Journal
of Oral Pathology 1976: 5: 295-304
Granular cell peripheral odontogenic fibroma J. F. LowNiE, M. At.i-iNr AND M. SHEAR
Department of Oral Pathology, School of Pathology, University of the Witwatersrand and South African Institute for Medical Researeh. South Africa Abstract. A case of a peripher-al odontogenic fibr-oma whieh contained aggregates of lar-ge granular eells is reported. These granular eells are similar to those pr-eviously described in t h e granular cell r-nyoblastoma, congenital epulis and the granular cell ameloblastic fibroma. Deep extensions of the basal layer of overlying gingival epithelium, in double-strand fasbion, ar-e frequently obser-ved in peripher-al odontogenie fibr-on-ras. These strands elosely resemble those seen in the tumor itself. On this basis, and as similar basal eell prolongations ar-e seen in other jaw lesions, it is postulated that residual eetomesenchymal influe n c e may be responsible for inducing the basal cell proliferations in a similar manner to t h a t which occur-s during ear-ly embryonic dental development. This, it is suggested, might possibly be the histogenesis of the odontogenic epithelial strands in the peripheral odontogenie fibroma. Received 3 February, accepted for publication I May 1976
^ T h e odontogenic fibroma is a benign odonr togenic neoplasm composed of whorling I and streaming fibroblasts interspersed with collagen fibers and containing varying amounts of odontogenic epithelium. Foei |: of dentinoid are also found. It can arise centrally within the jaws, or peripherally w h e r e it may be indistinguishable clinically L i f r o m a fibrous epulis. T h e term 'odontogenic fibroma' appears to have been introduced by Gorlin (1970) in order to distinguish this lesion from the ameloblastic fibroma and ameloblastoma. This terminology was accepted by the W o r l d Health Organization in their Histological Typing of Odontogenic Tttniottrs, Jaw C^ysts, attd Allied Lesiotts (Pindborg et al. 1971). Baden et al. (1968) deseribed the same tumor as an 'odontogenie gingival epithelial hamartoma'. The odontogenic fibroma is a relatively rare lesion. Cases have
been deseribed by Deeker & Lafitte (1967), Baden et al. (1968, 1973). Although the presence of large oxyphil granular cells has been described in other odontogenie tumors, sueh as the ameloblastie fibroma atid ameloblastoma, these cells have not been previously reported in the odontogenic fibroma. Little is known about the pathogenesis of this tumor, although Baden et al. (1968) made some intetesting observations which will be referred to in the Discussion. The purpose of this paper is to report a case showing granular cell change and to discuss a possible histogenesis of the tumor.
Case Report
A 40-year-old black female catne to the hospital with a peduticulated swelling in the
296
LOWNIE, ALTINI AND SHEAR
• «i-. - ; »-^l
F/g. i. Odontogenic fibroma, showmg streaming of fibroblasts, nests and strands of odontogenic epithelium and areas of dentinoid (D). H & E x 100.
Eig. 2. An area of granular eells (G) in the tumor mass. H & E X 100.
GRANULAR CELL PERIPHERAL ODONTOGENIC FIBROMA
297
Fig- 3. Granular eells closely associated with odontogenic epithelial cells. Masson's triehrome X 250. p a l a t a l gingiva of the maxillaty right third m o l a r . The lesion, measuring 1 X 1 X 0.5 cm, was not painful and had been present for t h e previous 2 months. Radiological examination revealed no abnormality of the maxilla on the affected side. The lesion was excised under general anesthesia, atid the postoperative course was uneventful. Histology Histologically, the tumor consisted of a densely cellular fibroblasfic mass exhibiting whorling and streaming (Fig. 1). Scattered throughout the tumor were numerous strands and islets of odontogenic epithelium. T h e strands consisted of a double layer of small cells with darkly staining nuclei. The islets were formed by clusters of cells, some of which were swollen (Figs. 2 and 3). The latter groups of cells were associated with still larger cells containitig granular eosino-
philic cytoplasm. These granular cells appeared, in fact, to be of epithelial origin as transitional forms wete seen in which the swollen epithelial cells showed aeeumulations of eosinophilic granules (Figs. 3 and 4). Some of the granular cells were isolated and It was not possible to determine whether these were of epithelial or fibroblastic origin. A nutnber of foci of dentinoid were present in the tumor (Fig. 5). Strands and islets of odontogenie epitheliutn were seen close to some dentinoid surfaces, suggesting that the epithelium may have had an inductive influence in their formation. The fibroblastie mass extended to the covering epithelium and in many areas the basal layer of the epithelium extended into the tumor as long double-stranded prolongatiotis similar to those seen deeper in the lesion (Fig. 6).
