The ameloblastoma, the controversial approach to therapy

j. max.-fac. Surg. 13 (1985) J. max.-fac. Surg. 13 (1985) 79-84 © Georg Thieme Verlag Stuttgart. New York

The Ameloblastoma, the Controversial Approach to Therapy Hellmutb Miiller, Pieter J. Slootweg Department of Maxillofacial Surgery (Head: Prof. Dr. P. Egyedi, M.D., D.M.D.) Department of Oral Pathology (Head: Dr. P. J. Slootweg, M.D., D.M.D.) State University of Utrecht, The Netherlands Submitted 7. 12. 83; Accepted 12.7. 84

79

Summary An investigation into the length of time which elapses after the treatment of an ameloblastoma before a recurrence becomes visible, has established that this only exceeds 5 years in 5 % of cases. In this study the findings after a follow-up period of at least 5 years after conservative or radical therapy have been extracted from the literature and compared with those of the authors' own series of 84 cases. It is concluded that the recurrence rate is 75 % in the cases of multilocular ameloblastomas treated conservatively. Following radical therapy the recurrence rate is 15 %. Conservative treatment of unilocular ameloblastomas can be expected to result in a recurrence rate of 20 %.

Key-Words Introduction Since the first detailed description of an ameloblastoma was provided by Koning in 1825, (Haneveld, 1977), no other tumour of the jaw has received so much attention in the literature. Nevertheless there is still no unanimity regarding its treatment. Some favour a conservative approach while others advise radical therapy. In our view, this division of opinion is mainly due to the following factors: 1. Many publications fail to make sufficient allowance for the fact that an ameloblastoma is a slowly developing tumour (Pilz and Nitzschke, 1979), consequently their periods of follow-up are far too short. 2. Histological criteria for ameloblastomas were in the past poorly defined (Sehdev et al., 1974). The number of such turnouts incorrectly diagnosed is variously stated as 50 % (Small and Waldron,1955), 26 % (Masson et al., 1959) and 63 % (Larsson and Almerdn, 1978). 3. No distinction is made between unilocular and multilocular ameloblastomas. Many authors have indicated that the recurrence rate after conservative treatment appears to be much lower for unilocular than for multilocufar tumours (Young and Robinson, 1962; Worth, 1963; Lee, 1970; Byrd et al., 1973; Daramola et al., 1975; Robinson and Martinez, 1977; Shteyer et al., 1978; Hardt and Steinhiiuser, 1979; Gardner and Pecak, 1980; McMiIfan and Smillie, 1981; Mi~ller, 1983). In a series of articles in this journal the results of a followup of 84 ameloblastomas treated in the Department of Maxillofacial Surgery in Utrecht, between 1935 and 1982, will be reported. The objects of this investigation have been: 1. To establish the recurrence-free interval after removal of an ameloblastoma. 2. To select from the literature those publications in which the length of follow-up conforms with the minimal period established in (1). 3. To determine the percentage of recurrences arising after treatment of an ameloblastoma in our department. 4. To re-assess the histological criteria applied to the material provided by the investigation. 5. To study tumour growth inside and outside the bone. 6. To arrive at a standard form of treatment for unilocular and multilocular ameloblastomas. Points 1-3 are considered in this article.

Ameloblastoma - Follow-up - Conservative Treatment - Radical Treatment

Material and Methods Between the years 1935 and 1982, ameloblastoma was diagnosed in 97 patients. In 10 cases insufficient data were available for meaningful evaluation. A further 3 patients were excluded from the study because after re-examination of the histology the diagnosis was changed to keratocyst in two of them, and a Pindborg tumour in the third. Eightyfour patients remained to be evaluated. In order to determine the recurrence-free period after treatment, the interval between operation and recurrent turnout was established. Seventy-nine recurrences in 45 patients could be evaluated in this way. Attention was also given to the degree of continuity in the follow-up of these patients. With the object of obtaining as homogeneous a collection of cases as possible, the 84 patients were divided into two groups. Group 1 contains those patients who were treated in Utrecht for their primary tumour, and Group 2 those patients who were referred to Utrecht with a recurrence after primary treatment elsewhere (Table 1). Our definition of radical treatment was a procedure in which the intention was to remove the tumour in toto together with a margin of surrounding healthy tissue. In the operation the tumour tissue is not visualized. Any procedure in which the intention differed from this was considered to be conservative. The incidence of recurrences after these two types of treatment was established. For reasons already mentioned in the introduction, cases have been divided into uni- and mul-

Table 1

Treatment of patients Conservative

Radical

Total

Primary treatment in Utrecht (group 1) Primary treatment elsewhere (group 2)

37

17

54

14

16

30

Total

51

33

84

80

]. max.-fac. Surg. 13 (1985)

HeIlmuth M~iller, Pieter J. Slootweg Number of recurrences

Number of recurrences

15

8~ 76-

10

5 43.

