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The relationship of the canine acanthomatous epulis to ameloblastoma
j. Comp. Path. 1993 Vol. 108, 47-55
The Relationship of the Canine Acanthomatous Epulis to Ameloblastoma D. G. G a r d n e r and D. C. Baker* Division of Oral Pathology and Oncology, University of Colorado School of Dentistry, Denver, CO 80262 and *Department of Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, U.S.A.
Summary This paper compares the microscopic f~atures and clinical behaviour of the acanthomatous epulis in dogs with those of ameloblastoma in human beings. The acanthomatous epulis has similar microscopic features to one histological variant of human ameloblastoma, the acanthomatous ameloblastoma. Moreover, its clinical behaviour is equivalent to that ofintraosseous ameloblastoma in human beings, not of the human peripheral (extraosseous) ameloblastoma, as has been suggested. The stroma ofacanthomatous epulides varies and does not always resemble periodontal ligament, a feature that in dogs has been used to distinguish them from ameloblastomas. It is concluded that the acanthomatous epulis (1) is an ameloblastoma, (2) arises from the gingival epithelium in some cases, but (3) may also arise intraosseously and then break out of bone. We recommend the term canine acanthomatous ameloblastoma as being appropriate for this lesion. Introduction The term acanthomatous epulis was first used by Dubielzig, Goldschmidt and Brodey (1979) in their attempt to standardize the nomenclature of canine epulides. Previously, these lesions had been included within the category of fibromatous and ossifying epulis (Head, 1976) or were referred to as adamantinomas and considered, because of their ability to invade bone, to be the malignant counterpart of the fibromatous and ossifying epulis (Langham, Keahey, Mostosky and Schirmer, 1965). This latter lesion, generally referred to simply as the fibromatous epulis, is, in turn, the canine counterpart of the peripheral odontogenic fibroma in man (Bostock and White, 1987; Gardner and Baker, 1991). Bostock and White (1987) considered the acanthomatous epulis to be a basal cell carcinoma of the gingiva, while Reichart, Philipsen and Dfirr (1989) believed it to be a peripheral (extraosseous) ameloblastoma originating from the surface epithelium of the oral cavity and Verstraete, Ligthelm and Weber (1992) have used this designation in a recent paper. At present, acanthomatous epulis is the most widely used term. The acanthomatous epulis consists of broad sheets and anastomosing cords Address for correspondence: Dr D. G. Gardner, University of Colorado School of Dentistry, Campus Box C284, 4200 East Ninth Avenue, Denver CO 80262, U.S.A. 0021-9975/93/010047 + 09 $08.00/0
© 1993 Academic Press Limited
48
D.G. Gardner and D. G. Baker
of epithelium within a connective tissue stroma. There is, however, some inconsistency in the literature concerning the nature of the stroma. Dubielzig et al. (1979) emphasized that acanthomatous epulides, like fibromatous epulides, exhibit dense cellular stroma consisting of stellate cells and tightly packed fibrillar collagen. This appearance is typical of periodontal ligament and Dubielzig and Thrall (1982) used it as a distinguishing feature between acanthomatous epulides and ameloblastomas, which, they state, do not exhibit this type of stroma. In contrast, Bostock and White (1987) stated that acanthomatous epulides exhibit a mature collagenous, relatively acellular, stroma and some published illustrations show this feature (Thrall, Goldschmidt and Biery, 1981). Barker and Van Dreumel (1985) do not c o m m e n t on the nature of the stroma, other than to indicate that small foci of metaplastic hard tissue may develop within it. Dubielzig et al. (1979) also noted that some examples exhibit foci of bone, cementum or dentine. T h e epithelium is the more significant component of acanthomatous epulides, but it is important to determine whether the stroma in these tumours consistently resembles periodontal ligament. There are two other questions that arise. T h e first is whether the acanthomatous epulis is truly an extraosseous lesion that subsequently invades bone. Its clinical behaviour appears to be that of the typical intraosseous ameloblastoma in man (a lesion that originates and eventually breaks out of bone) rather than of the peripheral ameloblastoma that Reichart et al. (1989) suggested as the h u m a n counterpart of acanthomatous epulis. T h e latter type of ameloblastoma, unlike the intraosseous ameloblastoma, in h u m a n beings generally does not invade bone (Gardner, 1977). A major problem is that once a lesion exhibits both intraosseous and extraosseous components, it is no longer possible to determine whether it was originally intraosseous or extraosseous. In h u m a n beings, numerous peripheral ameloblastomas have been excised which clearly did not involve the underlying bone (Gardner, 1977). T h e second question is why attempt to distinguish between acanthomatous epulides and ameloblastomas in dogs if their clinical behaviour is identical and their histopathology similar, except for the possible presence of stroma exhibiting periodontal ligament in acanthomatous epulides. The purpose of the present study is to compare the pathology of acanthomatous epulides in dogs with that of peripheral ameloblast~mas and intraosseous ameloblastomas in h u m a n beings in an attempt to answer the questions above.
M a t e r i a l s and M e t h o d s
Group 1 Haematoxylin and eosin(HE)-stained sections of all I3 examples of acanthomatous epulides accessioned by the Department of Pathology of the College of Veterinary Medicine of Colorado State University from June 1986 to January 1990 were examined and compared with the well-recognized histological features of human ameloblastomas, both peripheral and intraosscous. These features are illustrated in several books and articles (Pindborg, Kramer and Torloni, 1971; Gardner, 1977; Lucas, 1984). In addition, in all cases the radiographs were studied together with the
Acanthomatous Epulis
49
corresponding histopathological sections, to evaluate whether the lesiohs originated from within bone or from the surface. The criterion accepted for proof of extraosseous origin was a tissue section that exhibited an acanthomatous epulis that was entirely within the gingiva and the margins &which were clear of tumour. In addition, there must be no radiographic evidence of bony invasion.
