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Objectives The objective of this study was to demonstrate the clinical, radiologic, and histologic features of orthokeratinized odontogenic cyst (OOC); determine the characteristics of multiple OOCs; and present rare but significant manifestations of OOC. Study Design A clinical, radiologic, and histopathologic study of 65 primary and 2 recurrent OOC cases was performed retrospectively along with a comprehensive literature review. Results OOCs shared similar radiologic findings with odontogenic keratocyst, yet some showed features that have not been previously described: root resorption and radiopaque foci. Histologic review revealed a unique histiocytic lining and some findings suggestive of the multipotentiality of the odontogenic epithelium. The analysis of patients with multiple OOCs demonstrated that multiple OOCs occurred synchronously with a marked predilection for young male adults. Two unusual cases were also identified: an OOC combined with a BRAFV600E ameloblastoma and a recurrent OOC with malignant transformation. Conclusions This largest series presents previously unreported radiographic and histopathologic features that can be seen in OOC. Multiple OOCs have clinical characteristics distinct from those of solitary cases. The first reported OOC associated with ameloblastoma suggests the involvement of oncogenic mutations in odontogenic tumorigenesis. Although OOC shows a low recurrence rate, the possibility of malignant transformation of recurrent OOCs should be emphasized.

Background Although immunohistochemistry (IHC) along with molecular tests has been investigated in ameloblastoma for BRAF V600E detection, VE1 IHC has not been studied in odontogenic carcinomas (OCs) and benign mixed epithelial and mesenchymal odontogenic tumours (BMOTs). Here, we performed BRAF V600E mutation analysis, examined the expression pattern of VE1 IHC, and comparatively evaluated the performance of two VE1 antibodies in ameloblastomas, OCs and BMOTs. Methods BRAF V600E detection was performed using Sanger sequencing in a total of 47 odontogenic tumours: 28 ameloblastomas, 6 OCs and 13 BMOTs. VE1 IHC was conducted using two different antibodies (IHC-A and IHC-V), and their performance was analysed by calculating the sensitivity and specificity compared with sequencing. Results BRAF V600E mutations were identified in 24/28 (85.7%) ameloblastomas, 2/5 (40.0%) ameloblastic carcinomas (ACs), 3/7 (42.9%) ameloblastic fibromas and 1/2 (50.0%) ameloblastic fibro-odontomas. In the presence of the mutation, VE1 showed diffuse cytoplasmic staining in ameloblastomas and ACs, whereas all BMOTs were negative for VE1. IHC-A and IHC-V yielded a sensitivity of 76.7% and 60.0%, respectively, although both antibodies showed 100% specificity. Conclusion OCs and BMOTs have BRAF V600E mutations in common at lower frequencies than ameloblastoma. Diffuse VE1 cytoplasmic staining in AC suggests the utility of MAPK-targeted therapy as selectively applied in ameloblastoma, and consistent VE1 false-negative expression in BMOTs requires further investigation. Considering the high specificity but low sensitivity of VE1 IHC, molecular tests should be performed to determine the presence of BRAF V600E mutations in odontogenic tumours.

Abnormal expression of claudin-1 (CLDN1) has important roles in carcinogenesis and metastasis in various cancers. The role of CLDN1 in human oral squamous cell carcinoma (OSCC) remains unknown. Here, we report the functional role of CLDN1 in metastasis of human OSCC, as a potential target regulated by withaferin A. From gene expression profiling with microarray technology, we found that the majority of notable differentially expressed genes were classified into migration/invasion category. Withaferin A impaired the motility of human OSCC cells in vitro and suppressed metastatic nodule formation in an in vivo metastasis model, both associated with reduced CLDN1. CLDN1 overexpression enhanced metastatic nodule formation in vivo, resulting in severe metastatic lesions in lung tissue. Moreover, CLDN1 expression was positively correlated to lymphatic metastasis in OSCC patients. The impaired motility of human OSCC cells upon withaferin A treatment was restored by CLDN1 overexpression. Furthermore, upregulation of let-7a induced by withaferin A was inversely correlated to CLDN1 expression. Overall, these give us an insight into the function of CLDN1 for prognosis and treatment of human OSCC, substantiating further investigation into the use of withaferin A as good anti-metastatic drug candidate.

