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Salivary Gland Cancer

The salivary glands make saliva, which contains a range of enzymes which help digest food and protect against infections of the mouth and throat. There are 3 pairs of major salivary glands and hundreds of minor microscopic salivary glands:

  • Parotid glands: the largest salivary glands,located in front of and just below each ear. Aproximately 80% of salivary gland tumors begin in the parotid glands.
  • Submandibular glands: found below the jawbone. Between 10-15% of salivary gland tumours are found in the submandibular glands
  • Sublingual glands: found under the tongue in the floor of the mouth.
  • Minor salivary glands there are several hundred tiny salivary glands lining parts of the mouth, nose, and larynx.
More than half of all salivary gland tumours are benign (non cancerous). Malignant (cancerous) tumours are designated high-grade or low-grade, depending on how they look under the microsope.

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Latest Research Publications

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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Ouyang DQ, Liang LZ, Zheng GS, et al.
Risk factors and prognosis for salivary gland adenoid cystic carcinoma in southern china: A 25-year retrospective study.
Medicine (Baltimore). 2017; 96(5):e5964 [PubMed] Free Access to Full Article Related Publications
Adenoid cystic carcinoma (ACC) is characterized by slow growth, frequent local recurrences, and high incidence of distant metastasis (DM). The aim of this study was to evaluate predictive factors for local-regional (LR) recurrence, DM, and survival in ACC.A retrospective review of the medical records for patients with salivary glands ACC from 1990 to 2015 was performed. The clinical parameters were assessed to identify correlations with the development of LR recurrence, DM, and survival of these patients.Among 228 patients who underwent surgery as definitive treatment, 210 (92.1%) were followed up in the study. DM was detected in 64 (30.5%) patients, LR recurrence was detected in 58 (27.6%) patients. The estimated 5, 10, and 15-year overall survival rates were 84.7%, 70.8%, and 34.0%, respectively. Multivariate analysis revealed that the presence of lymphovascular invasion and a high T classification were very strong adverse factors, which independently influenced LR recurrence, DM, and survival of ACC patients. Positive/close margin and N+ status were independent risk factors for DM and LR recurrence, respectively. Survival of ACC patents was also affected by tumor location.Presence of lymphovascular invasion and a high T classification were very strong adverse factors and independent predictors for ACC patients' prognosis, which influenced LR control, DM control, and survival.

Cervical lymph node metastasis in adenoid cystic carcinoma of the major salivary glands.
J Laryngol Otol. 2017; 131(2):96-105 [PubMed] Related Publications
OBJECTIVE: To verify the prevalence of cervical lymph node metastasis in adenoid cystic carcinoma of major salivary glands, and to establish recommendations for elective neck treatment.
METHODS: A search was conducted of the US National Library of Medicine database. Appropriate articles were selected from the abstracts, and the original publications were obtained to extract data.
RESULTS: Among 483 cases of major salivary gland adenoid cystic carcinoma, a total of 90 (18.6 per cent) had cervical metastasis. The prevalence of positive nodes from adenoid cystic carcinoma was 14.5 per cent for parotid gland, 22.5 per cent for submandibular gland and 24.7 per cent for sublingual gland. Cervical lymph node metastasis occurred more frequently in patients with primary tumour stage T3-4 adenoid cystic carcinoma, and was usually located in levels II and III in the neck.
CONCLUSION: Adenoid cystic carcinoma of the major salivary glands is associated with a significant prevalence of cervical node metastasis, and elective neck treatment is indicated for T3 and T4 primary tumours, as well as tumours with other histological risk factors.

Lundberg M, Munsterhjelm B, Mäkitie A, Leivo I
Immunohistochemical Staining of Histological Fragments Derived from Salivary Gland Tumour Fine-Needle Biopsy Aspirates.
Acta Cytol. 2017; 61(1):17-20 [PubMed] Related Publications
OBJECTIVES: The aim of this study was to describe a method for analysing histological fragments derived from fine- needle aspirate biopsy (FNAB) of salivary gland tumours (SGTs), and to evaluate the use of immunohistochemistry (IHC) on them.
STUDY DESIGN: We reviewed all 509 FNAB pathology reports taken from SGTs at Helsinki University Hospital, Finland, between 1999 and 2009. In 51% of the cases (n = 209) "histo-fragments" had been obtained and 31 had been further analysed by IHC. Of these, 25 (81%) were available for review. We evaluated the benefit of IHC by relating its added value to the preoperative cytological diagnosis and its accuracy compared with the postoperative histological diagnosis.
RESULTS: Most of the samples analysed by IHC were assigned a malignant diagnosis, with 12 different types of malignancy represented. IHC was advantageous in 76% of the cases. In the 108 studies using IHC in this series, antibodies to 36 different antigens were used.
CONCLUSION: Analysis of histo-fragments in FNABs using IHC can be valuable in specific differential diagnostics and raises diagnostic accuracy in SGTs.

Lee DH, Yoon TM, Lee JK, Lim SC
Atheroma of the facial artery mimicking a parotid gland tumor: A case report.
Medicine (Baltimore). 2016; 95(46):e5403 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: Atheroma of the facial artery is an extremely rare disease.
CLINICAL FINDINGS/PATIENT CONCERNS: Herein, we report an extremely rare case of an atheroma arising from the facial artery, mimicking a parotid gland tumor.
DIAGNOSES: The preoperative diagnosis was a right-sided parotid gland tumor.
INTERVENTIONS: We performed removal of the right parotid gland tumor, via a modified face-lift incision.
OUTCOMES: Histological examination of the specimen revealed an atheroma of the facial artery.
CONCLUSION: Clinicians should consider atheroma in the differential diagnosis of tumors arising around the parotid gland.