Group2 The examples in Group 1 did not provide sufficient information to evaluate adequately whether acanthomatous epulides arise from the epithelial surface or from within bone. Consequently, a further 19 pathology sections, representing the acanthomatous epulides accessioned in 1989 and 1990 by a private veterinary pathology service in Guelph, Canada, were studied to evaluate the relationship of the tumours to the epithelial surface.
Results
Group 1 The clinical features of the 13 acanthomatous epulides are summarized in Table 1. The acanthomatous epulides consisted of islands and cords of squamous epithelium that had invaded irregularly throughout a connective tissue stroma (Fig. 1). In some examples the basal cells were unremarkable but, typically, in at least some parts of the tumour, they were columnar and arranged with their long axes perpendicular to the basement membrane, a feature referred to as palisading (Fig. 2). Moreover, their cytoplasm was vacuolated and their nuclei exhibited reverse polarization, i.e., they were situated at the ends of the cells distal to the basement membrane. These basal cells typically surrounded regularly arranged sheets of squamous epithelium, although in some tumours, or parts of a tumour, the central cells resembled basal cells more than
Table I The clinical features of 13 acanthomatous epulldes (Group 1)
Breeds Sex Age Location
8 (2 collies) 3 mixed 1 unknown 6 males, 7 females Range 4 to 14 years Mean 10'5 years Median 11 years Mandible Incisor region Premolar region Molar region Maxilla Incisor region Premolar region Molar region
Fig. 1.
Low power photomicrograph of an acanthomatous epulis illustrating islands and cords of squamous epithelium whi¢la have infiltrated through the stroma, T h e strorna varies from dense (ibrous eoanective tissue on the bottom of the illustration to looser connective tissue on the top. HE x55.
Fig. 2.
Higher magnification of an area similar to Fig. 1, illustrating the typical histological features of acanthvmatous epulis. T h e basal ceils are orientated with their long axes perpendicular to the basement m e m b r a n e (palisading), their cytoplasm is vaeuolated and their nuclei are located at the distal ends of the cells (reverse polarization). Tile central cells are squamous and separated by ocdema. H E x 2 1 9 .
Fig. 3.
A n area o f a c a n t h o m a t o u s epulis in which the central cells of the epithelial islands are basilar rather than squarnous. T h e stroma is of the fibroblastic type, typical of canine periodontal ligament. In fact, this tissue was scraped t~rom the root of a tooth. HE x 219.
Fig. 4.
A c a n t h o m a t o u s epuli~ exhibiting epithelial pearls and hyalinized material adjacent to the epithelium, q'hese epithelial islauds are not typical ofacanthomaLous epulls, but blend into areas of characteristic turnout. T h e cells are not cytologically malignant. HE x 110.
Acanthomatous Epulis
51
keratinocytes (Fig. 3). The intercellular bridges were usually quite prominent and sometimes the ceils were separated by oedema, accentuating this feature (Fig. 2). However, only rarely did this occur to the extent of resembling stellate reticulum, and then only focally. Microcysts were relatively common within the epithelial islands; epithelial pearls, however, occurred only occasionally and were never prominent (Fig. 4). The stroma varied, often within different regions of the same tumour. In some regions it consisted of dense fibrous connective tissue (Fig. 1), in others it was more cellular (Fig. 1) and in still others was fibroblastic, resembling periodontal ligament (Fig. 3). In the bone spaces, the stroma was quite delicate. In one example, hyalinized material was closely associated with the epithelium (Fig. 4). Here, the morphology of the epithelium was somewhat altered, presumably by the presence of this material. However, typical acanthomatous epulis was present nearby. Another example exhibited welldifl~rentiated new bone formation within the stroma. Eight of the acanthomatous epulides exhibited numerous foci of continuity between the t u m o u r and the surface epithelium along a considerable length of its surface, an appearance suggesting multifocal origin from the epithelium. In the sections studied, three exhibited no connection with the epithelium, one example exhibited a small focus of continuity with the surface epithelium and, in one example, the nature of the sections did not allow any conclusion concerning the relationship of the tumour to the surface epithelium. Three examples exhibited discrete, exophytic papillomas of the surface epithelium in the regions of the acanthomatous epulis. One appeared to be part of the tumour, one was clearly independent of the underlying tumour and may have been either reactive or coincidental and a third was equivocal. Another example exhibited a diffuse papillary surface, the fronds of which consisted of tumour. In no case did examination of the tissue sections confirm that the lesion was confined to the gingiva. All lesions either exhibited invasion of bone or were transected at the base and all radiographs exhibited bony destruction.