Background Despite being one of the leading cancer types in the world, the diagnosis of oral cancer and its suitable therapeutic options remain limited. This study aims to investigate the single and chemosensitizing effects of TW-37, a BH3 mimetic in oral cancer, on human oral cancer cell lines. Methods We assessed the single and chemosensitizing effects of TW-37 in vitro using trypan blue exclusion assay, Western blotting, DAPI staining, Annexin V–FITC/PI double staining, and quantitative real-time PCR. Mcl-1 overexpression models were established by transforming vector and transient transfection was performed to test for apoptosis Results TW-37 enhanced the cytotoxicity of human oral cancer cell lines by inducing caspase-dependent apoptosis, which correlates with the reduction of the myeloid cell leukemia-1 (Mcl-1) expression via transcriptional and post-translational regulation. The ectopic expression of Mcl-1 partially attenuated the apoptosis-inducing capacity of TW-37 in human oral cancer cell lines. Besides, TW-37 decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr705 and nuclear translocation in human oral cancer cell lines at the early time points. Furthermore, TW-37 potentiated chemosusceptibility of cryptotanshinone in human oral cancer cell lines by suppressing STAT3–Mcl-1 signaling compared with either TW-37 or cryptotanshinone alone, resulting in potent apoptosis. Conclusions This study not only unravels the single and chemosensitizing effects of TW-37 for treatment of human oral cancer but also highlights the likelihood of TW-37 as a good therapeutic strategy to enhance the prognosis of patients with oral cancer in the future.

Sinonasal mucosal melanoma (SNMM) in the maxillary sinus is a rare disease condition. Compared to oral mucosal melanoma, SNMM has a bulky, exophytic, and polypoid appearance, is weakly pigmented, and associated with unspecific symptoms. Due to these features, SNMM in the maxillary sinus has been misdiagnosed as nasal polyps and chronic sinusitis. In this case report, we described SNMM occurring in the right maxillary sinus simulated as a cystic or benign lesion. Cortical bone thinning and expansion were observed around the mass. The excised soft mass was encapsulated and weakly pigmented. The mass was clearly excised and covered with a pedicled buccal fat pad graft. Diagnosis using immunohistochemistry with S-100 and homatropine methylbromide-45 (HMB-45) is critical for proper treatment.

Nitidine chloride (NC) is a natural alkaloid compound derived from the plant Zanthoxylum nitidum and is known for its therapeutic anticancer potential. In this study, we investigated the effects of NC on growth and signaling pathways in human oral cancer cell lines and a tumor xenograft model. The apoptotic effects and related molecular targets of NC on human oral cancer were investigated using trypan blue exclusion assay, DAPI staining, Live/Dead assay, Western blotting, Immunohistochemistry/Immunofluorescence and a nude mouse tumor xenograft. NC decreased cell viability in both HSC3 and HSC4 cell lines; further analysis demonstrated that cell viability was reduced via apoptosis. STAT3 was hyper-phosphorylated in human oral squamous cell carcinoma (OSCC) compared with normal oral mucosa (NOM) and dephosphorylation of STAT3 by the potent STAT3 inhibitor, cryptotanshinone or NC decreased cell viability and induced apoptosis. NC also suppressed cell viability and induced apoptosis accompanied by dephosphorylating STAT3 in four other oral cancer cell lines. In a tumor xenograft model bearing HSC3 cell tumors, NC suppressed tumor growth and induced apoptosis by regulating STAT3 signaling without liver or kidney toxicity. Our findings suggest that NC is a promising chemotherapeutic candidate against human oral cancer.

Several studies have examined the correlation between nestin expression and the degree of tumor invasion in cutaneous melanoma. However, no information has been reported on nestin in primary mucosal melanoma of the head and neck. The present study examined the expression and prognostic significance of nestin in patients with primary mucosal melanoma of the oral cavity. Nestin expression was examined immunohistochemically in 39 patients (six oral melanoma in-situ cases and 33 invasive oral melanoma cases) and analyzed for association with disease progression. Age, sex, anatomic site, stage, level of invasion, regional lymph node metastasis, surgical margin involvement, and treatment modality were also analyzed. In the 33 invasive melanoma cases, invasion depth correlated significantly with prognosis in univariate and multivariate analyses. High-intensity nestin staining was observed in 14 of the 33 cases and a high proportion of nestin-positive cells was observed in 16 cases. In stage III oral melanoma cases, nestin expression was not significantly associated with disease progression. However, in stage IV cases, both the intensity and the proportion of nestin expression were significantly associated with disease progression (P=0.022 and 0.005, respectively). In all 33 invasive cases, multivariate analyses showed that both the intensity and the proportion of nestin were significantly associated with a poor prognosis (P=0.014 and 0.009; hazard ratio, 3.59 and 4.05; 95% confidence interval, 1.29-9.98 and 1.42-11.56, respectively). In conclusion, nestin can be a valuable prognostic indicator in the advanced-stage (stage IV) cases of oral mucosal melanoma.

