Ameloblastoma: A clinical, radiographic, and histopathologic analysis of 71 cases

Su-Gwan Kim, DDS, PhD,a and Hyun-Seon Jang, DDS, PhD,b Kwang-Ju, Korea
CHOSUN UNIVERSITY

Objectives. The purpose of this study was to compare the clinical, radiologic, and histopathologic features of 71 intraosseous
ameloblastomas.

Study design. Data with respect to the patients ages, sex, tumor locations, and surgical treatment history, as well as the radiographic findings and number of recurrences, were analyzed. The histologic types of and radiologic findings regarding tumors with higher recurrence rates were also investigated. Results. The patients ages at biopsy ranged from 11 to 70 years (mean, 30.4 years). Thirty-nine (54.9%) of the 71 subjects were males, and 32 (45.1%) were females. Sixty-two (87.3%) of the 71 ameloblastomas were located in the mandible. Swelling was the most common symptom and was experienced by 27 (38.0%) patients. Radiographically, 42 (59.2%) of the 71 tumors were unilocular with a well-demarcated border. Of the remaining 29 cases, 14 were multilocular, 2 were of soapbubble shape, and 13 were unknown in appearance. The most common histologic pattern was plexiform, rather than follicular or acanthomatous. Sixteen cases of ameloblastoma had developed in a cyst. The overall recurrence rate was 21.1%, and the average age of the patient at recurrence was 26.4 years. Conclusions. When the diagnosis of ameloblastoma in young people remains in doubt after clinical and radiologic examination, a biopsy is necessary. Long-term follow-up at regular intervals after surgery is also recommended.

(Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:649-53)

Ameloblastomas are an enigmatic group of oral tumors. Their name implies a resemblance to cells of the enamel-forming organ. The general agreement that ameloblastomas are odontogenic in origin occurs largely on the basis of the histologic similarities of the tumor and the developing enamel organ.1-5 Ameloblastomas in young people (ie, those 19 years old and younger) are thought to be rare. They account for approximately 10% to 15% of all reported cases of ameloblastoma.6,7 Kahn8 is generally credited with proposing the theory that an ameloblastoma arises in a dentigerous cyst. Numerous authors have confirmed this, describing their findings in case reports; in addition, several articles have discussed possible pathogenic mechanisms.9-11 Several causative factors have been proposed, including (1) nonspecific irritating factors such as extraction, caries, trauma, infection, inflammation, or tooth eruption; (2) nutritional deficit disorders; and (3) viral pathogenesis.12 The plexiform-unicystic pattern is less aggressive and has a significantly lower recurrence rate. Robinson and
Supported by research grants from Brain Korea 21. aAssistant Professor, Department of Oral and Maxillofacial Surgery, Oral Biology Research Institute, College of Dentistry, Chosun University. bLecturer, Department of Oral Pathology, College of Dentistry, Chosun University. Received for publication Jul 13, 2000; returned for revision Oct 26, 2000; accepted for publication Jan 4, 2001. Copyright 2001 by Mosby, Inc. 1079-2104/2001/$35.00 + 0 7/12/114160 doi:10.1067/moe.2001.114160

Martinez13 studied 20 patients with unicystic ameloblastoma to define more precisely the biological behavior of ameloblastomas. The relative infrequency of recurrence observed in their study suggests that unicystic ameloblastomas are less aggressive than solid or multicystic ameloblastomas. They also suggested that enucleation, rather than partial or complete jaw resection, is an appropriate therapy for unicystic ameloblastoma. Numerous cases of ameloblastoma have been reported in the literature. However, only a few articles discuss ameloblastomas in children and adolescents, and few closely examine their nature and pathogenesis. In this study, we analyzed the clinical, radiologic, and histopathologic features of intraosseous ameloblastomas in 71 patients. We also compared these features with the biological behavior of the tumors.

SUBJECTS AND METHODS Seventy-one patients with ameloblastoma were treated at our hospital between September 1989 and September 1999. All clinical and radiologic information with respect to age, sex, symptoms, and location were verified. The patients were treated conservatively (ie, with enucleation and curettage, or both) or radically (ie, with partial or complete jaw resection). Histology slides from each case were reviewed and classified according to histologic patterns. The minimum length of follow-up was 1 year. The recurrence rate was evaluated at follow-up. Outcome criteria were determined by analyzing the recurrence rates after treatment.
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Fig 1. Unilocular radiolucency with well-demarcated border.