Group 2 Fourteen examples of acanthomatous epulis exhibited continuity with the epithelial surface. O f these, two were confined completely to the gingiva, the margins of the specimen being clear of tumour by a substantial zone. Five examples exhibited no continuity with the surface epithelium. Discussion
O n the basis of this study, we conclude that the acanthomatous epulis is a form of ameloblastoma. Its persistent invasion of bone with no tendency to metastasize is the clinical behaviour of human intraosseous ameloblastoma and its histological features are similar to one microscopical pattern of ameloblastoma in man (Fig. 5). This variant is referred to as the acanthomatous pattern or simply as acanthomatous ameloblastoma (Pindborg et al., 1971), but it is
.52
Fig, 5,
D . G . G a r d n e r a n d D. C. B a k e r
Human acanthomatous arneloblastoma, The basal cells exhibit palisading, reverse polarization and cytoplasmic vacuolation, HE x 300.
recognized that its clinical behaviour is no different from that oI" other histological patterns. H u m a n ameloblastomas are divided into three clinical types (Gardner and Pegak , 1980), as opposed to their numerous histological variants. T h e most c o m m o n is the typical intraosseous ameloblastoma, also known as the solid or multicystic type. The second is the unicystic ameloblastoma, which is also intraosseous, but takes the form of a cyst. It has no known counterpart in animals. The third clinical type is the relatively rare peripheral or extraosseous ameloblastoma that occurs on the gingiva. Reichart et al. (1989) believe the canine acanthomatous epulis to be equivalent to the peripheral (gingival) ameloblastoma in h u m a n beings. However, its biological behaviour, of infiltrating cancellous bone, is more like that of the h u m a n intraosseous ameloblastoma. T h e h u m a n peripheral ameloblastoma, in contrast, does not tend to invade bone (Gardner, 1977). This study has confirmed that some acanthomatous epulides arise from the epithelial surface; two small examples were located entirely within the gingiva and were continuous with the surface epithelium. In addition, their margins were free of tumour. However, it also appears that other acanthomatous
Acanthonaatous
Epulis
53
epulides arise from within bone, eventually breaking out to form extraosseous growths. The support for this statement is that, on histological examination, eight examples appeared to be deep lesions that exhibited no continuity with the surface epithelium. The origin of these intraosseous tumours could be rests of odontogenic epithelium within the bone. These rests are accepted as one source of human ameloblastomas. There is no way of knowing h o w m a n y acanthomatous epulides arise intraosseously and how many arise extraosseously, because most exhibit both intraosseous and extraosseous growth at surgery. The reason that all canine acanthomatous epulides have been previously considered to be extraosseous tumours that invade bone m a y be that the first clinical evidence of the lesion is as a growth of the gingiva. In contrast, in h u m a n beings, an ameloblastoma may be detected on routine radiographic examination or when there is only a slight expansion of the jaw, i.e., before there is extraosseous growth. Over the years there have been a number of other suggestions concerning the nature of acanthomatous cpulides. At one time they were referred to as adamantinomas, b u t this term is obsolete and seldom used now in either veterinary or h u m a n medicine; in human beings it was a synonym for ameloblastoma. Bostock and White (1987) have suggested that the acanthomatous epulis be considered a basal cell carcinoma, rather than a form of ameloblastoma, because of the close resemblance of its neoplastic epithelium to cells of the stratum germinativum, lack of stellate reticulum and the presence of anastomosing ribbons of cells similar to those seen in basal cell carcinoma of the skin. There are a number of reasons why we disagree with this suggestion. First, the ceils of the acanthomatous epulis for the most part are clearly squamous, although admittedly some acanthomatous epulides are composed, in part, of cells that more closely resemble basal cells than keratinocytes. Second, although a few basal cell carcinomas of the gingiva have been reported in man, it is now generally accepted that they probably represent the basal cell pattern of ameloblastoma (Gardner, 1977; Buchner and Sciubba, 1987; Verstraete el al., 1992). In any event, the clinical behaviour of peripheral ameloblastomas and basal cell carcinomas is the same. Third, the absence of stellate reticulum in acanthomatous epulides does not preclude the diagnosis of ameloblastoma, because, in a number of histological variants of ameloblastoma in h u m a n beings, the stellate reticulum is replaced by other cells, e.g., squamous cells in the acanthomatous pattern and basal cells in the basal cell pattern. Barker and V a n Dreumel (1985) suggested that the acanthomatous epulis may be a form of squamous cell carcinoma, based on the fact that some acanthomatous epulides transform into squamous cell carcinomas when they invade bone. We are unaware of any examples that have done so spontaneously, although some have transformed into squamous cell carcinoma after treatment by therapeutic irradiation (Thrall el al., 1981; Thrall, 1984). There are three reasons against considering acanthomatous epulides as squamous cell carcinomas. First, they are locally invasive tumours that do not fit the definition of malignancy in that they have no potential to metastasize, unlike squamous cell carcinoma. In this respect they exhibit the same clinical behaviour as the h u m a n intraosseous ameloblastoma, which is considered a
54
D . G . Gardner and D. C. Baker
