Benign Salivary Gland Tumors

Allen Young; Oluwafunmilola Okuyemi

Benign Salivary Gland Tumors

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Continuing Education Activity

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 World Health Organization (WHO) in 2017 recognized 11 different benign epithelial salivary gland tumors. This activity reviews the evaluation and treatment of benign salivary gland tumors and highlights the role of the interprofessional team in evaluating and treating patients with this condition.

Objectives:

Summarize the epidemiology of benign salivary gland tumors.
Outline the typical presentation of a patient with a benign salivary gland tumor.
Review the management of patients with benign salivary gland tumors.

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

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]

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]

Canalicular adenoma has a recurrence rate of 3%, likely due to its multifocal presentation and incomplete excision.[44] There have been no reports of malignant transformation.[41]

Membranous BCA has a recurrence rate of 25%.[125] BCA can transform into basal cell adenosarcoma or adenoid cystic carcinoma in up to 4.3% of cases. Rarer transformations include adenocarcinoma, salivary duct carcinoma, and myoepithelial carcinoma.[126][127]

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.

Details

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