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Pediatric salivary gland lesions
Seminars in Pediatric Surgery (2006) 15, 76-84
Pediatric salivary gland lesions Deepak Mehta, MD, Jay Paul Willging, MD From the Department of Pediatric Otolaryngology & Head and Neck Surgery, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio. INDEX WORDS Salivary gland neoplasms; Parotid lesions; Acute suppurative sialadenitis; Chronic sialectasis; Mucoceles; Warthin tumor
The salivary glands comprise three main pairs of glands (ie, the parotid, the submandibular, and the sublingual) and a number of minor glands found in the mucosa of the upper aerodigestive tract. Lesions may be inflammatory or obstructive in nature or may stem from granulomatous or neoplastic disease. As such, establishing a definitive diagnosis is often quite challenging. This article reviews widely used diagnostic approaches and briefly describes various salivary gland lesions within an etiologic framework. © 2006 Elsevier Inc. All rights reserved.
The salivary glands comprise three main pairs of glands: the parotid, the submandibular, and the sublingual. There are also many other small glands throughout the oral cavity, pharynx, and paranasal sinuses that consist entirely of mucus-secreting cells. These glands differ in the type of secretion they produce. The parotid glands produce serous, watery secretions, whereas the sublingual glands produce mucous secretions. The submandibular glands produce a mixed serous and mucous secretion. Salivary gland flow is under autonomic control. The submandibular glands are the dominant source of saliva in the basal state, whereas parotid secretions are maximal at meal times, after gustatory stimulation. Salivary gland lesions are associated with a wide spectrum of etiologies. They may be inflammatory or obstructive in nature or may stem from granulomatous or neoplastic disease. As such, establishing a definitive diagnosis is often challenging. This discussion presents an overview of current diagnostic approaches and briefly describes various salivary gland lesions within an etiologic framework. Address reprint requests and correspondence: Jay Paul Willging, MD, Department of Pediatric Otolaryngology & Head and Neck Surgery, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229. E-mail: [email protected].
1055-8586/$ -see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1053/j.sempedsurg.2006.02.004
Diagnostic approaches History and physical examination The onset and duration of the problem may offer insight into the pathologic nature of the problem. Lesions present at birth may be hemangiomas or lymphatic malformations. Lesions that demonstrate rapid growth and that are accompanied by pain and fever may be inflammatory disorders; however, it is not uncommon for congenital lesions to develop acute inflammatory changes. A diffuse swelling of the gland is generally associated with inflammatory conditions, whereas a discrete palpable mass may be a neoplasm, inflammatory node, or a stone. Atypical mycobacterial infections have a predilection for the preauricular and submandibular areas. Painless lesions with violaceous skin changes overlying the area suggest this granulomatous infection. Bilateral involvement signifies systemic conditions, such as autoimmune disorders or immune deficiency. If intermittent swelling and pain are associated with mealtime, obstruction of the salivary ductal system should be considered. A history of trauma to the area of the glands or ductal openings may suggest disruption of the drainage system of the gland or secondary ductal stenosis.
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Pediatric Salivary Gland Lesions
Physical examination requires palpation of the gland, and bimanual palpation is optimal. This is done with the fingers of one hand examining the intraoral aspect of the gland while the other hand externally manipulates the gland. Expressing saliva from the salivary duct by compressing the gland posteriorly and stripping secretions anteriorly is helpful in determining whether there is any blockage of the gland’s ductal system and in ascertaining the nature of the retained secretions, normal versus purulent. The facial nerve courses through the substance of the parotid gland. Inflammatory lesions generally do not interfere with facial nerve function. If facial nerve deficits are identified on physical examination, the presence of an aggressive malignancy should be considered.
Laboratory studies Inflammatory lesions are associated with elevated leukocyte counts. C-reactive protein is a nonspecific marker of a bacterial process that can be followed longitudinally during the treatment of the infection. In cases of bilateral parotid gland enlargement, risk factors associated with human immunodeficiency virus (HIV) should be elicited and specific testing performed when necessary. Cultures obtained from the salivary gland orifice identify pathologic organisms and assist in the selection of appropriate antibiotic therapy. A purified protein-derivative skin test and a chest radiograph are appropriate when considering mycobacterial infections.
Radiographic studies In most case of salivary gland pathology, radiographic studies are not required; however, plain radiographs may allow visualization of radiopaque stones within the ductal system of the gland. Eighty percent of stones occurring in the submandibular gland are radiopaque, whereas 20% of parotid stones are visible on plain x-rays. Although sialography is not an approach that is currently preferred, historically it has been a widely used diagnostic procedure. It requires the injection of contrast into the salivary ductal system through the natural orifice. An outline of the ducts is obtained, pinpointing areas of obstruction that may represent stones or masses within the ductal system or extrinsic compression of the duct from a salivary gland mass. Signs of chronic inflammatory conditions can be seen on sialography, with alternating areas of dilation and narrowing. If performed at the time of an acute inflammatory condition, this procedure may exacerbate the condition; it should thus be delayed until the acute infection has been controlled. Traumatic lacerations of the ductal system of the gland can be visualized by the extravasation of contrast material into the parenchyma. Computed tomography (CT) and magnetic resonance imaging (MRI) have largely replaced sialography. They are able to visualize both intrinsic and extrinsic salivary gland lesions. Estimations of the nature of lesions (benign or malignant) can
77 be obtained, and the involvement of the mass within the superficial or deep lobe of the parotid gland can be demonstrated. Involvement of other compartments in the head and neck can be visualized, allowing for optimal preoperative surgical planning.1,2 Ultrasonography (US) is a diagnostic modality that is playing an increasingly important role in the management of head and neck lesions. It may be used to assess the size of a lesion, to distinguish a diffuse from a focal lesion, and to determine the vascularity and relationship of the mass to adjacent vascular structures. US can also distinguish solid from cystic lesions, and in the older child, can be used to assist fine-needle aspiration (FNA). The low cost and avoidance of radiation make this imaging modality desirable in the pediatric age group. Radioisotope studies evaluate the parenchymal function of the salivary gland. Technetium is injected intravenously and is concentrated in the salivary glands. Mass lesions can be visualized as a filling void. Emptying of saliva from the gland can be estimated after stimulating salivary gland secretion.
Pathology examination FNA provides a cytologic specimen for examination. The correlation of FNA results to final histopathologic reports varies with the quality of the FNA specimen and the specific disease process involving the gland. Differentiation of hematologic malignancies from hyperplastic nodal changes is unlikely on FNA. Chronic inflammatory changes within the salivary gland may be identified on FNA. Salivary gland neoplasms are reliably identified.3 Open biopsies are occasionally necessary. An excisional biopsy is appropriate when an FNA is nondiagnostic or when there is a high level of concern for a malignancy or minor salivary gland tumors. Incisional biopsies are inappropriate, except in select cases in which the determination of the cell type of a neoplasm directly affects treatment management. Incisional biopsy carries the risk of facial nerve injury, tumor spillage, and compromise of the discrete compartments of the neck, all of which may complicate further management. Excisional biopsy of the parotid gland generally requires a superficial parotidectomy with identification and preservation of the facial nerve. Lesions isolated to the tail of the parotid gland may be excised without a complete superficial parotidectomy in select cases. Excisional biopsy of lesions within the submandibular gland generally requires complete excision of the gland as the biopsy procedure.
