Sclerosing Epithelioid Fibrosarcoma of the Bone With Rare EWSR1-CREB3L3 Translocation Driving Upregulation of the PI3K/mTOR Signaling Pathway.

Sclerosing epithelioid fibrosarcoma (SEF) is an uncommon neoplasm that rarely presents in bone. It is characterized by epithelioid cells arranged in nests and single-file cords within a sclerotic stromal background which may mimic neoplastic bone. SEF harbors an EWSR1 translocation, which may complicate its distinction from Ewing sarcoma in cases with histomorphologic overlap. We present a diagnostically challenging case of SEF in the mandible of a 16-year-old girl. Our experience highlights the lack of specificity of traditional morphology and EWSR1 break-apart fluorescent in situ hybridization. Open-ended RNA-based fusion gene testing coupled with MUC4 immunohistochemistry aided the eventual diagnosis in this case. Herein, we report the third case of SEF with EWSR1-CREB3L3 translocation and show that this fusion leads to aberrant upregulation of the phosphoinositide 3-kinase/mammalian target of rapamycin signaling pathway in heterologous cell models.

Clinicopathologic study on a rare variant of ameloblastoma with basal cell features.

OBJECTIVES: To investigate the clinical features, pathologic manifestations, and biologic behaviors of a variant of ameloblastoma with basal cell features (AM-BC). MATERIALS AND METHODS: Following retrospective review of the clinical and pathological data of six cases of AM-BC, we described their histological and immunohistochemical (IHC) features and discussed the biologic behaviors, prognoses, pathogenesis, and clinical relevance of AM-BC. Direct sequencing of polymerase chain reaction products was also performed in all cases. RESULTS: The six cases of AM-BC involved four women and two men, aged 22-82 years. Four lesions occurred in the maxilla and two in the mandible. Histologically, the basal cells tended to be arranged as unequally sized follicles, strands, or cords of odontogenic epithelium in the connective tissue stroma. Little or no stellate reticulum was present in the central portion of the nest. Expression of CKs was consistent with other histological variants of ameloblastoma (AM), but AM-BC had significantly higher p53 and Ki-67 (p < 0.05) labeling indices than other histological variants of AM. Two patients had BRAF gene mutations. CONCLUSION: Ameloblastoma with basal cell features is a very rare variant of AM. Our study showed the differences and relationships that exist between AM-BC and other variants of AM, which could enhance understanding of AM-BC.

Tumor-induced Osteomalacia in a 3-Year-Old With Unresectable Central Giant Cell Lesions.

Tumor-induced osteomalacia (TIO) is a rare cause of hypophosphatemia involving overproduction of fibroblast growth factor 23. TIO has been described largely in adults with small mesenchymal tumors. We report a case of TIO in a child who presented with knee pain and radiographic findings concerning for rickets, and was found to have maxillomandibular giant cell lesions. The patient was treated with oral phosphorus and calcitriol, surgical debulking, and intralesional corticosteroids, which resulted in tumor regression and normalization of serum fibroblast growth factor 23 and phosphorus. This case illustrates the occurrence of this rare paraneoplastic syndrome in children and adds to our knowledge about clinical manifestations and pathologic findings associated with pediatric TIO.

Clinicopathological and cell proliferation evaluation of ameloblastomas and keratocystic odontogenic tumors: a 10 year retrospective study.

