The odontogenic keratocyst

oral pathology Editor: CHARLES E. TOMICH, D.D.S., M.S.D. American Academy of Oral Pathology Indiana University School of Dentistry 1121 West Michigan Street Indianapolis, Indiana 46202

The odontogenic keratocyst A clinicopathologic Histologic features

Robert B. Brannon, ORAL

PATHOLOGY

study

Lieutenant

DEPARTMENT,

of 312

cases.

Part

II.

Colonel, UXAP (DC)” SCHOOL

OF DENTISTRY,

INDIANA

UNIVERSITY

The histopathologic features of 312 odontogenic keratocysts are described. These features are discussed in relation to their pathogenesis and behavioral characteristics, including recurrence factors ,and neoplastic potential. In addition, a discussion and comparison of the histologic features found in solitary keratocysts, keratocysts associated with the basal-cell nevus-bifid rib syndrome, multiple keratocysts in patients with no other syndrome manifestations, and recurrent keratocysts is presented.

I

t is well recognized that keratinization is among the potentialities of odontogenie cyst epithelium. Many case reports of cysts with keratinizing epithelium appeared in the literature prior to Philipsen’s’ article in 1956 in which he suggested the term odontogenic keratocyst. In 1957 Gorlin2 reported on the multipotentialities of odontogenic cyst epithelium and noted that keratinization was not an uncommon finding in the lining epithelium of 200 dentigerous cysts. Following Gorlin’s report, several investigators began to study the interesting clinical and histologic features of the keratocyst. Shear,3 in 1960, and Pindborg, Philipsen, and Henriksen,* in 1962, established the histologic criteria for these keratinizing cysts. The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Department of the Air Force or of Defense. This article is abstracted from a thesis submitted by the author in partial fulfillment of the requirements for the degree of Master of Science in Dentistry in the graduate school at Indiana University School of Dentistry. *Senior Resident in Oral Pathology, Oral Pathology Department, Dental and Oral Pathology Section, Armed Forces Institute of Pathology.

233

234

Oral February,

Branno?&

METHODS

AND

Surg. 1977

MATERIALS

In order to evaluate the histologic features, the biopsy specimens and clinical histories of :312 odontogenic keratocysts accessioned by the Department of Oral Pathology, Indiana University School of Dentistry, from Oct. 1, 1950, through July 1, 1972, were reviewed. These 312 keratocysts were from a total of 283 patients. The specimens reviewed were all those cysts coded under odontogenic keratocysts, dentigerous cysts, eruption cysts, lateral periodontal cysts, primordial cysts, globulomaxillary cysts, median mandibular cysts, median alveolar cysts, residual cysts, unclassified odontogenic cysts, and cysts associated with the basal-cell nevus syndrome. The selection of cases acceptable as examples of odontogenic keratocysts was made on the basis of the following histologic criteria as set forth by Pindborg and assoeiates4 : 1. The lining epithelium is usually very thin and uniform in thickness, with little or no evidence of rete ridges. 2. There is a well-defined basal-cell layer, the component cells of which are cuboidal or columnar in shape and often in a palisaded arrangement. 3. There is a thin spinous-cell layer which often shows a direct transition from the basal-cell layer. 4. The cells of the spinous-cell layer frequently exhibit intracellular edema. 5. Keratinization is predominantly parakeratotic, but it may be orthokeratotic. 6. The keratin layer is often corrugated. 7. The fibrous cyst wall is generally thin and usually uninflamed. The microscopic characteristics of each odontogenic keratocyst were recorded for comparison under the following major headings: The Lining Epithelium, The Capsule, The Lumen, and Relation to Teeth. In addition, the following categories of keratocysts were designated so that certain histologic features could be compared : 278 solitary keratocysts, sixteen syndrome keratocysts, eighteen keratocysts from patients with multiple jaw cysts but no other features of the syndrome, and fifty recurrent keratocysts. A keratocyst was considered to be recurrent if it was in the exact area of a previously removed keratoeyst or if there was a past history of cyst removal in the same location. In all cases, the recurrent cyst and, when available, the original cyst, fulfilled the histologic criteria for odontogenic keratocysts. In twelve cases both the original keratocysts and recurrent keratocysts were available for examination. There were twenty-five cases in which only the recurrent keratocysts were available and one case consisting of the original keratocyst but not its recurrence. HISTOLOGIC RESULTS The lining epithelium

Two cysts in this series of 312 kerat.ocysts did not have an intact lining epithelium; however, because their lumina were full of keratin and their thin, fibrous capsules contained rests of odontogenic epithelium and no inflammation, they

Odontogenic

Volume 43 Number 2

keratocyst

235

Fig. 1. Photomicrograph of the epithelial lining of an odontogenic keratocyst exhibiting a corrugated, parakeratotic keratin layer, a relatively thin spinuous-cell layer, and a basal-cell layer of cuboidal cells. Note that the nuclei of the cuboidal basal cells are situated on or near the basement membrane. (Hematoxylin and eosin stain. Original magnification, x450.)

Table

I. State of keratinization

in 310 odontogenic keratocysts

Solirary cysts No. of cysts examined PK PK + GCL PK+OK PK+OK+GCL :f:

+ GCL

276 219

Syndrome CYSlS

Multiple cysts

2

18 18

Total cysts in series 310 253

: 19

8

8

: 19

2:

80

80

2:

Key

to abbrev(ation.9: PK = Parakeratosis. OK = Orthokeratosis. GCL = Granular-cell layer. PK + OK + GCL = Parakeratosis jacent to the orthokeratin layer.

and orthokeratosis

with

the granular-cell

layer

sub-

were classified as keratocysts. For this reason, the statistics quoted for the lining epithelium are based on 310 keratocysts. Table I lists the states of keratinization in 310 keratocysts. Total parakeratinization was the most frequent finding, occurring in 258 cysts (83.2 per cent) (Fig. 1). In twenty-two cysts (7.1 per cent) the lining epithelium contained areas of parakeratinization and orthokeratinization. Orthokeratinization was the sole pattern of keratinization in thirty cysts (9.7 per cent) (Fig. 2). All of the keratocysts associated with the syndrome and patients with multiple keratocysts exhibited parakeratinization. Of the fifty recurrent keratocysts, forty-seven (94.0 per cent) had parakeratinization and three (6.0 per cent) had a lining with parakeratinization and orthokeratinization. There were fifty-two keratocysts which

236

Brannon

keratocyst Fig. 2. Photomicrograph of an odontogenic epithelial lining. Note the prominent granular-cell layer keratin. (Hematoxylin and eosin stain. Original magnification,

