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.

T HE DEVELOPMENT OF AMELOBLASTOMA IN
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*20In 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.
T h e authors are indebted to Mrs. Shirley Snow for prepa-
ration of the manuscript.
Accepted for publication April 1, 1977.
2278
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
No. 5 AMELOBLASTOMA Robinson and Martinez
UNICYSTIC 2279

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.
Th e 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.

MATERIALS
A N D 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 2281
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
noted at the end Of year after therapy' Flc;, 4, (Case 5) Photomicrograph showing lining epithe-
This patient is now 2b' years postrecurrence lium of cyst (a), and islands of ameloblastic epithelium
with no further evidence of disease. Another pa- within connective tissue portions of cyst wall, with cystic
tient (20) was lost to follow-up after 2 years. change (b) (X160).

FIG. 5. (Case 5) Preoperative ra-

diograp h.
2282 CANCER
flovernber 1977
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
Vol. 40
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 DiehlZ1showing 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. I n
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 Martinez 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 Mandibular 3rd molar swelling after tooth 12/61-11/75 No clinical or radiographic evidence
J.B. extraction; unilocular radiolucency just distal 14 yr of disease
18 WM to extraction site; gross appearance of cyst

#2 Mandibular 3rd molar swelling after tooth 4/62-12/75 No clinical or radiographic evidence
R.J.P. extraction; large multilocular radiolucency of 13% yr of disease
47WF distal body and ramus

#3 Large dentigerous cyst involving mandibular 3rd 4/64-11/75 Recurrence 1972 (8 yr post-therapy);
G.D. molar high up in ramus 1 1 %y r treated by local excision; now 3 yr
17 BF postrecurrence with no clinical or
radiographic evidence of disease

#4 Large dentigerous cyst involving mandibular 1/64-12/74 No clinical or radiographic evidence

R.C. 3rd molar 11 yr of disease
15 BF

#5 Large dentigerous cyst involving mandibular 7/67-1/75 Recurrence 1971 (4 yr post-therapy);

M.S. 3rd molar crown present high up in ramus 8 Yr treated by local excision; now 4 yr
12 BF postrecurrence with no clinical or
radiographic evidence of disease

fi Dentierous cyst in relation to mandibular 3rd 10/63-10/69 No clinical or radiographic evidence

E.B. molar 6 Y' of disease
12 BM

#7 Dentigerous cyst in relation to mandibular 3rd 11/70-10/75 No clinical or radiographic evidence

V.D. molar 5 Y' of disease
13 WF

#8 Dentigerous cyst in relation to mandibular 2nd 4/71-4/76 No clinical or radiographic evidence

L.D. molar; developing 3rd molar 5 Y' of disease
10 BM

89 Dentigerous cyst in relation to mandibular molar 1/71-10/75 No clinical or radiographic evidence

G.D. present high up in ramus 4 % yr of disease
14 BF

#lo Dentigerous cyst in relation to mandibular 3rd 12/74-11/76 No clinical or radiographic evidence
P.H. molar 2 Yr of disease
27WF

#I1 Dentigerous cyst in relation to mandibular 3rd 10/75- Postoperative period too short
F.H. molar
35 BM

XI2 Dentigerous cyst in relation to mandibular 2nd 10/75- Postoperative period too short
J.R.T. molar; developing 3rd molar displaced into
13WM ramus