298
LOWNIE, ALTINI AND SHEAR
Fig. 4. Swollen epithelial cells showing transition to granular cells. Masson's trichrome X 400.
Fig. 5. Foci of dentinoid closely associated with odontogenic epithelium. H & E X 100.
GRANULAR CELL PERIPHERAL ODONTOGENIC FIBROMA
299
. 6. Another case of odontogenic fibroma, showing extensions of the basal cells of surface epithelium in a double strand fashion. Note the epithelium streaming deeply into the lesion (arr o w s ) . H & E X 64.
Discussion
G r a n u l a r cells in lesions of the oral eavity and jaws are well doeumented. These include the granular eell myoblastoma (Shear 1960), eongenital epulis (Custer & Fust 1952), gratiular eell ameloblastoma (MeCal-
lum & Cappell 1957), granular eell ameloblastic fibroma (Couch et al. 1962) and more recently in the epithelium of some odontogenie cysts (Gold & Christ 1970, Buchner 1972). The histogenesis of the granular cells in the granular cell myoblastoma, as well as in
300
LOWNIE, ALTINI AND SHEAR
the eongenital epulis, is controversial. There is an extensive literature on the subject, but the main theories as to the origin of these lesions explain them as neoplasms of primitive myoblasts, as a degenerative or regenerative change in mature striated musele, as a product of neural tissue or of fibroblasts, or as a collection of histioeytes storing an abnormal metabolite. Shear (1960) states that these eells are not neoplastie, but t-epresent a metabolie change which can oecur in muscle cells, fibroblasts and epithelial cells and suggests the term 'oxyphil granular change' as an alternative to granular cell myoblastoma. It is agreed that the granular cells of the ameloblastoma, as well as those of the odontogenie eyst are epithelial in origin (Gorlin 1970, Buehner 1972). Investigation into the ultrastructure of the granular cell at-neloblastoma t-eveals that the granules are pleomorpbic electron-dense granules identifiable as lysosomes (Navo-
rette & Smitb 1971). The granular eells of the ameloblastic fibroma seem clearly to be of mesodermal origin, representitig an ageing or degenerative process of the mesodermal component, although there is no histochemical evidenee to support this (Waldron et al. 1963). The majority of granular eells in the present ease, beeause of their close relationship with the odontogenic epithelium, and in view of the presenee of transitional forms, would appear to be epithelial in origin. We cannot, however, absolutely exclude the possibility that some of the granular cells are of fibroblastic origin, iti which case it would be necessary to postulate a dual origin for these cells. Narrow extensions of the basal layer of eells of the covering epithelium, many of them double-stranded, are a histological feature which we have observed repeatedly in normal gingiva (Eig. 7), in fibrous epulides (Eig. 8) and in peripberal odontogenie fi-
Fig. 7. Nor-mal attached gingivae from lower third molar region showing double-stranded extensions (arrowed) of the basal cells of some rete ridges, into the lamina propria. H & E X 100.