Oral surg. 1“ehruarr “, 1977

exhihiting a hyperorthokeratotic beneath the thick layer of orthox450.)

exhibited either total or partial orthokeratosis, and twenty-four (46.2 per cent) of these were in a dentigerous cyst relationship to an impacted tooth. The surface keratin layer exhibited a corrugated or wavy appearance in 264 cysts (85.2 per cent) (Fig. 1). For the most part, cysts with an orthokeratotic surface failed to show corrugations. On the basis of subjective interpretation, the keratin layer was characterized by thinness in 245 cases (79.0 per cent). Six cases (1.9 per cent) had a thick layer. In fifty-nine cases (19.0 per cent) t,he keratin layer showed a variation in thickness. The keratin layer in orthokeratotic keratocysts tended to be thicker (Fig. 2). Table I shows the incidence of a granular-cell layer in the keratocysts examined. A total of forty-nine keratocysts (15.8 per cent) exhibited a granular-cell layer. In general, this granular layer was prominent beneath orthokeratin (Fig. 2) and tended to be focal and milder in prominence beneath parakeratin, often being confined to a few cells. A spinous-cell layer eight cells or less in thickness was found in 229 (73.9 per cent) of the total number of cysts examined. Intracellular edema of the spinous cells was found in 258 (83.2 per cent) of the cysts reviewed (Fig. 3). This tended to be an uncommon feature of the orthokeratotic epithelium. Six cysts (1.9 per cent), of which three were maxillary, two were mandibular,

Volume 43 Number 2

Odontogenic

keratocyst

237

Pig. J’. Photomicrograph of the lining epithelium of a keratocyst in which a few of the superficial spinous cells exhibit intracellular edema. Note the mitotic figure in the parabasilar region. The cells of the basal layer range from cuboidal to low columnar, and their nuclei tend to be polarized away from the basement membrane. (Hematoxylin and eosin stain. Original magnification, x450.) Fig. 4. Photomicrograph of an odontogenic keratocyst exhibiting irregular acanthosis. Note that the lining epithelium shows a scalloped interface with the subjacent connective tissue. (Hematoxylin and eosin stain. Original magnification, x115.)

and one was unspecified, contained mucous cells. Three keratocysts (1.0 per cent) exhibited sebaceous glands. One cyst (0.3 per cent), a primordial cyst in a Negro male, contained abundant melanin pigment. in the basal-cell layer. Table II shows the incidence of irregular acanthosis (scalloping) in 310 odontogenic keratocysts. Fig. 4 illustrates this phenomenon. Forty-four keratocysts (14.2 per cent) exhibited irregular acanthosis. In all cases this effect was associated with an overlying layer of parakeratin. Irregular acanthosis was noted concurrently in twenty-two keratocysts (50.0 per cent) in which rete ridge proliferation under parakeratosis and orthokeratosis was occurring. Of the fifty re-

Pig. 5. Photomicrograph of the lining epithelium of a kcratocyst showing the broad, bluntshaped type of r&e ridge formation. Note that the kcratinization process is altered and that a mild to moderate inflammatory cell infiltrate is present. (Hematoxylin and eosin stain. Original magnification, x100.) Pig. 6’. Photomicrograph of the lining epithrlium of a keratoeyst showing rete ridge formation with budding and proliferation of the basal-cell layer. The nests which are budding off the basal layer may eventually form microcysts like the ones which are seen in the upper righthand corner of the photograph. (Hematoxylin and eosin stain. Original magnification, x100.)

current keratocysts examined, only four (8.0 per cent) exhibited irregular acanthosis. The two most common forms of rete ridge formation observed in this series were a broad, blunt type (Fig. 5) and a budding type (Fig. 6). The broad, blunt type tended to occur in areas of inflammation where the lining epithelium and the keratinization process were being altered, while the budding type was usually seen in keratinized lining epithelium where inflammation was minimal or absent. Over all, rete ridge formation was found in the keratinized lining epithelium of fifty keratocysts (16.1 per cent), of which three (1.0 per cent) were orthokeratot-

Volume 43 Number 2

Odontogenic

II. Incidence of irregular odontogenic keratocysts

Table

No. of cysts examined Irregular acanthosis RR under PK RR under OK RR in Non-kerat. Key to RR RR RR

Solitary cysts 276 41 42 3:

keratocyst

acanthosis and rete ridge proliferation

Syndrome

cysts 16

Multiple cysts 18 2

f !

239 in 310

Total cysts in series 310 i;

ii 3

abbreviations. under PK = Rete ridge proliferation under parakeratosis. under OK = Rete ridge proliferation under orthokeratosis. in Non-kerat. = Rete ridge proliferation occurring in nonkeratinizing

4:

epithelium.

ic and forty-seven (15.2 per cent) were parakeratotic. Table II summarizes iu detail the rete ridge proliferation in the types of lining epithelium occurring in each category of keratocyst. In the fifty recurrent keratocysts, rete ridge proliferation was found in the parakeratinized and nonkeratinized lining epithelium of five (10.0 per cent) and six (12.0 per cent) keratocysts, respectively. Mitotic activity was recorded by subjective analysis in twenty-five keratocysts (8.1 per cent). In all cases the mitotic figures were in the parabasilar and midspinous areas (Fig. 3). In forty-three cysts (13.8 per cent) the basal cells were predominantly tall columnar (Fig. 7)) while in ninty-five cysts (30.4 per cent) the basal cells were predominantly cuboidal to low columnar (Figs. 1 and 3). In most instances (172 cysts, 55.1 per cent) both types of basal cell were present and a transition from cuboidal to columnar basal cells was often a notable feature. The nuclei in the columnar basal cells tended to be polarized away from the basement membrane (Fig. 7)) while the nuclei of the cuboidal cells were situated at the basement membrane (Fig. 1). In 293 cysts (94.0 per cent) the lining epithelium was separated from the underlying fibrous capsule. In 111 cysts (35.6 per cent), strips of epithelium were separated at the suprabasilar level, leaving behind an intact basal layer. Prominent infoldings of the epithelial lining were present in 271 of the keratocysts (86.9 per cent) (Fig. 8). A total of twenty-three of the cysts (7.4 per cent) exhibited minimal infoldings, and in eighteen (5.8 per cent) they were absent. The epithelial linings of two keratocysts exhibited epithelial atypia, neither of which demonstrated inflammatory infiltrates. One cyst was a residual keratocyst from the posterior mandible of a 49-year-old man (Fig. 9). The second case showing epithelial atypia was that of a primordial cyst from the mandible of a 14-yearold boy who had been symptomatic for 2 years. None of the keratocysts examined exhibited carcinomatous changes. The epithelial linings of two keratocysts exhibited ameloblastomatous transformation. One cyst, from a 24-year-old man, was in a dentigerous cyst relationship associated with a mandibular first molar. The lining epithelium exhibited a layer of parakeratin, and the basal-cell layer demonstrated the preameloblastic