Bacterial inflammatory lesions Acute suppurative sialadenitis Acute suppurative sialadenitis most frequently involves the parotid gland. The bacteriostatic activity of the thin serous
78 secretions from this gland is less active than that in the submandibular gland. The primary cause of this condition is salivary stasis; this may either be secondary to ductal obstruction from a stone or mass or due to decreased salivary flow, as occurs with dehydration. The most common organisms associated with acute suppurative sialadenitis are Staphylococcus aureus and Streptococcus viridans. Localized pain and tenderness are hallmark clinical features of acute suppurative sialadenitis. Also, there is swelling of the affected gland due to inflammatory edema and the obstructed outflow of saliva. Pain is caused by stretching of the investing fascia of the gland. Nonoperative management includes massaging of the gland to express and clear the infection, adequate hydration to increase salivary flow, sialogogues (eg, sour candy) to increase salivary production, and the administration of systemic antibiotics. For severe cases, intravenous antibiotics may be required. Occasionally, operative management is required. Before operation, complete assessment of contiguous regions of the head and neck should be performed; this is done to avoid missing unappreciated areas of involvement that would necessitate multiple procedures. When significant suppuration within the gland occurs, the resulting abscess requires drainage. When a parotid abscess is present, a preauricular incision is made and the parotid fascia is then identified and incised parallel to the facial nerve. Loculations should then be broken down and a drain placed. Drainage of submandibular abscesses is usually less complicated, requiring a standard submandibular incision and drainage approach. Recurrent parotitis of the parotid gland is the most common form of recurrent sialadenitis. Infections are generally unilateral, although bilateral cases are not uncommon. Recurrent infections alter glandular architecture, thus leading to sialectasia. Opportunistic infections from oral flora may then develop.4 Recurrent infections are managed using the same approach as used for acute suppurative sialadenitis. To maximize hydration, children may require free access to water throughout the day and, as previously described, sialogogues to maintain salivary flow. For children with a history of recurrent sialadenitis, infections can often be averted by ensuring hydration and salivary flow and massaging the gland. These recurrent salivary gland infections often spontaneously resolve by puberty. In rare cases in which infections cannot be cleared despite prolonged courses of intravenous antibiotic therapy, surgical intervention is required. When the parotid gland is involved, performing a total parotidectomy is generally required, in that performing a superficial parotidectomy alone raises the risk of recurrent infections. When the submandibular gland is involved, excision of the gland is also necessary.
Neonatal sialadenitis Salivary gland infections in neonates most commonly involve the parotids, and 40% of cases occur in premature
Seminars in Pediatric Surgery, Vol 15, No 2, May 2006 infants. Staphylococcus aureus remains the most frequent causative agent, although many other bacterial etiologies occur. When possible, it is prudent to obtain cultures from the orifice of the duct. Blood cultures are infrequently positive. Intravenous antibiotics are generally effective in clearing the infection, and recurrence is uncommon.5
Viral inflammatory lesions Mumps Since the institution of a pediatric vaccination program, the number of reported cases of mumps has steadily declined. Mumps is most commonly encountered during the winter and spring. The mumps virus not only affects the salivary glands, but also the gonads, meninges, and pancreas. Swelling of the parotid duct orifice is often seen and salivary secretions are clear. When confirmation of the virus is desirable, amylase levels, compliment fixation studies, and hemagglutination studies are useful. The incubation period is 14 to 21 days. The virus is contagious from 3 days before the onset of swelling until the resolution of swelling.6 Treatment consists of supportive care.
Human immunodeficiency virus (HIV) All major salivary glands may be affected by HIV infections; however, parotid enlargement is most commonly seen. HIV infection is evidenced by lymphoproliferative changes or cystic lesions. Bilateral cystic enlargement of the parotid glands is pathognomonic for HIV infection. Management of HIV cystic lesions is nonoperative. Needle aspiration may be performed if a lesion is painful and expanding. Open surgical excisions are reserved for those lesions in which malignancy is considered in the differential diagnosis.7
Chronic obstructive lesions Chronic sialectasis Chronic inflammation of the salivary gland tissue leads to alteration in the drainage system of the gland, thus increasing the likelihood of infection. Strictures may form as a result of congenital malformations, recurrent infection, trauma, or neoplasms. Progressive dilation of the ductal system proximal to the obstruction occurs and leads to salivary gland enlargement. Painful swelling of the gland in the postprandial period is the hallmark feature of this disorder. Secretions eventually are expressed and the swelling subsides. If complete ductal obstruction is present, the salivary gland remains swollen and is prone to recurrent infection.8
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Pediatric Salivary Gland Lesions
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Sialolithiasis Sialolithiasis, or salivary gland stones, involves both the submandibular gland (90% of cases) and the parotid gland (10% of cases); it is more common in adults.9 The submandibular glands are more prone to calculi formation due to the alkaline nature and increased viscosity of their secretions, and also because submandibular gland salivary flow courses in an upward direction through a long duct. Salivary gland stones may be palpated on bimanual examination. Probing the salivary duct with a lacrimal probe may also allow the lesion to be appreciated. Radiographs may be useful in delineating obstructing calculi. Eighty percent of submandibular stones are radiopaque, whereas 80% of parotid stones are radiolucent. Management of salivary gland stones focuses on removal of the obstructing mass. Small intraoral incisions are effective in opening the parotid or submandibular ducts sufficiently to allow for the removal of many stones located distal to the gland parenchyma. Intraductal stones located within the parenchyma of the gland may be retrieved by endoscopically deployed urologic stone-retrieval baskets currently available in sizes that allow use in the ductal system of the salivary glands. If the stones cannot be removed in this manner, gland excision is necessary to alleviate recurring symptoms. To facilitate stone retrieval, extracorporeal shock-wave lithotripsy has been used to break up large stones.10
Mucoceles Mucoceles, also termed mucous retention cysts, generally involve the minor salivary glands. These lesions are most commonly seen on the lip and are generally associated with localized trauma. Ductal obstruction occurs with enlargement of the gland. Surgical excision is recommended for problematic lesions and is curative. Children have a tendency to further traumatize the lesion with their teeth, leading to local foreign body reactions and increasing size of the lesion. Ranulae (cysts or pseudocysts) usually derive from the sublingual glands. They present as painless swellings on the floor of the mouth (Figure 1a and b). When large, ranulae may extend below the level of the mylohyoid muscle; such plunging ranulae are best accessed through a transcervical operative approach. Ranulae remaining above the level of the mylohyoid are removed trans-orally; during resection, the lingual nerve must be identified and preserved.
Granulomatous disease Mycobacterial disease Extrathoracic tuberculous disease presents in about 30% of children with tuberculosis. The most common sites of ex-
Figure 1 (A) Ranula involving the right floor of mouth. (B) CT of ranula involving right floor of mouth. (Color version of figure is available online.)
trathoracic spread are the cervical and supraclavicular lymph nodes. Primary tuberculosis of the salivary glands is extremely uncommon. A positive Mantoux skin test (induration ⬎10 mm) establishes the diagnosis of tuberculosis and chest x-rays demonstrate mediastinal adenopathy. Patients are managed with standard antituberculous drugs. With the increasing incidence of resistant strains of Mycobacterium tuberculosis, culture and sensitivity testing of the organism is recommended.11
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Seminars in Pediatric Surgery, Vol 15, No 2, May 2006 in the region of the mass. Draining sinuses are common. A planned incision and drainage procedure may improve the cosmetic result if the lesion appears ready to spontaneously drain. Curettage may be considered at the time of the incision and drainage procedure to debulk the lesion and improve the chances for spontaneous recovery. When lesions are not painful, are stable in size, and appear unlikely to spontaneously drain, observation has been used effectively. As these children are asymptomatic, fibrosis and even complete resolution of lesions have been observed on follow up. For children in whom a residual mass exists, surgical excision of this remnant is performed; this procedure is far less difficult than when it is performed during an acute infectious period.13
Actinomycosis Actinomycosis is a Gram-positive anaerobic organism found in the oral cavity. Infection in the cervicofacial area often involves the salivary glands. Infections often follow a history of oral trauma or dental procedures. A painless, slowly progressive inflammatory process develops, and multiple areas of necrosis may be seen on imaging. Draining fistulae commonly develop. The presence of sulfur granules present on biopsy or FNA is pathognomonic for actinomycosis. Effective treatment often requires a 6-week course of intravenous penicillin therapy followed by 6 months of oral penicillin.14 Figure 2 Atypical mycobacteria infection with a painless selling of the preauricular area with the typical violaceous coloration of the skin. (Color version of figure is available online.)