5

2-

15

I0

20

15

1

2'5

2

3

4

5

6

7

8

g

10 11 12 13

Follow up in years

Follow up in years

Fig. 1 The period of time after operation before a recurrence was diagnosed.

Fig. 2 The length of the recurrence-free interval in 22 patients in whom follow-up was uninterrupted.

Number of recurrences

tilocular ameloblastomas. Whether the turnout was uni- or multilocular depended on the gross appearance at operation. The incidence of recurrences after primary conservative treatment in Utrecht of uni- and multilocular ameloblastomas was also established. These 84 patients underwent a total of 186 procedures, the results of which are discussed separately.

15

I0

Results

The Recurrence-free Interval

5

I0

15

20

25

Follow up in years Fig. 3 The broken curve represents the period of time after operation before a recurrence was diagnosed in patients in whom observation was interrupted.

Table 2

Articles from authors favouring conservative therapy Total no. Consercases vative

Recurrencefree >5 year conservative

Author

Year

1. Stout et al. 2. Monks 3. Huffman and Thatcher 4, Robinson and Martinez 5. Crawteyand Levin 6. Vedtofte et al.

1963 1964 1974

5 9 4

5 9 4

1977

20

20

7/11

64 %)

1978

4

4

0/-3

0 %)

1978

12

12

5/ 8

63%)

2/ 4 ( 5 0 % ) 3/ 4 ( 7 5 % ) 1/ 1 (100%)

follow-up <5 year conservative 1 5 3

Fig. 1 shows the period of time after operation before a recurrence was diagnosed. It varied from 1-25 years. Although the majority of recurrences occurred in the early years after treatment, some arose very much later. However, the type of follow-up must be taken into consideration. Where patients attended irregularly, the curve in Fig. 1 would be more an indication of the accuracy of the followup examination than of the true time at which the recurrence first revealed itself. Fig. 2 shows the length of the recurrence-free interval in 22 patients in whom follow-up was uninterrupted. In 95 % of these 22 patients the recurrence was diagnosed within the first five years after treatment. Only an occasional tumour recurred later. In Fig. 3 the broken curve represents the recurrence-free interval in patients in whom observation was interrupted. If Fig. 2 and 3 are compared it can be seen that some very late recurrences occurred in our series also. However, these were seen in patients who had not been kept under continuous observation. Probably the diagnosis would have been made many years earlier had the patient attended regularly for follow-up. It must be concluded that a follow-up period of at least 5 years is required before the results of treatment of ameloblastomas can be assessed.

Literature Tables 2 and 3 represent an analysis of articles selected from the literature in which the results of treatment for ameloblastoma are reported after, so far as possible, a minimum follow-up period of 5 years.

The Ameloblastoma, the Controversial Approach to Therapy Table 3

J. max.-/)c. Surg. 13 (1985)

81

Articles from authors favouring radical therapy

Author

Year

Total no. Consercases vative

1. 2. 3. 4, 5, 6. 7. 8. 9. 10,

1954 1967 1968 1969 1972 1972 1974 1976 1980 1980

40 34 153 44 101 124 88 19 27 74

Rankow and Hickey Beckerund Pert/ Vandenbussche Sigrist Koch Mehlisch et al. Sehdevet al. Krgnzl et al, Tsaknis and Nelson Adekeye

20 6 93 36 19 98 15 13 7 -

Recurrence-free >5 years conservative 0/ 2/ 16/ 2/ 8/ 23/ 4/ 6/ 1/

0%) 20 2 100%) 69 23%) 7%) 31 19 42 %) 86 27%) 14 29 %) 9 66%) 7 14%)

Follow-up <5 years conservative

4 24 5 12 1 4

Radical

Recurrence-free >5 years radical

20 28 60 8 82 26 73 6 20 74

17/ 11/ 27/ 2/ 68/ 11/ 33/ 3/ 15/ 31/

20(85%) 15(73%) 31 ( 8 7 % ) 2(100%) 82 ( 83 %) 14(79%) 44 ( 75 %) 3(100%) 19(79%) 34 ( 9 1 % )

