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.

A Case of Spindle Cell Squamous Cell Carcinoma Manifesting in the Mandible Following Resection of Buccal Mucosal Squamous Cell Carcinoma.

Spindle cell squamous cell carcinoma (SCSCC) represents a distinctive subtype of squamous cell carcinoma, characterized by a marked malignancy and sarcomatoid transformations predominantly comprising spindle-shaped cells. In this context, we executed a surgical resection of a buccal mucosal squamous cell carcinoma, encompassing the mandibular periosteum, for a case where buccal mucosal cancer had pervaded the mandibular gingival mucosa. Notably, in a period of one year and four months subsequent to this procedure, a spindle cell squamous cell carcinoma emerged as an intraosseous carcinoma, originating from the periosteum resection. This report delineates the occurrence of this rare pathology. The subject of this case is an 83-year-old female. She underwent a resection of a buccal mucosal squamous cell carcinoma, including the mandibular gingival periosteum, for cancer on the right buccal mucosa. The histopathological evaluation post-surgery confirmed the diagnosis of squamous cell carcinoma with clear margins. A computed tomography (CT) scan, conducted one year and four months postoperatively, disclosed a contrast-enhanced tumorous growth in the mandible. Owing to the considerable restriction in opening caused by scarring and the attendant challenges in biopsy acquisition, an expedited intraoperative diagnosis was rendered. This preliminary assessment indicated a spindle cell sarcoma, leading to a hemimandibular resection. The final histopathological diagnosis was spindle cell squamous cell carcinoma. Twelve months have elapsed since the surgical intervention, with no evidence of recurrence or metastasis observed to date.

Carcinoma primario intraóseo de mandíbula. Presentación de un caso clínico y revisión de la literatura / Intraosseous carcinoma of the mandible: a case report and review of the literature

El carcinoma primario intraóseo se describe como una neoplasia maligna que aparece únicamente en los huesos maxilares, pues deriva de los remanentes epiteliales odontogénicos. Es un tumor de muy baja incidencia que requiere el cumplimiento de unos criterios clínicos, radiológicos y anatomopatológicos para su diagnóstico. Las manifestaciones clínicas son inespecíficas, predominantemente dolor y tumefacción, por lo que suele diagnosticarse en estadio avanzado, y requiere un tratamiento radical, incluyendo cirugía y radioterapia. Presentamos el caso de un varón de 66 años con diagnóstico de carcinoma primario intraóseo de cuarto cuadrante, atendido en el Hospital Universitario Ramón y Cajal, las pruebas complementarias realizadas y el tratamiento recibido incluyendo la reconstrucción primaria con un colgajo osteomiocutáneo libre microvascularizado de peroné. (AU)

Primary intraosseous carcinoma is described as a malignant neoplasm that appears only in the maxillary bones, since it derives from odontogenic epitelial remnants. It is rare, and requires compliance with clinical, radiological and pathological criteria for its diagnosis. The clinical manifestations are non-specific, predominantly pain and swelling, which is why it is usually diagnosed in an advanced stage, and requires radical treatment including surgery and radiotherapy. A case of a 66 year old man diagnosed and treated of a primary intraosseous carcinoma of lower right quadrant at Ramon y Cajal Univeristy Hospital is reported. The complementary test performed and the treatment received, including inmediate reconstruction with a free osteocutaneous fibula flap are presented. (AU)

Carcinoma escamocelular intraóseo primario mandibular: reporte de caso / Primary intraosseous squamous cell carcinoma of the mandible: case report / Carcinoma mandibular intra-ósseio primário de células escamosas: relato do caso

El carcinoma escamocelular intraóseo primario mandibular se encuentra, de acuerdo con la clasificación de la Organización Mundial de la Salud, dentro de los carcinomas odontogénicos. Se trata de una neoplasia poco común, con una relación hombre:mujer de 3,5:1 y una mayor frecuencia de presentación entre la quinta y la sexta década de vida. Su localización más común es en la región posteroinferior mandibular, siendo localmente agresivo, con metástasis a ganglios linfáticos regionales. Debido a que su comportamiento es intraóseo y a que no presenta lesiones iniciales intraorales, su diagnóstico clínico es difícil, durando largos periodos sin que se sospeche su presencia. Confirmar su diagnóstico requiere de un estudio anatomopatológico que detecte la presencia de células epiteliales carcinomatosas intraóseas. Imagenológicamente se evidencia como una lesión quística atípica, mal definida en la mayoría de los casos, radiolúcida y con osteolisis. El tratamiento de elección, con fines curativos, es la realización de una exéresis con amplios márgenes de seguridad oncológica y una posterior cirugía reconstructiva. Se presenta en este artículo el caso de un paciente de 31 años de edad con un carcinoma escamocelular intraóseo primario de la mandíbula tipo sólido, al que se le realizó una resección mandibular derecha en bloque, seguida de cirugías reconstructivas hasta obtener un adecuado resultado funcional y estético...

The primary intraosseous squamous cell carcinoma of the mandible is classified by the World Health Organization within the odontogenic carcinomas. It is a rare disease. Epidemiologically the male: female ratio is 3,5:1. The highest incidence is in the fifth and sixth decades of life. The most affected area is the posteroinferior mandibular region. It is a locally aggressive tumor that metastasizes to regional lymph nodes. The clinical diagnosis is difficult, because their behavior is intraosseous so it can last long periods of time before the diagnosis is made. It requires a pathological study which detects the presence of intraoseus carcinomatous epithelial cells. Imaging shows a radiolucent lesion with osteolysis in the form of atypical cystic lesions poorly defined in most cases. The treatment of choice for curative purposes is to provide an excision with wide safety margins and subsequent reconstructive surgery. We present a 31 years old patient with a primary mandibular intraosseous squamous cell carcinoma (solid type), whose treatment consisted of an en bloc resection and right mandibular reconstructive surgeries to obtain an adequate functional and aesthetic result...

O carcinoma de preliminar intrabony escamocelular a mandibular está, no acordo com a classificação da organização World-wide da saúde, dentro dos carcinomas dos odontogénicos. Neoplasia é um pouco comum, com um homem da relação: mulher de 3,5:1 e uma freqüência mais grande da apresentação entre a quinta e sexta década da vida. Sua posição mais comum está na região do posteroinferior a mandibular, sendo localmente aggressive, com o metástasis ao ganglia lymphatic regional. Porque seu comportamento é intrabony e àquele não se apresentar/exposição os ferimentos iniciais intraoral, seu diagnóstico clínico é períodos longos difíceis, durando sem sua presença é suspeitado. Confirmar seu diagnóstico requer de um estudo do anatomopatológico que detecte a presença de pilhas epithelial dos carcinomatosas intrabony. Imagenológicamente é demonstrado como um ferimento atypical do quística, bad definido em a maioria dos casos, radiolúcida e com o osteolisis no formulário do L. O tratamento da eleição, com alvos dos curativos, é a realização de um exéresis com margens de segurança amplas do oncológica e uma cirurgia mais atrasada do reconstructiva. O exemplo de um paciente de 31 anos de idade com um carcinoma aparece neste artigo de preliminar intrabony escamocelular do tipo contínuo da maxila, a que um resección lhe foi feito à direita mandibular no bloco, seguido de cirurgias dos reconstructivas até obter um resultado funcional e aesthetic apropriado...