Background Granular cell tumor (GCT) is a benign soft tissue tumor of neural origin and is characterized by eosinophilic granular cells showing positivity for neuronal markers. Herein, we report the first case of primary intraosseous GCT arising in the maxilla of an adolescent girl. Methods and Results A 16-year-old female patient presented with palatal swelling. Radiographic findings revealed a well-defined radiolucent lesion centrally located in the right maxilla. Mass excision was performed, and histopathologic examination showed sheets and cords of eosinophilic granular cells with cellular pleomorphism. Tumor cells were strongly positive for vimentin, S-100 protein, and CD56, and negative for cytokeratin, desmin, smooth muscle actin, and c-kit. High expression of p53 and Ki-67 was found. The final diagnosis was atypical GCT. Conclusion When evaluating an intraosseous radiolucent lesion with histopathologic features of granular cells, clinicians and pathologists should include GCT in the differential diagnosis. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Summary Objectives The staging significance of bone invasion is controversial in oral squamous cell carcinoma (OSCC) cases with tumors measuring 4 cm or less according to the American Joint Committee on Cancer (AJCC). Our aim was to retrospectively examine a large group of patients with OSCC to determine the staging significance of bone invasion. Materials and Methods Three hundred and twenty-three patients with primary OSCC were classified based on tumor size. Bone invasion was categorized as absent, one side bone, and both buccal and lingual bones, and analyzed for association with disease progression. Regional lymph node metastasis (N), perineural invasion, vascular invasion, surgical margin involvement, and adjuvant treatment were also analyzed. Results In all OSCC cases, bone invasion ( p = 0.007) with stage N, perineural invasion, and surgical margin involvement were significant independent prognostic factors of disease progression. However, in OSCC cases with tumors measuring 4 cm or less, bone invasion was not significantly associated with disease progression. Nevertheless, invasion of both buccal and lingual bones was significantly associated with disease progression ( p = 0.03). In multivariate analysis, both buccal and lingual bone invasion ( p = 0.04; hazard ratio = 3.4; 95% confidence interval, 1.0–11.0), stage N2, and perineural invasion were also independent prognostic factors. Conclusion Although OSCC bone invasion was an independent prognostic factor, bone invasion in small OSCC was not. However, small OSCC with both buccal and lingual bone invasion had a significantly worse prognosis. The AJCC T system is of limited prognostic value for small OSCC with bone invasion. But other elements should be examined before a modification can be accepted.

Objective:Chondrosarcoma is the second most common sarcoma arising in the bone, but it rarely involves the temporomandibular joint (TMJ). To date, 30 cases of TMJ chondrosarcoma have been reported in the English literature, and the authors report an additional case arising from a cystic lesion in a 60-year-old female patient.Clinical presentation:The clinical and radiological diagnosis of the lesion was initially synovial cyst, and periodic check-ups were done after aspiration of the lesion. After three years, the patient perceived swelling of the lesion, and surgical excision was performed. The final diagnosis was grade I chondrosarcoma.Conclusion:When clinicians detect a cystic lesion in the radiographic imaging of the TMJ, chondrosarcoma should be included in the differential diagnosis. In addition, computed tomography (CT) as well as magnetic resonance imaging (MRI) is recommended for the accurate diagnosis and proper preoperative planning in TMJ chondrosarcoma.

