HEAD AND NECK
CHAPTER 30 HEAD AND NECK CANCER AND SALIVARY GLAND TUMORS
DAVID M. OTTERBURN AND PIERRE B. SAADEH
Head and neck cancers account for 3% to 5% of all cancers in the United States, with an annual cancer mortality of around 2%. They are most common in men and in people over the age of 50 years and are more prevalent in the African American population. Over the past few decades, survival has generally improved for head and neck cancers. The improved survival is due to early detection and early therapy. However, these survival curves have plateaued in recent years. Cancers in the oral cavity, which are easily detected by physical examination, have historically had the best outcomes. However, improved imaging using magnetic resonance imaging, positron emission tomography, and fiberoptic endoscopy has led to earlier detection of previously difficult to evaluate areas such as the posterior pharynx.
Ninety percent of all head and neck cancers are squamous cell in origin. Common etiologic factors include tobacco and alcohol, which seem to have a synergistic effect. Regional causative agents may include betel quid in Asia and mate, a hot tea-like beverage, in South America. Over the past decade, the incidence of head and neck tumors in younger patients has increased. This has been linked with human papilloma virus (HPV) infections and is thought to be associated with exposure through oral sex. Fortunately, these tumors are more responsive to therapies and generally portend a better prognosis. The use of HPV vaccinations, which are effective in preventing cervical cancer, may also be effective against these tumors as they are also caused by HPV serotypes 16, 18, and 31.
Cutting-edge advances in reconstruction following extirpative procedures include the use of robotics to inset microsurgical flaps and virtual planning. Although the indications and operative techniques utilizing these advances are still evolving, early reports are promising and have shown decreased operative morbidity and possibly improved outcomes.
Small tumors in most head and neck regions have a 90% cure rate when treated by radiation or surgical resection. These survival figures decrease significantly with moderately advanced tumors, resulting in average 5-year survival rates of approximately 50%. The use of neoadjuvant therapy has also been an advance and has increased the potential for surgical resection of previously unresectable tumors. Overall survival based on stage is listed in Table 30.1. The distribution of these cancers based on anatomic subsite is displayed in Figure 30.1.1 Reconstruction of head and neck defects is critically dependent on a number of factors including anatomy, physiology, pathology of head and neck tumors, staging, and adjuvant therapy. This chapter will discuss the pertinent details of head and neck cancer and salivary gland cancer with the relevant anatomy.
HEAD AND NECK ANATOMY AND STAGING
A standardized approach to head and neck anatomy facilitates discussion and treatment among medical professionals. The primary site/subsite approach currently used for head and neck cancer reflects both unique regional tumor behavior and specific treatment-related considerations. This section of the chapter focuses on sites with the greatest incidence of pathology and on subsites with specific reconstructive challenges. Primary tumor sites include the oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx (Tables 30.2 to 30.7).
Figures 30.2 to 30.10 present the relevant anatomy and T staging of each region and the anatomy of the neck. The tumor, node, metastases (TNM) classification developed by the American Joint Committee on Cancer (AJCC) in 2010 is the standard system used to establish stage grouping and to facilitate determination of both prognosis and treatment.2 Because T stage definitions vary depending on the primary site location, these definitions are included with the primary site figures. Changes in the new edition of the AJCC for head and neck cancer reflect the aggressive nature of surgical resection. The monikers “unresectable and resectable” were changed to “very advanced and moderately advanced.” This differentiation leads to stage IV disease being split into IVa “moderately advanced local/regional disease,” IVb “very advanced local/regional disease,” and IVc “distant metastatic disease.” Neither nonepithelial tumors (lymphoid tissue, soft tissue, bone, and cartilage) nor mucosal melanomas are included in this classification system. Melanomas are discussed in Chapter 14, and thyroid cancers, which rarely lead to reconstructive procedures, will not be discussed.
The cervical lymph nodes are a primary site of metastasis for most head and neck cancers. As such, lymph node dissection, when appropriate, is important for tumor staging. Table 30.83 defines the primary site locations of the neck. Figure 30.8 demonstrates the anatomy and regional lymph node groups of the neck. To facilitate and standardize discussion of neck metastases and neck dissection, the neck has been divided into nodal group levels.
