Chapter 20: Malignant salivary tumours. Michael Gleeson. Normal structure and pathological classification

Transcription

1 Chapter 20: Malignant salivary tumours Michael Gleeson Malignant neoplasms arising in salivary tissue are uncommon. While fewer than 3% of all neoplasms originate in salivary glands (OPCS Cancer Statistics, 1983), at least 75% of these are benign. Most salivary gland tumours are pleomorphic adenomata which, despite their benign nature, pose considerable management problems as they recur locally if inadequately resected, ruptured or biopsied and also because of their potential to undergo carcinomatous change. The malignant character of some salivary tumours has only recently been appreciated as their natural history must be measured in decades rather than years. The slow growth pattern of these tumours does not lessen their malignant nature. Despite treatment they often recur or manifest as metastatic disease at a relatively late stage and thus exert a considerable morbidity and mortality. Normal structure and pathological classification Normal salivary tissue has a complex structure consisting of secretory cells, which may be either serous or mucous, arranged in acini and drained by a duct system. The major glands - the parotid, submandibular and sublingual - are composed of collections of acini of differing character which secrete into a complex duct system. Around the acini lie myoepithelial cells which display features common to both epithelial and smooth muscle cells. Their probable function is to propel the contents of the acini along the duct system. While the parotid gland is predominantly serous, the submandibular and sublingual glands produce mucoid secretions. There are numerous collections of salivary acini scattered throughout the oral mucosa which are referred to as the minor glands. The histopathology of salivary neoplasms poses many problems to the pathologist. Like most other tumours they are rarely homogeneous in structure, many present a variety of patterns and some are so uncommon that few pathologists have the opportunity to acquire expertise in their diagnosis. A widely recognized system of classification has been established (Thackray and Sobin, 1972) which divides these lesions into four sub-groups: epithelial, non-epithelial, unclassified tumours and a group of conditions that may give rise to diffuse or discrete salivary enlargement (Table 20.1). Epithelial tumours predominate in all series. Distribution Salivary tumours are more common in the parotid gland than in any of the other glands. The frequency of malignant tumours varies according to the site, being relatively lower in the parotid than elsewhere (Table 20.2). Malignancy is far more frequent in the submandibular, sublingual and minor glands. Furthermore, even within the minor glands groups there is much variation in the proportion of frankly malignant tumours, the lip being the least common site, while those tumours arising in the sublingual glands, albeit rare, are nearly always malignant (Table 20.3). The most common sites for tumours of the minor glands are the palate, lip and buccal mucosa. 1

2 Benign tumours (the mono- and pleomorphic adenomata) outnumber malignant tumours at all sites except in the sublingual glands. The available data show that the relative incidence of the more common varieties of malignant neoplasm differs widely between the major and minor glands (Table 20.4). Thus mucoepidermoid tumours and adenoid cystic carcinomata are the most common neoplasms overall. Table 20.1 WHO histological classification of salivary gland neoplasms Epithelial tumours Adenomata pleomorphic monomorphic adenolymphoma oxyphilic adenoma others Mucoepidermoid tumour Acinic cell tumour Carcinomata adenoid cystic carcinoma adenocarcinoma epidermoid carcinoma undifferentiated carcinoma carcinoma ex pleomorphic adenoma Non-epithelial tumours Haemangioma Lymphangioma Neurofibroma Lymphoma Unclassified tumours Allied conditions Benign epithelial lesion Sialosis Oncocytosis. Malignant salivary gland tumours are more frequent in women than men and have a peak age of incidence in the seventh decade. Adenomata and non-epithelial tumours present at a much younger age and, indeed, many have been reported in infancy. Even discounting congenital anomalies, the salivary tumours arising in infancy have a different distribution from those of adult life (Table 20.5). Pleomorphic adenoma still predominates but, in infants, the mucoepidermoid tumour is the most common malignancy (Byers, Piorkowski and Luna, 1984). 2

