CC
The patient is a 64-year-old female referred for evaluation of a mass on the right posterior hard palate. (Mucoepidermoid carcinoma occurs across a wide age range and has a slight female predilection. Adenoid cystic carcinoma [ACC] has a relatively equal male-to-female distribution and is most commonly seen in the older adult population.)
HPI
The patient first noticed a lump on her hard palate approximately 6 months earlier. (The parotid gland is the most common site for mucoepidermoid carcinoma; minor salivary glands, especially from the palate, are the second most common.) The patient is asymptomatic, although the mass has been slowly increasing in size. (Mucoepidermoid carcinoma usually presents as progressively enlarging, asymptomatic swelling.) She denies pain, fever, chills, night sweats, nausea, vomiting, weight loss, and other constitutional symptoms. She also denies any history of dental pain or sinus congestion. (ACCs are more common in the submandibular gland and lower lips. Late-stage ACCs can present with progressive anesthesia on the lip because of the propensity for perineural invasion.)
PMHX/PDHX/medications/allergies/SH/FH
The patient denies tobacco and alcohol use.
Although exposure to ionizing radiation has been implicated as a cause of salivary gland cancer, the etiology of most salivary gland cancers cannot be determined. Occupations that may be associated with an increased risk for salivary gland cancers include rubber product manufacturing, asbestos mining, plumbing, and some types of woodworking. Tobacco and alcohol consumption do not seem to have a causal relationship with salivary gland tumors.
Examination
General. The patient is a well-developed and well-nourished White female who appears her stated age and is in no apparent distress. She is not cachexic. (Cachexia may be a sign of advanced disease.)
Maxillofacial. The face is symmetrical and without any extraoral swelling. The patient has no proptosis (maxillary sinus malignancies can invade both the palate and orbit). The infraorbital nerves are intact (low-grade mucoepidermoid carcinoma typically does not display perineural invasion).
Intraoral. A 2-cm × 2-cm submucosal swelling is present on the right posterior hard palate ( Fig. 74.1 ). The mass is firm, nonmobile, nonpulsatile, and nontender to palpation (highly suggestive of a neoplastic process). The overlying mucosa is pink (may present with a bluish or reddish color) and nonulcerated. The greater and lesser palatine nerves are intact. The dentition is in good repair, and all teeth are vital without pain on percussion. There are no other intraoral lesions or masses.
Neck. There is no lymphadenopathy (regional lymph node metastasis is uncommon, especially for low-grade lesions, but may occur with high-grade lesions or advanced disease).
Imaging
The workup for a biopsy-proved mucoepidermoid carcinoma involves a complete head and neck physical examination, CT scan of the head and neck (with intravenous [IV] contrast) for delineation of the primary tumors and regional metastasis, a panoramic radiograph (initial screening examination), and a chest radiograph for evaluation of pulmonary metastasis. Newer imaging modalities, such as positron emission tomography (PET) scanning, have become powerful tools for delineation of local and distant disease. Most PET studies are performed using the glucose analog 18F-fluorodeoxyglucose (18F-FDG), which has been shown to accumulate in areas of higher metabolic activity. This is especially important in ACCs because these tumors have a predilection for distant metastasis.
In the current patient, no abnormalities of the dentition or surrounding bony structures were identified on the panoramic radiograph. Axial and coronal views from the CT scan of the head and neck performed with IV contrast (for improved delineation of soft tissue) demonstrated a 2-cm × 1-cm enhancing soft tissue mass of the right posterior hard palate that did not appear to involve the underlying bone. No cervical lymphadenopathy was noted. The chest radiograph was normal.
Labs
For the biopsy procedure, routine laboratory studies are not indicated in an otherwise healthy patient. A complete blood count, electrolyte studies, and coagulation studies may be performed to establish a baseline before the definitive surgery. Liver function tests are not routinely obtained because liver metastasis is rare.
Differential diagnosis
The differential diagnosis in the case of a submucosal mass of the posterior hard palate should include benign (pleomorphic adenoma, monomorphic adenoma, canicular adenoma) and malignant minor salivary gland tumors (mucoepidermoid carcinoma, ACC, polymorphous low-grade adenocarcinoma, acinic cell carcinoma, and adenocarcinoma). Lesions of infectious etiology should be considered but are unlikely given the presentation. Sarcomas can also occur on the palate and should be considered in the differential diagnosis. An incisional biopsy is indicated for the current patient.
Biopsy
Mucoepidermoid carcinoma is graded on a scale of I to III (low, intermediate, and high grade, respectively); features of high-grade tumors include nuclear atypia, necrosis, perineural spread, mitoses, bony invasion, lymphatic and vascular invasion, intracystic component, and tumor front invading in small nests and islands. The grading system for mucoepidermoid carcinoma is subjectively assessed based on the degree of epidermoid versus mucinous cellular components. High-grade tumors have a relatively higher proportion of epidermoid cells (squamous and intermediate cells) and few mucus-producing cells, whereas low-grade tumors have a high proportion of mucus cells ( Fig. 74.2 ).