GRANULAR CELL PERIPHERAL ODONTOGENIC EIBROMA
301
I
Fig. 8. Eibrous epulis showing similar proliferations of the basal layer of cells as seen in normal gingivae and in peripheral odonlogenie fibromas. H & E X 160. b r o m a s (Fig. 6). Ameloblastic cells originating from the overlying oral epithelium in an ameloblastic sarcoma bave been reported (Villa 1955). In the field of keratocysts, Stoelinga (1971) suggests that besides their possible development from remnants of dental lamina or epithelial inclusiotis, origin : from basal cell hamartias of the oral mucosa should be considered. The apparent
origin of some ameloblastomas from the basal layer of oral epithelium is a phenomenoti which is ofteti seen by pathologists (Chatnpion et al. 1951, Lee et al. 1971). There has been a tendency to ascribe this apparent epithelial origin to 'collision' of the tumor with overlying tnucosa (Lucas 1972, Shafer et al. 1974). In 1968, Baden et al. reported a series of
302
LOWNIE, ALTINI AND SHEAR
cases, which would, in terms of the WHOreeommended notnnenclature, be ealled 'peripberal odontogenic fibromas'. These authors suggested the term 'odontogenic gingival epithelial hamartoma'. In their disetission they stated their belief that these lesions originate from odontogenie epithelial rests of the dental lamina. They also, however, referred to what they ealled a more remote possibility. They described the same focal proliferations from the basal epithelium of the gingiva which we have described here. In all three of their cases, clusters of odontogenic epithelial cells appeared in direct continuity witb tbe basal layer of the stratified squamous epithelium and they noted a resemblanee to the focal budding of basal eells in basal eell carcinoma of the skin. They eontinued: "Sueh a pathogenic meehanism eould be theorized since the dental lamina originates from the gingival epithelium in the embryo. Perhaps the potential for differentiation remains, only to be provoked onee more by unknown stimuli under exceptional conditions in adulthood. The rarer cases of extra-osseous ameloblastomas deseribed in the literature lend support for such a view". 'We should like to support these latter views, but also to extend them by attempting to explain tbe various forms of basal eell proliferation in terms of the following hypothesis. It is now widely accepted tbat embryonie tooth development in vertebrates appears to be initiated by eetomesenehyme. This eetomesenehyme is of neural crest origin and migrates into tbe developing mandibular and maxillary proeesses where it interacts with adjacent epithelium to initiate proliferation of the basal layer and the dental lamina (Gaunt et al. 1971, Slavkin 1974). This odontogenie epithelium, onee induced, itself possesses inductive potential. It is now well reeognized that this mutual interaction may be exerted in tbe patho-
genesis of a variety of odontogenie tumors, so that this inductive phenomenon is not eonfined to embryonic tooth development. It may be, therefore, that residual ectomesenchymal influence may persist in the gingivae after eompletion of development of the dentition. If this is indeed so, then the double strand proliferations seen in normal gingiva, fibrous epulides and the peripheral odontogenic fibroma; as well as the apparent surface origin of some ameloblastomas and other odontogenie tumors, and the basal cell proliferations observed in some 'keratoeysts', may possibly be explicable on this basis. There are of course, other examples of odontogenie lesions recapitulating dental ontogeny. ln 1966, Main & Dawe reported a study of odontogenic tumor induction in transplanted tooth buds of mice infeeted witb polyotna virus. In this paper they stated that it still remained to be determined whether the action of polyoma virus, in inducing speeifie epithelial tumors in miee. is entirely attributable to a direct effect of virus on the genome of the responding epithelium, or whether it is to some extent dependent on altered epitheliomesenehymal interactions. Main (1972) pointed out that cultures of