Odontogenic tumors (OTs) are important lesions of the gnathic bones due to their clinicopathological heterogeneity and variable biological behavior; therefore, epidemiological studies are needed to outline the incidence and behavior of these tumors. To evaluate the incidence and epidemiological profile of ameloblastoma (AMB) and keratocystic odontogenic tumor (KCOT) from an oral pathology service, and correlate morphological findings of these tumors with the immunoexpression of a cellular proliferation marker (Ki-67), a retrospective study (2002-2012) was conducted to characterize demographic, clinical, radiological, and morphological data of AMBs and KCOTs. Then, a representative sample composed of 49 cases of each tumor was selected to perform immunohistochemical (IHC) analysis of Ki-67 through the streptavidin biotin peroxidase technique. For statistical analysis, we used Fisher's exact test (p < 0.05). A total of 279 OTs were found in the service, in which 91 (32.6%) were AMB and 98 (35 %) were KCOT. Most cases occurred in white women, and the average age of patients with AMB and KCOT was 32 and 33 years, respectively. The maxilla-mandible ratio was 1:6 and 1:3.6 for AMB and KCOT, respectively. Regarding IHC analysis, AMB and KCOT had similar levels of cellular proliferation. However, KCOTs with intense inflammation showed higher Ki-67 expression (p < 0.001). Recurrent cases had similar Ki-67 immunoexpression. The demographic profile of the studied tumors corroborates with data reported in the literature, and the levels of cellular proliferation were similar in both tumors, although the inflammation seems to induce a differential proliferative behavior in KCOT.

Differential expression of the epithelial mesenchymal transition factors Snail, Slug, Twist, TGF-ß, and E-cadherin in ameloblastoma.

Epithelial mesenchymal transition (EMT), the transition of epithelial cells into motile mesenchymal cells, plays an important role in embryogenesis, cancer invasion, and metastasis. Ameloblastomas are common epithelial odontogenic tumors, occurring exclusively in the mandible with locally invasive growth. Thirty-seven ameloblastoma cases were evaluated for the involvement of EMT by immunohistochemical staining and western blotting using antibodies against Slug, Snail, Twist, TGF-ß, and E-cadherin. Double immunostaining was also performed. Slug and TGF-ß were expressed in the nuclei of peripheral and stellate reticulum cells of ameloblastoma nests. Twenty cases of Snail, 36 of Slug, 8 of Twist, and 19 of TGF-ß showed strong expression in tumor cells in follicular and plexiform patterns. Expression of Slug and TGF-ß increased in regions where the expression of E-cadherin was reduced. EMT was found to be associated with the local invasive growth of ameloblastoma. These data suggest that reduced expression of E-cadherin and over-expression of Slug, Snail, and TGF-ß induce EMT. Given that ameloblastomas are characterized by local invasiveness, EMT might be related to their development. Thus, strong expression of Slug and TGF-ß and reduced expression of E-cadherin might be related to the local invasiveness of ameloblastoma.

Survivin, cyclin D1, and p21hras in keratocystic odontogenic tumors before and after decompression.

OBJECTIVES: The aim of this study was to investigate survivin, cyclin D1, and p21hras expression in keratocystic odontogenic tumors before and after decompression, as well as in pericoronal follicles. A potential correlation between the expression levels of these proteins was also investigated. MATERIALS AND METHODS: We analyzed eighteen keratocystic tumors treated by decompression and subsequent enucleation along with seven pericoronal follicles using immunohistochemistry. RESULTS: Keratocystic tumor samples, both before and after decompression, were positive for each of the investigated proteins. In pericoronal follicles, survivin exhibited cytoplasmic staining in contrast to nuclear staining in keratocystic tumors. Cyclin D1 expression was negative in pericoronal follicles, and p21hras expression was similar in both groups. Survivin showed significantly higher expression after decompression, while cyclin D1 and p21hras remained unchanged (P = 0.039, P = 0.255, P = 0.913, respectively). There was no correlation between these proteins neither before nor after decompression. CONCLUSIONS: Within the limits of the study, we can conclude that following decompression, keratocystic odontogenic tumors preserve distinct immunohistochemical profiles of cyclin D1 and p21hras expression, despite substantial reduction in size of the lesions. Significant increase of survivin expression after decompression might be attributed to higher level of epithelial proliferation caused by this procedure.

Wnt/ß-catenin-YAP axis in the pathogenesis of primary intraosseous carcinoma NOS, deriving from odontogenic keratocyst.

