UNICYSTIC AMELOBLASTOMA A Prognostically Distinct Entity

LEONARD ROBINSON, DMD, MD, AND MARIO G. MARTINEZ, DMD, MS

The occurrence of unicystic ameloblastoma has been studied in 20 patients presenting with unilocular cystic lesions whose clinical, radiographic and gross features were those of non-neoplastic cysts. In the majority of these, the lesion mimicked dentigerous cyst. The rate of recurrence for this group of lesions as determined by long term follow-up observation available for the majority of patients was distinctly lower than that associated with multicystic and solid ameloblastoma. This, coupled with preservation of the unicystic character of the lesion throughout its course, is indicative of a much less aggressive variety of neoplasm. The adequacy of simple enucleation as a modality of treatment in the majority of patients with this type of lesion is suggested. It was not possible to answer the question whether or not the ameloblastoma began in antecedent non-neoplastic cyst.

Canccr 40:2278-2285, 1977.

HE DEVELOPMENT OF AMELOBLASTOMA IN T the wall of cysts has been the subject of a number of publications. In the majority of these, one or two cases have been reported. In most of these, of which selected and more recent reports are cited, the dentigerous cyst was implicated as the pre-existent lesion. 2.4.6- 8,11,13,14,23,24,27.28 I n a much smaller number of patients, the amelo- blastoma arose allegedly in other types of cysts. 1***s~10~1’*18 For most of the patients, the postoperative period of observation was 1 year or less. In addition to these case reports, there are several studies of the occurrence of amelo- blastoma in cysts that involve much larger num- bers of patients. 12*1B*20 In these, the frequency of occurrence ranged from 14 to 33%.

Evaluation of these reports has been ham- pered in many cases by absence or inadequate documentation of microscopic features. In many instances, the authors have referred to the pres- ence of ameloblastic epithelium without in- dicating the parameters used to warrant such a characterization. However, the information available indicates that the ameloblastic epithe-

From the Department of Pathology, Schools of Medicine and Dentistry, University of Alabama in Birmingham, Bir- mingham, Alabama.

Address for reprints: Leonard Robinson, MD, Depart- ment of Pathology, Schools of Medicine and Dentistry, Uni- versity of Alabama in Birmingham, University Station, Bir- mingham, AL 35294.

The authors are indebted to Mrs. Shirley Snow for prepa- ration of the manuscript.

Accepted for publication April 1, 1977.

lium occurred a ) within the lining epithelium, b ) as a mural nodule or nodules within the walls of the cyst, or c) occupied the lumen of the cyst either completely or incompletely. The unicystic character of the “antecedent” cyst was pre- served. In some instances, the assumption was made that ameloblastomas developed sub- sequent to the removal of what was considered on clinical and radiographic grounds to be a cyst without microscopic confirmation of the latter.

The clinical and radiographic presentations and gross features of unicystic ameloblastoma, when it develops in relation to an unerupted tooth, are indistinguishable from those of dentigerous cysts. Therefore, on the basis of these parameters, it is impossible to distinguish between these two types of lesions. The diagno- sis of unicystic ameloblastoma can only be made when the presence of ameloblastic epithelium can be established unequivocally. Furthermore, the hypothesis that ameloblastoma arises in a dentigerous cyst is defensible only when it can be demonstrated that a non-neoplastic cyst ex- isted prior to the appearance of the ameloblas- toma or when both the lining epithelium seen normally in odontogenic non-neoplastic cysts and ameloblastic epithelium are present side by side.

Several features suggest that the ameloblas- toma that arises allegedly in an antecedent odontogenic cyst exhibits a biological behavior different from that of the solid and multicystic forms of this neoplasm. The age range (10-29 years) for the patients reported in this group is

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No. 5 UNICYSTIC AMELOBLASTOMA Robinson and Martinez

considerably lower than the average age of 37.5 years reported by Robinson. That the lesion has maintained a sharply defined unicystic char- acter raises the possibility of a lesser degree of invasiveness.

