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J Oral Maxillofac 48:871-877,
Surg
1990
Central Mucoepidermoid of the Jaws:
Carcinoma
Report of Four Cases With Analysis of the Literature and Discussion of the Relationship to Mucoepidermoid, Sialodontogenic, and Glandular Odontogenic Cysts CHARLES A. WALDRON,
DDS, MSD,* AND MAY LING KOH, BDS, MDSt
Salivary gland tumors occurring intraosseously in the jaws are rare lesions. Although several histologic types, including mixed tumors,‘-3 trabecular adenoma,4 and adenoid cystic carcinoma’ have been reported, there is general agreement that mucoepidermoid carcinoma is the most common salivary gland tumor found in an intraosseous location. While its occurrence is generally considered to be uncommon, it may not be as rare as generally believed. In a recently reported study of 426 minor salivary gland tumors obtained from 11 different institutions,6 one of us (C.A.W.) noted 6 examples of intraosseous mucoepidermoid carcinoma. To our knowledge, none of these has been previously reported. A recent discussion regarding a consultation case prompted us to review the files of the Department of Oral Pathology, Emory University School of Postgraduate Dentistry and report 4 additional cases which have been accessioned since the report by Browand and Waldron in 1975.’ The subject of central mucoepidermoid carcinomas was more recently reviewed in 1983 by Grubka et al8 who restricted their review to mandibular lesions, and in 1984 Gingell et al9 who included both mandibular and maxillary cases. We have reviewed the English language literature and have noted five additional cases which have been reported’0-‘3 since the reviews of Grubka et al8 and * Professor Emeritus and Consultant, Department of Oral Pathology, Emory University School of Postgraduate Dentistry, Atlanta, GA. t Registrar, Singapore General Hospital, Republic of Singapore; formerly, Chief Resident, Department of Oral Maxillofacial Surgery, Emory University School of Postgraduate Dentistry, Atlanta, GA. Address correspondence and reprint requests to Dr Waldron: 1197 Hunter’s Dr. Stone Mountain, GA 30083. 0 1990 American geons
Association
0278-2391/90/4808-0018$3.00/O
of Oral and Maxillofacial
Sur-
Gingell et a1.9 Including the cases we are reporting, it appears that at least 66 cases of mucoepidermoid carcinoma of the jaws have been reported. Report of Cases Case 1 A white male dentist, age 63, noted some discomfort and apparent elongation of his mandibular left second premolar tooth. Periapical radiographs revealed a wellcircumscribed 0.6-cm unilocular radiolucency located in the apical area between the roots of the second premolar and first molar teeth (Fig 1). This was suspected to represent a lateral periodontal cyst. Since the crowned second premolar was somewhat uncomfortable, the patient elected to have this tooth extracted and the radiolucent lesion was removed by curettage through the extraction site. A well-circumscribed 0.5 X 0.5 x 0.5 cm soft tissue mass was removed intact. The microscopic diagnosis was low-grade cystic mucoepidermoid carcinoma. After the diagnosis was rendered, the patient obtained several consultations. Block excision of the area was suggested by several consultants, whereas others recommended close follow-up with no further surgery. He elected to keep the area under observation rather than to submit to a wider resection. The patient was contacted 10 years after the enucleation of the lesion and is well, without any evidence of recurrence. Case 2 An edentulous white woman, age 78, complained of slight tenderness of the alveolar mucosa in the mandibular right posterior region. Clinical examination revealed normal-appearing edentulous alveolar mucosa with no evidence of a mass or area of ulceration. Palpation of the ridge in the third molar region revealed an apparent dehiscence of bone on the buccal aspect of the alveolar ridge which was slightly tender. A panoramic radiograph revealed a 2.0-cm unilocular radiolucent lesion with somewhat irregular margins extending into the ascending ramus (Fig 2). The clinical diagnosis was probable residual dental cyst or granuloma. The lesion was removed from the bony defect by curettage, and the overlying mucosa was excised. The gross specimen was a mass of soft tissue measuring 2.0 x 2.0 x 1.0 cm. Microscopic study
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FIGURE 1. Case 1. Unilocular radiolucency which resembles a lateral periodontal cyst.
