Long noncoding RNA KCNQ1OT1 promotes proliferation, migration, and invasion in maxillary sinus squamous cell carcinoma by regulating miR-204/EphA7 axis.

Long noncoding RNAs have been demonstrated to contribute to the development and progression of various cancers. However, the underlying regulatory mechanisms of KCNQ1OT1 in tumorigenesis of maxillary sinus squamous cell carcinoma (MSSCC) remain unknown. Herein, we found that KCNQ1OT1 expression was markedly upregulated in MSSCC tissues and MSSCC cell line (IMC-3) by using quantitative reverse transcription-polymerase chain reaction. Loss-of-function experiments revealed that the deletion of KCNQ1OT1 inhibited cell proliferation, migration, and invasion. Moreover, we confirmed KCNQ1OT1 could directly interact with miR-204 by bioinformatic prediction and dual luciferase assay, and miR-204 inhibitor markedly reversed MSSCC tumor phenotypes induced by shKCNQ1OT1. Finally, we demonstrated that KCNQ1OT1/miR-204 facilitated MSSCC progression by regulating Eph receptor A7 (EphA7). Taken together, these results revealed a novel regulatory mechanism KCNQ1OT1/miR-204/EphA7 axis, which could provide a new understanding of MSSCC tumorigenesis and develop potential targets for MSSCC therapy.

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.

Suppression of SESN1 reduces cisplatin and hyperthermia resistance through increasing reactive oxygen species (ROS) in human maxillary cancer cells.

INTRODUCTION: Cisplatin is used as a standard chemotherapeutic agent for head and neck cancer treatment. However, some head and neck cancers have cisplatin resistance, leading to difficulty in treatment and poor prognosis. Overcoming cisplatin resistance remains an important strategy to improve prognoses for head and neck cancer patients. OBJECTIVE: Elucidation of the mechanisms underlying cisplatin resistance can suggest novel targets to enhance the anticancer effects of cisplatin for treating head and neck cancers. MATERIAL AND METHODS: We used a cisplatin-resistant human maxillary cancer cell line, IMC-3CR to analyse the cisplatin resistance mechanisms. Cisplatin-induced genes were analysed in IMC-3CR cells using PCR array. Among the genes with expression increased by cisplatin, we specifically examined SESN1. SESN family reportedly regenerates peroxiredoxin and suppresses oxidative DNA injury by reactive oxygen species (ROS), which can be induced by chemotherapeutic agents such as cisplatin, radiation, and hyperthermia. The function of SESN1 in cisplatin resistance and ROS generation were analysed using specific RNAi. RESULTS: Results show that SESN1 was induced by cisplatin treatment in IMC-3CR cells. Suppression of SESN1 by RNAi induced apoptosis and reduced cell viability through enhancement of ROS after cisplatin treatment. Moreover, suppression of SESN1 enhanced the cell-killing effects of hyperthermia with increased ROS, but did not affect the cell-killing effects of radiation. CONCLUSIONS: This study demonstrated the participation of SESN1 in cisplatin and hyperthermia resistance of human head and neck cancers. SESN1 is a novel molecular target to overcome cisplatin resistance and hyperthermia resistance and improve head and neck cancer treatment.

Leiomyosarcoma of maxilla: a case report with review of literature.

OBJECTIVE: One challenging feature of head and neck pathology is that a dizzying array of spindle cell lesions occurs here which ranges all the way from reactive, very aggressive forms to malignant lesions. Leiomyosarcoma is one such malignant tumour of mesenchymal origin exhibiting smooth muscle differentiation; presenting generally nonspecific signs and symptoms. Here we present a case of leiomyosarcoma in a 21 year old female patient associated with single reddish pink swelling present in the posterior right maxillary tuberosity region with moderate facial asymmetry. On histopathological analysis, all the classic features were noted and diagnosis of a spindle cell neoplasm was made without any obscurity. There are many lesions like rhabdomyosarcoma, fibrosarcoma, liposarcoma, multiple peripheral nerve sheath tumour, angiosarcomas, melanomas, kaposi sarcoma, solitary fibrous tumors, etc., which mimic leiomyosarcoma clinically and histopathologically and therefore immunohistochemical staining with specific markers plays a vital role in arriving at a conclusive diagnosis.

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.