Pig. 7. Photomicrogruph of the lining epithelium of a keratocyst showing a well-differentiated basal-cell layer of tall columnar cells. Note that the nuclei of these cells show reversed polarity. (Hematoxylin and cosin stain. Original magnification, x450.) Fig. 8. Photomicrograph of the typical keratocyst. The capsule exhibits prominent infold ings and virtually no inflammation. The thin, uniform epithelial lining possess a corrugated layer of parakeratin. Vacuolated cells are scattered throughout the spinous layer, and the basal-cell layer appears well differentiated. (Hematoxylin and eosin stain. Original magnification, x40.)

changes described by Vickers and Gorlin.” These changes consisted primarily of cytoplasmic vacuolizations and basilar cells with hyperchromatic, polarized nuclei (Fig. 10). Mural proliferations of ameloblastomatous islands were evident in the capsule (Fig. 11). The second specimen revealing ameloblastomatous transformation was from the maxillary cuspid region of a 42-year-old woman who had been edentulous in this region for 5 years. The

capsule

The walls of eighty-one keratocysts (26 per cent) were composed of a loose arrangement of collagen fibers. In many cysts the collagen fibers and supporting

Volume Number

43 2

fhiontogenic

keratocpt

241

Pig. 9. Photomicrograph of epithelial atypia in an odont,ogenic keratocyst. Note loss of polarity, basilar hyperplasia: a budding type of rete ridge proliferation, severe acanthosis with loss of a normal stratification pattern, dyskeratosis, cellular pleomorphism, hyperchromatism, dyskaryosis, and prominent nucleoli. Note also the lack of inilammation in the underlying connective tissue. (Hematoxylin and eosin stain. Original magnification, x210.)

Pig. 10. Photomicrograph of an odontogenic keratocyst exhibiting ameloblastomatous transformation. In the central portion of the photomicrograph the keratocyst epithelium is apparent. The cells of the basal layer exhibit cytoplasmic vacuolizations and reversed polarity. Some proliferative activity int,o the connective tissue is evident. (Hematoxylin and eosin stain. Original magnification, x450.)

stroma appeared somewhat immature. The collagen was arranged in a predominantly dense fashion in fifty-seven cysts (18.3 per cent). The capsules of 175 cysts (56.1 per cent) varied in consistency, exhibiting collagen in both loose and dense patterns. In twenty-seven keratocysts (8.7 per cent), hyalinization of the collagen was present (Fig. 12). This change was usually found at the subepithelial

Oral Burg. February, 1977

Fig. 22. Photomicrograph showing mural ameloblastomatous keratocyst. (Hematoxylin and rosin stain. Original magnification,

proliferation xl 15.)

in an odontogenic

Ill. Type of inflammation and incidence of cholesterol clefts and hyaline bodies in 312 odontogenic keratocysts

Table

Number of keratocysts

Absent or virtually absent Acutely inflamed Subacutely inflamed Chronically inflamed Cholesterol clefts Hvaline bodies

103 5: 154 :z

Per cent

33.0 0.3 17.3 49.4 12.5 11.2

level. The age range of the patients with hyalinization was 12 to 72 years, with an average age of 49 years 7 months. The degree or severity of the inflammatory cell infiltrate was as follows: (1) absent or nearly so in 103 cysts (33.0 per cent) ; (2) a mild to moderate intlltrate scattered throughout the capsule in fourteen cysts (4.5 per cent) ; (3) focal collections or nodules of inflammatory cells in which there was loss of keratinization in the lining epithelium in 123 cysts (39.4 per cent) (Fig. 13) ; (4) a diffuse infiltration of inflammatory cells throughout the capsule without altering the keratinization process in seventeen cysts (5.4 per cent) ; and (5) a diffuse infiltrate throughout the capsule in which there was alteration in the keratinization process in seventeen cysts (5.4 per cent). In addition, the capsules of fortyfive cysts (14.4 per cent) showed a wide range in the degree of inflammation and contained two or more of the aforementioned patterns. Table III shows the type of inflammation found, as well as the incidence of cholesterol clefts and hyaline bodies (Rushton bodies). Dystrophic calcifications were present in the capsules of fifty-three kerato-

Odontogenic

keratocyst

243

18. Photomicrograph of hyalinization of the collagen in the capsule of an odontogenic (Hematoxylin and eosin stain. Original magnification, x40.) Fig. 13. Photomicrograph of the lining epithelium of a keratocyst showing loss of keratinization in an area of severe inflammation (left half of photograph). (Hematoxylin and eosin stain. Original magnification, x300.) Fig.

keratocyst.

cysts (17.0 per cent). These calcifications were found in forty-seven (16.9 per cent) of the 278 solitary keratocysts, in none of the syndrome keratocysts, and in six (33.3 per cent) of the keratocysts removed from patients with multiple keratocysts with no other manifestations of the syndrome. Although not specifically recorded, there were several cases in which nests of odontogenic epithelium appeared to be either associated with or undergoing calcification. Sixty-eight (21.8 per cent) of the 312 keratocysts examined contained satellite cysts. In forty-two (61.8 per cent) of these sixty-eight cysts, epithelial rests were also present. The most frequent location for keratocysts with satellite cysts was the mandibular third molar region and/or ramus (ten cysts), the anterior maxilla

Oral Frbruary,

Table

IV. Incidence

ot’ sattllite

cysts and cpithelial

Solitaq cysts

No. of cysts examined Satellite cysts Epithelial rests

278 2

Association with tooth

With impacted tooth Not associated with impacted tooth

Total No. of keratocysts

rests in cyst categork

Syndrome

Multiple cysts

CYSfS

16 3 4

18 1:

Table V. Incidence of satellite cysts and epithelial

Total cysts in series

312 68 93

rests as to tooth relationship

Keratocysts with satellite cysts

Keratocysts with epithelial rests

83

21 (25.3%)

35 (42.1%)

229

47 (20.5%) 68 (21.8%)

58 (25.3%) 93 (29.8%)