Odontogenic tumors (OGTs), which originate from cells of odontogenic apparatus and their remnants, are rare entities. Primary intraosseous carcinoma NOS (PIOC), is one of the OGTs, but it is even rarer and has a worse prognosis. The precise characteristics of PIOC, especially in immunohistochemical features and its pathogenesis, remain unclear. We characterized a case of PIOC arising from the left mandible, in which histopathological findings showed a transition from the odontogenic keratocyst to the carcinoma. Remarkably, the tumor lesion of this PIOC prominently exhibits malignant attributes, including invasive growth of carcinoma cell infiltration into the bone tissue, an elevated Ki-67 index, and lower signal for CK13 and higher signal for CK17 compared with the non-tumor region, histopathologically and immunohistopathologically. Further immunohistochemical analyses demonstrated increased expression of ADP-ribosylation factor (ARF)-like 4c (ARL4C) (accompanying expression of ß-catenin in the nucleus) and yes-associated protein (YAP) in the tumor lesion. On the other hand, YAP was expressed and the expression of ARL4C was hardly detected in the non-tumor region. In addition, quantitative RT-PCR analysis using RNAs and dot blot analysis using genomic DNA showed the activation of Wnt/ß-catenin signaling and epigenetic alterations, such as an increase of 5mC levels and a decrease of 5hmC levels, in the tumor lesion. A DNA microarray and a gene set enrichment analysis demonstrated that various types of intracellular signaling would be activated and several kinds of cellular functions would be altered in the pathogenesis of PIOC. Experiments with the GSK-3 inhibitor revealed that ß-catenin pathway increased not only mRNA levels of ankyrin repeat domain1 (ANKRD1) but also protein levels of YAP and transcriptional co-activator with PDZ-binding motif (TAZ) in oral squamous cell carcinoma cell lines. These results suggested that further activation of YAP signaling by Wnt/ß-catenin signaling may be associated with the pathogenesis of PIOC deriving from odontogenic keratocyst in which YAP signaling is activated.

Proteomics study of bone tissue around ameloblastoma and the potential mechanism of CD36 in bone remodelling.

Ameloblastoma (AM) is characterised by local aggressiveness and bone resorption. To our knowledge, the proteomic profile of bone adjacent to AM has not previously been explored. We therefore looked at the differential proteins in cancellous bone (CB) adjacent to AM and normal CB from the mandible. CB proteins were extracted, purified, quantified, and analysed by liquid chromatography-mass spectrometry (LC-MS) using samples from five patients with AM. These proteins were further investigated using gene ontology for additional functional annotation and enrichment. Proteins that met the screening requirements of expression difference ploidy > 1.5-fold (upregulation and downregulation) and p < 0.05 were subsequently deemed differential proteins. Immunohistochemical staining was performed to confirm the above findings. Compared with normal mandibular CB, 151 differential proteins were identified in CB adjacent to the mandibular AM. These were mainly linked to cellular catabolic processes, lipid metabolism, and fatty acids (FA) metabolism. LC-MS and immunohistochemistry showed that CD36 was one of the notably decreased proteins in CB bordering the AM compared with normal mandibular CB (p = 0.0066 and p = 0.0095, respectively). CD36 expression in CB correlates with bone remodelling in AM, making CD36 a viable target for therapeutic approaches.

Expression of proliferative markers in ameloblastomas and malignant odontogenic tumors.

OBJECTIVE: To compare the proliferative activity in ameloblastoma and malignant odontogenic tumors, as assessed by Ki-67 immunostaining and determine whether expression of substance P (SP) and NK-1 receptor (NK-1R) is related to cell proliferation in these tumors. MATERIALS AND METHODS: Immunohistochemistry was used to evaluate protein expression in 44 benign and malignant odontogenic tumors from 39 patients. Immunohistochemistry was performed with anti-SP, anti-NK-1R, and anti-Ki-67 monoclonal antibodies, and the clinical and pathological data of the patients with odontogenic tumor were evaluated. RESULTS: Expression of Ki-67 in malignant odontogenic tumors was significantly higher than in ameloblastomas (P < 0.001), and the expression level was associated with higher expression of NK-1R. Among the ameloblastomas, there was significantly higher expression of Ki-67 in peripheral ameloblastic-like cells (3.3 ± 4.1) than in stellate reticulum-like cells (2.6 ± 3.7) (P = 0.04). In the majority of tissue locations of the malignant tumors, expression of SP and NK-1R was positively correlated with higher expression of Ki-67. CONCLUSION: These findings show that the expression level of Ki-67 in ameloblastomas was positively correlated with the rate of growth of odontogenic tumors. Overexpression of NK-1R complex in malignant odontogenic tumors could be part of the trigger stimulus that results in higher proliferative activity of the tumor.

