* University of Louisville School of Dentistry, Department of Periodontics,Endodontics, and Dental Hygiene, Louisville, KY.

† Department of Surgical and Hospital Dentistry.‡ School of Dentistry, University of Illinois and private practice,

Chicago, IL.

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This case report describes an unusual odontogeniccarcinoma, which was detected during routine peri-odontal examination. The lesion occurred in adentigerous cyst associated with an impacted thirdmolar in an otherwise asymptomatic 66-year-old malepatient. The impacted tooth and lesion were excisedbased on evidence of radiographic change and clin-ical findings. An unusual histopathologic presenta-tion is reported. The treatment provided for this tumorand the management of impacted teeth is reviewed.J Periodontol 2000;71:1365-1370.

KEY WORDSCarcinoma, odontogenic; dentigerous cyst; molar;tooth, impacted.

The dentigerous cyst is the second most commonlyoccurring odontogenic cyst. Rarely, the lining of thedentigerous cyst can undergo neoplastic transfor-mation to an ameloblastoma or to an odontogeniccarcinoma.1-6 Odontogenic carcinomas may differ-entiate as squamous cell carcinomas, mucoepider-moid carcinomas, and clear cell odontogenic carci-nomas.2,7 Early odontogenic carcinomas may arisein dentigerous cysts and often present as asympto-matic lesions resembling dentigerous cysts radi-ographically. An increase in size of the cyst or motheaten appearance of the cyst wall may be radi-ographic indications of such transformation.4,7 Laterlesions may demonstrate ill-defined borders, markedincrease in size; multilocular appearance; alveolardestruction; root resorption and cortical plate perfo-ration radiographically; and pain, swelling, paresthe-sia or anesthesia of anatomically related areas clin-ically.6 Soft tissue invasion and cervical metastasiscan occur in late stage disease.

Approximately 22 to 25% of odontogenic carcino-mas arise in dentigerous cysts.3,6,7 Often evidenceof a squamous cyst lining, dysplastic cyst lining, ormucous modulated cyst lining is noted in earlylesions. A transitional zone from dysplastic squamousodontogenic epithelium to invasive squamous cellcarcinoma is considered a pathognomonic featurefor the designation of epidermoid carcinoma arisingin a dentigerous cyst; however, larger lesions fre-quently lack this feature. The degree of differentia-tion of the squamous cell carcinoma may vary fromhighly keratinizing to anaplastic. A sclerosing odon-togenic carcinoma was recently presented byLandwehr and Allen8 in which a clinically malignanttumor resembling a malignant desmoplasticameloblastoma was described. This histopathologywas reminiscent of adenocarcinoma of the breast andmetastatic breast cancer was ruled out.

CASE DESCRIPTION AND RESULTSThis 66-year-old white man was first seen by one ofthe authors (JWO) at the University of LouisvilleSchool of Dentistry for periodontal osseous surgeryof the mandibular right quadrant. Clinical examina-tion and review of past dental history revealed that

Odontogenic Carcinoma Occurring in a Dentigerous Cyst: Case Report and Clinical ManagementJohn W. Olson,* Richard L. Miller,† George M. Kushner,† and Tracy M. Vest‡

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an impacted mandibular third molar (#17) had notbeen extracted as previously planned. This tooth(#17) was horizontally impacted with radiolucencyconsistent with the clinical impression of a dentiger-ous cyst (Fig. 1). The radiolucent lesion appeared tohave widened in the last 25 months to involve theinferior coronal portion of the crown (Fig. 2). Thegingiva and alveolar mucosa appeared normal withno lesions, inflammation, swelling, or evidence of cor-tical expansion (Fig. 3). Periodontal probing revealeda 5 mm pocket at the distal of tooth #18 extendingto the coronal area of impacted #17. The initial exam-ination and treatment plan completed 30 months pre-viously had indicated that teeth #16, 17, and 32 wereto be extracted. The extraction of these teeth wasdeferred as they were asymptomatic and the patientrefused this treatment. They were to be evaluated atregular maintenance intervals.

