Salivary Gland Cancer
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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:

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.

Menu: Salivary Gland Cancer

Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications

Information Patients and the Public (6 links)


Information for Health Professionals / Researchers (7 links)

Latest Research Publications

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

Shah AA, LeGallo RD, van Zante A, et al.
EWSR1 genetic rearrangements in salivary gland tumors: a specific and very common feature of hyalinizing clear cell carcinoma.
Am J Surg Pathol. 2013; 37(4):571-8 [PubMed]
The Ewing sarcoma breakpoint region 1 (EWSR1) is translocated in many sarcomas. Recently, its rearrangement has been described in salivary gland hyalinizing clear cell carcinomas (HCCCs) and in a subset of soft tissue myoepitheliomas. This study examines the presence of the EWSR1 rearrangement in a variety of salivary gland lesions including classic myoepitheliomas and HCCCs. Using a tissue microarray and whole-mount sections, fluorescence in situ hybridization (FISH) was performed on a variety of salivary gland lesions including HCCCs. The EWSR1 rearrangement was detected in 87% of HCCCs (13 of 15); all other salivary gland lesions including classic myoepitheliomas had intact EWSR1. Patients with HCCCs with rearranged EWSR1 included 1 man, 10 women, and 2 of unknown sex. Ages ranged from 35 to 83 years; the tumor size ranged from 0.8 to 5.5 cm, and the involved locations included: palate (2), base of the tongue (2), mandible (2), submandibular gland (2), lip (1), floor of the mouth (1), sublingual gland (1), inner cheek (1), and nasopharynx (1). All HCCCs were composed of sheets and nests of monotonous cells with clear cytoplasm within a hyalinized stroma. All tested cases were immunoreactive with antibodies to p63 and were nonreactive with antibodies to more conventional myoepithelial antigens (e.g., smooth muscle actin and S100 protein). These findings show that the EWSR1 rearrangement is almost a defining feature of HCCCs and also confirm that classic salivary gland myoepitheliomas are distinct from these tumors and do not share a pathogenetic relationship with their soft tissue counterparts.


Huang MW, Zhang JG, Zhang J, et al.
Oncocytic carcinoma of the parotid gland.
Laryngoscope. 2013; 123(2):381-5 [PubMed]
OBJECTIVES/HYPOTHESIS: The incidence of oncocytic carcinoma of the parotid gland is low, so a systematic evaluation of treatment strategies is lacking. We aimed to describe our experiences in treating this malignancy.
STUDY DESIGN: Retrospective study.
METHODS: We reviewed the files for 18 patients (14 males) of oncocytic carcinoma of the parotid gland in our institution from 1991 to 2011. Four patients underwent surgery alone, four surgery and postoperative radiotherapy, nine surgery and postoperative brachytherapy, and one radiotherapy alone. Median follow-up was 36 months (range 2-108 months).
RESULTS: The 5-year local control rate was 66.9%, overall survival 68.6%, disease progression-free survival 46.2%, and 5-year freedom from distant metastasis 61.0%. Clinical N category, local recurrence, and distant metastasis significantly influenced overall survival.
CONCLUSIONS: Conservative parotidectomy is not radical enough to treat oncocytic carcinoma of the parotid gland. Elective neck dissection is recommended for patients with cancer stage T2 to 4. Surgery with postoperative (125) I brachytherapy leads to good local control for patients with advanced disease or with positive or close resection margins.


Brusić SK, Pusić M, Cvjetković N, et al.
Osteosarcoma of the mastoid process following radiation therapy of mucoepidermoid carcinoma of the parotid gland--a case report.
Coll Antropol. 2012; 36 Suppl 2:223-5 [PubMed]
Radiation therapy is frequently used method in treatment of the head and neck malignancies. Osteosarcoma is a rare complication of radiation therapy and usually occurs after a long latent period. We report the case of 75-year-old female with osteosarcoma of the mastoid process. Twelve years before presentation she received radiation therapy after total parotidectomy and radical neck dissection in treatment of mucoepidermoid carcinoma of the parotid gland. Diagnostic procedures included contrast-enhanced CT and MRI of the head and neck and HRCT of the temporal bone. The final diagnosis of the low grade osteosarcoma was confirmed by biopsy. Diagnostic criteria were fulfilled and the lesion was classified as a radiation induced osteosarcoma.


Ostović KT, Luksić I, Virag M, et al.
The importance of team work of cytologist and surgeon in preoperative diagnosis of intraoral minor salivary gland tumours.
Coll Antropol. 2012; 36 Suppl 2:151-7 [PubMed]
Tumours arising from oral minor salivary glands may exhibit an overlap of clinical and morphological features that may produce diagnostic and therapeutic dilemmas. The aim of this study is to asses the value of fine needle aspiration cytology (FNAC) in differentiation of benign and malignant tumours and to render a specific diagnosis. We evaluated the team work of surgeon and cytologist to improve diagnostic accuracy. Two steps are important for accuracy: sampling aspirate that should be done together by surgeon and cytologist and cytological microscopic analysis of the smears that should be performed by an experienced cytologist. The study included 132 patients with intraoral minor salivary gland tumours between 2002 and 2011. Adequate material was obtained from 121 (91.7%) patients. FNAC was usually performed by cytologist in a team with maxillofacial surgeon at cytology department that is more convenient for preparing the samples and especially for ROSE procedure (rapid-on site evaluation) of smears. In such a way the cytologist checked the adequacy of samples and decided whether some ancillary techniques should be used and therefore repeat FNAC. A total of 82 patients underwent surgery, 40 with malignant and 42 with benign tumours. Preoperative cytological diagnoses were compared with histopathological ones using histopathology as a gold standard. The most common benign tumour was pleomorphic adenoma and among malignant tumours adenoid cystic carcinoma. The most commonly affected site was the palate. The team work of surgeon and cytologist achieved specificity of 95.1%, sensitivity of 97.6% and diagnostic accuracy of 96.3%. We can conclude that although subclassification of some tumour types of salivary glands remains poor, FNAC is invaluable in patient triage and therefore should be considered in the first line investigations of these lesions by the cytologist and surgeon.