Sood S, McGurk M, Vaz F
Management of Salivary Gland Tumours: United Kingdom National Multidisciplinary Guidelines.
J Laryngol Otol. 2016; 130(S2):S142-S149 [PubMed] Free Access to Full Article Related Publications
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. Salivary gland tumours are rare and have very wide histological heterogeneity, thus making it difficult to generate high level evidence. This paper provides recommendations on the assessment and management of patients with cancer originating from the salivary glands in the head and neck. Recommendations • Ultrasound guided fine needle aspiration cytology is recommended for all salivary tumours and cytology should be reported by an expert histopathologist. (R) • Adjuvant radiotherapy (RT) following surgery is recommended for all malignant submandibular tumours except in cases of small, low-grade tumours that have been completely excised. (R) • For benign parotid tumours complete excision of the tumour should be performed and offers good cure rates. (R) • In the event of intra-operative tumour spillage, most cases need long-term follow-up for clinical observation only. These should be raised in the multidisciplinary team to discuss the merits of adjuvant RT. (G) • As a general principle, if the facial nerve function is normal pre-operatively then every attempt to preserve facial nerve function should be made during parotidectomy and if the facial nerve is divided intra-operatively then immediate microsurgical repair (with an interposition nerve graft if required) should be considered. (G) • Neck dissection is recommended in all cases of malignant parotid tumours except for low-grade small tumours. (R) • Where malignant parotid tumours lie in close proximity to the facial nerve there should be a low threshold for adjuvant RT. (G) • Adjuvant RT should be considered in high grade or large tumours or in cases where there is incomplete or close resection margin. (R) • Adjuvant RT should be prescribed on the basis of clinical factors in addition to histology and grade, e.g. stage, pre-operative facial weakness, positive margins, peri-neural invasion and extracapsular spread. (R).

Kamata YU, Sumida T, Murase R, et al.
Blockade of Androgen-induced Malignant Phenotypes by Flutamide Administration in Human Salivary Duct Carcinoma Cells.
Anticancer Res. 2016; 36(11):6071-6075 [PubMed] Related Publications
BACKGROUND/AIM: Androgens are known to play a critical role in prostate cancer progression, but their effect on malignant phenotypes in salivary gland cancer is unclear. The androgen-androgen receptor (AR) axis may be involved in malignant phenotypes of salivary duct carcinoma (SDC) cells and therefore may be a new target for SDC treatment. To test this hypothesis, we investigated the effect of the androgen 5α-dihydrotestosterone (DHT) on proliferation, migration, and invasiveness of SDC cells.
MATERIALS AND METHODS: We used a wound-healing assay to measure cell migration and a Boyden chamber invasion assay to investigate SDC cell invasive capacity.
RESULTS: DHT treatment increased cell proliferation, migration, and invasion. However, treatment with flutamide, an AR inhibitor, blocked the effects of DHT.
CONCLUSION: These results suggest that the androgen-AR axis is involved in SDC malignancy and may be an effective therapeutic target for treatment of human SDC.

Abu-Ghanem Y, Mizrachi A, Popovtzer A, et al.
Recurrent pleomorphic adenoma of the parotid gland: Institutional experience and review of the literature.
J Surg Oncol. 2016; 114(6):714-718 [PubMed] Related Publications
BACKGROUND: Recurrent pleomorphic adenoma (PA) of the parotid gland is a challenging surgical issue with controversy regarding management and long term outcome.
METHODS: All patients who were operated for recurrent PA of the parotid gland between the years 1991 and 2013 were reviewed. Patient demographics, clinicopathologic variables, and operative details were collected retrospectively.
RESULTS: A total of 22 patients were operated for recurrent PA of the parotid gland. Mean interval between recurrences was 7 and 6 years for first recurrence and second recurrence, accordingly. Second recurrence was significantly influenced by younger age at initial treatment (P = 0.009). Only two patients (9%) with a recurrence developed facial nerve paralysis following surgery. Adjuvant radiotherapy was given to nine patients with no evidence of disease progression or recurrence. There were no cases of malignant transformation.
CONCLUSIONS: Recurrent PA of the parotid gland tends to occur in long intervals in a multifocal pattern. Adjuvant radiotherapy could be suggested as an alternative for surgery. J. Surg. Oncol. 2016;114:714-718. © 2016 Wiley Periodicals, Inc.

Liao PW, Chen YL, Chen JW
Pedunculated carcinoma ex pleomorphic adenoma of the nasal cavity: A unique case report.
Medicine (Baltimore). 2016; 95(39):e5004 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: A carcinoma ex pleomorphic adenoma (CXPA) is an epithelial malignancy arising in or from a benign pleomorphic salivary adenoma. The parotid gland is the most common location of CXPAs. Minor salivary gland CXPAs of the nasal cavity are exceedingly rare, with only 6 documented in the literature.
METHODS AND RESULT: We present a 7th case: an unusual pedunculated intranasal CXPA, which had a favorable outcome after a wide endoscopic excision and the longest follow-up period reported to date. The clinical features, immunohistochemical characteristics, treatment choices, and disease outcomes of the intranasal CXPAs reported in previous studies are also reviewed.
CONCLUSION: This case demonstrates the importance of considering the possibility of CXPA in the differential diagnosis of minor salivary gland malignancies in the nasal cavity.