trypsin-separated odontogenic epithelium infected with polyoma virus would not survive on their own for much longer than 10 days. The epithelial proliferation seen in eultures of whole tooth germs eould mean that the mesenchyme serves only an indireet funetion by aeting in a supportive or nutritive manner to tbe epithelium. Main, however, indieated two other hypothetical possibilities for the mesenchymal role in epithelial tumor induction. One was, as he and Dawe had suggested in the 1966 paper, that tbe mesenehyme may, under normal circumstances, be inbibitory. In neoplasia removal of this inhibition may permit tbe epitbelium to manifest an in-
GRANULAR CELL PERIPHERAL ODONTOGENIC EIBROMA
herent proliferative tendency. The other is t h a t the mesenchymal role may be inductive and, on analogy with seeondary embryological induction, it tnay induce epithelial proliferation under certain pathological conditions. Main points out that more than o n e of the hypothetical relationships may coexist and that it is possible that the interaction may be more subtle and more complex than any of these. T h e whole question of the possible role of ectomesenchyme in the pathogenesis of some oral lesions is an intriguing one whieh we a r e further investigating in our department. W e prefer the term 'odontogenic fibroma' to 'odontogenic gingival epithelial hamartoma'. Besides the faet that the latter term is l o n g and cut-nbersome, it was the belief of B a d e n et al. (1968) that the lesion was exclusively of epithelial origin. There can be little doubt, however, that histologieal examination of these lesions indicates a definite 'fibroma' component. Tbe histomorphology of this 'fibroma' is unlike that seen in the ameloblastic fibroma. In the latter lesion, the fibromatous tissue resembles that seen in tbe dentine papilla where the , fibroblasts tend to be widely sepat-ated by ^'intercellular stroma and ground substance. In t h e odontogenic fibroma, the fibroblasts are closely packed. References ; Baden, E., Hackensack, M. J. & Splaver, T. '- (1973) Odontogenic gingival epithelial hamarton-ia - r-eport of a case. Journal of Oral
Surgery 31, 932-935. B a d e n , E., Moskow, B. S. & Moskow, R. (1968) Odontogenic gingival epithelial har-nartor-na. Journal of Oral Surgety 26, 702-714. Buchner, A. (1972) Gr-anular cell odontogenic cyst. Oral Surgery, Oral Medicine and Oral Pathology 36, 707-712. C h a m p i o n , A. R. H., Moule, A. W. & Wilkins o n , F . C. (1951) An ameloblastoma of the m a n d i b l e . British Detital Journal 90, 143150.
303
Couch, R. D., Morris, E. H. & Veilios, F. (1962) Granular cell ameloblastic fibroma report of 2 cases in adults with obser-vation on its similarity to congenital epulis. American Jourtial of Clinical Pathology 37, 398404. Custer, R. P. & Fust, 1. A. (1952) Congenital epulis. Americuti Journal of Clinical Pathology 22, 1044-1053. Decker, R. M. & Lafitte, H. B. (1967) Peripheral calcifying odontogenic tumor-. Oral Surgery, Oral Medicine and Oral Pathology 23, 398-402. Gaunt, W. A., Osbor-n, 1. W. & Ten Cate, A. R. (1971) Advanced Dental Histology, 2nd ed., p. 27. Bristol: John Wright and Sons. Gold, L. & Christ, T. (1970) Granular cell odontogenic cyst. Oral Surgery, Oral Medicine and Oral Pathology 29, 437-442. Goriin, R. 1. (1970) Thoma's Oral Pathology, ed. Gorlin, R. J. & Goldman, H. M., Vol. 1, 6th Ed., p. 495 and 503. St. Louis: C. V. Mosby Co. Lee, K. W., Chin, T. C. & Paul, G. (1971) Peripheral ameloblastoma. Journal of Oral Surgety 8, 150-153. Lucas, R. B. (1972) Pathology of Tutnours of the Oral Tissues, 2nd Ed., p. 45. Edinburgh and London: Chur-chill Livingstone. Main, J. H. P. (1972) Developmental consider-ations: car-cinogenesis and oncology. In Deyetoptnetital Aspects of Oral Biology, ed. Slavkin, H. C. & Bavetta, L. A., p. 385. New York and London: Academic Press. Main, 1. H. P. & Dawe, C. J. (1966) Tumor induction in transplanted tooth buds infected with polyoma virus. Jourtial of the National Cancer Itistitute 36, 1121-1136. McCallum, H. M. & Cappell, B. L. (1957) Adamantinoma with granular