10 7

10/ 10 100%) 6/ 7 86%)

Mean Follow-up conservative

1 i. Goldwyn eta}. 12. Shatkin and Hofmeister 13. Hartman 14. Smatland Waldron

1963 1965

26 20

16 13

4/ 16 2/ 13

25 %) 15%)

1974 1955

13 315

8 193

0/ 8 104/193

0%) 54%)

4/ 5 107/122

5 122

4.7

80%) 88%)

Follow-up < 5 years radical * 13 29 6 12 29 3 1 30 Mean Followup radical 18 1918-1963 11.6 5.1"*

* figures after correction by Hickey et at. (1956) and Hoffman et al. (1968). ** only maxillary tumours.

Table 4

Results of Utrecht Series Total no. cases

Primary treatment in Utrecht (Group 1) Primary treatment elsewhere (Group 2)

Conservative

radical

Recurrence-free > 5 years conservative radical

Follow-up <5 years conservative

radical

54

37

17

12/25 (48%)

6/ 8 (75%)

12

9

30

14

16

3/11 (27%)

11/12 (92%)

3

4

In Table 2, the results of those authors favouring conservative therapy are reviewed while in Table 3 the results of those preferring radical therapy are shown. Results after conservative and radical therapy are compared in Table 3 after a minimum 5 year follow-up period.

Our Treatment Results The results of our own series of patients (group 1 and 2) are analysed in a similar manner in Table 4. There were 54 patients in Group 1, 37 of whom underwent conservative and 17 underwent radical therapy. Of the 37 patients who underwent conservative therapy, 12 failed to complete the minimum 5 year follow-up. Of the remaining 25 patients, 12 (48 %) were recurrence-free after more than 5 years and 13 (52 %) developed a recurrence. Among the 17 patients who underwent radical therapy, 9 failed to complete the minimum 5 year follow-up. Of the remaining 8 patients, 6 (75 %) were recurrence-flee after more than 5 years and 2 patients (25 %) developed a recurrence. One of these latter 2 patients had had a bone transplant 3 months before the radical operation and the recurrence was diagnosed within the bone transplant 25years later! The other patient had undergone a hemimaxillectomy during which tumour tissue was found in the orbital fossa very close to the ethmoid. Further

resection assisted by frozen sections failed to prevent a recurrence in the ethmoid. There were 30 patients in group 2, of whom 14 underwent conservative therapy and 16 radical therapy. Of the 14 patients treated conservatively, 3 failed to complete the minimum 5 years of follow-up. Of the remaining 11 patients, 3 (27%) were recurrence-flee after more than 5 years and 8 (73 %) developed a recurrence. Of the 16 patients who underwent radical therapy, 4 failed to complete the minimum 5 years follow-up. Of the remaining 12 patients, 11 (92 %) were recurrence-flee after more than 5 years and one patient (8 %) developed a recurrence. In this last patient the turnout extended from the skull base into the contralateral half of the mandible (Fig. 4).

Treatment of Recurrent Tumours In total, 45 patients out of group 1 and 2 developed recurrence after the very first treatment (15 patients of group 1 and all patients of group 2, because group 2 were all recurrences of primary treatment elsewhere). Forty-three of these patients had been treated conservatively and two radically. One of the latter 2 patients refused further treatment. The other was treated conservatively and has remained turnout-free for 12 years. Twenty-seven of the 43 patients treated by conservative therapy ultimately

82

J. max.-fac. Surg. 13 (1985)

Hellmuth Miiller, Pieter J. Slootweg underwent a radical operation, sometimes after repeated conservative procedures. The results are shown in Table 5. Of the 16 patients who developed a recurrence after conservative therapy, but did not subsequently undergo a radical operation: one patient refused further treatment, 8 patients disappeared from follow-up after their last conservative treatment, 1 died from an inoperable recurrence at the base of the skull 7 years later, and 6 patients remain recurrencefree more than 5 years after their last conservative treatment.

