes tested (in- traperitoneal, intranasal, periglandular and intraglandular), only intraglandular SG inoculation of tcMCMV was able to prevent splenic necrosis and hepatitis while limit- ing SG viral titers. Delivering tcMCMV into the SG was also shown to correlate with maintaining SG leukocyte infiltrates.
In the present study, 65 cases of major salivarygland lesions were included irrespective of their age and sex. Of the 65 cases studied, the present study observed the age range of 6 to 75 years with mean age of 37 years and had a female preponderance. The non-neoplastic and benign lesions were seen more common in younger age group whereas malignant lesions were seen in older population. This is in concordance with the study done by Ameli et al  .