showed a low-grade mucoepidermoid carcinoma. The patient was lost to follow-up after 2 years, but at the last examination there was no clinical or radiographic evidence of recurrence. Case 3 A white man, age 63, had noted dull pain in his left posterior mandible for several months before consulting an oral and maxillofacial surgeon. Clinical examination revealed a full dentition, and the gingival and alveolar mucosa appeared clinically normal. A panoramic radiograph showed a horizontally impacted mandibular left third molar with a 2.5cm well-demarcated radiolucent defect surrounding the crown. The clinical impression was dentigerous cyst, and aspiration of the radiolucent area was attempted. No fluid was obtained. An incisional biopsy was then made through the intact alveolar mucosa over the third molar tooth. Microscopic study showed an intact oral mucosa with the underlying lamina propria being completely replaced by neoplastic epithelial cells. Numerous clear cells were interspersed among the squamous cells. Occasional clear cells were positive on mucicarmine staining and a diagnosis of mucoepidermoid carcinoma was rendered. The patient was referred to an oncologic surgeon who performed a hemimandibulectomy with in-continuity neck dissection because clinical signs made him suspicious of involved cervical lymph nodes. The mandibulectomy specimen was divided with a band saw, and the extent of the tumor in the medullary portion of the mandible was considerably more extensive than was suggested by the radiograph of the surgical specimen (Fig 3). The tumor had eroded through the lower border of the mandible in one area, but enough cortical bone was still present so that the area of destruction was not apparent on the radiographs. The microscopic diagnosis was highgrade mucoepidermoid carcinoma. One enlarged lymph node in the submandibular area contained metastatic tumor, but 43 other lymph nodes recovered from the dissection were negative for carcinoma. The immediate postoperative course was uneventful, but 6 months after surgery the patient returned with a firm submental swelling. A needle-aspiration biopsy was positive for tumor. A course of 7,200 rads of external beam
FIGURE 2. Case 2. Unilocular radiolucency with irregular margins in the retromolar area. radiation therapy failed to control the recurrence. The patient died of uncontrolled local disease 9 months after the initial surgery. Permission for an autopsy was not granted, but there was no clinical or radiologic evidence of metastatic disease at the time of death. Case 4 A black woman, age 57, complained of a slightly tender swelling in her mandibular left third molar area of several months’ duration. Clinical examination showed a smooth, nonulcerated nodule on the alveolar ridge in the third molar area. The patient related that an erupted left third molar had been extracted 6 months previously. A panoramic radiograph showed a u&ocular 1.5cm radiolucent lesion involving the crest of the alveolar ridge (Fig 4). The margins were slightly irregular and a thin rim of bone was present on the superior surface of the defect. The surgeon extracted the second molar and removed multiple fragments of soft tissue by curettage from the intrabony defect. The gross specimen consisted of multiple soft tissue fragments measuring in aggregate 3.0 X 2.5 x 1.O cm. The microscopic diagnosis was low-grade mucoepidermoid carcinoma. Unfortunately, this patient was lost to follow-up shortly after the immediate postoperative course, and attempts to contact her have been unsuccessful. MICROSCOPIC
FINDINGS
Cases 1,2, and 4 demonstrated similar microscopic features and were diagnosed as low-grade mucoepidermoid carcinomas. These showed multiple cystic and ductlike structures of varying size that were lined by epidermoid and mucous-producing cells in a dense fibrous connective tissue stroma. Squamous nests, occasionally containing foci of clear cells were interspersed among the cystic and ductlike structures. No evidence of keratinization was seen in any of these cases (Fig 5).
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and nuclear hyperchromatism were present. Occasional keratin pearls were also identified. Mucous cells were relatively sparse, although in focal areas clear cells that stained positive for mucin were present. No areas of cystic change were noted on study of sections from multiple blocks (Fig 6).
Discussion
FIGURE 3. Case 3. A, Radiograph of mandibular resection specimen showing a unilocular radiolucency which is associated
with a horizontally impacted third molar. B, Photograph of bisected gross specimen showing an extensive intramedullary tumor. The extent of the tumor is much greater than suggested by the radiograph shown in A.
Case 3 was interpreted as a high-grade mucoepidermoid carcinoma and demonstrated irregular islands and trabeculae of epidermoid cells in a dense fibrous connective tissue stroma. Considerable cellular pleomorphism
FIGURE 4. Case 4. Unilocular radiolucency in the third molar region with a thin, intact rim of bone on the superior aspect.
