Annals of the Royal College of Surgeons of England (1992) vol. 74, 186-191
Carcinoma of the major salivary glands S E Afify MS FRCS Research Fellow
J D Maynard MS FRCS Consultant Surgeon
Guy's Hospital, London
Key words: Salivary glands; Carcinoma
The results of a prospective survey of planned management of 28 primary carcinomas of the parotid, and five primary carcinomas of the submandibular gland over a period of 22 years are discussed. High- and low-grade carcinomas are distinguished and less radical treatment for the latter appears justified.
Neoplasia of salivary tissue is relatively uncommon and only approximately 11 new cases per million population occur in the United Kingdom (1), although the incidence may be increasing (2). Nearly 75% occur in the parotid and less than 10% in the submandibular gland, although these figures differ slightly in various parts of the world (2,3). Of the neoplasms, 15-20% arising in the parotid gland are carcinomas, but the incidence in the submandibular gland is higher, ranging between 40% and 50% (2). The occurrence of sublingual gland neoplasms is rare and often difficult to distinguish from tumours arising in minor salivary glands. Spiro classified such tumours as salivary carcinomas arising in the floor of the mouth of either sublingual or minor gland origin and they are not considered further (3). From the viewpoint of the different presentation and prognosis it is useful to classify carcinomas as low and high grade (Table I) (3-5). Review of the literature reveals that not only is the incidence of carcinomas higher in the submandibular gland (3), but, also, the incidence of high-grade carcinomas; namely, 94% compared with 66% in the parotid (6). Because of the rarity of carcinomas in these two salivary glands, few surgeons have sufficient individual experience of their management, and much of the literature is devoted to retrospective analysis of collections of cases over many years in. those institutes with a particular interest in head and neck oncology. Different surgeons have been involved over many years and treatment has Correspondence to: S E Afify MS FRCS, Mayday Hospital, Mayday Road, Thornton Heath, Surrey CR4 7YE
Table I. Malignant neoplasms of the parotid 11 4
Lymphoma Metastatic
Mucoepidermoid Malignant pleomorphic Adenocarcinoma Anaplastic carcinoma Squamous cell Adenoidcystic Acinic cell
High-grade
Low-grade
3 6 5 5 2 2
3
Total
23
Sarcoma Overall total
5 48
1
1 5
varied considerably (3,6-9). The management of carcinoma of the parotid is generally agreed (5,10-14) and in this small series a plan is illustrated in Fig. 1. Carcinoma of the submandibular gland occurs so infrequently and calculus obstruction is so much more common that a suggested form of management is illustrated in Fig. 2
(15).
Patients and methods of treatment During a period of 22 years a personal series of 251 primary parotidectomies was carried out for previously untreated neoplasms, of which 48 were malignant, an incidence of 19%. During the same period, 10 submandibular salivary glands were excised for previously untreated neoplastic lesions of which five were malignant, an incidence of 50%. Although this is a very small series, it is a prospective survey of planned management.
Carcinoma of the major salivary glands
187
Superficial or deep tumour
Superficial or deep tumour no clinical evidence of malignancy. Approx. 80%
clincially or on exposure possibly malignant. Approx. 20%
I
Expose facial nerve
Involvement of branch| BIOPSY-FROZEN SECTION or trunk of nerve
No involvement of nerve
j
Benign
Excisin, no
Excision of neoplasm with wide cuff of normal tissue
Pleomorphic adenoma or low-grade Ca.
sacrifice of nerve
|FROZEN SECTION -
Benign j
I
NO FURTHER TREATMENT /
Local sacrifice of branches or trunk and graft
x
Pleomorphic adenoma or low-grade Ca.
High-grade carcinoma
Block dissection and radiotherapy
High-grade carcinoma
/
Radical parotidectomy and sacrifice of all or part of facial nerve as necessary, and graft.
Figure 1. Surgical management of parotid neoplasms. (Reprinted with kind permission of Selwyn Taylor from Surgical Management, 1st Edition. London: Heinemann Medical Books.)
Firm swelling, or mass in gland No fluctuation in size
/
Swelling or mass with deep or superficial fixation and/or lymph node involvement
\
Obvious calculus No calculus Excision of gland follow-up
or
|EXPLORE
BIOPSY FROZEN SECTION
Confined to gland
Infiltration of
~; surrounding
I
Excise gland
structures
1I |FROZEN SECTION
Carcinoma
Benign 1.
No further treatment
Pleomorphic adenoma
8I
Low-grade \carcinoma
High-grade
Block dissection only if lymph node involvement suspected
Block dissection
8
carcinoma
ideally in continuity
Radiotherapy
LONG-TERM FOLLOW-UP
Figure 2. Surgical management of submandibular neoplasms. (Reprinted with kind permission of Preece PE from Head and Neck Oncology for the General Surgeon. London: Bailliere Tindall Ltd, 1991.