Foley H, Hopley S, Brown E, et al.
Conformal orbit sparing radiation therapy: a treatment option for advanced skin cancer of the parotid and ear region.
J Med Radiat Sci. 2016; 63(3):186-94 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: New surgical methods have enabled resection of previously in-operable tumours in the region of the parotid gland and ear. This has translated to deeper target volumes being treated with adjuvant radiotherapy. Due to the limitations of existing conformal techniques, alternative planning approaches are required to cover the target volume with appropriate sparing of adjacent critical structures. Although intensity modulated radiation therapy (IMRT) may be able to achieve these goals compared with the existing conformal method, a new orbital sparing radiation therapy (OSRaT) technique was evaluated as an alternative conformal planning process. The study objective was to evaluate the dosimetry of three planning methods: pre-existing conformal, IMRT and OSRaT techniques.
METHODS: Ten patients were planned retrospectively using the existing three-dimensional conformal radiotherapy (3DCRT), IMRT and OSRaT techniques. Dosimetry was analysed using the homogeneity index (HI), conformity index (CI), the volume of planning target volumes (PTV) under and over treated by the 95% isodose and dose to critical structures.
RESULTS: OSRaT achieved superior 95% coverage of the high-dose PTV while delivering HI similar to IMRT for intermediate and high-dose PTVs. The CI for the high-dose PTV was comparable between the three techniques, however IMRT was statistically better for the low- and intermediate dose PTVs. All three techniques showed adequate orbital sparing, however OSRaT and IMRT achieved this with less under dosing of the PTVs.
CONCLUSION: For the treatment of patients with advanced skin cancer of the parotid and ear, both IMRT and the OSRaT techniques are viable options.

Yaga US, Gollamudi N, Mengji AK, et al.
Adenoid cystic carcinoma of the palate: case report and review of literature.
Pan Afr Med J. 2016; 24:106 [PubMed] Free Access to Full Article Related Publications
Adenoid Cystic Carcinoma (ACC) is a rare tumor constitutes for less than 1% of head and neck malignancies and 10% of all salivary gland tumors. Palate is the most common site to be involved in the oral cavity followed by parotid gland and submandibular gland. They are usually asymptomatic, slow growing, characteristically shows infiltrative growth and perineural invasion. This paper reports a case of Adenoid Cystic Carcinoma in a 35 year old female man reported with a swelling on the left side of palate involving the hard and soft palate since 8 months which was diagnosed histopathologically and review of literature of the peculiar clinical, and histopathological features.

Abdel Razek AA, Samir S, Ashmalla GA
Characterization of Parotid Tumors With Dynamic Susceptibility Contrast Perfusion-Weighted Magnetic Resonance Imaging and Diffusion-Weighted MR Imaging.
J Comput Assist Tomogr. 2017; 41(1):131-136 [PubMed] Related Publications
PURPOSE: To characterize parotid tumors with dynamic susceptibility contrast perfusion-weighted magnetic resonance (MR) imaging and diffusion-weighted MR imaging.
MATERIAL AND METHODS: Prospective study was conducted upon 48 consecutive patients (27 men, 21 women; aged 15-75 years; mean, 45 years) with parotid tumors that underwent dynamic susceptibility contrast perfusion-weighted MR imaging was performed after bolus injection of gadopentate dimeglumine and diffusion-weighted MR imaging. The dynamic susceptibility contrast percentage (DSC%) and apparent diffusion coefficient (ADC) values of parotid tumors were calculated and correlated with histopathological findings.
RESULTS: The DSC% of malignant parotid tumors (33.53% ± 3.99%) was significantly different (P = 0.001) from that of benign parotid tumors (22.29% ± 4.13%). The threshold values of DSC% and ADC used in differentiating malignant from benign parotid tumors were 26.5% and 1.07 × 10 mm/s, respectively, with area under the curve (AUC) of 0.96 and 0.81, respectively. The DSC% of malignant parotid tumors was significantly different from that of Warthin tumors (P = 0.001). The cutoff DSC% used to differentiate malignancy from Warthin tumors was 26.9% with an AUC of 0.99. There was a significant difference in DSC% and ADC values between pleomorphic adenomas and Warthin tumors (P = 0.001). The threshold values of DSC% and ADC used in differentiating pleomorphic adenomas from Warthin tumors was 22.5% and 0.99 × 10 mm/s, respectively, with AUC of 0.88 and 0.98, respectively.
CONCLUSIONS: Dynamic susceptibility contrast-enhanced perfusion-weighted MR imaging and diffusion-weighted MR imaging are noninvasive promising methods that are used for differentiation of malignant from benign parotid tumors and for characterization of some benign parotid tumors.

