- 928-930 Smoking predisposes to parotid Br. J. Surn. 1992, Vol. 79, September,

M. Cadier, G. Wa and M. Hobsley

Department of Surgery, College and Middlesex I

adenolymphoma

Of 574 patients with previously untreated, unremarkable parotid lumps, 194 proved to have pleomorphic adenomas and 73 adenolymphornas. ABO blood group details were available in 59 and 85 per cent of patients respectively. Smoking details were available in 84per cent of a randomly chosen 46 per cent subgroup of patients with pleomorphic adenomas and in 86 per cent of all those with adenolymphomas. The incidences of smoking and of the ABO blood groups in these two diagnoses were compared with standard sources. There was no evidence that either histological diagnosis of parotid tumours was linked to an abnormal pattern of ABO blood groups. However, there was a much greater incidence of smoking among the adenolymphoma than in the pleomorphic

kin

lniversit y chool of adenoma group: o d y one o f63 patients with adenolymphoma as opposed

to 31 of 75 with pleomorphic adenoma had never smoked, while the Medicine, The Ra yne Institute, University Street, London W C l E 6JJ, UK mean number of cigarettes smoked by each patient with an Correspondence to: adenolymphoma was estimated to be 300 000 as opposed to 80 000 for Professor M. Hobsley those with pleomorphic adenoma.

An association has been suggested between cigarette smoking and parotid adenolymphoma’ , and this has been implicated in the apparently increasing incidence of this tumour in women’. In addition, several reports have suggested an association between specific parotid tumours and certain of the ABO blood groups, in p a r t i ~ u l a r ~ . ~ that pleomorphic adenomas and adenolymphomas may be linked to blood group A.

The present paper explores whether these two associations are present in patients with parotid tumours referred to this department.

control group of pleomorphic adenomas the mean age of patients was 45 years and the age range was broader (18-95 years). The sex distribution was roughly equal, and the tumour was unilateral in all cases.

The changes of incidence and the male:female ratio over successive 5-year periods for each of the two groups are shown in Figures 2 and 2 respectively. Smoking details are shown in Figures3 and 4. With the ABO blood groups there were no statistically significant differences between patients with

Patients and methods The patients studied were referred to one of the authors (M.H.) in the 24-year period from 1966 to 1989. Data were collected prospectively and entered on to index cards, subsequently being transferred to a computer database to facilitate manipulation.

A total of 574 patients with previously untreated, unremarkable, parotid lumps were treated by the department’s usual method of formal parotidectomy. On histological examination it was found that 73 were adenolymphomas and 194 pleomorphic adenomas. From the database, blood group details were available for 85 and 59 per cent of the patients respectively.

The medical records of all the patients with adenolymphoma were examined, as were 46 per cent of those of the pleomorphic adenoma group, these being randomly selected from the group on the basis of their hospital number. From these medical records smoking details were extracted; these were available in 86 and 84 per cent of the adenolymphoma and pleomorphic adenoma groups respectively.

Patients were categorized as non-smokers, ex-smokers and current smokers, and the average number of cigarettes smoked per day and duration of smoking recorded.

Several different control groups were used. The pleomorphic adenoma group served as the initial controls. However, to eliminate age-sex bias and the possibility of associations of smoking and/or blood group with pleomorphic adenoma, other control groups were also utilized. For smoking, the figures obtained were compared with similarly age-sex stratified national census figures5. For blood group, data from the local regional blood transfusion centre at Edgware (where the records of 14000 patients were available) and figures quoted for England and Wales in a standard haematological textbook6 were used.

Results The mean age at presentation with adenolymphoma was 61 (range 33-78) years. There was a large male preponderance ( 8 : l ) and the tumour was bilateral in seven patients. In the

1969-1 973 1974-1978 1979-1983 1984-1 988

Figure 1 Number of’adenolwnphomas and pleomorphic adenomas over sequentitrl ~ - ? . c L I I . prviod.7. 0. Adeno!\mphon?as: , pleoniorphic atkef7OlI In.\

4

- 3 U

f. g 2 m

X

m 1

0 L 11 1969-1 973 1974-1 9 7 8 1979-1983 1984-1 988

Figure 2 Sex ratios (A4.F) over sequential 5-year periods. 0, Adenolymphomas; H ~ pleomorphic adenomas

928 0007-1323/92/090928-03 8 1992 Butterworth-Heinemann Ltd

Smoking and parotid adenolymphoma: M. Cadier et al.

this because, first, this department acts as a national referral centre with an undeterminable catchment population, and second, the pattern of referrals is not fixed, so that any apparent increase may not be a true one. These points probably also apply to some of the other studies reported.

What could, however, be justifiably examined is the relative incidence of adenolymphoma to pleomorphic adenoma. Overall there are always more pleomorphic adenomas, and in the present series the proportion of such adenomas was actually found to be rising. This is in contrast to previous reports'.'.

The sex distribution remained relatively constant in the control groups, and although there was a slight female preponderance in the early years the distribution was roughly equal. In the adenolymphoma group there was always a male preponderance, which rose over the years from a 2: 1 to a 4: 1 ratio. This ratio is in keeping with other reports for a similar time although series reported in the 1950s and 1960s suggested a greater male preponderance (7: 1 )8,9. An increasing incidence in women has been previously suggested' and, although this cannot be confirmed in the present series, it is probably more a reflection of the small numbers involved in the early years.