3 Epidemiology The reported incidence of salivary gland tumours is variable, for example, 2.5 per million in Norway, 7.5 per million in Sweden and 15 per million in Caucasians living in the USA (Dorn and Cutler, 1959; Soder, 1973). The developing nations would appear to experience a similar incidence (Davies, Dodge and Burkitt, 1964; Loke, 1967). Table 20.2 Frequency (%) of all primary epithelial salivary gland tumours and malignancy (%) analysed by site Site Absolute Frequency Malignant no. (%) (%) Parotid Submandibular Sublingual Minor (oropharyngeal) glands Unknown Total 2410 The peak incidence of salivary neoplasms is in the sixth and seventh decades for both men and women. In the major series, salivary tumours have been found to be slightly more common in females than males. This tendency, while present throughout life, becomes most marked in the eighth and ninth decades when there is a female predominance in the population and ratios of 1.6:1 and 1.9:1 are recorded respectively. Table 20.3 Distribution of salivary tumours in minor glands and malignancy (%) Site Absolute no. % of total Malignant (%) Palate Lip Buccal mucosa Tongue Pharynx Tonsil Retromolar Alveolar ridge Tuberosity Ethmoid Total 336 Predisposing and associated factors Several possible predisposing factors have been postulated including race, diet, occupation, Epstein-Barr virus, etc (Lanier et al, 1976; Lennox et al, 1978; Saemundsen et 3

4 al, 1982; Spitz et al, 1984). Only previous radiation has been shown convincingly to have any significant influence. In a study of survivors of the Hiroshima atomic bomb, Takeichi, Hirose and Yamamoto (1976) found that the incidence of benign and malignant salivary gland tumours was 2.6 times higher than that of a comparable non-exposed population, while that of malignant tumours was 10 times greater. This risk of salivary malignancy was higher in those closes to the hypocentre of the explosion and in those returning early to the city. As with similarly induced thyroid neoplasms there would appear to be a latent period of years after exposure before development of the tumour. In a later study of the same population it was established that this increased susceptibility was shared by both the parotid and submandibular glands (Takeichi et al, 1983). Patients given low dosage radiotherapy to the tonsil and nasopharyngeal area for benign conditions have also shown identical trends (Shore-Freedman et al, 1983). Table 20.4 Frequency (%) of primary epithelial salivary gland tumours by site Tumour type Parotid Submand Sublingual Minor Benign Pleom ad Adenolymphoma Oxyphil adenoma Other monomorphics Malignant Mucoepidermoid ca Acinic cell tumour Adenoid cystic ca Adenocarcinoma Epidermoid ca Undifferentiated ca Ca ex pleom ad Total no of cases Some authors have found that patients with salivary tumours are more likely to develop a second primary tumour at any site. A link with hormone-dependent tumours has been suggested as the breast is structurally similar to salivary tissue. Women are more likely to develop a later breast tumour, but in men skin cancer is the only growth with a significantly increased incidence, despite early claims suggesting an association with prostatic carcinoma (Prior and Waterhouse, 1977; Abbey et al, 1984; Spitz et al, 1985). Histopathology and natural history of the common tumour types Mucoepidermoid tumour Mucoepidermoid tumour is the most common salivary neoplasm to arise in childhood but only the second most common salivary malignancy overall (see table 20.5). The parotid 4