Parotid There was a total of 48 patients (Table I). Sarcomas, lymphomas and metastatic tumours were excluded, leaving a total of 28 primary carcinomas. Of these, five were low-grade carcinomas and are considered separately (Tables I and III). High-grade carcinoma The flow diagram (Fig. 1) illustrates the plan of management. The principles of management can be summarised as follows. Wide excision of benign tumours, pleomorphic adenomas and low-grade carcinomas. Sacrifice of the seventh nerve or its branches when obviously involved by tumour. This rarely, if ever, occurs in the case of pleomorphic adenomas. Block dissection of the posterior triangle in all patients with high-grade carcinomas. Postoperative radiotherapy can be considered after paraffin section. The analysis of the results is best viewed in table form. The overall results are presented in Table II. Thirteen patients have died of their disease and one died without recurrence. The 5-year survival rate was 61%, but four patients died of their disease between 8 and 10 years after treatment (43% 10-year survival). Although radical surgery and regional block dissection was considered the ideal (5,16), treatment was modified for various reasons (Table II). Five patients were treated by wide excision only because frozen section was either not available or difficult to interpret. In view of their age or general state of health, subsequent block dissection was not performed and four patients are still alive without recurrent disease.
188
S E Afify andJ3 D Maynard
Table II. Parotid, high-grade carcinoma Follow-up period
Survival Surgery (n) Total (23) Wide excision (5) Radical excision Radical and block (8)
Sex
Age
Alive
Died
Alive
Died
DXT
Average
Range
Male
Female
10 4 2 3
13 1 2 5
1-14 years 4-8 3-12 1-12
1-10 years 3 3-8 1-9
64 69 74 49
27-85 66-73 68-83 27-56
16
7
1
5
2
1-2
12 0 2 4 2 preop 5 postop 3
65
57-73
Inoperable (6)
Table III. Parotid, low-grade carcinoma Follow-up Survival
Surgery Total number (5)
Age
Sex
period
Alive
Died
Alive
Died
DXT
Female
Male
Average
Range
5
0
1-13 years
0
0
4
1
42
12-57
Four patients were treated by radical excision but did not undergo block dissection, although the histology was known, for the same reason. The eight patients who underwent radical surgery and block dissection were much younger. Six patients were thought to be inoperable. One has survived 5 years after radiotherapy. Ideally, radiotherapy should have been employed to treat all patients in this group (5,13,17,18). Early in the 22-year period some radiotherapists thought carcinomas were not radiosensitive (19). This view has subsequently changed (Table II). Two patients with potentially inoperable tumours underwent preoperative radiotherapy and subsequently radical excision and block dissection of the regional nodes (20). Both of them died of metastatic disease, one 8 years later. It is said that preoperative facial nerve palsy carries an ultimately poor prognosis (6,21,22); eight patients had initial facial nerve involvement. Of these, five died of disease after treatment-63%. The nerve was functionally intact in the remaining 14 patients and seven died of their disease-50%. All eight patients who underwent radical surgery and block dissection were thought, on clinical examination, not to have lymph node involvement. Of these patients, six were found to have microscopic lymph node metastases. In all, 12 patients who undewent radical parotidectomy, and therefore sacrifice of part or the whole of the facial nerve, an immediate interposition nerve graft was carried out, using the great auricular nerve or part of the cervical plexus. It has been suggested that postoperative radiotherapy decreases the chances of successful nerve grafting (24), but denied by others (9,25,26). Of the 10 patients with partial or complete nerve grafts, six showed partial
Table IV. Neoplasms of the submandibular gland Lymphoma Adenoidcystic Squamous cell carcinoma Pleomorphic adenoma Benign conditions (Dermoid cyst lymphoepithelial lesion of Godwin; gross enlargement hypertrophy?)
1 3 1 5 3
recovery of nerve function. Radiotherapy bore no obvious relationship to the success of grafting.
Low-grade carcinoma There were five patients whose tumours were considered to be low-grade carcinomas histologically (Tables I and III). They were managed according to plan and the 5year survival rate in the five cases followed for up to 13 years was 100%. Submandibular carcinoma Of the ten neoplasms, four were carcinomas and all high-grade tumours (Table IV). Adenoidcystic tumours occurred most frequently and the overall results are shown in Table V. Patient 1 (Table V) was treated early in the series by wide excision, and after developing a local recurrence underwent radical surgery but died of the disease 2 years later. Patient 3 was considered too old and frail to stand radical surgery, but survived for 9 years after radiotherapy without any obvious recurrence of her
Carcinoma of the major salivary glands In the two patients who underwent radical and block dissection there was no clinical evidence of node involvement but both had microscopic lymph node metastases. tumour.