Xiao H, Wen T, Liu X
Submandibular oncocytic carcinoma: A case report and literature review.
Medicine (Baltimore). 2016; 95(37):e4897 [PubMed] Related Publications
BACKGROUND: Oncocytic carcinoma (OC) arising in the submandibular gland is an unusual malignant neoplasm, with <20 cases previously reported. The cancer is characterized by numerous morphologically abnormal mitochondria present in the cytoplasm and marked cellular pleomorphism. At its most severe, the tumor may invade into the surrounding tissues, including intravascular, lymphatic, or perineural invasion, and lead to regional nodal or distant metastasis.
METHODS: The current study describes a novel OC case in a 46-year-old male, the youngest case of the review. The patient presented with a 5-month history of an intermittently painful mass.
RESULTS: Following magnetic resonance imaging, excisional biopsy, hematoxylin-eosin staining, phosphotungstic acid-hematoxylin staining, and immunohistochemical examination, an OC of the submandibular gland was diagnosed.
CONCLUSION: The current study summarizes the pathogenesis, diagnosis, therapeutics, and the prognosis of OC. The literature review regarding this rare disease is also presented to emphasize the lack of specific markers of OC and the risk of cervical lymph metastasis.

Aisagbonhi OA, Tulecke MA, Wilbur DC, et al.
Fine-Needle Aspiration of Epithelial-Myoepithelial Carcinoma of the Parotid Gland With Prominent Adenoid Cystic Carcinoma-Like Cribriform Features: Avoiding a Diagnostic Pitfall.
Am J Clin Pathol. 2016; 146(6):741-746 [PubMed] Related Publications
OBJECTIVES: Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland malignancy associated with an overall good prognosis. Fine-needle aspiration (FNA) typically shows a dual population of myoepithelial and ductal cells. Rarely, acellular matrix globules are present, raising a differential diagnosis of adenoid cystic carcinoma (AdCC), a more aggressive salivary gland malignancy associated with a poor long-term prognosis. We report an FNA case of EMC containing a predominant pattern of AdCC-like spherical globules.
METHODS: We compare features of an unusual case of EMC with those of cribriform AdCC to arrive at morphologic clues to the correct diagnosis.
RESULTS: Distinguishing features of EMC on FNA include (1) a prominent population of myoepithelial cells vs the predominance of basaloid cells in AdCC and (2) cohesive matrix globules with a peripheral rim of pale-staining basement membrane material compared with the dyscohesive matrix globules of AdCC. Immunochemical markers (S100, CD117, and MyB) are also useful.
CONCLUSIONS: Although EMC and AdCC can both contain spherical matrix globules, close evaluation of the cytomorphology of the globules and their relationship to surrounding cells provides a clue to distinguish the two neoplasms.

Hellquist H, Skalova A, Azadeh B
Salivary gland hybrid tumour revisited: could they represent high-grade transformation in a low-grade neoplasm?
Virchows Arch. 2016; 469(6):643-650 [PubMed] Related Publications
Salivary gland hybrid tumour, first described in 1996, is a very rare neoplasm for which exact morphological criteria have not been universally agreed upon. In contrast, the concept of high-grade transformation (HGT) in salivary neoplasms has been widely accepted during the last decade, and the number of reported cases is rapidly increasing. A review of the literature revealed 38 cases of hybrid tumour reported in 22 publications. During approximately the same time period, well over 100 cases of HGT in salivary neoplasms have been reported. There are important histological similarities between hybrid tumours and salivary tumours with HGT. In the latter, containing one tumour component of low-grade malignancy and the other of high grade, the two tumour components are not entirely separated and appear to originate in the same area. Virtually, all cases reported as hybrid tumour had no clear lines of demarcation between the two tumour types. We are inclined to suggest that most of the 38 cases of hybrid tumours described in the literature would today better be called tumour with HGT rather than hybrid tumour. The relative proportion of the two components may vary, and the high-grade component is sometimes very small, which emphasises the importance of very generous sampling of the surgical specimen. The molecular genetic mechanisms responsible for HGT, including what used to be called hybrid tumour, remain largely unknown. Abnormalities of a few genes (including p53, C-MYC, cyclin D1, HER-2/neu) have been documented. As insufficient data exist on gene abnormalities in these lesions, conclusions as to whether or not they have a common origin and which mechanisms are involved in transformation cannot be drawn. Due to the small number of cases reported, many of which lack follow-up details; indicators of prognosis of hybrid tumours are not available, but their behaviour seems to be similar to that of tumours with HGT, i.e. an accelerated aggressive course. HGT of salivary gland neoplasms greatly influences macroscopic and microscopic evaluation of the specimen but also, given the high incidence of metastases and morbidity, carries significant treatment implications.