In contrast, nontuberculous mycobacterial infection of the salivary gland is common in children (Figure 2). Most children with atypical mycobacteria infection present between 16 and 36 months of age. Mycobacterium avium intracellulare accounts for up to 90% of the infections. Periparotid and submandibular lymph nodes are commonly affected. There is a characteristic violaceous hue to the overlying skin, but lesions are not painful. Some lesions may spontaneously drain. The Mantoux test is either negative or weakly positive (up to 10 mm). A chest x-ray is usually negative, differentiating this disease from tuberculosis. Antituberculosis drugs are not generally effective against atypical mycobacteria. Macrolide antibiotics may show some limited activity.12 Cultures obtained from needle aspiration or open incision and drainage procedures have a 6-week incubation period. Twenty to 50% of smears demonstrate the acid fast bacillus. Surgical treatment is controversial. Excision is especially challenging during the acute infectious period in that there is much granulation tissue and it is difficult to recognize tissue planes during dissection. Also, acute infection makes it is difficult to visualize important structures (eg, facial nerve trunk, marginal mandibular branch of the facial nerve)
Sarcoidosis Sarcoidosis is an idiopathic granulomatous disease that may affect the salivary glands; it is uncommon in children. Biopsy of the minor salivary glands of the lip or tail of the parotid confirms the disorder. No specific treatment is necessary for salivary gland involvement. Uveoparotid fever (Heerfordt’s syndrome), which is sometimes seen in patients with sarcoidosis, is characterized by uveitis, parotid enlargement, and facial paralysis. Systemic steroids may hasten the resolution of these symptoms.15
Necrotizing sialometaplasia Necrotizing sialometaplasia is a self-limited disease that mimics a destructive malignancy. It has been reported in adolescents and can be found anywhere that salivary gland tissue is present. This condition presents as a painless, ulcerated mass. Histologically, granulation tissue and chronic inflammation is present, along with squamous metaplasia. Spontaneous healing occurs within 6 to 12 weeks.16
Sjögren syndrome Sjögren disease is characterized by destruction of the exocrine glands, leading to xerostomia and keratoconjunctivitis.
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Table 1 Histologic types and frequencies of pediatric salivary gland neoplasms Benign Epithelial (50%)
Malignant Epithelial (50%)
Pleomorphic adenoma 86.6% Mucoepidermoid 49.6% Plexiform neurofibroma 3.2% carcinoma Warthin tumour 2% Acinic cell carcinoma 12.2% Cystadenoma 2% Undifferentiated 8.9% Embryoma 1.2% carcinoma Lymphoepithelial 1.2% Adenocarcinoma 7.7% lesion Adenoid cystic 6.5% Monomorphic adenoma 0.4 carcinoma Others 3.4% Malignant mixed 4.1% tumour Malignant nerve 2.0% sheath tumour Unclassified 1.6% carcinoma Squamous cell 1.2% carcinoma Others 6.2%
Sialadenitis is frequently seen due to the diminished salivary flow. Serologic studies demonstrate antinuclear antibodies and antibodies to Sjögren syndrome antigens A and B. Biopsy of the minor salivary glands in the lip or tail of the parotid indicates the characteristic sialectasis. Patients with this disorder have an increased risk of lymphoma.17
81 age group tend to arise in the oral cavity, although lesions in the pharynx, larynx, and bronchus have also been reported.19,20 Most patients with a salivary gland neoplasm present with a painless, slow-growing mass in the parotid region. A sudden increase in size may be secondary to infection, cystic degeneration, hemorrhage, or malignant transformation. This may result in a previously painless lesion becoming painful and tender. Benign and low-grade malignant lesions may have a similar clinical progression. The average duration from the presence of a lump being noticed to definitive diagnosis is close to 21 months. Clinical features that suggest malignancy are facial nerve involvement, pain, fixation of the mass, involvement of the overlying skin or underlying structures, and associated cervical adenopathy.21,22 Patients with a submandibular tumor present with a painless swelling or mass in the submandibular triangle. Involvement of skin or fixation to the mandible indicates local extension of a malignant tumor. Ipsilateral weakness or numbness of the tongue suggests perineural spread along the hypoglossal or lingual nerves.23 Minor salivary gland lesions are rare. Benign lesions tend to present as a painless submucosal mass with normalappearing overlying mucosa; however, a malignant lesion may present as a submucosal mass or an ulcerative lesion. The palate is the most common site involved with minor salivary gland neoplasms, although such lesions may be found anywhere in the upper aerodigestive tract.24
Hemangiomas and vascular malformations
Salivary gland neoplasms Overview and clinical presentation Salivary gland neoplasms are far less common in children than are inflammatory conditions. They comprise less than 10% of all pediatric head and neck tumors. Clinically, salivary gland neoplasms fall into three histologic groups: benign, low-grade malignancy, and high-grade malignancy (Table 1). When a solitary salivary gland tumor is present, the chance of malignancy is greater in the child than in the adult. The most common benign neoplasms affecting the major salivary glands in children are vascular and lipomatous lesions. Most pediatric epithelial salivary tumors occur in children older than 10 years of age; if malignant, most of these tumors are low-grade. Malignant tumors in children younger than age 10, however, tend to be high-grade neoplasms associated with a poor prognosis. The parotid gland is involved in up to 90% of all pediatric salivary gland tumors, and 50% of these tumors are malignant.18 Malignant tumors are generally low-grade; however, a malignant tumor in a child younger than age 10 is more likely to be a high-grade neoplasm, portending a poor prognosis. Minor salivary gland tumors in the pediatric
Hemangiomas are the most common vascular tumors in childhood. They are characterized by vascular endothelium that undergoes a phase of growth followed by slow spontaneous involution that occurs gradually over several years and is generally complete by the first decade of life. These lesions account for 60% of all pediatric salivary gland neoplasms. Of these salivary gland hemangiomas, 80% arise in the parotid glands, 18% arise in the submandibular glands, and 2% arise in the minor salivary glands. In contrast to hemangiomas, vascular malformations are structural anomalies thought to represent errors in vascular or lymphatic morphogenesis. They encompass a wide range of anomalies and are classified according to their components as capillary, venous, lymphatic, arterial, and combined malformations. In some patients, lymphatic malformations may involve the salivary glands. Discussions that focus on cervicofacial hemangiomas and lymphatic malformations are provided in other articles within this issue of Seminars in Pediatric Surgery.
Pleomorphic adenoma Pleomorphic adenoma is a common benign pediatric salivary gland tumor; lesions are also referred to as benign
82 mixed tumors. These tumors typically manifest as hard, painless, slow growing masses, and occur in all pediatric age groups (median, 15 years). On ultrasonography (US), pleomorphic adenomas appear hypoechoic to isoechoic relative to the uninvolved parotid gland. CT and MRI findings vary depending on the tumor size. Smaller tumors are generally homogeneous and well defined, whereas larger tumors are heterogeneous and less well defined, with areas of hemorrhage or necrosis. Pleomorphic adenomas have both mesenchymal and epithelial cell lines. Although these tumors appear to be encapsulated, on microscopic examination they may have pseudopod extensions into adjacent tissues. As such, simple enucleation results in up to 30% recurrence rates. Tumors arising from the superficial lobe of the parotid gland minimally require a superficial parotidectomy. Deeplobe parotid tumors may manifest as a parapharyngeal mass with medial displacement of the tonsil and intraoral swelling. These tumors require a total parotidectomy. Lesions arising from the submandibular region are managed by surgical excision with adequate margins.