Although head and neck cancers are a devastating group of diseases, site- and stage-specific survival reveals that many invasive tumors exhibit a 5-year survival of over 60% (Table 30.9).4 In addition, the overall mortality for most subsets has fallen from 1997 to 2002 in almost every subsite, and most dramatically in those locations that are not readily palpable (Table 30.10).5 The incidence of squamous cell carcinoma of the head and neck has been decreasing in the United States, from 18 per 100,000 in 1974 to 14 per 100,000 in 2007,6 possibly paralleling a decrease in smoking rates. Cumulative DNA alterations caused by the synergistic effects of cigarette smoking and alcohol use are thought to underlie a majority of mucosally derived head and neck squamous cell carcinomas.
Over the past decade, there has been a spike in the incidence of head and neck tumors in younger patients. The etiology of these tumors is thought to be related to HPV virus infection, with the majority of tumors demonstrating the same serotypes (16, 18, and 31) associated with cervical cancer, a finding that is thought to be due to increased rates of oral sex. This association is most prominent in women between the ages of 15 and 34 years and occurs in the salivary glands and tongue.7,8 Fortunately, the cure rate from these cancers is higher than the typical squamous cell cancers, and recent evidence suggests that the use of the HPV vaccination for cervical cancer may also be beneficial in preventing HPV-induced head and neck cancers.
FIGURE 30.1. Distribution of head and neck cancer in the United States.1
FIGURE 30.2. Anatomy and T staging of the oral cavity.2
FIGURE 30.3. Anatomy and T staging of the nasopharynx.2
FIGURE 30.4. Anatomy and T staging of the oropharynx.2
FIGURE 30.5. Anatomy and T staging of the hypopharynx and cervical esophagus.2
FIGURE 30.6. Anatomy and T staging of the larynx.2
FIGURE 30.7. Anatomy and T staging of the nasal cavity and paranasal sinuses.2
FIGURE 30.8. Nodal levels of the neck. 1A Submental, 1B Submandibular, II Jugulodigastric, III Middle jugular IV Low jugular, V Posterior triangle, VI pre-laryngeal/tracheal
As a result of “field cancerization,”9 the entire upper aerodigestive tract mucosa is at risk for both synchronous (5%) and metachronous (5% to 15%) second primary malignancies. Lymph node dissections are generally performed when clinically positive nodes are noted. Consideration of tracheostomy and/or gastrointestinal feeding tube should be part of the preoperative plan of any extensive resection/reconstruction of the head and neck. The surgical treatment of other oral malignancies is generally similar to squamous cell carcinoma and is outlined below.
FIGURE 30.9. AJCC staging for paranasal and maxillary sinus tumors, laryngeal tumors, hypopharyngeal tumors, oral cavity, and oropharyngeal tumors.2
FIGURE 30.10. Staging for nasopharyngeal cancer.2
Precancerous lesions of the oral cavity include leukoplakia, which is common among smokers, and erythroplakia. Dysplastic leukoplakia and erythroplakia require, at a minimum, close serial observation. Additionally, treatment options include either chemoprevention (isotretinoin) or ablation with cryotherapy, electrocautery, or surgery.
Because of the accessibility of the oral cavity, and the morbidity of radiation-induced xerostomia, early tumors of this area (stages I and II) are generally treated surgically. Most small tumors in the oral cavity and lip have cure rates greater than 90%. However, lesions thicker than 0.5 cm, stage III or IV or positive margins, typically require surgery and external beam radiation or brachytherapy.10,11 Although there is no consensus, many surgeons will perform a supraomohyoid neck dissection (SOHND) (levels I–III) for N0 oral cavity cancers unless it is known preoperatively that adjuvant radiation therapy will also be administered. In contrast, patients with clinically palpable neck disease are usually treated with either an extended (levels I–IV) or a complete (levels I–V) dissection and postoperative adjuvant radiation. Midline tongue and floor of the mouth masses are indications for bilateral SOHNDs. The oral cavity has multiple subsites that are described below.