surgery
Discussion Parotid This series of patients is obviously too small to draw any definite conclusions. No attempt has been made to distinguish clinical features of different types of carcinomas other than by labelling them high or low grade, depending on the histologist's opinion. The plan of management (Fig. 1) is designed to recognise high-grade carcinomas before or during definitive surgery in patients with operable tumours. It is also designed to avoid unnecessary sacrifice of the facial nerve and its branches (5). It is generally held that the first operation is the best and that local recurrence is associated with a poor prognosis (4,27,28). It follows that radical initial surgery for high-grade tumour combined with block dissection of the regional nodes and followed by radiotherapy gives the best and probably only chance of control (11,13,18). Such counsel of (possible) perfection has to be modified by the general condition of the patient and frailty due to age and concurrent disease. In the early stages of this survey frozen section was less accurate and radiotherapists were unwilling to employ radiotherapy. It seems clear from the literature that the earlier in the progress of the disease treatment is started, the better the prognosis (2,3,5,7). The five patients in this series (Table II) who underwent wide excision of their tumours only, had none of the clinical stigmata of carcinoma and the histology was unexpected. The facial nerve was not involved by the tumours and radical surgery was unnecessary. Four out of the five survived without
regional block dissection or radiotherapy. These five patients were also in an older age group. Facial nerve involvement may indicate a later stage in the disease and the lower survival rate of patients with facial nerve palsy before operation is illustrated in this series. The paradox of the high ultimate mortality in those patients undergoing radical surgery and regional block dissection is perhaps related to the younger age of these patients, and more aggressive tumour behaviour. These tumours were more advanced as six of eight patients had lymph node metastases, which seems to be associated with a worse prognosis (7). It is said that regional block dissection is justified because of the frequency of occult lymph node metastasis (1). The eight patients who underwent block dissection were not thought to have involved lymph nodes on clinical assessment but six had microscopic metastases. Before the availability of CT scanning, six patients were found to have inoperable tumours at exploration. Now patients may be spared unnecessary surgery. Aspiration needle biopsy may have a place in histological diagnosis in such patients but this is by no means certain, and the risks of late implantation recurrence are not yet resolved. Preoperative radiotherapy may permit subsequent radical surgery (20). Two patients in this series underwent preoperative radiotherapy, but despite subsequent radical surgery they died later of their disease (Table IV) (20). It is common practice to gauge the results of treatment by the 5-year survival rate (6). It is worth noting that of the 14 patients who survived for 5 years in this series, no less than four of them subsequently died of their disease (Table II). A 10-year survival rate might be more illuminating (3,27,29). The results of this small series bear out that early diagnosis is the key to successful salvage of patients with these rare carcinomas. The results also suggest that the
Table V. Submandibular carcinoma Clinical
lymph node
Sex and age
Histology
involvement
1
F 45
Adenoidcystic
No
2
F 45
Adenoidcystic
3
F 78
4
F 50
RT Radiotherapy
189
Operation
RT
Result
Wide excision
No
No
Radical and block. Nodes positive
Yes
Adenoidcystic
No
Yes
Squamous cell carcinoma
No
Inoperable, biopsy only Radical and block. Nodes positive. ? 2nd but no other primary
Local recurrence, radical excision of mandible. Died 2 years 9 years alive + pulmonary metastases positive needle biopsy 7 years alive and well
Yes
1 year alive and well
190
S E Afify andj7 D Maynard
incidence of lymph node metastasis is perhaps higher than expected and strengthen the view that radical surgery and regional block dissection is justified (11).
Low-grade carcinoma The results so far in this series confirm the generally held view that the mutilation of regional block dissection is unnecessary and the disadvantages of radiotherapy can be avoided (3-5,7).
Carcinoma of the submandibular gland The rarity of submandibular salivary tumours means that very few individual surgeons have much personal experience. As calculus obstruction of this salivary gland is relatively common, neoplasia is rarely suspected until the diagnosis becomes obvious and definite treatment is therefore often late in the course of the disease (3,7,30). The proportion of carcinomas in submandibular neoplasms is higher than in the parotid, and the most frequently occurring carcinoma is adenoidcystic, which is entirely unpredictable in its behaviour after radical or conservative treatment (Seifort G, 1988, personal communication). These tumours persist and recur over a long period and patients with pulmonary metastases may survive for 5 years or more (21). The proportion of highgrade tumours is higher than in the parotid. The involvement of lymph nodes at presentation was as high as 76% in one paper (30). Other authors reported distal metastases at presentation in 50% of their patients (7). The 10year survival rate was reported as 20% overall, but 41% when lymph nodes were found not to be involved at operation, and only 9% when the nodes contained metastases (6). In those patients with enlargement or a mass in the submandibular gland without detectable calculi, the possibility of a neoplasm must be considered. The plan of management illustrated in Fig. 2 may result in earlier diagnosis and treatment. High-grade carcinomas should receive radiotherapy after radical excision and block dissection of the regional nodes (9,16,28).
References I Schneider AB, Favus MJ, Stachura ME, Arnold MJ, Frobman LA. Salivary gland neoplasms as a late consequence of head and neck irradiation. Ann Intern Med 1977;87: 160-64. 2 Eveson JW, Cawson RA. Salivary gland tumours. A review of 2410 cases with particular reference to histologic types, site, age and sex distribution. J Pathol 1985;146:51-8. 3 Spiro RH. Salivary neoplasms: Overview of a 35 year experience with 2807 patients. Head Neck Surg 1986;8: 17784. 4 Spiro RH, Huvos AG, Berk R, Strong EW. Mucoepidermoid carcinoma of salivary gland origin. A clinicopathologic study of 367 cases. Am J Surg 1978;136: 461-8.
