Logic and clinical significance of the new WHO classification of ameloblastoma in 2017 / 口腔疾病防治

@#A substantial revision of the classification of ameloblastoma was made by the World Health Organization (WHO) in the fourth edition of the Classification of Head and Neck Tumors in 2017, which was based on the review and summary of much clinical research data and prospective evaluation of the latest results of genetic research. The new classification is simpler and more practical. It retains two subtypes, the unicystic type and extraosseous/peripheral type, classifies the remaining types as ameloblastoma (classic), defines metastatic ameloblastoma as a benign tumor and simplifies the classification of ameloblastic carcinoma, which has important guiding significance for clinical diagnosis and treatment. Moreover, the new classification included the latest advances in the genetic research on ameloblastoma, demonstrating that the BRAF gene mutation was found in approximately 60% of ameloblastoma cases. The classification provides a new concept and direction for studying the pathogenesis of ameloblastoma, and BRAF-targeted therapy may be an emerging therapy for some ameloblastoma patients with multiple recurrence or surgical contraindications. This article analyzes the intrinsic logic of these changes via a review of the relevant literature and combination of clinical experiences to better understand the new classification. In 2017, the WHO′s new classification of ameloblastoma summarized the experience and achievements in histopathology and clinical treatment of ameloblastoma in the prior 10 years, indicating that BRAF-targeted treatment may bring new treatment options and hope for patients with recurrent or inoperable ameloblastoma.

Estudo da expressão imunohistoquímica de SO2, FGF-10 e WNT-1 em lesões odontogênicas epiteliais benignas / Study of the immunohistochemical expression of SO2, FGF-10 and WNT-1 in benign epithelial odontogenic lesions

Os dentes desenvolvem-se a partir de interações sequenciais entre o epitélio e o mesênquima derivado da crista neural em diferentes estágios de histodiferenciação e morfodiferenciação. Ao final da odontogênese, espera-se que as estruturas que participaram da formação destes tecidos desapareçam ou permaneçam quiescentes. Não é incomum que os remanescentes epiteliais da odontogênese originem lesões, como cistos e tumores odontogênicos. No desenvolvimento dentário precoce, a manutenção das células-tronco é regulada por uma série de fatores de transcrição específicos, que inclui OCT-4, SOX-2, Nanog, Stat-3 e c-Myc e diversos outros genes Homeobox e vias de transcrição (SHH, Wnt/ß-catenina, FGF, BMP) contribuem para o destino e diferenciação celular. No entanto, há a participação destes genes e vias na patogênese de vários tipos de tumores. O objetivo do presente estudo foi avaliar a imunoexpressão de SOX2, FGF-10 e Wnt-1 em uma série de casos de lesões odontogênicas e alguns espécimes de germes dentários. A amostra consistiu de 20 Ceratocistos Odontogênicos (CO), 20 Ameloblastomas sólidos (AM), 20 Tumores odontogênicos adenomatoides (TOA), 10 Tumores odontogênico epitelial calcificante (TOEC) e 05 casos de germes dentários usados comparativamente. A imunoexpressão foi avaliada de acordo com o percentual de células epiteliais imunomarcadas e intensidade de células positivas resultando na pontuação de imunomarcação total (PIT) que variou de 0 a 7. A análise da imunoexpressão da SOX2 revelou positividade na maioria dos casos das lesões estudadas. A pontuação de imunomarcação para SOX2 revelou haver diferença estatisticamente significativa entre os grupos de lesões estudadas, com maior frequência em CO e TOEC (p <0,001). Após o pareamento, observou-se diferença significativa entre AM e CO, AM e TOEC, CO e TOA, CO e TOEC e, TOA e TOEC (p <0,05). A análise da imunoexpressão da FGF-10 e Wnt-1 revelou positividade em todos os casos das lesões estudadas, mas sem diferença estatisticamente significativa entre os grupos de lesões estudadas (p = 0,628). Houve diferença significativa em relação aos escores de positividade para Wnt-1 (p <0,001) com maior frequência em CO e TOA. Após o pareamento, observou-se existir diferença estatisticamente significativa entre AM e CO, AM e TOEC, CO e TOEC e, TOA e TOEC (p <0,05). O padrão de expressão de SOX2, FGF-10 e Wnt-1, em germes dentários e nas lesões odontogênicas aqui avaliadas, confirma a participação destas vias na odontogênese e também no desenvolvimento das lesões odontogênicas (AU).