benign but locally invasive tumour. Second, they do not exhibit cytological evidence of malignancy and third, the characteristic features of the basal cells of acanthomatous epulis are not found in squamous cell carcinomas. A further suggestion has been that acanthomatous epulides are the malignant counterpart of the fibromatous epulis (Langham el al., 1965), Again, acanthomatous epulides are locally invasive, not malignant, turnouts and, in any event, do not appear to be related to the fibromatous epulis. The variable nature of the stroma associated with the acanthomatous epulis probably only reflects the various types of connective tissue found in the jaws, i.e., the dense fibrous connective tissue of the gingiva, the fibroblastic connective tissue of the periodontal ligament and the loose connective tissue of bone marrow. The tumour infiltrates through these tissues, which in fact are stroma and not an integral part of the lesion, as in the fibromatous epulis. Since the stroma varies, it follows that the presence of the so-called periodontal ligament stroma is not necessary, as has been suggested by Dubielzig and Thrall (1982), to make the diagnosis of acanthomatous epulis or to distinguish it from the ameloblastoma. The finding of papillomas and ulceration histologically in some examples reflects the clinical description given by Bostock and White (1987) of acanthomatous epulides. They stated that in some examples the epithelium exhibited irregular, fungating processes, while in others it was ulcerated with extensive areas of necrosis. Material that has been considered osteoid or metaplastic bone has been noted as occurring occasionally in acanthomatous epulides (Barker and Van Dreumel, 1985; Bostock and White, 1987). Similar material was present adjacent to the epithelium in one example in Group 1 of the present series (Fig. 4), However, in that the acanthomatous epulis appears to be an odontogenic tumour, this material would be better considered dysplastic dentine (dentinoid) rather than osteoid. Osteoid and dentine are both collagenous tissues and, in the absence of dentinal tubules, indistinguishable histologically. If this osteoid-like material is found adjacent to odontogenic epithelium, as in the acanthomatous epulis, this is strong evidence that the material is, in fact, dysplastic dentine. This hypothesis has been used in the classification of h u m a n odontogenic tumours based upon inductive changes (Pindborg et al., 1971) and is discussed in detail by these authors and by Gardner and Farquahar (1979). True bone also occasionally occurs in the stroma of acanthomatous epulides away from the epithelium and is probably a reaction to the tumour. The acanthomatous epulis appears to be equivalent to the ameloblastoma in man and there is little scientific justification in separating it from another tumour in dogs that has been designated an ameloblastoma. The ameloblastoma in man exhibits a varied histological appearance and this may also be true in dogs. In this connection, a tumour having a different histological appearance from the acanthomatous epulis has been described by Dubielzig and Thrall (1982) as keratinizing ameloblastoma. We recommend that acanlhomatous epulis be replaced as the designation for this tumour by canine acanlhomatous ameloblastoma, a term that implies the clinical behaviour associated with ameloblastomas and emphasizes the tumour's acanthomatous appearance, but does not imply that it necessarily arises from the gingiva, as epulis does.
Acanthomatous Epulis
55
Acknowledgments We thank Drs B. Wilcock and J. Vager of Guelph, Canada, for kindly providing access to their material. References Barker, I. K. and Van Dreumel, A. A. (1985). The alimentary system. In: Pathology of Domestic Animals, 3rd Edit. J. V. F. Jubb, P. C. Kennedy and N. Palmer, Eds, Academic Press, London, pp. 17-19. Bostock, D. E. and White, R. A. S. (1987). Classification and behaviour after surgery of canine epulides. Journal of Comparative Pathology, 97, 197-205. Buchner, A. and Sciubba, J. J. (1987). Peripheral epithelial odontogenic tumors: a review. Oral Surgery, Oral Medicine and Oral Pathology, 63, 688-97. Dubielzig, R. R., Goldschmidt, M. H. and Brodey, R. S. (1979). The nomenclature of periodontal epulides in dogs. Veterinary Pathology, 16, 209-214. Dubielzig, R. R. and Thrall, D. E. (1982). Ameloblastoma and keratinizing ameloblastoma in dogs. Veterinary Pathology, 19, 596-607. Gardner, D. G. (1977). Peripheral ameloblastoma. A study of 21 cases, including 5 reported as basal cell carcinoma of the gingiva. Cancer, 39, 1625-1633. Gardner, D. G. and Baker, D. C. (1991). The fibromatous epulis in dogs and the peripheral odontogenic fibroma in human beings: two equivalent lesions. Oral Surgery, Oral Medicine and Oral Pathology, 71,317-321. Gardner, D. G. and Farquahar, D. A. (1979). A classification ofdysplastic forms of dentin. Journal of Oral Pathology, 8, 28-46. Gardner, D. G. and Pe~ak, A. M.J. (1980). The treatment ofameloblastoma based on pathologic and anatomic principles. Cancer, 46, 2514--2519. Head, K. W. (1976). Turnouts of the upper alimentary tract. Bulletin of the World Health Organization, 53, 145-167. Langham, R. F., Keahey, K. K., Mostosky, U. V. and Schirmer, R. G. (1965). Journal oj'the American Veterinary Medical Association, 146, 474-480. Lucas, R. B. (1984). Pathology of Tumours of the Oral Tissues, 4th Edit. Churchill Livingstone, Edinburgh, pp. 31-60. Pindborg, J. j., Kramer, I. R. H. and Torlonl, H. (1971). Histological Typing of Odontogenic Turnouts, Jaw Cysts, and Allied Lesions. World Health Organization, Geneva. Reichart, P. A., Philipsen, H. P. and Dfirr, U-M. (1989). Epulides in dogs. Journal of Oral Pathology and Medicine, 18, 92-96. Thrall, D. E. (1984). Orthovoltage radiotherapy of acanthomatous epulides in 39 dogs. Journal of the American Veterinary Medical Association, 184, 826-829. ThraU, D. E., Goldschmidt, M. H. and Biery, D. N. (1981). Malignant tumor formation at the site of previously irradiated acanthomatous epulides in four dogs. Journal of the American Veterinary Medical Association, 178, 127-132. Verstraete, F.J.M., Ligthelm, A. J., and Weber, A. (1992). The histological nature of epulides in dogs. Journal of Comparative Pathology, 106, 169-182.