5 Guillamondeguy OM, Byers RM, Luna MA. Aggressive surgery in treatment for parotid cancer: The role of adjunctive postoperative radiotherapy. AJR 1975:123:49-54. 6 Spiro RH, Huvos AG, Strong EW. Tumours of the submaxillary gland. Am J Surg 1976;132:468. 7 Borthne A, Kjellevold K, Kaalhus 0, Vermund H. Salivary gland malignant neoplasms: Treatment and prognosis. IntJ7 Radiat Oncol Biol Phys 1986;12:747-54. 8 Eneroth GM, Hjertman L, Moberger G. Malignant tumours of the submandibular gland. Acta Otolaryngol 1967;64:514-36. 9 Shidnia H, Hornback NB, Hamaker RC, Lingeman R. Carcinoma of major salivary glands. Cancer 1980;45:693-7. 10 Matsuba HM, Simpson JR, Mauney M, Thawley SE. Adenoidcystic salivary gland carcinoma: A cinicopathologic correlation. Head Neck Surg 1986;8:200-204. 11 Simpson JR, Matsuba HM, Thawley SE, Mauney M. Improved treatment of salivary adenocarcinomas: Planned combined surgery and irradiation. Laryngoscope 1986;96: 904-7. 12 Spiro RH, Huvos GA, Strong EW. Adenocarcinoma of salivary origin. Am Jf Surg 1982;144:423-31. 13 Hodkinson DJ, Woods JE. The influence of facial nerve sacrifice in surgery of malignant parotid tumours. 7 Surg Oncol 1976;8:425-32. 14 Chung CT, Sagerman RH, Ryoo MC, King GA, Yu WS, Dalal PS. The changing role of external beam irradiation in the management of malignant tumours of the major salivary glands. Radiology 1982;145:175-7. 15 Spiro HR, Huvosa AG, Strong EW. Malignant mixed tumour of salivary origin. A clinicopathologic study of 146 cases. Cancer 1977;39:288-396. 16 Fu KK, Leibel SA, Levine ML, Friedlander LM, Boles R, Phillips TL. Carcinoma of the major and minor salivary glands. Analysis of treatment, results and sites and causes of failure. Cancer 1977;40:2882-90. 17 Shidnia H, Hornback NB, Hamaker RC. Carcinoma of major salivary glands. Cancer 1980;45:693-7. 18 Kagan AR, Nussbaum H, Handler S. Recurrences from malignant salivary gland tumours. Cancer 1976;37:26002604. 19 McNaney D, McNeese MD, Guillamanodegui OM, Fletcher GH, Oswald MJ. Postoperative irradiation in malignant epithelial tumours of the parotid gland. Int. Radiat Oncol Biol Phys 1983;9:1289-95. 20 Corcoran MO, Cook HP, Hobsley M. Radical surgery following radiotherapy for advanced parotid carcinoma. Br J Surg 1983;70:261-3. 21 Spiro RH, Huvos AG, Strong EW. Adenoidcystic carcinoma of salivary origin. Am J Surg 1974;128:512-20. 22 Conley J, Hanamaker RC. Prognosis of malignant tumours of the parotid gland with facial paralysis. Arch Otolaryngol
1975;101:39-41. 23 Skolnik EM, Friedman M, Becker S. Tumours of the major salivary glands. Laryngoscope 1977;87:843-61. 24 Berger PS, Bataini JP. Radiation induced nerve palsy. Cancer 1977;40:152-5. 25 Conley J. Salivary Glands and the Facial Nerve. Stuttgart: Georg Thieme Publishers, 1975. 26 Rampling R, Catterall M. Facial nerve damage in the treatment of tumours of the parotid gland. Clin Oncol 1984;1O:345-5 1. 27 Rosenfeld L, Sessions DG, McSwain B, Graves H. Malignant tumours of salivary gland origin. Ann Surg 1966;163:726-34.
Carcinoma of the major salivary glands 28 Byun YS, Fayos JV, Kim YH. Management of salivary gland tumours. Laryngoscope 1980;90:1052-60. 29 Livolsi VA, Perzin KH. Malignant mixed tumours arising in salivary glands. Cancer 1977;39:2209-30.
191
30 Trail ML, Lubitz J. Tumours of the submandibular gland. Laryngoscope 1974;84:1225-32.
Received 20 August 1991
Assessor's comment This article is a scholarly and shrewd contribution to the literature of carcinoma of the salivary glands. It reflects the tremendous advantage of a series compiled by a single consultant and one moreover in which treatment was tailored prospectively to a logical plan. To my mind, the important message of this paper is that the low-grade malignancies are a distinctly different entity to the high-grade ones, and it is likely that the lowgrade tumours only need much the same treatment as a pleomorphic or monomorphic adenoma, that is excision with a wide margin of normal tissue and preservation of the facial nerve, provided the circumstances at operation permit, ie provided the tumour does not seem to be growing into the nerve. This is precisely the same conclusion that we reached recently (1). In our practice, we differ from Mr Maynard only in that we do not use frozen section examination during the operation: the reason is partly that we do not wish to accept the risk of implantation recurrence of what turns out in the end to be a benign tumour, partly because of the well-known difficulty of making an accurate diagnosis of histological type and grade of the tumour, and partly because of the fact that the less malignant tumours-the adenoid cystic carcinoma, the mucoepidermoid tumour, and the acinic cell tumour-behave in a variable fashion between the limits of very benign and very malignant without neces-
sarily any correspondence between that behaviour and the histological appearances. I strongly endorse Mr Maynard's cautious attitude towards aspiration cytology of lumps in the regions of the salivary glands. The difficulties of histological diagnosis already alluded to, even when the whole specimen is out and available to the histopathologist, plus the posssible risk of implantation recurrence, prevents both our groups from its use in potentially benign lesions. For the lesions that in clinical terms cannot be benign, we prefer a generous open biopsy before embarking on our cycle of radiotherapy-massive ablation-radiotherapy that Mr Maynard and Mr Afify have kindly referred to (2). MICHAEL HOBSLEY TD FRCS Head of Department of Surgery The Rayne Institute London
References I Nnochiri CC, Watkin GT, Hobsley M. Unremarkable parotid tumours that prove to be malignant. Br 7 Surg 1990; 77:917-18. 2 Gallegos NC, Watkin G, Cook HP, Sanders R, Hobsley M. Further evaluation of radical surgery following radiotherapy for advanced parotid carcinoma. BrJ Surg 1991;78:97-100.
