The 5th edition of the World Health Organization (WHO) Classification of Head and Neck Tumors opened to online access in March 2022. This edition is conceptually similar to the previous classification of odontogenic lesions. The only newly defined entity in odontogenic lesions is adenoid ameloblastoma, which is classified under benign epithelial odontogenic tumors. While not odontogenic, the surgical ciliated cyst is a new entry to the cyst classification of the jaws. In other respects, a very important change was made in the new blue books that added ‘essential and desirable diagnostic criteria’ for each entity to highlight the features considered indispensable for diagnosis. In this article, we review the odontogenic tumors and cysts of the jaw sections of the Odontogenic and Maxillofacial Bone Tumors Chapter, outlining changes from the 2017 WHO classification and summarizing the essential diagnostic criteria and new developments.

We demonstrate that structured illumination microscopy has the potential to enhance fluorescence lifetime imaging microscopy (FLIM) as an early detection method for oral squamous cell carcinoma. FLIM can be used to monitor or detect changes in the fluorescence lifetime of metabolic cofactors (e.g. NADH and FAD) associated with the onset of carcinogenesis. However, out of focus fluorescence often interferes with this lifetime measurement. Structured illumination fluorescence lifetime imaging (SI-FLIM) addresses this by providing depth-resolved lifetime measurements, and applied to oral mucosa, can localize the collected signal to the epithelium. In this study, the hamster model of oral carcinogenesis was used to evaluate SI-FLIM in premalignant and malignant oral mucosa. Cheek pouches were imaged in vivo and correlated to histopathological diagnoses. The potential of NADH fluorescence signal and lifetime, as measured by widefield FLIM and SI-FLIM, to differentiate dysplasia (pre-malignancy) from normal tissue was evaluated. ROC analysis was carried out with the task of discriminating between normal tissue and mild dysplasia, when changes in fluorescence characteristics are localized to the epithelium only. The results demonstrate that SI-FLIM (AUC=0.83) is a significantly better (p-value=0.031) marker for mild dysplasia when compared to widefield FLIM (AUC=0.63).

Despite of the ease accessibility of the oral cavity, only ~30% of oral cancer patients are diagnosed at early stages. Some of the factors that contribute to this low rate of early detection are: asymptomatic oral cancer lesions, similarity to benign lesions, and sampling error during biopsy procedures. Progression of oral cancer is accompanied by alterations in the intrinsic fluorescence properties of the oral tissue, making fluorescence lifetime imaging (FLIM) suitable for the diagnosis of oral cancer. In this study, in vivo human oral lesions from 70 patients were imaged using a multispectral FLIM endoscopy system. The collected database consisted of 50 benign lesions, and 20 dysplastic and early stage cancerous lesions, as determined by histopathological diagnosis. For each pixel, three fluorescence decays were collected corresponding to three emission bands (390 nm, 450 nm, 500 nm), and analyzed using a biexponential decay model. Selected parameters of this fitting algorithm along with the normalized intensities at each emission band were used as features for a quadratic discriminant analysis (QDA) classifier. The classification performance was estimated using a 10 fold cross-validation approach, resulting on levels of sensitivity and specificity >85%, and an ROC AUC of 0.9 for detecting dysplastic and cancerous oral lesions from benign lesions. These results demonstrate the potential of endogenous FLIM endoscopy for automated early detection of oral cancer.

The aim of this case report is to present a distinct subtype of gingival inflammatory hyperplasia, providing information to avoid diagnostic mistakes and overtreatment. Also, an unexpected progression of the lesion is shown. Furthermore, a review of the literature to discuss the pathogenesis, diagnosis, treatment, and the need for new therapeutic approaches is presented. The authors report four cases of localized juvenile spongiotic gingival hyperplasia involving the anterior maxillary gingiva with distinct clinical features. The patients were followed for a period of 1 to 9 years, and the evolution of the lesions was documented. Surgical excision or therapy by topical steroids was used to treat the lesions. The long-term follow-up provides important information for clinicians not to eliminate older patients for lesion diagnosis. Although surgical excision should not be recommended for all cases, considering the risk of esthetic problems, the treatment modality using topical steroids was not permanently effective in the authors’ cases. Investigations about new esthetic treatment modalities for lesions are needed.