Luksić I, Suton P, Manojlović S, et al.
Pleomorphic adenoma in ectopic salivary gland tissue in the neck.
Coll Antropol. 2012; 36 Suppl 2:133-6 [PubMed]
A case of pleomorphic adenoma originating from ectopic salivary gland tissue (ESGT) of the upper neck is reported. A 34-year-old male patient was referred to our Department for a painless swelling in the right submandibular region. Preoperative evaluation (clinical examination, fine-needle aspiration cytology (FNAC) and imaging studies) was performed and the finding was that of pleomorphic adenoma in ESGT A modified "S" incision with extension to the submandibular region was performed and the tumour was extirpated. The histopathological report confirmed our initial diagnosis. No recurrence was obtained during a four-year follow-up period. Isolated neck mass may be overlooked as ectopic salivary gland tissue neoplasm (ESGTN). Proper preoperative assessment and optimal surgical treatment are the keys for successful management of these rare tumours. The distinction between metastatic lesion from a head and neck tumour and ESGTN may present considerable diagnostic problem. A review of the literature on ESGT and associated tumours with emphasis on clinical features, diagnosis and treatment is also presented.


Southorn B, Manor E, Bodner L, et al.
Metachronous pleomorphic adenomas occurring in the parotid and a minor salivary gland with genetic changes detected by comparative genomic hybridization.
J Oral Maxillofac Surg. 2013; 71(4):805-8 [PubMed]
A 32-year-old female underwent an extracapsular dissection for a pleomorphic adenoma (PA) of the parotid gland. Six months later, she presented with an increasing lump on the upper lip that, following excision, was confirmed to be a second PA. Formalin-fixed paraffin embedded tissues were analyzed for chromosomal aberrations. Comparative genomic hybridization analysis showed multiple chromosomal aberrations in the parotid PA. In comparison, no chromosomal aberrations were found in the lip PA. To our knowledge, metachronous benign pleomorphic adenomas occurring in both a major and minor salivary gland is unreported, and furthermore, there are no comparative genomic hybridization reports of this rare occurrence. We discuss the clinicopathological implications.


Tsuneki M, Maruyama S, Yamazaki M, et al.
Podoplanin is a novel myoepithelial cell marker in pleomorphic adenoma and other salivary gland tumors with myoepithelial differentiation.
Virchows Arch. 2013; 462(3):297-305 [PubMed]
The expression of podoplanin, one of the representative immunohistochemical markers for lymphatic endothelium, is upregulated in various kinds of cancers. Based on our previous studies, we have developed a hypothesis that podoplanin plays a role in cell adhesion via its association with extracellular matrix (ECM). Since salivary pleomorphic adenoma is histologically characterized by its ECM-enriched stroma, we firstly wanted to explore the expression modes of podoplanin in pleomorphic adenoma and related salivary tumors by immunohistochemistry. In normal salivary gland, podoplanin was specifically localized in myoepithelial cells, which were also positively labeled by antibodies against P63, of the intercalated duct as well as acini. In pleomorphic adenoma, podoplanin was colocalized with P63 and CD44 in basal cells of glandular structures as well as in stellate/spindle cells in myxochondroid matrices, where perlecan and hyaluronic acid were enriched. The expression of podoplanin was confirmed at both protein and mRNA levels in pleomorphic adenoma cell systems (SM-AP1 and SM-AP4) by using immunofluorescence, western blotting, and reverse transcription polymerase chain reaction. Podoplanin was localized on the cell border as well as in the external periphery of the cells. Moreover, podoplanin expression was also confirmed in tumor cells with myoepithelial differentiation in myoepithelioma and intraductal papilloma. The results indicate that podoplanin can be regarded as a novel myoepithelial marker in salivary gland tumors and suggest that podoplanin's communication with ECM molecules is essential to phenotypic differentiation to myoepithelial cells.


