Introduction
Salivary gland neoplasms encompass a wide array of different histologies and locations, including the parotid, submandibular gland, sublingual gland, and minor salivary glands of the upper aerodigestive tract. The majority (80%) of these neoplasms are benign but are heterogeneous in their ability to recur and/or transform into malignant lesions.[1][2] Therefore, correct diagnosis is essential in dictating the proper treatment. The World Health Organization (WHO) in 2017 recognized 11 different benign epithelial salivary gland tumors.[3]
The most common benign subtypes identified include pleomorphic adenoma (PA), Warthin’s tumor (WT), and myoepithelioma (MYO), followed by rarer histologies including lymphadenoma (LA), sebaceous adenoma (SA), oncocytoma (OC), cystadenoma, sialadenoma papilliferum (SP), ductal papilloma (intraductal and inverted), canalicular adenoma (CA), and basal cell adenoma (BCA).[2][3]
Etiology
Register For Free And Read The Full Article
- Search engine and full access to all medical articles
- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Etiology
The etiology of benign salivary tumors is unknown but has been linked to radiation, smoking, trauma, viruses, and genetics. Studies have shown a correlation between salivary gland tumors and prior radiation exposure with 50% of radiation-induced tumors being pleomorphic adenoma.[4] Although exposure to tobacco and alcohol is not associated with an increased risk of some salivary tumors, studies have reported a strong association between Warthin’s tumor and tobacco smoking.[5][6] Increased IgG4-positive plasma cells in lymphadenoma suggest a role for immunomodulation in its development.[7]
Ductal papilloma (intraductal type) is suspected to occur secondary to oral trauma and is usually found at the lower lip, floor of mouth, palate, and tongue.[3] Ductal papilloma (inverted type) has been associated with Human Papillomavirus (HPV) types 6 and 11, as well as oral trauma.[8][9] A chromosomal translocation involving 8q12 and rearrangement at 12q13-15 activates the pleomorphic adenoma gene 1 (PLGA1) and high-mobility group AT-hook 2 (HMGA2), respectively. PLGA1 and HMGA2 are highly specific for pleomorphic adenomas and carcinoma ex-pleomorphic adenomas.[10][11][12]
Epidemiology
Salivary gland neoplasms most commonly affect women with an overall male to female ratio of 1 to 1.5 and a male to female ratio of 1:1.6 for benign tumors.[13] Children account for less than 5% of all salivary gland tumor cases, with the majority of the histology favoring benign and vascular tumors.[14]
The parotid gland is the most common location for salivary gland tumors, comprising 60-75% of all cases.[15] Around 85% of parotid tumors reside in the superficial lobe, 11% in the deep lobe, and 1% in the accessory lobe.[5][16] The most common benign neoplasms found in the parotid are pleomorphic adenoma (53.3%-85%), Warthin's tumor (25%-32%), Basal cell adenoma (2% to 7%), Myoepithelioma (1% to 3%), Oncocytoma (1%).[17][18][19][20][21]
The submandibular gland encompasses 10 to 15% of all salivary gland tumors with an even distribution of benign and malignant neoplasms. The most common benign submandibular tumor is a pleomorphic adenoma, which consists of 36% of all submandibular tumors.[15][22]
Sublingual gland tumors are extremely rare.[1] The most common benign sublingual gland tumor is pleomorphic adenoma.
Minor salivary glands comprise 9.5% to 14.7% of all salivary gland tumors, with the most commonly affected site being the palate.[13][23]There is an equal distribution between benign and malignant tumors.[24] The most common benign minor salivary gland tumors are pleomorphic adenoma, cystadenoma, and canalicular adenoma.[5]
In a series of 216 benign salivary tumors, 138 (64%) were pleomorphic adenomas (PA), followed by Warthin's tumor (23%), recurrent pleomorphic adenoma (5.1%), oncocytoma (2.8%), myoepithelioma (1.9%), cystadenoma (1.4%) and basal cell adenoma (0.9%).[2]
- Pleomorphic adenoma, also known as a benign mixed tumor, is the most common salivary gland tumor and comprises 60 to 70% of all benign salivary gland neoplasms.[25] It has a predilection for females and those in the 3rd to 5th decade of life.[26] It occurs in the parotid in 63 to 80% of cases, mostly in the superficial lobe (>80%).[5][22][26] About 10% of cases affect the deep parotid lobe and can present as a pre-styloid parapharyngeal mass.[3] Pleomorphic adenoma can arise in the submandibular gland in 10% of cases and in the sublingual gland in 0.1% of cases.[25] Pleomorphic adenoma is the most common neoplasm of the minor salivary glands encompassing 39% of all cases.[27] The most common site for a minor salivary gland PA is the palate (10%), followed by the lip (4%).[26] In rare cases of incomplete excision, metastasizing pleomorphic adenomas (MPA) without malignant features on histology have been documented up to 51 years after initial surgery with a mean time of 15 years.[28] The 3 most common sites for MPA are the bone (36.6%), lung (33.8%), and cervical lymph nodes (20.1%), followed by kidneys, skin, liver, and the brain.[29][30]
- Papillary cystadenoma lymphomatosum, also known as a Warthin tumor, is the second most common benign salivary tumor and comprises 15% to 36% of all benign salivary gland tumors with 94.7% of cases located in the parotid.[1][14][31] It has a predilection for males and those in the 4th to 7th decade of life. It can present bilaterally in 7-10% of cases, either metachronously (90%) or synchronously (10%).[32]
- Myoepithelioma occurs in the parotid in 40% to 90% of cases. The palate is the most common site when minor salivary glands are involved.
- Lymphadenoma is most commonly found in the parotid in over 80% of cases. It has no gender predilection and usually affects patients after the 3rd decade of life.[3]
- Sebaceous adenoma accounts for 0.1% of all salivary neoplasms. Approximately 60% of cases occur in the major salivary glands, mainly in the parotid gland. When found in the minor salivary glands, the most common site is the buccal mucosa.[33]
- Oncocytoma accounts for 2% of all salivary gland neoplasms and is mainly found in the parotid gland. It has a predilection for those in the 5th to 6th decade.[34]
- Cystadenoma comprises 4% of all benign salivary gland tumors.[35] It resides in the parotid gland in 45% to 60% of cases but can be found intraorally in the minor salivary glands.[36]
- Sialadenoma papilliferum consists of 0.4% to 1.2% of all salivary gland tumors, with 80% occurring on the hard palate.[37] It has a peak incidence for patients in the 6th decade of life.[38]
- Ductal papilloma (Intraductal type) occurs mainly in the minor salivary glands with rare appearances in the parotid.[3] On average, it affects those aged 50 to 70 years with an equal distribution between the genders.[39]
- Ductal papilloma (Inverted type) is more common than the intraductal type. It is almost always reported in the minor salivary glands, with exceedingly rare cases found in the major salivary glands.[3] It has an equal distribution between men and women with a predilection for adults in the 5th to 6th decades.[40]
- Canalicular adenoma is virtually mostly seen in the minor salivary glands. Approximately 60 to 80% are seen in the upper lip, followed by the buccal mucosa and hard palate.[41] It has a predilection for patients in the 5th decade of life. In western countries, it comprises up to 7 to 12% of all benign salivary tumors, whereas its prevalence is significantly lower in studies from China.[42][43][44]
- Basal cell adenoma accounts for about 1.8% to 5% of all salivary gland tumors. Around 75% to 80% are seen in the parotid glands, followed by 5% in the submandibular glands. The upper lip is the most common site for minor salivary gland involvement. It has a predilection for females, patients in the 7th decade of life, and in western countries.[3][18][45]
Pathophysiology
Salivary gland tumors are heterogeneous in their morphology and are postulated to develop from the same stem-cell differentiation pathways as normal salivary gland tissues. Four main theories have been proposed. These include the basal reserve cell theory, pluripotent unicellular reserve cell theory, semi-pluripotent bicellular reserve cell theory, and the multicellular theory.[46][47]
