A clinicopathological study of malignant odontogenic tumours.

AIMS: Malignant odontogenic tumours (MOTs) are rare neoplasms occurring primarily within the jaw. The objective of this study was to determine the incidence, demographics and clinicopathological features of the MOTs from two institutions. METHODS AND RESULTS: The records of the Department of Oral Pathology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand and the Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, USA were searched from 1991 to 2010; we identified 17 cases of previously diagnosed MOTs. All cases were reviewed independently of the previous diagnosis by two blinded oral pathologists and reclassified based on the 2005 World Health Organization classification of head and neck tumours. In this study we describe in detail these 17 cases which presented with an average age of 50.29 years and a male to female ratio of 2.4:1. These cases included five ameloblastic carcinomas, four atypical ameloblastomas, three primary intraosseous squamous cell carcinomas, three intraosseous mucoepidermoid carcinomas and two clear cell odontogenic carcinomas. All cases were treated by surgical resection and one patient with ameloblastic carcinoma received postoperative radiotherapy. CONCLUSIONS: Malignant odontogenic tumours are considered rare central odontogenic lesions. Awareness of their existence, rapid diagnosis and successful treatment using surgery, radiation and/or chemotherapy is critical to patient survival.

Zoledronic acid directly suppresses cell proliferation and induces apoptosis in highly tumorigenic prostate and breast cancers.

BACKGROUND: Bisphosphonates (BPs) were designed for the prevention of skeletal-related events secondary to bone metastases. The purpose of this study was to show that zoledronic acid (ZA) directly eradicates highly tumorigenic and potentially metastatic cancer cells. MATERIALS AND METHODS: Human prostate and breast highly tumorigenic (PC3, MCF 7) and low- or non-tumorigenic (LNCaP, MCF 10a) cell lines, respectively, were exposed to different concentrations of ZA (0-10 µM). Reverse transcriptase double quantitative polymerase chain reaction was used for quantitative gene expression analysis. Apoptosis and cell proliferation were determined using microscopic observation and MTS assays. Western blot was used to confirm the translational effects of apoptotic genes on protein expression. RESULTS: Human prostate and breast highly tumorigenic (PC3, MCF 7) and low- or non-tumorigenic (LNCaP, MCF 10a) cell lines, respectively, showed multiple genes demonstrating differential expressions, including TRAF, TRADD, BCL2, CASPASES and IAP families. Increasing ZA concentrations showed a greater concentration-time response on cell proliferation and apoptosis in the highly tumorigenic cells. These results were confirmed by both reversing and enhancing the effect of ZA on cell proliferation with caspase 3, 7 or survivin siRNA, respectively. Pro-apoptotic proteins bax and caspase 2, 3, 7 and 9 were up-regulated, while the anti-apoptotic proteins bcl2, birc3 and survivin were down-regulated only in the highly tumorigenic cells. CONCLUSIONS: This explains the ability of ZA to inhibit bony metastasis in highly tumorigenic cells compared with the low- or non-tumorigenic cells through a significant decrease in cell proliferation and increase in apoptosis through gene-regulated and translational-mediated down-regulation of survivin coupled with the inhibition of caspase 3 or 7. This has significant implications toward understanding the pharmacophysiology of BPs in metastasis and supports the clinically observed effect of BPs when administered adjunctively with anticancer drugs such as cyclophosphamide/methotrexate/5-fluorouracil, epirubicin in combination with cyclophosphamide or docetaxel, and doxorubicin.

Protection of the oral mucosa by salivary histatin-5 against Candida albicans in an ex vivo murine model of oral infection.

The oral cavity is a primary target for opportunistic infections, particularly oral candidiasis caused by Candida albicans. A commensal fungus commonly colonizing mucosal surfaces, under conditions of immune dysfunction, C. albicans can become a pathogen causing recurrent infections. Yet, the role of host oral innate immunity in the development of candidiasis is not fully elucidated. Specifically, the host salivary antimicrobial peptide histatin-5 (Hst-5) has been proposed to play a protective role in the oral cavity against C. albicans. However, investigations demonstrating its efficacy on oral tissue have been lacking. To this end, in this study, an ex vivo murine model of oral infection was developed. Viable C. albicans counts and histopathological analyses demonstrated a significant protective effect for Hst-5 on mouse oral tissue against C. albicans. More importantly, host saliva exerted a comparable anticandidal effect. However, this effect was neutralized upon treatment of saliva with proteases and C. albicans, previously shown to degrade Hst-5, indicating that Hst-5 is likely the salivary component responsible for the observed protection. Combined, the findings from this study demonstrate for the first time the efficacy of salivary Hst-5 in protecting host oral tissue against C. albicans infection, thereby affirming the therapeutic potential of this natural host peptide.