Ach T, Zeitler K, Schwarz-Furlan S, et al.
Aberrations of MET are associated with copy number gain of EGFR and loss of PTEN and predict poor outcome in patients with salivary gland cancer.
Virchows Arch. 2013; 462(1):65-72 [PubMed]
Hepatocyte growth factor receptor (MET) is a key driver of oncogenic transformation. Copy number gain and amplification of MET positively enhance tumour growth, invasiveness and metastasis in different cancer types. In the present study, 266 carcinomas of the major and minor salivary glands were investigated for genomic MET status by fluorescence in situ hybridization and for protein expression by immunohistochemistry. Results were matched with clinicopathological parameters, long-term survival and the status of epidermal growth factor receptor (EGFR) and phosphatase and tensin homologue (PTEN). Low polysomy (n = 42), high polysomy (n = 27), amplification (n = 2) and deletion (n = 18) were found as aberrations of genomic MET in certain subtypes. MET aberrations were associated with increased patient age (>70 years, p = 0.003), male gender (p = 0.01), increased tumour size (p = 0.002), lymph node metastases (p < 0.001), high-grade malignancy (p < 0.001) and unfavourable overall survival (p < 0.001). Both copy number gain (p < 0.001) and deletion (p = 0.031) of MET correlated with copy number gain of EGFR. Tumours with genomic loss of PTEN (n = 48) concurrently presented aberration of genomic MET (p < 0.001). MET gene status significantly correlated with protein status (p = 0.038). In conclusion, gain but also loss of genomic MET activity correlates with aggressive tumour growth, nodal metastasis and worse overall survival in salivary gland cancer. Moreover, aberrations of MET are associated with EGFR and PTEN signalling and might possess relevance for targeted therapies of salivary gland carcinomas in the future.


Agaimy A, Ihrler S, Märkl B, et al.
Lipomatous salivary gland tumors: a series of 31 cases spanning their morphologic spectrum with emphasis on sialolipoma and oncocytic lipoadenoma.
Am J Surg Pathol. 2013; 37(1):128-37 [PubMed]
Lipomatous neoplasms of the salivary glands are rare. Their wide histologic spectrum has not been sufficiently studied. We collected 31 fat-containing salivary gland lesions excluding pleomorphic adenoma and myoepithelioma with lipometaplasia. There were 19 male and 12 female patients aged 7 to 89 years (mean, 53 y). Tumors originated in the parotid (n=29) and the submandibular (n=2) gland. On the basis of the proportion and distribution of adipose tissue and the epithelial type, tumors could be categorized into 3 main groups: ordinary lipoma (n=20) identical to soft tissue lipoma but located within the salivary gland, oncocytic lipoadenoma (n=6) composed predominantly of oncocytes with variable fatty component, nononcocytic sialolipoma (n=4) composed of lobular fatty tissue (≥70%) with evenly distributed normal salivary tissue recapitulating the composition of normal salivary glands and microcystic lipoadenoma (n=1) composed of cystic ducts admixed with adipose tissue. The mean tumor size was 3.3, 3.8, and 2.9 cm for lipoma, oncocytic lipoadenoma, and nononcocytic sialolipoma, respectively. Associated diseases included Madelung disease with bilateral atypical lipomatous tumors of the neck and bilateral parotid lipoma (1), oncocytic lipoadenoma after irradiation for sinonasal adenocarcinoma (1), and periparotideal lipoma excised years before oncocytic lipoadenoma (1) and nononcocytic sialolipoma (1). No recurrence was recorded at a mean follow-up of 72 months (range, 6 to 184 mo). Sebaceous islands were seen in 5/6 oncocytic lipoadenomas and in 2/4 sialolipomas. Periductal inflammation/fibrosis was common in sialolipoma and oncocytic lipoadenoma. This study demonstrates the wide morphologic spectrum of fatty salivary gland lesions. Oncocytic lipoadenoma is an epithelial-predominant tumor that is distinct from the fat-dominated nononcocytic sialolipoma, but the 2 types seem to merge in some cases.


Chow TL, Choi CY, Lam SH
Parotidectomy under local anesthesia--report of 7 cases.
Am J Otolaryngol. 2013 Jan-Feb; 34(1):79-81 [PubMed]
OBJECTIVE: Parotidectomy is usually carried out under general anesthesia. We reported our early experience of performing parotidectomy under local anesthesia.
STUDY DESIGN: Case series reviewed.
SETTING: Head and neck services of a regional hospital. PATIENTS, INTERVENTION, AND RESULTS: Seven patients underwent parotidectomy under local anesthesia. The indications were high risk for general anesthesia due to co-morbidity in 2 patients and personal preference for the rest. The operations were performed by retrograde facial nerve dissection after superficial cervical plexus block and incision wound infiltration with local anesthetics. There was no conversion to general anesthesia. Six operations were carried out in the setting of ambulatory procedure and were discharged on the same day. Transient mild facial paresis occurred in 2 patients.
CONCLUSION: Parotidectomy under local anesthesia can be conducted successfully and avoid the adverse effect of general anesthesia.


Friedman ER, Saindane AM
Pitfalls in the staging of cancer of the major salivary gland neoplasms.
Neuroimaging Clin N Am. 2013; 23(1):107-22 [PubMed]
The major salivary glands consist of the parotid, submandibular, and sublingual glands. Most neoplasms in other subsites in the head and neck are squamous cell carcinoma, but tumors of the salivary glands may be benign or malignant. Surgical treatment differs if the lesion is benign, and therefore preoperative fine needle aspiration is important in salivary neoplasms. The role of imaging is to attempt to determine histology, predict likelihood of a lesion being malignant, and report an imaging stage. This article reviews the various histologies, imaging features, and staging of major salivary gland neoplasms.