SRY-related HMG-box 7(SOX7), a transcription factor belonging to the SOX family, has been reported to be down-regulated in some types of cancers. However, its biologic role in oral squamous cell carcinoma (OSCC) remains unknown. We found expression of SOX7 protein was decreased in OSCC tissues compared with normal oral mucosa. SOX7 expression in patients with OSCC was inversely associated with positive lymph node metastasis, advanced TNM stage, and poor prognosis. These results were in accordance with data obtained from our in vitro experiments on the OSCC cell lines. Moreover, ectopic expression of SOX7 suppressed cell proliferation, migration, and invasion in HSC-4 and SCC-9 cells. Importantly, we discovered that SOX7 expression likely inhibited vasculogenic mimicry formation associated with clinically poor outcome and impaired expression of VE-cadherin in OSCC cell lines as well as lung cancer and breast cancer cells. Our findings suggest that SOX7 could be a potential marker for predicting the prognosis of patients with OSCC and plays an important role as a tumor suppressor in oral tumorigenesis and progression. This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning [2017R1D1A1B03029317, 2018R1D1A1B07043080, and 2019R1A2C1085896]. Citation Format: Chi-Hyun Ahn, Kyoung Ok Hong, Ji-Ae Shin, Seong-Doo Hong, Sung-Dae Cho. The regulation of SOX7 and its tumor suppressive role in oral squamous cell carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 362.

Background BRAF V600E mutations are activating mutations that have recently been detected in ameloblastoma. However, their prevalence has not been reported in East Asian patients with ameloblastoma and their clinicopathological significance remains unclear. In this study, we examined the prevalence and clinicopathological significance of BRAF V600E mutations in Korean patients with ameloblastoma. In addition, we investigated the relationship between BRAF V600E mutations and epithelial-mesenchymal transition, which has not been studied in ameloblastoma. Methods Thirty ameloblastoma tissue samples were collected, and DNA isolation, polymerase chain reaction, and Sanger sequencing were performed to detect BRAF V600E mutations. Immunohistochemistry was carried out using antibodies against two epithelial-mesenchymal transition-inducing transcription factors, Twist and Snail. Associations of BRAF V600E mutations with clinicopathological factors and expression of Twist and Snail were statistically analyzed. Results We found a high frequency (90.0%) of BRAF V600E mutations, and mutation status was not associated with clinicopathological factors including age, tumor location, and recurrence. Positive expression of Twist and Snail was observed in 33.3% and 56.7% of cases, respectively, and associated with recurrence (P = 0.020 and 0.010, respectively). There was no correlation between BRAF V600E mutation status and expression of Twist and Snail (P = 1.000, for both). Conclusions A higher prevalence of BRAF V600E mutations was identified in Korean patients with ameloblastoma compared with previous studies, which indicates that BRAF-targeted therapies can be widely used for refractory ameloblastomas. Furthermore, our findings suggest that BRAF V600E mutations and epithelial-mesenchymal transition may act independently in the development of ameloblastoma.

In this study, we aimed to identify whether tumor budding is associated with the progression and prognosis of oral squamous cell carcinoma (OSCC) and investigate the correlation between tumor budding and regulators of epithelial-mesenchymal transition (EMT). Fifty-six cases of OSCC were selected and their tumor budding status was reviewed using archived hematoxylin and eosin-stained slides. In addition, the expression of EMT regulators was evaluated by immunohistochemistry using antibodies against Snail and Twist. Tumor budding was observed in 19 (33.9%) of the 56 cases of OSCC. Tumor budding was strongly associated with lymph node metastasis (P = .001) and shorter overall survival (P = .002). The expression of Snail and Twist was correlated with lymph node metastasis (P .001 and .002, respectively) and poorer overall survival (P = .024 and .024, respectively). Tumor budding was significantly associated with the expression of Snail (P = .003) and showed a tendency toward higher expression of Twist (P = .08). Therefore, our results suggest that tumor budding is significantly associated with poor prognosis in patients with OSCC and histologically represents an EMT process in OSCC.