With the inclusion of the four cases reported here, it appears that at least 66 cases of central mucoepidermoid carcinoma of the jaws have been reported. Although some reports vary in completeness, the available clinical data on these cases are shown in Table 1. Intraosseous mucoepidermoid carcinomas occur about three times more commonly in the mandible than in the maxilla. Although there can be little question that the mandibular tumors represent intraosseous lesions, some reported maxillary tumors may be questionable because mucoepidermoid carcinomas may arise from mucous glands in the antral mucosa. Without adequate examination of a resection specimen, it may be very difficult to determine if a maxillary tumor actually arose within the substance of the maxilla or only represents intraosseous extension of a tumor originating within the sinus mucosa. Commonly accepted criteria for the diagnosis of a central mucoepidermoid carcinoma suggested by several authors include the following: 1) presence of intact cortical plates, 2) radiographic evidence of bone destruction, 3) histologic confirmation, 4) positive mucin staining, 5) absence of a primary lesion in the salivary glands or elsewhere which can mimic the histologic features of a mucoepidermoid carcinoma, and 6) exclusion of an odontogenic tumor.7V14,‘5The requirement of intact cortical plates
FIGURE 5. Case 4. Photomicrograph of low-grade mucoepidermoid carcinoma showing multiple cystic spaces lined by mucous-producing cells. Tumor islands showing squamous differentiation are interspersed among the cystic areas. Identical histologic features were present in cases 1 and 2. (Hematoxylineosin stain. Original magnification, X 100.)
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Table 1. Clinical Data on 66 Cases of Central Mucoepidermoid Carcinoma Age Range (61 cases) Mean Sex Male Female Not stated Location Maxilla Mandible Signs and symptoms* Swelling or enlargement Pain or paresthesia Drainage
1-85 yr 51.02 yr 28 36 2 18 48 38 24 5
* Several reports indicated more than one sign or symptom.
FIGURE 6. Case 3. A, Photomicrograph showing irregular islands of squamous and clear cells in a fibrous stroma. No mucous cysts are apparent. (Hematoxylin-eosin stain. Original magnification, x40.) B, Photomicrograph showing keratin pearl and atypical, hyperchromatic squamous cells. (Hematoxylin-eosin stain. Original magnification, x 100.) C, Higher magnification of A showing clear cell foci present in squamous nests in this tumor. Positive stains for mucin were present in some of the cells. (Original magnification, X400.)
before accepting a given case as being a central mucoepidermoid carcinoma may be open to question. Case 2 in this study, as well as other previously reported cases, showed a defect in the cortical plate overlying the radiolucent lesion within the mandible. This, however, was not associated with an ob-
vious soft tissue tumefaction that would indicate a primary tumor arising in the soft tissues. It is most unlikely that a mucoepidermoid carcinoma arising in the mucous glands of the lamina propria of the oral mucosa could invade the underlying bone resulting in a large radiolucent lesion without being associated with a clinically obvious soft tissue tumefaction. This feature was conspicuously absent in our case 2 and in other reported examples. The radiographic findings in central mucoepidermoid carcinomas are varied and nondiagnostic. Reported radiographic findings in about half of the cases indicated a unilocular radiolucent lesion, and about half have been stated to be multilocular lesions. The margins are usually well defined, although frequently scalloped. An unerupted tooth has been associated with the lesion in some cases. Due to the rarity of this tumor, the lesion is seldom suspected on clinical and radiological examination, and the process in question is usually believed to represent an odontogenic cyst or tumor such as ameloblastoma. The histogenesis of central mucoepidermoid carcinomas of the jaws is uncertain. The commonly proposed theories include mucous metaplasia of the epithelial lining of odontogenic cysts and embryologic or developmental entrapment of salivary gland tissue within the jaws. Although there is circumstantial evidence that neoplastic alteration in a preexisting odontogenic cyst may be the mechanism in a some cases, 9,16~17the histogenesis in most cases remains speculative. Regardless of histogenic mechanism, the pathological features in the four cases reported here and the descriptions and photomicrographs of previously published cases leave little doubt that these lesions would be acceptable instances of mucoepidermoid carcinoma had they been located in a ma-