Arias-Santiago S, Aneiros-Fernández J, Arias-Santiago B, et al.
MTNR1A receptor expression in normal and pathological human salivary glands.
Anticancer Res. 2012; 32(11):4765-71 [PubMed]
AIM: To analyze and compare the expression of MTNR1A receptor in normal and pathological major and minor salivary glands.
MATERIALS AND METHODS: Twenty samples of major and minor salivary glands and 10 with Warthin's tumor were studied. Expression of the MTNR1A receptor (goat polyclonal antibody raised against a peptide mapping at the N-terminus of MEL-1A R of human origin) was analyzed.
RESULTS: The excretory ducts of major salivary glands demonstrated intense intracytoplasmic positivity but scant cytoplasmic membrane positivity for MTNR1A. The studied Warthin's tumors showed intense cytoplasmic positivity for MT1 receptor in all cylindrical epithelial cells lining spaces and a less intense positivity in basal cells. The lymphoid component accompanying the tumor was negative for MT1 receptor.
CONCLUSION: Intense intracytoplasmic positivity for the MTNR1A receptor in the excretory ducts of human major and minor salivary glands and Warthin's tumor was found. The intense expression of MTNR1A receptors observed in this study in the excretory ducts of major and minor salivary glands may be related to salivary regulation.


Noroozi N, Modabber A, Hölzle F, et al.
Carotid sinus syndrome as the presenting symptom of cystadenolymphoma.
Head Face Med. 2012; 8:31 [PubMed] Free Access to Full Article
Carotid sinus syndrome is a serious manifestation of head and neck malignancy. The purpose of this study was to clarify the presence of carotid sinus syndrome in a patient with cystadenolymphoma. To our knowledge carotid sinus syndrome secondary to cystadenolymphoma has not been reported to date. A 45-year-old woman with one-week-old swelling in the left mandibular angle having disturbing symptoms of vertigo, consciousness and sinus arrest. Holter monitoring revealed several episodes of sinus arrest. Ultrasonography showed a well-defined space-occupying lesion of about 31 mm in length and 17 mm in width located in the deep lobe of the left parotid gland. Computerized tomography (CT) showed a large mass extending into the carotid space and protruding into the parapharyngeal space. Parotidectomy was performed. Surgical removal of the tumor resulted in complete amelioration of symptoms and disappearance of electrocardiogram abnormalities. Here we report on a clinical case of carotid sinus syndrome associated with cystadenolymphoma. To our knowledge carotid sinus syndrome secondary to cystadenolymphoma has not been reported to date, and is made more remarkable as a possible differential diagnosis after clarification of all possible causes. Early diagnosis and immediate management can minimize complications.


Shao C, Tan M, Bishop JA, et al.
Suprabasin is hypomethylated and associated with metastasis in salivary adenoid cystic carcinoma.
PLoS One. 2012; 7(11):e48582 [PubMed] Free Access to Full Article
BACKGROUND: Salivary gland adenoid cystic carcinoma (ACC) is a rare cancer, accounting for only 1% of all head and neck malignancies. ACC is well known for perineural invasion and distant metastasis, but its underlying molecular mechanisms of carcinogenesis are still unclear.
PRINCIPAL FINDINGS: Here, we show that a novel oncogenic candidate, suprabasin (SBSN), plays important roles in maintaining the anchorage-independent and anchorage-dependent cell proliferation in ACC by using SBSN shRNA stably transfected ACC cell line clones. SBSN is also important in maintaining the invasive/metastatic capability in ACC by Matrigel invasion assay. More interestingly, SBSN transcription is significantly upregulated by DNA demethylation induced by 5-aza-2'-deoxycytidine plus trichostatin A treatment and the DNA methylation levels of the SBSN CpG island located in the second intron were validated to be significantly hypomethylated in primary ACC samples versus normal salivary gland tissues.
CONCLUSIONS/SIGNIFICANCE: Taken together, these results support SBSN as novel oncogene candidate in ACC, and the methylation changes could be a promising biomarker for ACC.


Thariat J, Vedrine PO, Temam S, et al.
The role of radiation therapy in pediatric mucoepidermoid carcinomas of the salivary glands.
J Pediatr. 2013; 162(4):839-43 [PubMed]
OBJECTIVE: To investigate the role of radiation therapy in rare salivary gland pediatric mucoepidermoid carcinoma (MEC).
STUDY DESIGN: A French multicenter retrospective study (level of evidence 4) of children/adolescents treated for MEC between 1980 and 2010 was conducted.
RESULTS: Median age of the 38 patients was 14 years. Parotid subsite, low-grade, and early primary stage tumors were encountered in 81%, 82%, and 68% of cases, respectively. All except 1 patient were treated by tumoral surgical excision, and 53% by neck dissection (80% of high grades). Postoperative radiation therapy and chemotherapy were performed in 29% and 11% of cases. With a median 62-month follow-up, overall survival and local control rates were 95% and 84%, respectively. There was 1 nodal relapse. Lower grade and early stage tumors had better survival. Postoperative radiation therapy and chemotherapy were associated with similar local rates. Patients with or without prior cancer had similar outcomes.
CONCLUSIONS: Pediatric salivary gland MEC carries a good prognosis. Low-intermediate grade, early-stage tumors should be treated with surgery alone. Neck dissection should be performed in high-grade tumors. Radiation therapy should be proposed for high grade and/or advanced primary stage MEC. For high-grade tumors without massive neck involvement, irradiation volumes may be limited to the primary area, given the risk of long-term side effects of radiation therapy in children. Pediatric MEC as second cancers retain a similar prognosis. Long-term follow-up is needed to assess late side effects and second cancers.