Lip. Squamous cell carcinoma of the lip comprises approximately 30% of oral cavity malignancies, and the vast majority of these occur on the lower lip (Chapter 14). In contrast, the majority of tumors of the upper lip are basal cell carcinomas. Unlike squamous cell carcinomas of other regions of the head and neck, sun exposure is thought to play a major role in the pathogenesis of upper lip squamous cell tumors. The conspicuous appearance of these tumors often leads to early diagnosis, with 90% to 100% cure rates of small lesions. Furthermore, occult metastatic spread is unusual for most lip tumors except for those located in the commissures, which have a 20% risk. In situ lesions may be treated with shave excision, topical 5-fluorouracil, or imiquimod (Aldara; 3M, St. Paul, MN), whereas more advanced lesions require assessment of mandibular and/or mental nerve involvement prior to excision with adequate margins. Because of the difficulty reconstructing the commissure, less extensive malignancies of this area may be treated with radiotherapy; however, large or ulcerated lesions are best treated with resection and reconstruction. Upper lip and commissure malignancies may drain to periparotid or neck lymph nodes. Preoperative mapping may aid in surgical planning. Patients with more advanced tumors and clinically negative lymph node examination are usually treated with sentinel lymph node biopsy followed by superficial parotidectomy or neck dissection (depending on the drainage pattern) if the sentinel lymph node is positive. Lip reconstruction is discussed inChapter 35.
Anterior (Oral) Tongue. The anterior tongue is the site of malignancy in 25% to 50% of oral cavity cancers, with the midlateral aspect most frequently affected. Because of the lack of anatomic barriers to spread, tongue cancer has a propensity for diffuse, infiltrative involvement, which is often difficult to gauge clinically. Curative resection, therefore, mandates an adequate margin (generally 1 cm) around the lesion. T1 or T2 lesions are usually amenable to transverse wedge excision with a 70% to 85% cure rate. Larger T2 and posteriorly situated lesions often require lip split and mandibulotomy to obtain adequate exposure for tumor resection and, if indicated, incontinuity neck dissection. More recently, advances in robotic surgery have enabled resection of these tumors without mandibulotomy; however, this technique has yet to gain widespread acceptance.
Small tongue resections (1 cm or less) are treated with primary closure or skin-grafting, whereas larger defects generally require tissue transfer to maintain tongue mobility and optimize oral function. T3 or larger lesions, or lesions with aggressive histologic characteristics, may benefit from radiation therapy to decrease local recurrence rates of 30% to 40%.
Floor of Mouth. Floor of mouth cancer accounts for 30% of oral cavity malignancies and may extend locally into the tongue or the mandible, with the alveola being the usual entry site. Mandibular invasion may result in infiltration into the cancellous bone and tumor tracking in a perineural fashion along the inferior alveolar nerve. Poor dentition is a risk factor for mandibular invasion as dentition maintains alveolar height, thereby serving as a barrier to tumor invasion. Further, loss of alveolar height in the edentulous patient places the alveolar canal in proximity to the mucosal surface and affords portal of entry via empty tooth sockets.
Because of the proximity of floor of mouth tumors to the mandible as well as their propensity for bony invasion, oncologically sound management of this structure for complete tumor excision is an essential aspect of treatment. Surgical guidelines include 1-cm margins, which include a marginal mandibulectomy (rather than segmental mandibular resection) for tumors intimately adjacent to the mandible. In contrast, radiologic evidence of cortical invasion usually mandates segmental mandibulectomy, with bone cuts 1 cm away from the soft-tissue portion of the malignancy and evaluation of inferior alveolar nerve margins when possible. Larger tumors that do not require segmental mandibulectomy may be resected in continuity with planned neck dissection through a transcervical route. This subsite also has a propensity for bilateral occult neck metastasis.
Retromolar Trigone. Tumors of this subsite are generally difficult to treat because of challenging access and because of their locally aggressive nature, which often requires segmental mandibular resection and inferior alveolar nerve sacrifice. Resections of large or aggressive tumors in this area often result in complex defects involving the mandible, lateral pharynx, and soft palate, making reconstruction particularly challenging.
Alveolar Ridge. Malignancies occur in this subsite uncommonly and are treated in a similar fashion as floor of mouth cancers. Small tumors can be excised with marginal mandibulectomy and adequate soft-tissue margins; large tumors usually require segmental mandibulectomy and reconstruction. Lymph node evaluation is performed clinically and neck dissection is indicated for clinically positive examinations as occult metastases are rare.