12

Surg. 1977

(ten cysts), and the maxillary third molar region (nine cysts). All three types of satellite cyst, as described by Browne,G were observed in this series, but no attempt was made to record their specific incidence. An example of a keratocyst containing satellite cysts is seen in Fig. 14. Table IV shows the incidence of keratocysts exhibiting satellite cysts occurring in each category of keratocyst. Table V summarizes the incidence of keratocysts with satellite cysts according to their association with teeth. Satellite cysts were present in nine (18.0 per cent) of fifty recurrent cysts. Of the sixty-eight cysts with satellite cysts, nine (13.2 per cent) were found to be either recurrent keratocysts or cysts which eventually did recur. However, there were only twelve patients in whom both the original and recurrent cysts were available for histologic examination. In these twelve cases, it was found that four original cysts possessed satellite cysts, while their recurrences did not. Conversely, in three cases the recurrent cyst contained satellite cysts, but not the original cysts. In no instance were satellite cysts found concurrently in both the original cyst and the recurrent cyst. Ninety-three (29.8 per cent) of the 312 keratocysts reviewed contained islands or rests of odontogenic epithelium. In forty-two (45.2 per cent) of these ninetythree cysts, satellite cysts were also present. Keratocysts with epithelial rests showed a predilection for the mandibular third molar and/or ramus (twenty-one cases), the maxillary third molar area (fifteen cases), and the maxillary cuspid area (eleven cases). Although not specifically recorded, in several cases the epithelial rosettes and islands were keratinizing in their central portions (Fig. 15). Proliferations of these islands were also noted in several insta.nces (Fig. 15). Strands of dental lamina, as illustrated by Soskolne and Shear,7 were present in an occasional keratocyst. Table IV illustrates the incidence of odontogenic keratocysts with epithelial rests found in the various categories of keratocysts. The association of odontogenic keratocysts containing epithelial rests with teeth is presented in Table V. Epithelial rests were present in seven (14.0 per cent) of the fifty recurrent

Volume 43 Number 2

Fig. 14. Photomicrograph of an its connective tissue wall. The main and eosin stain. Original magnification, Fig. 15. Photomicrograph of the tion and microcyst formation in rests ing epithelial islands. (Hematoxylin

Odontogenic

keratocyst

245

odontogenic keratocyst with numerous satellite cysts in cyst cavity shows prominent infoldings. (Hematoxylin x3.) wall of an odontogenic keratocyst showing keratinizaof odontogenic epithelium. Note the actively proliferatand eosin stain. Original magnification, x450.)

keratocysts. Of the ninety-three cysts with epithelial rests, seven (7.5 per cent) were found to be either recurrent keratocysts or cysts which eventually did recur. In the twelve cases which included both the original cyst and the recurrent cyst, three cysts with epithelial rests recurred, while in one case epithelial rests were present in the recurrent cyst but not in the original cyst. In no instance were epithelial rests present concurrently in both the original cyst and its recurrence. There were twenty-one cases in which sufficient tissue was removed to permit a study of the keratocyst’s relationship to t,he surrounding bone. In all cases the fibrous capsule of the cyst separated the surrounding marrow spaces from its epithelial lining, or satellite cysts when present. In an additional fourteen kera-

tocysts (4.5 per cent). fragments of residual bone wart present deep within the fibrous capsulr.Thc significance of these fintlings has been previously dis~nssccl. Thirty-five (11.2 per cent) of the 312 keratocysts examined histologically wcw intimately associated with surrounding soft-tissue structures, such as skeletal muscle, salivary gland acini, oral mucosa, adipose tissue, and antral epithelium. In sixteen keratocysts (5.1 per cent), large peripheral nerves or large neurovascular bundles were found in the fibrous capsule, often near the main cyst lumen. The lumen

In ninety-six cysts (30.8 per cent) the lumen was full of keratin, while in 111 cysts (35.6 per cent) the lumen was predominantly empty, containing only shreds of keratin. The lumen was empty in ninety-three cysts (29.8 per cent) and filled with blood in twelve (3.8 per cent). In sixteen cysts (5.1 per cent) a foreign-body reaction to the luminal keratin was present. In these cysts the lining epithelium was replaced by focal collections of multinucleated foreign-body giant cells. Relation

to teeth

In seven cases the associated tooth and t,hc attached keratocyst were available for histologic examination. In two cases the cysts were attached to the lateral root surfaces of erupted vital mandibular premolars. These were considered to be lateral periodontal cysts. In one case a keratocyst was attached to the apex of a vital maxillary cuspid. In the four remaining cases, the keratocysts were in a dentigerous cyst relat,ionship to the teeth. The histologic features of these aforementioned dentigerous keratocysts have been discussed.x DISCUSSION

Histologic examination of the 312 keratocysts showed that their basic structure met the histologic criteria described by Pindborg and associates.4 Tabulation of the results of this study indicates that the keratocyst is most often characterized by the following features: a thin, uniform lining of stratified squamous epithelium; a thin layer of corrugated parakeratin; a spinous-cell layer eight cells or less in thickness, often showing intracellular edema ; a well-differentiated basal layer, the component cells of which range from cuboidal to columnar in shape; a relatively thin, inflammation-free capsule; and a lumen which contains varying amounts of desquamated keratin. Figs. 1 and 8 illustrate the typical keratocyst. In addition to the characteristics listed above, there were many other less common features, as well as some unusual features, which justify discussion. Although parakeratinization was the most frequent state of keratinization, Table I shows that a significant number had signs of orthokeratinization, either total or partial. These findings are in general agreement with those of Browne.F The series of Rud and Pindborgg and Soskolne and Shear7 showed a much higher incidence of orthokeratin. These differences are probably due to interpretation. All of the keratocysts associated with the syndrome and patients with multiple cysts exhibited parakeratinization. Of the fifty recurrent keratocysts examined, forty-seven (94.0 per cent) had total parakeratinization of the epithelial lining. These findings would suggest that orthokeratin in keratocysts from syndrome and