Total Number of Procedures It is important to establish the average number of procedures which appear necessary to ensure a recurrence-free period of more than 5 years. Table 6 shows the results of all conservative and radical procedures. Eighty-four patients underwent a total of 186 procedures. A recurrence-flee period of more than 5 years occurred in 16 % of the patients treated conservatively. After a radical procedure the incidence was 80 %. Table 7 shows the results of conservative therapy for primary tumours treated in Utrecht when these were subdivided into unilocular and multilocular ameloblastomas. In 12 of the 37 patients the follow-up period was less than 5 years. Of the remaining 25 patients, 10 had unilocular- and 15 had multilocular ameloblastomas. Two (20 %) of the 10 unilocular tumours recurred and 8 patients (80 %) were recurrence-free after more than 5 years. Eleven (63 %) of the 15 muttilocular tumours recurred and 4 patients (27 %) were recurrence-free after more than 5 years. Discussion Fig. 4 The resection specimen of a large tumour entended from the skull base into the contratateral half of the mandible.

Table 5

Results of radical treatment of recurrent tumours

No. patients

Recurrence-free > 5 years

Follow-up < 5 years

27

18/20 (90 %)

7 (5, follow-up too short; 1, died postoperatively; 1, disappeared from follow-up)

Table 6

The results of all conservative and radical procedures

Conservative Radical

Table 7

Total no. cases

Recurrence-free Follow-up > 5 year < 5 year

140 46

19/119 (16%) 24/ 30 (80%)

21 16

The results of conservative therapy for primary tumours

Total no. cases

Recurrence-free > 5 y e a r s un[Iocular multilocular

Follow-up < 5 years

37

8/10 (80%)

12

4/15 (27%)

Many of the publications to be found in the literature contain premature conclusions regarding the results of various forms of treatment for ameloblastomas, since the period of follow-up has been too short. This investigation has shown that only results obtained after follow-up for a minimum period of 5 years can be considered to be significant. A study of the results reported after conservative and radical therapy fails to reveal any publication which shows that ameloblastomas can be treated successfully conservatively. Table 2 indicates that Robinson and Martinez (1977), after the most rigorous selection of material, concluded that unilocular tumours are less inclined to recur after conservative treatment than are multilocular and solid turnours. Their incidence of recurrence-free patients was 6 4 % . Vedtofte et al. (1978), reported an identical percentage, again after careful selection of their material. Excluded from their series were: a. Tumours which had invaded the bony cortex of the lower border of the mandible. b. Tumours which showed extensive multilocular radiolucent areas on X-ray. c. Tumours invading soft tissues. d. Maxillary tumours. e. Recurrent tumours. The results of conservative compared with radical treatment speak for themselves (Table 3). Certain percentages are striking. Becker und Pertl (1967) and Koch (1972) only treated small, unilocular ameloblastomas conservatively. Although Kriinzl et al. (1976) report a low incidence of recurrent turnouts after conservative therapy, these authors go on to say: " . . . although in earlier years conservative

The A m e l o b l a s t o m a , the Controversial A p p r o a c h to Therapy

operation for tumour removal were often performed with good results, more recently preference has been given to radical extirpation of the affected bone together with resection of healthy surrounding tissue." The reason for the change in therapeutic approach after such a low recurrence rate is not clear. Small and Waldron's article in 1955 is included in Table 3 because it is so widely quoted. They reported the recurrence-free incidence after conservative treatment to be 54 %. However, the follow-up period was on the short side, consisting of an average of 4.7 years after conservative, and an average of 5.1 years after radical therapy. Moreover many of the tumours in this investigation were stated to be "non-ameloblastomas". The authors themselves state: "The reviewer is at a disadvantage in attempting to be critical of a report and not having first hand information. As a result any case that was stated to be an ameloblastoma was accepted." Tables 2 and 3 show an apparent recurrence rate of around 75 % after conservative treatment compared to around 15 % after radical treatment. It can be seen from Table 4 that the recurrence-free percentage after conservative therapy in patients whose primary was treated in Utrecht (group 1), was 48 %. This percentage is high in comparison with published reports but it is due to our method of patient selection. All unilocular ameloblastomas in our series were treated conservatively. Table 7 shows the difference in the results of treatment of unilocular and multilocular tumours. After over 5 years, 80 % of unilocular tumours are recurrence-free compared to only 27 % of multilocular turnouts. These percentages agree with those found in the literature. The 2 7 % recurrence-free rate for multilocular tumours treated conservatively in the group of patients whose primary tumour was treated in Utrecht (group 1), is in agreement with the 27 % recurrence-free rate in the group of patients treated for a secondary in Utrecht after treatment of the primary elsewhere (group 2), since if unilocular tumours have little tendency to recur, they will scarcely, if ever, be found in such a group of patients. The clinical problem of a swelling of the jaw diagnosed as a cyst but found after operation to be an ameloblastoma histologically, only occurred in our series in the case of unilocular ameloblastomas. Both our findings and the literature reports justify no further treatment of these cases but observation only. Such patients must be most rigorously followed up since the occasional recurrence has been known to occur (Small et al. 1958). Our own results as well as those of others show that radical surgical treatment of multilocular ameloblastomas can prevent their otherwise frequent recurrence. N o t only is the incidence of tumourfree patients far higher after radical therapy than after conservative treatment but, in addition, the majority (63 %) of patients who underwent conservative treatment had to undergo a radical operation later. The ineffectiveness of conservative therapy for multilocular ameloblastomas is illustrated by the large number of procedures to which such patients were subjected before a 5 year recurrence-free period could be obtained (Table 6).

