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Oral and Maxillofacial Pathology Case of the Month Diagnosis and Management
ORALand maxillofacial pathology diagnosis and management—from page 280
Discussion
The calcifying epithelial odontogenic tumor (CEOT) (or “Pindborg tumor”) represents a rare, benign odontogenic neoplasm. Its exact histogenesis is uncertain, although an origin from the stratum intermedium or dental lamina has been proposed.1 The tumor exhibits a predilection for the posterior mandible, with a peak age at diagnosis in the 4th decade and no significant gender predilection.2,3 Most patients exhibit a painless, slowly enlarging swelling. The majority of cases are intraosseous, although peripheral (i.e., gingival soft tissue) lesions also are possible. Radiographic examination shows a unilocular to occasionally multilocular radiolucency, often with associated opacification. Other possible findings include cortical bone resorption or perforation and tooth displacement.2 Many examples develop in association with an impacted tooth, especially a mandibular molar.1 The differential diagnosis for a mixed radiopaqueradiolucent lesion associated with the crown of impacted tooth may include other odontogenic tumors that produce calcification, including calcifying odontogenic cyst, ameloblastic fibro-odontoma, and adenomatoid odontogenic tumor. Ameloblastic fibroodontoma and adenomatoid odontogenic tumor tend to occur in somewhat younger patients compared to CEOT. Both CEOT and ameloblastic fibro-odontoma exhibit a predilection for the posterior mandible. In contrast, adenomatoid odontogenic tumor most often occurs in the anterior maxilla, and the calcifying odontogenic cyst exhibits an approximately even distribution between the maxilla and mandible. In addition, depending on the amount of calcification, some CEOTs may appear entirely radiolucent. In the present case, the lesion in the mesiolateral root area of the mandibular second premolar appeared entirely radiolucent, and the radiographic differential diagnosis included primarily a lateral periodontal cyst or odontogenic keratocyst.
As exemplified by the current case, typical microscopic findings of CEOT include a proliferation of eosinophilic epithelial cells with associated pools of an amyloid protein. This material exhibits applegreen birefringence with Congo red staining and may form basophilic, lamellar calcifications (Liesegang ring calcifications). Investigators have identified odontogenic ameloblast-associated protein (ODAM) within the amyloid deposits of CEOT; this protein has been implicated in
ameloblast differentiation and tooth development.4,5 Pleomorphism at times may be observed among the tumor cells in CEOT but should not lead to misdiagnosis as malignancy. Unusual histomorphologic variants include clear cell, microcystic/cystic, and noncalcifying Langerhans cell-rich types.6-9 The latter also may be classified as the amyloid-rich variant of central odontogenic fibroma.
Treatment of CEOT may range from enucleation or curettage for smaller lesions to resection for larger, more aggressive lesions. Although CEOT is a benign neoplasm, there is the potential for locally aggressive behavior. Malignant transformation is extremely rare.10 In their review of more than 300 previously reported cases, Chrcanovic and Gomez noted an overall recurrence rate of 12%, with recurrence varying by treatment rendered (24% for lesions treated by excision or curettage, 15% for lesions treated by enucleation, 0% for lesions treated by marginal resection, and 8% for lesions treated by segmental resection).2 Given the possibility of recurrence, periodic clinical and radiographic follow-up is advisable.
Multifocal CEOT is a rare phenomenon. A review of the English language literature reveals only 9 prior cases, with the number of lesions per patient ranging from 2 to 13.11-19 All cases represented synchronous lesions except for that described by Sedghizadeh et al.12 Affected patients exhibited intraosseous and/or extraosseous lesions. The clinical and radiographic features of the individual lesions seen in these multifocal cases were similar to those of isolated lesions. One patient also exhibited a concurrent squamous odontogenic tumor.19 No syndromic associations have been noted.
One might speculate whether underlying genetic mutations could account for the development of multifocal CEOT, although currently little is known about the molecular etiopathogenesis of CEOT. Interestingly, somatic mutations in PTCH1—a tumor suppressor gene that maps to chromosome 9q— have been demonstrated in two cases of localized CEOT.20 This gene participates in the Sonic hedgehog pathway, which has functions in tissue patterning and odontogenesis. PTCH1 mutations also have been detected in other pathologic conditions, such as the nevoid basal cell carcinoma syndrome (a heritable condition characterized by multiple odontogenic keratocysts of the jaws, cutaneous basal cell carcinomas, palmar/ plantar pits, skeletal abnormalities, and, rarely, medulloblastoma) as well as sporadic cases of odontogenic keratocyst, basal cell carcinoma, and medulloblastoma.20,21 In addition, in a small number of CEOT cases, investigators have detected mutations in various other genes, including AMBN, PTEN, CDKN2A, MET, and JAK3. 22,23 However, the significance, if any, of mutations identified thus far is uncertain, and further studies are needed.
ORALand maxillofacial pathology, continued
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