The following is a report of our study of 20 patients with unicystic ameloblastoma, which was undertaken in an attempt to define more precisely the biological behavior of this variety of ameloblastoma. The cystic lesions in all 20 pa- tients were treated by enucleation only. Follow- up studies ranging from 10-14 years are avail- able for five of the 20, while 5 to 9 year follow-up studies are available on an additional six. Thus, 11 of the 20 patients have been studied for longer than 5 years. Follow-up studies ranging from 2 to 5 years are available for an additional five patients.

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MATERIALS AND METHODS

With the exception of one case, the patient material for this study was obtained from speci- mens carrying the tentative diagnosis of cyst (dentigerous, residual, primordial) and sub- mitted to the Diagnostic Pathology Services of University Hospital and the School of Dentistry, University of Alabama in Birmingham. Thus, detailed gross descriptions were available for each of the cystic lesions. In the majority of instances, a careful search was made for any unusual features (intraluminal projections, un- usual thickness of cyst wall).

For microscopic evaluation, multiple blocks were submitted after initial microscopic ap- praisal suggested the possibility that the lesion could be a unicystic ameloblastoma. Micro- scopic sections were prepared from several levels of each of the blocks submitted. An average of 15 slides stained with hematoxylin and eosin were studied from each lesion in 13 of the patients. In each of the remaining seven, 100 sections were studied.

Ameloblastic epithelium was considered to be present when any of the following, either singly or in combination, were present:

1. A lining epithelium in which the basal cells were clearly columnar, with hy- perchromatic nuclei, and the overlying cells were only loosely textured with absence of cohesiveness; ’’ this separation of the supra-

basilar cells could not be explained on the basis of inflammatory edema (Figs. 1, 2, and 4).

( <

FIG. 1. (Case 1 ) Low power view of cyst wall to show lining epithelium and epithelial islands within connective portion of cyst wall (Xl60). Insert is a higher magnification of lining epithelium (X640).

2. Downgrowth of the epithelium de- scribed in (1) into the connective tissue por- tion of the cyst wall (Fig. 1).

3. The presence within the connective tis- sue portion of the cyst wall of epithelial islands composed of a periphery of colum- nar epithelial cells and a center identical with stellate reticulum (Figs. 1, 3, and 4).

4. Intraluminal nodules composed of anastomosing cords and islands of epithe- lium; the cells comprising these cords and islands are identical to those described in 3.

RESULTS

For purposes of this presentation, unicystic ameloblastomas have been divided into two groups. In one group are those that mimic denti- gerous cysts, while the second group comprises lesions whose clinical and radiographic repre- sentations are those of residual or primordial cysts. Representative radiographs are seen in Figures 5 and 6. Figure 5 is the preoperative film of the lesion present in Patient 5. In Figure 6

2280 CANCER Nouember 1977 Vol. 40

FIG. 2a. (Case 15) and 2B (Case 17) Sections of cyst wall showing loss of cohesiveness of lining epithelium ( X 160).

(Patient 15), the radiographic representation of the lesion preoperatively and 13 years following enucleation is seen.

Table 1 is a summary of the patients in whom unicystic ameloblastoma mimicked dentigerous

cyst. Of these, 10 were below the age of 20 years; of the remaining four, two were in the 20-29- year age group, and two were in the 40-49-year age group. In all 14 patients, the lesion was located in the mandible and was associated with

FIG. 3. (Case 18) Cyst wall with islands of ame- loblastic epithelium in connective tissue portion of wall (Xl60).

No. 5 UNICYSTIC AMELOBLASTOMA Robinson and Martinez

an unerupted third molar. Postoperative periods of observation varying from 5 to 14 years are available for eight of the 14 patients. In six of the eight, the lesion has not recurred. Two patients (3 and 5 ) have experienced local recurrence. In one, the recurrence appeared 8 years post- enucleation; this patient is now 3 years post- recurrence with no further evidence of disease. In the second, the recurrence was noted 4 years after initial therapy; this patient is now 4 years postrecurrence with no clinical or radiographic evidence of disease.