Liver heterotopia in the head of a patient with osteosarcoma of the maxilla. A paracrine tumor-induced hepatogenesis?

Heterotopia of liver tissue is uncommon. It has been reported at various sites, more frequently near the orthotopic liver, including gallbladder, hepatic ligaments, omentum, and retroperitoneum, rarely within the diaphragm and the thoracic cavity, and never within the head. We report here a 22-year-old patient surgically treated for a maxillary osteosarcoma in which microscopic liver tissue islands were incidentally detected in the respiratory mucosa of the surgical margin. The islands comprised well-differentiated HepPar-1-positive hepatocytes and were surrounded by cytokeratin-7- and cytokeratin-19-positive bile duct-like structures. This case, which is unique in the medical literature, may suggest an inductive paracrine effect of the osteosarcoma cells by secretion of factors promoting hepatocyte specification of primitive endodermal progenitors and subsequent liver morphogenesis.

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.

Clinicopathological features of melanotic neuroectodermal tumor of infancy: Report of two cases.

Melanotic neuroectodermal tumor of infancy (MNTI) is an extremely rare, pigmented neoplastic entity of neural crest origin. Histological and immunohistochemical profiles indicate the presence of two components, small rounded neuroblast-like cellular areas and areas with large melanin-containing cells which consist of combination of neural, melanocytic, and epithelial cell types. Here we present two interesting cases of infants with MNTI which have different clinicopathological features. The first case is a 3-month-old female with rapidly growing MNTI involving the lacrimal sac and inferior wall of the orbital cavity, treated with total maxillectomy without orbital exenteration followed by chemotherapy. The second case is a 7-month-old male with slow-growing maxillary MNTI treated with complete surgical excision. In the female patient, histological findings revealed a predominance of neuroblast-like cellular areas and a high Ki67 index indicating rapid cellular proliferation. In the male patient however, large melanin-containing cells were dominant in this slow-growing tumor. These findings support the presence of two different types of MNTI, rapid-growing and slow-growing types, determined by the component of neuroblast-like cellular areas.

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.

BRAFV600E Mutation in Melanotic Neuroectodermal Tumor of Infancy: Toward Personalized Medicine?

The melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm that primarily affects the maxilla of infants during their first year of life. Complete resection is the conventional treatment and recurrence rates vary from 10% to 60%. The recurrent tumors grow more aggressively and can invade other anatomic structures, such as the nasal cavity, the orbit, and the skull base. The aggressive behavior of MNTIs may require radical resection, which may not be possible in some cases because of its rapid and invading growth together with invasion of vital structures. In these situations, adjunct radiotherapy or chemotherapy has been used. However, as there are no conclusive data regarding the molecular profile of this tumor, currently there is no targeted therapy that may be used in the treatment of selected aggressive cases. On the basis of MNTI similarities with melanomas, such as derivation from the neural crest cells and presence of large melanin-containing cells, we hypothesized that MNTIs also may harbor the BRAFV600E oncogenic mutation. We show for the first time that this important pediatric tumor may harbor the oncogenic BRAFV600E mutation, providing the first insights to their personalized treatment.

Pigmented ameloblastic fibro-odontoma: clinical, histological, and immunohistochemical profile.

Ameloblastic fibro-odontoma (AFO) is a slow-growing, expansive, benign odontogenic tumor, composed of ameloblastic epithelium embedded in an ectomesenchymal stroma resembling dental papilla, containing hard dental tissue in variable degrees of maturation, including enamel, dentin, and sometimes cementum. AFO typically affects the posterior mandible, causing bony expansion. We report a case of pigmented AFO in a 5-year-old boy, comprising clinical and histological features illustrated by immunohistochemistry using a large panel of antibodies, polarized light microscopy and scanning electron microscopy.

Tumor of the maxilla-odontogenic or glandular? A diagnostic challenge and the role of immunohistochemical markers.