cells. Journal of Pathology and Bacteriology 74, 365-369. Navorette, A. R. & Smith, M. (1971) Ultrastructure of granular cell ameloblastoma. Cancer 27, 948-955. Pindborg, 1. J., Kr-ar-r-rer, 1. R. H. & Torloni, H. (1971) Histotogicat Typing of Odontogenic Tumours, Jaw Cysts, atid Allied Lesions, p. 30. Geneva: World Health Or-ganization. Shafer, W. G., Hine, M. K. & Levy, B. M. (1974) Textbook of Oral Pathology, 3r-d Ed., p. 252. Philadelphia; W. B. Saunders Co. Shear, M. (1960) The histogenesis of the socalled 'granular cell myoblastoma'. Journal of Pathology and Bacteriology 80, 225-228. Slavkin, H. C. (1974) Embryonic Tooth Forma-
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LOWNIE, ALTINI AND SHEAR
tion, Otal Sciences Review, ed. Meleher, A. ll. & Zarb, G. A., 4th Ed., p. 15-19. Copenhagen: Munksgaard. Stoelinga, P. 1. 'W. (1971) Over Kaakkysten, p. 130. M. D. Thesis. University of Nijmegen, Central Drukkerij, Nijmegen. Villa, V. G. (1955) Ameloblastie sarcoma in the mandible - report of a ease. Oral Surgery. Oral Medicine and Orai Pathology 8, 123-129. 'Waldron, C. A., Thompson, C. 'W. & Corner,
W. A. (1963) Granular eell ameloblaslic fibroma. Oral Surgery, Oral Medicine and Oral Pathology 16, 1203-1213. Address: J. F. Lowtiie Dept. of Oral Pathology University of Witwatersrand Jan Smuts Avenue Johannesburg 2001 South Africa
, _:: '
of Oral Pathology 1976: 5: 295-304
Granular cell peripheral odontogenic fibroma J. F. LowNiE, M. At.i-iNr AND M. SHEAR
Department of Oral Pathology, School of Pathology, University of the Witwatersrand and South African Institute for Medical Researeh. South Africa Abstract. A case of a peripher-al odontogenic fibr-oma whieh contained aggregates of lar-ge granular eells is reported. These granular eells are similar to those pr-eviously described in t h e granular cell r-nyoblastoma, congenital epulis and the granular cell ameloblastic fibroma. Deep extensions of the basal layer of overlying gingival epithelium, in double-strand fasbion, ar-e frequently obser-ved in peripher-al odontogenie fibr-on-ras. These strands elosely resemble those seen in the tumor itself. On this basis, and as similar basal eell prolongations ar-e seen in other jaw lesions, it is postulated that residual eetomesenchymal influe n c e may be responsible for inducing the basal cell proliferations in a similar manner to t h a t which occur-s during ear-ly embryonic dental development. This, it is suggested, might possibly be the histogenesis of the odontogenic epithelial strands in the peripheral odontogenie fibroma. Received 3 February, accepted for publication I May 1976
^ T h e odontogenic fibroma is a benign odonr togenic neoplasm composed of whorling I and streaming fibroblasts interspersed with collagen fibers and containing varying amounts of odontogenic epithelium. Foei |: of dentinoid are also found. It can arise centrally within the jaws, or peripherally w h e r e it may be indistinguishable clinically L i f r o m a fibrous epulis. T h e term 'odontogenic fibroma' appears to have been introduced by Gorlin (1970) in order to distinguish this lesion from the ameloblastic fibroma and ameloblastoma. This terminology was accepted by the W o r l d Health Organization in their Histological Typing of Odontogenic Tttniottrs, Jaw C^ysts, attd Allied Lesiotts (Pindborg et al. 1971). Baden et al. (1968) deseribed the same tumor as an 'odontogenie gingival epithelial hamartoma'. The odontogenic fibroma is a relatively rare lesion. Cases have
been deseribed by Deeker & Lafitte (1967), Baden et al. (1968, 1973). Although the presence of large oxyphil granular cells has been described in other odontogenie tumors, sueh as the ameloblastie fibroma atid ameloblastoma, these cells have not been previously reported in the odontogenic fibroma. Little is known about the pathogenesis of this tumor, although Baden et al. (1968) made some intetesting observations which will be referred to in the Discussion. The purpose of this paper is to report a case showing granular cell change and to discuss a possible histogenesis of the tumor.
