References

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22. Cordeiro PG, Santamaria E, Kraus DH, et al. Reconstruction of total maxillectomy defects with preservation of the orbital contents. Plast Reconstr Surg 1998;102:1874-84.

23. Parsons JT, Stringer SP, Mancuso AA, Million RR. Nasal vestibule, nasal cavity, and paranasal sinus. In: Million RR, Cassisi NJ, editors. Management of head and neck cancer—A multidisciplinary approach. Philadelphia (PA): JB Lippincott Co.; 1994.

24. Wade PM, Smith RE, Johns ME. Response of esthesioneu-

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25. Levine PA, Debo RF, Meredith SD, et al. Craniofacial resec tion at the University of Virginia (1976-1992): survival analysis. Head Neck 1994;16:574-7.

26. McElroy EA Jr, Buckner JC, Lewis JE. Chemotherapy for advanced esthesioneuroblastoma: the Mayo Clinic experience. Neurosurgery 1998;42(5):1023-7.

27. Ketcham AS, Hoye RC, Van Buren JM, Johnson RH. Com plications of intracranial facial resection for tumors of the paranasal sinuses. Am J Surg 1966;112:591-6.

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cephalus: treatment with controlled decompression via a closed water-seal drainage system. J Neurosurg 1991;74: 139-42.

29. Richtsmeier WJ, Briggs RJS, Koch WM, et al. Complications and early outcome of anterior craniofacial resection. Arch Otolaryngol Head Neck Surg 1992;118:913-7.

30. Terz JJ, Young HF, Lawrence W. Combined craniofacial resection for locally advanced carcinoma of the head and neck: tumors of the skin and soft tissues. Am J Surg 1980;140:613-7.

31. Terz JJ, Young HF, Lawrence W. Combined craniofacial resection for locally advanced carcinoma of the head and neck: carcinoma of the paranasal sinuses. Am J Surg 1980;140:618-24.

32. Cantu G, Solero CL, Mariani L, et al. Anterior craniofacial resection for malignant ethmoid tumors—a series of 91 patients. Head Neck 1999;21:185-91.

33. McCaffrey TV, Olsen KD, Yohanan JM, et al. Factors affect ing survival of patients with tumors of the anterior skull base. Laryngoscope 1994;104:940-5.

34. Catalano PJ, Hecht CS, Biller HF, et al. Craniofacial resec tion: an analysis of 73 cases. Arch Otolaryngol Head Neck Surg 1994;120:1203-8.

35. Ketcham AS, Van Buren JM. Tumors of the paranasal sinuses:

a therapeutic challenge. Am J Surg 1985;150:406-13.

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37. Janecka IP, Sen C, Sekhar L, Curtin H. Treatment of paranasal sinus cancer with cranial base surgery: results. Laryngoscope 1994;104:553-5.

38. Van Tuyl R, Gussak GS. Prognostic factors in craniofacial surgery. Laryngoscope 1991;101:240-4.

39. Kraus DH, Sterman BM, Levine HL, et al. Factors influenc ing survival in ethmoid sinus cancer. Arch Otolaryngol Head Neck Surg 1992;118:367-72.

40. Clayman GL, DeMonte F, Jaffe DM, et al. Outcome and complications of extended cranial-base resections requiring microvascular free-tissue transfer. Arch Otolaryngol Head Neck Surg 1995;121:1253-7.

41. Saito K, Fukata K, Takahashi M, et al. Management of the cavernous sinus in en bloc resections of malignant skull base tumors. Head Neck 1999;21:734-42.

42. Fisch U, Pillsbury HC. Infratemporal fossa approach to lesions in the temporal bone and base of the skull. Arch Otolaryngol Head Neck Surg 1979;105:99-107.

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45. Janecka IP. Classification of facial translocation approach to the skull base. Otolaryngol Head Neck Surg 1995; 112: 579-85.

46. Guedea F, Mendenhall WM, Parsons JT, Million RR. Radio therapy for chemodectoma of the carotid body and ganglion nodosum. Head Neck 1991;13:509-13.

47. Cole JM, Beiler D. Long-term results of treatment for glomus jugulare and glomus vagale tumors with radiotherapy. Laryngoscope 1994;104:1461-5.