Mitsimponas KT, Agaimy A, Schlittenbauer T, et al.
Oncocytic lipoadenoma of the parotid gland: a report of a new case and review of the literature.
Int J Clin Exp Pathol. 2012; 5(9):1000-6 [PubMed] Free Access to Full Article
Oncocytic lipoadenoma is a rare salivary gland tumour composed of adipose tissue and oncocytic epithelial cells in varied proportions. This tumour is still not included in the current WHO classification of salivary gland neoplasms. We herein report a further case of oncocytic lipoadenoma originating in the parotid gland of a 55-year-old woman. The tumour presented as a slowly growing asymptomatic left-sided parotid gland mass. The resected tumour measured 2.7 cm in maximum diameter and was composed of oncocytoma-like epithelial component admixed with mature adipocytes that made up 10% of the whole mass. Foci of sebaceous differentiation were seen. This rare variant of lipomatous salivary gland tumours is in need of more recognition and should be distinguished from other fat-containing salivary gland lesions, particularly lipomatous pleomorphic adenoma and myoepithelioma.


Balasundram S, Mustafa WM, Ip J, et al.
Conservative neck dissection in oral cancer patients: a 5 year retrospective study in Malaysia.
Asian Pac J Cancer Prev. 2012; 13(8):4045-50 [PubMed]
OBJECTIVE: The impact of ablative oral cancer surgery was studied, with particular reference to recurrence and nodal metastasis, to assess survival probability and prognostic indicators and to elucidate if ethnicity influences the survival of patients.
METHODS: Patients who underwent major ablative surgery of the head and neck region with neck dissection were identified and clinical records were assessed. Inclusion criteria were stage I-IV oral and oropharyngeal malignancies necessitating resection with or without radiotherapy from 2004 to 2009. All individuals had a pre-operative assessment prior to the surgery. The post operative assessment period ranged from 1 year to 5 years. Survival distributions were analyzed using Kaplan-Meier curves.
RESULTS: 87 patients (males:38%; females:62%) were included in this study, with an age range of 21-85 years. Some 78% underwent neck dissections while 63% had surgery and radiotherapy. Nodal recurrence was detected in 5.7% while 20.5% had primary site recurrence within the study period. Kaplan-Meier survival analysis revealed that the median survival time was 57 months. One year overall survival (OS) rate was 72.7% and three year overall survival rate dropped to 61.5%. On OS analysis, the log-rank test showed a significant difference of survival between Malay and Chinese patients (Bonferroni correction p=0.033). Recurrence-free survival (RFS) analysis revealed that 25% of the patients have reached the event of recurrence at 46 months. One year RFS rate was 85.2% and the three year survival rate was 76.1%. In the RFS analysis, the log-rank test showed a significant difference in the event of recurrence and nodal metastasis (p<0.001).
CONCLUSION: Conservative neck is effective, in conjunction with postoperative radiotherapy, for control of neck metastases. Ethnicity appears to influence the survival of the patients, but a prospective trial is required to validate this.


Andry G, Hamoir M, Locati LD, et al.
Management of salivary gland tumors.
Expert Rev Anticancer Ther. 2012; 12(9):1161-8 [PubMed]
Surgery after proper imaging (MRI or CT scan) is the main stay of treatment for salivary gland tumors. Although excision margins should be ≥5 mm for malignant tumors in cases of parotid gland carcinoma, the facial nerve should be preserved whenever it is not infiltrated. Adjuvant external radiation is indicated for malignant tumors with high-risk features such as close (or invaded) margins, perineural speed, lymphatic and/or vascular invasion, lymph-node involvement and high-grade histology. A Phase II trial testing adjuvant concomitant cisplatin plus radiation therapy versus adjuvant radiation therapy alone after surgery is currently under investigation for high-risk salivary gland cancer. For inoperable cancers, photons combined with proton boost seem to be a valuable option. Even if protons or carbon ions are promising, access to the latter is limited for usual treatment. For recurrent and/or metastatic cancer, polychemotherapy (cisplatin based) gives a 25% response rate in adenoid cystic carcinoma and should be used when the disease is overtly in progression. Targeted therapies with anti-EGF receptor molecules, antiangiogenic agents and tyrosine kinase inhibitors are ongoing, but more trials are needed to establish their efficacy, as is the use of bortezomib followed by doxorubicin. The products of fusion oncogenes, which have a pathogenic role in some adenoid cystic carcinoma and mucoepidermoid carcinomas, are of interest as potential therapeutic targets.


De Stefano A, Kulamarva G, Citraro L, et al.
Malignant peripheral nerve sheath tumour (malignant epithelioid Schwannoma) of the parotid gland.
Bratisl Lek Listy. 2012; 113(10):628-31 [PubMed]
PROBLEMS/OBJECTIVES: Malignant peripheral nerve sheath tumours are uncommon soft tissue tumours originating from Schwann cells or nerve sheath cells. Malignant epithelioid schwannoma is an aggressive variant of malignant peripheral nerve sheath tumour, and unfortunately is related with a high rate of recurrence and poor prognosis.
METHODOLOGY: In this study we present a rare case of malignant epithelioid schwannoma of the parotid gland and we discuss its origin, unusual presentation, and possible treatments options.
RESULTS: Patient underwent total parotidectomy without neck dissection. Postoperative radiotherapy and chemotherapy management were not necessary.
CONCLUSION: Patients with malignant epithelioid schwannomas typically present with pain and/or rapid enlargement of a pre-existing lesion but the diagnosis of these tumours remains difficult as it is based primarily on clinical suspicion. There is no recognized management for this tumour yet while the prognosis seems to correlate best with the extent of surgical resection (Fig. 4, Ref. 16).