Carcinoma of the major salivary glands S E Afify MS FRCS Research Fellow
J D Maynard MS FRCS Consultant Surgeon
Guy's Hospital, London
Key words: Salivary glands; Carcinoma
The results of a prospective survey of planned management of 28 primary carcinomas of the parotid, and five primary carcinomas of the submandibular gland over a period of 22 years are discussed. High- and low-grade carcinomas are distinguished and less radical treatment for the latter appears justified.
Neoplasia of salivary tissue is relatively uncommon and only approximately 11 new cases per million population occur in the United Kingdom (1), although the incidence may be increasing (2). Nearly 75% occur in the parotid and less than 10% in the submandibular gland, although these figures differ slightly in various parts of the world (2,3). Of the neoplasms, 15-20% arising in the parotid gland are carcinomas, but the incidence in the submandibular gland is higher, ranging between 40% and 50% (2). The occurrence of sublingual gland neoplasms is rare and often difficult to distinguish from tumours arising in minor salivary glands. Spiro classified such tumours as salivary carcinomas arising in the floor of the mouth of either sublingual or minor gland origin and they are not considered further (3). From the viewpoint of the different presentation and prognosis it is useful to classify carcinomas as low and high grade (Table I) (3-5). Review of the literature reveals that not only is the incidence of carcinomas higher in the submandibular gland (3), but, also, the incidence of high-grade carcinomas; namely, 94% compared with 66% in the parotid (6). Because of the rarity of carcinomas in these two salivary glands, few surgeons have sufficient individual experience of their management, and much of the literature is devoted to retrospective analysis of collections of cases over many years in. those institutes with a particular interest in head and neck oncology. Different surgeons have been involved over many years and treatment has Correspondence to: S E Afify MS FRCS, Mayday Hospital, Mayday Road, Thornton Heath, Surrey CR4 7YE
Table I. Malignant neoplasms of the parotid 11 4
Lymphoma Metastatic
Mucoepidermoid Malignant pleomorphic Adenocarcinoma Anaplastic carcinoma Squamous cell Adenoidcystic Acinic cell
High-grade
Low-grade
3 6 5 5 2 2
3
Total
23
Sarcoma Overall total
5 48
1
1 5
varied considerably (3,6-9). The management of carcinoma of the parotid is generally agreed (5,10-14) and in this small series a plan is illustrated in Fig. 1. Carcinoma of the submandibular gland occurs so infrequently and calculus obstruction is so much more common that a suggested form of management is illustrated in Fig. 2
(15).
Patients and methods of treatment During a period of 22 years a personal series of 251 primary parotidectomies was carried out for previously untreated neoplasms, of which 48 were malignant, an incidence of 19%. During the same period, 10 submandibular salivary glands were excised for previously untreated neoplastic lesions of which five were malignant, an incidence of 50%. Although this is a very small series, it is a prospective survey of planned management.
Carcinoma of the major salivary glands
187
Superficial or deep tumour
Superficial or deep tumour no clinical evidence of malignancy. Approx. 80%
clincially or on exposure possibly malignant. Approx. 20%
I
Expose facial nerve
Involvement of branch| BIOPSY-FROZEN SECTION or trunk of nerve
No involvement of nerve
j
Benign
Excisin, no
Excision of neoplasm with wide cuff of normal tissue
Pleomorphic adenoma or low-grade Ca.
sacrifice of nerve
|FROZEN SECTION -
Benign j
I
NO FURTHER TREATMENT /
Local sacrifice of branches or trunk and graft
x
Pleomorphic adenoma or low-grade Ca.
High-grade carcinoma
Block dissection and radiotherapy
High-grade carcinoma
/
Radical parotidectomy and sacrifice of all or part of facial nerve as necessary, and graft.
Figure 1. Surgical management of parotid neoplasms. (Reprinted with kind permission of Selwyn Taylor from Surgical Management, 1st Edition. London: Heinemann Medical Books.)
Firm swelling, or mass in gland No fluctuation in size
/
Swelling or mass with deep or superficial fixation and/or lymph node involvement
\
Obvious calculus No calculus Excision of gland follow-up
or
|EXPLORE
BIOPSY FROZEN SECTION
Confined to gland
Infiltration of
~; surrounding
I
Excise gland
structures
1I |FROZEN SECTION
Carcinoma
Benign 1.
No further treatment
Pleomorphic adenoma
8I
Low-grade \carcinoma
High-grade
Block dissection only if lymph node involvement suspected
Block dissection
8
carcinoma
ideally in continuity
Radiotherapy
LONG-TERM FOLLOW-UP
Figure 2. Surgical management of submandibular neoplasms. (Reprinted with kind permission of Preece PE from Head and Neck Oncology for the General Surgeon. London: Bailliere Tindall Ltd, 1991.
