Malignant tumours of the submandibular salivary gland: a 15-year review

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1 British Journal of Plastic Surgery (1998), 51, The British Association of Plastic Surgeons BRITISH JOURNAL PLASTIC SURGERY Malignant tumours of the submandibular salivary gland: a 15-year review I. (3. Camilleri, C. M. Malata, N. R. McLean and C. G. Kelly* Head and Neck Unit, Department of Plastic Surgery and *Northern Regional Centre for Cancer Treatment, Newcastle General Hospital, Newcastle-upon-Tyne, UK SUMMARY. Malignant tumours of the submandibular salivary gland are rare, difficult to distinguish clinically from benign disease and often only diagnosed after initial excision of the enlarged gland. In this study of 70 patients (46 male, 24 female) with a mean age of 64 years (range 1%94), and an average duration of symptoms of 3 months, a painless submandibular swelling was the most common presentation. Of the 69 primary tumours, the most frequent histological types were adenoid cystic carcinomas (26 patients, 37%) and carcinoma ex-psa (18 patients, 26%). One tumour was metastatic in origin, arising from a parotid primary. A total of 65 patients were treated by primary excision of the gland while five patients who presented with advanced disease were treated by radiotherapy alone. Adjuvant postoperative radiotherapy was utilised in 53 (75%) of patients. After a mean follow-up of 5 years, 32 (46%) of patients are still alive. Metastatic disease accounted for 21 deaths (30%). The clinical stage at presentation was the most significant factor predicting survival. The rarity of carcinoma of the submandibular gland combined with the much more frequent occurrence of calculus obstruction, contributes to late diagnosis and delayed treatment of this condition. 1-3 Cases are frequently referred from peripheral hospitals after initial excision of the gland and this poses an obvious management problem for the specialist, as the details of the initial findings at the primary operation are frequently not clear. In addition, histology of the tumours is varied, with adenoid cystic carcinoma, the most common form of malignancy, having an unpredictable behaviour, locoregional recurrence occurring years later. Although general management protocols are available, 1,4,6 these tend to vary considerably from centre to centre. Despite the changes over the last three decades, the management of submandibular gland carcinoma remains debatable. The roles of postoperative radiotherapy and elective neck dissection ~'2'7-H are hotly disputed, with much of the controversy stemming from the limited number of patients and the relatively few published series on the topic. Patients and methods A retrospective analysis of 70 patients with tumours of the submandibular salivary gland treated at the Northern Centre for Cancer Therapy in Newcastle over 15 years ( ) was undertaken. From the clinical notes and operating records, data was collected on the source of referral, clinical presentation, diagnostic investigation, surgical and radiation management and outcome. Survival rates and disease recurrence data were used to determine the significance of independent prognostic indicators against survival and recurrence. 181 Results Malignant tumours of the submandibular gland occurred in 24 females and 46 males with a mean age at presentation of 64 years (range 17-94) and an average duration of symptoms of 3 months. Smoking more than 10 cigarettes daily was a feature in 14 (20%) patients and a painless, progressively enlarging submandibular mass was the most common mode of presentation (50 patients, 71%). Pain was only present in 13 (19%) of the patients at presentation and in two cases the tumour was discovered during investigation for unrelated disease. Two elderly patients presented late with fungating tumours (Fig. 1). The pattern of referral of these patients showed that the great majority (58 patients, 83%) were referred after excision of the gland on the presumption that benign disease was the cause of the enlargement. None of these cases had any attempt at histological diagnosis made prior to surgery. Fine needle aspiration cytology (FNAC) was performed in all 12 (17%) patients who presented primarily to our unit, giving a 90% sensitivity (l 1 patients) in diagnosing malignancy. Conclusive histology was however only obtained in 8 (65%) of cases. CT or MRI scans were utilised in 64 patients (91%) to delineate the extent of local disease and neck node status. Because of the evolution of the histological classification of salivary gland neoplasms, all cases in this series were reclassified according to the 1990 WHO classification& Adenoid cystic carcinoma was the most common form of malignancy (26 patients, 37%), followed by carcinoma ex-psa i.e. carcinoma arising in pre-existing pleomorphic adenoma (18 patients, 26%) (Table 1). Adenoid cystic carcinoma also showed an even distribution across the age groups (Figs 2-5) in contrast to