Today's practice in medicine has reached remarkable change mainly due to the advances in the field. Odontogenic tumors represent a spectrum of lesions ranging from hamartomas to benign and malignant neoplasms. Rarely, odontogenic tumors pose a challenge due to varied histological features. But appropriate and accurate diagnosis is crucial for further treatment and follow-up as these have an influence on the prognosis. In such situations, immunohistochemical. (IHC) markers play a significant role in the differentiating various lesions. Within its palette of histology, there are multiple histopathological presentations, many a times these features come in an intermixed pattern simulating different origin. We here, report such a case presented in a 70-year-old female came with a complaint of swelling in the posterior maxilla. The microscopic findings were indicative of a benign neoplasm. To know the nature of the lesion and arrive at a diagnosis, many IHC markers were used. Based on all these findings, a final diagnosis of unicystic ameloblastoma was arrived.

Sclerosing rhabdomyosarcoma: report of a case arising in the head and neck of an adult and review of the literature.

Sclerosing rhabdomyosarcoma is a unique rhabdomyosarcoma variant, characterized by a prominent hyalinizing matrix. A notable pitfall is the potential for the unusual matrix and often pseudovascular growth pattern of this lesion to lead to confusion with other sarcoma types, including osteosarcoma, chondrosarcoma, and angiosarcoma. Here we report a case of sclerosing rhabdomyosarcoma arising in a 40-year old male. The tumor was centered in the pterygomaxillary fossa with extensive infiltration into adjacent structures. Fine needle aspiration yielded a preliminary diagnosis of high-grade pleomorphic undifferentiated sarcoma, for which he received neoadjuvant chemotherapy and surgical resection. Microscopic examination showed a malignant spindled to round cell neoplasm with prominent osteoid-like, hyaline stroma. Focal rhabdomyoblastic differentiation and diffuse immunoreactivity for desmin and myogenin aided in diagnosis. Nineteen months status post primary resection, the patient expired with multiple lung and bony metastases. Among 39 cases reported thus far (including the present case), there is a broad age range (0.3-79 years), with an average age at presentation of 27 years. The most commonly involved sites are the extremities (n = 19) and head and neck (n = 15). Most cases have been treated by resection, often combined with radiation and/or chemotherapy. Out of 31 cases with follow-up information provided, 6 patients developed local recurrence, 7 patients developed regional or distant metastasis, and 5 patients died of disease. Herein we discuss the ongoing controversy regarding how sclerosing rhabdomyosarcoma might best fit into existing rhabdomyosarcoma classification schemes, based upon current clinicopathologic and molecular genetic evidence.

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.

Immunohistochemical expression of thymosin ß4 in ameloblastomas and odontomas.

Ameloblastoma is regarded to be a benign odontogenic tumor, but it is destructive, locally invasive and presents a high rate of recurrence. Thymosin ß4 (Tß4) is closely associated with tooth germ development. Tß4 also plays a role in malignant progression and invasion. However, little is known about the function of Tß4 in odontogenic tumors. Thus, we investigated Tß4 expression in ameloblastomas and compared it with odontomas. We immunohistochemically evaluated the expression of Tß4, ameloblastin (AMBN), amelogenin (AMEL) and enamelin (ENAM) in 57 samples of ameloblastomas from 40 patients, and also assessed the expression of these molecules in 11 cases of odontomas, two of ameloblastic fibro-odontomas and one of tooth germ-like structures without the formation of enamel and dentin. Tß4 signals were observed in almost all of the ameloblastomas. The signals were observed in both peripheral columnar cells and central polyhedral/angular cells. Similar findings were observed in tooth germ-like structures, and in the ameloblastomatous nests in the ameloblastic fibro-odontomas. These samples had negative results for AMBN, AMEL and ENAM. Meanwhile, Tß4 signals were not seen in the odontomas, although immunolabeling for AMBN, AMEL and ENAM was observed in the enamel matrix and in some ameloblasts. Ectomesenhymal regions in the odontomas were negative for staining with the antibodies for AMBN, AMEL and ENAM. These results suggest that Tß4 could be associated with morphogenesis and tumor invasion in the ameloblastoma, and that Tß4 may play a role in the behavior of ameloblastoma.

Nasolabial cyst: case report with respect to immunohistochemical findings.