Parotid There was a total of 48 patients (Table I). Sarcomas, lymphomas and metastatic tumours were excluded, leaving a total of 28 primary carcinomas. Of these, five were low-grade carcinomas and are considered separately (Tables I and III). High-grade carcinoma The flow diagram (Fig. 1) illustrates the plan of management. The principles of management can be summarised as follows. Wide excision of benign tumours, pleomorphic adenomas and low-grade carcinomas. Sacrifice of the seventh nerve or its branches when obviously involved by tumour. This rarely, if ever, occurs in the case of pleomorphic adenomas. Block dissection of the posterior triangle in all patients with high-grade carcinomas. Postoperative radiotherapy can be considered after paraffin section. The analysis of the results is best viewed in table form. The overall results are presented in Table II. Thirteen patients have died of their disease and one died without recurrence. The 5-year survival rate was 61%, but four patients died of their disease between 8 and 10 years after treatment (43% 10-year survival). Although radical surgery and regional block dissection was considered the ideal (5,16), treatment was modified for various reasons (Table II). Five patients were treated by wide excision only because frozen section was either not available or difficult to interpret. In view of their age or general state of health, subsequent block dissection was not performed and four patients are still alive without recurrent disease.
188
S E Afify andJ3 D Maynard
Table II. Parotid, high-grade carcinoma Follow-up period
Survival Surgery (n) Total (23) Wide excision (5) Radical excision Radical and block (8)
Sex
Age
Alive
Died
Alive
Died
DXT
Average
Range
Male
Female
10 4 2 3
13 1 2 5
1-14 years 4-8 3-12 1-12
1-10 years 3 3-8 1-9
64 69 74 49
27-85 66-73 68-83 27-56
16
7
1
5
2
1-2
12 0 2 4 2 preop 5 postop 3
65
57-73
Inoperable (6)
Table III. Parotid, low-grade carcinoma Follow-up Survival
Surgery Total number (5)
Age
Sex
period
Alive
Died
Alive
Died
DXT
Female
Male
Average
Range
5
0
1-13 years
0
0
4
1
42
12-57
Four patients were treated by radical excision but did not undergo block dissection, although the histology was known, for the same reason. The eight patients who underwent radical surgery and block dissection were much younger. Six patients were thought to be inoperable. One has survived 5 years after radiotherapy. Ideally, radiotherapy should have been employed to treat all patients in this group (5,13,17,18). Early in the 22-year period some radiotherapists thought carcinomas were not radiosensitive (19). This view has subsequently changed (Table II). Two patients with potentially inoperable tumours underwent preoperative radiotherapy and subsequently radical excision and block dissection of the regional nodes (20). Both of them died of metastatic disease, one 8 years later. It is said that preoperative facial nerve palsy carries an ultimately poor prognosis (6,21,22); eight patients had initial facial nerve involvement. Of these, five died of disease after treatment-63%. The nerve was functionally intact in the remaining 14 patients and seven died of their disease-50%. All eight patients who underwent radical surgery and block dissection were thought, on clinical examination, not to have lymph node involvement. Of these patients, six were found to have microscopic lymph node metastases. In all, 12 patients who undewent radical parotidectomy, and therefore sacrifice of part or the whole of the facial nerve, an immediate interposition nerve graft was carried out, using the great auricular nerve or part of the cervical plexus. It has been suggested that postoperative radiotherapy decreases the chances of successful nerve grafting (24), but denied by others (9,25,26). Of the 10 patients with partial or complete nerve grafts, six showed partial
Table IV. Neoplasms of the submandibular gland Lymphoma Adenoidcystic Squamous cell carcinoma Pleomorphic adenoma Benign conditions (Dermoid cyst lymphoepithelial lesion of Godwin; gross enlargement hypertrophy?)
1 3 1 5 3
recovery of nerve function. Radiotherapy bore no obvious relationship to the success of grafting.
Low-grade carcinoma There were five patients whose tumours were considered to be low-grade carcinomas histologically (Tables I and III). They were managed according to plan and the 5year survival rate in the five cases followed for up to 13 years was 100%. Submandibular carcinoma Of the ten neoplasms, four were carcinomas and all high-grade tumours (Table IV). Adenoidcystic tumours occurred most frequently and the overall results are shown in Table V. Patient 1 (Table V) was treated early in the series by wide excision, and after developing a local recurrence underwent radical surgery but died of the disease 2 years later. Patient 3 was considered too old and frail to stand radical surgery, but survived for 9 years after radiotherapy without any obvious recurrence of her
Carcinoma of the major salivary glands In the two patients who underwent radical and block dissection there was no clinical evidence of node involvement but both had microscopic lymph node metastases. tumour.