Seminars in Pediatric Surgery, Vol 15, No 2, May 2006
Mucoepidermoid carcinoma Mucoepidermoid carcinoma is the most common salivary gland malignancy in children, accounting for 50% of malignant salivary tumors. This tumor is also the most common radiation-induced salivary gland tumor in children. It is generally found between the ages of 10 and 16 years. Tumors consist of a combination of squamous and mucous cells arranged in cords, sheets, or cystic configurations. They are histologically classified as low-, intermediate-, and high-grade tumors, with most pediatric tumors being low-grade. CT findings demonstrate cystic low-attenuation areas and, rarely, focal calcifications. High-grade mucoepidermoid carcinomas tend to be more solid with fewer cystic areas, and are more homogeneous on both CT and MRI. Mucoepidermoid carcinoma requires surgical excision. Low-grade lesions may be treated with wide local resection. High-grade neoplasms often require treatment of the cervical lymph nodes by a selective neck dissection, radiation, or both.27,28
Acinic cell carcinoma Warthin tumor Warthin tumor, also known as papillary cystadenoma, lymphomatosum, or adenolymphoma, manifests as a painless slowgrowing mass; it presents bilaterally in up to 10% of cases. Warthin tumors are thought to be a direct result of the unique embryologic development of the parotid gland, which allows the incorporation of lymphatic elements and heterotopic salivary gland ductal epithelium within intraparotid and periparotid nodes. Histologically, these tumors consist of a double layer of oncocytes resting on a dense lymphoid stroma. On CT and MR imaging, Warthin tumors appear as well-circumscribed, homogeneous cystic or solid lesions, often located in the tail of the parotid gland. Multiple or bilateral parotid or periparotid masses strongly suggest the diagnosis of Warthin tumor. Treatment includes surgical resection. Recurrences may be a result of the tumor’s propensity for multifocal lesions within the same gland.22,25
Sialoblastoma (embryoma) Sialoblastoma is an extremely rare tumor unique to children that is diagnosed at birth or shortly thereafter. It represents an embryonic anlage of the minor salivary glands. Histopathologically, the cells are mitotically active. Primitive cell masses with formative ducts and pseudoductular spaces without acinar differentiation are seen in a loose investing mesenchyma with an embryonic appearance. These tumors arise at any of the sites of minor salivary glands and can be locally aggressive. Although the majority of these neoplasms are benign, there have been reports of neck metastasis. Wide surgical excision is the treatment of choice.26
Acinic cell carcinoma is the second most frequent salivary carcinoma in children and, as with mucoepidermoid carcinoma, generally presents between 10 and 16 years of age. On pathologic examination, acinic cell carcinoma appears fairly well circumscribed with nests of cells with basophilic cytoplasm and lymphoid infiltrate into the surrounding stroma. This tumor generally is regarded as a low-grade malignancy and seldom metastasizes. It has a high tendency to recur locally if lesions are incompletely excised.29
Adenoid cystic carcinoma Adenoid cystic carcinoma usually exhibits a protracted course characterized by an indolent growth pattern and a relentless tendency for local and perineural invasion. It is associated with a high recurrence rate and relatively poor long-term survival. Although distant metastasis generally occurs within the first 5 years of diagnosis, it can occur up to 20 years after initial diagnosis.30
Adenocarcinoma Adenocarcinoma is observed in early childhood and is associated with a high potential for metastases. In two series with a total of eight patients having an average age of 6 years at presentation, there was an overall mortality rate of 75%. This suggests that adenocarcinoma is an aggressive disease that may require more radical resection and/or adjuvant therapy than is suggested by histology alone.21,31
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Undifferentiated carcinoma Undifferentiated carcinoma is the only carcinoma reported in the perinatal period; however, it more commonly occurs in children younger than age 10. This tumor tends to be highly aggressive and has a poor prognosis despite aggressive treatment protocols.32
Surgical resection Surgical resection is the therapeutic mainstay for treatment of salivary gland neoplasms. Resection should provide complete removal of the neoplasm without tumor spillage or facial nerve damage. For parotid tumors, a parotidectomy with adequate margins is ideal. Superficial parotidectomy may be adequate for control of most benign and malignant tumors of the lateral lobe; however, deep-lobe tumors require a total parotidectomy. Surgery should be aimed at preservation of the facial nerve unless the nerve is directly invaded or the intact nerves limit the complete resection of the tumor. Facial-nerve grafting can restore deficits resulting from facial nerve section. For submandibular gland neoplasms, it is prudent to perform a regional dissection of the submandibular triangle to reduce the risk of recurrence.33 The incidence of cervical lymph node metastasis is estimated to be less than 15%. Neck dissection is indicated only when clinically enlarged cervical lymph nodes are present. Prophylactic neck dissection can be considered in patients with poorly differentiated lesions, including high-grade mucoepidermoid squamous cell carcinoma, undifferentiated carcinoma, adenoid cystic carcinoma, and adenocarcinoma.21
Management of recurrent neoplasms Children with pleomorphic adenoma who have undergone superficial parotidectomy have a recurrence rate of 19.5%, which sharply contrasts to the 1% recurrence rate reported in adults. This may represent an increased risk of violation of the tumor capsule and resultant seeding of the resection bed and wound. It may also reflect inappropriate initial treatment of a parotid lesion that is mistaken for a high cervical node.34 Tumor recurrence is most common with adenoid cystic carcinoma (50%), followed by mucoepidermoid carcinoma (38%) and acinic cell carcinoma (20%). The high recurrence rate in pediatric patients is in part due to an inadequate surgical procedure at the initial presentation, thus necessitating a second, more extensive operation. To ensure complete removal of the tumor, it is imperative that salivary gland tumors are properly evaluated preoperatively and that the proper procedure is performed at initial presentation.19,28,29
83 Patients with recurrence may require salvage procedures. Results of such procedures have been reported in only 2 pediatric series, with a total of 15 patients. In one series, 5 patients referred after primary surgery and radiotherapy underwent salvage procedures. Of these patients, 2 died of disease within 6 years of salvage surgery; both had been diagnosed with high-grade parotid cancers. In another series, 10 patients with recurrences underwent salvage operations. Two of these 10 patients died of disease at 8 and 13 years, respectively, after their initial operations.35,36
Radiation Because of the potential for radiation-induced sequelae, radiation in children must be used with extreme caution. Radiation-induced complications include dental caries, delayed dental development, trismus, and radiation-induced tumors. Radiation is generally recommended for treatment of high-grade tumors, in cases in which: (1) microscopic residual disease is found, (2) there is positive cervical node involvement with extracapsular spread, or (3) perineural invasion or spread has been identified.
References 1. Garcia CJ, Flores PA, Arce JD, et al. Ultrasonography in the study of salivary gland lesions in children. Pediatr Radiol 1998;28:418-25. 2. Som PM, Curtin HD. Head and neck imaging. In: Mosby Year Book, 4th edition, vol 2, chap 39. St. Louis, MO: Mosby, 1996:1-30. 3. Eisenhut CC, King DE, Nelson WA, et al. Fine-needle biopsy of pediatric lesions: a three-year study in an outpatient biopsy clinic. Diagn Cytopathol 1996;14:43-50. 4. Chitre VV, Premchandra DJ. Recurrent parotitis. Arch Dis Child 1997;77:359-63. 5. Weibel L, Goetschel P, Meier R, et al. Neonatal suppurative submandibular sialadenitis. Pediatr Infect Dis J 2005;24:379-81. 6. Pachman DJ. Mumps. Am J Dis Child 1979;133:332. 7. Pinto A, De Rossi SS. Salivary gland disease in pediatric HIV patients: an update. J Dent Child (Chic) 2004;71:33-7. 8. Guntinas-Lichius O, Jungehulsing M. Treatment of chronic parotid sialectasis with botulinum toxin A. Laryngoscope 2002;112:586-7. 9. Lindman JP, Woolley AL. Multiple intraparenchymal parotid calculi: a case report and review of the literature. Ear Nose Throat J 2003;82:615-7. 10. McGurk M, Escudier MP, Brown JE. Modern management of salivary calculi. Br J Surg 2005;92:107-12. 11. Kim YH, Jeong WJ, Jung KY, et al. Diagnosis of major salivary gland tuberculosis: experience of eight cases and review of the literature. Acta Otolaryngol 2005;125:1318-22. 12. Luong A, McClay JE, Jafri HS, et al. Antibiotic therapy for nontuberculous mycobacterial cervicofacial lymphadenitis. Laryngoscope 2005;115:1746-51. 13. Rieu PN, van den Broek P, Pruszczynski M, et al. Atypical mycobacterial infection of the parotid gland. J Pediatr Surg 1990;25:483-6. 14. Rice DH. Chronic inflammatory disorders of the salivary glands. Otolaryngol Clin North Am 1999;32:813-8. 15. Wu JJ, Schiff KR. Sarcoidosis. Am Fam Physician 2004;70:312-22. 16. Brannon RB, Fowler CB, Hartman KS. Necrotizing sialometaplasia. A clinicopathologic study of sixty-nine cases and review of the literature. Oral Surg Oral Med Oral Pathol 1991;72:317-25.