Increased metabolic activity, a hallmark of epithelial cell malignant transformation, induces subtle changes in the oral tissue autofluorescence. The optical “redox-ratio”, defined as the autofluorescence intensity of NADH divided by that of FAD, is sensitive to changes in the cellular metabolic rate. A decrease in the redox-ratio indicates increased cellular metabolic activity, as is typically observed in malignant cells. Specific changes in the fluorescence lifetime of both NADH and FAD have also been associated with increased metabolic activity in malignant oral epithelial cells. We therefore hypothesized that more specific biomarkers of oral cancer and dysplasia can more accurately be quantified by endogenous fluorescence lifetime imaging (FLIM). In this work, FLIM images of benign, dysplastic and early stage cancerous oral lesions from 52 patients were acquired at three emission channels (390±20nm, 452±22.5nm and >500nm) using a handheld multispectral FLIM endoscope. For each pixel, the fluorescence decays collected at the three emission bands were analyzed using a biexponential decay model, resulting on 16 FLIM-derived parameters per pixel. Statistical analysis was performed on each of the computed FLIM parameters (Wilcoxon test: Normal vs. Benign, Normal vs. Dysplasia/Cancer; Mann-Whitney test: Benign vs. Dysplasia/Cancer). Results from this analysis revealed that FLIM-derived parameters associated with collagen lifetime, NADH lifetime, FAD autofluorescence, and the optical redox ratio were statistical different between dysplastic/cancerous vs. benign oral lesions. This study provides the first demonstration for the clinical imaging of autofluorescence biochemical and metabolic biomarkers of oral epithelial cancer and dysplasia, which could potentially enable early detection of oral cancer.

IntroductionThe aim of this case report is to present a distinct subtype of gingival inflammatory hyperplasia, providing information to avoid diagnostic mistakes and overtreatment. Also, an unexpected progression of the lesion is shown. Furthermore, a review of the literature to discuss the pathogenesis, diagnosis, treatment, and the need for new therapeutic approaches is presented.Case SeriesThe authors report four cases of localized juvenile spongiotic gingival hyperplasia involving the anterior maxillary gingiva with distinct clinical features. The patients were followed for a period of 1 to 9 years, and the evolution of the lesions was documented. Surgical excision or therapy by topical steroids was used to treat the lesions.ConclusionsThe long‐term follow‐up provides important information for clinicians not to eliminate older patients for lesion diagnosis. Although surgical excision should not be recommended for all cases, considering the risk of esthetic problems, the treatment modality using topical steroids was not permanently effective in the authors’ cases. Investigations about new esthetic treatment modalities for lesions are needed.

The 4th edition of the World Health Organization’s Classification of Head and Neck Tumours was published in January of 2017. This article provides a summary of the changes to Chapter 4 Tumours of the oral cavity and mobile tongue and Chapter 8 Odontogenic and maxillofacial bone tumours. Odontogenic cysts which were eliminated from the 3rd 2005 edition were included in the 4th edition as well as other unique allied conditons of the jaws. Many new tumors published since 2005 have been included in the 2017 classification.

OBJECTIVES:Several imaging techniques have been advocated as clinical adjuncts to improve identification of suspicious oral lesions. However, these have not yet shown superior sensitivity or specificity over conventional oral examination techniques. We developed a multimodal, multi-scale optical imaging system that combines macroscopic biochemical imaging of fluorescence lifetime imaging with subcellular morphologic imaging of reflectance confocal microscopy for early detection of oral cancer. We tested our system on excised human oral tissues.STUDY DESIGN:In total, 4 tissue specimens were imaged. These specimens were diagnosed as either clinically normal, oral lichen planus, gingival hyperplasia, or superficially invasive squamous cell carcinoma. The optical and fluorescence lifetime properties of each specimen were recorded.RESULTS:Both quantitative and qualitative differences among normal, benign, and squamous cell carcinoma lesions can be resolved with fluorescence lifetime imaging reflectance confocal microscopy. The results demonstrate that an integrated approach based on these two methods can potentially enable rapid screening and evaluation of large areas of oral epithelial tissue.CONCLUSIONS:Early results from ongoing studies of imaging human oral cavity illustrate the synergistic combination of the 2 modalities. An adjunct device based on such optical characterization of oral mucosa can potentially be used to detect oral carcinogenesis in early stages.

Successful early detection and demarcation of oral carcinoma can greatly impact the associated morbidity and mortality rates. Current methods for detection of oral cancer include comprehensive visual examination of the oral cavity, typically followed by tissue biopsy. A noninvasive means to guide the clinician in making a more objective and informed decision toward tissue biopsy can potentially improve the diagnostic yield of this process. To this end, we investigate the potential of fluorescence lifetime imaging (FLIM) for objective detection of oral carcinoma in the hamster cheek pouch model of oral carcinogenesis in vivo. We report that systematically selected FLIM features can differentiate between low-risk (normal, benign and low-grade dysplasia) and high-risk (high-grade dysplasia and cancer) oral lesions with sensitivity and specificity of 87.26% and 93.96%, respectively. We also show the ability of FLIM to generate disease maps of the tissue which can be used to evaluate relative risk of neoplasia. The results demonstrate the potential of multispectral FLIM with objective image analysis as a noninvasive tool to guide comprehensive oral examination.