Approximately 20% of all salivary gland cancer patients who are treated with current treatment modalities will ultimately develop metastases. Its most common form, mucoepidermoid carcinoma (MEC) is a highly aggressive tumor with an overall 5-year survival rate of ~30%. Until now, several chemotherapeutic drugs have been tested for the treatment of salivary gland tumors, but the results have been disappointing and the drugs often cause unwanted side effects. Therefore, several recent studies have focused on the potential of alternative and/or complementary therapeutic options, including the use of silymarin. The effects of silymarin and its active component silibinin on salivary gland cancer-derived MC3 and HN22 cells and their underlying molecular mechanisms were examined using trypan blue exclusion, 4′-6-diamidino-2-phenylindole (DAPI) staining, Live/Dead, Annexin V/PI staining, mitochondrial membrane potential (ΔΨm) measurement, quantitative RT-PCR, soft agar colony formation and Western blotting analyses. We found that silymarin and silibinin dramatically increased the expression of the pro-apoptotic protein Bim in a concentration- and time-dependent manner and, concomitantly, induced apoptosis in MC3 and HN22 cells. We also found that ERK1/2 signaling inhibition successfully sensitized these cells to the apoptotic effects of silymarin and silibinin, which indicates that the ERK1/2 signaling pathway may act as an upstream regulator that modulates the silymarin/silibinin-induced Bim signaling pathway. Taken together, we conclude that ERK1/2 signaling pathway inhibition by silymarin and silibinin increases the expression of the pro-apoptotic Bcl-2 family member Bim which, subsequently, induces mitochondria-mediated apoptosis in salivary gland cancer-derived cells.

A 2-year-old boy presented with a giant mass in the masticatory space. The mass exhibited a lobulating ossification, with no attachment to the adjacent normal bone. An enucleation was performed under the tentative diagnosis of extra-articular synovial chondromatosis, benign ossifying neoplasm, non-neoplastic heterotopic ossification, or low-grade malignancy. Upon microscopic examination, the excised mass was composed of multiple osteocartilaginous areas. We hereby present detailed clinicopathological findings.

Malignant pigmented villonodular synovitis (PVNS) is an extremely rare lesion. Approximately 30 cases of malignant PVNS have been reported to date and of these, only 1 case involved the temporomandibular joint. Owing to the rarity of well-documented cases and the heterogeneous histologic features of this group of tumors, there has been some confusion regarding its diagnosis. The heterogeneous features of the sarcomatous areas contain fibrosarcomatous, myxosarcomatous, malignant fibrous histiocytomalike or giant cell tumorlike patterns. However, despite the absence of frank sarcomatous change in the histopathogy of PVNS, there have been 3 reported cases of metastatic lesions in the lung or lymph nodes. Here we present an additional case of clinically malignant PVNS with pulmonary metastasis after recurrence. A 29-year-old man presented in our hospital with a recurrent swelling and pain in the right preauricular area, where benign tumor had been previously resected. MRI demonstrated a large mass with a low signal intensity that seemed to demonstrate a ferromagnetic effect. Surgical resection of the lesion was performed and the diagnosis of PVNS with focal atypical cells was made. Unfortunately, at 30 months post surgery, a thoracic CT found a metastatic nodule in the left lower lobe of the lung.

J Oral Pathol Med (2011) 40: 243–249 Background: Multiple calcifying hyperplastic dental follicles (MCHDF) is a rare disorder that is characterized by multiple impacted teeth and enlarged dental follicles that include calcifications. The current lack of information characterizing MCHDF impedes clinicians from making prompt differential diagnoses. We describe five cases of MCHDF and analyze their clinical and histopathological features in an effort to compare MCHDF with hyperplastic dental follicles (HDF) of singly impacted teeth. Methods: Our five cases of MCHDF were examined and clinically/histologically compared with data from 50 singly impacted teeth with HDFs. Results: The five patients described in this study were all male. The pattern of impaction varied, but every second molar was impacted in all the patients. Alterations in the number of teeth, such as supernumerary or congenitally missing teeth were observed. Upon microscopic examination, most of the calcifications consisted of basophilic droplets that were fused to one another, and were surrounded by whirling spindle cells. Another type of calcification that was observed less frequently resembled woven bone. These features were consistent with three previously reported cases and observed in HDFs of 20 singly impacted teeth. While the average period of impaction and the time to reach some level of calcification in MCHDFs was shorter than in single calcifying HDFs, the calcification was more generalized in MCHDFs. Conclusions: This study indicates that MCHDF is a separate pathologic entity with exclusive male predilection and earlier calcifications, different to HDF. Further studies are needed to understand the etiology of MCHDFs to provide various options for treatment, and to clarify the mechanisms of eruption.