Immunohistological features in adenomatoid odontogenic tumor: review of the literature and first expression and mutational analysis of ß-catenin in this unusual lesion of the jaws.

PURPOSE: To investigate for the first time the immunohistochemical and mutational status of ß-catenin in a mandibular case of adenomatoid odontogenic tumor (AOT) and to review the immunohistochemical expression data of various markers (cytokeratins, metalloproteinases, etc) in such a lesion. MATERIALS AND METHODS: A case of follicular-type AOT in a young male patient was analyzed in regard to the immunohistochemical expression of ß-catenin and mutations of the ß-catenin gene (CTNNB1). Its expression is altered in some odontogenic tumors. RESULTS: We found a strong cytoplasmic expression of ß-catenin, but no molecular anomaly within the exon 3 of CTNNB1. ß-catenin is considered to play a role in cell differentiation processes. CONCLUSION: Our results were consistent with previous findings in ameloblastoma and malignant odontogenic tumors. However, ß-catenin alterations had not been explored in AOT so far. Further studies are necessary to understand the specific regulation of ß-catenin in the AOT pathogenesis.

Comparison of Immunohistochemistry and DNA Sequencing for BRAF V600E Mutation Detection in Mandibular Ameloblastomas.

This study aimed to investigate the presence of BRAF V600E mutation in mandibular ameloblastoma by comparing the results of molecular detection and immunohistochemical analysis. A 128 cases of mandibular ameloblastoma and 30 cases of dentigerous cyst (control group) were selected for analysis. Detection of BRAF V600E mutation was performed with immunohistochemistry (IHC) and polymerase chain reaction techniques. Clinico-pathologic data were collected in order to investigate possible associations with the mutation. Of the 128 cases submitted to IHC, 81.2% (108 cases) showed positivity for anti-BRAF V600E antibody, whereas 24 were negative (18.8%). Molecular analysis of the BRAF V600E mutation by polymerase chain reaction was possible in 116 cases due to DNA quality. Of these cases, 96 were positive (82.8%) and 20 negative (17.2%). All cases of dentigerous cyst were negative for BRAF V600E mutation in both techniques. Considering the sequencing as a gold standard method, the receiver operating characteristics curve analysis showed sensitivity of 0.99 and specificity of 1 (area under the curve=0.995, standard error=0.006; P<0.001; 95% confidence interval=0.983 to 1). We also tested the agreement between the techniques by using the Cohen's κ coefficient, with κ being 0.97 (P<0.001). IHC is a reliable test for identifying the BRAF V600E mutation in ameloblastomas, presenting advantages such as being more frequently used in surgical pathology laboratories and requiring fewer critical steps for paraffin-embedded tissue compared with molecular biology techniques.

Odontogenic myxofibroma with HMGA2 overexpression and HMGA2 rearrangement.