The patient’s past medical history was significantfor myocardial infarction, heart murmur, and arthri-tis. A consultation with his cardiologist revealed mitralvalve stenosis with regurgitation and antibiotic pro-phylaxis for indicated dental procedures was imple-mented according to American Heart Associationguidelines. Medications included digoxin and quini-dine. No allergies were reported. The patient gave ahistory of cigarette smoking of 48 pack years, whichwas discontinued 15 years previously. He was a socialalcohol user and continued to consume 2 to 3 mixeddrinks per week.

At this presenting appointment, the patient was

informed of the possibility of a pathologic lesion andimmediately referred to oral and maxillofacial surgeryfor extraction of impacted #17 and histopathologicalexamination of associated tissues.

The pericoronal soft tissue measured 1.1 × 1.1 ×0.3 cm. Microscopically, a dense fibrous connectivetissue cyst wall was lined by remnants of dysplastickeratinizing stratified squamous odontogenic epithe-lium. The lining cells demonstrated a degree ofnuclear and cellular pleomorphism and nuclear hyper-chromatism (Fig. 4). In focal areas, islands andstrands of cells invaded the cyst wall. These invasivecords demonstrated two distinct morphologic pat-terns. In one area the cords were composed of ker-atinizing squamous cells (Fig. 5). These cells werepleomorphic and hyperchromic and occasionalmitotic activity was notable. The cords were sepa-rated by collagenous fibrous connective tissue andfocal areas showed chronic inflammatory cell infil-trates. No evidence of nuclear palisading or reversepolarity of cells was noted within the islands. Theample eosinophilic cytoplasm showed occasionalintracellular keratin formation (Fig. 6).

The deeper portions of the cyst wall demonstratedelongated cords of poorly differentiated cells char-acterized by scanty eosinophilic cytoplasm, markedhyperchromatism, and nuclear pleomorphism. Thecords often appeared parallel to each other withbranching and anastomosis. The intervening stromain this area was composed of dense collagenous

Figure 1.Periapical and panoramic radiographs, impacted mandibular leftthird molar.

Figure 2.Periapical and panoramic radiographs, impacted mandibular leftthird molar revealing enlargement of radiolucent lesion. (Note the 2year time interval between Figure 1 and Figure 2 radiographs.)

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fibrous connective tissue and widely separated thepoorly differentiated cords of cells imparting theappearance of desmoplastic ameloblastoma (Fig. 7).Both areas stained positive for high molecular weightcytokeratin (AE3) and negative for low molecularweight cytokeratin (AE1). All external controlsreacted appropriately. A preliminary diagnosis ofodontogenic carcinoma resembling malignant desmo-plastic ameloblastoma was rendered. Several oraland maxillofacial pathology consultants concurredwith the diagnosis of odontogenic carcinoma.

A CT scan with contrast of the affected arearevealed: 1) a mandibular defect on the left consis-tent with a postsurgical defect secondary to the recentextraction of #l7; 2) asymmetry of the soft tissue witha suggestion of some thickening on the left side ofthe oropharynx which was interpreted as either post-

operative swelling or tumor; and 3) a slightly enlargedsubmandibular node on the left side. The patient wasreferred to a head and neck surgical oncologist forfurther examination. The patient subsequently under-went left posterior segmental mandibulectomy andmodified radical neck dissection. Mandibular integritywas immediately restored with an iliac crest bonegraft and reconstruction plate (Fig. 8). The surgicalexcisional biopsy report revealed tumor free margins,no lymph node involvement, and no residual tumor.Therefore, radiation therapy was not indicated. Thepatient recovered well. He has been seen for peri-odontal maintenance every 3 months for the subse-

Figure 3.Clinical photographs of left posterior mandible, A (top) buccal and B (bottom) lingual.

Figure 4.Dysplastic keratinizing stratified squamous epithelial cyst lining(hematoxylin-eosin, original magnification ×200).

Figure 5.Keratinizing squamous cords invading the cyst wall (hematoxylin-eosin, original magnification ×400).

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quent 24 months following the resection. No recur-rence has been noted.

DISCUSSIONThe importance of a thorough medical and dentalhistory during the examination process has been wellestablished and is considered to be a requirement forcomprehensive medical and dental care.9,10 Accord-ing to Little et al., “It is important to know what hasbeen done in the past, when it was done, and theoutcome of the previous treatment.”11 Any compli-cation with the treatment plan should be documented.