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JC. Long-term outcomes after radiosurgery for acoustic neuromas. N Engl J Med 1998;339:1426-33.

50. Kasper ME, Parsons JT, Mancuso AA, et al. Radiation ther apy for juvenile angiofibroma: evaluation by CT and MRI, analysis of tumor regression, and selection of patients. Int J Radiat Oncol Biol Phys 1993;25:689-94.

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Salivary Tumors

JEFFREY D. SPIRO, MD, FACS RONALD H. SPIRO, MD, FACS

The salivary glands are an uncommon site for cancer arising in the upper aerodigestive tract. Tumors arising in these glands comprise only about 7 percent of epithelial malignant neoplasms encountered in the head and neck, with an incidence of 1 per 100,000 population per year.1-3 Considering the variety of anatomic sites and the number of different histologic subtypes encountered, it is easy to understand how oncologists may accumulate only limited experience with specific types of salivary gland cancer. Many of these tumors behave in an indolent fashion and the need for prolonged follow-up complicates the ability of the clinician to draw conclusions about the efficacy of treatment. For these reasons, most of the data about results are based on the experience reported from major referral centers.

ANATOMY

Salivary glands encountered in the head and neck consist of the "major" salivary glands and the "minor" salivary glands. The term "major" refers to the paired parotid, submandibular, and sublingual glands (Figure 13-1). The minor glands are small, predominantly mucus-secreting glands located beneath the mucosa of the upper aerodigestive tract. These glands are found in highest concentration in the palate, nasal cavity and oral cavity.

The parotid gland overlies the angle of the mandible and is closely related to the cartilage of the ear canal posteriorly, the zygoma superiorly, the parapharyngeal space medially, and the sternomastoid and posterior digastric muscles inferiorly. The facial nerve

Accessory parotid tissue

Sublingual gland

Accessory parotid tissue

Sublingual gland

Parapharyngeal Space

Figure 13-1. The major, or paired salivary glands consist of the parotid, submandibular and sublingual glands. About 1 percent of parotid neoplasms—so called accessory parotid tumors—arise from a small portion of glandular tissue just anterior to the gland which drains directly into the Stensen's duct.

Parotid gland

Submaxillary gland

Figure 13-1. The major, or paired salivary glands consist of the parotid, submandibular and sublingual glands. About 1 percent of parotid neoplasms—so called accessory parotid tumors—arise from a small portion of glandular tissue just anterior to the gland which drains directly into the Stensen's duct.

Parotid gland

Submaxillary gland exits the stylomastoid foramen and runs through the substance of the parotid gland, splitting into its 5 main branches in the process. The exact pattern of arborization of the nerve is quite variable.4 The plane of the facial nerve is used to divide the gland into its "superficial" and "deep" lobes, with about 20 percent of the substance of the gland lying beneath the nerve.

The submandibular gland abuts the body of the mandible superolaterally, the lingual and hypoglossal nerves medially, the mylohyoid muscle anteriorly and the tail of the parotid gland posteriorly

(Figure 13-2). The marginal branch of the facial nerve runs along the lateral surface of the gland, just deep to the platysma.

DIAGNOSIS

As summarized in Figure 13-3, the parotid gland is the most common site of origin of salivary neoplasms, almost 80 percent of which are benign.5-7 Submandibular gland neoplasms are far less common, and about half will be malignant. According to

Opening of submandibular duct

Sublingual gland and ducts

Mylohyoid muscle

Opening of submandibular duct

Sublingual gland and ducts

Mylohyoid muscle

Lingual nerve

Hyoglossus muscle

Stylohyoid muscle

Superficial and deep portions of submandibular gland

Mylohyoid muscle

Facial artery

Submandibular lymph node Submental vein

Figure 13-2. A, The relation of the submandibular gland to its muscular "bed" (digastric, mylohyoid and hyoglossus muscles) and major nerves is illustrated. B, Coronal view showing the location of the gland between the lingual cortex of the mandible and the floor of the mouth.

Sublingual gland

Duct of submandibular gland Lingual nerve

Mylohyoid muscle

Lingual nerve

Hyoglossus muscle

Stylohyoid muscle

Superficial and deep portions of submandibular gland

Facial artery

Superficial portion of submandibular gland

Submandibular lymph node Submental vein

Figure 13-2. A, The relation of the submandibular gland to its muscular "bed" (digastric, mylohyoid and hyoglossus muscles) and major nerves is illustrated. B, Coronal view showing the location of the gland between the lingual cortex of the mandible and the floor of the mouth.