Oral melanoacanthoma in an adolescent.

The etiopathogenesis of oral pigmentation is diverse. One such process is the oral melanoacanthoma, a reactive, melanocytic lesion, infrequently found in the pediatric subpopulation. To extend the knowledge of this lesion, we provide a case of gingival melanoacanthoma in a 17-year-old male patient. In addition, a comprehensive differential diagnosis for gingival hyperpigmentations in young patients is detailed.

Farnesol-induced apoptosis in Candida albicans.

Farnesol, a precursor in the isoprenoid/sterol pathway, was recently identified as a quorum-sensing molecule produced by the fungal pathogen Candida albicans. Farnesol is involved in the inhibition of germination and biofilm formation by C. albicans and can be cytotoxic at certain concentrations. In addition, we have shown that farnesol can trigger apoptosis in mammalian cells via the classical apoptotic pathways. In order to elucidate the mechanism behind farnesol cytotoxicity in C. albicans, the response to farnesol was investigated, using proteomic analysis. Global protein expression profiles demonstrated significant changes in protein expression resulting from farnesol exposure. Among the downregulated proteins were those involved in metabolism, glycolysis, protein synthesis, and mitochondrial electron transport and the respiratory chain, whereas proteins involved in folding, protection against environmental and oxidative stress, actin cytoskeleton reorganization, and apoptosis were upregulated. Cellular changes that accompany apoptosis (regulated cell death) were further analyzed using fluorescent microscopy and gene expression analysis. The results indicated reactive oxygen species accumulation, mitochondrial degradation, and positive terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) in the farnesol-exposed cells concurrent with increased expression of antioxidant-encoding and drug response genes. More importantly, the results demonstrated farnesol-induced upregulation of the caspase gene MCA1 and the intracellular presence of activated caspases. In conclusion, this study demonstrated that farnesol promotes apoptosis in C. albicans through caspase activation, implying an important physiological role for farnesol in the fungal cell life cycle with important implications for adaptation and survival.

Effect of zoledronic acid on oral fibroblasts and epithelial cells: a potential mechanism of bisphosphonate-associated osteonecrosis.

Osteonecrosis of the jaw secondary to bisphosphonate infusion (zoledronic acid-ZA) is assumed to be a bone disease. This study investigated the effects of ZA on soft tissues using oral mucosal cells as an in vitro model of soft tissue cell death in the pathogenesis of bone necrosis. Human gingival fibroblast and keratinocyte cell lines were exposed to different concentrations of ZA (0.25-3 micromol/l), using 1 micromol/l as the expected baseline concentration. A dose-response effect on apoptosis and cell proliferation [Terminal deoxynucleotidyl transferase-mediated dUTP-Biotin End Labelling and Annexin V or Coulter counter and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium), respectively] was observed with increasing ZA concentrations; both reversed using siRNA against caspase 3 or 9. Gene expression analysis using RT(2) Profiler polymerase chain reaction Arrays demonstrated the differential expression of multiple genes involved in apoptosis including those that encode TNF, BCL-2, Caspase, IAP, TRAF and Death Domain families. Western blot analysis confirmed the presence of activated forms of caspase 3 and 9 and underexpression of survivin protein expression. This study demonstrated that low concentrations of ZA rapidly and directly affected the oral mucosal tissues though the induction of a gene-regulated apoptotic process. These findings support the potential for soft tissue injury as an initiating/potentiating event for osteonecrosis.

A novel bioassay model to determine clinically significant bisphosphonate levels.

