Classificatory updates in verrucous and cuniculatum carcinomas:Insights from the 5^(th) edition of WHO-IARC head and neck tumor classification

The International Agency for Research on Cancer(IARC)and World Health Organization(WHO)collaboratively produce the'WHO Blue Books'essential tools standardizing the diagnostic process for human cancers.Regular updates in this classification accommodate emerging molecular discoveries,advances in immunohistochemical techniques,and evolving clinical insights.The 5th edition of the WHO/IARC classification of head and neck tumors refines the'Oral Cavity and Mobile Tongue'chapter,including sections for non-neoplastic lesions,epithelial tumors,and tumors of uncertain histogenesis.Notably,the epithelial tumors section is rearranged by tumor behavior,starting with benign squamous papillomas and progressing through potentially malignant oral disorders to oral squamous cell carcinoma(OSCC).The section on OSCC reflects recent information on epidemiology,pathogenesis,and histological prognostic factors.Noteworthy is the specific categorization of verrucous carcinoma(VC)and carcinoma cuniculatum(CC),both associated with the oral cavity and distinct in clinical and histologic characteristics.This classification adjustment emphasizes the oral cavity as their predominant site in the head and neck.Designating specific sections for VC and CC aims to provide comprehensive insights into these unique subtypes,elucidating their clinical features,distinct histological characteristics,prevalence,significance,and clinical relevance.By categorizing these subtypes into specific sections,the 5th edition of the WHO classification aims to provide a more nuanced and detailed account,enhancing our understanding of these specific variants within the broader spectrum of head and neck tumors.

Current concepts in ameloblastoma-targeted therapies in B-raf proto-oncogene serine/threonine kinase V600E mutation: Systematic review

BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in the progression of these tumors have been identified.B-raf proto-oncogene serine/threonine kinase(BRAF)is a protein involved in the behavior of ameloblastomas,and it is related to many cell mechanisms.BRAF gene mutations have been identified in ameloblastomas,of which the BRAF V600E(valine substituted by glutamic acid at amino acid 600)mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior.Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.AIM To document the presence of BRAF V600E and additional mutations,their behavior,and targeted therapies in these tumors.METHODS An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE,Cochrane,EMBASE,and SpringerLink using the terms“ameloblastomas”,“BRAF V600E”,“additional mutations”,and“targeted therapies”.Ameloblastomas were classified according to WHO guidelines.Inclusion criteria were articles in English,published not more than 10 years ago,and studies with laboratory works related to BRAF V600E.Articles were evaluated by two independent reviewers and retrieved for full-text evaluation.The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies.Descriptive statistical analysis was performed.RESULTS Two independent reviewers,with a substantial concordance indicated by a kappa coefficient of k=0.76,evaluated a total of 19 articles that were included in this study.The analysis registered 521 conventional ameloblastomas(AM),81 unicystic ameloblastomas(UA),13 ameloblastic carcinomas(AC),three metastatic ameloblastomas(MA),and six peripheral ameloblastomas(PA),of which the histopathological type,anatomic location,laboratory tests,expression of BRAF mutation,and additional mutations were registered.The BRAF V600E mutation was found in 297 AM(57%),63 UA(77.7%),3 AC(23%),1 MA(50%),and 5 PA(83.3%).Follicular type predominated with a total of 116 cases(40%),followed by plexiform type with 63 cases(22.1%).Furthermore,both types presented additional mutations,in which alterations in JAK3 P132T,SMARCB1,PIK3CA,CTNNB1,SMO,and BRAF G606E genes were found.Four case reports were found with targeted therapy to BRAF V600E.CONCLUSION The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.

Mixed odontogenic tumors:A review of the clinicopathological and molecular features and changes in the WHO classification

BACKGROUND Ameloblastic fibromas and ameloblastic fibrosarcomas are rare odontogenic tumors,and controversy exists in the classification of cases presenting hard-tissue production:Ameloblastic fibrodentinoma(AFD)and ameloblastic fibro-odontoma(AFO).These cases are currently considered“developing odontomas”(hamartomatous lesions).AIM To analyze the clinicopathologic features of these lesions and discuss the changes in the 2017 World Health Organization classification.METHODS An electronic literature search was performed in the PubMed/MEDLINE database.An electronic search of the English language literature was performed and last updated in September 2020 in the PubMed/MEDLINE database using the following terms:“ameloblastic fibroma”,“ameloblastic fibrodentinoma”,“ameloblastic fibro-odontoma”,“ameloblastic sarcoma”,“ameloblastic fibrosarcoma”,“ameloblastic fibrodentinosarcoma”,“ameloblastic fibroodontosarcoma”and“odontogenic carcinosarcoma”.The inclusion criteria were odontogenic tumor series,case reports and systematic reviews that provided sufficient clinical,radiological and microscopic documentation to confirm the diagnosis.RESULTS The database search strategy resulted in 947 papers.Articles focusing on other topics,articles that were not in English,duplicate articles,and articles without fulfilling the inclusion criteria were excluded.Finally,96 publications were included in this review to describe and discuss the main features of the searched entities.Several aspects of AFO and AFD,such as biological behavior,age of occurrence,amount of hard tissue,and potential for malignant transformation into odontogenic sarcomas,support the neoplastic nature in most of the reported cases.Considering the clinical,radiographic,histopathological and molecular characteristics of odontogenic lesions with hard tissue production,we suggest that these types of lesions should continue to be recognized as odontogenic tumors by maintaining the classically used terms.CONCLUSION This recommendation will be relevant for future clinical,microscopic,and molecular studies to better understand the biology of these interesting odontogenic tumors.

Molecular biomarkers of cell proliferation in ameloblastomas

Cell proliferation is a vital biological process that is important for all living organisms because of its role in growth and the maintenance of tissue homeostasis.The control of this important process differs greatly among benign and malignant neoplasms,and the evaluation of cell proliferation in neoplasms has become a common tool used by pathologists to provide useful information pertaining to diagnosis,clinical behavior,and treatment.The usefulness of information regarding cell proliferation has led to numerous studies on the value of these methods for diagnosing different types of tumors and for clinical decision making.Ameloblastomas are no exception.This review discusses the use of several classical molecular proliferation markers,including Ki-67,proliferating cell nuclear antigen,cyclin D1 and DNA topoisomeraseⅡalpha,to characterize ameloblastomas and proposes the use of new proliferation markers used previously to characterize other neoplasms.The use of these biomark-ers offers valuable opportunities to evaluate the biological behavior of this type of odontogenic tumor.

Stomatological management of head and neck cancer patients treated with chemotherapy and radiotherapy

Treatment of head and neck cancer with radiotherapy and/or chemotherapy can cause oral damage.Longterm treatment can damage the salivary glands,the oral mucosa,and the maxilla,leading to altered production of saliva and to multiple infections.These lesions can be prevented,limited or avoided by thorough evaluation prior to treatment and by therapeutic followup and preventive measures.The dentist must have strong medical knowledge of the possible short-,medium-,and long-term oral complications of the cancer treatment,and must have knowledge of the protocols for oral management of cancer patients.The availability of a multidisciplinary medical team together with a dentist to attend to the patient prior to the cancer treatment,as well as close communication between team members during and after treatment,is crucial.The aim of the present study was review the stomatological management of head and neck cancer patients treated with chemotherapy and radiotherapy and summarizing current treatments,therapeutic innovation and tissue regeneration perspectives.