Objectives The purpose of this study is to report 6 cases of ameloblastic carcinoma and to analyze all published cases regarding demographic features, clinical behavior, treatment, and prognosis. Study design We reviewed our 6 cases of ameloblastic carcinoma and 98 cases previously reported in the English literature. Available follow-up data from 59 cases was analyzed. Results In the analysis of our cases, the average age of 6 patients was 61 years and there was a predilection for the maxilla and male. Five cases arose de novo, whereas 1 case was secondary type of ameloblastic carcinoma. Microscopically, our cases showed malignant cytologic features with some histologic features of ameloblastoma. Malignant cytologic features included nuclear pleomorphism, hyperchromatism, and high mitotic activity (33.3%). Necrosis and vascular invasion were also seen in 4 cases and 1 case, respectively. Immunostaining for cytokeratins 5, 14, and 18 was all positive and labeling index of Ki-67 was 13.91%. Two patients (33.3%) had a metastatic lesion in the regional lymph nodes without distant metastasis. In the analysis of the literature, the mean age was 49.2 years with a wide age range (7-91 years). The rate of occurrence was higher in males, and the most common site of occurrence was the mandible. The male-to-female ratio was 1.97:1 and the mandible-to-maxilla ratio was 1.71:1. Most cases (70%) involved the posterior portion of the jaw. The most common symptom was swelling, followed by pain, ulceration, paresthesia, and trismus. The recurrence rate in patients treated with surgical resection was 28.3%, whereas the rate in cases of conservative therapy was 92.3%. There was a significant correlation between treatment modality and recurrence (P = 0.000). Metastatic lesions were detected in 22% of patients during follow-up, and the lung was the most common area of distant metastasis. The 5- and 10-year survival rates were 72.9% and 56.8%, respectively. There was a significant decrease in the 5-year survival rate in patients with metastasis (21.4%; P = 0.0000). Conclusion Metastasis from an ameloblastic carcinoma is significantly correlated with poor prognosis. Therefore, diagnosis at an early stage and close periodic screening for metastasis are necessary to improve patient prognosis.

Keratocystic odontogenic tumor is characterized by benign intraosseous neoplasm of odontogenic origin with high recurrence rates. Conservative or aggressive management has been suggested a method of treatment. Conservative approaches have some advantages in that they avoid adverse effects on the development of involved teeth and the jaw when the patient is young, although aggressive methods, including surgical resection, can be recommended considering the nature of the neoplasm. Here we report a case of a 7-year-old patient with a recurrent keratocystic odontogenic tumor treated by marsupialization for normal development of the involved teeth.

Downregulated expression of KiSS-1 has been correlated with tumor progression, metastasis, and patient prognosis in various human malignancies. However, there is no information regarding the expression of KiSS-1 in oral squamous cell carcinoma (OSCC). Our aims were to examine KiSS-1 expression in OSCC tissue samples and cell lines and to determine its prognostic significance. KiSS-1 expression was significantly lower in lymph node (LN) metastases than in primary tumor tissues. Five of six OSCC cell lines showed absence or relatively low expression of KiSS-1. Correlations between KiSS-1 expression and clinicopathological parameters were statistically assessed. There were significant correlations between KiSS-1 expression and LN metastasis (p = 0.007), TNM stage (p = 0.024), and local recurrence (p = 0.012). In the Kaplan-Meier survival analysis, negative KiSS-1 expression significantly correlated with poorer overall survival (OS) and disease-free survival (DFS) (p = 0.000 and 0.000, respectively). Multivariate analysis using Cox regression modeling revealed that KiSS-1 expression was an independent prognostic factor for both OS and DFS (p = 0.001 and 0.000, respectively). Our findings suggested that KiSS-1 downregulation may play a role in tumor progression and metastasis of OSCC and may be a reliable biomarker for predicting clinical outcome in OSCC.