Case Report
A 40-year-old black female catne to the hospital with a peduticulated swelling in the
296
LOWNIE, ALTINI AND SHEAR
• «i-. - ; »-^l
F/g. i. Odontogenic fibroma, showmg streaming of fibroblasts, nests and strands of odontogenic epithelium and areas of dentinoid (D). H & E x 100.
Eig. 2. An area of granular eells (G) in the tumor mass. H & E X 100.
GRANULAR CELL PERIPHERAL ODONTOGENIC FIBROMA
297
Fig- 3. Granular eells closely associated with odontogenic epithelial cells. Masson's triehrome X 250. p a l a t a l gingiva of the maxillaty right third m o l a r . The lesion, measuring 1 X 1 X 0.5 cm, was not painful and had been present for t h e previous 2 months. Radiological examination revealed no abnormality of the maxilla on the affected side. The lesion was excised under general anesthesia, atid the postoperative course was uneventful. Histology Histologically, the tumor consisted of a densely cellular fibroblasfic mass exhibiting whorling and streaming (Fig. 1). Scattered throughout the tumor were numerous strands and islets of odontogenic epithelium. T h e strands consisted of a double layer of small cells with darkly staining nuclei. The islets were formed by clusters of cells, some of which were swollen (Figs. 2 and 3). The latter groups of cells were associated with still larger cells containitig granular eosino-
philic cytoplasm. These granular cells appeared, in fact, to be of epithelial origin as transitional forms wete seen in which the swollen epithelial cells showed aeeumulations of eosinophilic granules (Figs. 3 and 4). Some of the granular cells were isolated and It was not possible to determine whether these were of epithelial or fibroblastic origin. A nutnber of foci of dentinoid were present in the tumor (Fig. 5). Strands and islets of odontogenie epitheliutn were seen close to some dentinoid surfaces, suggesting that the epithelium may have had an inductive influence in their formation. The fibroblastie mass extended to the covering epithelium and in many areas the basal layer of the epithelium extended into the tumor as long double-stranded prolongatiotis similar to those seen deeper in the lesion (Fig. 6).
298
LOWNIE, ALTINI AND SHEAR
Fig. 4. Swollen epithelial cells showing transition to granular cells. Masson's trichrome X 400.
Fig. 5. Foci of dentinoid closely associated with odontogenic epithelium. H & E X 100.
GRANULAR CELL PERIPHERAL ODONTOGENIC FIBROMA
299
. 6. Another case of odontogenic fibroma, showing extensions of the basal cells of surface epithelium in a double strand fashion. Note the epithelium streaming deeply into the lesion (arr o w s ) . H & E X 64.