PURPOSE: Bisphosphonate-associated osteonecrosis (BON) is a recently recognized oral complication of bisphosphonate (BP) therapy. Currently, research into the pathogenesis of BON has been hampered by being deficient in studies capable of measuring the level of BP in saliva or at the bone-soft tissue interface. The objective of this current study was to develop a novel bioassay model representative of the oral levels of BPs in patients presenting with or at risk for BON. METHODS: Zoledronic acid (ZA) injectable was used to develop standardized MTS cell proliferation assay curves at concentrations of 0-10 microM, which were used either in a dilution in normal media, mimicking BP freed from bone or used to "spike" saliva individuals not taking BPs and mimicking BP levels being excreted. This bioassay was then used to estimate BP levels from samples of saliva and bone ex vivo from patients with and without BON. RESULTS: Saliva and bone from patients with existing BON showed levels of BP ranging from 0.4 to 4.6 microM, while patients receiving IV infusion of BP and naïve to BON showed levels in saliva ranging from 0.4 to 5 microM. All control specimens and patients naïve to BP showed levels at 0 microM. CONCLUSIONS: Given the fact that BPs are poor candidates for detection using standard methods (HPLC), this bioassay provides us with the ability to estimate clinically relevant concentrations of BP capable of producing apoptosis and the inhibition cell proliferation of oral mucosal cells based on previous studies. Subsequently, apoptosis and the inhibition of proliferation could lead to BON, secondary to the exposure of the bone in the unique microenvironment of the oral cavity.

Multifocal melanoacanthoma of the gingiva and hard palate.

BACKGROUND: Gingival melanoacanthoma is an uncommon reactive lesion, typically appearing as a solitary pigmented macule. This article reports a previously undescribed case of multifocal melanoacanthoma affecting the maxillary and mandibular gingiva and the hard palate. A literature review of melanoacanthoma of the gingiva is also provided. METHODS: An otherwise healthy 60-year-old white female sought care for a periodic dental prophylaxis. The intraoral examination was remarkable for numerous painless, brown macular lesions in all four gingival quadrants and on the hard palate (eight on the gingiva and six on the palate). The lesions ranged in size from 2 to 4 mm. The patient had only been aware of one of these lesions, estimating its existence to be <1-year duration. The unusual and widespread presentation of these lesions warranted biopsy. RESULTS: On microscopy, all surgical specimens revealed an acanthotic population of epithelium, with dendritic melanocytes distributed throughout, and numerous melanophages contained in the connective tissue. The dendritic melanocytes were immunoreactive for HMB-45 and S-100. Ultrastructural studies confirmed the presence of keratinocytes and dendritic melanocytes containing melanosomes. A 5.5-month follow-up recall disclosed six new pigmented lesions (four on the gingiva and two on the hard palate), clinically identical to the previously discerned melanoacanthomas. There has been no recurrence of any of the biopsied lesions. CONCLUSIONS: Gingival melanoacanthomas may present as a solitary lesion or involve multiple sites. Pigmented gingival lesions of recent origin and without etiologic factors should undergo histopathologic review. A conservative biopsy for gingival melanoacanthoma may be sufficient for lesion identity and definitive treatment.

Follicular lymphoid hyperplasia of the palate: case report and literature review.

Follicular lymphoid hyperplasia (FLH) of the palate is a very rare benign, proliferative process, with only 20 cases published so far in the English language literature. We describe a case, in a 55-year-old Caucasian female, who developed a swelling in the left posterior hard palate. Bony involvement was absent. Importantly, the medical history was positive for a previous non-Hodgkin lymphoma. Following incisional biopsy, histological examination revealed a vaguely nodular lymphoid proliferation composed of small well-differentiated lymphocytes. The lymphoid follicles were positive for CD20, CD79a, CD10, CD21 and BCL6, while negative for BCL2. The parafollicular areas revealed positivity for CD3, CD5, CD30, and CD15. Both areas were CD45 positive. Subsequent immunoglobulin heavy chain gene rearrangement analysis revealed a polyclonal lesion. No further treatment was instituted, and the patient is currently being followed-up every three months. This report demonstrates that FLHs are especially important due to their clinical and, occasionally, microscopic resemblance to follicular lymphomas. Morphologic and immunohistochemical analyses and molecular studies are essential to achieve accurate diagnosis and to implement appropriate management.

Granulomatous foreign-body reaction involving oral and perioral tissues after injection of biomaterials: a series of 7 cases and review of the literature.