Vidal MT, de Oliveira Araújo IB, Gurgel CA, et al.
Density of mast cells and microvessels in minor salivary gland tumors.
Tumour Biol. 2013; 34(1):309-16 [PubMed]
The aim of this study was to investigate the density of mast cells and microvessels in minor salivary gland tumors. Forty-one cases of minor salivary gland tumors (pleomorphic adenoma, n = 10; adenoid cystic carcinoma, n = 11; mucoepidermoid carcinoma, n = 10; and polymorphous low-grade adenocarcinoma) were investigated using immunohistochemistry for mast cell tryptase and von-Willebrand factor. Density of mast cells was higher in mucoepidermoid carcinoma; however, no differences in the number of these cells were observed between the different types of tumors (p > 0.05). The number of mast cells was higher in periparenchymal areas in all tumors, but the difference was not significant (p > 0.05). Mucoepidermoid carcinoma showed the largest number of periparenchymal mast cells, whereas pleomorphic adenomas showed the smallest number of intraparenchymal mast cells (p > 0.05). The highest microvessel density was observed in mucoepidermoid carcinomas, being this difference statistically significant when mucoepidermoid carcinoma was compared to pleomorphic adenoma (p = 0.0034) and polymorphous low-grade adenocarcinoma (p = 0.004). Microvessel density was significantly higher in adenoid cystic carcinoma when compared to pleomorphic adenoma (p = 0.0406) and polymorphous low-grade adenocarcinoma (p = 0.0123). Comparison of mast cells and microvessel densities showed no significant difference between tumors. A quantitative difference in mast cells and microvessels was observed, particularly in mucoepidermoid carcinoma, a finding supporting the aggressive behavior of malignant salivary gland tumors without myoepithelial differentiation. Further studies are needed to determine the role of mast cells in angiogenesis, as well as in the development and biological behavior of these tumors.


Saleh KA, Nurishmah MI, Firouzeh GN, Goh BS
Primary clear cell carcinoma of minor salivary gland of the soft palate: a case report.
Med J Malaysia. 2012; 67(3):335-6 [PubMed]
Clear cells can be found in numerous salivary and non-salivary tumors in the head and neck region, including metastatic lesions. They are rare low-grade tumors accounting for less than 1% of all salivary gland tumors and occur almost exclusively in the intra-oral minor salivary glands. Hyalinizing clear cell carcinoma (HCCC) is an extremely rare and recently described neoplasm predominantly affecting the oral cavity. Histologically, it is characterized by nests of glycogen-rich monomorphic clear cells within a hyaline stroma. HCCC often follows an indolent course with a limited metastatic potential. It is therefore important to differentiate this entity from other more aggressive clear cell tumors including metastatic tumors such as renal cell carcinoma. We hereby report a case of HCCC localized in minor salivary glands specifically in soft palate for its rarity, as well as to discuss the role of immunohistochemical stains, essential for its definitive diagnosis.


Skalova A, Altemani A, Di Palma S, et al.
Pleomorphic adenoma of the salivary glands with intravascular tumor deposits: a diagnostic pitfall.
Am J Surg Pathol. 2012; 36(11):1674-82 [PubMed]
The diagnosis of pleomorphic adenoma (PA) of salivary glands is usually straightforward posing few diagnostic problems for the general surgical histopathologist. The purpose of our investigation was to present a series of 22 cases of PA of major salivary glands, each of which contained small foci of tumor within vascular spaces. This feature has previously been described very rarely in PA and may represent a significant diagnostic pitfall. The patients included 12 women and 10 men, ranging in age at diagnosis from 17 to 82 years. Histopathologically, all 22 tumors displayed the features of PA with mixed epithelial and myoepithelial growth patterns and chondromyxoid areas. None of these neoplasms showed any cytologic evidence of malignancy. In all cases, there were multiple dilated thin-walled and/or muscular thick-walled blood vessels containing small intraluminal collections of neoplastic cells with or without myxoid stromal components. The intravascular tumor cells expressed cytokeratins, and in some cases they were also immunoreactive for S-100 protein, GFAP, D2-40, and p63 protein. The intravascular location of the neoplastic cells was confirmed by CD31, CD34, and factor VIII-related antigen immunostains. Reaction for D2-40 was negative in the endothelium of the involved vessel in all cases, confirming that they were vascular rather than lymphatic channels. Seven patients (36%) underwent fine-needle aspiration biopsy 25 days to several years before excision of the tumor. Follow-up of the patients in our series revealed no cases of recurrence or metastasis (range, 6 mo to 9.5 y; mean 3.8 y; median 3.5 y). The biological significance of intravascular tumor in PA is not clear, but there is growing evidence that it is an innocuous phenomenon that might be related to artifactual spillage caused by tumor injury presumably by either fine-needle aspiration or intraoperative trauma.