- Basal reserve cell theory – The basal cells of both excretory and intercalated ducts develop into functional salivary units and are capable of tumor development.[48]
- Pluripotent unicellular reserve cell theory – The basal cells of excretory ducts are responsible for developing the functional salivary unit and tumor differentiation.[48]
- Semi-pluripotent bicellular reserve cell theory –The basal cells of the excretory duct form the progenitor cells of the intercalated ducts, which then form the striated ducts and acinar units. The basal cells of the excretory duct and the progenitor cells of the intercalated ducts are capable of cellular division and tumor development. In contrast, the acinar unit and striated ducts are terminally differentiated and cannot undergo either.[49] This is the most common theory of salivary gland tumor histogenesis.[48]
- Multicellular theory – all cellular types in normal salivary glands, including those of acinar units and striated ducts, can cellular division and development into salivary tumors. Each tumor develops from a specific cell of origin.[50]
Histopathology
Pleomorphic adenoma consists of varying amounts of epithelial and mesenchymal components. The epithelial elements give rise to ducts, whereas the mesenchymal elements give rise to cartilaginous, osseous, hyaline, and myxoid tissues. The mesenchymal component develops from a metaplastic process of the myoepithelial cells.[3] Pleomorphic adenomas of the major salivary glands are encapsulated, whereas those from minor salivary glands are not.[51] Pleomorphic adenoma often has an irregular border with finger-like projections (pseudopodia) that grow into the surrounding tissue making local recurrence a frequent occurrence if these tumors are not completely excised.[52] In metastasizing pleomorphic adenoma (MPA), the histology resembles the original pleomorphic adenoma with occasional mitotic figures and pleomorphism but is not overtly histologically malignant.[28][53]
Warthin tumor presents with a classic bi-layered eosinophilic, oncocytic epithelium with papillary projections and interspersed goblet cells. The epithelium is surrounded by a stroma of varying amounts of lymphoid tissue and germinal centers.[14][49][54] The lymphocytic component, poor blood supply, and cystic spaces surrounding oncocytic cells make Warthin's tumor especially suspective to infarction, parotitis, and a 10x higher risk of inflammation following invasive procedures.[55][56]
Myoepitheliomas are well-circumscribed, encapsulated masses of myoepithelial cells with spindle, epithelial, plasmacytoid, and clear cytoplasmic features.[51] The cells are surrounded by mucoid, collagenous, or vascular stroma. The absence or minimal presence of ductal structures distinguishes myoepithelioma from pleomorphic adenoma.[3]
Lymphadenoma is a well-circumscribed, encapsulated tumor of epithelial and lymphoid components. The non-sebaceous lymphadenoma variant contains epithelial (squamous or basaloid) cells surrounded by an intense lymphoid stroma. The sebaceous variant is more common (60%) and has epithelial cells with sebaceous differentiation. Lymphadenoma can be misdiagnosed as metastatic adenocarcinoma or lymphoepithelial carcinoma.[3]
Sebaceous adenoma is a well-circumscribed, encapsulated mass with solid nests of sebaceous cells in a fibrous stroma. Occasional oncocytic metaplasia and foreign body giant cells can be present.[3]
Oncocytoma is a well-circumscribed tumor with large epithelial, oncocytic cells with granulated eosinophilic cytoplasm surrounded by fibrovascular stroma nests, sheets, trabeculae, or ductal structures.[57]
Cystadenoma is a well-circumscribed, non-encapsulated, multi-cystic mass. It contains a proliferative, papillary, and oncocytic epithelium and with papillary projections into the lumen. The lumen is filled with inflammatory, squamous, and foamy cells. There is no cellular atypia, mitotic figures, or invasive growth.[3]
Sialadenoma papilliferum is a non-encapsulated, biphasic tumor consisting of an exophytic, hyperplastic squamous epithelium overlying deeper ductal elements (often creating cleft-like cystic spaces where both cell types are fused) in a papillary growth pattern. These tumors most commonly (>80%) occur in the oral cavity.[38] Essentially, the salivary ductal cells expand in a biphasic growth pattern into the surrounding squamous keratotic epithelium and can cause hyperplasia and papillomatosis.[3]
Ductal papilloma (intraductal type) consists of a papillary network of vascular fronds lined with the same columnar-cuboidal cells found on dilated salivary ducts. The papilla is often filling part of the cystic cavity. Cellular atypia and mitosis are usually absent.[3]
Ductal papilloma (inverted type) presents with epithelial cells that form a broad papillary projection. Columnar cells, mucous cells, and microcysts can be present. There are few mitotic figures, and it is similar in histology to sinonasal inverted papilloma.[3]
Canalicular adenoma consists of a bi-layered strand formed by columnar and cuboidal cells with eosinophilic cytoplasm. A vascular stroma separates the strands. squamous balls (morules), microliths, and tyrosine crystals may be present.[3]
Basal cell adenoma is an encapsulated mass comprised of uniform basaloid epithelial cells and inner ductal epithelial cells with 4 distinct growth patterns: solid, trabecular, tubular, and membranous.[3][51] The solid type is similar to the skin's basal cell carcinoma with solid nests of basaloid cells surrounded by an outer layer of columnar/cuboidal cells. The trabecular type has basaloid cells arranged in narrow strands and cords separated by a fibrous and vascular stroma. The tubular type has basaloid cells and multiple small duct lumens lined by eosinophilic, cuboidal cells. A combination of a tubule-trabecular pattern is often present and more common than the solid type.[58][59] The membranous type differs from the other 3 patterns in that it is unencapsulated with multiple nests of basaloid cells, palisading peripheral cells, and thick hyaline material surrounding the epithelial islands. It can be multinodular with an invasive growth pattern.[60]
History and Physical
Patients with salivary gland tumors often present with a long-standing history of a painless, palpable mass. A detailed history, including pain symptoms, the onset of the mass, growth rate, swallowing difficulties, and facial weakness symptoms, should be obtained. Past medical history, surgical history, family history of malignancies, and social risk factors (such as smoking, past radiation exposure, and occupational hazards) should be elicited.
Physical exam should include a focused head and neck exam. Both benign and malignant tumors can present as painless, fixed masses. Parotid masses most commonly occur at the superficial lobe. Deep parotid lobe tumors are often asymptomatic but can present with oropharyngeal airway narrowing, sleep apnea, or dyspnea on exertion.[5] Submandibular tumors present with overall glandular enlargement, and sublingual tumors present with diffuse swelling at the mouth floor. Bimanual palpation of salivary masses can help elicit the tumor size and mobility.
- Pleomorphic adenoma presents as a painless, slow-growing, and well-circumscribed mass. As the tumor grows, the overlying skin may become attenuated and bosselated.[5]
- Warthin’s tumor presents as a painless, cystic, compressible encapsulated mass, usually at the tail of the parotid. A bilateral exam is warranted as it can present with bilateral lesions.[14]
- Myoepithelial tumors present as well-circumscribed encapsulated tumors commonly located in the parotid.
- Sialadenoma papilleferum can present as a painless exophytic papillomatous mass, most often seen on the hard palate (80%).[37] It can sometimes be misdiagnosed as a squamous cell papilloma, verrucous carcinoma, or warty dyskeratoma.[61]
- Ductal papilloma (intraductal type) can present as a unicystic, well-circumscribed, and encapsulated lesion. It can present in the parotid gland or on the lower lip, floor of mouth, palate, and tongue.