5 and minor glands are the most commonly affected sites, and of the latter group, the glands in the palate predominate. Table 20.5 Distribution of juvenile salivary tumours by site and type Tumour type Parotid Submand Subling Intraoral Lip Unknown Pleomorphic 26 (55%) 14 (29.8%) 0 4 (8.5%) 0 3 (6.4%) Warthin's 1 (100%) Monomorp 1 (100%) Mucoepiderm 3 (50%) 2 (33%) 1 (17%) Acinic cell 1 (100%) Adenoid cy 1 (100%) Adenoca Undifferent 1 (33%) 1 (50%) 1 (50%) Unclassified 1 (100%) 2 (67%) Others 9 (90%) 1 (10%) Total 44 (61%) 17 (24%) 6 (8%) 3 (3.5) 3 (3.5%) Mucoepidermoid tumours grow slowly and recur locally. Lymph node metastases arise in up to 30% of patients and are present ab initio in 15%. Metastases to the lungs, bones and brain develop in approximately 15%. It has been claimed that recurrence and survival rates are strongly influenced by the histological grading of the tumour and its size at presentation. Low grade tumours are said to be compatible with an 80% 15-year determinate cure rate, while a comparable figure for high grade tumours is reported to be only 33% (Spiro et al, 1978). However, even the most apparently benign tumours can prove to be unexpectedly invasive. It is this feature of the mucoepidermoid tumour that has caused it to be called a carcinoma in some areas of the world. Mucoepidermoid tumour is composed of two distinct cell types: epidermoid cells and mucous cells, both of which may show varying degrees of differentiation. Mucus is secreted into the stroma of the tumour giving rise to a partially cystic structure. This neoplasm has been graded according to its cellular content. Tumours are designated high grade if 90% or more of their area is made up of tumour cells and less than 10% from intracystic spaces. Low grade tumours display a reversal of this ratio (Evans, 1984). Increased mitotic activity is not necessarily seen even in high grade tumours - a feature partially responsible for the unpredictable nature of this particular neoplasm Low grade tumours should be managed by local resection and prolonged follow-up. High grade lesions require more radical resection with adjunctive radiotherapy. Local recurrence normally appears within 12 months of the primary procedure. Acinic cell tumour Acinic cell tumour accounts for 2.5% of all salivary gland tumours and predominantly affects the parotid gland, where it is said, a very small proportion are found to be bilateral. Like adenoid cystic carcinoma this tumour is very slow growing, a feature that belies its 5

6 malignant potential. Local recurrence or the development of metastases after a prolonged disease-free interval are common. This tumour exerts a mortality many years after other salivary neoplasms would have been considered cured. Determinate survival rates of 85%, 65% and 50% for 5, 10 and 15 years respectively, have been reported (Batsakis et al, 1979; Perzin and LiVolsi, 1979; Hickman, Cawson and Duffy, 1984). Microscopically, a solid pattern is usually seen with varying degrees of organization into an acinar arrangement. Microcystic, papillary-cystic, follicular and poorly differentiated patterns are also recognized, but are rare. Tumours are often not homogeneous and some are multifocal. The constituent cells contain zymogen granules, thus bearing a close resemblance to the serous salivary gland cell. The management of this tumour is excision of the gland with conservation of all uninvolved nerves. Since nodal disease is uncommon and develops in no more than 10%, elective neck dissection is not indicated. Carcinomata Adenoid cystic carcinoma Adenoid cystic carcinoma is the most common malignant salivary neoplasm. As with the other tumours, its distribution varies between sites. It is far more common in the submandibular, sublingual and minor glands, where it constitutes 16%, 28% and 13% of all neoplasms respectively. However, in the parotid gland only 2% of tumours are of this type (see Table 20.4). Adenoid cystic carcinoma grows slowly and insidiously with a characteristic propensity for perineural infiltration and spread along the haversian systems and neural canals of bones. This pattern is reflected in the local recurrence and cumulative mortality rates for this tumour, namely 5-year survival - 62%; 10-year survival - 39%; 15-year survival - 26%; and 20-year survival - 21% (Spiro, Huvos and Strong, 1974). Nodal involvement is normally the result of direct spread of tumour rather than by lymphatic spread. Metastases develop late in the disease and are usually pulmonary (Shannon, Allen and Marsh, 1976). Local recurrence is common and appears in at least 50% of patients, but even multiple local recurrences or distant metastases are compatible with prolonged survival (Conley and Dingman, 1974). Indeed, while 33% of patients die within one year of the recognition of their metastatic disease, 20% of those with pulmonary secondaries survive with this increased tumour load for longer than 5 years. Four histological patterns can be recognized, namely cribriform, basaloid or solid, cylindromatous, and tubular (Batsakis and Regezi, 1979). Type and grade of tumour appear to affect survival. The more solid types are reported to have the worst prognosis, display greater cellular atypia and, thus, are of higher grade than the tubular and cribriform varieties. These latter types are usually better differentiated, of lower grade and are reported to impart a superior survival rate (Perzin, Gullane and Clairmont, 1978; Szanto et al, 1984). Clinically, adenoid cystic carcinoma usually presents as a painless mass or a submucosal swelling. It is usually non-ulcerated unless it is traumatized. Facial palsy develops 6

