Making sense of giant cell lesions of the jaws (GCLJ): lessons learned from next-generation sequencing.

Next-generation sequencing has revealed mutations in several bone-related lesions and was recently used to uncover the genetic basis of giant cell lesions of the jaws (GCLJ). Consistent with their benign nature, GCLJ show a low tumor mutation burden. They also harbor somatic, heterozygous, mutually exclusive mutations in TRPV4, KRAS, or FGFR1. These signature mutations occur only in a subset of lesional cells, suggesting the existence of a 'landscaping effect', with mutant cells inducing abnormal accumulation of non-mutant cells that form the tumor mass. Osteoclast-rich lesions with histological similarities to GCLJ can occur in the jaws sporadically or in association with genetically inherited syndromes. Based on recent results, the pathogenesis of a subgroup of sporadic GCLJ seems closely related to non-ossifying fibroma of long bones, with both lesions sharing MAPK pathway-activating mutations. In this review, we extrapolate from these recent findings to contextualize GCLJ genetics and we highlight the therapeutic implications of this new information. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Solitary plasmacytoma of the jaws: therapeutical considerations and prognosis based on a case reports systematic survey / Solitary plasmacytoma of the jaws: therapeutical considerations and prognosis based on a case reports systematic survey

Abstract Introduction: Solitary plasmacytoma is a rare malignant tumor of plasma cells with no evidence of systemic proliferation. There are two known subtypes: extramedullary solitary plasmacytoma and solitary bone plasmacytoma. The etiology is still unknown. Both lesions present a risk of progression to multiple myeloma. A number of approaches have been used for treatment of solitary plasmacytoma. Objective: To carry out a systematic review of the case reports described in the literature, focusing on therapeutic and prognostic aspects. Methods: A search of clinical case reports was performed in the PubMed database using Mesh Terms related to "plasmacytoma" under the following criteria: type of study (case report), articles in English language, conducted in humans, with no publication date limits. Results: Of the 216 articles found, only 21 articles met the pre-established inclusion criteria. Conclusion: The occurrence of solitary bone plasmacytoma in the bones of the face is a rare condition prevalent between the 4th and 6th decades of life, located in the posterior region of the mandible in most cases. Histopathological examination and systemic investigation are mandatory for confirmation of diagnosis.

Resumo: Introdução: O plasmocitoma solitário é um tumor maligno raro de células plasmáticas sem evidência de proliferação sistêmica e engloba dois subtipos: plasmocitoma solitário extramedular e plasmocitoma solitário ósseo. A etiologia ainda é desconhecida. Ambas as lesões apresentam risco de progressão para mieloma múltiplo. Uma série de abordagens tem sido usada para seu tratamento. Objetivo: Realizar uma revisão sistemática da literatura com enfoque nos aspectos terapêuticos e prognósticos. Método: Realizou-se uma busca de relatos de caso clínico na base de dados PubMed com termos de busca relacionados com "plasmocitoma" sob os seguintes critérios: tipo de estudo (relato de caso), artigos na língua inglesa, estudos realizados apenas em humanos, sem limites de data de publicação. Resultados: Dos 216 artigos encontrados, apenas 21 preencheram os critérios de inclusão pré-estabelecidos. Conclusão: A ocorrência de plasmocitoma solitário ósseo nos ossos da face é uma condição rara prevalente entre a 4a e a 6a décadas de vida, localizada na região posterior de mandíbula na maioria dos casos. O exame histopatológico e a investigação sistêmica são mandatórios para confirmação do diagnóstico.

Solitary plasmacytoma of the jaws: therapeutical considerations and prognosis based on a case reports systematic survey.

INTRODUCTION: Solitary plasmacytoma is a rare malignant tumor of plasma cells with no evidence of systemic proliferation. There are two known subtypes: extramedullary solitary plasmacytoma and solitary bone plasmacytoma. The etiology is still unknown. Both lesions present a risk of progression to multiple myeloma. A number of approaches have been used for treatment of solitary plasmacytoma. OBJECTIVE: To carry out a systematic review of the case reports described in the literature, focusing on therapeutic and prognostic aspects. METHODS: A search of clinical case reports was performed in the PubMed database using Mesh Terms related to "plasmacytoma" under the following criteria: type of study (case report), articles in English language, conducted in humans, with no publication date limits. RESULTS: Of the 216 articles found, only 21 articles met the pre-established inclusion criteria. CONCLUSION: The occurrence of solitary bone plasmacytoma in the bones of the face is a rare condition prevalent between the 4th and 6th decades of life, located in the posterior region of the mandible in most cases. Histopathological examination and systemic investigation are mandatory for confirmation of diagnosis.

Prognostic importance of FGF2 and FGFR1 expression for patients affected by ameloblastoma.