- Ductal papilloma (inverted type) can present as a well-circumscribed, unencapsulated endophytic papillomatous mass at the junction of the salivary gland and the surrounding oral mucosa.[3]
Evaluation
The evaluation may include:
Ultrasound: Ultrasound is the initial non-invasive modality for localizing superficial tumors; distinguishing solid masses from cystic collections, and helping guide fine-needle aspiration biopsy.[22][62][63]
Computerized tomography (CT): Conventional CT and MRI have similar sensitivity and specificity in determining tumor location, tumor margin, and tumor infiltration.[64][65][66][67][68] Although CT has a lower resolution than MRI for soft tissue, CT provides an advantage in detecting early cortical bony invasion of the mandible.[64]
Magnetic resonance imaging (MRI): For lesions in the deep parotid lobe, sublingual glands, and minor salivary glands, MRI provides an accurate extent of the tumor, the location of the tumor, and its relationship to the facial nerve, for preoperative planning purposes.[51] MRI can quantify the diffusion properties of water in tumor tissue into the apparent diffusion coefficient (ADC). Diffusion-weighted MRI is useful for PA due to its higher ADC.[69] Salivary gland malignancies have significantly smaller ADC than benign tumors, although the ADC of Warthin’s tumor is even smaller than that of malignancies due to excessive lymphoid tissue resembling lymphoma.[70][71]
Positron emission tomography (PET). Compared with conventional CT, PET may be more accurate in demonstrating tumor extension, nodal involvement, local recurrence, and distant metastasis due to the tissues’ higher levels of standardized uptake values (SUV).[72][73] However, PET is unable to differentiate between benign and malignant tumors due to pleomorphic adenoma and Warthin’s tumor both exhibiting high glucose uptake values.[74]
Biopsy. Imaging is unable to completely distinguish between benign and malignant lesions. Obtaining histological samples is key to determining treatment options. Fine needle aspiration (FNA) is a safe diagnostic tool with a high level of accuracy including sensitivity and specificity of 73% and 91%, respectively, in distinguishing benign from malignant tumors.[75][76][77] However, FNA may sometimes falter in its ability to determine the specific malignant subtype and tumor grade.[78] Ultrasound-guided core needle biopsy (CNB) is able to obtain larger tissue specimens with histologic architecture which improves recognition of tumor grading and subtyping. However, disadvantages of CNB include more pain, need for local anesthesia, and increased risk of facial nerve injury and hematoma.[79] The intraoperative frozen section has a sensitivity and specificity of 90% and 99%, respectively in distinguishing between benign and malignant lesions.[80]
Treatment / Management
The mainstay of treatment for benign salivary lesions is complete surgical excision with negative margins. Radiation and medical therapy play little role in the treatment of benign salivary tumors. However, radiation has been utilized in cases of recurrent disease, extensive facial nerve involvement, and non-surgical candidates to improve local control. Repeated surgical interventions increase the risk of tumor spillage and facial nerve damage.[81][82][83](B2)
Differential Diagnosis
- Malignant salivary gland tumors (mucoepidermoid carcinoma, adenoid cystic adenoma, acinic cell carcinoma, adenocarcinoma, salivary duct carcinoma, carcinoma ex pleomorphic adenoma, squamous cell carcinoma)
- Intra-parotid lymphadenopathy
- Neuroma of the facial nerve
- Lymphoma
- Paraganglioma
- Developmental cyst
- Plunging ranula
- Granulomatous disease (sarcoidosis, tuberculosis)
- Sialadenitis
- Sialoliths
- Mucocele
- Hemangioma
Surgical Oncology
Surgical excision is the treatment of choice for benign salivary tumors. Enucleation is not advised due to the higher rates of local recurrence.[84]
Lesions of the superficial lobe of the parotid gland can be excised with a superficial parotidectomy. Total parotidectomy with facial nerve preservation is performed for large superficial tumors, deep parotid tumors, or cases of metastasizing pleomorphic adenoma.[26][53] Superficial parotidectomy involves elevating the skin flap over the parotid capsule, identifying the facial nerve trunk, and dissecting along all its branches, preserving the facial nerve if uninvolved by malignancy, and removal of the superficial lobe of the parotid containing the tumor while maintaining the integrity of the tumor pseudocapsule.[15]
The disadvantages of superficial parotidectomy include excessive resection of parotid tissue leading to loss of parotid function, disruption of Stenson’s duct, facial contour defects, and facial nerve paralysis. Gland-preserving surgery has been recommended for benign tumors with a reduction in surgical complications and improvement in patient quality of life.[72][85][86] An alternative procedure, the partial superficial parotidectomy, has been proposed where the tumor is resected with a normal margin of parotid tissue, and the facial nerve is only dissected in the vicinity of the tumor. A comparison of the two techniques was studied by Roh et al who found better cosmesis, sensory, and salivary functions along with less facial nerve weakness and no difference in recurrence rate for partial superficial parotidectomy.[72]
Extracapsular dissection (ECD) is the most conservative approach and involves removing the tumor with only the immediate pseudocapsule without identifying nor dissecting the facial nerve branches. George et al showed that complications such as facial nerve damage, sialocele, and Frey syndrome were rare during ECD. In studies comparing ECD with superficial parotidectomy for benign tumors, superficial parotidectomy showed a higher rate of facial nerve complications.[86][87][88]
Extirpation of the entire submandibular gland is the treatment of choice for benign submandibular tumors.[89] However, this can lead to decreased resting salivary production. Studies that evaluated grand-preserving partial sialadenectomy for benign submandibular tumors showed that patients had higher postoperative resting saliva rates and less facial deformity with no difference in local control.[90][91] Gland preservation surgery is contraindicated for malignant tumors and central gland lesions that would risk damage to the vascular and ductal integrity of the remaining salivary tissue after partial sialoadenectomy.[90]
For benign minor salivary gland tumors of the palate, a wide local excision within the palatal mucosa is recommended with 5 to 10 mm margins and preservation of the pseudocapsule. The exposed palatine bone is left to heal by secondary intention or resected and reconstructed with soft tissue flap.[15]
Radiation Oncology
Surgical resection with negative margins achieves local control in over 95% of benign salivary gland tumor cases.[92][93] Postoperative radiation is usually not recommended in these cases due to the small benefit in local control and potential risk for radiation morbidity.[94] However, in cases of incomplete tumor resection or spillage, adjuvant RT was found to significantly reduce the rate of local recurrence and reduce the risk of facial nerve injury from reoperation.[81][82][83]
Recurrent PA can be seen in 0% to 23% of cases, and a second surgery is recommended for local control.[95] In cases of multinodular recurrence or metastasizing pleomorphic adenoma, adjuvant radiation has been shown to achieve improved local control.[96][97] Postoperative radiation has also been proposed to treat PA where surgery is unlikely to clear the disease, where there is facial nerve involvement, history of multiple recurrences, and in elderly patients who are poor surgical candidates.[51][95][98]
Prognosis
The prognosis of benign salivary gland tumors varies widely based on the myriad of tumor histologies with different rates of recurrence and malignant transformation.
