CLINICOPATHOLOGIC CONFERENCE
An incidentally discovered radiolucency in the posterior mandible
Stephen B. Hutton, BS,aSabah Kalamchi, BDS, DDS, LDSRCS, FFDRCS,aand John M. Wright, DDS, MSc,b Arizona School of Dentistry and Oral Health, Mesa, Arizona; and Baylor College of Dentistry, Dallas, Texas
(Oral Surg Oral Med Oral Pathol Oral Radiol 2012;113:17-20)
CLINICAL PRESENTATION
A 61-year-old woman presented to the general dentist for routine dental treatment. Her medical history in- cluded diabetes mellitus managed with metformin, a negative history of tobacco, alcohol, or drug use, and unremarkable family history for neoplastic disease.
Significant dental history included restorative treatment over several decades, and her third molars were ex- tracted without periapical or pericoronal pathology at age 19 years. Clinical examination revealed a normo- cephalic atraumatic head with a normal range of man- dibular movement, stable occlusion, and supple cervi- cal region without lymphadenopathy. The intraoral examination revealed no evidence of any soft tissue pathology. The patient was asymptomatic, and the den- tition was within normal limits. Panoramic radio- graphic examination revealed a large well circum- scribed radiolucency distal to the second molar, within the ramus of the left mandible (Figure 1). The radio- graphic findings prompted an incisional biopsy. Com- puterized tomography revealed a less discrete osteolytic lesion centered well within the mandible that had also penetrated the lingual cortical plate (Figure 2).
DIFFERENTIAL DIAGNOSIS
Differential diagnosis of a well circumscribed, noncor- ticated, radiolucent lesion of the retromolar region of the mandible comprises several classes of pathology, including odontogenic cysts and tumors, nonodonto- genic tumors, and other nonneoplastic conditions.
A significant number of intrabony jaw lesions have their origin from the tooth-forming tissues, and there- fore, odontogenic cysts and tumors are a logical place to start a differential diagnosis. Odontogenic cysts are more common than odontogenic neoplasms. Of the odontogenic cysts, odontogenic keratocyst (OKC; or
keratocystic odontogenic tumor) would be the most likely in the present case. Keratocysts affect the man- dible⬃75% of the time and exhibit a strong propensity for the posterior mandible and the ascending ramus.1 The majority of OKCs are found in people between ages 10 and 40 years, and radiographic findings most often demonstrate a benign process with well corticated borders.1 Additionally, a significant number of OKCs (38%) tend to be associated with an unerupted tooth or earlier extraction site.1 Finally, from the odontogenic cyst category, neither a residual dentigerous cyst nor residual apical periodontal cyst would be considered, because those conditions were not present at the time of third molar extraction.
Odontogenic tumors often present as well circum- scribed radiolucencies, which suggest that this lesion could be one of a variety of odontogenic neoplasms, such as ameloblastoma, odontogenic myxoma, and the outside possibility of a low-grade odontogenic malig- nancy. Many of the odontogenic tumors would be im- probable based on demographic features. Odontogenic myxoma is found in the posterior mandible⬃23% of the time with equal predilection for the maxilla and mandible, but the lesion in the present case did not demonstrate the “soap bubble” radiographic appear- ance spanning from the premolar region to the molars that is typical of a myxoma.2Yet, of the odontogenic tumors, ameloblastoma is the most likely in this case, given the location and presentation of the lesion in the posterior mandible. Excluding odontomas, ameloblas- toma is the most common odontogenic tumor in gen- eral, and ⬃80% are found in the mandible, with the molar-ramus area affected between 39% and 66% of the time.3,4 The average age of diagnosis for amelo- blastoma is middle to late 30s. Although our patient was significantly older, just over 10% of cases do affect patients in their seventh decade.3,4
Notably, the lesion did not appear to be associated with a tooth, and accordingly, nonodontogenic pathol- ogy must be entertained in the differential diagnosis.
Nonodontogenic mesenchymal neoplasms may include neurofibroma, desmoplastic fibroma of bone, and vas- cular lesions. Even though neurofibromas are most
aArizona School of Dentistry and Oral Health.
bBaylor College of Dentistry, Texas A&M Health Science Center.
Received for publication Mar 19, 2011; returned for revision Jul 27, 2011; accepted for publication Aug 3, 2011.
© 2012 Elsevier Inc. All rights reserved.