2 182 British Journal of Plastic Surgery other histological types which exhibited an increasing incidence with age. Clinical staging of disease was performed using the American Joint Committee on Cancer staging system (Tables 2, 3) which takes into account tumour size, local extension, spread to regional lymph nodes and distant metastases. 13Of the 70 patients in this series, 5 patients (8%) were classified QAnaplastic 1Adenoid Cystic madenoca 12 [ ] Ca ex-psa u 10 'S I m Mucoepidermoid ~ Age Fig. 2 Fig. 1 Figure 1--Advanced late presentation of anaplastic carcinoma needing airway diversion soon after admission. Table 1 Histology of salivary gland carcinoma B m '1! 8 No. (%) Clinical stage IV. i I,=-----! Adenoid cystic carcinoma Carcinoma ex-psa Adenocarcinoma Mucoepidermoid carcinoma Low grade High grade Anaplastic carcinoma Secondary 26 (37) 18 (26) 9 (13) 9 (13) (10) 1 (1.5) [ 2-o I 4o 8o 10u Survival (months) Fig. 3 Figure 2--Age distribution of submandibular gland carcinoma. Figure 3--Cumulative survival of salivary gland malignancies (Kaplan Meier analysis). Fig. 4 Figure 4~-Adenoid cystic carcinoma showingperineural invasion (photomicrograph). Figure 5--Adenocarcinoma developingin long-standing PSA (photomicrograph). Fig. 5

3 Malignant tumours of the submandibular salivary gland 183 Table 2 Clinical staging of salivary gland tumours Primary turnout (T) TX TO Primary tumour cannot be assessed No evidence of primary tumour T1 Tumour 2 cm or less in greatest dimension T2 Tumour more than 2 cm but not more than 4 cm in greatest dimension T3 T4 Tumour more than 4 cm but not more than 6 cm in greatest dimension Tumour more than 6 cm in greatest dimension Regional lymph nodes (N) NX Regional lymph nodes cannot be assessed NO No regional lymph node metastasis N1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension N2 Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph node, none more than 6 cm in greatest dimension, or in bilateral or contralateral!ymph nodes, none more than 6 cm in greatest dimension N2a Metastasis in ~,single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension N2b Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension N2c Metastasis in bilateral or contralateral lymph nodes, none more than 6 em in greatest dimension N3 Metastasis in a lymph node more than 6 cm in greatest dimension Distant metastasis (M) MX Presence of distant metastasis cannot be assessed MO No distant metastases M 1 Distant metastasis Note: All categories are subdivided (a) no local extension; (b) local extension. Local extension is clinical or macroscopic evidence of invasion of skin, soft tissues, bone, or nerve. Microscopic evidence alone is not local extension for classification purposes. Table 3 Stage grouping of salivary gland tumours Stage I Tla NO M0 T2a NO M0 Stage II Tlb NO NO T2b NO M0 T3a NO M0 Stage IlI Stage IV T3b NO M0 T4a NO M0 AnyT (except T4b) N1 M0 T4b AnyT Any N N2, N3 M0 M0 AnyT Any N M 1 as stage I, 18 patients (25%) as stage II, 29 patients (42%) as stage III and 18 patients (25%) as having stage 1V disease. Treatment The treatment protocol was largely based on primary surgery with adjuvant radiation therapy. Excision of the gland was performed in 65 patients and tumour clearance frequently required excision of adjacent structures such as the mylohyoid or digastric muscles, hypoglossal or lingual nerve, the lower border of the mandible in two cases and the floor of the mouth in four cases. Five patients (4 carcinoma ex-psa, 1 mucoepidermoid carcinoma) were treated by radiotherapy alone because they were medically unfit for major surgery. Prophylactic neck dissection was not performed and 14 patients (20%) who presented with positive necks had modified radical neck dissection at the time of primary surgery. Indications for neck dissection included positive nodes, high grade malignancy, perineural of perivascular infiltration an extracapsular spread of the primary tumour. The 13 patients (19%) who developed regional recurrence were managed by modified radical neck dissection and adjuvant radiotherapy. Local recurrence (19 patients, 27%) was treated aggressively with wide local excision. In three of these cases closure required free radial forearm flap reconstruction. Surgery was combined with brachytherapy if the grade of the tumour was high, if perineural or microvascular infiltration was present histologically or if external beam radiation had been given previously (12 cases, 17%). Follow-up The mean follow-up period was 9 years (range 3-17 years) and 33 (47%) of patients are currently alive and clinically disease free. Two patients (3%) are alive but have metastatic lung disease and seven patients (10%) died from unrelated causes. The cumulative 5-year survival rate was 47% and at 10 years this had dropped to 26%. Prognostic variables The single most significant prognostic indicator in our series was the clinical stage at presentation. Stage I disease carried a good prognosis, with an 85% 5-year survival. Stage II disease had a mean survival of 64.8 months. In contrast, advanced (stage IV) disease had a dismal prognosis, with only 20% of patients surviving 5 years in this series (mean survival 6.36, standard error 1.88, Kaplan Meier analysis (Fig. 3). Pain on initial presentation was associated with a poorer outcome.