Angiogenesis is an essential process for the growth and invasion of cancer. However, it is uncertain that anti-angiogenic effects can be a major treatment strategy of oral cancer. The aim of this study was to investigate whether thalidomide and paclitaxel, which are known to be potent inhibitors of angiogenesis, have inhibitory effects on the growth of oral squamous cell carcinoma (OSCC) xenotransplanted into nude mice and whether anti-angiogenesis can be included as a major treatment strategy of oral cancer. After human OSCC cell line, KB, was subcutaneously inoculated into 32 nude mice, the volume of tumor was measured every 3 days. When the tumor mass reached 300-500 mm3, thalidomide (200 mg/kg) and paclitaxel (13 mg/kg) were administered into the animals and tumor volume change was checked. The excised tumor masses on the 30th day after administration were frozen and processed for immunohistochemistry using vascular endothelial growth factor (VEGF) and CD31, and for real-time reverse transcription-polymerase chain reaction (RT-PCR). We evaluated VEGF expression and the expression of its mRNA and CD31 for vessel density. Paclitaxel showed an inhibitory effect on the growth of transplanted human OSCC and reduced the immunohistochemical expression of VEGF and CD31 and VEGF mRNA (P

Plasmablastic lymphoma (PBL) is an aggressive diffuse large B-cell lymphoma variant that is most frequently observed in the oral cavity of human immunodeficiency virus (HIV)-infected individuals. However, in recent years, some cases have emerged in patients without HIV infection and involve other sites like stomach, lung, nasal cavity, and jejunum. We report a rare case of PBL in the maxillary anterior area of a 62-year-old man without HIV infection. The tumor cells were characterized by non-cohesive round or oval shape cells with eccentrically-placed nuclei with a prominent perinuclear halo. Immunohistochemical studies showed that the tumor cells were strongly positive for MUM1, VS38c, VMT, and κ light chain, focally positive for LCA and CD79a, and negative for CD3, CD20, CD56, λ light chain, CK-pan, EMA, and HMB45. The patient was treated with chemotherapy using cyclophosphamide, doxorubicin, vincristine, and prednisone. The lesion showed partial remission.

Objective The present study investigated the densities of mast cells and CCL-11/eotaxin-1 expression of tumor cells in Langerhans cell histiocytosis (LCH) of the jaw. Study design Eleven LCH cases arising in the jaws were selected. We evaluated eotaxin-1 expression in LCH cells via immunohistochemical staining. Toluidine blue was used to stain mast cells, with 20 periapical granuloma specimens serving as the control group. Results In all 7 patients with multifocal LCH, jaw lesions were the earliest manifestation. Toluidine blue staining revealed that most of the mast cells involved in LCH were degranulated, and the number of mast cells in LCH lesions was not significantly higher than in periapical granulomas. Upon immunohistochemical examination, all patients but one showed positivity for eotaxin-1 in LCH cells. Conclusion This preliminary study suggests that eotaxin-1 expression in LCH cells may contribute to eosinophilic infiltration. Further studies of chemokine-receptor interactions will be needed to confirm this.

The present study investigated the histopathologic and radiographic features of stage 3 bisphosphonate–associated osteonecrosis of the jaw (BAONJ) in patients who were treated with partial mandibulectomies. Bisphosphonates had been orally administered to 10 patients with osteoporosis and intravenously administered to 1 patient with metastatic carcinoma. On radiographic images, massive osteolysis and periosteal bone formations were conspicuous, and a thin mandibular cortical width was observed in 5 of 10 osteoporosis patients despite the previous use of bisphosphonate. Microscopically, the mandibulectomy specimens of the patients could be divided into 4 distinct layers. Although there were few differences in overall histologic features between BAONJ and chronic suppurative osteomyelitis, a notable number of osteoclasts were found detached from the bony trabeculae in BAONJ.

Objective Ameloblastic carcinoma combines the histologic features of ameloblastoma with cytologic atypia, regardless of whether it has metastasized. Because of its rarity, there are few immunoprofile studies of ameloblastic carcinoma and few comparative studies of ameloblastic carcinoma and ameloblastoma. In this study, we compared the expression levels of cytokeratins (CKs), matrix metalloproteinases (MMPs), and Ki-67 between ameloblastoma and ameloblastic carcinoma, and assessed the usefulness of these markers for differentiating the tumors. Study design We assessed CK7, CK14, CK18, CK19, MMP-2, MMP-9, and Ki-67 expression by immunohistochemistry in 10 cases of ameloblastoma and 7 cases of ameloblastic carcinoma and then compared expression patterns between the 2 groups. Results Immunostaining for CK14 and CK19 was diffuse and strongly positive in both tumor types, but staining for CK7 was focally positive in only 1 case of ameloblastoma and absent in all cases of ameloblastic carcinoma. However, there was a significant difference in CK18 expression between the 2 tumors ( P = .000). Whereas 80% of ameloblastomas showed negative reactivity for CK18, most cases of ameloblastic carcinomas showed a moderate to strong intensity of immunostaining for CK18. Regarding the expression of MMPs, there were significant differences in parenchymal MMP-2 and stromal MMP-9 expression between the 2 tumors. Compared to ameloblastoma, ameloblastic carcinoma showed significantly strong expression of MMP-2 in parenchymal cells ( P = .001) and MMP-9 in stromal cells ( P = .013). However, there were no differences in MMP-2 expression of stromal cells and MMP-9 expression of parenchymal cells between ameloblastoma and ameloblastic carcinoma. The mean Ki-67 labeling index (LI) of ameloblastic carcinomas was 17.21%, which was significantly higher than that of ameloblastomas (3.57%; P = .002). Conclusions The significant expression of CK18, parenchymal MMP-2, stromal MMP-9, and Ki-67 could provide useful markers for differentiating ameloblastic carcinoma from ameloblastoma.