Fig 2. Multilocular radiolucency with well-demarcated border.

Table I. Age distribution of ameloblastoma

Age 0-9 10-19 20-29 30-39 40-49 50-59 60-69 No. of patients 0 20 22 10 7 8 3 % 0 28.2 31.0 14.1 9.9 11.3 4.2

Table IV. Chief complaint and symptoms

Symptom Swelling Pain Local discomfort Purulent discharge Symptomless Pain and paresthesia Swelling and discomfort Swelling and purulent discharge Pain and swelling Delayed healing of extraction socket Tooth mobility Pain and discomfort Pain, swelling and purulent discharge Unknown No. of patients 27 6 8 3 2 1 7 2 8 1 1 1 1 3 % 38.0 8.5 11.3 4.2 2.8 1.4 9.9 2.8 11.3 1.4 1.4 1.4 1.4 4.2

Table II. Sex distribution of ameloblastoma

Sex Male Female No. of patients 39 32 % 54.9 45.1

Table III. Site distribution of ameloblastoma

Site Mandible body Body and angle Angle Angle and ramus Body and ramus Ramus Maxilla Palate Unknown No. of patients 43 2 5 4 7 1 3 1 5 % 60.6 2.8 7.0 5.6 9.9 1.4 4.2 1.4 7.0

RESULTS The study group consisted of 39 males and 32 females with a mean age of 30 years (median, 40.5 years; range, 11-70 years; Tables I and II). The patients were followed up for a mean of 64.7 months (range, 13-110 months). In 62 cases (87.3%), the tumors were located in the mandible, and in 16 cases (22.5%), the tumors were cystic in origin. Of the 62 mandibular lesions, 43

(60.6%) were located primarily in the mandible body (Table III). Swelling was the most common symptom, experienced by 27 (38.0%) of the 71 patients (Table IV). Radiographically, 42 (59.2%) of the 71 cases were unilocular with a well-demarcated border, whereas 14 (19.7%) were multilocular in appearance (Table V, Figs 1 and 2). Two cases exhibited a soap-bubble appearance, and 13 cases could not be classified because of loss of the radiographs. If the locules are small, a multilocular lesion can be described as having a soap-bubble appearance. On the basis of established histologic criteria, we observed that 25 (35.2%) of 71 cases exhibited a plexiform pattern and 21 (29.6%) of 71 cases exhibited a follicular pattern (Tables VI and VII). Of the 71 patients, 15 (21.1%) experienced a recurrence of their tumor (Tables VIII-X). The average age of patients whose ameloblastoma recurred was 26.4 years (range, 11-52 years). Eight patients were followed up for 1 to 3 years; 23 patients were followed up for 3 to 5 years; and 40 patients were followed up for more than 5 years. The length of follow-up for patients experiencing recurrence was as follows: 4 cases were followed up for

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Table V. Distribution of radiographic appearance by age

Patients ages (y) Type Unilocular Multilocular Soap-bubble Unknown 0-19 13 2 1 3 20-29 13 5 1 3 30-39 3 1 0 2 40-49 6 1 0 1 50-59 2 3 0 3 60-69 1 2 0 0 70-79 1 0 0 0 Unknown 3 0 0 1 Total 42 14 2 13

Table VI. Distribution of histologic type by age

Patients ages (y) Type Plexiform Follicular Cystic Granular cell Acanthomatous Plexiform and follicular Follicular and acanthomatous Cystic and acanthomatous Cystic and granular cell 0-19 13 2 1 2 0 1 0 0 0 20-29 3 12 1 0 1 4 1 0 0 30-39 1 2 0 0 1 2 0 0 0 40-49 3 3 0 0 0 0 1 1 0 50-59 3 1 1 0 0 0 2 0 1 60-69 0 0 2 0 1 0 0 0 0 70-79 0 0 1 0 0 0 0 0 0 Unknown 2 1 0 0 0 0 0 1 0 Total 25 21 6 2 3 7 4 2 1