4 184 British Journal of Plastic Surgery Discussion Primary malignancies of the submandibular salivary gland are rare, constituting only 8% of all salivary gland malignancies? 6-~8 Because of this, and the fact that their presentation is frequently indistinguishable from benign disease, the management of this disease is particularly difficult for the surgeon and also accounts in part, for a worse prognosis in comparison with malignancies of the parotid gland. In addition, treatment protocols tend to vary significantly from centre to centre and there is controversy regarding the benefits of adjuvant radiation therapy 2,7,22 and neck dissection.l,2,6.7,8. ~4 With regard to presentation, our findings confirmed the observations reported in other studies, although pain as the initial presenting symptom was less frequenty Adenoid cystic carcinoma (Table 1) was the most frequently encountered malignancy in this and in other series, 2,7,~9'2 however carcinoma ex-psa featured highly in this study. The majority of these patients (55, 79%) were referred from district hospitals to the head and neck oncology unit and this may have contributed to some delay in their definitive management. Diagnostic FNAC was performed on all 12 primary referrals and this was found to be 90% accurate in diagnosing malignancy, although conclusive histology was obtained in only 8 (65%) of FNAC samples. CT and/or MRI scanning were beneficial in delineating the extent of local disease and the status of the neck lymph nodes, although MR! can be associated with a percentage of false positive resurs, because it cannot differentiate between metastatic and reactive nodes? Plain radiographs were found useful in giving information about bony involvement and for the planning of bony reconstruction. For primary disease, we advise a policy of wide local excision of the gland followed by adjuvant postoperative radiotherapy if there is perineural or microvascular infiltration, if the tumour is high grade or advanced (stage III and IV), in close or positive resection margins and in the presence of cervical lymph node metastases at presentation. For advanced tumours, surgical resection should involve excision of adjacent structures such as the mylohyoid or digastric muscles, hypoglossal or lingual nerves, floor of the mouth or the lower rim of the mandibley Modified radical neck dissection is only employed in the case of clinically or MRI positive nodes. In contrast Gronich et al advocate supraomohyoid neck dissection even in TI and TII tumours and radical neck dissection for palpable nodes or advanced disease with extraglandular spread? In patients presenting with recurrent disease, aggressive surgical excision with reconstruction, which may require free tissue transfer, is employed together with adjuvant tele or brachytherapy. In patients who are referred with marginally excised tumours, we adopt a policy of giving adjuvant radiotherapy only, unless the tumour is high grade, perineural invasion is present or cervical lymph nodes are present, in which case a similar treatment approach as for recurrent disease is adopted. The locoregional recurrence rate of 46% encountered in this series is comparable to other studies. 3'7'8'9'~9 The clinical stage at presentation is an undisputed significant factor in the overall prognosis of the disease 7'27 and predictably, pain on presentation in 13 patients (19%), though rare in this study also meant a worse prognosis, and this was confined to the higher grade tumours. Unlike in some studies, 26 inadequacy of primary excision of the tumour was also a positive predictor of local recurrence. The cumulative 5- and 10-year survival rates compare favourably with the results from other centres but are still lower than those reported for parotid malignancy. ~2,2~-2~ The relatively high local recurrence rate and the greater percentage of high grade malignancy in the submandibular gland suggests that more radical primary treatment is required which may not be available in district hospitals without a specialised cancer centre. Conclusion In this retrospective review of submandibular