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jor or minor salivary gland. Currently, mucoepidermoid carcinomas are commonly divided into categories of low- and high-grade malignancy, which has some bearing on treatment and prognosis.‘8 It is well appreciated, however, that mucoepidermoid tumors of salivary glands may pursue an unpredictable course, and tumors considered to be of lowgrade malignancy may occasionally metastasize. Although mucoepidermoid tumors were originally divided into benign and malignant types,” their unpredictable behavior has led most pathologists to consider them carcinomas. The designation mucoepidermoid carcinoma is almost universally used in the United States although some pathologists in Europe and Asia continue to designate them as mucoepidermoid tumors. Review of the histologic descriptions and photomicrographs of previously published cases indicates that the vast majority of central mucoepidermoid carcinomas of the jaws have been low grade, predominantly cystic lesions. Three of the four presently reported cases were of this type. Our review and experience with the currently reported cases shows that many questions still remain concerning the optimal treatment and prognosis of central mucoepidermoid carcinomas. Reported treatments have ranged from simple enucleation and/or curettage to en bloc or radical surgical resection. Radiotherapy has been used in several instances (Table 2). The relative rarity of central mucoepidermoid carcinomas and the fact that the majority of examples have been reported as isolated case reports, often with very brief follow-up, make evaluation of the behavior and prognosis difficult. To the best of our knowledge, only six deaths from such a tumor (including case 3 in the present study) have been reported. *O-** All of these deaths have been attributed to uncontrolled local recurrence or probable invasion of the base of the brain in one instance.** Regional lymph node metastasis has been reported Table 2.
in eight cases,“*20*21,23 which in one instance preceded discovery of the primary intrabony lesion.23 We have been unable to find any reports of distant metastases. The literature indicates that there is a significant incidence of local recurrence of central mucoepidermoid carcinomas, although the exact rate is difficult to determine. Our review indicates that this may approach 25%. Since about one third of reported cases had follow-up periods of less than 1 year, it suggests that the incidence of recurrence is likely to be higher than 25%. Enucleation or curettage of central mucoepidermoid carcinomas appears to be particularly likely to be associated with recurrence; our review indicates that the recurrence rate after curettage is approximately 40%. However, at least eight cases that were treated by curettage showed no recurrence for follow-up periods ranging from 5 to 32 years,7,16*20 indicating the unpredictable nature of this tumor. The lesion variously known as mucoepidermoid cyst,*4 sialodontogenic cyst,25 or glandular odontogenie cyst26 deserves consideration in the differential diagnosis of central mucoepidermoid carcinoma. This lesion is not well defined in the literature, and has seldom been reported, although we have seen several examples and are aware that others occasionally make this diagnosis. Radiologically, these lesions often present as multilocular radiolucent lesions (Fig 7). Histologically, they demonstrate multilocular cystic processes. The individual cysts are lined by a thin layer of squamous epithelium interspersed with foci of mucous goblet cells. Plaquelike thickenings of epithelium, similar to those seen in the botryoid odontogenic cyst,25,26 have been present in some instances (Fig 8). These lesions appear to have the potential for local recurrence after curettage.25’26 There is considerable overlap between the histologic features of the mucoepidermoid (sialodontogenie, glandular) cyst and those of some low-grade,
Results of Therapy in 66 Cases of Central Mucoepidermoid Carcinomas
Treatment
No. Cases
Details not given Conservative* Conservative + radiation Marginal excision? Marginal excision + radiation Radical excisionS Patient refused treatment Total
1 29 3 10 7 15 1 66
Recurrence 13 1
Metastasis 2
Death 2
1 1 2
5
4
17
8
6
* Enucleation, curettage with or without electrocoagulation. t En bloc excision with a margin of surrounding bone. $ Hemimaxillectomy or hemomandibulectomy with or without node dissection.