Hard Palate. The hard palate is an uncommon subsite for oral cavity tumors. Up to a third of tumors in this area are of minor salivary gland origin. Principles of resection are similar to those described for floor of the mouth and alveolar ridge. Similarly, because occult neck metastases are rare, lymph node dissections are usually reserved for patients with clinically palpable lymph nodes. Depending on the tumor size and location, resection may be performed perorally, through a transoral midface degloving approach, or through a Weber-Ferguson approach. The goals of hard palate reconstruction are to maintain speech and feeding, to separate the oral and nasal cavities, and when possible to restore nasal lining. In some cases, en bloc maxillary resections may include the inferior orbital rim necessitating reconstruction to restore orbital volume. Small defects may be addressed with local flap closure or prosthodontics, while large defects are often treated with free tissue transfer and/or maxillofacial prosthodontics.
Buccal Mucosa. Although also uncommon, buccal mucosal malignancies are locally aggressive and have a propensity to metastasize. Resection of these lesions may result in large, full-thickness soft-tissue deficits with significant cosmetic consequences. Free tissue reconstruction is frequently required but usually less than satisfactory since reconstruction often does not address facial nerve deficits resulting from full-thickness excision of facial musculature.
Although tumors of the nasopharynx are rare in the United States, these tumors occur commonly in China due to differences in exposure to Epstein-Barr virus and alcohol consumption. Unlike squamous cell cancers of other head and neck regions, there is no clear evidence that either cigarette smoking or moderate alcohol use increases the risk of these cancers in the nasopharynx.12,13 Stage I tumors have a 5-year survival rate of 72%. Stage II and III tumors have survival rates between 62% and 64%. Stage IV disease drops to a 38% 5-year survival.14 Due to late development of symptoms, locally advanced disease with invasion into local structures and (bilateral) neck involvement is a common presentation. Skull base extension into the cavernous sinus may present with associated cranial nerve (CN) involvement most commonly in CNs III, IV, V, and VI. The primary treatment for this highly radiosensitive tumor is chemoradiation, with surgery reserved for recurrent disease.15
These tumors are uncommon, affect men three to five times more than women, and usually occur in the fifth to seventh decades. They are associated with betel nut and mate consumption, HPV virus infection, and tobacco/alcohol use. Functional outcomes take on greater importance in this subsite as a result of the proximity of the digestive and respiratory tracts to one another. Tumors in this region are characterized by their relatively small size compared with much larger neck metastases, the propensity of near midline lesions for bilateral neck involvement, and the possibility of retropharyngeal nodal metastasis. Although most tumors are squamous in origin, the higher concentration of lymphatic tissue yields a proportionally higher incidence of lymphomas (mucosal-associated lymphoid tissue tumors), which are exquisitely radiosensitive.
Sixty percent of patients present with a mass in the neck as the primary tumor and are usually asymptomatic. However, CN IX or X involvement may present with referred otalgia and/or ipsilateral soft palate paresis. CN XII invasion can manifest as wasting and ipsilateral deviation of the tongue. In light of functional considerations, early lesions (T1 and T2) that cannot easily be resected are often best treated with radiation therapy. Advances in organ preservation chemoradiation protocols are increasingly relegating surgery to advanced lesions (T3 and T4) and to salvage for treatment failure or recurrence.16
The base of the tongue, similar to other tongue tumors, is susceptible to infiltrative spread and is the most frequently affected region of the oropharynx. While most base-of-tongue tumors are presently treated with chemoradiation and/or brachytherapy, there are multiple approaches to this area. Surgical access, depending on the lesion’s location and size, includes transoral excision, lateral pharyngotomy, supra/transhyoid pharyngotomy, lip splitting, and paramedian mandibulotomy. The latter approach implies a larger tumor, which generally mandates advanced reconstruction. Similarly, locally advanced pharyngeal wall tumors require advanced access, laryngopharyngectomy, and reestablishment of digestive continuity. Tumors close to or involving the mandible (ramus: tonsil, pharyngeal arches, and lateral pharyngeal wall) require marginal or segmental mandibulectomy, usually with reconstruction, as outlined in the section on oral cavity tumors. Except for early lesions of the soft palate and posterior pharynx, the propensity for neck metastasis by tumors of the oropharynx usually mandates neck dissection.