Discussion
G r a n u l a r cells in lesions of the oral eavity and jaws are well doeumented. These include the granular eell myoblastoma (Shear 1960), eongenital epulis (Custer & Fust 1952), gratiular eell ameloblastoma (MeCal-
lum & Cappell 1957), granular eell ameloblastic fibroma (Couch et al. 1962) and more recently in the epithelium of some odontogenie cysts (Gold & Christ 1970, Buchner 1972). The histogenesis of the granular cells in the granular cell myoblastoma, as well as in
300
LOWNIE, ALTINI AND SHEAR
the eongenital epulis, is controversial. There is an extensive literature on the subject, but the main theories as to the origin of these lesions explain them as neoplasms of primitive myoblasts, as a degenerative or regenerative change in mature striated musele, as a product of neural tissue or of fibroblasts, or as a collection of histioeytes storing an abnormal metabolite. Shear (1960) states that these eells are not neoplastie, but t-epresent a metabolie change which can oecur in muscle cells, fibroblasts and epithelial cells and suggests the term 'oxyphil granular change' as an alternative to granular cell myoblastoma. It is agreed that the granular cells of the ameloblastoma, as well as those of the odontogenie eyst are epithelial in origin (Gorlin 1970, Buehner 1972). Investigation into the ultrastructure of the granular cell at-neloblastoma t-eveals that the granules are pleomorpbic electron-dense granules identifiable as lysosomes (Navo-
rette & Smitb 1971). The granular eells of the ameloblastic fibroma seem clearly to be of mesodermal origin, representitig an ageing or degenerative process of the mesodermal component, although there is no histochemical evidenee to support this (Waldron et al. 1963). The majority of granular eells in the present ease, beeause of their close relationship with the odontogenic epithelium, and in view of the presenee of transitional forms, would appear to be epithelial in origin. We cannot, however, absolutely exclude the possibility that some of the granular cells are of fibroblastic origin, iti which case it would be necessary to postulate a dual origin for these cells. Narrow extensions of the basal layer of eells of the covering epithelium, many of them double-stranded, are a histological feature which we have observed repeatedly in normal gingiva (Eig. 7), in fibrous epulides (Eig. 8) and in peripberal odontogenie fi-
Fig. 7. Nor-mal attached gingivae from lower third molar region showing double-stranded extensions (arrowed) of the basal cells of some rete ridges, into the lamina propria. H & E X 100.
GRANULAR CELL PERIPHERAL ODONTOGENIC EIBROMA
301
I
Fig. 8. Eibrous epulis showing similar proliferations of the basal layer of cells as seen in normal gingivae and in peripheral odonlogenie fibromas. H & E X 160. b r o m a s (Fig. 6). Ameloblastic cells originating from the overlying oral epithelium in an ameloblastic sarcoma bave been reported (Villa 1955). In the field of keratocysts, Stoelinga (1971) suggests that besides their possible development from remnants of dental lamina or epithelial inclusiotis, origin : from basal cell hamartias of the oral mucosa should be considered. The apparent
origin of some ameloblastomas from the basal layer of oral epithelium is a phenomenoti which is ofteti seen by pathologists (Chatnpion et al. 1951, Lee et al. 1971). There has been a tendency to ascribe this apparent epithelial origin to 'collision' of the tumor with overlying tnucosa (Lucas 1972, Shafer et al. 1974). In 1968, Baden et al. reported a series of
302
LOWNIE, ALTINI AND SHEAR
cases, which would, in terms of the WHOreeommended notnnenclature, be ealled 'peripberal odontogenic fibromas'. These authors suggested the term 'odontogenic gingival epithelial hamartoma'. In their disetission they stated their belief that these lesions originate from odontogenie epithelial rests of the dental lamina. They also, however, referred to what they ealled a more remote possibility. They described the same focal proliferations from the basal epithelium of the gingiva which we have described here. In all three of their cases, clusters of odontogenic epithelial cells appeared in direct continuity witb tbe basal layer of the stratified squamous epithelium and they noted a resemblanee to the focal budding of basal eells in basal eell carcinoma of the skin. They eontinued: "Sueh a pathogenic meehanism eould be theorized since the dental lamina originates from the gingival epithelium in the embryo. Perhaps the potential for differentiation remains, only to be provoked onee more by unknown stimuli under exceptional conditions in adulthood. The rarer cases of extra-osseous ameloblastomas deseribed in the literature lend support for such a view". 