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this time. It is entirely possible that some cases previously diagnosed as central mucoepidermoid tumors may be reclassified as examples of glandular odontogenic cysts. Since there is evidence that a reasonable number of undoubted instances of central mucoepidermoid carcinomas originate from epithelial proliferation in preexisting odontogenic cysts, it is likely that both have a common odontogenie origin. Reporting and analysis of additional cases of mucoepidermoid (sialodontogenic, glandular) cysts may help to clarify this point. References
FIGURE 7. Multilocular cyst in retromolar area and ascending ramus of a man aged 55. Microscopic diagnosis of the curetted cystic specimen was glandular odontogenic cyst.
predominantly cystic, central mucoepidermoid carcinomas, and in selected microscopic fields the histologic picture may be identical. We believe the distinction between the two is largely a matter of degree of the epithelial proliferation. In the few cases we have diagnosed as mucoepidermoid cyst, the epithelial lining of the individual cysts has been uniformly thin without evidence of the more solid or microcystic epithelial proliferations seen in mucoepidermoid carcinomas. Whether this cystic lesion represents a separate entity of probable odontogenic origin or only the most benign end of the spectrum of central mucoepidermoid carcinoma cannot be determined at
FIGURE 8. Photomicrograph of a glandular odontogenic cyst in the anterior mandible of a man aged 47. Multiple cysts similar to this were present. These show a lining of uniform cuboidal cells and foci of clear cells. Weakly positive mucin staining was present in some areas. (Hematoxylin-eosin stain. Original magnification, X40.)
1. Simpson W: A Stafne’s defect containing a pleomorphic adenoma. J Oral Surg 23553, 1%5 2. St011 HC, Marchetta FC: Tumors of salivary gland origin presenting as primary jaw tumors. Oral Surg Oral Med Oral Pathol 10:1262, 1957 3. Freedman SI, Van der Velde RL, Kagan AR, et al: Primary malignant mixed tumor of the mandible. Cancer 30:167, 1972 4. Bret Day RC, Cawson RA: Cyst-like lesions of the mandible. Br Dent J 126:405, 1969 5. Gingell JC, Siegel MA: Adenoid cystic carcinoma of the mandible. J Am Dent Assoc 107600, 1983 6. Waldron CA, El-Mofty SK, Gnepp DR: Tumors of the intraoral minor salivary glands: A demographic and histoloeic studv of 426 cases. Oral Sura Oral Med Oral Path01 667323, 1987 7. Browand BC, Waldron CA: Central mucoepidermoid tumors of the jaws: Report of nine cases and review of the literature. Oral Surg Oral Med Oral Path01 40:633, 1975 8. Grubka JM, Wesley RK, Monaco F: Primary intraosseous mucoepidermoid carcinoma of the anterior part of the mandible. J Oral Maxillofac Surg 41:436, 1983 9. Gingell JC, Beckerman T, Levy BA, et al: Central mucoepidermoid carcinoma: Review of the literature and report of a case associated with an apical peridontal cyst. Oral Surg Oral Med Oral Path01 57:436, 1984 10. Pincock JL, El-Mofty SK: Recurrence of cystic central mucoepidermoid tumor of mandible: Report of case with 3 recurrences in 7 years. Int J Oral Surg 14:81, 1985 11. Ganz SD, Toth BB: Central mucoepidermoid carcinoma simulating odontogenic tumor. J Oral Med 40: 179, 1985 12. Unal T, Zeytinoglu B: Central mucoepidermoid carcinoma of the jaw. J Oral Med 40:202, 1985 13. Tomes K, Bang G, Moller P: Central mucoepidermoid tumors of the mandible: Report of 2 cases. J Cranio Maxillofac Surg 15:38, 1987 14. Alexander RW, Duperis RH, Holton HH: Central mucoepidermoid tumor (carcinoma) of the mandible. J Oral Surg 32:541, 1974 15. Silverglade LB, Alvares OF, Olech E: Central mucoepidermoid tumors of the jaws: Review of the literature and case report. Cancer 22:650, 1968 16. Eversole LR, Sabes WR, Rovin S: Aggressive growth and neoplastic potential of odontogenic cysts. Cancer 35:270, 1975 17. Marano PD, Hartman KS: Central mucoepidermoid carcinoma arising in a maxillary odontogenic cyst. J Oral Surg 32~915, 1974 18. Spiro RH, Huvos AG, Berk R, et al: Mucoepidermoid car_ cinema of salivary gland origin: A clinicopathologic study of 367 cases. Ann Sum 136461, 1978 19. Stewart FW, Foote FW-Jr, Becker WF: Mucoepidennoid tumors of salivary glands. Ann Surg 122:820, 1945