- Pleomorphic Adenoma recurrence has been reported in 1% to 5% of cases at 7-10 years after initial treatment, likely secondary to incomplete excision, capsule rupture, pseudopodia presence, and satellite lesions.[26][84][92] Metastasizing pleomorphic adenoma (MPA) is a rare condition with pleomorphic adenoma developing in bone (36.6%), lung (33.8%), and cervical lymph nodes(20.1%), liver, and skin without any metastatic features on histology.[32][99][100] MPA has been associated with incomplete excision, with 90% of cases also displaying local recurrence.[101][102] Patients with MPA have a 5-year disease-specific survival rate of 58%.[103] The WHO reports that 40% of the patients die with the disease, 47% live free of disease, and 13% live with it.[53][104] Carcinoma ex-pleomorphic adenoma can develop in 2% to 15% of cases and is the malignant transformation of PA arising from its epithelial components.[33][51][105]
- Warthin’s tumor recurs at a rate of 7% to 12% due to incomplete excisions, tumor spillage, multicentric tumors, or de novo growth.[32][106] Malignancy transformation is rare, but it can develop into squamous cell carcinoma (most common), mucoepidermoid carcinoma, oncocytic carcinoma, adenocarcinoma, salivary duct carcinoma, acinic cell carcinoma, and undifferentiated carcinoma.[3][107][108][109][110] Warthin's tumor may be associated with lymphoproliferative disorders such as Non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, T-cell lymphoma, and Mucosa-Associated Lymphoid Tissue (MALT)-related lymphoma.[111][112][113][114]
- Myoepithelioma recurrence is rare and is usually attributed to incomplete excision of the primary tumor.[115] Malignant transformation is also extremely rare.[116][117]
- Lymphadenoma rarely recurs. The sebaceous variant has been reported to transform into sebaceous carcinoma in 4 cases in the literature.[118][119]
- Sebaceous adenoma after adequate surgical resection has not been reported to recur. Sebaceous carcinoma has been documented to arise de novo and not from pre-existing sebaceous adenoma lesions.[120]
- Oncocytoma can present as a multifocal lesion and recur if not completely resected. There is no evidence that oncocytic carcinoma arises from existing oncocytoma.[3]
- Cystadenoma does not recur after complete surgical resection, but there are rare reports of cystadenocarcinoma developing from preexisting cystadenoma.[3][121]
- Sialadenoma papilliferum recurrence is extremely rare, with only 2 reported cases of suspected malignant transformation.[122][123]
- Ductal papilloma (intraductal and inverted type) have no tendency to recur or undergo malignant transformation.[3][124]
Complications
Surgical excision is the standard of treatment for all salivary gland tumors. This may lead to a loss of functional tissue and saliva secretion, causing xerostomia, dental caries, halitosis, periodontal disease, and oral infections.[107] The incidence of temporary facial nerve palsy after parotidectomy ranges from 10% to 65%, with permanent paralysis seen in less than 5%.[128][129][130] The incidence of Frey syndrome after parotidectomy varies widely from 2% to 80% due to the time interval since surgery as well as the surveillance criteria from the surgeons.[131]
Treatments for Frey syndrome have included antiperspirant ointment, botulinum toxin A injections, and barrier flaps such as superficial musculoaponeurotic system (SMAS) flap, temporoparietal flap, sternocleidomastoid flap, anterolateral thigh flap, or thick skin flap.[131][132][133][134] Additional complications from surgical resection include sialocele, salivary fistula, neuromas of the great auricular nerve, and preauricular skin anesthesia.[51]
Patients who undergo submandibular gland resection have a risk of neurological damage to the hypoglossal nerve, lingual nerve, and marginal mandibular branch of the facial nerve.[7][135][7]
Complications from radiation include sensorineural hearing loss, chronic otitis media/externa, otalgia, skin erythema, mucositis, dysphagia, dysgeusia, xerostomia, soft tissue fibrosis, osteoradionecrosis, and radiation-induced malignancy.[94][136] Approximately 36% of patients were found to develop hearing loss of 10 dB and higher at 4kHz.[137] Mandibular osteoradionecrosis (<2%) and RT-induced malignancy (1%) at 10 to 25 years are rare complications.[136][138][139][140]
Consultations
Diagnosis and management of salivary malignancies would need to consist of an interprofessional team, including an otolaryngologist, plastic surgeon, general surgeon, radiation oncologist, speech-language pathologist, and primary care physician.
Deterrence and Patient Education
Patient education on salivary tumors can be challenging due to the heterogeneous array of histologies and the need for multidisciplinary and multimodal management. Patients and their families should be educated on the different treatment options and timeline, including surgical resection, radiation therapy if indicated, and long-term follow-up for recurrence. Patients and parents should be counseled on the possible risks and complications of all treatment modalities and their comorbidities fully assessed by their primary care physicians to determine if they will be candidates for surgical resection. Long-term follow-up is crucial for benign salivary tumors and must be emphasized to patients, given the risk of recurrence and malignant transformation of certain histologies.
Enhancing Healthcare Team Outcomes
Patients with benign salivary gland tumors should be managed by a multidisciplinary team of otolaryngologists, plastic surgeons, general surgeons, pathologists, radiation oncologists, speech-language pathologists, and primary care physicians. Salivary tumors present with varying histologies and severities requiring therapy involving surgery and occasional radiation for recurrent or invasive diseases. Close communication and collaboration between the surgeons and radiation oncologists can provide a tailored approach for each patient. Difficulties with swallowing can occur from acute radiation toxicity.
Patients may need a consultation with general surgery for gastric tube placement to ensure optimal nutrition through treatment, especially if radiation therapy is planned. Early post-treatment intervention by speech-language pathologists can help patients regain pre-treatment function to prevent malnutrition and dependence on enteric feeding. Facial nerve paralysis may occur after parotid surgery, and consultation with an otolaryngologist or plastic surgeon for facial nerve rehabilitation is recommended.
Recurrence of salivary tumors can occur after incomplete excision, and malignant transformation can occur several years after initial treatment. Thus, routine close follow-up by the otolaryngologist, radiation oncologists, and primary care physician is advocated. Finally, patients may develop depression, social anxiety, and avoidance due to visible surgical scarring and facial nerve paralysis. Formal peer support groups can aid patients in addressing their concerns.
References
de Oliveira FA,Duarte EC,Taveira CT,Máximo AA,de Aquino EC,Alencar Rde C,Vencio EF, Salivary gland tumor: a review of 599 cases in a Brazilian population. Head and neck pathology. 2009 Dec; [PubMed PMID: 20596844]
Level 3 (low-level) evidenceIsrael Y,Rachmiel A,Ziv G,Nagler R, Benign and Malignant Salivary Gland Tumors - Clinical and Demographic Characteristics. Anticancer research. 2016 Aug; [PubMed PMID: 27466524]