Radunovic M, Nikolic N, Milenkovic S, et al.
The MMP-2 and MMP-9 promoter polymorphisms and susceptibility to salivary gland cancer.
J BUON. 2016 May-Jun; 21(3):597-602 [PubMed] Related Publications
PURPOSE: Matrix metalloproteinases (MMPs) are a family of endopeptidases that may play an important role in the development of salivary gland cancer (SGC). MMP-2 and MMP-9, members of the gelatinase protein family, are capable of degrading type IV collagen of basement membranes, and their overexpression is often associated with tumor aggressiveness and poor prognosis. The aim of this study was to establish the role of single nucleotide polymorphisms (SNPs) in MMP-2 and MMP-9 genes as putative susceptibility factors for the development of SGC.
METHODS: The MMP-2 -1306 C>T, MMP-2 -1575 G>A and MMP-9 -1562 C>T polymorphisms were analyzed in 93 SGC cases and 100 controls using PCR-RFLP.
RESULTS: The T allele for the MMP-2-1306 C>T polymorphism exhibited its effect in heterozygous carriers, increasing the risk for SGC (odds ratio/OR 1.98, 95% CI 1.07-3.65, p=0.03). According to the dominant model, CT+TT genotypes had a 2-fold increased risk of developing SGCs (p=0.02).When the dominant model was applied for the MMP2 -1575 G>A, individuals with GA+AA genotypes exhibited a 1.77-fold increase in cancer risk, but with borderline significance (p=0.049). Heterozygous carriers of the variant T allele for the MMP-9 -1562 C>T polymorphism had roughly a 2-fold increase in susceptibility for SGC compared to wild type homozygotes (CC) (p=0.02).
CONCLUSION: Our findings suggest MMP-2-1306 C>T and MMP-9-1562 C>T polymorphisms genotypes seem to influence the development of SGCs, whereas MMP-2 -1575 G>A seems to be of a minor importance.

Huang EC, Ghazikhanian V, Qian X
Giant cell-rich osteosarcoma of the parotid gland: An exceptionally rare entity at an unusual site.
Diagn Cytopathol. 2016; 44(12):1107-1111 [PubMed] Related Publications
Giant cell-rich osteosarcoma is a rare histologic variant of conventional osteosarcoma that affects mainly the extremities. Extraskeletal giant cell-rich osteosarcoma is therefore exceedingly rare. Here, we report the first case of this uncommon tumor involving the parotid gland in a 62-year-old male who presented with initial right jaw swelling. Radiologic work-up revealed a 6.2 cm mass involving the right parotid gland. Fine-needle aspiration cytology showed numerous multinucleated giant cells in a background of dyshesive epithelioid cells and rare clusters of spindle stromal cells, suspicious for malignancy. The subsequent excisional biopsy showed histopathologic features diagnostic for giant cell-rich osteosarcoma. Diagn. Cytopathol. 2016;44:1107-1111. © 2016 Wiley Periodicals, Inc.

Kiesewetter B, Lukas J, Dolak W, et al.
Gender Aspects in Extranodal Marginal Zone B-Cell Lymphoma of the Mucosa-Associated Lymphoid Tissue: Does Sex Matter?
Oncology. 2016; 91(5):243-250 [PubMed] Related Publications
OBJECTIVES: Gender-related aspects have been investigated in a variety of tumor entities including results on sex-specific differences in non-Hodgkin lymphoma. However, there are no data on gender differences in mucosa-associated lymphoid tissue (MALT) lymphoma.
METHODS: We have analyzed 327 patients treated between 1999 and 2015 with a median follow-up time of 55.2 months.
RESULTS: There was a female predominance, with 197 female (60.2%) and 130 male patients (39.8%, female-to-male ratio 1.5). The mean age was comparable between female and male patients (61.2 vs. 61.7 years, p = 0.777). Female patients less frequently had gastric MALT lymphoma (31.5 vs. 39.2%), but this was not statistically significant (p = 0.149). Extragastric manifestations were equally distributed, except for parotid (p = 0.003) and breast lymphoma (n = 8, 100% female) showing a female predominance. This was most likely related to a higher rate of active autoimmune disorders in women (35.6 vs. 11.0%, p < 0.001). β2-Microglobulin elevation at diagnosis occurred more often in female patients (42.8 vs. 26.0%; p = 0.008). However, this did not translate into a worse progression-free survival for female (56.0 months, 95% CI 30.1-81.9) versus male patients (49.0 months, 95% CI 25.4-72.5, p = 0.433). Overall survival did not differ between groups.
CONCLUSION: Our data show surprisingly little differences between female and male patients with MALT lymphoma. Both sexes appeared to have well-balanced clinical features and an identical prognosis.

Yang L, Wang T, Zhang J, et al.
Expression of BTBD7 in primary salivary adenoid cystic carcinoma and correlation with Slug and prognosis.
Cancer Biomark. 2016; 17(2):179-85 [PubMed] Related Publications
BACKGROUND: BTB/POZ domain-containing protein 7 (BTBD7) is recognized as a regulatory gene that regulates epithelial cell dynamics and branching morphogenesis. It is also reported for regulating epithelial-mesenchymal transition (EMT) molecules and involved in the process of invasion and metastasis of lung cancer and hepatocellular carcinoma. Slug is a transcriptional factor of EMT which plays a crucial role in the process of primary salivary adenoid cystic carcinoma (SACC). However, the role of BTBD7 in SACC and the correlation with Slug have not been identified. This study investigated the expression of BTBD7 and correlation with Slug, as well as the prognostic significance of BTBD7 in SACC.
METHODS: The expression of BTBD7 and Slug were examined in ACC-LM and ACC-83 cell lines and immunohistochemically in paraffin embedded tissue specimens from 66 primary SACC patients. Statistical analyses were performed to evaluate the correlation between BTBD7 expression and Slug expression and the prognostic significance of BTBD7 expression.
RESULTS: BTBD7 protein expression was initially verified in ACC-LM and ACC-83 cell lines. The positive rate of BTBD7 expression was 62.1% in SACC to 20% in normal salivary tissues comparatively. BTBD7 expression was significantly correlated with Slug expression in SACC (P< 0.05). Increased BTBD7 expression was significantly associated with the TNM stage, tissue typing, distant metastasis and patients' poor clinical outcome.
CONCLUSIONS: Positive expression of BTBD7 in SACC could play an important role in the development of cancer and may serve as a favorable predictor for diagnosis and poor prognosis of patients.