Melanotic neuroectodermal tumors of infancy (MNTI) are rapidly growing pigmented tumors that occur predominantly within bony head and neck structures. There are fewer than 400 cases reported in the literature with the majority affecting the maxilla. Locations in other intraosseous and extraosseous structures have been characterized, including the mandible (6% of MNTIs). Infants in the first year of life are primarily affected. Surgical resection is the primary treatment modality with and without adjuvant chemotherapy for malignant tumors, which comprise less than 25 cases in the literature, and of metatstatic mandibular tumors, which has only been documented in one other case. The purpose of this investigation is to review associated literature and present a case highlighting treatment considerations of a metastatic mandibular MNTI. We present the case of a six month old boy with a rapidly growing bluish mass of the right mandible. Preoperatively incisional biopsy led to a diagnosis of MNTI and subsequent surgical planning involved hemimandibulectomy from the right mandibular condyle to the left posterior body region with one centimeter margins. At the time of initial surgery, enlarged lymph nodes removed from the neck demonstrated abnormality consistent with metastatic spread of the tumor. Islands of tumor cells were noted: small, round, bluestaining cells resembling neuroblasts with mitotic activity as well as pigmented cells containing melanin. Because of regional node metastasis, chemotherapy was completed following surgery. The patient recovered and was followed without evidence of recurrence. At 3.5 years postresection, a secondary reconstruction was completed using a fibula osteocutaneous free flap combined with a costochondral rib graft. In reviewing similar cases of malignant MNTI reported in the literature, a search of the MEDLINE database until 2014 was performed. These were evaluated based on management type and outcome, including surgical and chemotherapeutic treatments and the incidence of recurrence or metastasis.

Hyperparathyroidism-jaw tumor (HPT-JT) was first observed by Jackson in 1958 in a family who exhibited hyperparathyroidism and recurrent pancreatitis. The author noticed the presence of jaw tumors in the affected family and reported them as fibrous dysplasia. However, it was not until 1990 that a familial variety of hyperparathyroidism with fibro-osseous jaw tumors was recognized as HPT-JT syndrome and reported as a clinically and genetically distinct syndrome. Hyperparathyroidism generally arises from glandular hyperplasia or parathyroid adenomas, with only about 1% of cases resulting from parathyroid carcinoma. However, parathyroid carcinoma develops in about 15% of HPT-JT patients. The true incidence of HPT-JT is unknown, although the prevalence of about 100 published cases suggests its rarity. Twenty percent of HPT-JT cases have renal hamartomas or tumors, and female patients with HPT-JT have been reported to have carcinoma of the uterus. This syndrome appears to arise from a variety of mutations that deactivate the tumor suppressor gene CDC73 (also known as HRPT2) and its production of the tumor suppressor protein parafibromin. Functional parafibromin has 531 amino acids, and mutations result in a short nonfunctional protein. CDC73 disorders exhibit dominant germline gene behavior, with varying degrees of penetration. In most cases an affected person has 1 parent with the condition, which raises the need for family investigation and genetic counseling. We report a case of HPT-JT syndrome in a male patient who presented to the local community hospital 6 years previously with a history of back pain. Investigations showed elevated serum parathyroid hormone and calcium levels, and a technetium 99m sestamibi parathyroid scan showed increased activity at the site of the lower left gland that proved to be a substernal parathyroid carcinoma. The patient's parathyroid hormone level dropped from 126 to 97 pg/mL at 5 minutes andwas 65 pg/mL at 10 minutes after excision of the gland, and the calcium chemistry findings returned to normal. Parathyroid histologic analysis showed substantial cytologic atypia with nuclear pleomorphism and prominent nucleoli, but infrequent mitoses. Although the capsule was described as showing foci of vascular invasion by the carcinoma, there has been no evidence of recurrence. Six years later, the patient presented with bilateral mandibular cemento-ossifying fibromas, but no evidence of hyperparathyroidism. The larger left tumor was excised and immediately reconstructed with an autogenous iliac crest bone graft, and the right lesion was enucleated. There has been no recurrence in 12 months. This case illustrates that the hyperparathyroidism and the fibro-osseous tumors are independent features of the persistent germline tumor suppressor gene (CDC73) mutation. The syndromic fibro-osseous tumors are odontogenic cemento-ossifying fibromas, which only occur in the jaws. (C) 2015 American Association of Oral and Maxillofacial Surgeons

Two cases of a rare variant of adenomatoid odontogenic tumor encompassed by a prominent reactive cemento-osseous proliferation are reported. This unique variant of adenomatoid odontogenic tumor has only been seen twice in the authors' collective experience. Literature documenting the histopathologic patterns of adenomatoid odontogenic tumor and the occurrence of other combined lesions other is reviewed and discussed.

This paper presents the use and characterization of an electrically focus tunable lens to perform axial scanning in a confocal microscope. Lateral and axial resolution are characterized over a >250 µm axial scan range. Confocal microscopy using optical axial scanning is demonstrated in epithelial tissue and compared to traditional stage scanning. By enabling rapid axial scanning, minimizing motion artifacts, and reducing mechanical complexity, this technique has potential to enhance in vivo three-dimensional imaging in confocal endomicroscopy.

We present the use of a commercially available electrically tunable lens to achieve axial scanning in a reflectance confocal microscope. Over a 255 μm axial scan range, the lateral and axial resolutions varied from 1-2 μm and 4-14 μm, respectively, dependent on the variable focal length of the tunable lens. Confocal imaging was performed on normal human biopsies from the oral cavity ex vivo. Sub-cellular morphologic features were seen throughout the depth of the epithelium while axially scanning using the focus tunable lens.

