Clear cell ameloblastoma—An odontogenic carcinoma

CASE REPORTS J Oral Maxillofac 43:707-717.

Surg

1995

Clear Cell Ameloblastoma -An Odon togenic Carcinoma CHARLES

A. WALDRON, DDS, MSD,* IRWIN A. SMALL, DDS,t HARVEY SILVERMAN, DDS*

The ameloblastoma is the most common, clinically significant odontogenic tumor. ’ This neoplasm is generally considered to be benign but locally invasive, and it demonstrates considerable tendency to recur.* The question of malignancy in ameloblastoma has been the subject of considerable discussion and controversy for many years. There can be little argument that the ameloblastoma which metastasizes is malignant. In other instances, ameloblastomas have been considered as malignant on the basis of an aggressive clinical course in the absence of metastasis. These lesions often show unusual or atypical histologic features.3 The range of histologic atypia which is still consistent with a diagnosis of ameloblastoma and at what point the lesion is best considered to be an odontogenic carcinoma remains controversial. Criteria for use of terms such as “atypical ameloblastoma,” “malignant ameloblastoma,” and “odontogenic carcinoma” do not appear to be well defined nor generally agreed on. The World Health Organization report on Histologic Typing of Odontogenic Tumors, Cysts and Allied Lesions4 classifies malignant epithelial odontogenic tumors under the general heading of odontogenic carcinoma with the following subtypes:4

AND

nection to the oral mucosa. These tumors presumably arise from residues of odontogenic epithelium. c. Other carcinomas arising from odontogenic epithelium including those arising from odontogenic cysts. The WHO definition for malignant ameloblastoma implies that the tumor must metastasize to be considered malignant. This appears to be an unnecessarily rigid definition and is not consistent with the definition of malignancy as applied to other neoplasms (i.e., squamous cell carcinoma, basal cell carcinoma, mucoepidermoid carcinoma, etc.). Elzay5 has recently reviewed the subject of primary intraosseous carcinoma of the jaws and has suggested a modification of the World Health Organization classification for malignant epithelial tumors related to the odontogenic apparatus. His suggested classification includes: Primary Type Type A. B. Type A. B.

a. Malignant ameloblastoma. This neoplasm exhibits the histologic features of ameloblastoma in both the primary and metastatic sites. This publication recommends that the term “malignant ameloblastoma” not be applied to ameloblastomas that endanger life by direct extension to vital anatomic sites. b. Primary intraosseous carcinoma, a squamous cell carcinoma arising in the jaw with no initial con-

intraosseous carcinoma of the jaws: 1. Arising ex-odontogenic cyst 2. Arising ex-ameloblastoma Well-differentiated (malignant ameloblastoma) Poorly differentiated (ameloblastic carcinoma) 3. Arising de novo Nonkeratinizing Keratinizing

We believe that this proposed classification has considerable merit and deserves further study and evaluation. Ameloblastomas with histologically documented metastases are well described in the literature and have been the subject of several reviews.6,7 While the lungs are the usual sites of metastatic deposits, spread to lymph nodes and other bones has been demonstrated.8*9 Based on a review of published photomicrographs and personal study of microscopic slides from a small number of cases, it appears that a substantial number of these cases meet the WHO criteria for malignant ameloblastoma in that both the primary tumor and secondary deposits were histologically acceptable ameloblastomas.