In ACC, three major forms are recognized histopathologically: the cribriform, tubular, and solid variants ( Fig. 74.3 ). Microscopically, ACC is composed of small cells arranged in groups that form glandular spaces filled with mucoid material or a hyaline plug. The cribriform variant is most common, and the solid variant has the worst prognosis.
In the current patient, an incisional biopsy of the central portion of the palatal mass was performed under local anesthesia. Histopathology of the specimen confirmed a low-grade mucoepidermoid carcinoma (high proportion of mucus cells with minimal cellular atypia). It is important to obtain a tissue sample from the center of the lesion in cases of suspected salivary gland neoplasms. A biopsy from the periphery may result in a nondiagnostic specimen because of inadequate depth.
Assessment
T1, N0, M0 (a tumor ≤ 2 cm in diameter, with no lymphadenopathy and no evidence of distant metastases) low-grade mucoepidermoid carcinoma of the right posterior hard palate.
Treatment
After a biopsy-proven diagnosis of low-grade mucoepidermoid carcinoma has been made, the lesion is definitively treated by wide local excision with 1-cm margins. High-grade lesions may require more extensive resection, with surgical management of the neck, to limit the potential for locoregional recurrence.
For the current patient, the treatment of choice was a right partial maxillectomy with a split-thickness skin graft and immediate placement of a prosthetic obturator (see Discussion). Adjuvant radiation therapy is not indicated for low-grade lesions that are completely excised.
The patient was placed under general anesthesia and underwent a formal right partial maxillectomy, with 1-cm, tumor-free margins, via a transoral approach. (A Weber-Ferguson incision may be indicated for larger tumors that require a more extensive ablative surgery.) A split-thickness skin graft (0.015 inch) was harvested from the right thigh and used to line the ablative defect. This was bolstered using Xeroform gauze packing (Coe-Soft [GC America] denture liner can also be used) and a preformed surgical stent, which was secured to the maxilla with a midpalatal screw. The stent was removed after 2 weeks, and an impression was taken for fabrication of a temporary maxillary obturator.
Complications
Complications associated with a partial maxillectomy include bleeding because of vascular injury of the terminal branches of the internal maxillary artery (greater and lesser palatine vessels) or the internal maxillary artery itself.
Hemorrhage can be controlled with direct pressure, hemostatic agents, electrocautery, or vessel ligation. Uncontrollable arterial bleeding may require angiography and embolization of the feeding vessels to obtain proximal control. The use of a maxillary stent helps promote hemostasis and improve patient comfort and speech in the healing period.
Local recurrence or regional metastases, although uncommon, is a major concern (see Discussion). Complications associated with the rehabilitation and reconstruction of the defect can also have a significant impact on the patient’s quality of life.
Discussion
Malignancies of the salivary glands are relatively rare, making up approximately 6% to 8% of all head and neck cancers, which equates to 2000 to 2500 cases in the United States each year. As can be seen from reviewing the evolution of the World Health Organization’s (WHO’s) classification of malignant salivary gland tumors, there is quite a significant number of tumors added with each iteration. This has gained pace recently with advances in molecular biology. Regardless, mucoepidermoid carcinoma, ACC, and acinic cell carcinoma remain mainstays and are among the most frequent malignant salivary gland carcinomas diagnosed. There is geographical variability in which salivary gland malignancy is the most common with ACC often quoted as being the most common in European countries but mucoepidermoid carcinoma typically being regarded as the most common in the United States. The presentation of the salivary gland tumors being discussed in this chapter is often similar and may include a swelling in the neck or face, pain or numbness in the face, difficulty swallowing or speaking, and a change in voice. These cancers may also cause facial deformities, difficulty breathing, and weight loss. Salivary gland tumors not only affect the major salivary glands but can also affect all the upper aerodigestive tract, including the oral cavity and pharynx.
Salivary gland malignancies can affect both the major and minor salivary glands. Benign masses of the salivary glands are more common; however, managing a salivary gland malignancy in the fashion of a benign lesion will likely lead to initial undertreatment, which will likely affect the patient’s prognosis. Therefore, when a mass of the salivary glands is noted, an appropriate workup is crucial. Of the utmost importance when a patient presents with a mass of the major salivary glands that is consistent with a neoplastic process, a fine-needle aspiration (FNA) is recommended. If the FNA is nondiagnostic or does not correlate with clinical findings, either a repeat FNA or a core biopsy is recommended. There is a theoretical risk that a core biopsy may result in seeding of malignant cells along the tract used to obtain the core biopsy, but practically, this has not been shown to be an issue. An open biopsy of a neoplastic process of the major salivary glands is frowned upon. With regard to the minor salivary glands, an open incisional biopsy is generally the preferred route of getting tissue for histopathological diagnosis. It is recommended that the biopsy be taken from the center of the mass. A punch biopsy facilitates this nicely.