Clinical PresentationA 61-year-old woman presented to the general dentist for routine dental treatment. Her medical history included 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 extracted without periapical or pericoronal pathology at age 19 years. Clinical examination revealed a normocephalic atraumatic head with a normal range of mandibular movement, stable occlusion, and supple cervical region without lymphadenopathy. The intraoral examination revealed no evidence of any soft tissue pathology. The patient was asymptomatic, and the dentition was within normal limits. Panoramic radiographic examination revealed a large well circumscribed radiolucency distal to the second molar, within the ramus of the left mandible (Figure 1) . The radiographic findings prompted an incisional biopsy. Computerized tomography revealed a less discrete osteolytic lesion centered well within the mandible that had also penetrated the lingual cortical plate (Figure 2) .Fig. 2Computerized tomography reveals 1.5 × 1.5 cm osteolytic lesion within the ramus of the mandible. Lingual cortical plate destruction is apparent.View Large Image Figure ViewerDownload (PPT)Differential DiagnosisDifferential diagnosis of a well circumscribed, noncorticated, radiolucent lesion of the retromolar region of the mandible comprises several classes of pathology, including odontogenic cysts and tumors, nonodontogenic tumors, and other nonneoplastic conditions.A significant number of intrabony jaw lesions have their origin from the tooth-forming tissues, and therefore, 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 mandible ∼75% of the time and exhibit a strong propensity for the posterior mandible and the ascending ramus.1Myoung H. Hong S.P. Hong S.D. Lee J.I. Lim C.Y. Choung P.H. et al.Odontogenic keratocyst: review of 256 cases for recurrence and clinicopathologic parameters.Oral Surg Oral Med Oral Pathol Oral Radiology Endod. 2001; 91: 328-333Abstract Full Text Full Text PDF PubMed Scopus (226) Google Scholar 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.1Myoung H. Hong S.P. Hong S.D. Lee J.I. Lim C.Y. Choung P.H. et al.Odontogenic keratocyst: review of 256 cases for recurrence and clinicopathologic parameters.Oral Surg Oral Med Oral Pathol Oral Radiology Endod. 2001; 91: 328-333Abstract Full Text Full Text PDF PubMed Scopus (226) Google Scholar Additionally, a significant number of OKCs (38%) tend to be associated with an unerupted tooth or earlier extraction site.1Myoung H. Hong S.P. Hong S.D. Lee J.I. Lim C.Y. Choung P.H. et al.Odontogenic keratocyst: review of 256 cases for recurrence and clinicopathologic parameters.Oral Surg Oral Med Oral Pathol Oral Radiology Endod. 2001; 91: 328-333Abstract Full Text Full Text PDF PubMed Scopus (226) Google Scholar 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 circumscribed 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 malignancy. Many of the odontogenic tumors would be improbable 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 appearance spanning from the premolar region to the molars that is typical of a myxoma.2Li T.J. Sun L.S. Luo H.Y. Odontogenic myxoma: a clinicopathologic study of 25 cases.Arch Pathol Laboratory Med. 2006; 130: 1799-1806PubMed Google Scholar Yet, 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, ameloblastoma is the most common odontogenic tumor in general, and ∼80% are found in the mandible, with the molar-ramus area affected between 39% and 66% of the time.3Odontogenic cysts and tumors.in: Neville B.W. Damm D.D. Allen C.M. Bouquot J.E. Oral and maxillofacial pathology. 3rd ed. Saunders and Elsevier, St Louis2009: 695-698Google Scholar, 4Reichart P.A. Philipsen H.P. Sonner S. Ameloblastoma: biological profile of 3,677 cases.Eur J Cancer B Oral Oncol. 1995; 31B: 86-99Abstract Full Text PDF PubMed Scopus (500) Google Scholar The average age of diagnosis for ameloblastoma is middle to late 30s. Although our patient was significantly older, just over 10% of cases do affect patients in their seventh decade.3Odontogenic cysts and tumors.in: Neville B.W. Damm D.D. Allen C.M. Bouquot J.E. Oral and maxillofacial pathology. 3rd ed. Saunders and Elsevier, St Louis2009: 695-698Google Scholar, 4Reichart P.A. Philipsen H.P. Sonner S. Ameloblastoma: biological profile of 3,677 cases.Eur J Cancer B Oral Oncol. 1995; 31B: 86-99Abstract Full Text PDF PubMed Scopus (500) Google ScholarNotably, the lesion did not appear to be associated with a tooth, and accordingly, nonodontogenic pathology must be entertained in the differential diagnosis. Nonodontogenic mesenchymal neoplasms may include neurofibroma, desmoplastic fibroma of bone, and vascular lesions. Even though neurofibromas are most commonly found on the buccal mucosa or the dorsum of the tongue, these lesions may arise within the bone as well.5Chi A.C. Carey J. Muller S. Intraosseous schwannoma of the mandible: a case report and review of the literature.Oral Surg Oral Med Oral Pathol Oral Radiology Endod. 