February 25th, ~Received, Accepted, September 1st,
1992-] 1992_]
The Relationship of the Canine Acanthomatous Epulis to Ameloblastoma D. G. G a r d n e r and D. C. Baker* Division of Oral Pathology and Oncology, University of Colorado School of Dentistry, Denver, CO 80262 and *Department of Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, U.S.A.
Summary This paper compares the microscopic f~atures and clinical behaviour of the acanthomatous epulis in dogs with those of ameloblastoma in human beings. The acanthomatous epulis has similar microscopic features to one histological variant of human ameloblastoma, the acanthomatous ameloblastoma. Moreover, its clinical behaviour is equivalent to that ofintraosseous ameloblastoma in human beings, not of the human peripheral (extraosseous) ameloblastoma, as has been suggested. The stroma ofacanthomatous epulides varies and does not always resemble periodontal ligament, a feature that in dogs has been used to distinguish them from ameloblastomas. It is concluded that the acanthomatous epulis (1) is an ameloblastoma, (2) arises from the gingival epithelium in some cases, but (3) may also arise intraosseously and then break out of bone. We recommend the term canine acanthomatous ameloblastoma as being appropriate for this lesion. Introduction The term acanthomatous epulis was first used by Dubielzig, Goldschmidt and Brodey (1979) in their attempt to standardize the nomenclature of canine epulides. Previously, these lesions had been included within the category of fibromatous and ossifying epulis (Head, 1976) or were referred to as adamantinomas and considered, because of their ability to invade bone, to be the malignant counterpart of the fibromatous and ossifying epulis (Langham, Keahey, Mostosky and Schirmer, 1965). This latter lesion, generally referred to simply as the fibromatous epulis, is, in turn, the canine counterpart of the peripheral odontogenic fibroma in man (Bostock and White, 1987; Gardner and Baker, 1991). Bostock and White (1987) considered the acanthomatous epulis to be a basal cell carcinoma of the gingiva, while Reichart, Philipsen and Dfirr (1989) believed it to be a peripheral (extraosseous) ameloblastoma originating from the surface epithelium of the oral cavity and Verstraete, Ligthelm and Weber (1992) have used this designation in a recent paper. At present, acanthomatous epulis is the most widely used term. The acanthomatous epulis consists of broad sheets and anastomosing cords Address for correspondence: Dr D. G. Gardner, University of Colorado School of Dentistry, Campus Box C284, 4200 East Ninth Avenue, Denver CO 80262, U.S.A. 0021-9975/93/010047 + 09 $08.00/0
© 1993 Academic Press Limited
48
D.G. Gardner and D. G. Baker
of epithelium within a connective tissue stroma. There is, however, some inconsistency in the literature concerning the nature of the stroma. Dubielzig et al. (1979) emphasized that acanthomatous epulides, like fibromatous epulides, exhibit dense cellular stroma consisting of stellate cells and tightly packed fibrillar collagen. This appearance is typical of periodontal ligament and Dubielzig and Thrall (1982) used it as a distinguishing feature between acanthomatous epulides and ameloblastomas, which, they state, do not exhibit this type of stroma. In contrast, Bostock and White (1987) stated that acanthomatous epulides exhibit a mature collagenous, relatively acellular, stroma and some published illustrations show this feature (Thrall, Goldschmidt and Biery, 1981). Barker and Van Dreumel (1985) do not c o m m e n t on the nature of the stroma, other than to indicate that small foci of metaplastic hard tissue may develop within it. Dubielzig et al. (1979) also noted that some examples exhibit foci of bone, cementum or dentine. T h e epithelium is the more significant component of acanthomatous epulides, but it is important to determine whether the stroma in these tumours consistently resembles periodontal ligament. There are two other questions that arise. T h e first is whether the acanthomatous epulis is truly an extraosseous lesion that subsequently invades bone. Its clinical behaviour appears to be that of the typical intraosseous ameloblastoma in man (a lesion that originates and eventually breaks out of bone) rather than of the peripheral ameloblastoma that Reichart et al. (1989) suggested as the h u m a n counterpart of acanthomatous epulis. T h e latter type of ameloblastoma, unlike the intraosseous ameloblastoma, in h u m a n beings generally does not invade bone (Gardner, 1977). A major problem is that once a lesion exhibits both intraosseous and extraosseous components, it is no longer possible to determine whether it was originally intraosseous or extraosseous. In h u m a n beings, numerous peripheral ameloblastomas have been excised which clearly did not involve the underlying bone (Gardner, 1977). T h e second question is why attempt to distinguish between acanthomatous epulides and ameloblastomas in dogs if their clinical behaviour is identical and their histopathology similar, except for the possible presence of stroma exhibiting periodontal ligament in acanthomatous epulides. The purpose of the present study is to compare the pathology of acanthomatous epulides in dogs with that of peripheral ameloblast~mas and intraosseous ameloblastomas in h u m a n beings in an attempt to answer the questions above.
M a t e r i a l s and M e t h o d s
Group 1 Haematoxylin and eosin(HE)-stained sections of all I3 examples of acanthomatous epulides accessioned by the Department of Pathology of the College of Veterinary Medicine of Colorado State University from June 1986 to January 1990 were examined and compared with the well-recognized histological features of human ameloblastomas, both peripheral and intraosscous. These features are illustrated in several books and articles (Pindborg, Kramer and Torloni, 1971; Gardner, 1977; Lucas, 1984). In addition, in all cases the radiographs were studied together with the
Acanthomatous Epulis
49
corresponding histopathological sections, to evaluate whether the lesiohs originated from within bone or from the surface. The criterion accepted for proof of extraosseous origin was a tissue section that exhibited an acanthomatous epulis that was entirely within the gingiva and the margins &which were clear of tumour. In addition, there must be no radiographic evidence of bony invasion.