84 17. Franklin DJ, Smith RJ, Person DA. Sjogren’s syndrome in children. Otolaryngol Head Neck Surg 1986;94:230-5. 18. Bradley PJ. Epidemiology: statistics in a defined UK population. In: McGurk M, Renehan A, eds. Controversies in the Management of Salivary Gland Disease, chap 1. Oxford: Oxford University Press, 2001:6-12. 19. De Campora E, Croce A, Bicciolo G, et al. Adenoid-cystic carcinoma (cylindroma) of the pyriform sinus in pediatric age. Int J Pediatr Otorhinolaryngol 1987;14:235-42. 20. Javadi M, Bafrouee FM, Mohseni M, et al. Laryngeal adenoid cystic carcinoma in a child: a case report. Ear Nose Throat J 2002;81:34-5. 21. Baker SR, Malone B. Salivary gland malignancies in children. Cancer 1985;55:1730-6. 22. Bentz BG, Hughes CA, Ludemann JP, et al. Masses of the salivary gland region in children. Arch Otolaryngol Head Neck Surg 2000;126:1435-9. 23. Hockstein NG, Samadi DS, Gendron K, et al. Pediatric submandibular triangle masses: a fifteen-year experience. Head Neck 2004;26:675-80. 24. Brigger MT, Pearson SE. Management of parapharyngeal minor salivary neoplasms in children: a case report and review. Int J Pediatr Otorhinolaryngol 2006;70:143-6. 25. Lowe LH, Stokes LS, Johnson JE, et al. Swelling at the angle of the mandible: imaging of the pediatric parotid gland and periparotid region. Radiographics 2001;21:1211-27. 26. Batsakis JG, Mackay B, Ryka AF, et al. Perinatal salivary gland tumours (embryomas). J Laryngol Otol 1988;102:1007-11.
Seminars in Pediatric Surgery, Vol 15, No 2, May 2006 27. Goode RK, Auclair PL, Ellis GL. Mucoepidermoid carcinoma of the major salivary glands: clinical and histopathologic analysis of 234 cases with evaluation of grading criteria. Cancer 1998;82:1217-24. 28. Hicks J, Flaitz C. Mucoepidermoid carcinoma of salivary glands in children and adolescents: assessment of proliferation markers. Oral Oncol 2000;36:454-60. 29. Sato T, Kamata SE, Kawabata K, et al. Acinic cell carcinoma of the parotid gland in a child. Pediatr Surg Int 2005;21:377-80. 30. Bull PD. Salivary gland neoplasia in childhood. Int J Pediatr Otorhinolaryngol 1999;49:S235-8 (suppl 1). 31. Ogata H, Ebihara S, Mukai K. Salivary gland neoplasms in children. Jpn J Clin Oncol 1994;24:88-93. 32. Batsakis JG, Luna MA. Undifferentiated carcinomas of salivary glands. Ann Otol Rhinol Laryngol 1991;100:82-4. 33. Luna MA, Batsakis JG, el-Naggar AK. Salivary gland tumors in children. Ann Otol Rhinol Laryngol 1991;100:869-71. 34. Webb AJ, Eveson JW. Pleomorphic adenomas of the major salivary glands: a study of the capsular form in relation to surgical management. Clin Otolaryngol Allied Sci 2001;26:134-42. 35. Shikhani AH, Johns ME. Tumors of the major salivary glands in children. Head Neck Surg 1988;10:257-63. 36. Yu GY, Li ZL, Ma DQ, et al. Diagnosis and treatment of epithelial salivary gland tumours in children and adolescents. Br J Oral Maxillofac Surg 2002;40:389-92.
Pediatric salivary gland lesions Deepak Mehta, MD, Jay Paul Willging, MD From the Department of Pediatric Otolaryngology & Head and Neck Surgery, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio. INDEX WORDS Salivary gland neoplasms; Parotid lesions; Acute suppurative sialadenitis; Chronic sialectasis; Mucoceles; Warthin tumor
The salivary glands comprise three main pairs of glands (ie, the parotid, the submandibular, and the sublingual) and a number of minor glands found in the mucosa of the upper aerodigestive tract. Lesions may be inflammatory or obstructive in nature or may stem from granulomatous or neoplastic disease. As such, establishing a definitive diagnosis is often quite challenging. This article reviews widely used diagnostic approaches and briefly describes various salivary gland lesions within an etiologic framework. © 2006 Elsevier Inc. All rights reserved.
The salivary glands comprise three main pairs of glands: the parotid, the submandibular, and the sublingual. There are also many other small glands throughout the oral cavity, pharynx, and paranasal sinuses that consist entirely of mucus-secreting cells. These glands differ in the type of secretion they produce. The parotid glands produce serous, watery secretions, whereas the sublingual glands produce mucous secretions. The submandibular glands produce a mixed serous and mucous secretion. Salivary gland flow is under autonomic control. The submandibular glands are the dominant source of saliva in the basal state, whereas parotid secretions are maximal at meal times, after gustatory stimulation. Salivary gland lesions are associated with a wide spectrum of etiologies. They may be inflammatory or obstructive in nature or may stem from granulomatous or neoplastic disease. As such, establishing a definitive diagnosis is often challenging. This discussion presents an overview of current diagnostic approaches and briefly describes various salivary gland lesions within an etiologic framework. Address reprint requests and correspondence: Jay Paul Willging, MD, Department of Pediatric Otolaryngology & Head and Neck Surgery, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229. E-mail: [email protected].
1055-8586/$ -see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1053/j.sempedsurg.2006.02.004
Diagnostic approaches History and physical examination The onset and duration of the problem may offer insight into the pathologic nature of the problem. Lesions present at birth may be hemangiomas or lymphatic malformations. Lesions that demonstrate rapid growth and that are accompanied by pain and fever may be inflammatory disorders; however, it is not uncommon for congenital lesions to develop acute inflammatory changes. A diffuse swelling of the gland is generally associated with inflammatory conditions, whereas a discrete palpable mass may be a neoplasm, inflammatory node, or a stone. Atypical mycobacterial infections have a predilection for the preauricular and submandibular areas. Painless lesions with violaceous skin changes overlying the area suggest this granulomatous infection. Bilateral involvement signifies systemic conditions, such as autoimmune disorders or immune deficiency. If intermittent swelling and pain are associated with mealtime, obstruction of the salivary ductal system should be considered. A history of trauma to the area of the glands or ductal openings may suggest disruption of the drainage system of the gland or secondary ductal stenosis.
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Physical examination requires palpation of the gland, and bimanual palpation is optimal. This is done with the fingers of one hand examining the intraoral aspect of the gland while the other hand externally manipulates the gland. Expressing saliva from the salivary duct by compressing the gland posteriorly and stripping secretions anteriorly is helpful in determining whether there is any blockage of the gland’s ductal system and in ascertaining the nature of the retained secretions, normal versus purulent. The facial nerve courses through the substance of the parotid gland. Inflammatory lesions generally do not interfere with facial nerve function. If facial nerve deficits are identified on physical examination, the presence of an aggressive malignancy should be considered.
Laboratory studies Inflammatory lesions are associated with elevated leukocyte counts. C-reactive protein is a nonspecific marker of a bacterial process that can be followed longitudinally during the treatment of the infection. In cases of bilateral parotid gland enlargement, risk factors associated with human immunodeficiency virus (HIV) should be elicited and specific testing performed when necessary. Cultures obtained from the salivary gland orifice identify pathologic organisms and assist in the selection of appropriate antibiotic therapy. A purified protein-derivative skin test and a chest radiograph are appropriate when considering mycobacterial infections.
Radiographic studies In most case of salivary gland pathology, radiographic studies are not required; however, plain radiographs may allow visualization of radiopaque stones within the ductal system of the gland. Eighty percent of stones occurring in the submandibular gland are radiopaque, whereas 20% of parotid stones are visible on plain x-rays. Although sialography is not an approach that is currently preferred, historically it has been a widely used diagnostic procedure. It requires the injection of contrast into the salivary ductal system through the natural orifice. An outline of the ducts is obtained, pinpointing areas of obstruction that may represent stones or masses within the ductal system or extrinsic compression of the duct from a salivary gland mass. Signs of chronic inflammatory conditions can be seen on sialography, with alternating areas of dilation and narrowing. If performed at the time of an acute inflammatory condition, this procedure may exacerbate the condition; it should thus be delayed until the acute infection has been controlled. Traumatic lacerations of the ductal system of the gland can be visualized by the extravasation of contrast material into the parenchyma. Computed tomography (CT) and magnetic resonance imaging (MRI) have largely replaced sialography. They are able to visualize both intrinsic and extrinsic salivary gland lesions. Estimations of the nature of lesions (benign or malignant) can
77 be obtained, and the involvement of the mass within the superficial or deep lobe of the parotid gland can be demonstrated. Involvement of other compartments in the head and neck can be visualized, allowing for optimal preoperative surgical planning.1,2 Ultrasonography (US) is a diagnostic modality that is playing an increasingly important role in the management of head and neck lesions. It may be used to assess the size of a lesion, to distinguish a diffuse from a focal lesion, and to determine the vascularity and relationship of the mass to adjacent vascular structures. US can also distinguish solid from cystic lesions, and in the older child, can be used to assist fine-needle aspiration (FNA). The low cost and avoidance of radiation make this imaging modality desirable in the pediatric age group. Radioisotope studies evaluate the parenchymal function of the salivary gland. Technetium is injected intravenously and is concentrated in the salivary glands. Mass lesions can be visualized as a filling void. Emptying of saliva from the gland can be estimated after stimulating salivary gland secretion.