2003; 96: 54-65Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar 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.6Said-Al-Naief N. Fernandes R. Louis P. Bell W. Siegal G.P. Desmoplastic fibroma of the jaw: a case report and review of literature.Oral Surg Oral Med Oral Pathol Oral Radiology Endod. 2006; 101: 82-94Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar However, desmoplastic fibroma was not likely, because 84% occur in people <30 years old.6Said-Al-Naief N. Fernandes R. Louis P. Bell W. Siegal G.P. Desmoplastic fibroma of the jaw: a case report and review of literature.Oral Surg Oral Med Oral Pathol Oral Radiology Endod. 2006; 101: 82-94Abstract Full Text Full Text PDF PubMed Scopus (70) Google ScholarFinally, 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 reported 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.7August M. Faquin W. Troulis M. Kaban L. Clear cell odontogenic carcinoma: evaluation of reported cases.J Oral Maxillofac Surg. 2003; 61: 580-586Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar Primary mucoepidermoid carcinoma (MEC) was also possible; despite its rarity, its favored site is the posterior mandible.8Brookstone M.S. Huvos A.G. Central salivary gland tumors of the maxilla and mandible: a clinicopathologic study of 11 cases with an analysis of the literature.J Oral Maxillofac Surg. 1992; 50: 229-236Abstract Full Text PDF PubMed Scopus (138) Google ScholarDiagnosisA 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 polyhedral 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 mucicarmine special stain demonstrated intracytoplasmic staining of the mucus cells (Figure 5) . A positron-emission tomography (PET) scan showed no indication of metastatic disease throughout the body, nor suggestion of another primary neoplasm. A diagnosis of intraosseous MEC was made.Fig. 3Photomicrograph showing small infiltrating cords and islands of neoplastic epithelium with micro- and macrocystic areas. Hematoxylin and eosin stain. Original magnification ×13.View Large Image Figure ViewerDownload (PPT)Fig. 4Photomicrograph showing epidermoid cells mixed with larger more lightly staining mucus cells. Hematoxylin and eosin stain. Original magnification ×33.View Large Image Figure ViewerDownload (PPT)Fig. 5Mucicarmine stain demonstrating mucus cells with bright red intracytoplasmic mucin. Original magnification × 33.View Large Image Figure ViewerDownload (PPT)ManagementFollowing confirmation from PET of no independent primary site, definitive surgical treatment commenced. The lesion was resected with 1-cm margins; the coronoid 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 during 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 reconstruction 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 ascending 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 integrated into the recipient site, occlusion was stable, and the patient again could exercise the muscles of mastication to open 37 mm.DiscussionPrimary intraosseous adenocarcinoma is rare is and mainly confined to the jaws, particularly the mandible. The most frequent histopathologic type is MEC.8Brookstone M.S. Huvos A.G. Central salivary gland tumors of the maxilla and mandible: a clinicopathologic study of 11 cases with an analysis of the literature.J Oral Maxillofac Surg. 1992; 50: 229-236Abstract Full Text PDF PubMed Scopus (138) Google Scholar Most often, central salivary malignancies are reported in either the body or ramus of the mandible.8Brookstone M.S. Huvos A.G. Central salivary gland tumors of the maxilla and mandible: a clinicopathologic study of 11 cases with an analysis of the literature.J Oral Maxillofac Surg. 1992; 50: 229-236Abstract Full Text PDF PubMed Scopus (138) Google Scholar, 9Li Y. Li L.J. Huang J. Han B. Pan J. Central malignant salivary gland tumors of the jaw: retrospective clinical analysis of 22 cases.J Oral Maxillofac Surg. 2008; 66: 2247-2253Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar The 3 most common subtypes of intraosseous adenocarcinoma are MEC, adenoid cystic carcinoma, and adenocarcinoma not otherwise specified, with MEC being the most prevalent.8Brookstone M.S. Huvos A.G. Central salivary gland tumors of the maxilla and mandible: a clinicopathologic study of 11 cases with an analysis of the literature.J Oral Maxillofac Surg. 1992; 50: 229-236Abstract Full Text PDF PubMed Scopus (138) Google Scholar, 9Li Y. Li L.J. Huang J. Han B. Pan J. Central malignant salivary gland tumors of the jaw: retrospective clinical analysis of 22 cases.J Oral Maxillofac Surg. 2008; 66: 2247-2253Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar Fewer than 200 cases of central salivary gland tumors have been reported in the literature, the majority of which (n = 135) have been primary intraosseous MEC.9Li Y. Li L.J. Huang J. Han B. Pan J. Central malignant salivary gland tumors of the jaw: retrospective clinical analysis of 22 cases.J Oral Maxillofac Surg. 2008; 66: 2247-2253Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar The 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 salivary 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 odontogenic cysts.8Brookstone M.S. Huvos A.G. Central salivary gland tumors of the maxilla and mandible: a clinicopathologic study of 11 cases with an analysis of the literature.J Oral Maxillofac Surg. 1992; 50: 229-236Abstract Full Text PDF PubMed Scopus (138) Google Scholar, 9Li Y. Li L.J. Huang J. Han B. Pan J. Central malignant salivary gland tumors of the jaw: retrospective clinical analysis of 22 cases.J Oral Maxillofac Surg. 2008; 66: 2247-2253Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar, 10Eversole L.R. Malignant epithelial odontogenic tumors.Semin Diagn Pathol. 