Odontogenic myxofibromas are variants of odontogenic myxomas that contain considerable amounts of collagen fibers in the myxoid stroma. Cytogenetic studies of odontogenic myxomas/myxofibromas have rarely been reported. This report describes the first case of an odontogenic myxofibroma presenting with HMGA2 protein overexpression and HMGA2 rearrangement in a 40-year-old woman. A 2.7-cm tumor in the premolar region of the right mandible was curettaged. There was no evidence of recurrence or metastasis at 12 months after the surgery. Histological examination revealed that the tumor comprised spindle or stellate cells with mild nuclear pleomorphism, abundant myxoid matrix and partly dense collagen fibers. Mitotic figures were rarely observed. Immunohistochemically, the tumor cells were diffusely positive for vimentin and HMGA2. Less than 1% of the tumor cells were positive for Ki-67. We detected split signals by interphase fluorescence in situ hybridization (FISH) in paraffin sections using HMGA2 break-apart probes. The breaks were certainly located within or near the HMGA2 gene. No rearrangement of the FUS gene was detected by FISH, implying discrimination from low-grade fibromyxoid sarcoma. It is suggested that HMGA2 rearrangement and HMGA2 protein overexpression may be associated with the tumorigenesis of odontogenic myxomas/myxofibromas, similar to the case for many other benign mesenchymal tumors.

Squamous odontogenic tumor of the mandible: a case report demonstrating immunoexpression of Notch1, 3, 4, Jagged1 and Delta1.

BACKGROUND: Squamous odontogenic tumor (SOT) is a rare benign odontogenic epithelial neoplasm. A slow-growing painless expansive swelling is the common presenting symptom. Histopathologically, SOT can be easily misdiagnosed as an acanthomatous ameloblastoma. Although Notch receptors and ligands have been shown to play a role in cell fate decisions in ameloblastomas, the role of these cell signaling molecules in SOT is unknown. CASE REPORT: This paper describes a case of SOT affecting the anterior mandible of a 10-year-old Indian female. The patient was treated by local surgical excision and there has been no follow-up clinical record of recurrence 5 years after primary treatment. Histo?pathological examination revealed a solid, locally-infiltrative neoplasm composed of bland-looking squamatoid islands scattered in a mature fibrous connective tissue stroma and the diagnosis was SOT. Immunohistochemical evaluation showed positive reactivity of varying intensity in the neoplastic epithelial cells for Notch1, Notch3, Notch4, and their ligands Jagged1 and Delta1. Expression patterns showed considerable overlap. No immunoreactivity was detected for Notch2 and Jagged2. CONCLUSIONS: Present findings suggest that Notch receptors and their ligands play differential roles in the cytodifferentiation of SOT.

Immunoexpression of Ki67, proliferative cell nuclear antigen, and Bcl-2 proteins in a case of ameloblastic fibrosarcoma.

Ameloblastic fibrosarcoma (AFS), regarded as the malignant counterpart of the benign ameloblastic fibroma, is an extremely rare odontogenic neoplasm with only 68 cases reported in the English literature up to 2009. It is composed of a benign odontogenic epithelium, resembling that of ameloblastoma, and a malignant mesenchymal part exhibiting features of fibrosarcoma. Due to the rarity of the lesion, little is known about its molecular pathogenesis; therefore, in the current study, we sought to evaluate the immunoexpression of Ki67, proliferative cell nuclear antigen, and Bcl-2 proteins in AFS, comparing the results obtained with its benign counterpart, as well as to report a new case of this rare entity affecting a 19-year-old female patient. The results obtained revealed that all the proteins evaluated were overexpressed in the malignant mesenchymal portion of AFS if compared with ameloblastic fibroma, suggesting that nuclear proliferative factors such as Ki67 and proliferative cell nuclear antigen, in association to histopathologic features, may be useful markers for identifying the malignancy and that, despite the lack of molecular analysis in the case reported, Bcl-2 alteration may play a role in AFS pathogenesis.

Burkitt's lymphoma in a young Brazilian boy.