Odontogenic

keratocyst

247

multiple-cyst patients is uncommon and that keratocysts exhibiting orthokeratin do not often recur. Rud and Pindborgg reported a recurrence rate of 33.3 per cent in twenty-one keratocysts, of which seven possessed total orthokeratotic epithehum and one had partial orthokeratosis. However, only one of their recurrent cysts exhibited orthokeratosis. Another interesting finding concerning the presence of orthokeratin involves those keratocysts which were in a dentigerous cyst relationship with an impacted tooth. It appears that keratocysts in a. dentigerous cyst relationship are more likely to exhibit orthokeratin in some or all of their lining epithelium than are keratocysts in a nontooth-associated relationship. In this series, twenty-four (28.9 per cent) of the eighty-three dentigerous keratocysts examined exhibited total or partial orthokeratosis, whereas only twenty-eight (12.2 per cent) of 229 keratocysts which were not in a dentigerous relationship exhibited this feature. Of the twenty-four cysts in a dentigerous relationship containing orthokeratin, eighteen (75 per cent) exhibited total orthokeratosis, the remainder exhibiting both orthokeratosis and parakeratosis. The significance of this relatively high incidence of orthokeratin in dentigerous cysts is not known. It may be argued that these dentigerous cysts with orthokeratosis do not represent true keratocysts but possibly represent a keratin metaplasia as described by Browne,l” who states that this phenomenon usually occurs in cysts of long standing and is most common in the older age groups. In this series, however, the averags age of the patients with these orthokeratotic dentigerous cysts was 34.7 years, which would indicate that these cysts were not necessarily of long duration. Furthermore, six (25 per cent) of these cysts also contained the parakeratotic lining epithelium typically seen in keratocysts. In addition, two teeth in this series were in a classic dentigerous cyst relationship with the keratocysts, one exhibiting an orthokeratotic lining, and the other a parakeratotic lining.8 This suggests that not all dentigerous keratocysts are extrafollicular in origin, but that a keratocyst may develop from reduced enamel epithelium. Shear3 has postulated that rests of the dental lamina which are undifferentiated possess the ability to form keratin, whereas the epithelium which has completed its tooth-forming function, such as is found in dentigerous cysts, has differentiated and does not form keratin. The present study does not support this theory in its entirety. The fact that none of the recurrent keratocysts, syndrome keratocysts, and multiple keratocysts which were examined exhibited total orthokeratinization of their epithelial lining may suggest that those keratocysts which contain orthokeratinizing epithelium have an origin different from keratocysts in which parakeratinization is present. It seems logical, on the basis of the present material, to assume that the reduced enamel epithelium of dentigerous cysts may be orthokeratinized, parakeratinized, or both, and thus be a type of odontogenic keratocyst. Further studies should be carried out concerning orthokeratinization in keratocysts, in particular dentigerous cysts. The frequency of recurrence and incidence of orthokeratotic keratocysts in patients with multiple keratocysts and the syndrome needs further investigation.

248

Brannon

The incidence of mucous cells, sebaceous glands, and melanin in this series is in close agreement with the findings of Crawfordl’ and Brownc.” One cyst in this series, from a Negro, contained abundant melanin pigment. In Browne’s” series two keratocysts from a West. Indian were said to contain numerous melanocytes in the basal layer. These findings support the pluripotential capability of keratocyst epithelium. Irregular acanthosis or scalloping has been described by Crawfordll and illustrated by Payne.12 This phenomenon (Fig. 4) occurred in forty-four (14.2 per cent) of the keratocysts in this study. In all instances it was a.ssociated with an overlying layer of parakeratin. This phenomenon may represent a precursor to rete ridge formation, as evidenced by the concurrent presence of rete ridge proliferation in keratinized epithelium in 50 per cent of the keratocysts exhibiting irregular acanthosis. There did not appear to be a predilection for any one category of cyst. The over-all presence of rete ridge formation in keratinizing epithelium in this series closely paralleled the appearance of irregular acanthosis. This activity was found predominantly under parakeratotic epithelium, and the frequency was evenly distributed throughout the cyst categories. In many instances inflammation was present in some part of the cyst wall, although it was not always associated directly with the area of rete ridge formation. Inflammation may conceivably be the initiating factor of this activity ; however, this phenomenon may also occur as the inherent ability of this type of epithelium to actively proliferate. Mitotic activity was observed in twenty-five (8.1 per cent) of the keratocysts examined. In many cases mitotic activity was taking place throughout the lining epithelium. It is realized that this 8.1 per cent incidence is probably lower than might be expected because of the method used in arriving at this figure. Toller,l” Main,14 and Browne6 have proved by accurate methods that the rate of mitosis in keratocysts is much higher than for other odontogenic cysts. The findings in this study support the fact that keratocysts possess an active epithelial lining. In most instances the component cells of the basal-cell layer ranged from cuboidal to columnar. In the cysts where one cell type predominated, the cuboidal basal cells were more common than the columnar cell type by a ratio of approximately 2 :l. Without exception, the nuclei of the tall columnar cells were polarized away from the basement membrane (Fig. 7). Some investigators33 g have suggested that these cells are more highly differentiated. These columnar cells resemble ameloblasts morphologically and are usually palisaded with polarization of their hyperchromatic nuclei. The several cases of ameloblastomas which have been reported to arise in keratocysts present an interesting relationship to consider. Two common histologic features of the keratocyst-hyperchromatism of basal-cell nuclei and palisading with nuclear polarization of basal cells-have been consistently observed in cystic lesions that have been associated with ameloblastoma in a high percentage of cases.” Two solitary keratocysts in this study exhibited ameloblastomatous transformation, for an incidence of 0.6 per cent. The findings in this study indicate that the frequency of ameloblastomatous transformation arising in keratocysts may be higher than would be expected in other types of odontogenic cyst.