Pathology examination FNA provides a cytologic specimen for examination. The correlation of FNA results to final histopathologic reports varies with the quality of the FNA specimen and the specific disease process involving the gland. Differentiation of hematologic malignancies from hyperplastic nodal changes is unlikely on FNA. Chronic inflammatory changes within the salivary gland may be identified on FNA. Salivary gland neoplasms are reliably identified.3 Open biopsies are occasionally necessary. An excisional biopsy is appropriate when an FNA is nondiagnostic or when there is a high level of concern for a malignancy or minor salivary gland tumors. Incisional biopsies are inappropriate, except in select cases in which the determination of the cell type of a neoplasm directly affects treatment management. Incisional biopsy carries the risk of facial nerve injury, tumor spillage, and compromise of the discrete compartments of the neck, all of which may complicate further management. Excisional biopsy of the parotid gland generally requires a superficial parotidectomy with identification and preservation of the facial nerve. Lesions isolated to the tail of the parotid gland may be excised without a complete superficial parotidectomy in select cases. Excisional biopsy of lesions within the submandibular gland generally requires complete excision of the gland as the biopsy procedure.
Bacterial inflammatory lesions Acute suppurative sialadenitis Acute suppurative sialadenitis most frequently involves the parotid gland. The bacteriostatic activity of the thin serous
78 secretions from this gland is less active than that in the submandibular gland. The primary cause of this condition is salivary stasis; this may either be secondary to ductal obstruction from a stone or mass or due to decreased salivary flow, as occurs with dehydration. The most common organisms associated with acute suppurative sialadenitis are Staphylococcus aureus and Streptococcus viridans. Localized pain and tenderness are hallmark clinical features of acute suppurative sialadenitis. Also, there is swelling of the affected gland due to inflammatory edema and the obstructed outflow of saliva. Pain is caused by stretching of the investing fascia of the gland. Nonoperative management includes massaging of the gland to express and clear the infection, adequate hydration to increase salivary flow, sialogogues (eg, sour candy) to increase salivary production, and the administration of systemic antibiotics. For severe cases, intravenous antibiotics may be required. Occasionally, operative management is required. Before operation, complete assessment of contiguous regions of the head and neck should be performed; this is done to avoid missing unappreciated areas of involvement that would necessitate multiple procedures. When significant suppuration within the gland occurs, the resulting abscess requires drainage. When a parotid abscess is present, a preauricular incision is made and the parotid fascia is then identified and incised parallel to the facial nerve. Loculations should then be broken down and a drain placed. Drainage of submandibular abscesses is usually less complicated, requiring a standard submandibular incision and drainage approach. Recurrent parotitis of the parotid gland is the most common form of recurrent sialadenitis. Infections are generally unilateral, although bilateral cases are not uncommon. Recurrent infections alter glandular architecture, thus leading to sialectasia. Opportunistic infections from oral flora may then develop.4 Recurrent infections are managed using the same approach as used for acute suppurative sialadenitis. To maximize hydration, children may require free access to water throughout the day and, as previously described, sialogogues to maintain salivary flow. For children with a history of recurrent sialadenitis, infections can often be averted by ensuring hydration and salivary flow and massaging the gland. These recurrent salivary gland infections often spontaneously resolve by puberty. In rare cases in which infections cannot be cleared despite prolonged courses of intravenous antibiotic therapy, surgical intervention is required. When the parotid gland is involved, performing a total parotidectomy is generally required, in that performing a superficial parotidectomy alone raises the risk of recurrent infections. When the submandibular gland is involved, excision of the gland is also necessary.
Neonatal sialadenitis Salivary gland infections in neonates most commonly involve the parotids, and 40% of cases occur in premature
Seminars in Pediatric Surgery, Vol 15, No 2, May 2006 infants. Staphylococcus aureus remains the most frequent causative agent, although many other bacterial etiologies occur. When possible, it is prudent to obtain cultures from the orifice of the duct. Blood cultures are infrequently positive. Intravenous antibiotics are generally effective in clearing the infection, and recurrence is uncommon.5
Viral inflammatory lesions Mumps Since the institution of a pediatric vaccination program, the number of reported cases of mumps has steadily declined. Mumps is most commonly encountered during the winter and spring. The mumps virus not only affects the salivary glands, but also the gonads, meninges, and pancreas. Swelling of the parotid duct orifice is often seen and salivary secretions are clear. When confirmation of the virus is desirable, amylase levels, compliment fixation studies, and hemagglutination studies are useful. The incubation period is 14 to 21 days. The virus is contagious from 3 days before the onset of swelling until the resolution of swelling.6 Treatment consists of supportive care.
Human immunodeficiency virus (HIV) All major salivary glands may be affected by HIV infections; however, parotid enlargement is most commonly seen. HIV infection is evidenced by lymphoproliferative changes or cystic lesions. Bilateral cystic enlargement of the parotid glands is pathognomonic for HIV infection. Management of HIV cystic lesions is nonoperative. Needle aspiration may be performed if a lesion is painful and expanding. Open surgical excisions are reserved for those lesions in which malignancy is considered in the differential diagnosis.7
Chronic obstructive lesions Chronic sialectasis Chronic inflammation of the salivary gland tissue leads to alteration in the drainage system of the gland, thus increasing the likelihood of infection. Strictures may form as a result of congenital malformations, recurrent infection, trauma, or neoplasms. Progressive dilation of the ductal system proximal to the obstruction occurs and leads to salivary gland enlargement. Painful swelling of the gland in the postprandial period is the hallmark feature of this disorder. Secretions eventually are expressed and the swelling subsides. If complete ductal obstruction is present, the salivary gland remains swollen and is prone to recurrent infection.8
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Sialolithiasis Sialolithiasis, or salivary gland stones, involves both the submandibular gland (90% of cases) and the parotid gland (10% of cases); it is more common in adults.9 The submandibular glands are more prone to calculi formation due to the alkaline nature and increased viscosity of their secretions, and also because submandibular gland salivary flow courses in an upward direction through a long duct. Salivary gland stones may be palpated on bimanual examination. Probing the salivary duct with a lacrimal probe may also allow the lesion to be appreciated. Radiographs may be useful in delineating obstructing calculi. Eighty percent of submandibular stones are radiopaque, whereas 80% of parotid stones are radiolucent. Management of salivary gland stones focuses on removal of the obstructing mass. Small intraoral incisions are effective in opening the parotid or submandibular ducts sufficiently to allow for the removal of many stones located distal to the gland parenchyma. Intraductal stones located within the parenchyma of the gland may be retrieved by endoscopically deployed urologic stone-retrieval baskets currently available in sizes that allow use in the ductal system of the salivary glands. If the stones cannot be removed in this manner, gland excision is necessary to alleviate recurring symptoms. To facilitate stone retrieval, extracorporeal shock-wave lithotripsy has been used to break up large stones.10
Mucoceles Mucoceles, also termed mucous retention cysts, generally involve the minor salivary glands. These lesions are most commonly seen on the lip and are generally associated with localized trauma. Ductal obstruction occurs with enlargement of the gland. Surgical excision is recommended for problematic lesions and is curative. Children have a tendency to further traumatize the lesion with their teeth, leading to local foreign body reactions and increasing size of the lesion. Ranulae (cysts or pseudocysts) usually derive from the sublingual glands. They present as painless swellings on the floor of the mouth (Figure 1a and b). When large, ranulae may extend below the level of the mylohyoid muscle; such plunging ranulae are best accessed through a transcervical operative approach. Ranulae remaining above the level of the mylohyoid are removed trans-orally; during resection, the lingual nerve must be identified and preserved.