Lopes ML, Barroso KM, Henriques ÁC, et al.
Pleomorphic adenomas of the salivary glands: retrospective multicentric study of 130 cases with emphasis on histopathological features.
Eur Arch Otorhinolaryngol. 2017; 274(1):543-551 [PubMed] Related Publications
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 49.7 years. 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.

Mardani M, AndishehTadbir A, Khademi B, et al.
Decreased Serum Monocyte Chemoattractant Protein1 in Salivary Gland Tumor Patients.
Asian Pac J Cancer Prev. 2016; 17(7):3601-4 [PubMed] Related Publications
BACKGROUND: The monocyte chemoattractant protein1 (MCP1/CCL2) is a potent chemoattractant for natural killer cells, monocytes, and memory T lymphocytes. However, any role in the genesis of salivary gland tumors (SGT) is unknown. To assess the diagnostic relevance of chemokines in SGT, MCP1 levels in the serum of patients were investigated in association with tumor progression and clinical aggressiveness.
MATERIALS AND METHODS: Using an ELISA kit, we assessed and compared the circulating levels of MCP1 in blood serum of 70 SGT patients with 44 healthy control samples.
RESULTS: The results of this study showed that the concentration of MCP1 was significantly lower in patients with benign (463.8±158.5pg/ml, P=0.033) and malignant (454.8±190.4pg/ ml, P=0.007) SGT than in healthy subjects (645.7±338.9). No significant difference in mean serum levels of MCP1 was observed between the benign and malignant group (p=0.9). While MCP1 levels were lower in patients with an advanced clinical stage, advanced tumor size, higher tumor grade, or lymph node involvement, but the mean MCP1 level between groups showed no statistically significant difference (p>0.05).
CONCLUSIONS: MCP1 levels in the serum of patients with SGT were decreased, indicating that this might a good marker for discriminating patients with SGT from healthy people. However, no clearcut relationship was detected between MCP1 levels and clinicopathologic factors, and MCP1 is not a good marker for evaluating tumor dissemination.

Park SW, Eade T, Pang L, et al.
Role of neck dissection in metastatic squamous cell carcinoma to the parotid gland.
J Laryngol Otol. 2016; 130 Suppl 4:S54-9 [PubMed] Related Publications
OBJECTIVE: To investigate the rate of occult neck disease in patients with metastatic squamous cell carcinoma to the parotid gland following parotidectomy and neck dissection.
METHODS: A consecutive series of patients treated between 2000 and 2014 for metastatic squamous cell carcinoma to the parotid were analysed. Patients were included if they had no clinical or radiological evidence of neck disease. Pathology of parotidectomy and neck dissection specimens was reviewed. Other variables analysed included patient immune status, surgery type, complications, use of positron emission tomography scanning and treatment with radiotherapy.
RESULTS: Sixty-five patients had no clinical or radiological evidence of neck disease initially. Forty-six patients (70.8 per cent) underwent neck dissection. Occult neck disease was only found in 8 of the 46 patients (17.3 per cent). Occult neck disease was found more often in those with immunocompromise (5.7 vs 38.5 per cent, p = 0.003). Patients who were immunocompromised had a significantly worse disease-specific survival rate at five years (0 vs 92 per cent, p = 0.0001).
CONCLUSION: Occult neck disease was seen in 17.3 per cent of patients and immunosuppression was a significant predictor for this.

Fomete B, Adeosun OO, Awelimobor DI, Olayemie L
Niger J Med. 2015 Jul-Sep; 24(3):277-80 [PubMed] Related Publications
INTRODUCTION: Pleomorphic adenoma or mixed tumour is a benign salivary gland tumour, presenting usually in the parotid or submandibular glands. This tumour contains elements of both epithelial and mesenchymal origin. They are the most common tumours (50%), (60-65%) of the major and minor salivary glands. The palate is considered as the most common intraoral site (42.8-68.8%), followed by the upper lip (10.1%) and cheek (5.5%).
CASE REPORT: A 37 year old female Nigerian house wife was seen with a four year history of painless slowly progressive upper lip swelling. Prior to her presentation, she had surgery for same swelling in a peripheral hospital. All other histories were not significant.
CONCLUSION: PA remains the commonest benign minor salivary gland neoplasm and excision with safe margins the treatment of choice.