Liu H, Chen G, Zhang W, et al.
Overexpression of macrophage migration inhibitory factor in adenoid cystic carcinoma: correlation with enhanced metastatic potential.
J Cancer Res Clin Oncol. 2013; 139(2):287-95 [PubMed]
OBJECTIVES: Adenoid cystic carcinoma (ACC) is a malignant tumor frequently arising in salivary glands with poor long-term prognosis due to high rates of local recurrences and distant metastases. Macrophage migration inhibitory factor (MIF) is a multi-functional cytokine and has recently emerged as a pro-tumorigenic factor in various cancers. This study is designed to investigate the expression status and functional significance of MIF in ACC.
METHODS: Immunohistochemical staining was performed to evaluate the expression levels of MIF, HIF-1α, MMP-9, p53, and p-JNK in ACC tissues. In vitro, ACC-2 cells were exposed to recombinant human MIF (rMIF) or ISO-1 (an inhibitor of MIF) at different concentrations and times, followed by the detection of cell growth, viability, migration, and invasion, as well as the expression levels of several cellular signals.
RESULTS: The immunohistochemical results demonstrated the overexpression of MIF in ACC tissues as well as its association with the distant metastasis. Further analyses showed a significant correlation between the staining of MIF and p-JNK. Moreover, the in vitro studies revealed that the treatment for ACC cells with ISO-1 significantly attenuated cell migratory and invasive capacity, as opposed to the limited promotive effects of rMIF. More importantly, MIF inhibition could cause the activation of JNK, correlating with the immunohistochemical findings on ACC tissues.
CONCLUSIONS: The results suggest that MIF is likely to be an important player in the pathogenesis of ACC and may promote cancer metastasis, which possibly involves JNK inactivation. Further investigation of MIF-mediated molecular events may provide novel insights into the treatment for ACC.


Zbären P, Vander Poorten V, Witt RL, et al.
Pleomorphic adenoma of the parotid: formal parotidectomy or limited surgery?
Am J Surg. 2013; 205(1):109-18 [PubMed]
BACKGROUND: Optimal surgery for pleomorphic adenoma of the parotid is controversial. In the present review, we discuss the advantages and disadvantages of the various approaches after addressing the surgical pathology of the parotid pleomorphic adenoma capsule and its influence on surgery.
DATA SOURCES: PubMed literature searches were performed to identify original studies.
CONCLUSIONS: Almost all pleomorphic adenomas can be effectively treated by formal parotidectomy, but the procedure is not mandatory. Extracapsular dissection is a minimal margin surgery; therefore, in the hands of a novice or occasional parotid surgeon, it may result in higher rates of recurrence. Partial superficial parotidectomy may be a good compromise. The tumor is removed with a greater cuff of healthy parotid tissue than in extracapsular dissection. This may minimize the recurrence rate. On the other hand, the removal of healthy parotid tissue compared with formal parotidectomy is limited, thus minimizing complications such as facial nerve dysfunction and Frey syndrome.


Brunamonti Binello P, Bandelloni R, Labanca M, et al.
Osteonecrosis of the jaws and bevacizumab therapy: a case report.
Int J Immunopathol Pharmacol. 2012 Jul-Sep; 25(3):789-91 [PubMed]
Bevacizumab is a humanized recombinant monoclonal antibody that blocks vascular endothelial growth factor (VEGF). Recently, its use has been related with osteneocrosis of the jaws (ONJ), a disease showing a histological pattern similar to bisphosphonate-related ONJ. The aim of this study is to describe an ONJ case-report following bevacizumab chemotherapy without bisphosphonate therapy. We monitored ONJ development associated with the use of bevacizumab in a 47-year-old male with primitive adenocarcinoma of the parotid gland. Our results could suggest a possible correlation between the eruption of the lower third molar tooth and ONJ development following bevacizumab therapy. Clinicians should be aware of the potential risk of bevacizumab-related ONJ complication; moreover, since there are no effective therapeutic protocols for ONJ treatment, it is very important that patients develop good oral hygiene habits and undergo regular dental status evaluation by dentists.


Laco J, Kamarádová K, Vítková P, et al.
Cribriform adenocarcinoma of minor salivary glands may express galectin-3, cytokeratin 19, and HBME-1 and contains polymorphisms of RET and H-RAS proto-oncogenes.
Virchows Arch. 2012; 461(5):531-40 [PubMed]
The aim of the study was to further elucidate the immunohistochemical and genetic characteristics of cribriform adenocarcinoma of minor salivary glands (CAMSG). The study comprised five CAMSG from two males and three females, aged 21-72 years. Four tumors were localized at the base of tongue and one in the floor of mouth. At the time of diagnosis, four tumors had metastasised to regional lymph nodes. After tumor resection, two patients were treated by radiotherapy and one by chemoradiotherapy. During the follow-up (median 14 months), two patients developed lymph node metastasis. Microscopically, all tumors showed cribriform, papillary, follicular, and microcystic growth patterns. The tumor cells displayed vesicular nuclei with intranuclear grooves. Immunohistochemically, all tumors showed expression of cytokeratin (CK) 7, CK8, CK18, vimentin, smooth muscle actin, calponin, S-100 protein, and p16 protein. In addition, we observed expression of galectin-3, CK19, and HBME-1, but not of thyroglobulin and TTF-1. No mutations of RET, BRAF, K-RAS, H-RAS, and N-RAS proto-oncogenes were detected. However, in RET proto-oncogene, we found polymorphisms Gly691Ser (exon 11) and Ser904Ser (exon 15) in one case, p.Leu769Leu (exon 13) in one case, and variant p.IVS14-24 G/A of intron 14 in two cases, and in H-RAS proto-oncogene we found polymorphism 81 T-C (exon 1) in three cases. Thyroglobulin and TTF-1 are the only useful markers in the differential diagnosis between CAMSG and papillary thyroid carcinoma as both tumors may express galectin-3, CK19, and HBME-1. The RET, H-RAS, and N-RAS proto-oncoogenes are not mutated in CAMSG.