2212-4403/$ - see front matter doi:10.1016/j.tripleo.2011.08.007
Vol. 113 No. 1 January 2012
17
commonly found on the buccal mucosa or the dor- sum of the tongue, these lesions may arise within the bone as well.5 In the present case, the location is favorable for desmoplastic fibroma, with 84% being found in the mandible and 70% of mandibular lesions affecting the ascending ramus.6 However, desmo- plastic fibroma was not likely, because 84% occur in people ⬍30 years old.6
Finally, lack of cortication and cortical perforation would raise the possibility of malignancy. Metastatic disease is usually symptomatic, but not uncommonly the oral metastasis can precede the discovery of the primary site. An intra-alveolar carcinoma, such as clear cell odontogenic carcinoma, may be feasible. Clear cell odontogenic carcinoma is quite uncommon, but re- ported demographic features, such as presenting in the mandible ⬃80% of the time, cortex perforation, soft tissue involvement, and age of the patient, make it a
possibility as well.7 Primary mucoepidermoid carci- noma (MEC) was also possible; despite its rarity, its favored site is the posterior mandible.8
DIAGNOSIS
A biopsy was performed by accessing the lesion from the crest of the alveolar ridge. Histologic examination revealed numerous nests and larger sheets of epithelial cells associated with both microcystic and macrocystic areas (Figure 3). The neoplastic cells were often poly- hedral and in areas; mature squamous differentiation was noted. Well formed mucus cells were mixed with the epidermoid cells (Figure 4). Mitoses were rarely encountered, and perineural invasion, necrosis, and high-grade cytologic atypia were absent. A mucicar- mine special stain demonstrated intracytoplasmic stain- ing of the mucus cells (Figure 5). A positron-emission tomography (PET) scan showed no indication of met- astatic disease throughout the body, nor suggestion of another primary neoplasm. A diagnosis of intraosseous MEC was made.
MANAGEMENT
Following confirmation from PET of no independent primary site, definitive surgical treatment commenced.
The lesion was resected with 1-cm margins; the coro- noid process and condyle were left intact. The buccal section was subperiosteal with the cortical plate intact.
However, the lingual section was supraperiosteal to include the lingual mucosa, sacrificing the lingual nerve. Multiple frozen tissue samples were taken dur- ing the surgery to verify clear margins. The patient was placed in intermaxillary fixation in preparation for the second-stage surgery and to allow for accurate recon- struction of the mandibular discontinuity with the use of a stereolithographic model to contour the plate.
Following the harvesting of a bicortical bone graft from the iliac crest, the proximal segment of the as- cending ramus and the distal portion of the body of the mandible were exposed. The mandibular discontinuity was reconstructed with a 2.3 mm Stryker Leibinger fixation plate. Postoperative recovery was uneventful.
The 12-month follow-up radiographic examination revealed osteogenesis; the donor tissue was well inte- grated into the recipient site, occlusion was stable, and the patient again could exercise the muscles of masti- cation to open 37 mm.
DISCUSSION
Primary intraosseous adenocarcinoma is rare is and mainly confined to the jaws, particularly the mandible.
The most frequent histopathologic type is MEC.8Most often, central salivary malignancies are reported in ei- ther the body or ramus of the mandible.8,9The 3 most Fig. 1. Panoramic radiograph showing a 1.5⫻ 1.5 cm well
defined and noncorticated radiolucent lesion, located within the ascending ramus of the left mandible (arrow).
Fig. 2. Computerized tomography reveals 1.5 ⫻ 1.5 cm osteolytic lesion within the ramus of the mandible. Lingual cortical plate destruction is apparent.
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18 Hutton, Kalamchi, and Wright January 2012
common subtypes of intraosseous adenocarcinoma are MEC, adenoid cystic carcinoma, and adenocarcinoma not otherwise specified, with MEC being the most prevalent.8,9 Fewer than 200 cases of central salivary gland tumors have been reported in the literature, the majority of which (n ⫽ 135) have been primary in- traosseous MEC.9The prevalence of intraosseous MEC is unknown.