PURPOSE: Injectable implants used for soft-tissue augmentation may lead to a granulomatous foreign-body reaction. The aim of this report is to present 7 new cases of foreign-body granulomas involving the oral and perioral tissues, after injection of biomaterials to achieve soft-tissue augmentation. In addition, the clinical and epidemiological profile of this condition is summarized, based on a review of the English-language literature of all previously described cases. PATIENTS AND METHODS: We report on 7 new cases of granulomatous foreign-body reaction involving the oral and perioral tissues after the injection of biomaterials. A comprehensive literature review is also presented. RESULTS: The literature search revealed 49 cases of this condition affecting the oral and perioral tissues. Our 7 patients were female, with a mean age of 52.8 years (range, 34 to 70 years). The lower lip was affected in 4 cases, 1 case was located in the upper lip, 1 case in the buccal mucosa, while 1 case involved 2 different sites (upper lip and buccal mucosa). Histopathologic examination revealed numerous cells with clear, often multiple, cytoplasmic vacuoles, bearing a resemblance to lipoblasts. Immunohistochemistry revealed diffuse positivity for the histiocytic marker CD68. CONCLUSIONS: The diagnosis of granulomatous foreign-body reactions may be challenging because of their microscopic resemblance to liposarcoma, and because of the occasional reluctance of patients to report the previously performed esthetic procedure. A clinical history, histopathologic examination, and immunohistochemical analysis (as needed) are essential in achieving an accurate diagnosis.

Oral lipoma: report of three cases.

Oral lipomas are benign lesions that are seen infrequently in the dental practice. This article details the clinical and histopathologic findings of three cases of intraoral lipomas. All of the lesions exhibited a yellow color. Two of the tumors were located on the buccal mucosa, while the other mass arose on the mandibular buccal/labial vestibule, was considerably larger in size, produced extraoral swelling, and necessitated a preoperative MRI due to close approximation to the mental nerve. None of the patients elicited any history of attendant symptomatology. Excisional biopsies in each case revealed well-circumscribed masses surrounded by a thin fibrous capsule and composed of sheets of mature adipocytes arranged in a "chicken wire" configuration. The tumor adipocytes were similar to normal adult fat cells and contained a small, uniformly eccentric nucleus with a single, clear cytoplasmic vacuole. Surgical excision is the modality of treatment and malignant transformation or recurrence is rare.

High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma.

BACKGROUND: HMGA2 expression has been shown to be associated with enhanced selective chemosensitivity towards the topoisomerase (topo) II inhibitor, doxorubicin, in cancer cells. Although the roles of signaling cascades and proteins as regulatory factors in development, neoplasia and adaptation to the environment are becoming well established, evidence for the involvement of regulatory small RNA molecules, such as microRNAs (miRNAs) as important regulators of both transcriptional and posttranscriptional gene silencing is presently mounting. RESULTS: Here we report that HMGA2 expression in head and neck squamous cell carcinoma (HNSCC) cells is regulated in part by miRNA-98 (miR-98). Albeit HMGA2 is associated with enhanced selective chemosensitivity towards topoisomerase (topo) II inhibitor, doxorubicin in HNSCC, the expression of HMGA2 is thwarted by hypoxia. This is accompanied by enhanced expression of miRNA-98 and other miRNAs, which predictably target HMGA2. Moreover, we show that transfection of pre-miR-98trade mark during normoxia diminishes HMGA2 and potentiates resistance to doxorubicin and cisplatin. These findings implicate the role of a miRNA as a key element in modulating tumors in variable microenvironments. CONCLUSION: These studies validate the observation that HMGA2 plays a prominent role in governing genotoxic responses. However, this may only represent cells growing under normal oxygen tensions. The demonstration that miRNA profiles are altered during hypoxia and repress a genotoxic response indicates that changes in microenvironment in eukaryotes mimic those of lower species and plants, where, for example, abiotic stresses regulate the expression of thousands of genes in plants at both transcriptional and posttranscriptional levels through a number of miRNAs and other small regulatory RNAs.

COX-independent antineoplastic effects of sulindac in oral cancer are mediated by survivin down-regulation.