Odontogewic

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According to the literature, most cases of ameloblastoma arising in keratocysts have developed in cysts associated with the basal-cell nevus syndrome. It seems feasible that there would be a higher incidence of ameloblastomas in syndrome patients, since these patients also have the propensity to develop cutaneous cysts and neoplasms as well as odontogenic keratoeysts. TWO of the keratocysts in this series were considered to exhibit an epithelial atypia in which there was no inflammatory infiltrate present. The information in the literature on epithelial dysplasia and atypia is sparse. Rud and Pindborg” are the only authors to date who have discussed this subject to any extent. They found three of twenty-one keratocysts exhibiting epithelial atypia based on the following criteria : basal-cell hyperplasia, increased mitotic activity, and loss of a normal stratification pattern. It was not within the scope of the review to study epithelial atypia in any great detail. According to the criteria of Rud and Pindborg9 for keratocyst atypia, several keratocysts in this series could have been classified as such. However, in all but t.wo of these keratocysts, the cytologic alterations were interpreted as being secondary to inflammation. The two keratocysts with atypia in this series and the three reported by Rud and Pindborg” were parakeratotic cysts. In addition, Toller13 reported a case which he considered similar to Ilud and Pindborg’sg three cases. No information was available as to whether the two cysts in this series recurred. The fibrous connective tissue capsule was characteristically thin, tending to be thicker in areas of diffuse inflammation and areas containing satellite cysts. Hyalinization of the collagen occurred in 8.7 per cent of the cysts examined, the average age of the patients being 47 years 7 months. These findings are in close agreement with those of Browne,” who found the incidence and average age to be 13.7 per cent and 47.4 years. Thus, hyalinization appears to be a feature of keratocysts removed from older patients. Cholesterol clefts were found in thirty-nine cysts, (12.5 per cent) which is most likely due to the low incidence of inflammation in the capsule. The paucity of inflammation is in agreement with other studies.6 Hyaline bodies (Rushton bodies) were present in 11.2 per cent of the cysts examined, which is in agreement with the previous findings of Browne.6 These were usually associated with areas of inflammation. Of interest is the finding that hyaline bodies were present in 9.3 per cent of the solitary keratocysts but were present in 26.4 per cent of the syndrome keratocysts and in patients with multiple keratocysts. The significance of this is not known, but it may be of interest for future investigations. From the observations in this study, it appears that satellite cysts may arise from cystic changes in rests of odontogenic epithelium or from proliferations of the lining epithelium, the former being the most common. Fig. 6 shows evidence of satellite cyst formation via proliferations from the epithelial lining of the main cyst cavity. Fig. 15 shows the most commonly observed phenomenon by which satellite cysts arose, that is, cystic changes in adjacent rests of epithelium. Of the sixty-eight keratocysts containing satellite cysts, forty-two (61.8 per cent) also contained epithelial rests. Furthermore, the most common location for keratocysts with satellite cysts was the third molar region, the same as for keratocysts with

epitheial rests. This association supports the concept that satellite cysts arise from epithelial rests. There was also convincing evidence that satellite cysts ma? possess a life cycle as proposed by Browne.‘i A total of 25.3 per cent of the keratocysts associated with impacted teeth eontained satellite cysts, with a 20.5 per cent frequency in the keratocysts which were not associated with teeth. It would appear that the frequency relationship of satellite cysts in the various keratocysts is insignificant. A total of 42.1 per cent of the keratocysts associated with impacted teeth contained epithelial rests, compared with 25.3 per cent of the keratocysts which were not associated with teeth. The fact that epithelial rests were frequently observed undergoing cystic changes and proliferations and that their most frequent anatomic location corresponds to the most common location for keratocysts supports the opinion that keratocysts may arise from remnants of the dental lamina. There was greater frequency of epithelial rests in keratocysts associated with impacted teeth (Table V). In most cases the cystic cavities were virtually empty. The keratin flakes were no doubt lost during surgical removal in most instances. In ninety-six cysts (30.8 per cent) the lumina were full of keratin, which usually appeared amorphous although shreds of parakeratin were evident in a few of these. In several cases colonies of bacteria and an admixture of inflammatory cells were scattered throughout the luminal keratin, indicating infection. The odontogenic keratocysts in this series which appeared clinically and histologically in a dentigerous cyst relationship to an impacted tooth have been previously discussed.8 As stated earlier, the evidence found in this study supports the existence of a true dentigerous cyst type of odontogenic keratocyst. It is known that the basal-cell nevus syndrome has a variable expressivity.15 On the basis of the proposal by BrowneG that all cases of multiple cysts should be considered in this syndrome complex, it was decided to combine the syndrome keratocysts and the keratocysts from patients with multiple cysts but without the other features of the syndrome and compare them to the keratocysts from patients with single cysts. All the syndrome patients had multiple keratocysts, with the exception of one who was included in this group. The major difference observed in multiple and solitary keratocysts was the presence of rests of odontogenic epithelium and satellite cysts. The frequency was 50 per cent with epithelial rests and 35.2 per cent with satellite cysts in patients with multiple cysts. The incidence of epithelial rests and satellite cysts in single cysts was 27.3 per cent and 20.1 per cent, respectively. Both of these findings are in agreement with Waldron’s*6 reported findings on the differences between syndrome keratocysts and nonsyndrome keratocysts. Browne6 also reported the frequency of satellite cysts to be higher in cysts from patients with multiple cysts. In addition, he found a higher incidence of mineralizations in cysts from multiple cyst patients; however, in this study the incidence was essentially the same. Nonetheless, the over-all incidence of calcifications in the keratocysts of this series is considerably higher than in other odontogenic cysts, as noted by Browne.G Rete ridge proliferation and irregular acanthosis were essentially the same for the two groups in this series. Waldron Ifi has suggested that syndrome cysts exhibit a tendency toward rete ridge formation.

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Patients with multiple keratocysts, with or without the other syndrome manifestations, probably have some hereditary factor or genetic abnormality which is involved in keratocyst formation. This factor may control not only the number of keratocysts but their degree of activity as well. This could account for the fact that the keratocysts from the syndrome and multiple-cyst patients have a higher incidence of satellite cysts and epithelial rests in their capsules. It may well be that this factor is responsible for the formation and activity of solitary keratocysts. The high incidence of dystrophie calcifications in the 312 keratocysts in this series may be the manifestations of a metabolic. disturbance involving calcification. Patients with the syndrome are known to have soft-tissue calcifications elsewhere, such as the falx cerebril: and pelvic vessels. l* In addition, calcifications in neoplasms, such as the ovarian fibromals and the basal-cell carcinoma,19 have been reported. Of the fifty-three keratocysts in this series which had calcifications in their walls, thirty had rests of odontogenic epithelium. It was not unusual to see these rests associated with the calcifications. Whether these calcifications occurred from any epithelial influence is not known, but the evidence is at least suggestive. Several explanations have been suggested as to why keratocysts have a high propensity for recurrence. Unfortunately, from the results of this study, the reason for their recurrence remains only speculative. Technical or surgical difficulties in removal, a thin, friable capsule, bony perforation, and adherence to softtissue structures have been implicated as possible factors responsible for recurrence. In this study there were thirteen cases in which the original keratocyst was available for evaluation. Slightly more than one half of these cysts were classified as being large to extensive in size. Furthermore, drainage and perforation of bone with adherence to surrounding soft-tissue structures was evident in nearly 50 per cent of these cysts. Satellite cysts and rests of odontogenic epithelium have often been suggested as recurrence factors. Satellite cysts were present in nine of the fifty recurrent keratocysts examined ; however, the majority of keratocysts (86.8 per cent) with satellite cysts were not recurrent keratocysts. The following observation was made in seven of the twelve cases in which both the original and recurrent keratoFour primary cysts with satellite cysts cysts were available for examination: recurred, whereas in three cases satellite cysts were present in the recurrent cysts but not in the original. In no instances were satellite cysts found concurrently in both the original cyst and the recurrent cyst. It should be pointed out that serial sections were not done, and it is quite possible that satellite cysts were present in portions of the cyst wall which were not sectioned. Nevertheless, from these findings, it would appear there is no significant correlation between the presence of satellite cysts and the recurrence of the cyst. Epithelial rests were present in seven of the fifty recurrent cysts examined. The majority of the keratocysts (92.5 per cent) with epithelial rests were not recurrent keratocysts. Browne” found a firm trend in his series suggesting that cysts containing epithelial rests were less likely to recur. The same phenomenon that was observed with satellite cysts also occurred with epithelial rests in that, among four cases with epithelial rests, there was no instance in which rests were present concurrently in both the original cyst and its recurrence. Again, serial