Burkitt's lymphoma is not an uncommon malignancy in the paediatric population. It is a high-grade non-Hodgkin B-cell lymphoma which may present as endemic, sporadic and human immunodeficiency-associated subtypes. The African, or endemic, variant usually involves the maxilla and other facial bones while head and neck manifestations in sporadic Burkitt's lymphoma are rare. We described a case of oral Burkitt's lymphoma involving the right jaw in a 4-year-old boy. The patient presented with a rapidly-enlarging swelling of one month duration, toothache-like pain and radiographical appearance of 'floating teeth' in the right mandible. Incisional biopsy revealed small round tumour cells with scarce cytoplasm and multiple small nuclei interspersed by phagocytic macrophages. The tumour cells were immunopositivity for CD20 and CD10, expressed weak positivity for CD3, negative for CD5 and showed > 90% positivity for Ki-67. Tumour remission was achieved with six cycles of chemotherapy with the CHOP regime.

Immunohistochemical Investigation of Predictive Biomarkers for Mandibular Bone Invasion in Oral Squamous Cell Carcinoma.

The accurate preoperative determination of the extent of mandibular resection remains a challenge for the surgeons. The purpose of the present study was to immunohistochemically investigate predictive markers for histological bone invasion of oral squamous cell carcinoma (OSCC). The medical records of primary OSCC patients with mandibular bone contact in preoperative computed tomography scans between January 2003 and December 2017 were retrospectively reviewed and an immunohistochemical investigation was performed. Forty-five OSCC patients with mandibular bone contact radiographically were included in this study. Histopathologically, infiltrative bone invasion was observed in 19 patients (42.2%) and compressive bone invasion in 15 (33.3%). A correlation was noted between the histological pattern of bone invasion and mode of invasion (chi-squared test, p < 0.05). At the tumor surface, a correlation was observed between the expression of IL-6 and bone invasion (the Wilcoxon test, p < 0.05), although the expression was so weak. At the bone contact area, the expression of both ɑ-SMA and OPG correlated with infiltrative bone invasion (ɑ-SMA; the Wilcoxon test, p < 0.05, OPG; p < 0.05). These results suggest that predictive markers for aggressive (infiltrative) bone invasion in OSCC patients with a higher mode of invasion are the expression of ɑ-SMA and OPG.

Central angioleiomyoma of the mandible: A rare entity.

The leiomyoma is a benign smooth-muscle neoplasm commonly found in the female genital tract, gastrointestinal tract, or skin. Leiomyomas of the oral cavity are unusual. Oral leiomyomas are uncommon due to the paucity of the smooth muscle in the mouth (except in blood vessels) and thus the involvement of jaw bones is extremely rare. Leiomyomas have been classified as solid angiomyoma, angioleiomyoma (vascular leiomyoma), and epithelioid variants. Angioleiomyomas are benign mesenchymal tumors derived from smooth muscle, which rarely occur in the oral cavity. Malignant transformation probably does not occur but careful histopathologic examination is still necessary to differentiate these benign lesions from their malignant counterparts due to different prognosis. Although uncommon in the maxilla and mandible, they should be included in the differential diagnosis of radiolucent lesions of jaw bones. An extensive search of literature was carried out on the Medline-PubMed and Google Scholar database using the keywords such as leiomyoma, angioleiomyoma, jaw bones, maxilla, mandible, intra-osseous to thoroughly search and collect all the reported cases of intraosseous leiomyoma (but our search was not limited to these terms only). To the best of our knowledge, only 23 cases of intraosseous leiomyomas have been reported so far in the jaw bones, among which only 8 belonged to angioleiomyomas. Herein, we report the 9th case of intraosseous angioleiomyoma, one of the variants of leiomyoma and overall 24th intraosseous leiomyoma in a 6-year-old female child, together with conventional histopathologic and immunohistochemical findings.

Central granular cell odontogenic tumor: a histopathologic and immunohistochemical study.