1999; 16: 317-324PubMed Google Scholar Lack of details surrounding this particular 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 supported by the fact that between 32% and 48% of cases have been associated with an impacted tooth or an odontogenic cyst,8Brookstone M.S. Huvos A.G. Central salivary gland tumors of the maxilla and mandible: a clinicopathologic study of 11 cases with an analysis of the literature.J Oral Maxillofac Surg. 1992; 50: 229-236Abstract Full Text PDF PubMed Scopus (138) Google Scholar, 11Eversole L.R. Sabes W.R. Rovin S. Aggressive growth and neoplastic potential of odontogenic cysts: with special reference to central epidermoid and mucoepidermoid carcinomas.Cancer. 1975; 35: 270-282Crossref PubMed Scopus (205) Google Scholar although a recent report showed no correlation.9Li Y. Li L.J. Huang J. Han B. Pan J. Central malignant salivary gland tumors of the jaw: retrospective clinical analysis of 22 cases.J Oral Maxillofac Surg. 2008; 66: 2247-2253Abstract Full Text Full Text PDF PubMed Scopus (43) Google ScholarGenetic analysis has demonstrated a subset of soft tissue and intraosseous MEC with the chromosomal translocation t(11;19), resulting in the fusion transcript CRTC1/MAML2.12Tirado Y. Williams M.D. Hanna E.Y. Kaye F.J. Batsakis J.G. El-Naggar A.K. CRTC1/MAML2 fusion transcript in high grade mucoepidermoid carcinomas of salivary and thyroid glands and Warthin's tumors: implications for histogenesis and biological behavior.Genes Chromosomes Cancer. 2007; 46: 708-715Crossref PubMed Scopus (152) Google Scholar, 13Bell D. Holsinger C.F. El-Naggar A.K. CRTC1/MAML2 fusion transcript in central mucoepidermoid carcinoma of mandible-diagnostic and histogenetic implications.Ann Diagn Pathol. 2010; 14: 396-401Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Preliminary evidence suggests that this mutation imparts an increased likelihood of metastasis.12Tirado Y. Williams M.D. Hanna E.Y. Kaye F.J. Batsakis J.G. El-Naggar A.K. CRTC1/MAML2 fusion transcript in high grade mucoepidermoid carcinomas of salivary and thyroid glands and Warthin's tumors: implications for histogenesis and biological behavior.Genes Chromosomes Cancer. 2007; 46: 708-715Crossref PubMed Scopus (152) Google Scholar Additionally, the TORC1/MAML2 gene fusion has been reported in central MECs.14Kahn H.A. Loya A. Azhar R. Din N.U. Bell D. Central mucoepidermoid carcinoma, a case report with molecular analysis of the TORC1/MAML2 gene fusion.Head and Neck Pathol. 2010; 4: 261-264Crossref PubMed Scopus (18) Google ScholarCentral 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.8Brookstone M.S. Huvos A.G. Central salivary gland tumors of the maxilla and mandible: a clinicopathologic study of 11 cases with an analysis of the literature.J Oral Maxillofac Surg. 1992; 50: 229-236Abstract Full Text PDF PubMed Scopus (138) Google Scholar, 9Li Y. Li L.J. Huang J. Han B. Pan J. Central malignant salivary gland tumors of the jaw: retrospective clinical analysis of 22 cases.J Oral Maxillofac Surg. 2008; 66: 2247-2253Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar, 11Eversole L.R. Sabes W.R. Rovin S. Aggressive growth and neoplastic potential of odontogenic cysts: with special reference to central epidermoid and mucoepidermoid carcinomas.Cancer. 1975; 35: 270-282Crossref PubMed Scopus (205) Google Scholar The mandible is affected about 3 times more frequently than the maxilla with a predilection for the posterior mandible.8Brookstone M.S. Huvos A.G. Central salivary gland tumors of the maxilla and mandible: a clinicopathologic study of 11 cases with an analysis of the literature.J Oral Maxillofac Surg. 1992; 50: 229-236Abstract Full Text PDF PubMed Scopus (138) Google Scholar Rarely are the anterior jaws affected. Many patients are asymptomatic, but as the neoplasm expands, pain and swelling are encountered.Radiographically, central MEC presents as a unilocular 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.15Raut D.L. Khedkar S.A. Primary intraosseous mucoepidermoid carcinoma of the maxilla: a case report and review of literature.Dentomaxillofac Radiol. 2009; 38: 163-168Crossref PubMed Scopus (19) Google ScholarRetrospective case studies of intraosseous MEC have led some investigators to develop criteria for diagnosis, which include presence of an intact cortical plate.8Brookstone M.S. Huvos A.G. Central salivary gland tumors of the maxilla and mandible: a clinicopathologic study of 11 cases with an analysis of the literature.J Oral Maxillofac Surg. 1992; 50: 229-236Abstract Full Text PDF PubMed Scopus (138) Google Scholar, 15Raut D.L. Khedkar S.A. Primary intraosseous mucoepidermoid carcinoma of the maxilla: a case report and review of literature.Dentomaxillofac Radiol. 