7 in up to 20% of parotid tumours and palpable lymph node involvement or direct invasion of adjacent tissues is found in 15%. The management of this tumour is the widest possible excision followed by radiotherapy to improve local control. For a parotid tumour this implies total parotidectomy. The facial nerve is conserved only if there is no evidence of invasion by tumour. Subtotal petrosectomy has been advocated for patients with facial nerve invasion. It is essential to appreciate that the tumour spreads perineurally both distally and proximally. Great care must therefore be given to excision of neural spread in both directions. Part of the mandible and the contents of the infratemporal fossa must also be resected in some of these patients. A radical neck dissection is only indicated for those patients with obvious nodal disease or those in whom a large soft tissue cuff must be removed. Submandibular disease is best managed by a monobloc resection of the gland encompassing the lingual, hypoglossal and marginal mandibular nerves, together with a suprahyoid nodal clearance. Palatal tumours require wide local resection to include the floor of the maxillary sinus at least. Perhaps it is because this is a relatively simple surgical procedure that disease at this site enjoys slightly better survival rates (Eneroth, Hjertman and Moberger, 1968). Recurrent tumour is best dealt with by surgery followed by radiotherapy if possible. Advanced and incurable disease is sometimes palliated by radiotherapy which, in a few, makes salvage surgery feasible (Simpson, Thawley and Matsuba, 1984; Matsuba et al, 1984). Adenocarcinoma This is an uncommon tumour which, by virtue of the overall higher incidence of parotid growths, it most frequently found at that site. However, it constitutes only 25.-4% of all parotid neoplasms and forms a much larger proportion of the tumours in other glands - 5% of submandibular tumours and 12-14% of sublingual and minor gland neoplasms (see Table 20.4). Several histological patterns of adenocarcinoma are now recognized, non-mucin producing types being the most common. Mucinous, papillary, trabecular, clear cell and sebaceous variants are also seen and are more frequent in the minor glands. As a group they display a wide structural range, but have in common neoplastic duct or tubule formation and, by definition, lack any evidence of pre-existing pleomorphic adenoma. Clinicopathological surveys do not implicate any particular histological pattern with increased or decreased survival. The grade of the neoplasm as judged by mitotic rate, cellular pleomorphism and stromal invasion correlates better than the clinical stage and outcome. Most of the high grade tumours are the non-mucin producing type, while the rarer variants are usually of a lower grade. The high grade neoplasms tend to present with locally advanced disease, often with nodal involvement, and are reported to have significantly poorer prognosis (Spiro, Huvos and Strong, 1982). Clinically, 80% present as masses, half of which are fixed; 85% have been present for less than 5 years, but only 35% for less than 12 months. About 20% are painful but, of those arising in the parotid gland, only 5% produce a facial palsy. Nearly 20% of patients have 7