Group2 The examples in Group 1 did not provide sufficient information to evaluate adequately whether acanthomatous epulides arise from the epithelial surface or from within bone. Consequently, a further 19 pathology sections, representing the acanthomatous epulides accessioned in 1989 and 1990 by a private veterinary pathology service in Guelph, Canada, were studied to evaluate the relationship of the tumours to the epithelial surface.
Results
Group 1 The clinical features of the 13 acanthomatous epulides are summarized in Table 1. The acanthomatous epulides consisted of islands and cords of squamous epithelium that had invaded irregularly throughout a connective tissue stroma (Fig. 1). In some examples the basal cells were unremarkable but, typically, in at least some parts of the tumour, they were columnar and arranged with their long axes perpendicular to the basement membrane, a feature referred to as palisading (Fig. 2). Moreover, their cytoplasm was vacuolated and their nuclei exhibited reverse polarization, i.e., they were situated at the ends of the cells distal to the basement membrane. These basal cells typically surrounded regularly arranged sheets of squamous epithelium, although in some tumours, or parts of a tumour, the central cells resembled basal cells more than
Table I The clinical features of 13 acanthomatous epulldes (Group 1)
Breeds Sex Age Location
8 (2 collies) 3 mixed 1 unknown 6 males, 7 females Range 4 to 14 years Mean 10'5 years Median 11 years Mandible Incisor region Premolar region Molar region Maxilla Incisor region Premolar region Molar region
Fig. 1.
Low power photomicrograph of an acanthomatous epulis illustrating islands and cords of squamous epithelium whi¢la have infiltrated through the stroma, T h e strorna varies from dense (ibrous eoanective tissue on the bottom of the illustration to looser connective tissue on the top. HE x55.
Fig. 2.
Higher magnification of an area similar to Fig. 1, illustrating the typical histological features of acanthvmatous epulis. T h e basal ceils are orientated with their long axes perpendicular to the basement m e m b r a n e (palisading), their cytoplasm is vaeuolated and their nuclei are located at the distal ends of the cells (reverse polarization). Tile central cells are squamous and separated by ocdema. H E x 2 1 9 .
Fig. 3.
A n area o f a c a n t h o m a t o u s epulis in which the central cells of the epithelial islands are basilar rather than squarnous. T h e stroma is of the fibroblastic type, typical of canine periodontal ligament. In fact, this tissue was scraped t~rom the root of a tooth. HE x 219.
Fig. 4.
A c a n t h o m a t o u s epuli~ exhibiting epithelial pearls and hyalinized material adjacent to the epithelium, q'hese epithelial islauds are not typical ofacanthomaLous epulls, but blend into areas of characteristic turnout. T h e cells are not cytologically malignant. HE x 110.
Acanthomatous Epulis
51
keratinocytes (Fig. 3). The intercellular bridges were usually quite prominent and sometimes the ceils were separated by oedema, accentuating this feature (Fig. 2). However, only rarely did this occur to the extent of resembling stellate reticulum, and then only focally. Microcysts were relatively common within the epithelial islands; epithelial pearls, however, occurred only occasionally and were never prominent (Fig. 4). The stroma varied, often within different regions of the same tumour. In some regions it consisted of dense fibrous connective tissue (Fig. 1), in others it was more cellular (Fig. 1) and in still others was fibroblastic, resembling periodontal ligament (Fig. 3). In the bone spaces, the stroma was quite delicate. In one example, hyalinized material was closely associated with the epithelium (Fig. 4). Here, the morphology of the epithelium was somewhat altered, presumably by the presence of this material. However, typical acanthomatous epulis was present nearby. Another example exhibited welldifl~rentiated new bone formation within the stroma. Eight of the acanthomatous epulides exhibited numerous foci of continuity between the t u m o u r and the surface epithelium along a considerable length of its surface, an appearance suggesting multifocal origin from the epithelium. In the sections studied, three exhibited no connection with the epithelium, one example exhibited a small focus of continuity with the surface epithelium and, in one example, the nature of the sections did not allow any conclusion concerning the relationship of the tumour to the surface epithelium. Three examples exhibited discrete, exophytic papillomas of the surface epithelium in the regions of the acanthomatous epulis. One appeared to be part of the tumour, one was clearly independent of the underlying tumour and may have been either reactive or coincidental and a third was equivocal. Another example exhibited a diffuse papillary surface, the fronds of which consisted of tumour. In no case did examination of the tissue sections confirm that the lesion was confined to the gingiva. All lesions either exhibited invasion of bone or were transected at the base and all radiographs exhibited bony destruction.