Clinical data and follow-up results of the pa- tients in whom the unicystic ameloblastoma mimicked primordial or residual cysts are sum- marized in Table 2. The age range for four of the six patients in this group was 44-79 years; the remaining two were 12 and 24 years of age. All six lesions occurred in the mandible. The length of postoperative observation ranged from 4 to 13 years, with no clinical or radiographic evidence of recurrence in four of the six. In one patient (17), a small focus of recurrent neoplasm was

2281

noted at the end Of year after therapy' Flc;, 4, (Case 5) Photomicrograph showing lining epithe- This patient is now b'2 years postrecurrence with no further evidence of disease. Another pa- tient (20) was lost to follow-up after 2 years.

lium of cyst (a), and islands of ameloblastic epithelium within connective tissue portions of cyst wall, with cystic change (b) (X160).

FIG. 5. (Case 5) Preoperative ra- diograp h.

2282 CANCER flovernber 1977 Vol. 40

DISCUSSION O n the basis of morphology, the epithelial

islands and portions of the lining epithelium seen in all of the cases included in this study are indistinguishable from ameloblastic epithelium. These can be delineated from inactive-appear- ing epithelial cell rests that are seen in the walls of tooth follicles and various types of cysts seen in the jaws. The criteria that were used in this study to characterize epithelium as ameloblas- toma coincide quite closely with those selected by Vickers and Gorlin" as representative of early ameloblastic change, although they were arrived at independently.

The age range of the 14 patients in whom the unicystic ameloblastoma mimicked dentigerous cysts is in agreement with the age range occur- ring in the various individual case reports cited, and differs from the average for solid and multi- cystic ameloblastomas as reported by Robinson in 1937." The age range of these 14 patients is compatible with the studies of Stanley, Krogh and Pannkuk" on the changes according to age in patients with the epithelial components of

FIG. 6. (Case 15) Preoperative ra- diograph (a), and follow-up radio- graph taken 13 years post- enucleation (b).

follicles associated with unerupted third molars. These investigators observed that enamel organ epithelium as either lining epithelium or as cell rests within the follicles predominated below age 22 years; above this age, the epithelium under- went squamous metaplasia. The studies of Stan- ley and DiehlZ1 showing an appreciable reduc- tion in the number of cases of ameloblastoma associated with follicles of unerupted teeth and/or follicular cysts after the age of 30 years, are also consistent with this observation.

In the current study, it was not possible to resolve the question of whether unicystic ame- loblastoma begins de novo as a unicystic lesion or whether it develops in a pre-existent cyst. In some portions of the lining of the unicystic ame- loblastomas studied, the lining epithelium con- sisted of several layers of flattened squamous cells bearing little resemblance to ameloblastic epithelium. This type of epithelium could repre- sent remnants of the epithelial lining of an an- tecedent non-neoplastic cyst. The possibility also exists that it represents ameloblastic epithe- lium altered by the pressure of intraluminal con-

No. 5 UNICYSTIC AMELOBLASTOMA Robinson and Mart inez 2283

tents or ameloblastic epithelium in which embryologically speaking, makes transition squamous metaplasia has occurred. That the from a non-neoplastic cyst to a neoplastic one a epithelium of odontogenic non-neoplastic cysts possibility, even though the frequency of occur- and ameloblastomas have a common ancestry, rence is uncommon. The presence of odonto-

TABLE 1. Summary of Data on Patients with Unicystic Ameloblastoma Mimicking Dentigerous Cysts

Mode of presentation Length of Patient (clinical and radiographic) post-op. period Comment