Cidlinsky N, Dogliotti G, Pukrop T, et al.
Inactivation of the LKB1-AMPK signaling pathway does not contribute to salivary gland tumor development - a short report.
Cell Oncol (Dordr). 2016; 39(4):389-96 [PubMed] Related Publications
PURPOSE: Activation of AMPK by the tumor suppressor LKB1 represents an essential gatekeeping step for cells under energetic stress to prevent their growth and proliferation by inhibiting mTOR activation, until the energy supply normalizes. The LKB1/AMPK pathway is frequently downregulated in various types of cancer, thereby uncoupling tumor cell growth and proliferation from energy supply. As yet, little information is available on the role of the LKB1/AMPK pathway in tumors derived from salivary gland tissues.
METHODS: We performed LKB1 protein expression and AMPK and mTOR activation analyses in several salivary gland tumor types and their respective healthy control tissues using immunohistochemistry.
RESULTS: No significant downregulation of LKB1 expression or decreased activation of AMPK or mTOR were observed in any of the salivary gland tumors tested. In contrast, we found that the salivary gland tumors exhibited an increased rather than a decreased AMPK activation. Although the PI3K/Akt pathway was found to be activated in most of the analyzed tumor samples, the unchanged robust activity of LKB1/AMPK likely prevents (over)activation of mTOR.
CONCLUSION: In contrast to many other types of cancer, inactivation or downregulation of the LKB1/AMPK pathway does not substantially contribute to the pathogenesis of salivary gland tumors.

Schneider V, Nobile A, Duvoisin B, et al.
Myoepithelioma of the parotid gland with extensive adipocytic metaplasia: Report of a case with intriguing aspects on fine needle aspiration and p63 immunohistochemical expression.
Diagn Cytopathol. 2016; 44(12):1090-1093 [PubMed] Related Publications
Myoepithelioma is a rare and usually benign salivary gland tumor derived from myoepithelial cells. Variability in cellular morphology and stromal composition leads to diagnostic pitfalls on fine-needle aspiration cytology; therefore, histology and immunohistochemistry are often required for definitive diagnosis. We describe a case of parotid gland myoepithelioma in a 76-year-old woman, which was discovered incidentally on cerebral magnetic resonance imaging. Fine-needle aspiration sampled cohesive aggregates of spindle-shaped cells embedded in a fibrillary matrix as well as abundant mature adipocytes, initially considered as part of normal salivary gland parenchyma. Histology of the resected specimen showed bundles of spindle-shaped cells embedded in loose connective tissue, admixed with numerous intralesional adipocytes. Immunohistochemical studies revealed a diffuse expression of p63 by this adipocytic population, an observation clearly indicating that myoepithelial cells can trans-differentiate and acquire the morphology of mature adipocytes. Knowledge of this phenomenon can be helpful in the work-up of salivary gland lesions. Diagn. Cytopathol. 2016;44:1090-1093. © 2016 Wiley Periodicals, Inc.

Kadletz L, Aumayr K, Heiduschka G, et al.
Overexpression of DCLK1 is predictive for recurrent disease in major salivary gland malignancies.
Eur Arch Otorhinolaryngol. 2017; 274(1):467-475 [PubMed] Related Publications
Salivary gland carcinomas are a rare malignancy. Therefore, little is known about biomarkers and cancer stem cells in salivary gland malignancies. Double cortin-like kinase 1 (DCLK1) is a promising therapeutic target and cancer stem cell marker, predominantly investigated in pancreatic and colorectal cancer. The purpose of this study was to investigate the expression of DCLK1 in major and minor salivary gland carcinomas and its influence on survival. We examined a total of 80 patients with major or minor salivary gland cancer in this retrospective study. Immunohistochemistry with anti-DCLK1 antibody was applied to assess the expression of DCLK1. Moreover, we evaluated the impact of DCLK1 on overall and disease-free survival. DCLK1 expression could be detected in 66.3 % of all examined cases. Overexpression of DCLK1 was associated with reduced overall and disease-free survival in patients with major salivary gland cancer. Disease-free survival reached statistical significance (p = 0.0107). However, expression of DCLK1 had no influence on survival in patients with minor salivary gland cancer. Since treatment of recurrent disease in oncologic patients is utterly challenging, DCLK1 may be a promising prognostic biomarker that helps to identify patients with a high risk for recurrence of major salivary gland carcinoma.

Sayan M, Vempati P, Miles B, et al.
Adjuvant Therapy for Salivary Gland Carcinomas.
Anticancer Res. 2016; 36(8):4165-70 [PubMed] Related Publications
AIM: We compared the clinical outcomes and toxicity profile among a retrospective cohort of patients with primary major salivary gland carcinomas (SGCs) treated with surgery followed by adjuvant radiation therapy (S+RT) versus surgery and adjuvant chemoradiotherapy (S+CRT).
PATIENTS AND METHODS: Twenty patients (71%) underwent S+RT and eight (29%) S+CRT at our Institution between 2006 and 2015. Microscopic positive margins were present in 54% of the patients.
RESULTS: The 3-year overall survival (OS) was 100% with S+RT and 87.5% with S+CRT (p=0.141) and locoregional control (LRC) was 95% with S+RT and 87.5% with S+CRT (p=0.383). There were no significant differences in the rate of acute (p=0.801) and late (p=0.714) toxicities.
CONCLUSION: While we await randomized data, adjuvant CRT may be considered as a viable therapeutic option for patients at high-risk of local or regional recurrence, especially in those with a positive microscopic margin where further surgery may result in functional cranial neuropathies.