Patient reviews are an ongoing process and areimportant, especially in universities or multi-groupand multi-specialty practices where patients may beseen in different clinics and by different providers/fac-ulty from one appointment to the next. The assump-tion that treatments have been completed as pre-scribed in the treatment plan (i.e., the removal of animpacted tooth) is not considered an acceptable stan-dard of care.

In dentistry, one of the most controversial areas ismanagement of impacted teeth. In the past, oral andmaxillofacial surgeons traditionally removed thirdmolars, usually in the teenage population. The pro-phylactic removal of impacted third molars (symp-tomatic/asymptomatic) was considered as removal ofpotentially pathologic tissue and felt to be preven-tive dentistry. The debate as to whether impactedteeth represent pathologic tissues or a variance ofnormal continues. Recently, primarily due to thirdparty policies and reimbursement criteria, the removalof asymptomatic impacted teeth has been ques-tioned.12 Practicing surgeons have anecdotally knownthat third molars extracted in the teenage populationhave a very low complication rate. With increasingage, comes an inherent increased surgical risk ofremoval of impacted teeth.13-16 The study of riskmanagement principles has provided new guidelinesand/or recommendations for practicing surgeons.Many practitioners feel that asymptomatic (clinicallyand radiographically) impacted teeth in the 30- to40-year-old patient should be observed and not

Figure 6.Anastomosing cords of tumor cells separated by collagenous fibroustissue (hematoxylin-eosin, original magnification ×400).

Figure 7.Poorly differentiated parallel cords of epithelial cells separated bydense collagenous fibrous tissue (hematoxylin-eosin, originalmagnification ×400).

Figure 8.Panoramic radiograph with iliac crest graft and rigid internal fixationplate.

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removed.12 The risk/benefit ratio in this age group isnot favorable and the teeth should be followed byperiodic radiographs and clinical examination.12,17

All too often, after the initial decision not to extracta tooth is made, no following radiographs or clinicalevaluation is performed. When following the patientclinically and radiographically, if changes are notedindicating pathosis, the tooth should then be removed.

In this case, a 66-year-old white male was foundto have a horizontally impacted tooth #17 that wasasymptomatic. He was referred to the Oral and Max-illofacial Surgery Clinic at the University of LouisvilleSchool of Dentistry where the risks and benefits of thesurgical procedure were reviewed with the patient.The possibility of paresthesia, infection, prolongedhealing, the development of an osseous defect distalto tooth #18, and mandible fracture were discussed.After weighing the risks and benefits, the patientelected to have this tooth followed clinically and radi-ographically. Most importantly, the patient received aperiodic examination and x-ray approximately 2 yearslater which revealed a periodontal pocket at the dis-tal of tooth #18 and an increase in size of the peri-coronal radiolucency, possibly signifying the devel-opment of a pathologic lesion. With this in mind, thetooth and pericoronal tissue were removed and sentfor histopathologic examination.

The histopathology of this lesion was consideredunusual and even somewhat controversial. Only smallfragments of the cyst lining were observed. Thesefragments showed keratinization, dyskeratosis, basalarhyperplasia, and nuclear changes suggestive of dys-plasia. The cyst wall adjacent to the lumen demon-strated islands interpreted as malignant squamouscells with intercellular bridging and intracellular cyto-keratin aggregates. Several histopathologic areaswithin the cyst wall indicated transition from differ-entiated to poorly differentiated carcinoma. Not allconsultants agreed with the above interpretations.

The clinical appearance of a dentigerous cyst canrepresent such entities as glandular odontogenic cyst,odontogenic keratocyst, odontogenic carcinoma,ameloblastoma, ameloblastic fibroma, and, althoughrare, other odontogenic and non-odontogenic lesions.Therefore, histopathologic evaluation of such lesionsis recommended. This case underscores the impor-tance of a histologic examination of such lesions. Thediagnosis of odontogenic carcinoma arising in adentigerous cyst was based on the histopathologicconsiderations and the temporal radiographic changesdescribed previously. Because of the poorly differen-tiated nature of many areas, since it was unknown

whether the original biopsy/extraction was excisional,and because the follow-up imaging was equivocal forresidual disease, the somewhat aggressive resectionwas recommended for optimal cure with least mor-bidity. The absence of evidence of tumor in the defin-itive surgical sections may represent sampling erroror confirm excision at the primary intervention. Thepatient is nevertheless being followed closely for anyevidence of recurrence of metastasis.