Table VII. Relationship between radiographic and histologic findings

Radiographic type Histologic type Plexiform Follicular Cystic Granular cell Acanthomatous Plexiform and follicular Follicular and acanthomatous Cystic and acanthomatous Cystic and granular cell Unilocular 15 15 4 1 1 3 2 1 0 Multilocular 1 3 2 1 1 3 2 1 0 Soap-bubble 2 0 0 0 0 0 0 0 0 Unknown 7 3 0 0 1 1 0 0 1 Total 25 21 6 2 3 7 4 2 1

1 to 3 years; 9 cases were followed up for 3 to 5 years; and 2 cases were followed up for more than 5 years. In the 15 patients who had recurrent tumors, 6 tumors (40.0%) were of a plexiform pattern, 4 were of a mixed follicular pattern, 1 was plexiform/follicular, and 3 were follicular/acanthomatous (Table X).

Table VIII. Period of recurrence

Follow-up period (y) 1 to <2 2 to <3 3 to <4 4 to <5 5 to <10 Total No. of patients followed up 4 4 8 15 40 71 No. of patients with recurrent symptoms 2 2 4 5 2 15

DISCUSSION It has been reported previously that unilocular ameloblastomas tend to occur in younger age groups. Our results confirmed this tendency. The unilocular pattern (59.2%) predominated over the other patterns. Moreover, in this study, 35 of the 42 cases of unilocular lesions occurred before the fifth decade of life (Table V). Larsson and Almeren14 report the incidence of ameloblastoma in Sweden as 0.3 cases per million people per year. The average age of patients with

intraosseous ameloblastoma has been reported to be 39 years. In this study, we documented the occurrence of ameloblastomas in a significantly younger age group than has been used in previous studies. The mean age of our patients at biopsy was 30 years (Table I). This variation may reflect ethnic differences or diagnosis within a health care system in which patients might be

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Table IX. Outcome after conservative therapy for ameloblastoma according to radiographic type (n = 71)
Result of therapy Radiographic type Unilocular Multilocular Soap-bubble Unknown Total No. of cases 42 14 2 13 71 Tumor-free 34 11 0 11 56 Recurrence 8 3 2 2 15

Table X. Outcome after conservative therapy for ameloblastoma according to histologic type (n = 71)
Result of therapy Histologic type Plexiform Follicular Cystic Granular cell Acanthomatous Plexiform and follicular Follicular and acanthomatous Cystic and acanthomatous Cystic and granular cell Total No. of cases 25 21 6 2 3 7 4 2 1 71 Tumor-free 19 17 5 2 3 6 1 2 1 56 Recurrence 6 4 1 0 0 1 3 0 0 15

more likely to have films, and so forth. Waldron and El-Mofty15 reported that in 116 tumors, the male-tofemale ratio was 1.2:1, which is in agreement with our results (Table II). Our study shows that ameloblastomas have a marked predilection for the mandible (93.9%). Waldron and El-Mofty15 reported that the follicular pattern was the most prevalent (45%). However, we found that the plexiform pattern was the most prevalent; it was seen in 25 (35.2%) of the 71 cases. Two patients had changes in granular cells. Granular cells, which have been described as clinical indicators of tumor aggression, were found in the center of the follicular pattern areas.16 This finding contrasts with the observation that the follicular pattern is the most common pattern in intraosseous ameloblastomas.15 Waldron and El-Mofty15 identified 14 examples of the desmoplastic variant, representing 13% of the intraosseous tumors sampled. The desmoplastic pattern was not observed in our study. Swelling accounted for 38.0% of the symptoms and was the most common complaint of the patients in this study. Radiologic findings showed that 59.2% of cases had unilocular radiolucent lesions. By correlating histologic type with age, we found that most teenaged patients had tumors with a plexiform pattern, whereas most patients in their twenties had tumors with a follicular pattern. By correlating radiographic findings with histologic type, we found that 15 cases each of the plexiform and follicular tumors manifested with unilocular radiographic findings. The benign nature of ameloblastoma often leads a surgeon to perform simpler extirpative procedures to avoid the potential morbidity associated with larger resections.17 The diagnosis of unicystic ameloblastoma is made on the basis of a combination of radiographic and microscopic findings. The lesion is definitively diagnosed retrospectively rather than preoperatively. Unilocular lesions were seen by radiologic examination in 11% of the cases, whereas the plexiform type was seen by histologic examination in 8%. Six (8.5%) of the 71 cases were of cystic origin.