Hypopharynx and Cervical Esophagus
Malignancies of the hypopharynx most frequently involve the pyriform sinus, with dysphagia and palpable neck disease as frequent presenting complaints. Referred otalgia from tumor invasion of the tympanic branch of the CN IX is also a common symptom and tumors spread locally by submucosal infiltration. Locally advanced hypopharyngeal tumors have the highest rate of distant metastases (usually to the lungs), resulting in the worst long-term survival among head and neck tumors. Traditionally, hypopharyngeal tumors were resected en bloc with the larynx (laryngopharyngectomy) due to the proximity of the tumor to this structure and the limited ability to preserve laryngeal function. However, currently stage III and IV tumors are usually treated with neoadjuvant chemotherapy and postoperative radiation therapy in an effort to shrink the tumor to preserve laryngeal function.17-19
There are no definitive studies to date to guide an evidence-based protocol for hypopharyngeal cancer. Generally T1 lesions are treated with radiation therapy alone, with all higher stages receiving surgery followed by radiation therapy. Some groups rely on radiation therapy alone, with adjuvant chemotherapy and surgery only for salvage procedures. The evidence for which approach is superior is still being gathered; however, it is clear that adjuvant and neoadjuvant therapy can lead to laryngeal preservation in select patients.
Small localized lesions of the pyriform sinus may be treated by partial laryngopharyngectomy, resulting in a hemicircumferential defect of the hypopharynx as contrasted with total laryngopharyngectomy, which results in complete disruption of gastrointestinal continuity. Reconstructive options usually favor free tissue reconstruction with fasciocutaneous flaps for resurfacing of both hemicircumferential and complete defects. The free jejunal flap was the traditional method of reconstruction for complete defects; however, fasciocutaneous flaps provide a better result for phonation, as they create a stiffer tube and do not secrete mucus or have peristalsis. For partial defects, rotational flap options include the pectoralis major flap and extended supraclavicular flaps. Early neck metastases with a propensity for bilaterality warrant an aggressive approach to the neck for hypopharyngeal lesions.
In 2010, there were 12,700 new cases of laryngeal cancer and 3,600 deaths.20 Not surprisingly, laryngeal cancers have a strong association with alcohol and tobacco use. Patients who stop smoking decrease their risk of laryngeal cancer, but remain at increased risk as compared with the general non-smoking population. Treatment considerations for carcinoma of the larynx center on tumor ablation, local control, and organ/voice preservation. There is also a high incidence of second primary tumors (25%). Some clinicians believe that treating all laryngeal cancers with isotretinoin may prevent secondary tumors; however, comparative studies have failed to show a survival benefit.21 The three parts of the larynx include the supraglottic, glottic, and subglottic regions.
Supraglottic Region. The supraglottic region is rich with lymphatic vessels, and as a result, tumors of this region commonly present with lymph node involvement (25% to 50%). They typically drain into the midjugular and jugulodigastric nodal groups. Stage I and II cancers can be treated with either surgery or radiation alone. Radiation avoids disrupting the larynx and therefore is the preferred modality. Stage III and IV cancers can be treated with either total laryngectomy or post-op radiation, definitive radiation with surgery left for salvage or radiation failure or chemoradiation with surgery for salvage procedures.22,23
Glottic Region. The glottic region is devoid of lymphatics and usually presents early because of its symptomatic involvement. Fortunately, this leads to earlier staging with better tumor outcomes. Small stage I tumors may be laser excised and treated surgically or with definitive radiation. Stage II lesions are treated with surgery alone or radiation therapy alone. Stage III and IV lesions are treated with surgery with possible postoperative radiation therapy, definitive radiation therapy with surgery for salvage, or chemotherapy and radiation with surgery for salvage.
Subglottic Region. Tumors in the subglottic region are rare; however, due to the rich lymphatic network in this region, these tumors are associated with earlier lymph node involvement in the pretracheal and paratracheal nodes, the inferior jugular node, and the mediastinal nodes. Stage I and II tumors are treated with radiation therapy alone; stage III and IV tumors are treated either with surgery or with radiation therapy in patients who are not surgical candidates. Radiation therapy may also be used in an adjuvant setting in addition to surgery in locally advanced or aggressive tumors.