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20. Smith RL, Dahlin DC, Waite DE: Mucoepidermoid carcinomas of the jawbones. J Oral Surg 26:387, 1%8 21. Dhawan IK, Bhargava S, Nayak NC, et al: Central salivary gland tumors of iaws. Cancer 26:211, 1970 22. Frehrickson C, Ch&rick HM: Central mucoepidermoid carcinema of the iaws. J Oral Med 33:80. 1978 23. Stoch RB, Smith”I: Mucoepidermoid carcinoma in the mandible: Report of case. .l Oral Surg 3856, 1980 24. Hodson JJ: Mucoepidermoid odontogenic cysts of the jaws
J Oral Maxlllofac 48:877-m,
with special reference to those in the mandible. Proc R Sot Med 49:637, 1956 25. Padayachee A, Van Wyk CW: Two cystic lesions with features of both the botryoid odontogenic cyst and the central mucoepidermoid tumor: Sialo-odontogenic cyst? J Oral Path01 16:499, 1987 26. Gardner DG, Kessler HP, Morency R, et al: The glandular odontogenic cyst: An apparent entity. J Oral Path01 17:360, 1988
Surg
1990
Hemangioma and Malignant Hemangioendothelioma of the Maxillary Sinus: Case Reports and Clinical Consideration TADASHI YASUOKA, DDS, DMSc,* YASUAKI OKUMURA, DDS,t TAKASHI OKUDA, DDS,t AND NOBUMITSU OKA, DDS, DMSc*
Hemangioma of the paranasal sinuses is rare; a review of the literature yielded only four cases.le3 All had a benign microscopic appearance, but some demonstrated an aggressive behavior requiring multiple surgical procedures for control. The malignant hemangioendothelioma rarely occurs in the maxilla or maxillary sinus.4 When it does occur, however, it may be mistaken both clinically and microscopically for a hemangioma.’ We report two cases: the first is a hemangioma of the maxillary sinus; the second is a malignant hemangioendothelioma of the maxillary sinus initially diagnosed as a hemangioma. We also describe the common differentiating features of hemangioma and malignant hemangioendothelioma of the maxillary sinus.
Received from the Department of Oral and Maxillofacial Sureerv. ., ,. Gifu Universitv School of Medicine, Gifu.._Janan. * Chief, Day Surgery Unit. t St& surgeon and research assistant. $ Professor and Head. Address correspondence and reprint requests to Dr Yasuoka: Department of Oral and Maxillofacial Surgery, Gifu University School of Medicine, 40 Tsukasamachi, Gifu 500, Japan. 0 1990 American Association
of Oral and Maxillofacial Sur-
geons 0278-2391/90/4808-0019$3.00/O
Report of Cases Case 1 Hemangioma of the maxillary sinus. A 38-year-old woman consulted a dentist on October 21, 1988, for evaluation of purulent discharge from the labial gingiva overlying the root of the maxillary left canine. Root canal treatment was performed on the canine, and the patient was referred to our department on November 21, 1988. During our initial examination of the patient, a fistula was discovered in the labial attached gingiva over the maxillary left canine. Palpation of this area produced no tenderness, but demonstrated an elastic hard mass extending from the maxillary left lateral incisor to the maxillary first molar. Her past medical history showed iron deficiency anemia diagnosed 12 years previously during her first pregnancy. A panoramic radiograph with 76% diatrizoate meglumine (Urographin, Schering, Tokyo, Japan) as a contrast medium revealed a radiolucency at the anterior aspect of the left maxillary sinus (Fig 1). Surgery performed on February 2, 1989, showed a S-mm-diameter bony defect in the maxillary left canine fossa after removal of granulation tissue adherent to the perioral muscles. Soft, smooth-, mucouslike masses, yellowish-white in appearance, were observed beneath the defect. Two masses 1.5 cm in diameter and two masses 1.O cm in diameter were extirpated, and apicoectomy of the canine was performed. Microscopic examination of the specimen showed proliferation of thin-walled blood vessels with irregular dilation beneath a ciliated columnar epithelium. A diagnosis of cavernous hemangioma of the left maxillary