#1 J.B. 18 WM

#2 R.J.P. 47WF

#3 G.D. 17 BF

#4 R.C. 15 BF

#5 M.S. 12 BF

f i E.B. 12 BM

#7 V.D. 13 WF

#8 L.D. 10 BM

89 G.D. 14 BF

#lo P.H. 27WF

#I1 F.H. 35 BM

XI2 J.R.T. 13 WM

#13

#14

G.C. 15 WM

J.O. 24WM

Mandibular 3rd molar swelling after tooth 12/61-11/75 No clinical or radiographic evidence extraction; unilocular radiolucency just distal 14 yr of disease to extraction site; gross appearance of cyst

Mandibular 3rd molar swelling after tooth 4/62-12/75 No clinical or radiographic evidence extraction; large multilocular radiolucency of 13% yr of disease distal body and ramus

Large dentigerous cyst involving mandibular 3rd 4/64-11/75 11%yr

Recurrence 1972 (8 yr post-therapy); treated by local excision; now 3 yr postrecurrence with no clinical or radiographic evidence of disease

No clinical or radiographic evidence

molar high up in ramus

Large dentigerous cyst involving mandibular 1/64-12/74 3rd molar 11 yr of disease

Large dentigerous cyst involving mandibular 3rd molar crown present high up in ramus

7/67-1/75 8 Yr

Recurrence 1971 (4 yr post-therapy); treated by local excision; now 4 yr postrecurrence with no clinical or radiographic evidence of disease

No clinical or radiographic evidence Dentierous cyst in relation to mandibular 3rd 10/63-10/69 molar 6 Y' of disease

Dentigerous cyst in relation to mandibular 3rd 11/70-10/75 No clinical or radiographic evidence molar 5 Y' of disease

Dentigerous cyst in relation to mandibular 2nd 4/71-4/76 No clinical or radiographic evidence molar; developing 3rd molar 5 Y' of disease

Dentigerous cyst in relation to mandibular molar 1/71-10/75 No clinical or radiographic evidence present high up in ramus 4 % yr of disease

Dentigerous cyst in relation to mandibular 3rd 12/74-11/76 No clinical or radiographic evidence molar 2 Yr of disease

Dentigerous cyst in relation to mandibular 3rd 10/75- Postoperative period too short molar

Dentigerous cyst in relation to mandibular 2nd molar; developing 3rd molar displaced into ramus

10/75- Postoperative period too short

Dentigerous cyst in relation to mandibular 3rd 8/9/68- Lost to follow-up molar

Dentigerous cyst in relation to mandibular 3rd 6/2/64- Lost to follow-up molar

2284 CANCER November 1977 Vol. 40

TABLE 2. Summary of Data on Patients with Unicystic Ameloblastoma Mimicking Residual or Primordial Cysts

Mode of presentation Length of Patient (clinical and radiographic) post-op. period Comment

#I5 Unilocular radiolucency in mandibular edentulous 10/62-10/75 No clinical or radiographic evidence of C.R. molar area; clinical impression: residual cyst; 13 yr disease 44 BF gross appearance: cyst

#16 Unilocular radiolucency in mandibular molar 11/67-4/76 No clinical or radiographic evidence of W.W. area; clinical impression: cyst; gross 8 M yr disease 24 BM appearance: cyst

#17 Radiolucency in left anterior mandible; clinical 9/69-4/75 Focal small recurrence 9/70 (1 yr M.B.J. impression: residual cyst; gross 5 % yr postinitial therapy); treated with 79 BF appearance: cyst local excision; now 4 V2 yr post-

recurrence with no clinical or radio- graphic evidence of disease

#la Unilocular sharply defined radiolucency in 2/5/72-4/76 No clinical or radiographic evidence of D.H. mandible between and displacing roots of 4 % yr disease 12 BF premolars

#19 Unilocular sharply defined radiolucency in 9/63-9/67 No clinical evidence of disease

53WM W.B.W. mandible; gross appearance: cyst 4 Y’

#20 Unilocular radiolucency in mandible, with 9/72-9/74 Lost to follow-up after 2 yr

70 BM G.C. portions of periphery indistinct 2 Y‘

genic epithelium in 3% of 200 mandibular denti- gerous cysts, as reported by Gorlin,’ could be interpreted as supportive of such a possibility. In this regard, it is interesting to recall Cahn’s 1933 publication‘ in which he stated that “A denti- gerous cyst may be a cystic expression of the adamantinoma,” and “A dentigerous cystic ad- amantinoma will reach a certain size and re- main stationary or at most grow very slowly.”