* Adjunct Professor of Oral Pathology, Washington University School of Dental Medicine, Saint Louis, Missouri. t In private practice of oral and maxillofacial surgery, Birmingham, Michigan. $ In private practice of oral and maxillofacial surgery, Lilbum. Georgia. Address correspondence and reprint requests to: Dr. Waldron: Washington University School of Dental Medicine, 4559 Scott Avenue, Saint Louis, MO 62110. 707

708

CLEAR CELL AMELOBLASTOMA

tumors were variously diagnosed as ameloblastoma, atypical ameloblastoma, malignant ameloblastoma, mucoepidermoid carcinoma, or odontogenie carcinoma by the attending hospital pathologist and several consultants. Retrospective analysis of the clinical course and histologic material in both cases suggests that these lesions should be considered as odontogenic carcinomas (malignant ameloblastomas). Their further subclassification in Elzay’s’ proposed scheme as Type 2A (well differentiated) or Type 2B (poorly differentiated) is debatable and must await further clarification and refinement of microsocpic criteria for these rare tumors, although we believe they are probably best considered as examples of poorly differentiated ameloblastic carcinomas. Report of Cases CASE I

FIGURE I (top). Radiograph demonstrating horizontally impacted lower right third molar with a radiohIcent area extending superiorly to the distal apsect of the crown and root. A small calcified mass is present between the crown of the impacted molar and the root of the second molar. Radiograph made I8 months after reFIGURE 2 (middle). moval of the impacted third molar and curettage of the radiolucent area. An irregular lytic area extends from the third molar region and involves approximately half of the anterior ascending ramus. FIGURE 3 (botrorn). Radiograph taken six years after resection. There is consolidation of the graft and no evidence of recurrence.

We are reporting two cases of clinically aggressive epithelial neoplasms of the jaws. Both neoplasms demonstrated a consistent “biphasic” histologic pattern with areas resembling follicular ameloblastoma, although with atypical features, and other areas with a conspicuous clear-cell epithelial component. During the course of treatment these

A 50-year-old white man was referred by his dentist to an oral and maxillofacial surgeon for removal of an impacted right mandibular third molar. The patient had noticed soreness in the area for a month; however, the mucosa was clinically normal. Radiographic examination revealed a horizontally impacted right mandibular third molar with an area of bone destruction about the crown of the tooth extending about 1 cm superior to the crown (Fig. 1). There was a small, round calcified mass about 3 mm in diameter lying between the crown and the root of the adjacent second molar. The lesion appeared to represent an odontogenic cyst or tumor. The past medical and surgical history was noncontributory. The tooth was removed, and the soft tissue occupying the radiolucent defect was thoroughly curetted. The specimen was submitted for microscopic examination and was reported as an ameloblastoma. The patient was seen at three-month intervals by the original surgeon for one year. He continued to complain of low-grade pain at the site of tooth removal. Clinically, the area appeared to have healed. and there was no inflammation or suppuration, but, radiographically, there was very little evidence of bone regeneration. The patient did not return for examination for six months. When again seen by the original surgeon, there was evidence of a large radiolucent lesion in the right ascending ramus (Fig. 2). He was then referred to one of us U.S.1 for treatment. Radiographic examination at this time demonstrated an ill-defined area of bone destruction extending to the inferior alveolar canal inferiorly, to the mandibular foramen posteriorly, and to just below the sigmoid notch superiorly. There was no cortical bone expansion clinically or radiographically, and the lesion appeared to penetrate the bone medially. Review of the previous biopsy was requested, and the oral pathologist stated that he believed the lesion to be an atypical ameloblastoma although there were some similarities to mucoepidermoid tumor. The patient was brought to the operating room and, under general anesthesia, a marginal resection of the lesion was carried out via both an intraoral and extraoral approach. The mandible was resected from posterior to the first molar to the posterior border of the ramus including the coronoid process. The neurovascular bundle

WALDRON ET AL.

was sacrificed. The inferior border of the mandible was preserved. The tumor appeared to extend medially into the medial pterygoid muscle and a portion of the muscle was resected. Following resection, a large round bur was used to trim all bone margins an additional 2-3 mm. An iliac crest bone graft was used to reconstruct the resected area. The submandibular lymph nodes were removed as an additional specimen since they were enlarged. A Penrose drain was inserted and the wound closed in the standard manner. The wound and graft healed without complication, and the patient has been followed for six and one-half years without evidence of recurrence and with good consolidation of the graft (Fig. 3). The surgical specimen was diagnosed by the hospital pathologist as an atypical ameloblastoma. The oral pathologist, who had reported the original biopsy specimen, also reviewed the surgical material. His diagnosis was odontogenic carcinoma, but he noted that there were features suggesting a mucoepidermoid carcinoma.