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

G.C. molar
15 WM

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

J.O. molar
24WM
2284 CANCER
November 1977
TABLE
2. Summary of Data on Patients with Unicystic Ameloblastoma Mimicking Residual or Primordial Cysts
Mode of presentation
Patient (clinical and radiographic)
#I5 Unilocular radiolucency in mandibular edentulous
C.R. molar area; clinical impression: residual cyst;
44 BF gross appearance: cyst
#16 Unilocular radiolucency in mandibular molar
W.W. area; clinical impression: cyst; gross
24 BM appearance: cyst
#17 Radiolucency in left anterior mandible; clinical
M.B.J. impression: residual cyst; gross
79 BF appearance: cyst
#la Unilocular sharply defined radiolucency in
D.H. mandible between and displacing roots of
12 BF premolars
#19 Unilocular sharply defined radiolucency in
W.B.W. mandible; gross appearance: cyst
53WM
#20 Unilocular radiolucency in mandible, with
G.C. portions of periphery indistinct
70 BM
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-
REFERENCES
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.
Vol. 40
Length of
post-op. period Comment
10/62-10/75 N o clinical or radiographic evidence of
13 yr disease
11/67-4/76 No clinical or radiographic evidence of
8 M yr disease
9/69-4/75 Focal small recurrence 9/70 (1 yr
5 % yr postinitial therapy); treated with
local excision; now 4 V2 yr post-
recurrence with no clinical or radio-
graphic evidence of disease
2/5/72-4/76 No clinical or radiographic evidence of
4 % yr disease
9/63-9/67 No clinical evidence of disease
4 Y’
9/72-9/74 Lost to follow-up after 2 yr
2 Y‘
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. I n 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. ’’,’*
4. Cahn, L. R.: The dentigerous cyst is a potential ada-
mantinoma. Dent. Cosmos 75:889, 1933.
5. Carpenter, L. S., and Thoma, K. H.: Adamantinoma
formed from a radicular cyst. Dent. Items Interest 55:716,
1933.
6. Carr, B. M., and Mohnac, A. M.: Simple ameloblas-
toma within a follicular cyst of the maxilla. Oral Surg.
15:1136, 1962.
7. Castner, D. V., McCully, A. C., and Hiatt, W. R.:
No. 5 UNICYSTIC
AMELOBLASTOMA Robinson and Martinez
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.
9. Gorlin, R.: Potentialities of oral epithelium manifest by
mandibular dentigerous cysts. Oral Surg. 10:271, 1957.
10. Lee, F. M.: Ameloblastoma of the maxilla with prob-
able origin in a residual cyst. Oral Surg. 29:799, 1970.
1 1 . Lubar, R. L., Williams, R. F., and Henefer, E. P.:
Mural ameloblastoma of mandible with post-extraction frac-
ture and repair by iliac cancellous bone graft: report of a
case. J . Oral Surg. 29:674, 1971.
12. Lucas, R. B . : Neoplasia in odontogenic cysts. Oral
Surg. 7:1227, 1954.
13. Madan, R.: Ameloblastoma developing from a denti-
gerous cyst. Oral Surg., 13:781, 1960.
14. Quinn, J. H., and Fournet, L. F.: Dentigerous cyst
with mural ameloblastoma-Report of a case. 3. Oral Surg.
27:662, 1969.
15. Robinson, H. 8. G.: Histologic study of ameloblas-
toma. Arch. Pafhol. 23:664, 1937.
16. Robinson, H. B. G.: Ameloblastoma-Review of 379
cases. Arch. Pafhol. 23331, 1937.
17. Selle, G., and Jacobs, H. G.: Zue Problematik der
Enstehung von Ameloblastomen aus odontogenen Cysten.
Oesferr. Zeitschr. Stomat. 69:54, 1972.
18. Small, G. S., Lattner, C. W., and Waldron, C. A,:
2285
Ameloblastoma of the mandible simulating a radicular cyst.
J . Oral Surg. 16:231, 1958.
19. Small, I. A., and Waldron, C. A.: Ameloblastomas of
the jaws. Oral Surg. 8:281,1955.
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.
25. Vickers, R. A,, and Gorlin, R. J.: Ameloblastoma-
Delineation of early histopathologic features of neoplasia.
C h c e r 26:699, 1970.
26. Waldron, C. A,: Ameloblastoma in perspective. 3.
Oral Surg. 24:331, 1966.
27. Wilson, D. L., and Roche, W. C.: Dentigerous cyst
with ameloblastomatous change.3. OralSurg. 18:173, 1960.
28. Young, D. R., and Robinson, M. : Ameloblastomas in
children. Oral Surg. 15:1155, 1962.