Ameloblastomas are treated by curettage only, enucleation and curettage, or radical surgery.18,19 Ameloblastomas of the maxilla should be treated as radically as possible. However, ameloblastomas that appear as unilocular lesions radiographically may be treated conservatively (ie, with enucleation or curettage, or both) whenever all areas of the cystic lumen can be controlled intraoperatively. Supraperiosteal resection of the bone is necessary when extensive thinning or perforation of the cortical plates is noted. Chemotherapy and radiation seem to be contraindicated.19 The reported recurrence rates after resection vary from 0% to 25%.20 In our study, the recurrence rate was 21.1% (15/71). The average age of patients whose ameloblastoma recurred was 26.4 years (range, 11-52 years). Postoperative follow-up is important in the management of ameloblastoma because more than 50% of all recurrences occur within 5 years of surgery. In contrast to other reports, we found that ameloblastomas occurred in younger patients and that a unilocular radiographic pattern predominated. The average age of patients experiencing recurrence was also younger (mean, 26.4 years). Therefore, when the diagnosis of ameloblastoma in young people remains in doubt after clinical and radiologic examination, a biopsy is necessary. Long-term follow-up at regular intervals after surgery is also recommended.

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Lucass pathology of tumors of the oral tissues. 5th ed. Hong Kong: Churchill Livingstone; 1998:25-32. Eveson JW, Scully C. Color atlas of oral pathology. 1st ed. Barcelona: MosbyWolfe; 1995. p. 43-5. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial Pathology. Philadelphia: WB Saunders; 1995. p. 512-20. Keszler A, Dominguez FV. Ameloblastoma in childhood. J Oral Maxillofacial Surg 1986;44:609-13. Ueno S, Nakamura S, Mushimoto K, Shirasu R. A clinicopathologic study of ameloblastoma. J Oral Maxillofac Surg 1986; 44:361-5. Kahn MA. Ameloblastoma in young persons: a clinicopathologic analysis and etiologic investigation. Oral Surg Oral Med Oral Pathol 1989;67:706-15. McMillan MD, Smillie AC. Ameloblastomas associated with dentigerous cysts. Oral Surg Oral Med Oral Pathol 1981;51:48996. Eversole LR, Leider AS, Strub D. Radiographic characteristics of cystogenic ameloblastoma. Oral Surg Oral Med Oral Pathol 1984;57:572-7. Leider AS, Eversole LR, Barkin ME. Cystic ameloblastoma: a clinicopathologic analysis. Oral Surg Oral Med Oral Pathol 1985;60:624-30. Csiba A, Okros I, Dzsinich CS, Szabo D. Virus-like particles in a human ameloblastoma. Arch Oral Biol 1970;15: 817-26. Robinson L, Martinez MG. Unicystic ameloblastoma: a prognostically distinct entity. Cancer 1977;40:2278-85.

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14. Larsson A, Almeren H. Ameloblastoma of the jaws. Acta Pathol Microbiol Scand 1978;86:337-49. 15. Waldron CA, El-Mofty SK. A histopathologic study of 116 ameloblastomas with special reference to the desmoplastic variant. Oral Surg Oral Med Oral Pathol 1987;63:441-51. 16. Hartman KS. Granular cell ameloblastoma. Oral Surg Oral Med Oral Pathol 1974;38:241-53. 17. Sampson DE, Pogrel MA. Management of mandibular ameloblastoma: the clinical basis for a treatment algorithm. J Oral Maxillofac Surg 1999;57:1074-7. 18. Isacsson G, Andersson L, Forsslund H, Bodin I, Thomsson M. Diagnosis and treatment of the unicystic ameloblastoma. Int J Oral Maxillofac Surg 1986;15:759-64. 19. Reichart PA, Philipsen HP, Sonner S. Ameloblastoma: biological profile of 3677 cases. Eur J Cancer B Oral Oncol 1995;31: 86-99. 20. Muller H, Slootweg PJ. The ameloblastoma: the controversial approach to therapy. J Maxillofac Surg 1985;13:79-84. Reprint requests: Su-Gwan Kim Department of Oral and Maxillofacial Surgery College of Dentistry Chosun University 588, SeoSeogDong, DongKu Kwang-Ju City Korea SGCKIM@mail.chosun.ac.kr

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