2009; 38: 163-168Crossref PubMed Scopus (19) Google Scholar However, any central malignancy may perforate the cortex if untreated, which means that cortical perforation should not preclude a diagnosis of intraosseous MEC. Brookstone and Huvos8Brookstone M.S. Huvos A.G. Central salivary gland tumors of the maxilla and mandible: a clinicopathologic study of 11 cases with an analysis of the literature.J Oral Maxillofac Surg. 1992; 50: 229-236Abstract Full Text PDF PubMed Scopus (138) Google Scholar proposed a clinical 3-stage system for classifying intraosseous MEC, in which the third stage includes cortical perforation and destruction of the 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.8Brookstone M.S. Huvos A.G. Central salivary gland tumors of the maxilla and mandible: a clinicopathologic study of 11 cases with an analysis of the literature.J Oral Maxillofac Surg. 1992; 50: 229-236Abstract Full Text PDF PubMed Scopus (138) Google Scholar 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.8Brookstone M.S. Huvos A.G. Central salivary gland tumors of the maxilla and mandible: a clinicopathologic study of 11 cases with an analysis of the literature.J Oral Maxillofac Surg. 1992; 50: 229-236Abstract Full Text PDF PubMed Scopus (138) Google Scholar, 9Li Y. Li L.J. Huang J. Han B. Pan J. Central malignant salivary gland tumors of the jaw: retrospective clinical analysis of 22 cases.J Oral Maxillofac Surg. 2008; 66: 2247-2253Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar Retrospective analyses of intraosseous MEC suggest that en bloc resection is the best approach to prevent recurrence.9Li Y. Li L.J. Huang J. Han B. Pan J. Central malignant salivary gland tumors of the jaw: retrospective clinical analysis of 22 cases.J Oral Maxillofac Surg. 2008; 66: 2247-2253Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar More conservative treatment might include enucleation, curettage, or marsupialization, which may be supplemented with adjuvant therapy, such as radiotherapy, but risks for recurrence and osteoradionecrosis clearly exist with little added value.9Li Y. Li L.J. Huang J. Han B. Pan J. Central malignant salivary gland tumors of the jaw: retrospective clinical analysis of 22 cases.J Oral Maxillofac Surg. 2008; 66: 2247-2253Abstract Full Text Full Text PDF PubMed Scopus (43) Google ScholarA systematic review of intraosseous salivary gland tumors showed that conservative treatment resulted in recurrence in 40% of cases, whereas aggressive surgical treatment yielded 4% recurrence.8Brookstone M.S. Huvos A.G. Central salivary gland tumors of the maxilla and mandible: a clinicopathologic study of 11 cases with an analysis of the literature.J Oral Maxillofac Surg. 1992; 50: 229-236Abstract Full Text PDF PubMed Scopus (138) Google Scholar Survival of patients 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% survival rates.11Eversole L.R. Sabes W.R. Rovin S. Aggressive growth and neoplastic potential of odontogenic cysts: with special reference to central epidermoid and mucoepidermoid carcinomas.Cancer. 1975; 35: 270-282Crossref PubMed Scopus (205) Google Scholar A retrospective chart review indicated high survival with 1 death in a group of 20.9Li Y. Li L.J. Huang J. Han B. Pan J. Central malignant salivary gland tumors of the jaw: retrospective clinical analysis of 22 cases.J Oral Maxillofac Surg. 2008; 66: 2247-2253Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar Reports on metastasis vary greatly, with as little as 9% in a group of 6611Eversole L.R. Sabes W.R. Rovin S. Aggressive growth and neoplastic potential of odontogenic cysts: with special reference to central epidermoid and mucoepidermoid carcinomas.Cancer. 1975; 35: 270-282Crossref PubMed Scopus (205) Google Scholar; however, another assessment of cases indicated that although none of the maxillary tumors metastasized, 39% of the mandibular cases were found to have metastatic cervical involvement before treatment.9Li Y. Li L.J. Huang J. Han B. Pan J. Central malignant salivary gland tumors of the jaw: retrospective clinical analysis of 22 cases.J Oral Maxillofac Surg. 2008; 66: 2247-2253Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar Cytogenetic analysis of soft tissue lesions demonstrated statistically significant correlation with CRTC1/MAML2 fusion and metastasis,12Tirado Y. Williams M.D. Hanna E.Y. Kaye F.J. Batsakis J.G. El-Naggar A.K. CRTC1/MAML2 fusion transcript in high grade mucoepidermoid carcinomas of salivary and thyroid glands and Warthin's tumors: implications for histogenesis and biological behavior.Genes Chromosomes Cancer. 