Hellquist H,Paiva-Correia A,Vander Poorten V,Quer M,Hernandez-Prera JC,Andreasen S,Zbären P,Skalova A,Rinaldo A,Ferlito A, Analysis of the Clinical Relevance of Histological Classification of Benign Epithelial Salivary Gland Tumours. Advances in therapy. 2019 Aug; [PubMed PMID: 31209701]
Level 3 (low-level) evidenceRice DH,Batsakis JG,McClatchey KD, Postirradiation malignant salivary gland tumor. Archives of otolaryngology (Chicago, Ill. : 1960). 1976 Nov; [PubMed PMID: 985205]
Level 3 (low-level) evidenceBradley PJ, Frequency and Histopathology by Site, Major Pathologies, Symptoms and Signs of Salivary Gland Neoplasms. Advances in oto-rhino-laryngology. 2016; [PubMed PMID: 27092790]
Level 3 (low-level) evidenceKotwall CA, Smoking as an etiologic factor in the development of Warthin's tumor of the parotid gland. American journal of surgery. 1992 Dec; [PubMed PMID: 1334381]
Level 2 (mid-level) evidenceKim J,Song JS,Roh JL,Choi SH,Nam SY,Kim SY,Cho KJ, Increased Immunoglobulin G4-positive Plasma Cells in Lymphadenoma of the Salivary Gland: An Immunohistochemical Comparison Among Lymphoepithelial Lesions. Applied immunohistochemistry [PubMed PMID: 27941558]
Haberland-Carrodeguas C,Fornatora ML,Reich RF,Freedman PD, Detection of human papillomavirus DNA in oral inverted ductal papillomas. Journal of clinical pathology. 2003 Dec; [PubMed PMID: 14645348]
Sala-Pérez S,España-Tost A,Vidal-Bel A,Gay-Escoda C, Inverted ductal papilloma of the oral cavity secondary to lower lip trauma. A case report and literature review. Journal of clinical and experimental dentistry. 2013 Apr 1; [PubMed PMID: 24455058]
Level 3 (low-level) evidenceMartins C,Fonseca I,Roque L,Pereira T,Ribeiro C,Bullerdiek J,Soares J, PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: a combined study using chromosome banding, in situ hybridization and immunocytochemistry. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2005 Aug; [PubMed PMID: 15920557]
Mito JK,Jo VY,Chiosea SI,Dal Cin P,Krane JF, HMGA2 is a specific immunohistochemical marker for pleomorphic adenoma and carcinoma ex-pleomorphic adenoma. Histopathology. 2017 Oct; [PubMed PMID: 28463429]
Andreasen S,von Holstein SL,Homøe P,Heegaard S, Recurrent rearrangements of the PLAG1 and HMGA2 genes in lacrimal gland pleomorphic adenoma and carcinoma ex pleomorphic adenoma. Acta ophthalmologica. 2018 Nov; [PubMed PMID: 29437290]
Al-Khateeb TH,Ababneh KT, Salivary tumors in north Jordanians: a descriptive study. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. 2007 May; [PubMed PMID: 17368055]
Level 2 (mid-level) evidenceBatsakis JG,Regezi JA, The pathology of head and neck tumors: salivary glands, part 1. Head [PubMed PMID: 756396]
Carlson ER,McCoy JM, Margins for Benign Salivary Gland Neoplasms of the Head and Neck. Oral and maxillofacial surgery clinics of North America. 2017 Aug; [PubMed PMID: 28709532]
Mantsopoulos K,Psychogios G,Agaimy A,Künzel J,Zenk J,Iro H,Bohr C, Inflamed benign tumors of the parotid gland: diagnostic pitfalls from a potentially misleading entity. Head [PubMed PMID: 24488708]
Level 2 (mid-level) evidenceSpiro RH, Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head [PubMed PMID: 3744850]
Level 3 (low-level) evidenceTian Z,Li L,Wang L,Hu Y,Li J, Salivary gland neoplasms in oral and maxillofacial regions: a 23-year retrospective study of 6982 cases in an eastern Chinese population. International journal of oral and maxillofacial surgery. 2010 Mar; [PubMed PMID: 19951834]
Level 2 (mid-level) evidenceZhan KY,Khaja SF,Flack AB,Day TA, Benign Parotid Tumors. Otolaryngologic clinics of North America. 2016 Apr; [PubMed PMID: 27040584]
Bradley PJ,McGurk M, Incidence of salivary gland neoplasms in a defined UK population. The British journal of oral [PubMed PMID: 23103239]
Ichihara T,Kawata R,Higashino M,Terada T,Haginomori S, A more appropriate clinical classification of benign parotid tumors: investigation of 425 cases. Acta oto-laryngologica. 2014 Nov; [PubMed PMID: 25315918]
Level 2 (mid-level) evidenceOrd RA,Carlson ER, Pediatric Salivary Gland Malignancies. Oral and maxillofacial surgery clinics of North America. 2016 Feb; [PubMed PMID: 26614703]
Ito FA,Ito K,Vargas PA,de Almeida OP,Lopes MA, Salivary gland tumors in a Brazilian population: a retrospective study of 496 cases. International journal of oral and maxillofacial surgery. 2005 Jul; [PubMed PMID: 16053874]
Level 2 (mid-level) evidenceCarlson ER,Schimmele SR, The management of minor salivary gland tumors of the oral cavity. Atlas of the oral and maxillofacial surgery clinics of North America. 1998 Mar; [PubMed PMID: 11905351]
Subhashraj K, Salivary gland tumors: a single institution experience in India. The British journal of oral [PubMed PMID: 18620785]
Level 2 (mid-level) evidenceEllis GL, Salivary gland neoplasms. Ear, nose, [PubMed PMID: 6088209]
Buchner A,Merrell PW,Carpenter WM, Relative frequency of intra-oral minor salivary gland tumors: a study of 380 cases from northern California and comparison to reports from other parts of the world. Journal of oral pathology [PubMed PMID: 17391298]
Level 3 (low-level) evidenceKoyama M,Terauchi T,Koizumi M,Tanaka H,Sato Y, Metastasizing pleomorphic adenoma in the multiple organs: A case report on FDG-PET/CT imaging. Medicine. 2018 Jun; [PubMed PMID: 29879077]
Level 3 (low-level) evidenceKnight J,Ratnasingham K, Metastasising pleomorphic adenoma: Systematic review. International journal of surgery (London, England). 2015 Jul; [PubMed PMID: 25958295]
Level 1 (high-level) evidenceWenig BM,Hitchcock CL,Ellis GL,Gnepp DR, Metastasizing mixed tumor of salivary glands. A clinicopathologic and flow cytometric analysis. The American journal of surgical pathology. 1992 Sep; [PubMed PMID: 1384375]
Level 2 (mid-level) evidenceLATHROP FD, Benign tumors of the parotid gland: a twenty-five year review. The Laryngoscope. 1962 Aug; [PubMed PMID: 14462675]
Ethunandan M,Pratt CA,Morrison A,Anand R,Macpherson DW,Wilson AW, Multiple synchronous and metachronous neoplasms of the parotid gland: the Chichester experience. The British journal of oral [PubMed PMID: 16207507]
Level 2 (mid-level) evidenceGnepp DR, Sebaceous neoplasms of salivary gland origin: a review. Pathology annual. 1983; [PubMed PMID: 6308548]
Thompson LD,Wenig BM,Ellis GL, Oncocytomas of the submandibular gland. A series of 22 cases and a review of the literature. Cancer. 1996 Dec 1; [PubMed PMID: 8940996]
Level 3 (low-level) evidenceSkálová A,Leivo I,Wolf H,Fakan F, Oncocytic cystadenoma of the parotid gland with tyrosine-rich crystals. Pathology, research and practice. 2000; [PubMed PMID: 11156328]
Level 3 (low-level) evidenceGoto M,Ohnishi Y,Shoju Y,Wato M,Kakudo K, Papillary oncocytic cystadenoma of a palatal minor salivary gland: A case report. Oncology letters. 2016 Feb; [PubMed PMID: 26893722]
Level 3 (low-level) evidenceBobos M,Hytiroglou P,Karkavelas G,Papakonstantinou C,Papadimitriou CS, Sialadenoma papilliferum of bronchus. Virchows Archiv : an international journal of pathology. 2003 Nov; [PubMed PMID: 12937978]
Level 3 (low-level) evidenceFowler CB,Damm DD, Sialadenoma Papilliferum: Analysis of Seven New Cases and Review of the Literature. Head and neck pathology. 2018 Jun; [PubMed PMID: 28887760]
Level 3 (low-level) evidenceSun S,Wang P,Wang Y,Su W,Wang F,Yang H, Intraductal papilloma arising from the accessory parotid gland: A case report and literature review. Medicine. 2018 May; [PubMed PMID: 29768362]