Histologic Findings The specimen curetted from the radiolucent defect associated with the crown of the impacted right mandibular third molar consisted of five small fragments of tissue. One fragment showed densely collagenized fibrous connective tissue containing a few epithelial rests and small basophilic calcified structures typical of features commonly noted in the wail of a detigerous cyst. No other cystic features. however, were noted in the specimen (Fig. 4). The other fragments were composed of fibrous connective tissue containing numerous nests of epithelial cells, many of which were surrounded by a narrow zone of hyahnized connective tissue. The nests were composed of cuboidal epithelial cells with vesicular nuclei and abundant cytoplasm that had a slightly granular appearance. Some of these nests demonstrated palisading of the peripheral cells with the nuclei showing reversed polarity. The central portions of these nests were composed of cells that were similar in appearance. Typical stellate reticulum and microcyst formation, however, was not present. Some of the centrally placed cells showed a vacuolated cytoplasm. Stains for mucin were negative (Figs. 5-7). Sections from the mandibular resection performed 18 months later showed an epithelial neoplasm extensively replacing the mandible and infiltrating into the adjacent soft tissue. The intrabony neoplasm demonstrated two distinct cellular patterns with areas showing an apparent transition between the two patterns. In some areas the neoplastic epithelial cells were arranged in a follicular pattern with columnar. palisaded peripheral cells that had reversed nuclear polarity. In occasional follicles, the central cells showed a stellate reticular pattern with small microcysts (Figs. 8.9). Other follicular-shaped epithelial islands were composed of cuboidal epithelial cells with vesicular nuclei and abundant eosinophilic cytoplasm. Most of these follicles contained a few to numerous cells with a centrally placed nucleus and a vacuolated cytoplasm. Peripheral palisading and reversed nuclear polarity of the peripheral cells was inconspicuous or absent in these areas. The second cellular pattern, which was present both in the intrabony sections and exclusively in the soft-tissue extension of the tumor, consisted of small nests and cords of epithelial cells with vesicular, centrally placed nuclei and faintly granular or vacuolated cytoplasm. Many of these nests were composed entirely of clear cells. Palisading and reversed polarity of the pe-

709

ripheral cells were absent (Figs. 10,ll). Mitoses were readily observed, particularly in the clear cell areas (Fig. 12). The clear cells negative with mucicarmine stain and the periodic acid-Schiff reaction and were very faintly positive with Alcian blue stains. The enlarged submandibular nodes showed reactive hyperplasia with no evidence of metastatic tumor. CASE 2