sections were not clone in this stucly, so that the possibility of epithclial rests being present in other areas of the cyst wall cannot be ruled out. In summary, it is believed that t,he number of cases in which both the original and recurrent cyst were available for evaluation was too small to permit any definite conclusions concerning the role of satellite cysts and epithelial rests in recurrence. In addition, the fact that serial sectioning was not performed and that, the number of paCents who were actually followed postoperatively was unknown tended to distort the results of this study. Another feature of t,he keratocyst as described by Brown@ and by Donoff and associates?” is the frequent finding of the lining epithelium separated from the subjacent connective tissue. This was observed in 293 (94.0 per cent) of the keratocysts in this series. Donoff and asso&ateP’ noted that this was not a constant, feature in the other types of cysts examined. If this separation represented artifact, it would seem that it would hart occurred in all types of cysts t,hey examined. It could be that keratocyst epithelium is more susceptible to mechanical manipulation because of its lack of rete ridges and its poorly developed basement membrane, as reportctl by Browne.” Donoff and associates’O have suggested the possibility of enzymatic activity as a cause. Whatever the reason, if it does indeed separate with ease, fragments could easily be left behind cluring removal, resulting in a recurrence. In view of the impressions gained from the results of this study and the literature review, the following factors seem the most tenable as mechanisms of recurrence : 1. Remnants of dental lamina cpithelium may exist within the jaws which are not associated with the original keratocyst. These rests are activated in certain patients to form keratocysts. This is not a true recurrent keratocyst, but one which has arisen de novo. 2. Incomplete removal of the original cyst lining is a probable factor. The thin, friable lining makes these cysts difficult to remove. This is complicated by the fact that frequently these cysts are extensive in size and have often perforated bone and have become tenaciously adherent to adjacent soft-tissue structures. Adherence to soft-tissue structures was evident histologically in 16.3 per cent of the keratocysts examined in this series. Any epithelial lining that remains in the tissues after surgery has the potential to keep on growing to form a recurrence. Toller13 has demonstrated the high mitotic activity of the epithelium in keratocysts. 3. Rests of dental lamina and satellite cysts remaining in the tissues following incomplete removal of the capsule cannot be ruled out. All of the cases in this series were treated by enucleation, with the exception of one ca,se which was marsupializecl. Therefore, an evaluation of treatment methods with regard to recurrence was not attempted. The various modes of therapy, excluding radical surgery, that have been advocated for the treatment of keratocysts include total enucleation,“1-‘3 marsupialization,g, pz enucleation and packing open,20, 24 decompression with secondary enucleation,?j and enucleation with removal of the mucosa overlying the keratocyst.26 Despite the various recom-

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mended methods of treatment, BrowneZ4 found no significant differences in recurrence among marsupialization, enucleation and packing open, and enucleation and primary closure. Supporting BrowneW findings are the earlier works of Pindborg and HansenZ3 and Hansen,27 who found no difference in recurrence among the types of surgical procedure employed (total enucleation, marsupialization, and fenestration). Forssell and his co-workcrsZ8 have reported that the method of treatment may have a considerable influence on the recurrence rate. In their series, no recurrences occurred when the keratocysts were enucleated totally in one piece, whereas keratocysts removed in several pieces recurred in nearly half the cases. They believed that fra,aentation of the keratocyst during removal was due to technical difficulties which were directly related to site, size, and shape of the cyst. Bramley2” has discussed the problems in treating the keratocyst and has offered a classification of treatment based on its radiographic appearance. It appears from these findings that early recognition and removal of keratoeysts when they are small, unilocular, and totally confined to bone without perforation will provide the least chance for recurrence. It was apparent from the 2,972 cysts reviewed that a number of cysts share some or all of the histologic criteria for keratocysts with one exception, that being keratinization. These features were found in all of the cyst types reviewed, especially the dentigerous, primordial, and residual cysts. In several cases there were difficulties in interpreting the existence of a keratin layer. Uncertainties exist with regard to the spectrum of histologic features which an odontogenic keratocyst may possess and whether an unkeratinized odontogenic cyst can keratinize to become an odontogenic keratocyst. Philipsenl considered keratinization of the epithelial lining a further development of odontogenic cysts. However, Rud and Pindborg” argue that there has been no evidence that a primary unkeratinized odontogenic cyst will become keratinized. Browne’O contends that keratinization does occur in cysts with simple stratified squamous epithelium, such as dentigerous cysts and radicular cysts, but he does not regard them as keratocysts. Obviously, many odontogenic cysts are in a gray zone of subjectivity. From the observations in this review, it is believed that the keratocyst, by definition, should always be lined with keratinizing epithelium since many other odontogenie cysts share some or all of the other characteristic features attributed to them. Perhaps an investigation into the clinical characteristics of these questionable cysts, especially behavioral patterns, would further elucidate this controversial matter. CONCLUSIONS