The central granular cell odontogenic tumor (CGCOT) is a rare lesion that usually affects the posterior region of the mandible of young adults. We present a case of CGCOT involving the mandible of a 20-year-old white woman, emphasizing the immunohistochemical characteristics using a large panel of antibodies. The lesion was removed surgically, and after 4 years of follow-up, there are no evidences of recurrences. The odontogenic epithelium (OE) showed positivity for cytokeratins (CKs) AE1/AE3, 34betaE12, CK5, CK7, CK8, CK14, CK19, E-cadherin, beta-catenin, CD138, and p63. The granular cells were positive for vimentin, CD68, lysozyme, muscle-specific actin, alpha-smooth muscle actin, calponin, neuron-specific enolase (NSE), CD138, and bcl-2. Dendritic-like cells surrounding the OE displayed positivity for vimentin, CD1a, S100, CD68, and bcl-2, but it was negative for factor XIIIa, supporting a Langerhans cell phenotype. Ki-67 labeling index was 1.8%, whereas p53 was negative. These data confirm the benign nature of CGCOT, the association of OE with Langerhans cells, and a variable phenotype of the granular cells.

Odontogenic myxoma: clinico-pathological, immunohistochemical and ultrastructural findings of a multicentric series.

The aim of this study was to analyze the clinico-pathological and immunohistochemical features of 62 cases of odontogenic myxoma (OM) diagnosed in three Oral Pathology Diagnostic Services in Latin America, as well as to describe the ultrastructural features of three of these cases. OM showed a wide age range (9-71 years), with a mean of 27.97 yr (SD: 11.01) and a male to female ratio of 1:2.2. Mandible was affected in 37 cases (59.6%) and maxilla in 25 (40.4%), with 61.3% located in the posterior region. Thirty-nine cases (62.9%) were multilocular and 23 (37.1%) unilocular. Size ranged from 1 to 13 cm, (mean: 5.2 cm). Thirty-seven multilocular (54.8%) and 6 unilocular lesions (26%) were larger than 4 cm (p<0.05). Epithelial islands were identified in 5 cases (8%) on H&E stained sections, but AE1/AE3 and CK14 disclosed these structures in 15 cases each (24.2%); CK5 was positive in 8 (12.9%); CK7 in 2 (3.2%) and CK19 in only 3 cases (4.8%). All cases were negative for CKs 8 and 18, S-100 protein, NSE and CD68, and showed a low index of expression of Bcl2 and ki-67 proteins (<1%). Mast cell antibodies showed these cells in 45 cases (72.6%). Myofibroblastic differentiation evidenced by myofilaments and fibronexi was found in one case out of the three studied by TEM and 29 cases (46.7%) were positive by immunohistochemistry for alpha actin. In conclusion, only a minority of OM had epithelial islands, and only 3 cases expressed CK 19, indicating an odontogenic epithelium origin. Immunohistochemical and ultrastructural findings suggest that OM is a mesenchymal neoplasm in which several factors may contribute to its pathogenesis, including myofibroblastic differentiation and the participation of mast cell products. However, further investigations are needed to better understand the participation of these elements in this particular neoplasm.

Recurrence of keratocystic odontogenic tumor: clinicopathological features and immunohistochemical study of the Hedgehog signaling pathway.

AIMS: Critical factors responsible for the recurrence of keratocystic odontogenic tumor (KCOT) were examined. METHODS: The clinicopathological features were retrospectively studied in 74 patients with 75 sporadic KCOTs. From the 75 KCOTs, 23 were examined for the expression of Sonic Hedgehog (SHH), Patched and Smoothened (SMO) by immunohistochemistry. RESULTS: Recurrence in multilocular lesions was more frequent than in unilocular lesions. Nine (64%) of 14 multilocular lesions recurred, in contrast to 2 (7%) of 27 unilocular lesions (p = 0.0350). The average length of recurrent lesions (62.8 +/- 6.5 mm) was larger than that of nonrecurrent lesions (43.0 +/- 4.0 mm; p = 0.0363). The immunoreactivity of proliferation-related SMO in KCOTs with recurrence was higher than that of those without recurrence (p = 0.0475), whereas the expressions of a ligand, SHH, and an inhibitory receptor, Patched, were not associated with KCOT recurrence. The expressions of SHH and SMO showed inverse correlation in whole KCOT (p = 0.0318). CONCLUSION: These findings suggest that recurrence of KCOT is associated with multilocular large lesions and high SMO expression.