salivary gland malignancy, a high incidence of carcinoma ex-psa was found. A combination of fine needle aspiration cytology and CT or MRI gives accurate preoperative information about the nature and extent of disease. Primary wide surgical resection combined with adjuvant radiotherapy is the treatment of choice and we recommend early referral to a regional head and neck centre when malignancy of the gland is suspected, as this seems to offer the best survival for the patient. References 1. McGregor I. Cancer of The Head and Neck. Edinburgh: Churchill Livingstone, Eneroth CM, Hjertman L, Moberger G. Malignant tumours of the submandibular gland. Acta Otolaryngol 1967; 64: Hui KK, Luna MA, Batsakis JG, Ordonez NG, Weber R. Undifferentiated carcinomas of the major salivary glands. Oral Surg Oral Med Oral Pathol 1990; 69: Andersen L J, Therkildsen MH, Ockelmann HH, Bentzen JD, Schiodt T, Hansen HS. Malignant epithelial tumors in the minor salivary glands, the submandibular gland, and the sublingual gland. Prognostic factors and treatment results. Cancer 1991; 68: Granick MS, Hanna DC, Douglas-Newton E. Management of benign and malignant primary salivary gland tumours. In Georgiade et al: Textbook of plastic, maxillofacial and reconstructive surgery. Baltimore: Williams and Wilkins, Trail ML, Lubritz J. Tumors of the submandibular gland. Laryngoscope 1974; 84: t225-32, 8. Spiro RH, Hajdu SI, Strong EW. Tumors of the submaxillary gland. Am J Surg 1976; 132: Byun YS, Fayos JV, Kim YH. Management of malignant salivary gland tumors. Laryngoscope 1980; 90: Wilson GR, McLean NR, Chippindale A, Campbell RSD, Soames JV, Reed ME The role of MRI scanning in the diagnosis of cervical lymphadenopathy. Br J Plast Surg 1994; 47: 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 failures. Cancer 1977; 40:

5 Malignant tumours of the submandibular salivary gland Seifert G, Brocheriou C, Cardesa A, Eveson JW. WHO International Histological Classification of Tumours: Tentative histological classification of salivary gland tumours. Pathol Res Pract 1990; 186: Beahrs OH, Henson DE, Hutter RVP, Myers MH. Manual for Staging of Cancer, 3rd ed. Philadelphia: Lippincott, Shah JP, Andersen PE. Evolving role of modifications in neck dissection for oral squamous carcinoma. Br J Oral Maxillofac Surg 1995; 33: 3-8, 15. Murray GD. Statistical aspects of research methodology. Br J Surg 1991; 78: Thackray A. Salivary gland tumours. Proc R Soc Med 1968; 61: Eneroth CM. Salivary gland tumors in the parotid gland, submandibular gland, and the palate region. Cancer 1971; 27: Polayes I. Surgical treatment of diseases of the salivary glands. McCarthy's Plastic Surgery. Philadelphia: Saunders, Afify SE, Maynard JD. Carcinoma of themajor salivary glands. Ann R Coll Surg Eng 1992; 74: Spiro RH, Huvos AG, Strong EW. Adenoid cystic carcinoma of salivary origin. A clinicopathologic study of 242 cases. Am J Surg 1974; 128: Shah JR Ihde JK. Salivary gland tumors. Curr Prob Surg 1990; 27: Simpson JR, Matsuba HM, Thawley SE, Mauney M. Improved treatment of salivary adenocarcinomas: planned combined surgery and irradiation. Laryngoscope 1986; 96: Witten J, Hybert F, Hansen HS. Treatment of malignant tumors in the parotid glands. Cancer 1990; 65: Parry J, Cummins C, Redman V, Wilson S, Woodman C. Incidence and survival of malignant parotid tumours in the West Midlands Region Clinical Oncol 1993; 5: Eveson JW. Cawson RA. Salivary Gland Tumours. A review of 2410 cases with particular reference to histological types, site, age and sex distribution. J Pathol 1985; 146: Spiro RH, Huvos AG, Strong EW Adenocarcinoma of salivary origin. Clinicopathologic study of 204 patients. Am J Surg 1982; 144: The Authors I. G. Camilleri C. M. Malata N. R. McLean Head and Neck Unit, Department of Plastic Surgery C. G. Kelly Northern Regional Centre for Cancer Treatment Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne NE4 6BE, UK. Correspondence to C. G. Kelly Presented at the Winter Meeting of the British Association of Plastic Surgeons, London, December Paper received 2 August Accepted 20 January 1998, after revision.