The nasolabial cyst is a rare, usually unilateral lesion arising in the soft tissues adjacent to the alveolar process of the anterior maxilla, above the apices of frontal teeth and below the alar base. The typical clinical features of nasolabial cysts are: swelling between the upper lip and nasal aperture caused by a smooth and fluctuant, well defined space-occupying lesion, elevation of the nasal ala and obliteration of the nasolabial fold. This report describes some clinical, radiological and morphological findings in a nasolabial cyst. The cyst was lined up with bilayered epithelium showing scattered goblet cells. The immunohistochemical analysis revealed that the basaloid epithelial cells exhibited nuclear positive reactions for p63. The proliferative activity of the epithelial cells was low (<5%). Reaction for podoplanin was only discretely positive in basal cells within the non-inflamed portions but was enhanced in areas with inflammatory changes of the cyst wall. Cytokeratin subtyping showed a distinct expression of intermediate filaments in the nasolabial cyst. Nasolabial cysts are developmental cysts that can be cured by adequate surgical techniques. The expression pattern of podoplanin in this entity points to an association of this protein expression with inflammatory reactions to the cyst.

Intraosseous fibrosarcoma of maxilla in an HIV patient.

Fibrosarcoma is a malignant mesenchymal neoplasm of fibroblasts that rarely affects the oral cavity and can cause local recurrences or metastasis. Fibrosarcomas account for 15% of all soft tissue sarcomas, which represent only 1% of all malignant tumors of the head and neck region. The clinical behavior of the fibrosarcoma is characterized by a high local recurrence rate, and low incidence of loco regional lymph node and/or distant hematogenous metastasis. The etiology for fibrosarcoma has no definite cause but is thought to occur from preexisting lesions or in previously irradiated areas of bone lesions. Immunosuppression associated with HIV infection and acquired immune deficiency syndrome (AIDS) has been consistently linked to various cancers, including Kaposi's sarcoma, non-Hodgkin's lymphoma, and invasive cervical cancer. Rare neoplasms like Hodgkin's disease, anal cancer, leukemia, basal cell carcinoma, and squamous cell carcinoma have also been demonstrated. This paper presents one such a rare incidence of an intraosseous fibrosarcoma occurring in an HIV-positive patient.

Low-grade myofibroblastic sarcoma of the maxillary region in a dog.

A subcutaneous tumour was identified in the maxillary region of a 14-year-old mixed breed dog. This tumour had grown rapidly over 2 weeks. Microscopically, the tumour had ill-defined borders and was composed of bundles and whorls of atypical spindle cells accompanied by abundant collagen fibres. Immunohistochemically, neoplastic cells were immunoreactive for vimentin, α-smooth muscle actin and calponin and negative for S100 protein, von Willebrand factor, desmin and smoothelin. These results suggested that the neoplastic cells were derived from myofibroblasts and that the tumour was a low-grade myofibroblastic sarcoma.

Central odontogenic fibroma: new findings and report of a multicentric collaborative study.

OBJECTIVE: The aim of this study was to describe the clinicopathologic and immunohistochemical characteristics of 14 cases of central odontogenic fibroma (COF), and the ultrastructural features of 2 of them. STUDY DESIGN: Collaborative retrospective study based on the records of 4 oral pathology diagnostic services in Latin America based on the current World Health Organization classification. RESULTS: There were 7 male and 7 female patients (mean age 31.8 years). Eight tumors occurred in the maxilla and 6 in the mandible. Thirteen cases were epithelium-rich and 1 epithelium-poor COF. Three were classified as hybrid COF with giant cell lesion. Mean size of the hybrid lesions were larger than pure COF (3.8 vs. 2.4 cm). Odontogenic epithelial islands were immunoreactive for cytokeratin (CK) AE1/AE3, CK5, CK14, CK19, and 34BE12 and negative for CK1 and CK18. Langerhans cells positive for S-100 and CD1a were found within the epithelial islands in 6/6 tested cases. CD68 was expressed in the giant cells of the hybrid lesions and in a few mononuclear cells of 2 cases of COF. Ki-67 index was <1% in all cases. In 6 tumors (42.8%), there were small globular eosinophilic droplets within the epithelial islands, which were positive for collagen type IV, and 9/13 cases (69.2%) were focally positive for smooth muscle actin. In addition to fibroblasts, myofibroblastic differentiation was found in the 2 cases studied ultrastructurally. CONCLUSIONS: Immunohistochemistry was useful to confirm the presence of epithelium and to exclude other central fibrous tumors. COF also contains a variable number of mast cells, Langerhans cells, and myofibroblasts, and further studies are needed to better understand the participation of these cells in COF histogenesis.