Objective We investigated the prognostic significance of CXC chemokine receptor CXCR-4 expression in patients with oral squamous cell carcinoma (OSCC) and its relationship with matrix metalloproteinase 2 (MMP-2), MMP-9, and Ki-67 expression. Study design The CXCR-4, MMP-2, MMP-9, and Ki-67 expression was assessed immunohistochemically in 74 OSCC patients. The results were analyzed in connection with clinicopathologic factors. Results The CXCR-4 expression was positive in 45 cases and significantly correlated with lymph node metastasis (P = .037), MMP-9 expression (P = .025), and Ki-67 expression (P = .001). Univariate analysis showed that CXCR-4 expression, MMP-9 expression, Ki-67 expression, tumor size, lymph node metastasis, clinical stage, and recurrence positively correlated with prognosis. Multivariate analysis indicated that CXCR-4 expression was an independent prognostic factor for poor survival in patients with OSCC. Conclusion Expression of CXCR-4 is a significant prognostic indicator for poor survival in patients with OSCC and correlates with expression of MMP-9 and Ki-67. The inhibition of CXCR-4 represents a possible molecular approach to the treatment of OSCC.

Odontogenic keratocyst (OKC) is of particular interest because of its high recurrence rate and aggressive behavior. Two hundred fifty-six cases of OKC were reviewed for the age of the patient at diagnosis, sex of the patient, OKC location, and radiographic findings, and 132 patients with OKC were observed to estimate recurrence, which was analyzed for age, sex, location, and several histopathologic findings. OKCs occurred more frequently in men (58.6%) than in women (41.4%), and they occurred in patients within a wide age range, most commonly in patients in the third decade of life (28.9%), followed by those in the second decade (25.0%); the mean age of patients with OKC was 30.8 years. One hundred ninety-six of the 256 cases (76.5%) occurred in the mandible, and the other 60 cases (23.5%) occurred in the maxilla. The mandibular molar and the premolar areas (51.2%) were the most common sites, and the most frequent clinical manifestations at first admission were swelling, pain, or both (82.4% of total cases). Radiographic impressions included dentigerous cyst (27.3%), OKC (25.4%), primordial cyst (14.8%), ameloblastoma (11.7%), residual cyst (9.8%), and radicular cyst (3.1%). The frequency of recurrence at the follow-up examination was 58.3%. There was no significant difference in the recurrence rate on the basis of the sex of the patient. However, OKCs had a significantly higher recurrence rate in patients in the fifth decade of life than in patients in the other age groups (P = .005).Recurrence rates were significantly dependent on the sites of involvement, and OKCs in the mandibular molar region had significantly higher recurrence rates than those in other sites (P = .001). The histopathologic presence of one or more daughter cysts was significantly related to recurrence (P = .03).

In order to evaluate the significance of matrix metalloproteinases (MMPs) in predicting the metastatic potential of oral squamous cell carcinomas (SCCs), we compared MMP-2 and -9 expression in 19 metastasizing oral SCCs with that in 25 non-metastasizing cases by immunohistochemistry and gelatin zymography. Immunohistochemistry showed that increased MMP-2 expression was not significantly related to metastasis; increased MMP-9 expression found in oral SCCs was, however, statistically significant (oral SCCs with metastasis, 73.7%; those without metastasis, 36.0%; P