A 66-year-old white woman was referred to an oral and maxillofacial surgeon by her local dentist in September 1969 for evaluation of a large radiolucent lesion associated with her upper left second premolar and second molar teeth noted on routine radiographic examination. (Fig. 13) Examination revealed an extensive radiolucent lesion displacing the roots of the second premolar and the second molar and involving the floor of the left maxillary sinus as well as producing buccal expansion into the vestibule. The mucosa was normal in color and consistency. and there was no complaint of sensory deficit or pain. Under local anesthesia the left maxillary premolar and molar teeth were extracted, and exploration revealed a cystic lesion involving the entire left maxilla with destruction of the floor of the maxillary sinus. The lesion was enucleated, and the specimen was submitted to an oral pathologist. The diagnosis was atypical ameloblastoma with a comment that this appeared to be ai: aggressive lesion. The patient was admitted to a hospital several weeks after the initial surgery, and a left subtotal maxillectomy was performed. The patient tolerated the procedure well, and at the conclusion of the operation there was no clinical evidence of remaining tumor. Histologic examination showed several small foci of residual ameloblastoma in the soft tissue and the decalcified bone specimens. The patient remained under close postoperative observation, and, in August of 1970. I I months after the original enucleation, a mass was noted in the left submandibular gland. The patient was referred to a general surgeon for evaluation. He admitted her to the hospital, and exploration of the left submandibular triangle was carried out. The submandibular gland and lymph nodes were removed. Histologic examination revealed a benign pleomorphic adenoma (mixed tumor). No lymph node involvement was identified. The patient remained under close postoperative supervision without further complaints until September 1975, when she complained of a vague, diffuse swelling of the left face. Biopsy of a thickened area in her left cheek was negative for tumor. In August 1976 the left face was slightly edematous with a slight tenderness over the left malar eminence and a thickened area in the region of the left infraorbital foramen. Shortly thereafter she developed a total left facial paresis with components of third nerve palsy. Radiographic examination of the skull and facial bones was nonconclusive, but panoramic radiographs showed destruction of bone in the left infraorbital region. There were some symptoms of infection, and the patient was placed on antibiotics. One week later the facial palsy had almost cleared, and the pain had greatly decreased. A biopsy of the left infraorbital region revealed recurrent ameloblastoma. At that time the patient was referred to one of the authors (H.S.) for further treatment. In October I976 a radical resection of the tumor was carried out using a Weber-Fergusson incision. The left zygomaticofrontal process and orbital floor were down-fractured

710

CLEAR CELL AMELOBLASTOMA

FIGURE 4 (top). Photomicrograph from one fragment of tissue removed by curettage at the initial operation consisting of dense fibrous connective tissue, scattered epithelial rests, and small basophilic calcifications. H&E, original magnification x450). FIGURE 5 (bortom). The major portion of the original surgical specimen consisted of dense fibrous connective tissue containing nests of epithelial cells resembling follicular ameloblastoma. Palisading of the peripheral cells with reversed nuclear polarity is seen in some of the epithelial islands. H&E, original magnification x 100.

WALDRON ET AL.

711

FIGURE 6 (top). High-magnification view of the original surgical specimen showing peripheral palisading and reversed nuclear polarity. The central portion of the epithelial island is composed of cuboidal epithelial cells with vesicular nuclei and slightly granular cytoplasm. H&E, original magnification x 450. FIGURE 7 (borrom). original magnification

Other epithelial islands contain numerous clear cells with little evidence of palisaded peripheral cells. H&E, X 4.50.

712

CLEAR

FIGURE 8 (top). Photomicrograph from resection specimen performed The multiple tumor islands are characteristic of follicular ameloblastoma. FIGURE 9 (botrorn). magnification X 100.

Higher

magnification

showing

an island of follicular

18 months later showing tumor H&E, original magnification ameloblastoma

with central

CELL

adjacent x 25. stellate

AMELOBLASTOMA

to cortex

reticulum.

of mandible. H&E,

original

WALDRON ET AL.

FIGURE 10 (top). Other tumor islands in the resection specimen are composed of nests of epithelial cells with clear or faintly granular cytoplasm. This pattern was seen in the intrabony sections and exclusively in the sections from the surrounding soft tissue. H&E, original magnification x 600. FIGURE 11 (bottom).

Clear-cell tumor island infiltrating medial pterygoid muscle. H&E, original magnification

x 450.

714

CLEAR CELL AMELOBLASTOMA

FIGURE 12. Mitoses in clear-cell areas of resection specimen. H&E, original magnification

