T HE AMERICAN JOURNAL OP- PATHOLOGY VOLUME XXII MAY, I946 NUMBER 3 ODONTOGENIC TUMORS A CLASSIFICATION BASED ON OBSERVATIONS OF THE EPITHELIAL, MESENCHYMAL, AND MIXED VARIETIES * KURT H. THOMA, D.M.D., and HENRY M. GOLDMAN, Captain, D.C., A.U.S. (From the Army Institute of Pathology, Washington 25, D.C., and the Harvard School of Dental Medicine, Boston z5, Mass.) INTRODUCTION Odontogenic tumors, derived from dental or potential dental tissue, are common and have been discussed extensively in the literature. They have been classified as ameloblastomas, dentinomas, cementomas, and odontomas, each having been regarded as a distinct entity. There have been a few cases described in which one type arose in conjunction with another, but no report has suggested the influence of one tissue upon another in the pathogenesis of these tumors. The purpose of this report is three-fold: (I) to formulate a classification of odon- togenic tumors in light of the large amount of material studied; (2) to describe their structure, especially that of the mixed group; and (3) to illustrate the inductive effects of one tissue on alother in the produc- tion of odontogenic mixed tumors. The material used in this study comprises 64 cases of odontogenic tumor selected from the files of the Registry of Dental and Oral Pathology and from the collection of one of us (K.H.T.). Twenty-six are chiefly epithelial tumors (Table I); 14, mesenchymal tumors (Table II), and 24, odontogenic mixed tumors (Table III). EMBRYOLOGY AND HISTOLOGY OF THE TOOTH GERM Since this study is concerned with tumors derived front dental tis- sues, a brief review of the normal embryology of the tooth seems es- sential. The precursor of the tooth bud appears as a thickening of the oral epithelium during the sixth week of embryonic life. This thicken- ing is the primordium of the ectodermal portion of the tooth known as the dental lamina. The tooth bud, in the form pf an invagination of the thickening, begins to take shape and the surrounding connective *Received for publication, June 11, 1945. 433 434 THOMA AND GOLDMAN tissue differentiates into the dental papilla. Text-Figure i is a draw- ing of a tooth germ during the sixth month. The dental lamina is rec- ognized at DL, while the permanent tooth bud is seen at A. At this stage the cells which form the tissues of the tooth have differentiated into the outer epithelial layer, the stellate reticulum, the ,tratum inter- medium, the ameloblastic layer, the odontoblastic layer, and the dental papilla. Between the ameloblastic and odontoblastic layers are enamel and dentin. Text-Fig. i. A diagrammatic drawing of a tooth germ in the sixth month of embry- onic life. Enamel and dentin have been laid down. DL, dental lamina; A, anlage of permanent tooth; OE, outer enamel epithelium; SR,, stellate reticulum; SI, stratum intermedium; AM, ameloblastic layer; E, enamel; D, dentin; OL, odontoblastic layer; P, dental pulp. CLASSIFICATION We are in accord with the classification of odontogenic tumors based on structure; however, certain terms are used in this paper with modi- fications in meaning. "Odontogenic fibroma" is used to indicate the ODONTOGENIC TUMORS 435 soft mesenchymal tumor, while "dentinoma" is reserved for the pure mesenchymal tumor composed of islands of dentin in a connective tissue stroma. "Odontoma" is regarded as a mixed tumor made up of epithelial and mesenchymal elements and is spoken of as "odon- togenic mixed tumor." Three types are recognized. The following classification is the one adopted by us: L. Epithelial tumors I. Adamantoblastoma 2. Enameloma II. Mesenchymal tumors I. Odontogenic fibroma 2. Dentinoma 3. Cementoma III. Odontogenic mixed tumors (odontomas) i. Soft odontoma-epithelium and mesoderm 2. Soft and calcified odontoma-adamantoblastoma arising in conjunction with a forming or completely formed odontoma; all sorts of histologic variations due to the inductive effects of one tissue on another 3. Completely formed odontoma with enamel, dentin, pulp, cementum, perio- dontal membrane a. Compound (many small teeth) b. Complex (irregular tooth structure) Tumors may arise from either odontogenic epithelium or mesenchy- ma and may be either soft or calcified. The soft epithelial tumor is commonly called adamantoblastoma; the calcified, enameloma. The mesenchymal odontogenic tumor arises as a fibroma: in the calcified stage, if dentin is produced it is called dentinoma; if cementum, cementoma. Tumors may also originate from both the odontogenic epithelium and mesenchyma. These are known as odontomas or odon- togeniGImixed tumors and may belong to any one of three groups: (i) soft odontomas, (2) soft and calcified odontomas, and (3) com- pletely calcified odontomas. Epithelial Tumors Adamantoblastoma. The adamantoblastoma is an epithelial odon- togenic tumor in which the cells may differentiate to a variety of forms depending to some extent on the development of the epithelium at the time when tumor formation begins. Solid and cystic types are dis- tinguished, both being of a slowly growing, benign nature, to judge from clinical observation. The frequency of recurrence after operation is due rather to the difficulty of removing the entire lesion by con- servative operation than to any malignancy of the tumor; however, several cases recorded 1, 2 indicate that it can be malignant. Microscopically, the tumor may appear solid, cystic, or a combina- tion of both. If solid, it is composed of cords or strands of epithelium growing in a connective tissue stroma,;or occasionally almost without 436 THOMA AND GOLDMAN TABLE I Adamantoblastoma Case A.I.P.