Granulomatous disease Mycobacterial disease Extrathoracic tuberculous disease presents in about 30% of children with tuberculosis. The most common sites of ex-
Figure 1 (A) Ranula involving the right floor of mouth. (B) CT of ranula involving right floor of mouth. (Color version of figure is available online.)
trathoracic spread are the cervical and supraclavicular lymph nodes. Primary tuberculosis of the salivary glands is extremely uncommon. A positive Mantoux skin test (induration ⬎10 mm) establishes the diagnosis of tuberculosis and chest x-rays demonstrate mediastinal adenopathy. Patients are managed with standard antituberculous drugs. With the increasing incidence of resistant strains of Mycobacterium tuberculosis, culture and sensitivity testing of the organism is recommended.11
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Seminars in Pediatric Surgery, Vol 15, No 2, May 2006 in the region of the mass. Draining sinuses are common. A planned incision and drainage procedure may improve the cosmetic result if the lesion appears ready to spontaneously drain. Curettage may be considered at the time of the incision and drainage procedure to debulk the lesion and improve the chances for spontaneous recovery. When lesions are not painful, are stable in size, and appear unlikely to spontaneously drain, observation has been used effectively. As these children are asymptomatic, fibrosis and even complete resolution of lesions have been observed on follow up. For children in whom a residual mass exists, surgical excision of this remnant is performed; this procedure is far less difficult than when it is performed during an acute infectious period.13
Actinomycosis Actinomycosis is a Gram-positive anaerobic organism found in the oral cavity. Infection in the cervicofacial area often involves the salivary glands. Infections often follow a history of oral trauma or dental procedures. A painless, slowly progressive inflammatory process develops, and multiple areas of necrosis may be seen on imaging. Draining fistulae commonly develop. The presence of sulfur granules present on biopsy or FNA is pathognomonic for actinomycosis. Effective treatment often requires a 6-week course of intravenous penicillin therapy followed by 6 months of oral penicillin.14 Figure 2 Atypical mycobacteria infection with a painless selling of the preauricular area with the typical violaceous coloration of the skin. (Color version of figure is available online.)
In contrast, nontuberculous mycobacterial infection of the salivary gland is common in children (Figure 2). Most children with atypical mycobacteria infection present between 16 and 36 months of age. Mycobacterium avium intracellulare accounts for up to 90% of the infections. Periparotid and submandibular lymph nodes are commonly affected. There is a characteristic violaceous hue to the overlying skin, but lesions are not painful. Some lesions may spontaneously drain. The Mantoux test is either negative or weakly positive (up to 10 mm). A chest x-ray is usually negative, differentiating this disease from tuberculosis. Antituberculosis drugs are not generally effective against atypical mycobacteria. Macrolide antibiotics may show some limited activity.12 Cultures obtained from needle aspiration or open incision and drainage procedures have a 6-week incubation period. Twenty to 50% of smears demonstrate the acid fast bacillus. Surgical treatment is controversial. Excision is especially challenging during the acute infectious period in that there is much granulation tissue and it is difficult to recognize tissue planes during dissection. Also, acute infection makes it is difficult to visualize important structures (eg, facial nerve trunk, marginal mandibular branch of the facial nerve)
Sarcoidosis Sarcoidosis is an idiopathic granulomatous disease that may affect the salivary glands; it is uncommon in children. Biopsy of the minor salivary glands of the lip or tail of the parotid confirms the disorder. No specific treatment is necessary for salivary gland involvement. Uveoparotid fever (Heerfordt’s syndrome), which is sometimes seen in patients with sarcoidosis, is characterized by uveitis, parotid enlargement, and facial paralysis. Systemic steroids may hasten the resolution of these symptoms.15
Necrotizing sialometaplasia Necrotizing sialometaplasia is a self-limited disease that mimics a destructive malignancy. It has been reported in adolescents and can be found anywhere that salivary gland tissue is present. This condition presents as a painless, ulcerated mass. Histologically, granulation tissue and chronic inflammation is present, along with squamous metaplasia. Spontaneous healing occurs within 6 to 12 weeks.16
Sjögren syndrome Sjögren disease is characterized by destruction of the exocrine glands, leading to xerostomia and keratoconjunctivitis.
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Table 1 Histologic types and frequencies of pediatric salivary gland neoplasms Benign Epithelial (50%)
Malignant Epithelial (50%)
Pleomorphic adenoma 86.6% Mucoepidermoid 49.6% Plexiform neurofibroma 3.2% carcinoma Warthin tumour 2% Acinic cell carcinoma 12.2% Cystadenoma 2% Undifferentiated 8.9% Embryoma 1.2% carcinoma Lymphoepithelial 1.2% Adenocarcinoma 7.7% lesion Adenoid cystic 6.5% Monomorphic adenoma 0.4 carcinoma Others 3.4% Malignant mixed 4.1% tumour Malignant nerve 2.0% sheath tumour Unclassified 1.6% carcinoma Squamous cell 1.2% carcinoma Others 6.2%
Sialadenitis is frequently seen due to the diminished salivary flow. Serologic studies demonstrate antinuclear antibodies and antibodies to Sjögren syndrome antigens A and B. Biopsy of the minor salivary glands in the lip or tail of the parotid indicates the characteristic sialectasis. Patients with this disorder have an increased risk of lymphoma.17
81 age group tend to arise in the oral cavity, although lesions in the pharynx, larynx, and bronchus have also been reported.19,20 Most patients with a salivary gland neoplasm present with a painless, slow-growing mass in the parotid region. A sudden increase in size may be secondary to infection, cystic degeneration, hemorrhage, or malignant transformation. This may result in a previously painless lesion becoming painful and tender. Benign and low-grade malignant lesions may have a similar clinical progression. The average duration from the presence of a lump being noticed to definitive diagnosis is close to 21 months. Clinical features that suggest malignancy are facial nerve involvement, pain, fixation of the mass, involvement of the overlying skin or underlying structures, and associated cervical adenopathy.21,22 Patients with a submandibular tumor present with a painless swelling or mass in the submandibular triangle. Involvement of skin or fixation to the mandible indicates local extension of a malignant tumor. Ipsilateral weakness or numbness of the tongue suggests perineural spread along the hypoglossal or lingual nerves.23 Minor salivary gland lesions are rare. Benign lesions tend to present as a painless submucosal mass with normalappearing overlying mucosa; however, a malignant lesion may present as a submucosal mass or an ulcerative lesion. The palate is the most common site involved with minor salivary gland neoplasms, although such lesions may be found anywhere in the upper aerodigestive tract.24
Hemangiomas and vascular malformations
Salivary gland neoplasms Overview and clinical presentation Salivary gland neoplasms are far less common in children than are inflammatory conditions. They comprise less than 10% of all pediatric head and neck tumors. Clinically, salivary gland neoplasms fall into three histologic groups: benign, low-grade malignancy, and high-grade malignancy (Table 1). When a solitary salivary gland tumor is present, the chance of malignancy is greater in the child than in the adult. The most common benign neoplasms affecting the major salivary glands in children are vascular and lipomatous lesions. Most pediatric epithelial salivary tumors occur in children older than 10 years of age; if malignant, most of these tumors are low-grade. Malignant tumors in children younger than age 10, however, tend to be high-grade neoplasms associated with a poor prognosis. The parotid gland is involved in up to 90% of all pediatric salivary gland tumors, and 50% of these tumors are malignant.18 Malignant tumors are generally low-grade; however, a malignant tumor in a child younger than age 10 is more likely to be a high-grade neoplasm, portending a poor prognosis. Minor salivary gland tumors in the pediatric
Hemangiomas are the most common vascular tumors in childhood. They are characterized by vascular endothelium that undergoes a phase of growth followed by slow spontaneous involution that occurs gradually over several years and is generally complete by the first decade of life. These lesions account for 60% of all pediatric salivary gland neoplasms. Of these salivary gland hemangiomas, 80% arise in the parotid glands, 18% arise in the submandibular glands, and 2% arise in the minor salivary glands. In contrast to hemangiomas, vascular malformations are structural anomalies thought to represent errors in vascular or lymphatic morphogenesis. They encompass a wide range of anomalies and are classified according to their components as capillary, venous, lymphatic, arterial, and combined malformations. In some patients, lymphatic malformations may involve the salivary glands. Discussions that focus on cervicofacial hemangiomas and lymphatic malformations are provided in other articles within this issue of Seminars in Pediatric Surgery.