Figure 13-3. This bar graph shows the relative incidence of parotid, submandibular and minor salivary gland tumors in the Memorial Hospital experience. Percentages represent the proportion malignant at each site. The incidence of malignant minor salivary gland tumors is probably much lower in community practice.

Figure 13-3. This bar graph shows the relative incidence of parotid, submandibular and minor salivary gland tumors in the Memorial Hospital experience. Percentages represent the proportion malignant at each site. The incidence of malignant minor salivary gland tumors is probably much lower in community practice.

reports from referral centers, minor salivary glands most often give rise to malignant tumors. The proportion of malignant minor salivary tumors arising in the oral cavity is lower in series from the community setting. It is uncommon to find a benign minor salivary neoplasm outside of the oral cavity or oropharynx.5,8

For cancer arising in major salivary glands, the most common presentation is a painless swelling of the affected gland. When small, malignant tumors of the major salivary glands are indistinguishable clinically from benign tumors. The duration of the swelling may be brief in patients with cancer, but it is not uncommon for patients with low-grade salivary cancers to present with a swelling that has been evident for years. Intermittent swelling of the submandibular gland related to salivary stimuli most likely represents inflammatory disease, and may be associated with pain. Because obstruction of the parotid gland is far less common, the presence of pain in association with a mass in the parotid may be suggestive of malignant disease.

Findings in patients with major salivary gland tumors that are highly indicative of malignancy include paralysis of all or part of the facial nerve, and the presence of associated lymphadenopathy. In patients with parotid cancer, these findings are noted at presentation in 9 to 25 percent and 13 to 25 percent, respectively.2,3,9-13 Fixation of the tumor to overlying skin or adjacent deep structures is also suggestive of a malignant neoplasm.

The presenting complaint of patients with minor salivary cancer obviously will vary depending on the site of the lesion, as will the findings on physical examination (Figure 13-4). Most often, these lesions present as a submucosal swelling (Figure 13-5), but they may be ulcerated when the overlying mucosa has been traumatized. As such, they may be clinically indistinguishable from squamous cell carcinomas.

Diagnostic imaging of major salivary cancers is not routinely indicated, but may be useful in various situations.14 For lesions fixed to adjacent bony structures, such as the mandible or temporal bone, radiographs can delineate the extent of bone involvement (Figure 13-6). In cases where a lesion appears to involve the parapharyngeal space, MRI can distinguish deep-lobe parotid or minor salivary tumors from other parapharyngeal neoplasms. Imaging studies are important in patients with minor salivary cancers arising in the palate, nasal cavity, nasopharynx and paranasal sinuses where the full extent of the tumor usually cannot be defined by clinical exam alone.

Tumors arising in major salivary glands are easily accessible to fine needle aspiration biopsy (FNAB). Experienced cytopathologists can reliably distinguish salivary from non-salivary pathology and benign from malignant,15-16 but precise histologic classification based only on an aspirate is an unrealistic goal. While some advocate routine FNAB of all major salivary neoplasms, it is our belief that such a practice adds little to the management of small, obvious parotid tumors. On the other hand, FNAB of sub-mandibular masses is important because only a minority will prove to be primary tumors arising in

Figure 13-4. Sites of origin of minor salivary gland tumors as seen at Memorial Hospital. The palate was involved in almost 40 percent of patients, reflecting the high density of minor salivary glands in this site. Black shading indicates malignant tumors, almost all of which arose in the oral cavity.

Figure 13-4. Sites of origin of minor salivary gland tumors as seen at Memorial Hospital. The palate was involved in almost 40 percent of patients, reflecting the high density of minor salivary glands in this site. Black shading indicates malignant tumors, almost all of which arose in the oral cavity.

the submandibular gland. Most minor salivary tumors are accessible for direct open biopsy in the office or the operating room. Care must be taken to insure that representative material is obtained for pathologic

Figure 13-5. A, Pleomorphic adenoma of right hard palate, and B, adenoid cystic carcinoma at junction of left hard and soft palate. Benign minor salivary tumors are clinically indistinguishable from their malignant counterparts. C, Mucoepidermoid carcinoma of the hard palate.

analysis, particularly if the lesion is located in the nasal cavity or paranasal sinuses where confusion with many other types of cancer is possible.