Because the rate of neck involvement in the clinically negative neck exceeds 20% in stage I and II supraglottic tumors, elective treatment of the neck (bilateral for midline or larger lesions) is advocated either with surgery or with radiation therapy. Management of the clinically lymph node–positive neck is variable and depends on the treatment modality selected for the primary lesion (i.e., either radiation or radiation and surgery).
Free flap reconstruction (commonly radial forearm free flap with palmaris longus tendon) of the vocal cord deficit in vertical partial laryngectomy defects has increased the predictability of the functional result in conservation laryngectomy (less than total) procedures.24 Following total laryngectomy, speech may be reestablished through esophageal speech, tracheoesophageal puncture, or an electrolarynx.
Nasal Cavity and Paranasal Sinuses
Similar to the nasopharynx, sinonasal tract squamous cell carcinoma occurs infrequently and has a relatively low association with cigarette smoking. The maxillary sinus is most frequently affected and tumors can grow considerably before becoming symptomatic. Tumors located below Ohngren’s line (a line extending from the medial canthus to the angle of the jaw) have a better prognosis than tumors located above it. Treatment of malignancies in this area is generally surgical and consideration must be given to possible involvement of surrounding structures, including the remaining sinuses, the nose, the orbital floor and orbit, and the anterior and middle cranial fossae. The functional and cosmetic deformities resulting from tumor extirpation with uninvolved margins present significant reconstructive challenges, including restoration of hard palate and orbital floor, dead space elimination, and prevention of cerebral spinal fluid leak. Postoperative radiation is usually indicated.
Because the rate of nodal metastasis in nasal cavity and paranasal tumors is less than 20%, most surgeons do not operate on clinically negative patients (i.e., N0 neck) but reserve complete neck dissections for patients with clinically evident disease.
Surgical therapy for stage I and II depends on the specific sinus involved. Typically those that can be readily accessed should be resected, otherwise they are radiated. Stage III and IV tumors generally undergo resection with postoperative radiation therapy. Tumors of the nasal vestibule are often treated with radiation either prior to surgery to shrink the tumor or as the primary means of treatment as wide resections in this area are severely deforming.
Management of the Neck
The prognostic and therapeutic implications of nodal metastases in the neck mandate a standardized approach both to the description of neck anatomy, as outlined previously, and to options of management. The traditional radical neck dissection involves unilateral removal of lymphatic groups I to V and sacrifice of the spinal accessory nerve, internal jugular vein, and sternocleidomastoid muscle. Numerous modifications of this operation have been described in an effort to limit morbidity or to more specifically target occult metastases (Table 30.11 and Figure 30.8). Neck dissections are classified as comprehensive (radical, modified radical) or selective, based on the nodal levels dissected and non-lymphatic structures preserved.
The proliferation of the various neck dissections is because cervical metastases in untreated patients proceed in a predicable fashion depending on the site of the primary tumor. In the N0 neck, treatment includes surgery or radiotherapy, generally depending on the treatment modality selected for treatment of the primary tumor (“split-modality therapy” describes treating the primary tumor with surgery and the neck with radiation or vice versa). Elective treatment is further dependent on the location of the primary tumor.
Occult metastases of oral cavity tumors increase with T3 or T4 lesions and tumors thicker than 3 mm, and such patients should undergo SOHND or radiotherapy. T2-4 tumors of the oropharynx, hypopharynx, and supraglottic larynx have a high incidence of occult cervical spread and should be treated with a lateral neck dissection or radiotherapy. However, because access to the oropharynx often necessitates a mandibulotomy, consideration should be given to an anterolateral neck dissection. All N0 nasopharynx, pyriform sinus, and base-of-tongue lesions should be considered for elective neck treatment. T1-2 glottic tumors have such a small risk of occult neck disease that elective radiotherapy should not be pursued. Elective surgical treatment of the neck is also indicated in unreliable patients and if the approach of surgical treatment of a primary tumor involves a neck approach (for either extirpation or reconstruction).
Treatment of the clinically positive neck (N+) generally involves comprehensive neck dissection with an effort to spare structures depending on tumor involvement. Selective neck dissection may be appropriate in many cases because of the rarity of level V involvement (except in nasopharyngeal malignancies) in the absence of multilevel involvement or level IV adenopathy.