and removed. The orbital contents and globe were free of tumor, but the tumor had invaded the infratemporal fossa, retroorbital region, and base of the skull and was essentially nonresectable. The procedure was therefore terminated. The patient was reconstructed prosthetically. Following the patient’s radical left maxillectomy in October 1976, she was followed closely and did well until January of 1978. At that time, recurrence of the tumor was felt to exist in the left infraorbital region and left cheek. The patient was admitted to the hospital, and exploration of the area confirmed the clinical impression. Resection of the areas in question was carried out. In January of 1979, tumor in the left infraorbital area and nasal labial fold necessitated further surgery. In July of 1979, a mass in the skin graft covering the soft tissue orbital floor was biopsied revealing a tumor. In August of 1979, multiple masses were identified in the left neck. Needle biopsy of one of these areas revealed tumor consistent with the previous specimens. Due to the development of a significant cardiac arrhythmia, further surgery was contraindicated at that time. In January of 1980, the patient began a full course of radiotherapy with a dose of 5400 rads to the left face, 6200 rads to the upper neck on the left side, and 5500 rads to the lower neck on the left side. Over the next six months, the masses in the left neck, left cheek, and left infraorbital region regressed, and the patient experienced an improved quality of life. In June 1982 tumor growth accelerated resulting in destruction of the skin and soft tissues of the left side of the face involving the left eye, left mandible, and commissure of the mouth. There were multiple episodes of bleeding from the defect (Fig. 14). The patient refused further surgery and entered a nursing home in February

X 1000.

of 1983. After a short period of clinical improvement, tumor growth again accelerated in July of 1983 involving the base of the skull and infratemporal fossa. Her cardiac status and general condition precluded further surgery. Uncontrolled local tumor growth continued, and the patient became seriously debilitated. She expired on February 24, 1984. An autopsy was not obtained.

Histologic Findings Sections from the excision in September 1969 showed remarkably similar microscopic features to those seen in case 1. The fibrous connective tissue stroma contained nests, cords, and islands of neoplastic epithelial cells. Many of these islands were microscopically consistent with the features of follicular ameloblastoma with palisading of peripheral cells and reversed nuclear polarity. The central portions of these islands, however, did not show the typical stellate reticular pattern, and microcyst formation was inconspicuous. Some of the central cells showed a vacuoiated cytoplasm. Other epithelial nests were composed of cuboidal cells with a faintly granular or vacuolated cytoplasm. Peripheral palisading and reversed nuclear polarity was essentially absent in these islands. Mitotic activity was noted. Some of the epithelial islands were surrounded by a narrow zone of hyalinized connective tissue (Figs. 15,16). Sections from the subsequent surgical procedures of October 1976 and April 1978 showed similar features. The relative proportion of areas resembling follicular ameloblastoma and areas consisting of clear-cell islands varied somewhat from section to section but areas consistent with a diagnosis of follicular ameloblastoma were present

715

WALDRON ET AL.

in all sections. The frequency of mitosis was successively greater in material removed at each procedure (Fig. 17). The needle biopsy obtained in November 1979 from one of the masses in the left neck showed fragments of fibrofatty and dense fibrous connective tissue containing small, solid islands of tumor cells. The peripheral cells were hyperchromatic and showed some palisading. The epithelial cells in the center of the islands had larger, vesicular nuclei, and occasional mitotic figures were noted. No lymph node tissue was identified in the needle biopsy specimen. Discussion

Although the histogenesis of these tumors may remain controversial, we believe the evidence clearly favors an odontogenic origin and that they are best considered as primary intraosseous carcinomas of the jaws. As a further subclassification it appears appropriate to designate them as malignant ameloblastomas. The resection specimen in case 1, and all sections from the multiple surgical procedures in case 2, showed areas clearly consistent with a diagnosis of follicular ameloblastoma. Varying numbers of tumor islands showed peripheral palisading of cuboidal or columnar cells with reversed nuclear polarity. Stellate reticulum or microcyst formation, however, was minimal to absent. Both tumors showed a prominent clear-cell component within the follicular nests with apparent transition to small islands and cords composed largely or exclusively of clear cells. A conspicuous component of clear cells is most unusual in ameloblastomas, and, in the experience of one of the authors (C.A.W.), has not been noted in the study of a large number of ameloblastomas over the last 35 years. With the exception of the clear-cell variant of the calcifying odontogenic epithelial tumor (C.E.O.T.), clear cells are not conspicuous in other odontogenic tumors. The clearcell calcifying odontogenic epithelial tumor in many respects appears analogous to the clear-cell ameloblastomas we were reporting. Krolls and Pindborglo observed that although the two neoplasms they reported were composed chiefly of mucicarmine-negative clear cells, areas of typical calcifying odontogenic epithelial tumor were present in each tumor. They pointed out that the clear-cell areas could be misinterpreted as a salivary gland clearcell adenocarcinoma, mucoepidermoid carcinoma, acinic cell adenocarcinoma, or metastatic hypernephroma and that an incisional biopsy or inadequate sampling might fail to demonstrate the odontogenic nature of the neoplasm. Clear-cell nests or islands may be a prominent feature in developmental lateral periodontal cysts and in the gingival cyst of the adult. 11 These lesions