8 nodal disease at presentation and a further 10% develop it later. Failure to control disease is usually manifest as local or regional recurrence but distant metastasis, usually to the lungs, is also common. The clinical management of this tumour is similar to that of the adenoid cystic carcinoma. Rare epithelial neoplasia Of these only the undifferentiated carcinoma and squamous cell carcinoma are sufficiently frequent to deserve mention. Undifferentiated carcinoma usually presents in middle age and constitutes 1.8% of all epithelial tumours. These neoplasms can be subdivided into small cell and large cell types, the small cell variety being twice as common as the large cell type (Nagao et al, 1982). Some of the lesions included in this group could be very poorly differentiated adenocarcinoma or epidermoid carcinoma. The acinar arrangement of very poorly differentiated adenocarcinoma can be demonstrated with monoclonal antibodies, thus facilitating a distinction between the groups (Heyderman et al, 1985). Such distinction is essentially academic as this disease is very aggressive and requires radical surgery combined with postoperative radiotherapy to achieve a 5-year survival rate of 20-30%. Squamous cell carcinoma of the salivary glands is very unusual but represents 1.1% of all salivary epithelial neoplasms. It tends to be restricted to the elderly. From a clinical standpoint, it is essential to establish that such a lesion does not represent a metastasis from a distant or regional site. Malignant mixed tumour Rapid growth of a pleomorphic adenoma, the development of facial palsy, or the onset of pain, all suggest malignant change. Malignant mixed tumour is a very rare entity and is in fact a collective term for three or more main tumour types. Almost all are adenocarcinomata or undifferentiated carcinomata which are clearly seen to arise close to, or within, a pleomorphic adenoma. This subtype is termed 'carcinoma ex pleomorphic adenoma'. It is an aggressive disease with reported 5-year survival rates of 50%, and all patients died in whom the carcinoma extended more than 8 mm beyond the residual benign tumour, its capsule or invaded bone (Tortoledo, Luna and Batsakis, 1984). Perhaps this is a pessimistic assessment of this disease as many more may have been missed due to the limitations of processing large pleomorphic tumours. Radical local resection and radiotherapy offer the best chance of control. The other subtypes of malignant mixed tumour are exceptionally rare. A highly malignant, biphasic neoplasm composed of both epithelial and mesenchymal elements - a carcinosarcoma - is occasionally found. Another type of tumour is completely indistinguishable from a benign pleomorphic adenoma but is found to metastasize to the lungs and bones (Batsakis, 1982). By definition, the diagnosis of this neoplasm is made at a time when therapeutic options are very limited. Indeed, experience with this tumour is anecdotal. 8

9 Malignant non-epithelial tumours: lymphomata Lymphomata comprise 40% of non-epithelial tumours and constitute the majority of the malignant lesions in this category. Non-Hodgkin's lymphomata predominate, grade 1 tumours being commoner than grade 2. Three-quarters of these lymphomata are found in the parotid gland, and it is therefore possible that they arise in lymph nodes normally present within the gland. However, for staging purposes they are categorized as an extranodal site. Most lymphomata arise between the fifth and seventh decades of life and some are found in association with a benign lymphoepithelial lesion. There is little evidence to suggest that Sjögren's syndrome predisposes to the development of a primary salivary lymphoma. Clinically, these lesions are firm and rapidly enlarging, and most give little more than a 6-month history. Pain and facial palsy are not prominent features, but the development of regional lymph node involvement is to be expected in those with a delayed presentation. In some instances, diagnostic suspicion may be so high as to justify open biopsy of a regionally involved node (Watkin, MacLennan and Hobsley, 1984), however, in view of the comparative rarity of these lesions this practice cannot be recommended for the inexperienced surgeon. The clinical stage and histological type of the lymphoma dictate the treatment regimen. Median survival for patients with this disease is 4 years. However, unlike other salivary tumours, advanced clinical stage does not appear to influence prognosis (Gleeson, Bennett and Cawson, 1986). Management of malignant salivary tumours Very few salivary tumours have specific features which are pathognomonic. Open biopsy is almost totally contraindicated in these lesions, the exception being neoplasms of the minor glands. Tumours spilt by biopsy will seed the area and result in the development of multiple recurrences within the biopsy scar. However, the precise histological diagnosis can only be made from tissue obtained at the operation. Despite this, a strong suspicion of malignancy can be aroused by the clinical history, examination and preoperative investigations. Most salivary neoplasms arise as painless masses which grow slowly. Rapid growth or acceleration of growth in a pre-existing lesion is a strong indication of malignancy, as is pain. It is almost impossible to distinguish by palpation alone whether a salivary mass is benign, malignant or inflammatory. Very few salivary tumours, including those that arise in the minor glands, present as ulcers from the outset. Facial, lingual and hypoglossal nerve palsies or evidence of infratemporal fossa infiltration (trismus) denote malignancy, but are uncommon. Similarly, enlarged regional lymph nodes or distant metastases, although indicative of malignancy are a most uncommon presentation. Despite frequent initial uncertainty about the character of the neoplasm it can always be clinically staged. Significant features for staging purposes are tumour size, local extension or fixation, neural involvement, nodal disease and distant metastases. The criteria for both the TNM and clinical staging systems are shown in Table 20.6 (Levitt et al, 1981). 9