Histologically, keratocyst,s present certain histologic features which distinguish them from other cysts of the jaws. Keratocysts may exhibit either parakeratosis, orthokeratosis, or a combination of the two. Keratocysts that have orthokeratin in their lining epithelium are prone to be of the dentigerous cyst type. The finding of mucous cells, sebaceous glands, and melanin indicates that the lining epithelium of keratocysts is pluripotential. Epithelial atypia and ameloblastomatous transformation appear to be more

common in keratocysts than in other odontogenic cysts and nonodontogenic cysts which were studied in this series. Satellite cysts ma,v arise from proliferations of the lining cpithelium or front adjacent rests of the dental lamina, the latter being the most common. Although satellite cysts and rests of odontogenic epithelium are more commonly found in keratocysts from patients with multiple keratocysts, with or without the syndrome, they also appear in solitary keratocysts, and therefore t,hese aforementioned cysts are histologically indistinguishable. The factor most commonly involved with the recurrence of a keratocyst is probably related to technical difficulties in surgical removal because of the size and aggressiveness of the cyst. Therefore, for most keratocysts, early recognition and removal are of paramount importance from the standpoint of recurrence. The findings in this study support the theory that the histologic appearance of an odontogenic keratocyst may be assumed by any of the odontogenic or nonodontogenic fissural cysts which were studied. They are also in agreement with the theory that keratocysts may arise from remnants of the dental lamina. The results of this study indicate that not all primordial cysts are keratocysts, as proposed by some. Finally, because of the keratocyst’s clinical behavior, association with the basal-cell nevus syndrome, and possible neoplastic potential, all cysts removed from the jaws should be submitted for microscopic examination and diagnosis. The author is grateful to Dr. William G. Shafer, Distinguished Professor, Department of Oral Pathology, Indiana University School of Dentistry, for his guidance and inspiration in the preparation of this study. I thank Dr. George P. Wysocki, Department of Pathology, The University of Western Ontario, for the preparation of the photomicrographs. REFERENCES

1. Philipsen, H. P.: Om Keratocyster (Kolesteatomer) I Kaeberne, Tandlaegebladet 60: 963-980, 1956. 2. Gorlin, R. J.: Potentialities of Oral Epithelium Manifest by Mandibular Dentigerous Cysts, ORAL SURG. 10: 271-284, 1957. 3. Shear, M.: Primordial Cysts, J. Dent. Assoc. S. Afr. 15: 211-217, 1960. 4. Pindborg, J. J., Philipsen, H. P., and Henriksen, J.: Studies on Odontogenic Cyst Epithelium. In Fundamentals of Keratinization, Publication No. 70 of the American Association for the Advancement of Science, Washington, D.C., 1962, pp. X1-160. 5. Vickers, R. A., and Gorlin, R. J.: Ameloblastoma: Delineation of Early Histopathologic Features of Neoplasia, Cancer 26: 699-710, 1970. 6. Browne, R. M.: The Odontogenic Keratocyst; Histological Features and Their Correlation With Clinical Behavior, Br. Dent. J. 131: 249-259, 1971. 7. Soskolne, W. A., and Shear, M.: Observations on the Pathogenesis of Primordial Cysts, Br. Dent. J. 123: 321-326, 1967. 8. Brannon, R. B.: The Odontogenic Keratocyst : A Clinicopathologic Study of 312 Cases. Part I. Clinical Features, ORAL SURG. 42: 54-72, 1976. 9. Rud, J., and Pindborg, J. J.: Odontogenic Keratocysts: A Follow-up Study of 21 Cases, J. Oral Surg. 27: 323-330, 1969. 10. Browne, R. M.: Metaplasia and Degeneration in Odontogenic Cysts in Man, J. Oral Pathol. 1: 145-158, 1972. 11. Crawford, W. H., Jr.: Keratinizing Cysts of the Oral Cavity, Master of Science Thesis, University of Southern California, Los Angeles, 1964. 12. Payne, T. F.: An Analysis of the Clinical and Histopathologic Parameters of the Odontogenie Keratocyst, ORAL SURG. 33: 538~546,1972. 13. Toller, P. A.: Autoradiography of Explants From Odontogenic Cysts, Br. Dent. J. 131: 57-61, 1971. 14. Main, D. M. G.: Epithelial Jaw Cysts: A Clinicopathological Reappraisal, Br. J. Oral Surg. 8: 114-125, 1970.

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15. Browne, R. M.: The Pathogenesis of the Odontogenic Keratocyst. I?z Fourth Proceedings of the International Academy of Oral Pathology, Ipswich, 1969, W. S. Cowell, Ltd., pp. 28-38. 16. Waldron. C. A.: Some Observations on the Jaw Cvsts in the Basal Cell Nevoid Carcinoma Syndrome. In Fourth Proceedings of t.he Inteinational Academy of Oral Pathology, Ipswich, 1969, W. S. Cowell, Ltd., pp. 220-226. J. J.: The Multiple Basal-Cell 17. Gorlin. R. J.. Viekers. R. A., Kelln. E.. and Williamson, Nevi Syndrome Cancer 18: 89-104, 1965.’ W. E., Block, J. B., and Radde, I. C.: Basal Cell Nevus Syndrome, Arch. 18. Clendenning, Dermatol. 90: 38-53, 1964. Basal Cell Tumors, Jaw Cysts, and Skeletal Defects: A Clinical 19. Maddox, TV. D.: Multiple Syndrome, Master of Science Thesis, Universrty of Minnesota, 1962. 20. Donoff, R. B., Guralnick, W. C., and Clayman, L.: Keratocysts of the Jaws, J. Oral Surg. 30: 800-804, 1972. H. C., and Kay, L. W.: Benign Cystic Lesion of the Jaws, Their Diagnosis and 21. Killey; Treatment, ed. 2, Edinburgh, 1972, Churchhill Livingstone, p. 94. of the Jaws, J. Oral Surg. 27: 22. Panders, A. K., and Hadders, H. N.: Solitary Keratocysts 931-938,’ 1969. ’ II. Clinical and 23. Pindborg, J. J., and Hansen J.: Studies on Odontogenic Cyst Epithelium. Roentgenographic Aspects of Odontogenic Keratocysts, Acta. Pathol. Microbial. &and. 58: 283-294, 1963. 24. Browne, R. M.: The Odontogenic Keratocyst; Clinical Aspects, Br. Dent. J. 128: 225-231,

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and Secondary 25. Tucker, W. M., Pleasents, J. E., and MacComb, W. 5.: Decompression Enucleation of a Mandibular Cyst: Report of a Case, J. Oral Surg. 30: 669-673, 1972. of the Jaws, 26. Stoelinga, P. J. W., and Peters, J. H.: A Note on the Origin of Keratocysts Int. J. Oral Surg. 2: 37-44, 1973. in the Jaws. In Husted, E., and Hjerting-Hansen, E. (editors) : 27. Hansen, J. : Keratocysts Oral Surgery, Transactions of the Second Congress of the International Association of Oral Surgeons, Copenhagen, 1967, Munksgaard, pp. 128-134. 28. Forssell. K.. Sorvari, T. E. and Oksala, E.: An Analysis of the Recurrence of Odontogenie Keratoiysts; Proc. Finn. Dent. Sot. 70:’ 135-140, 1974; 29. Bramley, P. A.: Treatment of Cysts of the Jaws, Proc. R. Sot. Med. 64: 547-550, 1971.