Level 3 (low-level) evidenceWhite DK,Miller AS,McDaniel RK,Rothman BN, Inverted ductal papilloma: a distinctive lesion of minor salivary gland. Cancer. 1982 Feb 1; [PubMed PMID: 7059911]
Level 3 (low-level) evidenceThompson LD,Bauer JL,Chiosea S,McHugh JB,Seethala RR,Miettinen M,Müller S, Canalicular adenoma: a clinicopathologic and immunohistochemical analysis of 67 cases with a review of the literature. Head and neck pathology. 2015 Jun; [PubMed PMID: 25141970]
Level 3 (low-level) evidenceSamar ME,Avila RE,Fonseca IB,Anderson W,Fonseca GM,Cantín M, Multifocal canalicular adenoma of the minor labial salivary glands. International journal of clinical and experimental pathology. 2014; [PubMed PMID: 25550873]
Level 3 (low-level) evidenceWang D,Li Y,He H,Liu L,Wu L,He Z, Intraoral minor salivary gland tumors in a Chinese population: a retrospective study on 737 cases. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. 2007 Jul; [PubMed PMID: 17577550]
Level 2 (mid-level) evidencePeraza AJ,Wright J,Gómez R, Canalicular adenoma: A systematic review. Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery. 2017 Oct; [PubMed PMID: 28890252]
Level 1 (high-level) evidenceWilson TC,Robinson RA, Basal cell adenocarcinoma and Basal cell adenoma of the salivary glands: a clinicopathological review of seventy tumors with comparison of morphologic features and growth control indices. Head and neck pathology. 2015 Jun; [PubMed PMID: 25141971]
Level 2 (mid-level) evidenceCheuk W,Chan JK, Advances in salivary gland pathology. Histopathology. 2007 Jul; [PubMed PMID: 17539914]
Level 3 (low-level) evidenceDwivedi N,Agarwal A,Raj V,Chandra S, Histogenesis of salivary gland neoplasms. Indian journal of cancer. 2013 Oct-Dec; [PubMed PMID: 24369218]
Sreeja C,Shahela T,Aesha S,Satish MK, Taxonomy of salivary gland neoplasm. Journal of clinical and diagnostic research : JCDR. 2014 Mar; [PubMed PMID: 24783163]
Regezi JA,Batsakis JG, Histogenesis of salivary gland neoplasms. Otolaryngologic clinics of North America. 1977 Jun; [PubMed PMID: 197465]
Dardick I,Jeans MT,Sinnott NM,Wittkuhn JF,Kahn HJ,Baumal R, Salivary gland components involved in the formation of squamous metaplasia. The American journal of pathology. 1985 Apr; [PubMed PMID: 2580442]
Level 3 (low-level) evidenceLingam RK,Daghir AA,Nigar E,Abbas SA,Kumar M, Pleomorphic adenoma (benign mixed tumour) of the salivary glands: its diverse clinical, radiological, and histopathological presentation. The British journal of oral [PubMed PMID: 19926180]
Henriksson G,Westrin KM,Carlsöö B,Silfverswärd C, Recurrent primary pleomorphic adenomas of salivary gland origin: intrasurgical rupture, histopathologic features, and pseudopodia. Cancer. 1998 Feb 15; [PubMed PMID: 9477091]
Soteldo J,Aranaga N, Metastasizing pleomorphic adenoma of the parotid gland. Ecancermedicalscience. 2017; [PubMed PMID: 28900471]
Cossman J,Deegan MJ,Batsakis JG, Warthin tumor. B-lymphocytes within the lymphoid infiltrate. Archives of pathology [PubMed PMID: 326225]
Level 3 (low-level) evidenceBahar G,Dudkiewicz M,Feinmesser R,Joshua BZ,Braslavsky D,Popovtzer A,Galil D,Shpitzer T, Acute parotitis as a complication of fine-needle aspiration in Warthin's tumor. A unique finding of a 3-year experience with parotid tumor aspiration. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2006 Apr; [PubMed PMID: 16564390]
Level 2 (mid-level) evidenceAlkan U,Shkedy Y,Mizrachi A,Shpitzer T,Popovtzer A,Bachar G, Inflammation following invasive procedures for Warthin's tumour: A retrospective case series. Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology [PubMed PMID: 28235157]
Level 2 (mid-level) evidenceMcHugh JB,Hoschar AP,Dvorakova M,Parwani AV,Barnes EL,Seethala RR, p63 immunohistochemistry differentiates salivary gland oncocytoma and oncocytic carcinoma from metastatic renal cell carcinoma. Head and neck pathology. 2007 Dec; [PubMed PMID: 20614263]
Sato M,Yamamoto H,Hatanaka Y,Nishijima T,Jiromaru R,Yasumatsu R,Taguchi K,Masuda M,Nakagawa T,Oda Y, Wnt/β-catenin signal alteration and its diagnostic utility in basal cell adenoma and histologically similar tumors of the salivary gland. Pathology, research and practice. 2018 Apr; [PubMed PMID: 29496310]
Jo VY,Sholl LM,Krane JF, Distinctive Patterns of CTNNB1 (β-Catenin) Alterations in Salivary Gland Basal Cell Adenoma and Basal Cell Adenocarcinoma. The American journal of surgical pathology. 2016 Aug; [PubMed PMID: 27259009]
Machado de Sousa SO,Soares de Araújo N,Corrêa L,Pires Soubhia AM,Cavalcanti de Araújo V, Immunohistochemical aspects of basal cell adenoma and canalicular adenoma of salivary glands. Oral oncology. 2001 Jun; [PubMed PMID: 11337269]
Argyres MI,Golitz LE, Sialadenoma papilliferum of the palate: case report and literature review. Journal of cutaneous pathology. 1999 May; [PubMed PMID: 10408352]
Level 3 (low-level) evidenceLee YY,Wong KT,King AD,Ahuja AT, Imaging of salivary gland tumours. European journal of radiology. 2008 Jun; [PubMed PMID: 18337041]
Kovacević DO,Fabijanić I, Sonographic diagnosis of parotid gland lesions: correlation with the results of sonographically guided fine-needle aspiration biopsy. Journal of clinical ultrasound : JCU. 2010 Jul; [PubMed PMID: 20544864]
Level 2 (mid-level) evidenceKoyuncu M,Seşen T,Akan H,Ismailoglu AA,Tanyeri Y,Tekat A,Unal R,Incesu L, Comparison of computed tomography and magnetic resonance imaging in the diagnosis of parotid tumors. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2003 Dec; [PubMed PMID: 14663442]
Seitz O,Chambron-Pinho N,Middendorp M,Sader R,Mack M,Vogl TJ,Bisdas S, 18F-Fluorodeoxyglucose-PET/CT to evaluate tumor, nodal disease, and gross tumor volume of oropharyngeal and oral cavity cancer: comparison with MR imaging and validation with surgical specimen. Neuroradiology. 2009 Oct; [PubMed PMID: 19727695]
Level 2 (mid-level) evidenceVidiri A,Guerrisi A,Pellini R,Manciocco V,Covello R,Mattioni O,Guerrisi I,Di Giovanni S,Spriano G,Crecco M, Multi-detector row computed tomography (MDCT) and magnetic resonance imaging (MRI) in the evaluation of the mandibular invasion by squamous cell carcinomas (SCC) of the oral cavity. Correlation with pathological data. Journal of experimental [PubMed PMID: 20565737]
Level 2 (mid-level) evidenceGu DH,Yoon DY,Park CH,Chang SK,Lim KJ,Seo YL,Yun EJ,Choi CS,Bae SH, CT, MR, (18)F-FDG PET/CT, and their combined use for the assessment of mandibular invasion by squamous cell carcinomas of the oral cavity. Acta radiologica (Stockholm, Sweden : 1987). 2010 Dec; [PubMed PMID: 20929295]
Level 2 (mid-level) evidenceEttl T,Schwarz-Furlan S,Gosau M,Reichert TE, Salivary gland carcinomas. Oral and maxillofacial surgery. 2012 Sep; [PubMed PMID: 22842859]
Yerli H,Agildere AM,Aydin E,Geyik E,Haberal N,Kaskati T,Oguz D,Ozluoglu LN, Value of apparent diffusion coefficient calculation in the differential diagnosis of parotid gland tumors. Acta radiologica (Stockholm, Sweden : 1987). 2007 Nov; [PubMed PMID: 17957512]
Level 2 (mid-level) evidenceWittekindt C,Burmeister HP,Guntinas-Lichius O, [Diagnostic and therapy of salivary gland diseases: relevant aspects for the pathologist from the clinical perspective]. Der Pathologe. 2009 Nov; [PubMed PMID: 19756611]
Level 3 (low-level) evidenceHabermann CR,Arndt C,Graessner J,Diestel L,Petersen KU,Reitmeier F,Ussmueller JO,Adam G,Jaehne M, Diffusion-weighted echo-planar MR imaging of primary parotid gland tumors: is a prediction of different histologic subtypes possible? AJNR. American journal of neuroradiology. 2009 Mar; [PubMed PMID: 19131405]