Pleomorphic adenoma Pleomorphic adenoma is a common benign pediatric salivary gland tumor; lesions are also referred to as benign
82 mixed tumors. These tumors typically manifest as hard, painless, slow growing masses, and occur in all pediatric age groups (median, 15 years). On ultrasonography (US), pleomorphic adenomas appear hypoechoic to isoechoic relative to the uninvolved parotid gland. CT and MRI findings vary depending on the tumor size. Smaller tumors are generally homogeneous and well defined, whereas larger tumors are heterogeneous and less well defined, with areas of hemorrhage or necrosis. Pleomorphic adenomas have both mesenchymal and epithelial cell lines. Although these tumors appear to be encapsulated, on microscopic examination they may have pseudopod extensions into adjacent tissues. As such, simple enucleation results in up to 30% recurrence rates. Tumors arising from the superficial lobe of the parotid gland minimally require a superficial parotidectomy. Deeplobe parotid tumors may manifest as a parapharyngeal mass with medial displacement of the tonsil and intraoral swelling. These tumors require a total parotidectomy. Lesions arising from the submandibular region are managed by surgical excision with adequate margins.
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Mucoepidermoid carcinoma Mucoepidermoid carcinoma is the most common salivary gland malignancy in children, accounting for 50% of malignant salivary tumors. This tumor is also the most common radiation-induced salivary gland tumor in children. It is generally found between the ages of 10 and 16 years. Tumors consist of a combination of squamous and mucous cells arranged in cords, sheets, or cystic configurations. They are histologically classified as low-, intermediate-, and high-grade tumors, with most pediatric tumors being low-grade. CT findings demonstrate cystic low-attenuation areas and, rarely, focal calcifications. High-grade mucoepidermoid carcinomas tend to be more solid with fewer cystic areas, and are more homogeneous on both CT and MRI. Mucoepidermoid carcinoma requires surgical excision. Low-grade lesions may be treated with wide local resection. High-grade neoplasms often require treatment of the cervical lymph nodes by a selective neck dissection, radiation, or both.27,28
Acinic cell carcinoma Warthin tumor Warthin tumor, also known as papillary cystadenoma, lymphomatosum, or adenolymphoma, manifests as a painless slowgrowing mass; it presents bilaterally in up to 10% of cases. Warthin tumors are thought to be a direct result of the unique embryologic development of the parotid gland, which allows the incorporation of lymphatic elements and heterotopic salivary gland ductal epithelium within intraparotid and periparotid nodes. Histologically, these tumors consist of a double layer of oncocytes resting on a dense lymphoid stroma. On CT and MR imaging, Warthin tumors appear as well-circumscribed, homogeneous cystic or solid lesions, often located in the tail of the parotid gland. Multiple or bilateral parotid or periparotid masses strongly suggest the diagnosis of Warthin tumor. Treatment includes surgical resection. Recurrences may be a result of the tumor’s propensity for multifocal lesions within the same gland.22,25
Sialoblastoma (embryoma) Sialoblastoma is an extremely rare tumor unique to children that is diagnosed at birth or shortly thereafter. It represents an embryonic anlage of the minor salivary glands. Histopathologically, the cells are mitotically active. Primitive cell masses with formative ducts and pseudoductular spaces without acinar differentiation are seen in a loose investing mesenchyma with an embryonic appearance. These tumors arise at any of the sites of minor salivary glands and can be locally aggressive. Although the majority of these neoplasms are benign, there have been reports of neck metastasis. Wide surgical excision is the treatment of choice.26
Acinic cell carcinoma is the second most frequent salivary carcinoma in children and, as with mucoepidermoid carcinoma, generally presents between 10 and 16 years of age. On pathologic examination, acinic cell carcinoma appears fairly well circumscribed with nests of cells with basophilic cytoplasm and lymphoid infiltrate into the surrounding stroma. This tumor generally is regarded as a low-grade malignancy and seldom metastasizes. It has a high tendency to recur locally if lesions are incompletely excised.29
Adenoid cystic carcinoma Adenoid cystic carcinoma usually exhibits a protracted course characterized by an indolent growth pattern and a relentless tendency for local and perineural invasion. It is associated with a high recurrence rate and relatively poor long-term survival. Although distant metastasis generally occurs within the first 5 years of diagnosis, it can occur up to 20 years after initial diagnosis.30
Adenocarcinoma Adenocarcinoma is observed in early childhood and is associated with a high potential for metastases. In two series with a total of eight patients having an average age of 6 years at presentation, there was an overall mortality rate of 75%. This suggests that adenocarcinoma is an aggressive disease that may require more radical resection and/or adjuvant therapy than is suggested by histology alone.21,31
Mehta and Willging
Pediatric Salivary Gland Lesions
Undifferentiated carcinoma Undifferentiated carcinoma is the only carcinoma reported in the perinatal period; however, it more commonly occurs in children younger than age 10. This tumor tends to be highly aggressive and has a poor prognosis despite aggressive treatment protocols.32
Surgical resection Surgical resection is the therapeutic mainstay for treatment of salivary gland neoplasms. Resection should provide complete removal of the neoplasm without tumor spillage or facial nerve damage. For parotid tumors, a parotidectomy with adequate margins is ideal. Superficial parotidectomy may be adequate for control of most benign and malignant tumors of the lateral lobe; however, deep-lobe tumors require a total parotidectomy. Surgery should be aimed at preservation of the facial nerve unless the nerve is directly invaded or the intact nerves limit the complete resection of the tumor. Facial-nerve grafting can restore deficits resulting from facial nerve section. For submandibular gland neoplasms, it is prudent to perform a regional dissection of the submandibular triangle to reduce the risk of recurrence.33 The incidence of cervical lymph node metastasis is estimated to be less than 15%. Neck dissection is indicated only when clinically enlarged cervical lymph nodes are present. Prophylactic neck dissection can be considered in patients with poorly differentiated lesions, including high-grade mucoepidermoid squamous cell carcinoma, undifferentiated carcinoma, adenoid cystic carcinoma, and adenocarcinoma.21
Management of recurrent neoplasms Children with pleomorphic adenoma who have undergone superficial parotidectomy have a recurrence rate of 19.5%, which sharply contrasts to the 1% recurrence rate reported in adults. This may represent an increased risk of violation of the tumor capsule and resultant seeding of the resection bed and wound. It may also reflect inappropriate initial treatment of a parotid lesion that is mistaken for a high cervical node.34 Tumor recurrence is most common with adenoid cystic carcinoma (50%), followed by mucoepidermoid carcinoma (38%) and acinic cell carcinoma (20%). The high recurrence rate in pediatric patients is in part due to an inadequate surgical procedure at the initial presentation, thus necessitating a second, more extensive operation. To ensure complete removal of the tumor, it is imperative that salivary gland tumors are properly evaluated preoperatively and that the proper procedure is performed at initial presentation.19,28,29
83 Patients with recurrence may require salvage procedures. Results of such procedures have been reported in only 2 pediatric series, with a total of 15 patients. In one series, 5 patients referred after primary surgery and radiotherapy underwent salvage procedures. Of these patients, 2 died of disease within 6 years of salvage surgery; both had been diagnosed with high-grade parotid cancers. In another series, 10 patients with recurrences underwent salvage operations. Two of these 10 patients died of disease at 8 and 13 years, respectively, after their initial operations.35,36
Radiation Because of the potential for radiation-induced sequelae, radiation in children must be used with extreme caution. Radiation-induced complications include dental caries, delayed dental development, trismus, and radiation-induced tumors. Radiation is generally recommended for treatment of high-grade tumors, in cases in which: (1) microscopic residual disease is found, (2) there is positive cervical node involvement with extracapsular spread, or (3) perineural invasion or spread has been identified.
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