FIGURE 13 (top). Periapical radiograph demonstrating a radiolucent area in the upper left first molar region. The roots of the second premolar and second molar are divergent, and some root resorption is evident. FIGURE 14 (bottom). Clinical photograph of patient in June 1982 showing extensive facial defect extending from the lower left eyelid to the oral commissure.

are believed to arise from the rests of the dental lamina. Wysocki and his associates” have pointed out that two distinct types of dental lamina rests occur. Most commonly, they appear as small islands of squamous epithelium. Less commonly, the dental lamina rests appear as single or multiple islands of polyhedral or cuboidal cells with vesicular nuclei and a clear or variably eosinophilic cytoplasm. These rests have also been designated as the glands of Serres. Since ameloblastomas are derived from the dental lamina, the presence of a clear-cell component in an ameloblastoma would seem theoretically possible although rarely encountered. Clear cells may also form a conspicuous or even exclusive component of a number of salivary gland clear cell carcinoma, l2 mucoepidertumors-i.e., moid tumor,13 acinic cell tumor,14 and epithelial-

716

CLEAR CELL AMELOBLASTOMA

FIGURE IS. Photomicrograph from original tumor excision showing islands of neoplastic epithelial cells in a fibrous connective tissue stroma. Some of the islands are characteristic of follicular ameloblastoma while others are composed chiefly of clear cells. H&E. original magnification x40.

FIGURE 16. High magnification of initial surgical specimen demonstrating the biphasic pattern. H&E. original magnification X 100.

FIGURE 17. Specimen obtained at the time of maxillectomy six years after original operation. This field shows the clearcell islands. Islands consistent with follicular ameloblastoma were present in other areas of the specimen. H&E, original magnification X 450.

717

WALDRON ET AL.

myoepithelial carcinoma of intercalated origin.ts Batsakist6 has pointed out that these clear cells may contain large amounts of cytoplasmic glycogen and a normal complement of subcellular organelles, contain little or no cytoplasmic glycogen and few organelles, or appear clear as a result of fixation artifact. Intraosseous mucoepidermoid tumors of the jaws are unusual but are not rare.17 Nonmucinous clear cells are seen in these neoplasms. The origin of these lesions is controversial. but there is evidence that a substantial number of them may arise in odontogenic cysts.‘* Several consultants who reviewed the slides in case 1 suggested the possibility or favored a diagnosis of mucoepidermoid carcinoma. In our experience, however, the microscopic features in our cases were not consistent with those seen in other central mucoepidermoid tumors we have studied, and the obvious “ameloblastic” features present in both cases cannot be discounted. We believe that the two cases reported should properly be considered as malignant ameloblastomas. One patient (case 1) remained well for six and one-half years following radical surgery with demonstration of tumor-free resection margins. The other patient (case 2) developed extension into the infratemporal fossa, retroorbital region, and base of the skull. Nodules in the left neck developed nine years after the original excision, which was clinically suggestive of lymph node metastasis. A needle biopsy of one of these masses demonstrated tumor cells that resembled the tumor seen in the previous surgical specimens. This patient expired in February 1984 from general debilitation and extensive local tumor growth. Permission for autopsy was refused. The development of a left submandibular gland mixed tumor one year after the original excision of the left maxillary ameloblastoma and nine years before development of the left neck mass complicates analysis of this case. The sections of the submandibular gland showed an encapsulated benign mixed tumor, although some areas showed increased nuclear pleomorphism and mitoses. Multiple sections, however, did not demonstrate penetration of the capsule by the tumor. During the next nine years the patient did not have any recurrent swelling in this area. The subsequent clinical course, with multiple recurrences of the maxillary ameloblastoma and the location of the neck mass in 1979, strongly suggests that the metastasis represented ameloblastoma. On the basis of experience with these two cases,