Roh JL,Kim HS,Park CI, Randomized clinical trial comparing partial parotidectomy versus superficial or total parotidectomy. The British journal of surgery. 2007 Sep; [PubMed PMID: 17701949]
Level 1 (high-level) evidenceJeong HS,Chung MK,Son YI,Choi JY,Kim HJ,Ko YH,Baek CH, Role of 18F-FDG PET/CT in management of high-grade salivary gland malignancies. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2007 Aug; [PubMed PMID: 17631549]
Keyes JW Jr,Harkness BA,Greven KM,Williams DW 3rd,Watson NE Jr,McGuirt WF, Salivary gland tumors: pretherapy evaluation with PET. Radiology. 1994 Jul; [PubMed PMID: 8208973]
Hughes JH,Volk EE,Wilbur DC, Pitfalls in salivary gland fine-needle aspiration cytology: lessons from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology. Archives of pathology [PubMed PMID: 15628905]
Level 2 (mid-level) evidenceBajaj Y,Singh S,Cozens N,Sharp J, Critical clinical appraisal of the role of ultrasound guided fine needle aspiration cytology in the management of parotid tumours. The Journal of laryngology and otology. 2005 Apr; [PubMed PMID: 15949083]
Level 2 (mid-level) evidenceDas DK,Anim JT, Pleomorphic adenoma of salivary gland: to what extent does fine needle aspiration cytology reflect histopathological features? Cytopathology : official journal of the British Society for Clinical Cytology. 2005 Apr; [PubMed PMID: 15787647]
Colella G,Cannavale R,Vicidomini A,Itro A, Salivary gland biopsy: a comprehensive review of techniques and related complications. Rheumatology (Oxford, England). 2010 Nov; [PubMed PMID: 20660500]
Level 1 (high-level) evidenceSchmidt RL,Hall BJ,Layfield LJ, A systematic review and meta-analysis of the diagnostic accuracy of ultrasound-guided core needle biopsy for salivary gland lesions. American journal of clinical pathology. 2011 Oct; [PubMed PMID: 21917673]
Level 1 (high-level) evidenceSchmidt RL,Hunt JP,Hall BJ,Wilson AR,Layfield LJ, A systematic review and meta-analysis of the diagnostic accuracy of frozen section for parotid gland lesions. American journal of clinical pathology. 2011 Nov; [PubMed PMID: 22031311]
Level 1 (high-level) evidenceBuchman C,Stringer SP,Mendenhall WM,Parsons JT,Jordan JR,Cassisi NJ, Pleomorphic adenoma: effect of tumor spill and inadequate resection on tumor recurrence. The Laryngoscope. 1994 Oct; [PubMed PMID: 7934593]
Robertson BF,Robertson GA,Shoaib T,Soutar DS,Morley S,Robertson AG, Pleomorphic adenomas: post-operative radiotherapy is unnecessary following primary incomplete excision: a retrospective review. Journal of plastic, reconstructive [PubMed PMID: 25287582]
Level 2 (mid-level) evidenceMendenhall WM,Mendenhall CM,Werning JW,Malyapa RS,Mendenhall NP, Salivary gland pleomorphic adenoma. American journal of clinical oncology. 2008 Feb; [PubMed PMID: 18376235]
Laskawi R,Schott T,Schröder M, Recurrent pleomorphic adenomas of the parotid gland: clinical evaluation and long-term follow-up. The British journal of oral [PubMed PMID: 9578257]
Yamashita T,Tomoda K,Kumazawa T, The usefulness of partial parotidectomy for benign parotid gland tumors. A retrospective study of 306 cases. Acta oto-laryngologica. Supplementum. 1993; [PubMed PMID: 8452007]
Level 2 (mid-level) evidenceMcGurk M,Thomas BL,Renehan AG, Extracapsular dissection for clinically benign parotid lumps: reduced morbidity without oncological compromise. British journal of cancer. 2003 Nov 3; [PubMed PMID: 14583757]
Barzan L,Pin M, Extra-capsular dissection in benign parotid tumors. Oral oncology. 2012 Oct; [PubMed PMID: 22727059]
Level 2 (mid-level) evidenceCristofaro MG,Allegra E,Giudice A,Colangeli W,Caruso D,Barca I,Giudice M, Pleomorphic adenoma of the parotid: extracapsular dissection compared with superficial parotidectomy--a 10-year retrospective cohort study. TheScientificWorldJournal. 2014; [PubMed PMID: 25401147]
Level 2 (mid-level) evidenceLaskawi R,Ellies M,Arglebe C,Schott A, Surgical management of benign tumors of the submandibular gland: a follow-up study. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 1995 May; [PubMed PMID: 7722716]
Level 2 (mid-level) evidenceGe N,Peng X,Zhang L,Cai ZG,Guo CB,Yu GY, Partial sialoadenectomy for the treatment of benign tumours in the submandibular gland. International journal of oral and maxillofacial surgery. 2016 Jun; [PubMed PMID: 26970852]
Springborg LK,Møller MN, Submandibular gland excision: long-term clinical outcome in 139 patients operated in a single institution. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2013 Mar; [PubMed PMID: 22941392]
Level 2 (mid-level) evidenceWitt RL, The significance of the margin in parotid surgery for pleomorphic adenoma. The Laryngoscope. 2002 Dec; [PubMed PMID: 12461331]
Level 2 (mid-level) evidenceRenehan A,Gleave EN,Hancock BD,Smith P,McGurk M, Long-term follow-up of over 1000 patients with salivary gland tumours treated in a single centre. The British journal of surgery. 1996 Dec; [PubMed PMID: 9038559]
Thomson DJ,Slevin NJ,Mendenhall WM, Indications for Salivary Gland Radiotherapy. Advances in oto-rhino-laryngology. 2016; [PubMed PMID: 27093301]
Level 3 (low-level) evidenceWitt RL,Eisele DW,Morton RP,Nicolai P,Poorten VV,Zbären P, Etiology and management of recurrent parotid pleomorphic adenoma. The Laryngoscope. 2015 Apr; [PubMed PMID: 25289881]
Renehan A,Gleave EN,McGurk M, An analysis of the treatment of 114 patients with recurrent pleomorphic adenomas of the parotid gland. American journal of surgery. 1996 Dec; [PubMed PMID: 8988685]
Level 2 (mid-level) evidenceRodríguez-Fernández J,Mateos-Micas M,Martínez-Tello FJ,Berjón J,Montalvo JJ,Forteza-González G,Galan-Hernández R, Metastatic benign pleomorphic adenoma. Report of a case and review of the literature. Medicina oral, patologia oral y cirugia bucal. 2008 Mar 1; [PubMed PMID: 18305442]
Level 3 (low-level) evidenceZbären P,Tschumi I,Nuyens M,Stauffer E, Recurrent pleomorphic adenoma of the parotid gland. American journal of surgery. 2005 Feb; [PubMed PMID: 15720991]
Level 2 (mid-level) evidenceChen Ih,Tu Hy, Pleomorphic adenoma of the parotid gland metastasizing to the cervical lymph node. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2000 Mar; [PubMed PMID: 10699827]
Level 3 (low-level) evidenceMarioni G,Marino F,Stramare R,Marchese-Ragona R,Staffieri A, Benign metastasizing pleomorphic adenoma of the parotid gland: a clinicopathologic puzzle. Head [PubMed PMID: 14648866]
Level 3 (low-level) evidenceNouraei SA,Ferguson MS,Clarke PM,Sandison A,Sandhu GS,Michaels L,Rhys-Evans P, Metastasizing pleomorphic salivary adenoma. Archives of otolaryngology--head [PubMed PMID: 16847191]
Level 1 (high-level) evidenceRaja V,China C,Masaki KH,Nakano G, Unusual presentations of uncommon tumors: case 1. Benign metastasizing pleomorphic adenoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2002 May 1; [PubMed PMID: 11981014]
Level 3 (low-level) evidenceSnyderman C,Johnson JT,Barnes EL, Extraparotid Warthin's tumor. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 1986 Feb; [PubMed PMID: 3083330]
McGarry JG,Redmond M,Tuffy JB,Wilson L,Looby S, Metastatic pleomorphic adenoma to the supraspinatus muscle: a case report and review of a rare aggressive clinical entity. Journal of radiology case reports. 2015 Oct; [PubMed PMID: 26629288]
Level 3 (low-level) evidenceAndreasen S,Therkildsen MH,Bjørndal K,Homøe P, Pleomorphic adenoma of the parotid gland 1985-2010: A Danish nationwide study of incidence, recurrence rate, and malignant transformation. Head & neck. 2016 Apr [PubMed PMID: 26382619]