'We should like to support these latter views, but also to extend them by attempting to explain tbe various forms of basal eell proliferation in terms of the following hypothesis. It is now widely accepted tbat embryonie tooth development in vertebrates appears to be initiated by eetomesenehyme. This eetomesenehyme is of neural crest origin and migrates into tbe developing mandibular and maxillary proeesses where it interacts with adjacent epithelium to initiate proliferation of the basal layer and the dental lamina (Gaunt et al. 1971, Slavkin 1974). This odontogenie epithelium, onee induced, itself possesses inductive potential. It is now well reeognized that this mutual interaction may be exerted in tbe patho-
genesis of a variety of odontogenie tumors, so that this inductive phenomenon is not eonfined to embryonic tooth development. It may be, therefore, that residual ectomesenchymal influence may persist in the gingivae after eompletion of development of the dentition. If this is indeed so, then the double strand proliferations seen in normal gingiva, fibrous epulides and the peripheral odontogenic fibroma; as well as the apparent surface origin of some ameloblastomas and other odontogenie tumors, and the basal cell proliferations observed in some 'keratoeysts', may possibly be explicable on this basis. There are of course, other examples of odontogenie lesions recapitulating dental ontogeny. ln 1966, Main & Dawe reported a study of odontogenic tumor induction in transplanted tooth buds of mice infeeted witb polyotna virus. In this paper they stated that it still remained to be determined whether the action of polyoma virus, in inducing speeifie epithelial tumors in miee. is entirely attributable to a direct effect of virus on the genome of the responding epithelium, or whether it is to some extent dependent on altered epitheliomesenehymal interactions. Main (1972) pointed out that cultures of trypsin-separated odontogenic epithelium infected with polyoma virus would not survive on their own for much longer than 10 days. The epithelial proliferation seen in eultures of whole tooth germs eould mean that the mesenchyme serves only an indireet funetion by aeting in a supportive or nutritive manner to tbe epithelium. Main, however, indieated two other hypothetical possibilities for the mesenchymal role in epithelial tumor induction. One was, as he and Dawe had suggested in the 1966 paper, that tbe mesenehyme may, under normal circumstances, be inbibitory. In neoplasia removal of this inhibition may permit tbe epitbelium to manifest an in-
GRANULAR CELL PERIPHERAL ODONTOGENIC EIBROMA
herent proliferative tendency. The other is t h a t the mesenchymal role may be inductive and, on analogy with seeondary embryological induction, it tnay induce epithelial proliferation under certain pathological conditions. Main points out that more than o n e of the hypothetical relationships may coexist and that it is possible that the interaction may be more subtle and more complex than any of these. T h e whole question of the possible role of ectomesenchyme in the pathogenesis of some oral lesions is an intriguing one whieh we a r e further investigating in our department. W e prefer the term 'odontogenic fibroma' to 'odontogenic gingival epithelial hamartoma'. Besides the faet that the latter term is l o n g and cut-nbersome, it was the belief of B a d e n et al. (1968) that the lesion was exclusively of epithelial origin. There can be little doubt, however, that histologieal examination of these lesions indicates a definite 'fibroma' component. Tbe histomorphology of this 'fibroma' is unlike that seen in the ameloblastic fibroma. In the latter lesion, the fibromatous tissue resembles that seen in tbe dentine papilla where the , fibroblasts tend to be widely sepat-ated by ^'intercellular stroma and ground substance. In t h e odontogenic fibroma, the fibroblasts are closely packed. References ; Baden, E., Hackensack, M. J. & Splaver, T. '- (1973) Odontogenic gingival epithelial hamarton-ia - r-eport of a case. Journal of Oral
Surgery 31, 932-935. B a d e n , E., Moskow, B. S. & Moskow, R. (1968) Odontogenic gingival epithelial har-nartor-na. Journal of Oral Surgety 26, 702-714. Buchner, A. (1972) Gr-anular cell odontogenic cyst. Oral Surgery, Oral Medicine and Oral Pathology 36, 707-712. C h a m p i o n , A. R. H., Moule, A. W. & Wilkins o n , F . C. (1951) An ameloblastoma of the m a n d i b l e . British Detital Journal 90, 143150.
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