Dental development occurs from sequential interactions between the epithelium and the mesenchyme derived from the neural crest at different stages of histodifferentiation and morphodifferentiation. At the end of tooth development, the structures that participated in the formation of these tissues are expected to disappear or remain quiescent. It is not uncommon that the epithelial remnants of the tooth development originate lesions such as odontogenic cysts and tumors. In early tooth development, stem cell maintenance is regulated by specific transcription factors, which includes OCT-4, SOX-2, Nanog, Stat-3 and c-Myc and several other Homeobox genes and transcription pathways (SHH, Wnt/ß-catenin, FGF, BMP) contribute to cell fate and differentiation. However, there is involvement of these genes and pathways in the pathogenesis of several types of tumors. The aim of the present study was to evaluate the immunoexpression of SOX2, FGF-10 and Wnt-1 in a case series of odontogenic lesions and some specimens of dental germs. The sample consisted of 20 Odontogenic Keratocysts (OK), 20 solid ameloblastomas (AM), 20 adenomatoid odontogenic tumors (AOT), 10 calcifying epithelial odontogenic tumors (CEOT) and 5 dental gerns for comparison. Immunoexpression was evaluated according to the percentage of immunostained epithelial cells and intensity of the positive cells resulting in total immunostaining score (PIT) ranging from 0 to 7. The analysis of SOX2 immunoexpression revealed positivity in most cases of the lesions studied. The immunostaining score for SOX2 revealed a statistically significant difference between the groups of lesions studied, with a higher frequency in OK and CEOT (p < 0.001). After pairing, we observed a significant difference between AM and OK, AM and CEOT, OK and AOT, OK and CEOT, and AOT and CEOT (p <0.05). Analysis of the FGF-10 and Wnt-1 immunoexpression revealed positivity in all cases of the lesions studied, with no statistically significant difference between the groups of lesions studied (p = 0.628). There was a significant difference in relation to the positivity scores for Wnt-1 (p <0.001) with higher frequency in OK and AOT. After pairing, there was a statistically significant difference between AM and OK, AM and CEOT, OK and CEOT and, AOT and CEOT (p <0.05). The expression pattern of SOX2, FGF-10 and Wnt-1 in dental germs and odontogenic lesions evaluated here confirms the participation of these pathways in the tooth development as well as in the development of odontogenic lesions (AU).

Immunohistochemical analysis of human homologue of drosophila patched (PTCH) in dental follicles of impacted third molars / Análisis imunohistoquímico del homólogo humano del gen parcheado de drosofila (PTCH) en folículos dentales de terceros molares retenidos

This study investigated the immunodetection of PTCH in epithelial components of dental follicles associated with impacted third molars without radiographic signs of pathosis. One hundred and five specimens of dental follicles associated with impacted third molars with incomplete rhizogenesis (between Nolla's stage 6 and 9) were surgically removed from 56 patients. Epithelial cell proliferation was determined by using immunohistochemical labeling. Statistical analysis was performed using Fisher exact test and a level of significance of 5 percent. Of the 105 dental follicles collected, 3 were PTCH-positive. The specimens with squamous metaplasia and epithelial hyperplasia had higher rates of positivity for PTCH, as well as those with active remnants of odontogenic epithelium. This study suggests that the odontogenic cells of the dental follicle might be proliferating during the rhizogenesis, while the squamous metaplasia and hyperplasia of the epithelial lining and proliferative odontogenic epithelial rests show the differentiation potential of dental follicles.

Se investigó la inmunodetección de PTCH en los componentes epiteliales de los folículos dentales asociados a terceros molares retenidos sin signos radiográficos y morfológicos de patología. Fueron quirúrgicamente extraídos de 56 pacientes 105 muestras de folículos dentales asociadas a terceros molares retenidos con rizogénesis incompleta (entre el estadio de Nolla 6 y 9). La proliferación de células epiteliales se deteminó mediante inmunohistoquímica. El análisis estadístico se realizó mediante la prueba exacta de Fisher. De los 105 folículos dentales recogidos, 3 fueron PTCH-positivos. Las muestras con metaplasia escamosa e hiperplasia epitelial tuvieron mayores tasas de positividad para PTCH, así como aquellos con los restos de proliferación del epitélio odontogénico. En conclusión, este estudio sugiere que las células odontogénicas del folículo dental podrían estar proliferando durante la rizogénesis, mientras que la metaplasia escamosa e hiperplasia del epitelio y de restos epiteliales odontogénicos en proliferación muestran el potencial de diferenciación de los folículos dentales.