Group 2 Fourteen examples of acanthomatous epulis exhibited continuity with the epithelial surface. O f these, two were confined completely to the gingiva, the margins of the specimen being clear of tumour by a substantial zone. Five examples exhibited no continuity with the surface epithelium. Discussion
O n the basis of this study, we conclude that the acanthomatous epulis is a form of ameloblastoma. Its persistent invasion of bone with no tendency to metastasize is the clinical behaviour of human intraosseous ameloblastoma and its histological features are similar to one microscopical pattern of ameloblastoma in man (Fig. 5). This variant is referred to as the acanthomatous pattern or simply as acanthomatous ameloblastoma (Pindborg et al., 1971), but it is
.52
Fig, 5,
D . G . G a r d n e r a n d D. C. B a k e r
Human acanthomatous arneloblastoma, The basal cells exhibit palisading, reverse polarization and cytoplasmic vacuolation, HE x 300.
recognized that its clinical behaviour is no different from that oI" other histological patterns. H u m a n ameloblastomas are divided into three clinical types (Gardner and Pegak , 1980), as opposed to their numerous histological variants. T h e most c o m m o n is the typical intraosseous ameloblastoma, also known as the solid or multicystic type. The second is the unicystic ameloblastoma, which is also intraosseous, but takes the form of a cyst. It has no known counterpart in animals. The third clinical type is the relatively rare peripheral or extraosseous ameloblastoma that occurs on the gingiva. Reichart et al. (1989) believe the canine acanthomatous epulis to be equivalent to the peripheral (gingival) ameloblastoma in h u m a n beings. However, its biological behaviour, of infiltrating cancellous bone, is more like that of the h u m a n intraosseous ameloblastoma. T h e h u m a n peripheral ameloblastoma, in contrast, does not tend to invade bone (Gardner, 1977). This study has confirmed that some acanthomatous epulides arise from the epithelial surface; two small examples were located entirely within the gingiva and were continuous with the surface epithelium. In addition, their margins were free of tumour. However, it also appears that other acanthomatous
Acanthonaatous
Epulis
53
epulides arise from within bone, eventually breaking out to form extraosseous growths. The support for this statement is that, on histological examination, eight examples appeared to be deep lesions that exhibited no continuity with the surface epithelium. The origin of these intraosseous tumours could be rests of odontogenic epithelium within the bone. These rests are accepted as one source of human ameloblastomas. There is no way of knowing h o w m a n y acanthomatous epulides arise intraosseously and how many arise extraosseously, because most exhibit both intraosseous and extraosseous growth at surgery. The reason that all canine acanthomatous epulides have been previously considered to be extraosseous tumours that invade bone m a y be that the first clinical evidence of the lesion is as a growth of the gingiva. In contrast, in h u m a n beings, an ameloblastoma may be detected on routine radiographic examination or when there is only a slight expansion of the jaw, i.e., before there is extraosseous growth. Over the years there have been a number of other suggestions concerning the nature of acanthomatous cpulides. At one time they were referred to as adamantinomas, b u t this term is obsolete and seldom used now in either veterinary or h u m a n medicine; in human beings it was a synonym for ameloblastoma. Bostock and White (1987) have suggested that the acanthomatous epulis be considered a basal cell carcinoma, rather than a form of ameloblastoma, because of the close resemblance of its neoplastic epithelium to cells of the stratum germinativum, lack of stellate reticulum and the presence of anastomosing ribbons of cells similar to those seen in basal cell carcinoma of the skin. There are a number of reasons why we disagree with this suggestion. First, the ceils of the acanthomatous epulis for the most part are clearly squamous, although admittedly some acanthomatous epulides are composed, in part, of cells that more closely resemble basal cells than keratinocytes. Second, although a few basal cell carcinomas of the gingiva have been reported in man, it is now generally accepted that they probably represent the basal cell pattern of ameloblastoma (Gardner, 1977; Buchner and Sciubba, 1987; Verstraete el al., 1992). In any event, the clinical behaviour of peripheral ameloblastomas and basal cell carcinomas is the same. Third, the absence of stellate reticulum in acanthomatous epulides does not preclude the diagnosis of ameloblastoma, because, in a number of histological variants of ameloblastoma in h u m a n beings, the stellate reticulum is replaced by other cells, e.g., squamous cells in the acanthomatous pattern and basal cells in the basal cell pattern. Barker and V a n Dreumel (1985) suggested that the acanthomatous epulis may be a form of squamous cell carcinoma, based on the fact that some acanthomatous epulides transform into squamous cell carcinomas when they invade bone. We are unaware of any examples that have done so spontaneously, although some have transformed into squamous cell carcinoma after treatment by therapeutic irradiation (Thrall el al., 1981; Thrall, 1984). There are three reasons against considering acanthomatous epulides as squamous cell carcinomas. First, they are locally invasive tumours that do not fit the definition of malignancy in that they have no potential to metastasize, unlike squamous cell carcinoma. In this respect they exhibit the same clinical behaviour as the h u m a n intraosseous ameloblastoma, which is considered a
54
D . G . Gardner and D. C. Baker