Mohapatra M, Satyanarayana S
Low grade mucoepidermoid carcinoma in a setting of Warthin's tumor.
Indian J Pathol Microbiol. 2012 Jul-Sep; 55(3):392-4 [PubMed]
Warthin's tumor also known as papillary cystadenoma lymphomatosum is a common benign salivary gland neoplasm that occurs exclusively in parotid gland. Rarely, the tumor can undergo carcinomatous or lymphomatous transformation of epithelial or lymphoid component, respectively. Herein, we describe a case of 55-year-old female who had undergone parotidectomy for a rapidly growing tumor in the right parotid gland. The case was diagnosed as mucoepidermoid carcinoma developed in a setting of Warthin's tumor based on the histomorphology, special staining characters, and immunohistochemical findings. The pathogenesis and differential diagnoses of such rare malignancy has been discussed briefly.


Tang CG, Schmidtknecht TM, Tang GY, et al.
Lymphoepithelial carcinoma: a case of a rare parotid gland tumor.
Perm J. 2012; 16(3):60-2 [PubMed] Free Access to Full Article
A 29-year-old woman presented from another hospital with a 10-month history of an enlarging left-sided facial mass. Computed tomographic scan revealed a mass in the superficial lobe of the left parotid gland with left-sided cervical lymphadenopathy. The patient received a total left parotidectomy and a selective neck dissection. Histopathologic slides revealed lymphoepithelial carcinoma (LEC) that stained positive for cytokeratin, as well as Epstein-Barr virus (EBV). An LEC of the parotid is a rare salivary gland tumor accounting for less than 1% of all salivary gland tumors. As reaffirmed in our case, LEC is more common in women, occurs primarily in the parotid gland, and has an ethnic predilection. Histologic analysis reveals an infiltrative, poorly differentiated tumor nestled in a lymphoid stroma, with near 100% positivity for EBV in endemic areas. Complete resection of this poorly differentiated carcinoma followed by postoperative radiation is essential for local control.


Sayar H, Öztarakçi H, Sayar Ç, Ağirbaş Ş
Adenocarcinoma arising in warthin tumor of the parotid gland.
Turk Patoloji Derg. 2012; 28(3):278-81 [PubMed]
Warthin tumor is a well-defined benign salivary gland neoplasm consisting of both epithelial and lymphoid components. The tumor is the second most common benign tumor next to pleomorphic adenoma. We present a case of adenocarcinoma, not otherwise classified, arising in unilateral Warthin tumor of the parotid gland in a 63-year-old male patient. Carcinomas arising in or from the epithelial component of a preexisting parotid Warthin tumor are rare and differential diagnosis of metastasis from an adenocarcinoma in Warthin tumor is important. The patient underwent a complete and thorough work-up, and no other primary malignant lesion was found. No other primary malignant lesion had manifested at the last one year follow-up period.


Vira D, Pesce J, Glasgow BJ, et al.
Parotidectomy and neck dissection in the management of conjunctival melanoma: are they necessary?
Laryngoscope. 2012; 122(11):2436-41 [PubMed]
OBJECTIVES/HYPOTHESIS: The objectives of this study were to review traditional techniques for the management of conjunctival melanoma and assess the need for parotidectomy and neck dissection in the management of conjunctival melanoma.
STUDY DESIGN: Retrospective review.
METHODS: This study was a retrospective review conducted in a tertiary academic medical center of patients diagnosed with conjunctival melanoma over a 20-year period
RESULTS: There were 39 patients diagnosed with conjunctival melanoma identified from January 1990 to December 2010. Follow-up varied from 2 to 201 months (median, 25 months). Of the patients, 16 (41%) had local recurrences at the primary site, two (13%) of whom later presented with parotid disease. One patient with parotid recurrence had a subsequent neck dissection for confirmed metastatic spread. No patient in this series had metastatic cervical disease without initial spread to the parotid. The probability of disease-free survival at 1, 2, and 5 years was 77%, 68%, and 50%, respectively. The probability of parotid free progression at 1, 2, and 5 years was 100%, 96%, and 90%, respectively.
CONCLUSIONS: Conjunctival melanoma is a rare malignancy traditionally managed with aggressive treatment to optimize local control. The role for staging parotidectomy with or without neck dissection has been heavily debated. Based on our review, parotidectomy only needs to be undertaken when high suspicion for metastatic spread is present, such as a palpable or radiographically evident mass. In addition, without documented parotid disease, neck dissection is not required.


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