2007; 46: 708-715Crossref PubMed Scopus (152) Google Scholar but the same has yet to be observed for the intraosseous type. In our case, the patient presented without metastasis and without recurrence at 12 months after treatment.In summary, the present case was of an intraosseous MEC, which presented as an asymptomatic, well circumscribed, noncorticated radiolucency of the retromolar 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. Clinical PresentationA 61-year-old woman presented to the general dentist for routine dental treatment. Her medical history included 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 extracted without periapical or pericoronal pathology at age 19 years. Clinical examination revealed a normocephalic atraumatic head with a normal range of mandibular movement, stable occlusion, and supple cervical region without lymphadenopathy. The intraoral examination revealed no evidence of any soft tissue pathology. The patient was asymptomatic, and the dentition was within normal limits. Panoramic radiographic examination revealed a large well circumscribed radiolucency distal to the second molar, within the ramus of the left mandible (Figure 1) . The radiographic findings prompted an incisional biopsy. Computerized tomography revealed a less discrete osteolytic lesion centered well within the mandible that had also penetrated the lingual cortical plate (Figure 2) . A 61-year-old woman presented to the general dentist for routine dental treatment. Her medical history included 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 extracted without periapical or pericoronal pathology at age 19 years. Clinical examination revealed a normocephalic atraumatic head with a normal range of mandibular movement, stable occlusion, and supple cervical region without lymphadenopathy. The intraoral examination revealed no evidence of any soft tissue pathology. The patient was asymptomatic, and the dentition was within normal limits. Panoramic radiographic examination revealed a large well circumscribed radiolucency distal to the second molar, within the ramus of the left mandible (Figure 1) . The radiographic findings prompted an incisional biopsy. Computerized tomography revealed a less discrete osteolytic lesion centered well within the mandible that had also penetrated the lingual cortical plate (Figure 2) . Differential DiagnosisDifferential diagnosis of a well circumscribed, noncorticated, radiolucent lesion of the retromolar region of the mandible comprises several classes of pathology, including odontogenic cysts and tumors, nonodontogenic tumors, and other nonneoplastic conditions.A significant number of intrabony jaw lesions have their origin from the tooth-forming tissues, and therefore, 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 mandible ∼75% of the time and exhibit a strong propensity for the posterior mandible and the ascending ramus.1Myoung H. Hong S.P. Hong S.D. Lee J.I. Lim C.Y. Choung P.H. et al.Odontogenic keratocyst: review of 256 cases for recurrence and clinicopathologic parameters.Oral Surg Oral Med Oral Pathol Oral Radiology Endod. 2001; 91: 328-333Abstract Full Text Full Text PDF PubMed Scopus (226) Google Scholar 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.1Myoung H. Hong S.P. Hong S.D. Lee J.I. Lim C.Y. Choung P.H. et al.Odontogenic keratocyst: review of 256 cases for recurrence and clinicopathologic parameters.Oral Surg Oral Med Oral Pathol Oral Radiology Endod. 2001; 91: 328-333Abstract Full Text Full Text PDF PubMed Scopus (226) Google Scholar Additionally, a significant number of OKCs (38%) tend to be associated with an unerupted tooth or earlier extraction site.1Myoung H. Hong S.P. Hong S.D. Lee J.I. Lim C.Y. Choung P.H. et al.Odontogenic keratocyst: review of 256 cases for recurrence and clinicopathologic parameters.Oral Surg Oral Med Oral Pathol Oral Radiology Endod. 2001; 91: 328-333Abstract Full Text Full Text PDF PubMed Scopus (226) Google Scholar Finally, from the odontogenic cyst category, neither a residual dentigerous cyst nor residual apical per

PURPOSE:Parents increasingly request esthetic restorations for their children's teeth. This split mouth, randomized controlled trial compared primary molars treated with white MTA pulpotomies and restored with either multi-surface composites (MSC) or stainless steel crowns (SSC).METHODS:Forty matched, contra-lateral pairs of molars received MTA pulpotomies and were randomly assigned to MSC or SSC restorations and evaluated clinically and radiographically at 6 and 12 months. Two calibrated, blinded examiners evaluated and scored radiographs.RESULTS:Thirty-seven matched pairs were evaluated at 6 months, and 31 were available at 12 months. All teeth in both groups were radiographically and clinically successful at 6 and 12 months. Dentin bridge formation was noted in 20% of the primary molars by 12 months. Although not significant, the composite group exhibited fewer intact clinical margins than the SSC group. The vast majority (94%) of teeth restored with composite displayed gray discoloration at follow-up exams, which did not appear to affect the quality of the restoration and is believed to be associated with the white MTA.CONCLUSIONS:The white MTA pulpotomies succeeded over 12 months regardless of the restoration; however, the teeth restored with composite were not as durable nor considered an esthetic alternative to the SSC.