Radiotherapy compares favorably to surgery in the elective treatment of N0 necks with regard to locoregional recurrence, and the decision to use it varies from center to center. Although there is controversy regarding the timing of radiation, radiotherapy is generally indicated in the treatment of N+ necks, particularly in the presence of multiple nodes or extracapsular extension.
SALIVARY GLAND TUMORS
Neoplasms of the salivary glands are a unique and rare (3% to 6% of all adults) subset of head and neck tumors. Their varied histology and infrequent occurrence, as well as their relationship to critical surrounding structures (facial nerve and mandible), often present a diagnostic and therapeutic challenge. They typically occur in the sixth or seventh decade and present as a painless mass. More than half of salivary gland tumors are benign, but signs of neural involvement or pain do point to malignant involvement.
There are three paired major salivary glands, the parotid, submandibular, and sublingual glands (Figure 30.11), and 600 to 1,000 minor salivary glands distributed primarily throughout the oral cavity and upper aerodigestive tract. Their purpose is to aid in digestion through the release of salivary amylase and the lubrication of the food. Whereas the output of the parotid gland is primarily serous, that of the submandibular and sublingual is mucous and that of the minor glands is mixed. In aggregate, the major and minor glands produce 500 to 1,500 mL of saliva daily.
Seventy to eighty percent of all adult salivary gland tumors occur in the parotid gland, 8% to 15% in the submandibular, and 5% to 8% in the minor salivary glands. Sublingual neoplasms are extremely rare (<1%). Mucoepidermoid carcinoma is the most common malignant tumor of the parotid, while adenoid cystic tumor is the most common in the submandibular and minor salivary glands. Adenoid cystic tumors have a tendency for perineural invasion.
Histologically, there are over 40 types of salivary gland tumors. They are the most diverse types of cancers in the human body. Classification by cellular type includes epithelial, nonepithelial, and malignant secondary neoplasms. Two theories of histogenesis have been postulated to explain the broad variation (more than nine types) in histopathologic tumor types. In the multicellular theory, mature differentiated cells of the glandular unit give rise to specific tumor histologies, although it requires dedifferentiation for some types. In the second and more popular theory, tumors arise from one of two undifferentiated reserve cells. The only known predisposition to salivary gland tumors is therapeutic external irradiation (acne and adenoid hypertrophy), with a latency, often, of one to three decades.
FIGURE 30.11. Location and staging of major salivary glands.2
Tumors are staged based on the same T, N, M classification as oral cavity cancer (Figures 30.2 and 30.12).25 Histologic classification into low grade and high grade is important for treatment options; however, tumor size may be a better indicator of long-term outcomes. For low-grade malignancies of the parotid, a superficial parotidectomy is required. All other malignant lesions require total parotidectomy. If there is facial nerve paralysis, the nerve is resected. In this setting with advanced disease, reconstruction is not usually indicated.
If tumor involves the facial nerve, but its function is preserved, the nerve branches should be resected and reconstructed if reasonable. Large tumors, or those with close margins, or with evidence of lymph node involvement may benefit from radiation therapy.26,27 It is currently not clear if chemotherapy is of any benefit in this pathology.
Common Benign Salivary Gland Tumors
Pleomorphic adenoma is the most common deep lobe parotid tumor. Because of their retromandibular position, it is common for deep lobe parotid tumors to achieve a significant size prior to diagnosis, as they are generally non-palpable. The diagnosis is often made as an incidental finding on diagnostic imaging studies obtained for other complaints. The operative approach is superficial parotidectomy and facial nerve dissection followed by dissection of the nerve branches from the tumor surface. The deep plane tumor is then delivered beneath transposed branches. Pleomorphic adenomas have a recurrence rate of 2% to 7% and conversion to carcinoma ex pleomorphic adenoma occurs in approximately 10% of cases.
Frey syndrome, also known as auriculotemporal nerve syndrome, is a complication of superficial parotidectomy occurring as a result of abnormal reinnervation of sympathetic nerve fibers of the parotid by the transected branches of the auriculotemporal nerve resulting in gustatory sweating. Although this pattern of reinnervation occurs in as many as 80% of patients who undergo superficial parotidectomy, only approximately 20% of patients notice the phenomenon or request treatment for it. Interposition of acellular dermal matrix may prevent the development of this phenomenon. Topical scopolamine cream and injected Botox are also used for severe cases.