Israel Y, Rachmiel A, Ziv G, Nagler R
Benign and Malignant Salivary Gland Tumors - Clinical and Demographic Characteristics.
Anticancer Res. 2016; 36(8):4151-4 [PubMed] Related Publications
AIM: To examine the demographic, ethnic, and clinical characteristics of salivary benign and malignant tumors for better etiological understanding.
PATIENTS AND METHODS: We examined medical records of 287 primary salivary gland tumor patients.
RESULTS: Overall, 216 tumors were benign and 71 malignant. The mean age at diagnosis was 56.4 years for those with malignant tumors and 48.5 years for those with benign, a highly significant difference (p=0.001). Females had 45% of malignant tumors and 59% of benign, a significant difference (p=0.037). Ethnic origin, alcohol consumption and cigarette smoking rates were not significantly different (p>0.05) between groups. A total of 87% of benign and 55% of malignant tumors were in the parotid glands, a highly significant predilection (p<0.0001), sublocated mostly in the superfacial lobe; 36.6% of malignant tumors and 4.7% of benign (p<0.0001) were in the minor salivary glands, mostly in the hard palate.
CONCLUSION: Baseline clinical, demographic and locational aspects of benign and malignant tumors are substantiated.

Mays AC, Feng X, Browne JD, Sullivan CA
Chemokine and Chemokine Receptor Profiles in Metastatic Salivary Adenoid Cystic Carcinoma.
Anticancer Res. 2016; 36(8):4013-8 [PubMed] Related Publications
AIM: To characterize the chemokine pattern in metastatic salivary adenoid cystic carcinoma (SACC).
MATERIALS AND METHODS: Real-time polymerase chain reaction (RT-PCR) was used to compare chemokine and chemokine receptor gene expression in two SACC cell lines: SACC-83 and SACC-LM (lung metastasis). Chemokines and receptor genes were then screened and their expression pattern characterized in human tissue samples of non-recurrent SACC and recurrent SACC with perineural invasion.
RESULTS: Expression of chemokine receptors C5AR1, CCR1, CCR3, CCR6, CCR7, CCR9, CCR10, CXCR4, CXCR6, CXCR7, CCRL1 and CCRL2 were higher in SACC-83 compared to SACC-LM. CCRL1, CCBP2, CMKLR1, XCR1 and CXCR2 and 6 chemokine genes (CCL13, CCL27, CXCL14, CMTM1, CMTM2, CKLF) were more highly expressed in tissues of patients without tumor recurrence/perineural invasion compared to those with tumor recurrence. CCRL1 (receptor), CCL27, CMTM1, CMTM2, and CKLF (chemokine) genes were more highly expressed in SACC-83 and human tissues of patients without tumor recurrence/perineural invasion.
CONCLUSION: CCRL1, CCL27, CMTM1, CMTM2 and CKLF may play important roles in the development of tumor metastases in SACC.

Sumida T, Kamata YU, Kobayashi Y, et al.
ID1 Controls Aggressiveness of Salivary Gland Cancer Cells via Crosstalk of IGF and AKT Pathways.
Anticancer Res. 2016; 36(8):3865-70 [PubMed] Related Publications
BACKGROUND: Inhibitor of differentiation or DNA binding 1 (ID1) is overexpressed in human salivary gland cancer (SGC). The insulin growth factor (IGF) system is an attractive target in cancer control because it is associated with various cancer progressions.
MATERIALS AND METHODS: The human SGC cell line HSY with abundant ID1 was used. ID1 knockdown and its effect on the IGF system were investigated. Cell proliferation and invasion, as well as associated protein expression, were analyzed. Phospho-AKT was also evaluated.
RESULTS: ID1 knockdown reduced cell proliferation and invasion, while the expression of proteins associated with malignant phenotypes was altered. IGF-II expression was suppressed, suggesting that this system is one of the mechanisms underlying effects of ID1 in SGC cells. c-Myc was up-regulated, whereas p21 and p27 were down-regulated. Moreover, phospho-AKT was reduced in ID1-knockeddown cells.
CONCLUSION: ID1 down-regulation induced parallel changes in the IGF and AKT pathways. The crosstalk of these pathways may enhance malignant phenotypes in SGCs.

Avadhani V, Cohen C, Siddiqui MT
PLAG1: An Immunohistochemical Marker with Limited Utility in Separating Pleomorphic Adenoma from Other Basaloid Salivary Gland Tumors.
Acta Cytol. 2016; 60(3):240-5 [PubMed] Related Publications
OBJECTIVE: Fine-needle aspiration (FNA) diagnosis of salivary gland neoplasms is often challenging. Differentiating between pleomorphic adenomas (PA) and other basaloid neoplasms, especially basal cell adenoma (BCA) and adenoid cystic carcinoma (AdCC), can be difficult in cellular aspirates. PLAG1 (PA gene 1) is a proto-oncogene, which is frequently rearranged in PAs, leading to the aberrant expression of its protein. PLAG1 IHC expression has been reported to be positive in most PAs. The aim of this study was to evaluate the sensitivity and specificity of PLAG1 to differentiate PA from other basaloid neoplasms.
STUDY DESIGN: Immunohistochemical evaluation of PLAG1 was performed on 125 cases (52 FNAs and 73 surgical excisions). Nuclear staining of tumor cells was scored by the intensity and percentage of positive tumor cells. A combined score of >5 was defined as positive.
RESULTS AND CONCLUSION: The sensitivity (55%) and specificity (75%) of PLAG1 in diagnosing PA in FNAs is relatively modest thus limiting its diagnostic utility. BCAs and AdCCs showed PLAG1 false positivity, in surgical excision specimens and less so in FNAs. This may be due to limited sampling or tumor heterogeneity. Hence, PLAG1 is a modest marker for PAs in FNAs.

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