BACKGROUND: Cyclooxygenase (COX) inhibitors are reported to exert anti-proliferative and pro-apoptotic effects on cancer. The effects of COX inhibitors on oral squamous cell carcinoma (SCC) and survivin expression were assessed. MATERIALS AND METHODS: Primary oral SCC were analyzed immunohistochemically, and oral SCC cell lines were assessed using RT-PCR, Western blot, cell proliferation and apoptosis assays, following treatment with various COX inhibitors, SiRNA against survivin, or survivin forced expression. RESULTS: Survivin was expressed in all studied tumors. SiRNA against survivin or treatment with sulindac, but not other COX inhibitors, decreased survivin expression and tumor cell proliferation and increased apoptosis. Forced expression of survivin attenuated sulindac's effects. CONCLUSION: Survivin is implicated as a marker and treatment target in oral SCC, inhibition of which causes reduction of cell proliferation and induction of apoptosis. Down-regulation of survivin expression by sulindac provides an explanation for its antineoplastic effects.

Myofibromatosis: a case report with a unique clinical presentation.

Myofibroma and myofibromatosis have been described under different names since 1951. These lesions are a benign fibroblastic and myofibroblastic proliferation containing a biphasic presentation of spindle-shaped cells surrounding a central zone of less differentiated cells focally arranged in a hemangiopericytoma-like pattern. Classically, these lesions are described in children younger than 2, with two thirds present at birth, and rarely in adults. The typical clinical presentation shows variable growth pattern of a painless purple to pink soft tissue mass, often showing secondary ulceration. Controversy exists as to an autosomal dominant or recessive inheritance versus sporadic occurrence. Presented here is a unique case of myofibromatosis presenting first as a superficial scalp lesion at age 2, followed by other primary lesions of the right mandibular vestibule, right temple, and left mandibular vestibule at ages 9, 12, and 23, respectively. All were treated with excision, without recurrence at the primary site.

Frequency of pain and correlation with clinical and histologic parameters in T1 squamous cell carcinoma of the tongue: a retrospective pilot study.

AIMS: To conduct a pilot retrospective study to investigate the frequency of pain among patients with early-stage oral squamous cell carcinoma (OSCC) of the tongue and to correlate the pain with clinical and histopathologic parameters. METHODS: Twenty-four archival cases of T1 OSCC of the tongue were reviewed. No power analysis was conducted due to the pilot nature of the study. Tumors were classified into two groups according to the presence or not of pain (P+ and P- groups). Clinical and histopathologic parameters, such as grade of differentiation, depth of invasion, and presence of vascular, muscular, and perineural invasion were recorded. Statistical analyses included parametric (Student t) and nonparametric (chi-square) tests. RESULTS: Pain was reported by 13 of the 24 patients. In the P+ group, 11 of the 13 had moderately differentiated and 2 well-differentiated tumors; in contrast, P- patients had moderately differentiated tumors in 5 of the cases and well-differentiated tumors in 6 cases (P = .082). Vascular invasion was observed in 5 of the 13 P+ and 5 of the 11 P- patients, muscular invasion in 5 P+ and 2 P- patients, and perineural invasion in 4 P+ and 1 P- patients, respectively. The mean depth of invasion was 1.51 mm for P+ patients and 1.25 mm for P- patients. Only lymphoplasmocytic infiltration differed significantly, with P+ tumors exhibiting more intense inflammation (P = .041). CONCLUSION: Despite the limited number of cases, the results of this study suggest that painful OSCCs of the tongue may be associated with more intense inflammation.

Endometrial carcinoma metastatic to the retromolar pad.

Metastatic carcinoma from the female genitalia to the oral mucosa is exceptionally rare, with only 11 such cases having been previously reported in the English-language literature. We describe a new case in a 65-year-old woman with a history of endometrial carcinoma who presented with swelling of the retromolar pad. Radiographic examination showed slight opacities and irregular trabecular bone in the left posterior mandible. Following an incisional biopsy, histologic examination and immunohistochemical studies revealed glandular adenocarcinoma with positivity for progesterone receptor, estrogen receptor, and cytokeratin 7. The patient was referred to her primary care physician for comprehensive treatment. This case illustrates the value of considering cancer metastasis in the differential diagnosis of an oral swelling, particularly in a patient with a history of cancer.

Expression of midkine in ameloblastomas and its correlation with clinicopathologic parameters.