it appears that the primary surgical management of the clear-cell ameloblastoma should be aggressive and that this clear-cell variant of the ameloblastoma should be regarded as a malignant neoplasm. Summary

Two cases of aggressive intraosseous epithelial tumor of the jaws are presented. Both tumors demonstrated an unusual biphasic pattern with areas of acceptable follicular ameloblastoma together with a conspicuous clear-cell component. The clinical course indicates these lesions should be considered as low grade odontogenic carcinomas. Further subclassification according to the World Health Organization classification and the recently proposed modification by Elzay5 is discussed. References I. Regezi JA, Kerr DA, Courtney RM: Odontogenic tumors: analysis of 706 cases. J Oral Surg 36:771, 1978 2. Small IA, Waldron CA: Ameloblastomas of the jaws. Oral Surg 8:281, 1955 3. Gorlin RJ, in Gorlin RJ, Goldman HM, eds: Thoma’s Oral Pathology. St. Louis. CV Mosby, 1970, p 488 4. Pindborg JJ, Kramer IRH: Histologic Typing of Odontogenic Tumors, Cysts and Allied Lesions. Geneva, 1971, World Health Organization, p 35 5. Elzay RP: Primary intraosseous carcinoma of the jaws. Oral Surg 54:299, 1982 6. Carr RF, Halperin V: Malignant ameloblastomas from 19.53 to 1966. Oral Surg 26:514, 1968 7. Herceg SJ, Harding RL: Malignant ameloblastoma with pulmonary metastasis. Plast Reconstr Surg 49:456. 1972 8. Ikemura K. Tashiro H, Fagino H, et al: Ameloblastoma of the mandible with metastasis to the lungs and lymph nodes. Cancer 29:930. 1972 9. Hoke HF Jr. Harrelson AB: Granular cell ameloblastoma with metastasis to the cervical vertebrae. Cancer 20:990. 1967 IO. Krolls SO, Pindborg JJ: Calcifying epithelial odontogenic tumor. Arch Pathol 98:206. 1974 I I. Wysocki GP, Brannon RB, Gardner DG. et al: Histogenesis of the lateral periodontal cyst and the gingival cyst of the adult. Oral Surg 50:327, 1980 12. Mohamed AH: Ultrastructure of glycogen-rich clear cell carcinoma of the palate. J Oral Pathol 5:103, 1976 13. Melrose RJ, Abrams AM, Howell FV: Mucoepidermoid tumors of the intraoral salivary glands: a clinicopathologic study of 54 cases. J Oral Pathol 2:314, 1973 14. Abrams AA, Melrose RJ: Acinic cell tumors of minor salivary gland origin. Oral Surg 46:220, 1978 15. Corio RL. Sciubba JJ. Brannon RB. et al: Eoithelial mvoepithelial carcinoma of intercalated duct origin. Oral S&g 53:280, 1982 16. Batsakis JG: Tumors of the Head and Neck, 2nd ed. Baltimore, Williams and Wilkins. 1979. p 47 17. Browand BC, Waldron CA: Central mucoepidermoid tumors of the jaws. Oral Surg 40:631, 1975 18. Eversole LR. Sabes WR, Rovin S: Aggressive growth and neoplastic potential of odontogenic cysts. Cancer 35:270, 1975