surgery
Discussion Parotid This series of patients is obviously too small to draw any definite conclusions. No attempt has been made to distinguish clinical features of different types of carcinomas other than by labelling them high or low grade, depending on the histologist's opinion. The plan of management (Fig. 1) is designed to recognise high-grade carcinomas before or during definitive surgery in patients with operable tumours. It is also designed to avoid unnecessary sacrifice of the facial nerve and its branches (5). It is generally held that the first operation is the best and that local recurrence is associated with a poor prognosis (4,27,28). It follows that radical initial surgery for high-grade tumour combined with block dissection of the regional nodes and followed by radiotherapy gives the best and probably only chance of control (11,13,18). Such counsel of (possible) perfection has to be modified by the general condition of the patient and frailty due to age and concurrent disease. In the early stages of this survey frozen section was less accurate and radiotherapists were unwilling to employ radiotherapy. It seems clear from the literature that the earlier in the progress of the disease treatment is started, the better the prognosis (2,3,5,7). The five patients in this series (Table II) who underwent wide excision of their tumours only, had none of the clinical stigmata of carcinoma and the histology was unexpected. The facial nerve was not involved by the tumours and radical surgery was unnecessary. Four out of the five survived without
regional block dissection or radiotherapy. These five patients were also in an older age group. Facial nerve involvement may indicate a later stage in the disease and the lower survival rate of patients with facial nerve palsy before operation is illustrated in this series. The paradox of the high ultimate mortality in those patients undergoing radical surgery and regional block dissection is perhaps related to the younger age of these patients, and more aggressive tumour behaviour. These tumours were more advanced as six of eight patients had lymph node metastases, which seems to be associated with a worse prognosis (7). It is said that regional block dissection is justified because of the frequency of occult lymph node metastasis (1). The eight patients who underwent block dissection were not thought to have involved lymph nodes on clinical assessment but six had microscopic metastases. Before the availability of CT scanning, six patients were found to have inoperable tumours at exploration. Now patients may be spared unnecessary surgery. Aspiration needle biopsy may have a place in histological diagnosis in such patients but this is by no means certain, and the risks of late implantation recurrence are not yet resolved. Preoperative radiotherapy may permit subsequent radical surgery (20). Two patients in this series underwent preoperative radiotherapy, but despite subsequent radical surgery they died later of their disease (Table IV) (20). It is common practice to gauge the results of treatment by the 5-year survival rate (6). It is worth noting that of the 14 patients who survived for 5 years in this series, no less than four of them subsequently died of their disease (Table II). A 10-year survival rate might be more illuminating (3,27,29). The results of this small series bear out that early diagnosis is the key to successful salvage of patients with these rare carcinomas. The results also suggest that the
Table V. Submandibular carcinoma Clinical
lymph node
Sex and age
Histology
involvement
1
F 45
Adenoidcystic
No
2
F 45
Adenoidcystic
3
F 78
4
F 50
RT Radiotherapy
189
Operation
RT
Result
Wide excision
No
No
Radical and block. Nodes positive
Yes
Adenoidcystic
No
Yes
Squamous cell carcinoma
No
Inoperable, biopsy only Radical and block. Nodes positive. ? 2nd but no other primary
Local recurrence, radical excision of mandible. Died 2 years 9 years alive + pulmonary metastases positive needle biopsy 7 years alive and well
Yes
1 year alive and well
190
S E Afify andj7 D Maynard
incidence of lymph node metastasis is perhaps higher than expected and strengthen the view that radical surgery and regional block dissection is justified (11).
Low-grade carcinoma The results so far in this series confirm the generally held view that the mutilation of regional block dissection is unnecessary and the disadvantages of radiotherapy can be avoided (3-5,7).
Carcinoma of the submandibular gland The rarity of submandibular salivary tumours means that very few individual surgeons have much personal experience. As calculus obstruction of this salivary gland is relatively common, neoplasia is rarely suspected until the diagnosis becomes obvious and definite treatment is therefore often late in the course of the disease (3,7,30). The proportion of carcinomas in submandibular neoplasms is higher than in the parotid, and the most frequently occurring carcinoma is adenoidcystic, which is entirely unpredictable in its behaviour after radical or conservative treatment (Seifort G, 1988, personal communication). These tumours persist and recur over a long period and patients with pulmonary metastases may survive for 5 years or more (21). The proportion of highgrade tumours is higher than in the parotid. The involvement of lymph nodes at presentation was as high as 76% in one paper (30). Other authors reported distal metastases at presentation in 50% of their patients (7). The 10year survival rate was reported as 20% overall, but 41% when lymph nodes were found not to be involved at operation, and only 9% when the nodes contained metastases (6). In those patients with enlargement or a mass in the submandibular gland without detectable calculi, the possibility of a neoplasm must be considered. The plan of management illustrated in Fig. 2 may result in earlier diagnosis and treatment. High-grade carcinomas should receive radiotherapy after radical excision and block dissection of the regional nodes (9,16,28).