Cohen MA,Batsakis JG, Warthin's tumor revisited. Michigan medicine. 1968 Nov; [PubMed PMID: 5699512]
Yu G,Peng X, Conservative and functional surgery in the treatment of salivary gland tumours. International journal of oral science. 2019 Aug 15; [PubMed PMID: 31413317]
Foschini MP,Malvi D,Betts CM, Oncocytic carcinoma arising in Warthin tumour. Virchows Archiv : an international journal of pathology. 2005 Jan; [PubMed PMID: 15455232]
Level 3 (low-level) evidenceMoore FO,Abdel-Misih RZ,Berne JD,Zieske AW,Rana NR,Ryckman JG, Poorly differentiated carcinoma arising in a Warthin's tumor of the parotid gland: pathogenesis, histopathology, and surgical management of malignant Warthin's tumors. The American surgeon. 2007 Apr; [PubMed PMID: 17439037]
Level 3 (low-level) evidenceBell D,Luna MA, Warthin adenocarcinoma: analysis of 2 cases of a distinct salivary neoplasm. Annals of diagnostic pathology. 2009 Jun; [PubMed PMID: 19433301]
Level 3 (low-level) evidenceMedeiros LJ,Rizzi R,Lardelli P,Jaffe ES, Malignant lymphoma involving a Warthin's tumor: a case with immunophenotypic and gene rearrangement analysis. Human pathology. 1990 Sep; [PubMed PMID: 2394439]
Level 3 (low-level) evidenceMelato M,Falconieri G,Fanin R,Baccarani M, Hodgkin's disease occurring in a Warthin's tumor: first case report. Pathology, research and practice. 1986 Oct; [PubMed PMID: 3786253]
Level 3 (low-level) evidencePescarmona E,Perez M,Faraggiana T,Granati L,Baroni CD, Nodal peripheral T-cell lymphoma associated with Warthin's tumour. Histopathology. 2005 Aug; [PubMed PMID: 16045788]
Level 3 (low-level) evidenceMarioni G,Marchese-Ragona R,Marino F,Poletti A,Ottaviano G,de Filippis C,Staffieri A, MALT-type lymphoma and Warthin's tumour presenting in the same parotid gland. Acta oto-laryngologica. 2004 Apr; [PubMed PMID: 15141762]
Level 3 (low-level) evidenceel-Naggar A,Batsakis JG,Luna MA,Goepfert H,Tortoledo ME, DNA content and proliferative activity of myoepitheliomas. The Journal of laryngology and otology. 1989 Dec; [PubMed PMID: 2559135]
Bombí JA,Alós L,Rey MJ,Mallofré C,Cuchi A,Trasserra J,Cardesa A, Myoepithelial carcinoma arising in a benign myoepithelioma: immunohistochemical, ultrastructural, and flow-cytometrical study. Ultrastructural pathology. 1996 Mar-Apr; [PubMed PMID: 8882360]
Level 3 (low-level) evidenceSavera AT,Sloman A,Huvos AG,Klimstra DS, Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 25 patients. The American journal of surgical pathology. 2000 Jun; [PubMed PMID: 10843278]
Croitoru CM,Mooney JE,Luna MA, Sebaceous lymphadenocarcinoma of salivary glands. Annals of diagnostic pathology. 2003 Aug; [PubMed PMID: 12913846]
Level 3 (low-level) evidenceSeethala RR,Thompson LD,Gnepp DR,Barnes EL,Skalova A,Montone K,Kane S,Lewis JS Jr,Solomon LW,Simpson RH,Khan A,Prasad ML, Lymphadenoma of the salivary gland: clinicopathological and immunohistochemical analysis of 33 tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2012 Jan; [PubMed PMID: 21892186]
Soares CD,Morais TML,Carlos R,Jorge J,de Almeida OP,de Carvalho MGF,Altemani AMM, Sebaceous adenocarcinomas of the major salivary glands: a clinicopathological analysis of 10 cases. Histopathology. 2018 Oct; [PubMed PMID: 29856905]
Level 3 (low-level) evidenceMichal M,Skálová A,Mukensnabl P, Micropapillary carcinoma of the parotid gland arising in mucinous cystadenoma. Virchows Archiv : an international journal of pathology. 2000 Oct; [PubMed PMID: 11097376]
Level 3 (low-level) evidencePonniah I, A rare case of sialadenoma papilliferum with epithelial dysplasia and carcinoma in situ. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. 2007 Aug; [PubMed PMID: 17630095]
Level 3 (low-level) evidenceShimoda M,Kameyama K,Morinaga S,Tanaka Y,Hashiguchi K,Shimada M,Okada Y, Malignant transformation of sialadenoma papilliferum of the palate: a case report. Virchows Archiv : an international journal of pathology. 2004 Dec; [PubMed PMID: 15455228]
Level 3 (low-level) evidenceAsirvatham JR,Jorns JM,Zhao L,Jeffries DO,Wu AJ, Outcomes of benign intraductal papillomas diagnosed on core biopsy: a review of 104 cases with subsequent excision from a single institution. Virchows Archiv : an international journal of pathology. 2018 Dec; [PubMed PMID: 30191301]
Level 3 (low-level) evidenceLuna MA,Tortoledo ME,Allen M, Salivary dermal analogue tumors arising in lymph nodes. Cancer. 1987 Mar 15; [PubMed PMID: 3815291]
Nagao T,Sugano I,Ishida Y,Matsuzaki O,Konno A,Kondo Y,Nagao K, Carcinoma in basal cell adenoma of the parotid gland. Pathology, research and practice. 1997; [PubMed PMID: 9198102]
Level 3 (low-level) evidenceIwai T,Baba J,Murata S,Mitsudo K,Maegawa J,Nagahama K,Tohnai I, Warthin tumor arising from the minor salivary gland. The Journal of craniofacial surgery. 2012 Sep; [PubMed PMID: 22976673]
Level 3 (low-level) evidenceGuntinas-Lichius O,Klussmann JP,Schroeder U,Quante G,Jungehuelsing M,Stennert E, Primary parotid malignoma surgery in patients with normal preoperative facial nerve function: outcome and long-term postoperative facial nerve function. The Laryngoscope. 2004 May; [PubMed PMID: 15126763]
Level 2 (mid-level) evidenceEisele DW,Wang SJ,Orloff LA, Electrophysiologic facial nerve monitoring during parotidectomy. Head [PubMed PMID: 19672866]
Lim YC,Lee SY,Kim K,Lee JS,Koo BS,Shin HA,Choi EC, Conservative parotidectomy for the treatment of parotid cancers. Oral oncology. 2005 Nov; [PubMed PMID: 16129655]
Level 2 (mid-level) evidenceSanabria A,Kowalski LP,Bradley PJ,Hartl DM,Bradford CR,de Bree R,Rinaldo A,Ferlito A, Sternocleidomastoid muscle flap in preventing Frey's syndrome after parotidectomy: a systematic review. Head [PubMed PMID: 21472880]
Level 1 (high-level) evidenceCurry JM,Fisher KW,Heffelfinger RN,Rosen MR,Keane WM,Pribitkin EA, Superficial musculoaponeurotic system elevation and fat graft reconstruction after superficial parotidectomy. The Laryngoscope. 2008 Feb; [PubMed PMID: 18030169]
Level 2 (mid-level) evidenceFilho WQ,Dedivitis RA,Rapoport A,Guimarães AV, Sternocleidomastoid muscle flap preventing Frey syndrome following parotidectomy. World journal of surgery. 2004 Apr; [PubMed PMID: 15022023]
de Bree R,van der Waal I,Leemans CR, Management of Frey syndrome. Head [PubMed PMID: 17230557]
Schauber MD,Fontenelle LJ,Solomon JW,Hanson TL, Cranial/cervical nerve dysfunction after carotid endarterectomy. Journal of vascular surgery. 1997 Mar; [PubMed PMID: 9081129]
Guzzo M,Locati LD,Prott FJ,Gatta G,McGurk M,Licitra L, Major and minor salivary gland tumors. Critical reviews in oncology/hematology. 2010 May; [PubMed PMID: 19939701]
Level 3 (low-level) evidenceRaaijmakers E,Engelen AM, Is sensorineural hearing loss a possible side effect of nasopharyngeal and parotid irradiation? A systematic review of the literature. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2002 Oct; [PubMed PMID: 12413668]
Level 1 (high-level) evidenceDawson AK,Orr JA, Long-term results of local excision and radiotherapy in pleomorphic adenoma of the parotid. International journal of radiation oncology, biology, physics. 1985 Mar; [PubMed PMID: 2982770]
Barton J,Slevin NJ,Gleave EN, Radiotherapy for pleomorphic adenoma of the parotid gland. International journal of radiation oncology, biology, physics. 1992; [PubMed PMID: 1313407]
Level 2 (mid-level) evidenceLeonetti JP,Marzo SJ,Zender CA,Porter RG,Melian E, Temporal bone osteoradionecrosis after surgery and radiotherapy for malignant parotid tumors. Otology [PubMed PMID: 20964249]
Level 2 (mid-level) evidence