- Roentgenologic no. accession Sex Race Age History and symptoms Location findings I 69715 M W 54 Noticed nodule 6 years Mandible Cystic destruction from previously, operated 5 symphysis to angle of years previously, swel- mandible ling 2 5I505 M W 24 Pain Mandible Dentigerous cyst in- volving 3rd molar and extending into ramus of mandible 3 75597 M W 52 Oral-antral sinus, 25 Maxillary Opacity of sinus years sinus 4 72782 F W 27 Swelling Mandible Cyst 5 75464 M W 42 Large movable mass in Maxilla tuberosity 6 85x84 M W 36 Removal of dentigerous Mandible Cyst in 3rd molar re- cyst 4 years previously gion, no tooth present 7 87202 M C 2I Mandible Cyst in 3rd molar re- gion 8 86153 M W 26 Removal of dentigerous Maxilla Cystic lesion from cen- cyst 4 years previously tral and incisor region to molar region 9 958I7 F C 37 24operationsperformed Mandible Cystic lesion involving during a period of I5 the body and ramus of years (metastasized to mandible lungs) 1O I08545 M W I9 Duringascufflereceived Mandible Dentigerous cyst in- a blow-pain and swel- volving crown of 3rd ling molar, dentigerous cyst on opposite side II 117002 M W 2I Tenderness and swel- Mandible Dentigerous cyst-six ling at angle of mandi- other dentigerous cysts ble of 48 hours' dura- present in mandible tion and maxilla 12 117378 M W 25 First noticed swelling 6 Mandible Multilocular lesion- years ago-area incised no teeth present and drained 13 120765 M W 25 Swelling of 6 months' Mandible Multilocular lesion in- duration-no pain volving entire body of mandible and extend- ing to inferior border 14 111372 F W 2½2 Mandible Monocystic lesion 15 IOIOIO M W 36 Tumor first recognized Mandible Cyst in body of mandi- 7 years previously ble I6 103102 M W 25 Slight swelling, with Mandible Cyst in region of 2nd mild dull pain, 2 years' premolar and Ist mo- duration lar ODONTOGENIC TUMORS 437 TABL I (Continued) Case A.I.P.* Roentgenologic no. accession Sex Race Age History and symptoms Location findings 17 109I69 M W 17 Previous operation, 3 Mandible Multilocular cyst be- teeth removed neath 3rd molar I8 103313 M W 23 Operation 5 years pre- Mandible Multilocular cyst from viously canine region extend- ing posteriorly into ramus-no teeth pres- ent I9 100372 M W 31 2nd molar removed 4 Mandible Dentigerous cyst years previously - roughening of gum i M years previously 20 94818 F W 2I Swelling for 4 years, Mandible Multilocular cyst two operations 21 86845 M W 28 Swelling Mandible Follicular cyst in 2nd and 3rd molar region 22 78638 M C 25 Drainage of purulent Mandible Dentigerous cyst in- exudate from area volving crown of 3rd molar 23 66686 M W Mandible 24 6509I F W 60 3rd molar extracted, re- Maxilla Radiolucent area in 3rd sulting in fistula into molar region antrum 25 1I18679 M W 32 Painless swelling, io Mandible Dentigerous cyst in- years' duration volving crown of ca- nine with radiopaque masses in cystic portion Enameloma 261 H.M.G. M W 65 No symptoms Mandible Found on examination of autopsy specimen * Army Institute of Pathology. stroma. The epithelial cords, which may form a network or take on a papillary structure, may resemble the anlage given off from the dental lamina and have a similar tendency to form small buds comparable with the earliest stage of the enamel organ. In the central portion of the cord or lobule the epithelium appears stellate, like the stellate reticulum of the enamel organ; in the periphery the cells are cuboidal to cylindrical. The cystic type is characterized by lobules or strands of adamantine epithelium with a peripheral layer of cylindrical cells which, in struc- ture, approach ameloblasts. These cells lie on a basement membrane. The central portion consists of stellate to squamous epithelium under- going cystic degeneration. Pressure of cystic fluid causes these spaces 438 THOMA AND GOLDMAN to enlarge; they often fuse and communicate with one another. Kron- feld3 believed this kind of adamantoblastoma to be the result of pro- gressive cyst formation in the solid type. He stated that the primary factor in the formation of cystic adamantoblastoma was degeneration of the stellate reticulum of the tumor, a concept supported by Robin- son4 and by data from this study.