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5 Guillamondeguy OM, Byers RM, Luna MA. Aggressive surgery in treatment for parotid cancer: The role of adjunctive postoperative radiotherapy. AJR 1975:123:49-54. 6 Spiro RH, Huvos AG, Strong EW. Tumours of the submaxillary gland. Am J Surg 1976;132:468. 7 Borthne A, Kjellevold K, Kaalhus 0, Vermund H. Salivary gland malignant neoplasms: Treatment and prognosis. IntJ7 Radiat Oncol Biol Phys 1986;12:747-54. 8 Eneroth GM, Hjertman L, Moberger G. Malignant tumours of the submandibular gland. Acta Otolaryngol 1967;64:514-36. 9 Shidnia H, Hornback NB, Hamaker RC, Lingeman R. Carcinoma of major salivary glands. Cancer 1980;45:693-7. 10 Matsuba HM, Simpson JR, Mauney M, Thawley SE. Adenoidcystic salivary gland carcinoma: A cinicopathologic correlation. Head Neck Surg 1986;8:200-204. 11 Simpson JR, Matsuba HM, Thawley SE, Mauney M. Improved treatment of salivary adenocarcinomas: Planned combined surgery and irradiation. Laryngoscope 1986;96: 904-7. 12 Spiro RH, Huvos GA, Strong EW. Adenocarcinoma of salivary origin. Am Jf Surg 1982;144:423-31. 13 Hodkinson DJ, Woods JE. The influence of facial nerve sacrifice in surgery of malignant parotid tumours. 7 Surg Oncol 1976;8:425-32. 14 Chung CT, Sagerman RH, Ryoo MC, King GA, Yu WS, Dalal PS. The changing role of external beam irradiation in the management of malignant tumours of the major salivary glands. Radiology 1982;145:175-7. 15 Spiro HR, Huvosa AG, Strong EW. Malignant mixed tumour of salivary origin. A clinicopathologic study of 146 cases. Cancer 1977;39:288-396. 16 Fu KK, Leibel SA, Levine ML, Friedlander LM, Boles R, Phillips TL. Carcinoma of the major and minor salivary glands. Analysis of treatment, results and sites and causes of failure. Cancer 1977;40:2882-90. 17 Shidnia H, Hornback NB, Hamaker RC. Carcinoma of major salivary glands. Cancer 1980;45:693-7. 18 Kagan AR, Nussbaum H, Handler S. Recurrences from malignant salivary gland tumours. Cancer 1976;37:26002604. 19 McNaney D, McNeese MD, Guillamanodegui OM, Fletcher GH, Oswald MJ. Postoperative irradiation in malignant epithelial tumours of the parotid gland. Int. Radiat Oncol Biol Phys 1983;9:1289-95. 20 Corcoran MO, Cook HP, Hobsley M. Radical surgery following radiotherapy for advanced parotid carcinoma. Br J Surg 1983;70:261-3. 21 Spiro RH, Huvos AG, Strong EW. Adenoidcystic carcinoma of salivary origin. Am J Surg 1974;128:512-20. 22 Conley J, Hanamaker RC. Prognosis of malignant tumours of the parotid gland with facial paralysis. Arch Otolaryngol
1975;101:39-41. 23 Skolnik EM, Friedman M, Becker S. Tumours of the major salivary glands. Laryngoscope 1977;87:843-61. 24 Berger PS, Bataini JP. Radiation induced nerve palsy. Cancer 1977;40:152-5. 25 Conley J. Salivary Glands and the Facial Nerve. Stuttgart: Georg Thieme Publishers, 1975. 26 Rampling R, Catterall M. Facial nerve damage in the treatment of tumours of the parotid gland. Clin Oncol 1984;1O:345-5 1. 27 Rosenfeld L, Sessions DG, McSwain B, Graves H. Malignant tumours of salivary gland origin. Ann Surg 1966;163:726-34.
Carcinoma of the major salivary glands 28 Byun YS, Fayos JV, Kim YH. Management of salivary gland tumours. Laryngoscope 1980;90:1052-60. 29 Livolsi VA, Perzin KH. Malignant mixed tumours arising in salivary glands. Cancer 1977;39:2209-30.
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30 Trail ML, Lubitz J. Tumours of the submandibular gland. Laryngoscope 1974;84:1225-32.
Received 20 August 1991
Assessor's comment This article is a scholarly and shrewd contribution to the literature of carcinoma of the salivary glands. It reflects the tremendous advantage of a series compiled by a single consultant and one moreover in which treatment was tailored prospectively to a logical plan. To my mind, the important message of this paper is that the low-grade malignancies are a distinctly different entity to the high-grade ones, and it is likely that the lowgrade tumours only need much the same treatment as a pleomorphic or monomorphic adenoma, that is excision with a wide margin of normal tissue and preservation of the facial nerve, provided the circumstances at operation permit, ie provided the tumour does not seem to be growing into the nerve. This is precisely the same conclusion that we reached recently (1). In our practice, we differ from Mr Maynard only in that we do not use frozen section examination during the operation: the reason is partly that we do not wish to accept the risk of implantation recurrence of what turns out in the end to be a benign tumour, partly because of the well-known difficulty of making an accurate diagnosis of histological type and grade of the tumour, and partly because of the fact that the less malignant tumours-the adenoid cystic carcinoma, the mucoepidermoid tumour, and the acinic cell tumour-behave in a variable fashion between the limits of very benign and very malignant without neces-
sarily any correspondence between that behaviour and the histological appearances. I strongly endorse Mr Maynard's cautious attitude towards aspiration cytology of lumps in the regions of the salivary glands. The difficulties of histological diagnosis already alluded to, even when the whole specimen is out and available to the histopathologist, plus the posssible risk of implantation recurrence, prevents both our groups from its use in potentially benign lesions. For the lesions that in clinical terms cannot be benign, we prefer a generous open biopsy before embarking on our cycle of radiotherapy-massive ablation-radiotherapy that Mr Maynard and Mr Afify have kindly referred to (2). MICHAEL HOBSLEY TD FRCS Head of Department of Surgery The Rayne Institute London
References I Nnochiri CC, Watkin GT, Hobsley M. Unremarkable parotid tumours that prove to be malignant. Br 7 Surg 1990; 77:917-18. 2 Gallegos NC, Watkin G, Cook HP, Sanders R, Hobsley M. Further evaluation of radical surgery following radiotherapy for advanced parotid carcinoma. BrJ Surg 1991;78:97-100.