Recurrent pleomorphic adenoma may be mono- or multinodular and may occur up to several decades after treatment of the index tumor. Tumor spill at the first procedure (capsular rupture) is not thought to predispose to this phenomenon. These recurrent tumors may occur in extraglandular soft tissues and may be aggressive and ultimately fatal (metastatic, locally invasive, and skull base). More commonly, this is the result of less-than-adequate surgery (i.e., nodulectomy, less-than-superficial parotidectomy). Treatment is reoperation with significant increase in the risk of permanent damage to the facial nerve with each subsequent procedure. Adjuvant external beam radiotherapy should be added in most cases of multinodular recurrence.
Warthin tumor (benign cystadenoma lymphomatosum) exhibits a 5:1 male-to-female preponderance, typically appearing in the fifth to seventh decade of life. Metachronous bilaterality has been observed in up to 6% of cases.
AIDS-related lymphoepithelioma is related to involvement of intraparotid lymph nodes and may result in ductal obstructive phenomena and multicystic glandular involvement, which may be both deforming and painful. Treatment is external beam radiotherapy.
Common Malignant Salivary Gland Tumors
Adenoid cystic carcinoma is neurophilic with a high incidence of occult perineural spread (outside the immediate operative field) and soft-tissue invasion. This feature mandates the use of postoperative adjuvant radiotherapy in most cases. Hematogenous metastases to the liver, lung, and bone are frequent and may occur with a long latency period. Patients may live with significant metastatic tumor burden for an extended period (years). Survival period statistics may exceed 5 years for this tumor, with survival curves diverging at 10 to 15 years. Carcinoma ex pleomorphic adenoma (malignant mixed tumor) may arise in isolation, but is more commonly the concomitant of a long-standing pleomorphic adenoma. Malignant transformation is rare, occurring in fewer than 10% of these tumors. Acinic cell carcinoma is bilateral in 3% of cases and is the second most common malignant salivary neoplasm in children.
FIGURE 30.12. AJCC nodal staging for head and neck cancer.24 Note: Nasopharyngeal cancer nodal staging is the same as the above except for: Nodes in the supraclavicular fossa defined as (1) the superior margin of the sternal end of the clavicle, (2) the superior margin of the lateral end of the clavicle, (3) the point where the neck meets the shoulder are stage N3b. Note that this would include caudal portions of levels IV and VB.
Squamous cell carcinoma is rarely of primary parotid origin; however, if it is, then it is most commonly high-grade mucoepidermoid carcinoma. More commonly, this entity represents metastasis from a frontotemporal scalp cutaneous carcinoma to a periparotid or intraparotid lymph node. The mass is noted 1 to 2 years after treatment of the primary lesion (usually large and long-standing) and represents a failure to adequately treat the original lesion, that is, postoperative adjuvant radiotherapy to the primary site and regional nodes (levels I, II, and III). Total parotidectomy is often required to remove all intraparotid nodes. Skip metastasis to the upper neck is also observed, but should also include parotidectomy for occult or in-transit disease. These treatment principles also apply to malignant melanomas of the temporal region. Lymphomas of the salivary glands are characterized by massive enlargement, and the role of surgery is limited to incisional biopsy. Adenocarcinoma of the parotid gland exhibits a 7:1 female-to-male preponderance.
A number of factors influence survival from malignant salivary cancer including histologic grade (Table 30.12), age greater than 35 to 50 years, site (submandibular, sinus, and larynx), clinical stages III and IV (Figure 30.9), and male gender. Multivariate analysis has shown that histologic grade and stage are the most important determinants of survival outcomes. Survival for stage I tumors is approximately 90%; this number drops to 65% for stage II and 20% for stage III malignant salivary tumors. Squamous and anaplastic carcinomas carry the worst prognosis. Acinic cell and low-grade mucoepidermoid carcinomas fare best. Parotid malignancies do better than those of other subsites. Tumor recurrence rates are 39%, 60%, and 65% for parotid, submandibular, and minor salivary gland malignancies, respectively. Because this may happen years after the initial treatment, long-term follow-up is essential. Survival for adenoid cystic carcinoma should be measured in decades as survival curves may only begin to diverge from the population around 15 years posttreatment.
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