The histogenesis of central salivary gland tumors has been widely debated. These malignancies may arise from developmental remnants of submandibular sali- vary gland, ectopic entrapment of retromolar minor mucous glands, glandular metaplasia of the epithelial cell rests of the dental lamina, or as an expression of the glandular potential of the epithelial lining of odonto- genic cysts.8-10Lack of details surrounding this partic- ular case prevents the opportunity to rule out a history
of a previous cyst or to evaluate the development of the lesion. An odontogenic origin for central MEC is sup- ported by the fact that between 32% and 48% of cases have been associated with an impacted tooth or an odontogenic cyst,8,11 although a recent report showed no correlation.9
Genetic analysis has demonstrated a subset of soft tissue and intraosseous MEC with the chromosomal translocation t(11;19), resulting in the fusion transcript CRTC1/MAML2.12,13 Preliminary evidence suggests that this mutation imparts an increased likelihood of metastasis.12 Additionally, the TORC1/MAML2 gene fusion has been reported in central MECs.14
Central MECs do not appear to have a significant gender predilection, although some series slightly favor female patients. They have been reported from the first to seventh decade of life but seem to have a predilection for middle age.8,9,11 The mandible is affected about 3 times more frequently than the maxilla with a predilection for the posterior mandible.8Rarely are the anterior jaws affected. Many patients are asymptomatic, but as the neo- plasm expands, pain and swelling are encountered.
Radiographically, central MEC presents as a uniloc- ular or multilocular radiolucency, which may be either well or ill-defined. Many are remarkably well defined.
The margins are generally noncorticated, but typically the cortical plate is intact.15
Retrospective case studies of intraosseous MEC have led some investigators to develop criteria for diagnosis, which include presence of an intact cortical plate.8,15 However, any central malignancy may perforate the cortex if untreated, which means that cortical perfora- tion should not preclude a diagnosis of intraosseous MEC.
Brookstone and Huvos8proposed a clinical 3-stage sys- tem for classifying intraosseous MEC, in which the third stage includes cortical perforation and destruction of the Fig. 3. Photomicrograph showing small infiltrating cords
and islands of neoplastic epithelium with micro- and mac- rocystic areas. Hematoxylin and eosin stain. Original mag- nification⫻13.
Fig. 4. Photomicrograph showing epidermoid cells mixed with larger more lightly staining mucus cells. Hematoxylin and eosin stain. Original magnification⫻33.
Fig. 5. Mucicarmine stain demonstrating mucus cells with bright red intracytoplasmic mucin. Original magnification⫻ 33.
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Volume 113, Number 1 Hutton, Kalamchi, and Wright 19
periosteum. These stages were recommended because a large tumor confined to the cortical plates undoubtedly would pose a better prognosis than a much smaller lesion that penetrated the cortical plate and invaded surrounding structures or demonstrated metastasis. In the same review, however, there appeared to be no association with grade of malignancy observed and prognosis with treatment.8 According to the proposed staging system, the present lesion would be classified as stage III, because the cortical plate was perforated.
Treatment may include either aggressive surgical resection or a more conservative approach.8,9 Retro- spective analyses of intraosseous MEC suggest that en bloc resection is the best approach to prevent recur- rence.9More conservative treatment might include enu- cleation, curettage, or marsupialization, which may be supplemented with adjuvant therapy, such as radiother- apy, but risks for recurrence and osteoradionecrosis clearly exist with little added value.9
A systematic review of intraosseous salivary gland tumors showed that conservative treatment resulted in recurrence in 40% of cases, whereas aggressive surgi- cal treatment yielded 4% recurrence.8Survival of pa- tients after 5 years is seldom addressed in the literature, but one group provided 2- and 5-year follow-up data after aggressive surgical treatment, reporting 100% sur- vival rates.11 A retrospective chart review indicated high survival with 1 death in a group of 20.9Reports on metastasis vary greatly, with as little as 9% in a group of 6611; however, another assessment of cases indicated that although none of the maxillary tumors metasta- sized, 39% of the mandibular cases were found to have metastatic cervical involvement before treatment.9 Cytogenetic analysis of soft tissue lesions demon- strated statistically significant correlation with CRTC1/
MAML2 fusion and metastasis,12but the same has yet to be observed for the intraosseous type. In our case, the patient presented without metastasis and without recur- rence at 12 months after treatment.
In summary, the present case was of an intraosseous MEC, which presented as an asymptomatic, well cir- cumscribed, noncorticated radiolucency of the retromo- lar region of the mandible. The differential diagnosis for a lesion with this presentation includes many classes of intrabony pathology, including primarily odontogenic cysts and tumors, but other nonodontogenic lesions as well. The histogenesis of intrasosseous MEC is debatable.
Surgical resection is associated with a good prognosis.
The authors of this article owe gratitude to Dr. Malcolm Harris for his unique and selfless contributions, which undoubtedly improved the quality of the research herein.
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Reprint requests:
Sabah Kalamchi
Department of Oral and Maxillofacial Surgery Mesa, AZ
skalamchi@atsu.edu
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