The classification of malignant salivary gland tumors is complex and challenging to pathologists (Tables 13-1 and 13-2). Specific histologic types of salivary cancer vary in incidence, depending on their site of origin. Mucoepidermoid carcinoma is the most common cancer of the parotid gland, and adenoid cystic carcinoma is the most common malignant tumor arising in the submandibular gland.2'3,5-717-28 In minor salivary sites, adenoid cystic carcinoma and adenocarcinoma are most prevalent.8,29,30

TREATMENT GOALS AND ALTERNATIVES

Role of Multidisciplinary Treatment

As with head and neck cancer in general, the goals of treatment for salivary cancer are cure of the disease while minimizing the morbidity of treatment. Surgical resection has long been the mainstay of treatment of salivary cancer, but has the potential to create significant functional deficits. For cancers arising in the parotid gland, loss of the facial nerve is the greatest functional concern, while the hypoglossal nerve, lingual nerve and marginal mandibular branch of the facial nerve are at risk when carcinomas of the submandibular salivary

2nd Trimester Abortion
Figure 13-6. Adenoid cystic carcinoma arising in the left retromo-lar trigone extending into the adjacent cheek mucosa. Tumors of this histologic type are always more extensive than can be appreciated either clinically or radiographically.
Adenoid Cystic Carcinoma Palate

Figure 13-5. A, Pleomorphic adenoma of right hard palate, and B, adenoid cystic carcinoma at junction of left hard and soft palate. Benign minor salivary tumors are clinically indistinguishable from their malignant counterparts. C, Mucoepidermoid carcinoma of the hard palate.

Table 13-1. MEMORIAL HOSPITAL CLASSIFICATION AND INCIDENCE OF MALIGNANT SALIVARY TUMORS

1939 through 1973

1988 through 1993

Number of Patients

Number of patients Incidence (%)

Mucoepidermoid carcinoma 439 34 119 34

Adenoid cystic carcinoma 281 22 72 21

Adenocarcinoma 225 17 73 21

Malignant mixed tumor 161 13 22 6

Acinic cell carcinoma 84 7 25 7

Epidermoid carcinoma 53 4 19 6

Anaplastic and other 35 3 16 5

Total 1278 100.0 346 100.0

gland are resected. Excision of malignant salivary gland neoplasms arising at minor salivary sites may jeopardize structures such as the larynx or the orbital contents. Unfortunately, more extensive surgery does not necessarily yield better salvage in patients with locally advanced salivary cancer.

In an effort to reduce the morbidity associated with "radical" surgical resection while maintaining or even improving chances for cure, there has been increasing use of combinations of surgery and radiotherapy during the past 2 decades. This strategy, which will be discussed later in this chapter, has proven to be effective in advancing these treatment goals.

Factors Affecting Choice of Treatment

The single most important factor affecting the choice of treatment for salivary gland cancer is the extent of the lesion at diagnosis (ie, the clinical stage). In general, smaller lesions arising in major or minor salivary glands are amenable to surgical resection with minimal morbidity and good control of disease. Larger tumors that have invaded adjacent structures not only will require more extensive resection, but also the addition of adjuvant radiotherapy to increase the chances of cure. In some cases, disease may be so extensive as to be unre-sectable. Finally, patients with disseminated disease usually will not benefit from aggressive local or regional therapy. The exception may be patients with adenoid cystic carcinoma, who can live for many years despite pulmonary metastases.

Location is also an important factor in treatment selection. Borderline resectable lesions in inaccessi ble locations, such as sinus tumors involving the base of the skull, may be better suited for nonsurgi-cal therapy such as chemoradiotherapy or neutron beam irradiation. When resection margins are close because of tumor proximity to vital structures, the evidence suggests that adjunctive radiotherapy can improve results.

Histology may influence treatment planning as well. Adenoid cystic carcinoma, for example, with its propensity for perineural spread and insidious local extension, is often very difficult to adequately encompass with surgical resection alone. Other lesions that are high grade histologically more often present with locally extensive disease, and also have a higher incidence of distant metastases than their low grade counterparts, which suggests the need for effective systemic therapy in this subset of patients.