Imaging is a prerequisite for the workup of all head and neck malignancies, salivary gland malignancies being no different. A neck computed tomography (CT) scan with contrast to evaluate the primary lesion and for any regional lymphadenopathy is favored by most as the initial imaging. This is typically done with a CT chest in line with National Comprehensive Cancer Network guidelines. These initial imaging modalities can be combined with magnetic resonance imaging (MRI) using institutionally determined protocol such as skull base protocol to evaluate for possible radiologic evidence of perineural invasion. This is of particular relevance in ACC because of its well-documented neurotropism. MRI is favored for evaluating soft tissues with CT generally being favored for the evaluation of bone invasion.
The majority of salivary gland malignancies are treated with surgical resection followed by any indicated adjuvant therapy. This is certainly the mainstay of treatment for the three malignant salivary gland tumors this chapter focuses on. Even though the presentation of these malignant salivary gland carcinomas can be similar, there is some variance in their management, which is discussed later. Long-term follow-up is crucial to monitor for recurrence. This is of particular relevance with respect to ACC because it tends to have good 5- and 10-year survival rates but a poor 20-year survival rate because hematogenous spread to the lungs is almost inevitable with this disease process. Often distant lung metastasis can be present at diagnosis, but surgical resection of the primary mass is generally recommended even in this scenario.
Mucoepidermoid carcinoma
Mucoepidermoid carcinoma arises from the glandular cells of the salivary glands and is characterized by the presence of three types of cells: mucous, intermediate, and epidermoid cells. Mucoepidermoid carcinoma is further classified into three subtypes based on the ratio of these cell types: low, intermediate, and high grade. Low-grade mucoepidermoid carcinoma is the most common subtype and is characterized by a low number of intermediate and epidermoid cells. High-grade mucoepidermoid carcinoma is characterized by a high number of intermediate and epidermoid cells. The majority of mucoepidermoid carcinomas occur in the major salivary glands and the parotid in particular. An unusual variant of mucoepidermoid carcinoma is when it presents in an intraosseous location. This is thought to result from malignant transformation of tissue within an odontogenic cyst. Molecular biology has shown that the majority of mucoepidermoid carcinomas have MAML2 rearrangement. This finding is particularly useful when the rare intraosseous mucoepidermoid carcinoma is encountered because traditional histopathological analysis can find it difficult to differentiate it from glandular odontogenic cysts. Clearly, the management of these entities is different, and evaluation of MAML2 rearrangement has been shown to be very helpful in these cases.
Within pediatric salivary gland malignancies, mucoepidermoid carcinoma accounts for the majority, and the parotid is the most frequent site of occurrence. Most pediatric cases present in the second decade of life; however, if it presents in the first decade, it is more likely to be high grade and associated with a poorer prognosis. The etiopathogenesis of pediatric mucoepidermoid carcinoma, like that in adults, is unknown. Epstein-Barr virus and exposure to radiation are frequently suggested, and there is some weak evidence to support this but the exact etiology is currently unknown. No prospective or randomized trials exist to help determine the best therapeutic strategy to adopt in the management of pediatric mucoepidermoid carcinoma much less the rarer intraoral variant. Therefore, data are limited to case series and individual case reports.
Most agree that primary surgical management is the best strategy. Surgical resection of the primary mass is indicated for all grades of mucoepidermoid carcinoma. This entails a superficial parotidectomy for those involving the superficial parotid with facial nerve preservation. The management of the neck varies with grade. For low-grade malignancies, surgical resection of the primary is generally all that is performed. Most manage intermediate-grade mucoepidermoid carcinomas the same as low-grade ones. When the primary site is the submandibular gland, a limited level 1B neck dissection is generally performed for low- and intermediate-grade mucoepidermoid carcinomas. If there is radiologically enlarged cervical lymph nodes in low- or intermediate-grade tumors, then consideration can be given to FNA of these lymph nodes to determine if a neck dissection is merited. A neck dissection is generally indicated in high-grade mucoepidermoid carcinomas. High-grade tumors and perineural invasion are noncontrollable factors that have been associated with recurrence of mucoepidermoid carcinoma along with positive surgical resection margins. There is some controversy with regard to the management of mucoepidermoid carcinoma of the palate. Some authors have advocated for resection of the soft tissue and the underlying bone regardless of the histologic grade or stage. On the other hand, other authors have shown that less invasive treatment is sufficient for low-grade tumors. Caccamese et al. managed low-grade mucoepidermoid carcinoma with wide local excision and stripping the periosteum off the palatal bone, which served as the deep margin. The ability to remove low-grade mucoepidermoid carcinoma of the palate without removing palatal bone without recurrence was emphasized in a larger study ( Fig. 74.4 ). Both of these studies advocating a less aggressive approach stated that if there is radiologic evidence of bone erosion or invasion, palatal bone should be removed.