10 The preoperative and intraoperative diagnosis of these lesions relies upon the interpretation of radiographs, aspiration cytology and frozen section histopathology, all considered in the context of the clinical findings. Table 20.6 TNM classification system for salivary tumours Tx T0 T1 T2 T3 T4a T4b N0 N1 Nx M0 M1 Recurrence / unstageable. No evidence of primary tumour cm in diameter, without significant local extension cm in diameter, without significant local extension cm in diameter, without significant local extension. > 6 cm in diameter, without significant local extension. Any size with significant local extension. No evidence of palpable regional nodes, including palpable but not suspicious regional nodes. Evidence of regional node involvement, including palpable and suspicious regional nodes. No assessment of regional nodes. No distant metastases. Evidence of distant metastases. Clinical staging Stage 1 T1 N0 M0 T2 N0 M0 Stage 2 T3 N0 M0 Stage 3 T1 N1 M0 T2 N1 M0 T4 N0 M0 Stage 4 T3 N1 M0 T4 N1 M0 T N M1 Radiological evaluation of malignant salivary disease Computerized tomography (CT) and magnetic resonance (MR) imaging have rendered other methods of demonstrating malignant salivary disease obsolete, for example, contrast sialography and isotope studies (McGahan, Walter and Bernstein, 1984). The precise relation of the tumour to major structures - the external carotid artery, facial nerve and retromandibular vein - can be identified in parotid disease. Careful scrutiny of the integrity of the fibrofatty planes that demarcate the major glands from their surrounding structures gives valuable information about the tumour margin and its regional extension. Obliteration of this plane and obvious infiltration of the surrounding muscles indicate malignancy. The general consistency of the mass is also significant. Non-homogeneous tumours are more likely to be malignant than those displaying an homogeneous structure. Coronal sections of the 10