Table 13-2. WORLD HEALTH ORGANIZATION (WHO) CLASSIFICATION OF MALIGNANT SALIVARY GLAND TUMORS

Acinic cell carcinoma

Mucoepidermoid carcinoma

Adenoid cystic carcinoma

Polymorphous low-grade adenocarcinoma

Epithelial-myoepithelial carcinoma

Basal cell adenocarcinoma

Sebaceous carcinoma

Papillary cystadenocarcinoma

Mucinous adenocarcinoma

Oncocytic carcinoma

Salivary duct carcinoma

Adenocarcinoma

Malignant myoepithelioma

Carcinoma in pleomorphic adenoma

Squamous cell carcinoma

Small cell carcinoma

Undifferentiated carcinoma

Surgical Treatment

Surgical resection remains the mainstay of treatment for salivary tumors. Specific considerations pertaining to various sites are discussed below.

Parotid Gland

In most cases, the minimum surgical procedure recommended for tumors arising in the parotid gland is excision of the superficial "lobe" of the parotid gland with dissection and preservation of the facial nerve. In carefully selected patients with small lesions arising in the tail of the gland, a more limited local excision without formal nerve dissection may be feasible. When surgery is performed for parotid cancer, every effort should be made to preserve the facial nerve unless it is imbedded in, or adherent to, the tumor. Piecemeal excision of a malignant parotid tumor in order to spare the nerve violates basic oncologic principles, and is mentioned only to be condemned. Sacrifice of all or part of the facial nerve has been required in 29 to 40 percent of reported patients with carcinoma of the parotid gland.101217 As discussed below, immediate cable grafting using branches of the cervical plexus or the sural nerve is indicated when feasible after facial nerve resection.

When a tumor arises deep to the facial nerve, several surgical approaches are possible. For small lesions that do not extend significantly into the parapharyn-geal space, the facial nerve is initially exposed by superficial parotidectomy and then the branches can be displaced to allow for tumor removal (Figure 13-7). When there is significant extension into the parapha-ryngeal space (Figure 13-8), the submandibular gland can be removed to facilitate transcervical access. A paramedian mandibulotomy will occasionally be required for adequate access to the parapharyngeal space in patients with large lesions.

Submandibular Gland

Excision of this gland will occasionally be adequate treatment when a carcinoma is small and surrounded by normal parenchyma. More often, the tumor extends to or through the gland capsule to involve adjacent structures. In this setting, the resection may have to include the "bed" of the gland (ie, digastric, mylohyoid and hyoglossal muscles), adjacent nerves (lingual, hypoglossal, ramus marginalis), the mandible or the floor of the mouth and/or sublingual gland. This is probably best acccomplished in conjunction with removal of levels 1, 2 and 3 lymph nodes as an "extended" supraomohyoid neck dissection. Tumor extent will obviously determine which additional structures to resect. Patients with high-stage tumors may actually require a composite resection. Given the difficulty in obtaining adequate microscopic margins of resection in adenoid cystic carcinoma, there has been a trend toward combining less radical surgery with postoperative radiotherapy.

Minor Salivary Sites

The surgical approach to tumors arising in minor salivary sites will obviously vary depending on the site of origin, but is generally similar to that utilized for squamous cell carcinoma arising at the same site. Lesions arising in the larynx may be amenable to either conservation laryngeal surgery or total laryn-gectomy. A tumor arising in the tongue base can be approached utilizing a paramedian mandibulotomy, and palatal salivary cancer may require a peroral partial or conventional subtotal maxillectomy. For those

Bath Salts Face Eating

Figure 13-7. Tumors situated lateral to the mandible but medial to the facial nerve are seldom diagnosed preoperatively as deep-lobe tumors. Only during the course of superficial parotidectomy was it appreciated that this pleomorphic adenoma was deep to the bifurcation of the nerve. With careful dissection, it is almost always possible to remove these tumors and preserve the facial nerve.