OBJECTIVE: Midkine (MK) is a heparin-binding growth factor that is overexpressed in various human cancers. The aim of this study was to investigate the expression of MK in ameloblastomas and correlate the results with clinicopathologic parameters. STUDY DESIGN: Cases of ameloblastoma seen between 1999 and 2010 were identified. Clinical information was collected regarding age, gender, race, and location of tumor. Cases were classified as solid/multicystic, unicystic, and peripheral. The expression of midkine was assessed using immunohistochemistry. A significant difference was considered present at P < 0.05. RESULTS: A total of 34 cases of ameloblastoma and 4 cases of ameloblastic carcinomas were identified. MK was expressed in 67% of lesions (23.5% weak expression; 14.7% moderate expression; 29.4% strong expression). A significant difference was seen between solid/multicystic and unicystic lesions. CONCLUSIONS: MK is expressed in the majority of ameloblastomas, suggesting a role of the protein in the tumor's development, progression, and behavior.

Synchronous Paget disease of bone and hyperparathyroidism: report of a case with extensive craniofacial involvement.

Paget disease of bone (PDB) and hyperparathyroidism (HPT) are metabolic osseous disorders which affect ≥2% of the population. As these diseases may share clinical, radiographic, biochemical, and histopathologic features, knowledge of their phenotypic overlap may provide diagnostic utility and improve clinical outcome. Scant information is available in the dental literature regarding patients concurrently affected with both pathologies. We present an unusual case report of a 63-year-old woman coaffected with primary HPT, attributed to a functional oxyphilic parathyroid adenoma, and PDB. Bone scintigraphy revealed pagetoid lesions of the skull, humeral head, spine, sacrum, and hemipelvis. Salient craniofacial features noted were bony involvement of the calvarium and midface, resulting in extensive maxillary overgrowth, hearing loss, telecanthus and consequent visual impairment, nasal deformity, and leontiasis ossea. The patient underwent a partial parathyroidectomy and bisphosphonate administration was to be initiated upon extraction of the remaining dentition.

Are we on the brink of nonsurgical treatment for ameloblastoma?

OBJECTIVE: Recent identification of altered molecular signaling pathways in neoplasia has begun to elucidate mechanisms of oncogenesis, differentiation, and tumor progression, and to suggest plausible nonsurgical considerations for treatment. Here we review the sonic hedgehog (SHH) and PI3K/Akt/mTOR signaling pathways, their role in ameloblastoma, a locally aggressive odontogenic tumor, and evidence for consideration of therapeutic approaches that target these molecular pathways. In so doing, some of the gaps will be revealed that may impel investigations and translate to patient care, helping to minimize or eliminate the need for extensive surgery. STUDY DESIGN: This is a comprehensive review of the literature regarding alterations in signaling mechanisms associated with ameloblastomas. In addition, this review attempts to explore and discuss possible inhibitors to these pathways that may have utility in treating ameloblastoma. RESULTS: The expression of SHH signaling molecules in ameloblastomas at the mRNA and protein levels has intimated that these molecules may play a role in cell proliferation of these tumors. Immunohistochemical analysis has revealed aberrant signaling in the PI3K/Akt/mTOR pathway in ameloblastomas and appears to be a valuable tool for elucidating pathogenesis and aggressiveness, and selecting optimal therapeutics. CONCLUSION: The understanding of altered pathways in ameloblastoma may soon provide nonsurgical options for the treatment of this condition. The demonstration of cross talk in SHH signal transduction with PI3K signaling through Akt has shown that these pathways converge to control the Gli transcription factors. Thus, tumors that entirely depend on active SHH signaling for survival/growth and maintenance may well be susceptible targets for combined chemotherapy with SHH-specific inhibitors together with PI3K, Akt, or mTOR blocking agents. Some of these inhibitors could be used locally, thereby minimizing major systemic effects.

Diminutive, interradicular "hybrid" desmoplastic/acanthomatous ameloblastoma.

Ameloblastomas are benign aggressive odontogentic tumors that exhibit insidious growth rates with attainment of extensive dimesions. Because ameloblastomas are not usually symptomatic until late in their clinical course, few are detected early. This article reports an atypical case of a small, painful ameloblastoma arising between the roots of the mandibular left canine and lateral incisor in a 66-year-old female. The patient underwent an en bloc resection of the mandible, and no recurrence was demonstrated on an 11-month recall examination. Histopathology revealed a "hybrid" ameloblastoma with a pronounced desmoplastic pattern and acanthomatous changes. Practitioners should be vigilant for diminutive radiolucent lesions of the jaws with poorly defined borders. Timely recognition and intervention of ameloblastomas may improve treatment outcomes.