11 facial canal may show expansion secondary to tumour infiltration in those cases with a facial palsy. However, tumour spread will always be far more proximal than the image indicates. Initial experience with MR imaging is encouraging. Imaging of salivary tumours by this method appears to be equal, if not superior, to CT (Schaefer et al, 1985). There are also many advantages to be exploited with MR. Extensive dental fillings impeded CT imaging in standard planes, but MR imaging does not suffer from metallic artefact, does not require iodine contrast and it gives superior information about vascular tumours. In addition, coronal and sagittal projections can be formatted without changing the patient's position. The role of biopsy in the management of suspected salivary malignancy Open biopsy of lesions in the major glands is totally contraindicated. Seeding of the area with neoplastic cells at the time of biopsy is inevitable, leading to local recurrence. Open biopsy as a prelude to treatment is only justified when the tumour arises in a minor gland, for example, the palate. In these sites the overlying and adjacent mucosa should be removed as part of the definitive resection and therefore the extent and outcome of the procedure remains uninfluenced. This is not feasible in a major gland where the overlying skin is normally preserved and only has to be excised if it is infiltrated by tumour or if previous biopsy has been performed. The concern about tumour spillage at the time of diagnostic biopsy has been overcome by fine needle (22 gauge) aspiration biopsy. Seeding of tumour by this technique has not been documented. Accurate interpretation of smears requires considerable experience and skill on the part of the cytologist. At best a diagnostic accuracy of 85% can be achieved, but only by a few individuals (Eneroth, Franzen and Zajicek, 1967; Sismanis et al, 1981), and this degree of cytological expertise is rare. It is prudent therefore to consider such information in conjunction with that obtained by perioperative frozen section biopsy. However, even frozen section analysis of salivary tumour tissue is difficult. Accurate histopathological diagnosis of neoplastic salivary tissue is not often achieved and false negative (malignant called benign) rates of 5-12% are commonplace (Hillel and Fee, 1983; Wheelis and Yarrington, 1984). It is evident that, in the majority of cases, histological diagnosis will prove impossible before surgery and that in a minority the definitive diagnosis will change from benign to malignant on examination of paraffin sections. The surgeon should be aware of this possibility and not compromise his surgical technique when the clinical findings conflict with the frozen section or cytological diagnosis. Surgical management of malignant salivary disease The high incidence of local recurrence following simple excision encouraged a more aggressive approach to the management of neoplastic salivary disease. Radical surgery, the removal of the entire gland, and more recently supraradical surgery, that is resection en bloc of the gland with its surrounding tissues and lymphatic drainage field, have been advocated for some tumours regardless of their stage (Conley and Dingman, 1974). There is little to 11

12 suggest that these larger operations improve survival unless there is preoperative evidence of neural infiltration or lymph node metastases. Parotid gland The operative details of parotidectomy are described in Chapter 19. The fundamental principles of surgery for malignant parotid disease are adequate resection of tumour together with the branches or main trunk of the facial nerve where these are either directly involved or potentially so. Frozen section confirmation of tumour clearance in the ends of the resected facial nerve is a prerequisite before any attempt at reconstruction. There should be no hesitation to combine parotidectomy with removal of the mandibular ramus, infiltrated masticatory muscles and maxillary tuberosity in order to obtain a monobloc clearance. In some cases it will be necessary to perform a subtotal petrosectomy or mastoidectomy for tumour removal or to facilitate facial nerve repair. If the facial nerve must be resected as many of its peripheral branches as possible should be identified at the outset, particularly those supplying the sphincters of the eye and mouth. The main trunk can be prepared at a site free of disease within the temporal bone. Bifurcated or multiple cable grafts can then be interposed to restore continuity. Suitable graft material may be obtained from the greater auricular nerve, sural nerve or cervical plexus. Meticulous attention to the accurate approximation and stabilization of the nerve and graft is essential for a good functional result (Fisch, 1974). Neck dissection is only indicated if there is palpable neck disease, strong evidence of lymph node involvement on CT examination, or to facilitate myocutaneous flap repair of the defect. The definitive operation must include excision of the scar and overlying skin or mucosa if the patient has previously undergone open biopsy or incomplete removal of the tumour. Submandibular gland It is unusual for a submandibular salivary neoplasm to present as a mass associated with a palsy of the hypoglossal nerve, lingual nerve or mandibular branch of the facial nerve. More commonly suspicion is aroused by the consistency of the growth which tends to be hard and craggy when malignant. It is also unusual for a tumour to present as duct obstruction with a history of recurrent pain and swelling at meal times. In these cases a radiograph of the floor of the mouth will fail to reveal a calculus and therefore help to distinguish between a tumour and chronic sialadenitis. The principles governing preoperative biopsy hold as well for the submandibular gland as they do for the parotid. Fine needle aspiration and frozen section diagnosis may indicate malignancy, in which case the resection should include all nerves in close proximity to the tumour together with all suprahyoid lymph nodes. The technique of removal of the submandibular gland is described in Chapter