It is well known and has been documented in theliterature that odontogenic cysts can undergo trans-formation to a more aggressive tumor such asameloblastoma and can have transformation to frankmalignancies.1,2,4 The mainstay of treatment of odon-togenic carcinoma remains surgical. Most commonly,the mandible is resected and often a neck dissectionis performed to evaluate the lymph nodes draining theaffected area. Carcinomas usually first metastasizeor spread throughout the body via the lymphaticchannels. In this case, mandibular resection was per-formed with immediate bone graft reconstruction fromthe iliac crest. The patient has been followed closelyand has done well. There is no evidence of diseaserecurrence after three years. The next step in histreatment plan includes dental implant reconstruc-tion to restore him to his presurgical status.

REFERENCES1. Waldron CA, Mustoe TA. Primary intraosseous carci-

noma of the mandible with probable origin in an odon-togenic cyst. Oral Surg Oral Med Oral Pathol 1989;67:716-724.

2. Johnson LM, Sapp JP, McIntire DN. Squamous cellcarcinoma arising in a dentigerous cyst. J Oral Max-illofac Surg 1994;52:987-900.

3. Eversole LR, Sabes WR, Rovin S. Aggressive growthand neoplastic potential of odontogenic cysts. Cancer1975;35:270-282.

4. Manganaro AM, Cross SE, Startzell JM. Carcinomaarising in a dentigerous cyst with neck metastasis. HeadNeck 1997;19:436-439.

5. Gardner AF. A survey of odontogenic cysts and theirrelationships to squamous cell carcinoma. J Can DentAssoc 1975;3:161-167.

6. Copete MA, Cleveland DB, Orban RE, Chen S-Y. Squa-mous carcinoma arising from a dentigerous cyst: Reportof a case. Compendium Contin Educ Dent 1996;17:202-204.

7. Neville BW, Damm DD, Allen CM, Bouquot JE. Oraland Maxillofacial Pathology. Philadelphia: WB Saun-ders Co; 1995:510-511.

8. Landwehr D, Allen C. Aggressive odontogenic neo-plasm mimicking metastatic breast carcinoma: Scle-rosing odontogenic carcinoma? Amer Acad Oral Max-illofac Path 1996;1:11.

9. Rose LF, Kaye D. Internal Medicine for Dentistry. St.Louis: The CV Mosby Company; 1990:1-11.

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10. Bricker SL, Langlais RP, Miller CS. Oral Diagnosis OralMedicine and Treatment Planning. Philadelphia: Leaand Febiger; 1994:32-45.

11. Little JW, Falace DA, Miller CS, Rhodus NL. DentalManagement. St. Louis: The CV Mosby Company; 1997:89.

12. Lytle JJ. Etiology and indications for management ofimpacted teeth. Oral Maxillofac Surg Clin N Amer 1993;5:63-75.

13. Osborn TP, Fredericksen G, Small IA. A prospectivestudy of complications related to mandibular thirdmolar surgery. J Oral Maxillofac Surg 1985;43:767-769.

14. Bruce RA, Fredericksen G, Small GS. Age of patientsand morbidity associated with mandibular third molarsurgery. J Am Dent Assoc 1980;101:240-245.

15. Fielding AF, Douglas AF, Whifley RD. Reasons for earlyremoval of impacted third molars. Clin Prev Dent 1981;3:19-21.

16. Helfrick J. Parameters of care for oral and maxillofa-cial surgery. J Oral Maxillofac Surg 1995;53(9):31-59.

17. Alling CC, Alling RA, Helfrick J. Impacted teeth.Philadelphia: WB Saunders Company;1993:46-64.

Send reprint requests to: Dr. John W. Olson, Departmentof Periodontics, Endodontics, and Dental Hygiene, Schoolof Dentistry, University of Louisville, 501 S. Preston Street,Room 236, Louisville, KY 40202.

Accepted for publication January 24, 2000.

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