Figure 13-7. Tumors situated lateral to the mandible but medial to the facial nerve are seldom diagnosed preoperatively as deep-lobe tumors. Only during the course of superficial parotidectomy was it appreciated that this pleomorphic adenoma was deep to the bifurcation of the nerve. With careful dissection, it is almost always possible to remove these tumors and preserve the facial nerve.

lesions arising in the nasal cavity or paranasal sinuses, adequate resection must include these structures, and occasionally a combined craniofacial resection or orbital exenteration is necessary in cases of more extensive disease.

Neck Treatment

Those few patients who initially present with obvious nodal involvement require therapeutic neck dissection. In carefully selected patients who have limited disease in the first echelon of nodal drainage, selective neck dissection may be adequate. Those with more extensive neck disease should undergo comprehensive neck dissection with preservation of the accessory nerve when feasible.

Because the incidence of occult neck disease in salivary cancer is low overall, elective dissection of the neck is not routinely indicated. It may be appropriate, however, in patients with sizeable NO squamous cell or high-grade mucoepidermoid carcinoma, which have a higher incidence of cervical lymph node metastases. In these cases, a selective neck dissection encompassing the nodal levels at greatest risk should be adequate to identify those patients with occult disease.

Nonsurgical Treatment

For many years, salivary cancer was believed to be resistant to radiation therapy. In recent years, radiotherapy has assumed an important role in the treatment of salivary cancer, particularly in combination with surgical resection. When malignant salivary neoplasms arise in locations that are relatively inaccessible, such as the nasopharynx or the base of the skull, primary radiotherapy becomes a more attractive option. The use of neutron beam irradiation has been advocated in recent years as a primary therapy for salivary cancer in this setting, particularly in patients with adenoid cystic carcinoma.31,32 Encouraging locoregional control rates are reported, but the significant associated morbidity raises the question of whether neutrons might best be reserved for patients with recurrent or unresectable tumors.

The indications for postoperative radiotherapy include: advanced stage disease, concern over ade quacy of surgical margins, and adverse findings in the surgical pathology report.13,33,34 Unilateral therapy is usually adequate for lesions arising in major salivary glands, and at least the first echelon lymphatic drainage basin is often included in the treatment field. When disease involves the nasal cavity or paranasal sinuses, careful treatment planning is obviously needed to minimize dose to the adjacent central nervous system or to orbital contents.

As noted previously, distant metastases are a frequent occurrence in certain types of salivary cancer,

Figure 13-8. A, Typical parapharyngeal presentation of a retromandibular, pleomorphic adenoma arising in the deep lobe of the left parotid gland. B, MRI scan showing the paraphyaryngeal tumor, contiguous with the parotid gland and extending through the stylo-mandibular window.

such as adenoid cystic carcinoma and high-grade lesions of any histology. This suggests the need for effective systemic therapy, but effective drug regimens are not presently available.

Sequelae, Complications and their Management

When salivary neoplasms are limited to the major glands, the aftereffects of treatment are usually limited. Unintentional injury to the facial nerve during parotidectomy, or disruption of the lingual or hypoglossal nerves during excision of the submandibular gland, are quite uncommon. If the resection is extended beyond the parotid or submandibu-lar gland to include adjacent structures such as the mandible or the temporal bone, the risk of complications increases.

When "salivary-type" tumors arise in locations other than the major salivary glands, potential treatment sequelae and complications will obviously vary according to the site of disease. These problems will be similar to those encountered when treating squamous cell carcinoma at similar sites, and are described elsewhere in this volume.

Rehabilitation and Quality of Life

As noted above, all or part of the facial nerve may be paralyzed at presentation in patients with parotid gland cancer. In addition, resection of the facial nerve may be required at the time of surgical resection. Loss of the mimetic function of the face has a significant negative impact on the quality of life, and inability to close the eye may result in problems from corneal exposure.

As mentioned above, primary cable grafting of the facial nerve at the time of ablative surgery is desirable, providing that proximal and distal disease-free nerve branches are available. Sensory nerve branches harvested from the cervical plexus provide the most convenient source of nerve grafts, but the sural nerves provide a good substitute when these are unavailable. Although the results of grafting often leave much to be desired, there is usually improvement in muscle tone, particularly in younger patients, regardless of postoperative radiotherapy.35,36

When the proximal stump of the facial nerve is not available, the hypoglossal nerve can be anasta-mosed to the distal portion of the facial nerve. Gold weight eyelid implants and fascial slings have proved useful when nerve grafting is not possible, or is unsuccessful.