Conclusion Since the length of the follow-up period is not mentioned, many series reported in the literature are of limited value in

J. max.-fac. Surg. ~_,~( t 985)

83

determining the percentage of patients who remain recurrence-free after various treatment modalities for ameloblastomas. The same applies to case reports, of which the follow-up is usually far too short. Investigation of the period which elapses after treatment before a recurrence is revealed, suggests that follow-up for at least 5 years is obligatory. The majority of tumours recur within this time. Conservative treatment of multilocnlar ameloblastomas appears to result in a recurrence rate of 75 %, judged by our own cases and those by others. Radical therapy reduces the incidence of recurrence to 15 %. A recurrence rate of 20 % is to be expected after conservative treatment of unilocular ameloblastomas.

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J. max.-fac. Surg. 13 (1985)

Miiller, H.: Het ameloblastoom, een klinisch en histopathologisch onderzoek. Thesis Utrecht 1983 Pilz, G., M. Nitzschhe: Ober die Sp/itrezidivierung der Ameloblastome. Stomatol. DDR 29 (1979) 107 Rankow, R. M., M. J. Hickey: Adamantinoma of the mandible: Analysis of surgical treatment. Surgery 36 (1954) 713 Robinson, L., M. G. Martinez: Unicystic ameloblastoma. Cancer 40 (1977) 2278 Shatkin, S., F. S. Hoffmeister: Ameloblastoma: a rational approach to therapy. Oral Surg. 20 (1965) 421 Sehdev, M. K., A. G. Huvos, E. W. Strong, F. P. Gerold, G. W. Willis: Ameloblastoma of maxilla and mandible. Cancer 33 (1974) 324 Shteyer, A., J. Lustmann, J. Lewin-Epstein: The mural ameloblastoma. J. Oral Surg. 36 (1978) 866 Sigrist, M. A.: Zur Histopathologie und Klinik des Kieferameloblastoms. Thesis Z/irich 1969 Small, G. S., C. W. Lattner, C. A. Waldron: Ameloblastoma of the mandible, simulating a radicular cyst. J. Oral Surg. 16 (1958) 231 Small, L A., C. A. Waldron: Ameloblastomas of the jaws. Oral Surg. 8 (1955) 281

Hellmuth Miiller, Pieter J. Slootweg: The Ameloblastoma Stout, R. A., J. B. Lynch, S. R. Lewis: The conservative surgical approach to ameloblastomas of the mandible. Plast. and Reconstr. Surg. 31 (1963) 554 Tsaknis, P. J., J. F. Nelson: The maxillary ameloblastoma. J. Oral. Surg. 38 (1980) 336 Vandenbussche, F.: Les tumeurs ameloblastiques des maxillaires. Thesis Lille 1968 Vedtofte, P., E. Hjorting-Hansen, B. Neumann-Jensen, B. RoedPetersen: Conservative surgical treatment on mandibular ameloblastomas. Int. J. Oral Surg. 7 (1978) 156 Worth, H. M.: Principles and practice of oral radiologic interpretation. Year Book Medical Publishers Chicago (1963) 476 Young, D. R., M. Robinson: Ameloblastomas in children. Oral Surg. 15 (1962) 1155 Dr. H. Mi~ller, M.D., D.M.D. Kliniek voor Mondziekten en Kaakchirurgie Aeadernisch Ziekenhuis Utrecht Catharijnesingel 101 3511 GV Utrecht The Netherlands