In those patients with unicystic ameloblas- toma in whom long term follow-up information was available, the recurrence rate was low. In the patients in whom the lesion mimicked denti- gerous cyst, the rate was 25% (2/8), while in the patients in whom the lesion presented as resid- ual or primordial cyst, two of six experienced recurrence; these patients are now 3 and 4 years postrecurrence, respectively, with no further evi-

dence of disease. In one of these (raucnt #17), the microscopic features supporting a diagnosis of ameloblastoma were minimal (Fig. 2b). In spite of this very banal appearance, the lesion recurred 1 year following enucleation. Thus, on occasion, there may be considerable disparity between morphological representation and bio- logical behavior. In unpublished data quoted by Waldron, 26 the recurrence rate for all ameloblas- tomas treated by curettage was 55%. The rela- tive infrequency of recurrence observed in this study suggests that unicystic ameloblastoma ex- hibits a less aggressive biologic behavior than does solid or multicystic ameloblastoma. There- fore, enucleation rather than partial or complete jaw resection appears to constitute appropriate therapy. This has been suggested in several pub- lications. ’’,’*

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1. Aisenberg, M. S., and Inman, B. W.: Ameloblastoma arising within a globulomaxillary cyst. Oral Surg. 13:1352, 1960.

2. Battle, R. J. V., and Winstock, D.: Adamantinoma of the mandible arising in a dentigerous cyst. Br. J . Phi. Surg. 13:349, 1961.

3. Byrd, D. L., Allen, J. W., and Dunsworth, A. R.: Arneloblastoma originating in the wall of a primordial cyst-Report of a case. J . Oral Surg. 31:301, 1973.

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7. Castner, D. V., McCully, A. C., and Hiatt, W. R.:

No. 5 UNICYSTIC AMELOBLASTOMA Robinson and Martinez 2285

Intracystic ameloblastoma in the young patient. Oral Surg. 23:127, 1967.

8. Dresser, W. J., and Segal, E.: Ameloblastoma asso- ciated with a dentigerous cyst in a 6 year old child-Report of a case. Oral Surg. 24:388, 1967.

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15. Robinson, H. 8. G.: Histologic study of ameloblas- toma. Arch. Pafhol. 23:664, 1937.

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17. Selle, G., and Jacobs, H. G.: Zue Problematik der Enstehung von Ameloblastomen aus odontogenen Cysten. Oesferr. Zeitschr. Stomat. 69:54, 1972.

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Ameloblastoma of the mandible simulating a radicular cyst. J . Oral Surg. 16:231, 1958.

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20. Sonesson, A.: Odontogenic cysts in cystic tumours of the jaws. Acta Radiol. (Suppl.) 81:l-159, 1950.

21. Stanley, H. R., and Diehl, D. L.: Ameloblastoma potential of follicular cysts. Oral Surg. 20:260, 1965.

22. Stanley, H. R., Krogh, H., and Pannkuk, E.: Age changes in the epithelial components of follicles (dental sacs) associated with impacted third molars. Oral Surg. 19:128, 1965.

23. Taylor, R. N., Collins, J. F., Menell, H. B., and Williams, A. C.: Dentigerous cyst with ameloblastomatous proliferation. J . Oral Surg. 29:136, 1971.

24. Thoma, K. H.: Follicular cysts and tumors associated with impacted third molars. Arch. Clin. Oraf Pathol. 4:292, 1940.

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