Outcomes and Results of Treatment

General Considerations

Several issues must be considered when assessing treatment results. Reported series are often small, and outcomes can vary widely depending on the anatomic sites of origin and the histologic subtypes included in the study population. More importantly, the indolent course of many salivary neoplasms mandates clinical follow-up of at least 10 years in order to draw valid conclusions. Finally, the inclusion of patients over an extended time period may mean that considerable variation exists in diagnostic and therapeutic capabilities over the study period.

In the Memorial Hospital experience with previously untreated major salivary gland carcinoma, the reported 5-, 10- and 15-year cumulative survival rates were 82 percent, 67 percent and 55 percent, respectively. Similarly, survival rates for those with previously untreated malignant minor salivary gland tumors were 73 percent, 56 percent, and 46 percent, respectively.3738

Results by Histology

Differences in treatment outcome have been noted depending on the specific histology of salivary cancer. For those tumor types where histologic grading is possible, such as mucoepidermoid carcinoma or ade-nocarcinoma, high-grade lesions carry a worse prognosis (Figure 13-9).37 High-grade cancers tend to be locally advanced at presentation, and are more often associated with regional and distant metastases.39,40

Results by Treatment

While surgery has historically been the mainstay of therapy for salivary cancer, considerable experience with adjuvant radiotherapy has accumulated over the past 2 decades. Results indicate that combining radiotherapy and surgery has resulted in improved

TIME IN YEARS

MAJOR SALIVARY CA: 1939-1982 SURVIVAL BY HISTOLOGY

MUCOEP GRI

( 72

PTS. .

58 CENSORED)

X

MUCOEP OTHER

(132

PTS. .

57 CENSORED)

A

ACINIC

( 56

PTS. .

4 6 CENSORED)

S

ADENOIDCYSTIC

( 53

PTS. .

?0 CENSORED)

MMT

( 67

PTS. .

25 CENSORED)

*

ADENO CA

( 47

PTS. .

?1 CENSORED)

0

Sa CA OR ANAPL CA

( 34

PTS. .

8 CENSORED)

TICK MARK (! ) INDICATES LAST FOLLOW-UP

Figure 13-9. Cumulative survival rates according to histologic diagnosis fall into 3 groups. The best prognosis was seen with low-grade mucoepidermoid carcinoma and acinic cell carcinoma (upper 2 curves). Epidermoid and anaplastic carcinoma had the lowest survival rates (lowest curve). Results were intermediate and similar for all other histologic tumor types.

Figure 13-10. T staging and stage groupings according to the 1997 edition of the AJCC Cancer Staging Manual. The N staging is identical to that used for squamous cell carcinoma.

Figure 13-11. Significant differences in survival were noted when tumors arising in all sites, regardless of histology, were analyzed according to the clinical stage. For those tumors that could be graded (mucoepidermoid, adenocarcinoma, squamous cell carcinoma) similar survival differences were noted.

1937 Willys Coupes For Sale

Figure 13-12. Cumulative survival curves for A, mucoepidermoid carcinoma and B, adenocarcinoma of minor salivary gland origin. For both tumor types, there was no difference in survival when low-grade tumors were compared to highgrade but low-stage lesions, confirming that clinical stage is more important than grade as a prognostic factor.

Figure 13-12. Cumulative survival curves for A, mucoepidermoid carcinoma and B, adenocarcinoma of minor salivary gland origin. For both tumor types, there was no difference in survival when low-grade tumors were compared to highgrade but low-stage lesions, confirming that clinical stage is more important than grade as a prognostic factor.

local and regional control of disease.33,34 Unfortunately, this has not always translated into improved survival, because of distant metastases, which again suggests the need for effective systemic therapy in salivary cancer.

Results by Stage of Disease

The stage of disease at presentation is the most reliable predictor of treatment outcome in salivary cancer (Figure 13-10).41 Cumulative survival according to clinical stage and histology is shown in Figure 13-11.5 This includes patients with minor salivary gland cancers, which were staged using the criteria for squamous carcinomas in similar sites (Figure 13-12).37 Aside from the fact that not all salivary gland carcinomas are gradeable, the data clearly indicate that clinical stage is a more important predictor of survival.

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