13 Minor salivary gland tumours Approximately 85% of these lesions arise in either the palate, lip or buccal mucosa. At these sites the differential diagnosis is from a retention cyst or squamous cell carcinoma. The clinical distinction of a cyst by palpation is usually easy. Resection with an adequate cuff of soft tissue can be achieved in most cases. The commonest site for one of these tumours is the hard palate which may be treated by partial maxillectomy. Since the overlying mucosa is removed in continuity with the tumour it is permissible to biopsy lesions of the minor glands. Great care must be taken in the assessment of tumours arising in the tonsillar and lateral oropharyngeal region. The clinically unwary may mistake a deep lobe of parotid tumour for one arising in a minor gland. Deep lobe tumours must be removed by an external approach and previous biopsy increases the complications. The role of radiotherapy Radiotherapy should only be used as an adjunct to surgery in the treatment of malignant salivary tumours. The sole exception to this rule is that of early stage lymphomata which can be cured by radiation alone. There is a good case for reserving radiotherapy for specific types of tumour. It is certainly indicated for any tumour that shows locally aggressive features, for example, perineural invasion, extensive soft tissue infiltration, lymph node spread and extranodal extension. It should also be given to those in whom the presence of residual disease is suspected after surgery, those whose disease lies close to a preserved facial nerve and in all who have undergone surgery for recurrent disease. It is claimed that with this management policy local recurrence rates are diminished. It is hard to prove these claims in diseases which are uncommon and run a very prolonged course. The evidence in favour of this policy is convincing only for adenoid cystic carcinoma (Jackson, Luna and Byers, 1983; Simpson, Thawley and Matsuba, 1984). Until such data become available patients should not be denied possible benefit, a local dose of 6000 cgy being the accepted norm. However, radiotherapy should be withheld from some patients, for example, those with low grade and stage tumours that have been adequately excised, and non-aggressive tumours in young patients in whom the possibility of inducing a subsequent neoplasm is high. Radiotherapy also has a role in the palliation of inoperable tumours. Pain can be alleviated to an extent and tumour progress retarded. Complete regression of tumour has been reported with fast neutron therapy but, to date, the experience with this modality has not been uniform (Catterall, Blake and Rampling, 1984). The role of chemotherapy Whether chemotherapy has a part to play in the management of these tumours has yet to be determined. Complete and partial responses to the administration of both single and multiple agents have been reported and either type of regimen would seem to be equally effective. Cisplatin, 5-fluorouracil and doxorubicin (Adriamycin) have all been claimed to be useful. No study to date has been able to determine whether chemotherapy prolongs survival 13

14 time, but it is clear that in a large proportion of inoperable cases regression of disease and pain can be achieved, albeit temporarily (Suen and Johns, 1982). Prognosis of salivary malignancy Survival times vary widely according to many factors, namely histological type of salivary tumour, grade and stage of disease, age and sex of the patient, method of diagnosis and type of treatment administered. Of these it is suggested that the stage of disease at presentation correlates the best with ultimate outcome, as perhaps would be expected. Unfortunately, the data from which survival figures have been calculated are based on clinical material collected over decades. During this time considerable advances in diagnosis, operative technique and radiotherapy have been made, all of which influence the validity and accuracy of any conclusions. As a guide to the natural behaviour of the epithelial tumours irrespective of their treatment, grade and stage, the figures in Table 20.7 are the compilation of all reliable series collected between 1964 and 1982 based on 2298 malignant salivary tumours. From this can be seen that the malignant mixed tumour is the least favourable with a collective 5-year survival rate similar to that of carcinoma of the breast, while the acinic cell tumours has the best prognosis (Hickman, Cawson and Duffy, 1984). Table 20.7 Prognosis of specific types of salivary gland tumours Tumour type No. cases 5-year 10-year survival (%) survival (%) Acinic cell tumour Mucoepidermoid tumour Adenoid cystic carcinoma Malignant mixed tumour