An association between adenolymphoma and smoking was suggested in 1986 by Ebbs and Webb' and confirmed in 1987 by Lamelas et a1.'. In the two groups of patients in the present study, smoking habits differed dramatically. Only one of the 63 patients with adenolymphoma had never smoked, as opposed to 31 of the 75 patients in the pleomorphic adenoma control group. This shows a clear and highly significant association of adenolymphoma with cigarette smoking (1' = 55.4, 2 d.f., P < 0.001 ). Furthermore, patients with adenolymphoma were heavier smokers than those in the pleomorphic adenoma control group, not only in that they smoked more cigarettes on average per day, but also in that they had done so for many more years. The average number of cigarettes smoked by each patient with adenolymphoma was estimated as 300000, as opposed to 80000 for smokers in the control group.

Albrecht and Arzt suggested in 1910 that adenolymphoma arises as a benign neoplastic change in salivary ductal inclusions in parasalivary and intrasalivary lymph nodest4, these inclusions having been previously demonstrated by Neise in 1898 in neonates15. These findings were later confirmed in 1950 by Thompson and Bryant'. However, in 1971 AllegraI6 rejected the concept that adenolymphomas were benign neoplasms and suggested instead that they represented a manifestation of delayed hypersensitivity to metaplastic ductal epithelium, this metaplasia having arisen as a result of nutritional, metabolic or other defect. Subsequently cigarette smoke has been considered as the cause of this metaplasia'.

The high frequency of heavy smoking in the patients in this study with adenolymphoma lends support to this theory. Additionally, all seven of the patients with bilateral tumours were heavy smokers ( > 19 per day) and in the two cases in which duration had been recorded, the number of cigarettes smoked exceeded 350 000, representing a higher than average consumption even for the adenolymphoma group. The presence

Never smoked

(31 1

Ex-smoker

C u r r e n t smoker

Pleomorphic adenomas ( n = 75)

Figure 3 Smoking history

Non-smokers

>

day 63 < day 11 p e r 11 -20 p e r

Pipe >20 p e r day

Never

C u r r e n t smoker

(531

Adenolymphomas ( n = 631

Non-smoker

Pleomorphic adenomas Adenolymphomas ( n = 7 5 ) (n= 631

Figure 4 Tobacco consumption

adenolymphoma (group 0 48 per cent, A 42 per cent, B 5 per cent, AB 5 per cent), those with pleomorphic adenoma (0 51 per cent, A 36 per cent, B 9 per cent, AB 4 per cent) and patients from the Edgware transfusion centre (0 45 per cent, A 41 per cent, B 10 per cent, AB 4 per cent) ( x 2 = 2.1 and 2.2, 3 d.f., P > 0.5) (F igure 5 )

Discussion Since the original report' of parotid adenolymphoma in 1895, there have been several large retrospective reviews of this turnour'-''. The first large series in the UK was reported in 1986 when Ebbs and Webb described 57 patients with histologically confirmed adenolymphoma presenting over a 33-year period'. In this department, over a 24-year period, 73 patients with this rare tumour have been seen, making this the largest British series reported.

Previous reports have put the proportion of adeno- lymphoma at between 2 and 6 per cent of all parotid tumours". More recent reports' have suggested that the figure is around 15 per cent, although the claim has been made that this tumour may now represent one-third of all parotid neoplasms".

The changing incidence over the study period in the present series shows that in both the adenolymphoma and pleomorphic adenoma groups there was a gradual increase in the number of patients. However, it is difficult to draw conclusions from

Adenolymphorna ( n = 62)

Figure 5 Blood group distributions

Pleomorphic adenoma ( n = 115)

0 (23657)

B (5335)

A (21 630)

A B (2014)

Edgware t rans fus ion cen t re ( n= 52 636)

Br. J. Surg., Vol. 79, No. 9, September 1992 929

Smoking and parotid adenolymphoma: M. Cadier et al.

of only one non-smoker in the adenolymphoma group is striking and leads us to advise caution in accepting the diagnosis of this tumour in a non-smoker.

Following the demonstration” in 1953 of an association between gastric carcinoma and blood group A, many other tumours have been investigated for similar associations. Because salivary glands secrete ABO antigenic substances, they have naturally become a focus for such investigations.

In 1958 Cameron3 found a strong association between all salivary gland neoplasms and blood group A. He further noted a statistically significant association with parotid pleomorphic adenoma, although he could find only a non-significant trend with parotid adenolymphoma, which he attributed to the small numbers in this group. This observation was subsequently confirmed by Osbourne and De George in 1961, with ABO group A association being specifically linked to mucinous tumours (this includes both pleomorphic adenomas and aden~lymphomas)~. However, in 1971 a further study by Garrett et a1.I8 failed to support these findings, the authors suggesting that the previous reports may have employed unsatisfactory and non-comparable control groups and also had inappropriately grouped various histological types.

In the present study the available blood group data were examined for the two groups (pleomorphic adenomas and adenolymphomas) and no differences were found in the distribution of ABO blood groups. Neither was any difference found in the distribution when data were compared with those from a local regional blood transfusion centre, or with the overall distribution of blood groups in England and Wales. Although these two latter population control groups may not be comparable to patients with parotid lumps in the present study, they represent the best available. Therefore, no association was found between either pleomorphic adenoma or adenolymphoma and any of the ABO blood groups.

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199-208.

923-3 1.

388: 13-38.

799-801.

Paper accepted 10 April 1992

930 Br. J. Surg., Vol. 79, No. 9, September 1992