benign but locally invasive tumour. Second, they do not exhibit cytological evidence of malignancy and third, the characteristic features of the basal cells of acanthomatous epulis are not found in squamous cell carcinomas. A further suggestion has been that acanthomatous epulides are the malignant counterpart of the fibromatous epulis (Langham el al., 1965), Again, acanthomatous epulides are locally invasive, not malignant, turnouts and, in any event, do not appear to be related to the fibromatous epulis. The variable nature of the stroma associated with the acanthomatous epulis probably only reflects the various types of connective tissue found in the jaws, i.e., the dense fibrous connective tissue of the gingiva, the fibroblastic connective tissue of the periodontal ligament and the loose connective tissue of bone marrow. The tumour infiltrates through these tissues, which in fact are stroma and not an integral part of the lesion, as in the fibromatous epulis. Since the stroma varies, it follows that the presence of the so-called periodontal ligament stroma is not necessary, as has been suggested by Dubielzig and Thrall (1982), to make the diagnosis of acanthomatous epulis or to distinguish it from the ameloblastoma. The finding of papillomas and ulceration histologically in some examples reflects the clinical description given by Bostock and White (1987) of acanthomatous epulides. They stated that in some examples the epithelium exhibited irregular, fungating processes, while in others it was ulcerated with extensive areas of necrosis. Material that has been considered osteoid or metaplastic bone has been noted as occurring occasionally in acanthomatous epulides (Barker and Van Dreumel, 1985; Bostock and White, 1987). Similar material was present adjacent to the epithelium in one example in Group 1 of the present series (Fig. 4), However, in that the acanthomatous epulis appears to be an odontogenic tumour, this material would be better considered dysplastic dentine (dentinoid) rather than osteoid. Osteoid and dentine are both collagenous tissues and, in the absence of dentinal tubules, indistinguishable histologically. If this osteoid-like material is found adjacent to odontogenic epithelium, as in the acanthomatous epulis, this is strong evidence that the material is, in fact, dysplastic dentine. This hypothesis has been used in the classification of h u m a n odontogenic tumours based upon inductive changes (Pindborg et al., 1971) and is discussed in detail by these authors and by Gardner and Farquahar (1979). True bone also occasionally occurs in the stroma of acanthomatous epulides away from the epithelium and is probably a reaction to the tumour. The acanthomatous epulis appears to be equivalent to the ameloblastoma in man and there is little scientific justification in separating it from another tumour in dogs that has been designated an ameloblastoma. The ameloblastoma in man exhibits a varied histological appearance and this may also be true in dogs. In this connection, a tumour having a different histological appearance from the acanthomatous epulis has been described by Dubielzig and Thrall (1982) as keratinizing ameloblastoma. We recommend that acanlhomatous epulis be replaced as the designation for this tumour by canine acanlhomatous ameloblastoma, a term that implies the clinical behaviour associated with ameloblastomas and emphasizes the tumour's acanthomatous appearance, but does not imply that it necessarily arises from the gingiva, as epulis does.
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55
Acknowledgments We thank Drs B. Wilcock and J. Vager of Guelph, Canada, for kindly providing access to their material. References Barker, I. K. and Van Dreumel, A. A. (1985). The alimentary system. In: Pathology of Domestic Animals, 3rd Edit. J. V. F. Jubb, P. C. Kennedy and N. Palmer, Eds, Academic Press, London, pp. 17-19. Bostock, D. E. and White, R. A. S. (1987). Classification and behaviour after surgery of canine epulides. Journal of Comparative Pathology, 97, 197-205. Buchner, A. and Sciubba, J. J. (1987). Peripheral epithelial odontogenic tumors: a review. Oral Surgery, Oral Medicine and Oral Pathology, 63, 688-97. Dubielzig, R. R., Goldschmidt, M. H. and Brodey, R. S. (1979). The nomenclature of periodontal epulides in dogs. Veterinary Pathology, 16, 209-214. Dubielzig, R. R. and Thrall, D. E. (1982). Ameloblastoma and keratinizing ameloblastoma in dogs. Veterinary Pathology, 19, 596-607. Gardner, D. G. (1977). Peripheral ameloblastoma. A study of 21 cases, including 5 reported as basal cell carcinoma of the gingiva. Cancer, 39, 1625-1633. Gardner, D. G. and Baker, D. C. (1991). The fibromatous epulis in dogs and the peripheral odontogenic fibroma in human beings: two equivalent lesions. Oral Surgery, Oral Medicine and Oral Pathology, 71,317-321. Gardner, D. G. and Farquahar, D. A. (1979). A classification ofdysplastic forms of dentin. Journal of Oral Pathology, 8, 28-46. Gardner, D. G. and Pe~ak, A. M.J. (1980). The treatment ofameloblastoma based on pathologic and anatomic principles. Cancer, 46, 2514--2519. Head, K. W. (1976). Turnouts of the upper alimentary tract. Bulletin of the World Health Organization, 53, 145-167. Langham, R. F., Keahey, K. K., Mostosky, U. V. and Schirmer, R. G. (1965). Journal oj'the American Veterinary Medical Association, 146, 474-480. Lucas, R. B. (1984). Pathology of Tumours of the Oral Tissues, 4th Edit. Churchill Livingstone, Edinburgh, pp. 31-60. Pindborg, J. j., Kramer, I. R. H. and Torlonl, H. (1971). Histological Typing of Odontogenic Turnouts, Jaw Cysts, and Allied Lesions. World Health Organization, Geneva. Reichart, P. A., Philipsen, H. P. and Dfirr, U-M. (1989). Epulides in dogs. Journal of Oral Pathology and Medicine, 18, 92-96. Thrall, D. E. (1984). Orthovoltage radiotherapy of acanthomatous epulides in 39 dogs. Journal of the American Veterinary Medical Association, 184, 826-829. ThraU, D. E., Goldschmidt, M. H. and Biery, D. N. (1981). Malignant tumor formation at the site of previously irradiated acanthomatous epulides in four dogs. Journal of the American Veterinary Medical Association, 178, 127-132. Verstraete, F.J.M., Ligthelm, A. J., and Weber, A. (1992). The histological nature of epulides in dogs. Journal of Comparative Pathology, 106, 169-182.
February 25th, ~Received, Accepted, September 1st,
1992-] 1992_]