BACKGROUND: Fibroblast growth factor 2 (FGF2) and FGF receptor 1 (FGFR1) have been investigated in different human neoplasms and were shown to play important roles in the pathogenesis of these diseases; however, very few are known regarding their prognostic importance in the context of ameloblastoma. Therefore, the aim of this study was to investigate whether the expression of FGF2 and FGFR1 is associated with ameloblastoma clinical behavior. METHODS: Fifty-eight cases of ameloblastoma arranged in tissue microarray were submitted to immunohistochemistry against FGF2 and FGFR1. Clinicopathological parameters regarding sex, age, tumor size, duration and location, treatment, recurrences, radiographic features, cortical disruptions, and follow-up data were obtained from patients' medical records and correlated with the molecules expression. Univariate and multivariate Cox regression analyses were used to investigate the prognostic potential of the biomarkers. RESULTS: Forty-four cases (75.9%) exhibited cytoplasmic positivity for FGF2 in central and peripheral epithelial cells, 46 of 58 (79.3%) showed FGFR1 cytoplasmic positivity predominantly in the columnar peripheral cells, and 43 cases (74.1%) were positive for both. Expression of FGF2 and FGF2 + FGFR1 was associated with tumor recurrences (P = .05). However, univariate and multivariate analyses did not demonstrate a significant influence of FGF2, FGFR1, or FGF2 + FGFR1 in the 5-year disease-free survival (DFS) rate (P = .27, P = .33, and P = .25, respectively). CONCLUSION: Cytoplasmic expression of FGF2 and FGF2 + FGFR1 is associated with ameloblastoma recurrence, but FGF2 and FGFR1 are not determinants of a lower DFS.

Clear cell odontogenic carcinoma: report of 7 new cases and systematic review of the current knowledge.

OBJECTIVE: The goal of this study is to describe 7 cases of clear cell odontogenic carcinoma among a Brazilian population and compare these data with a systematic review of the English-language literature. STUDY DESIGN: Descriptive statististics were used to compare the clinicopathologic data gathered retrospectively with those compiled from a review. Tumor sections were immunostained for Ki-67, p16, p53, and cytokeratins (CKs) 7, 8, 14, 18, and 19. Log-rank tests were performed for survival analysis. RESULTS: Most cases occurred in the posterior mandible (5/7, 71.4%), and recurrence was diagnosed in all treated patients. Metastatic disease occurred in 2 patients (28.6%). Tumors were focally positive for CKs 7, 8, 14, and 18 and diffusely positive for CK19, p53, and p16. The mean number of Ki-67-positive cells was 35.2 cells/high-power field. Our systematic review provided evidence that tumor size (P = .046), histologic pattern (P = .034), regional metastasis (P = .001), distant metastasis (P = .001), and local recurrence (P = .05) were of significant prognostic value. CONCLUSIONS: This study has contributed to improved characterization of clear cell odontogenic carcinoma, which is an aggressive odontogenic malignant neoplasm diagnosed mainly in the posterior mandible of middle-aged women and typically at an advanced stage. Radical surgical procedures remain the gold standard treatment.

Retrospective study of 25 cases of keratocystic odontogenic tumor: epidemiology and treatment.

AIM: Keratocystic odontogenic tumor (KOT) is a benign odontogenic neoplasm with locally aggressive behavior and high recurrence rates. It is associated with nevoid basal cell carcinoma syndrome which usually has a more rapid growth. The aim of the study is to report the experience of our service on diagnosis and treatment of KOT. MATERIALS AND METHODS: Twenty-five cases of KOT were diagnosed between the years of 1989 and 2006. Demographic data was collected as well as diagnose and treatment. RESULTS: Fifty-six percent were female with a mean age of 33 years old. Seventy percent occurred in mandibula and all received surgical treatment, associate or not with adjuvant therapy, such as cryotherapy and Carnoy's solution. Recidive was observed in 48% of cases with a mean period of time of 18 months. CONCLUSION: Our data analysis showed the importance of previous diagnosis before enucleation procedure and long-term follow-up for recurrence early detection. Recurrence incidence is more frequent on first year after diagnosis. CLINICAL SIGNIFICANCE: KOT is a benign tumor with local aggressive behavior and therefore its treatment must consider the high index of recidive. Reports of protocol treatment should raise new discussion to decrease recurrence rates.

Aspectos clínicos, radiográficos e terapêuticos do ameloblastoma / Clinical, radiological and therapeutcs aspects of ameloblastoma

Neste trabalho, foram avaliados 52 pacientes diagnosticados histopatologicamente com ameloblastoma na região maxilo-mandibular e tratados no Departamento de Estomatologia do Centro de Tratamento e Pesquisa do Hospital do Câncer - A. C. Camargo, no período de 1960 a 2001. Foram avaliadas as características radiográficas, clínicas, terapêuticas e taxas de recidivas. Não houve um predomínio em relação ao gênero e etnia na amostra estudada. As idades de diagnóstico da lesão variaram de 6 a 73 anos. As características radiográficas do ameloblastoma de maior incidência são de uma lesão multilocular, no ramo ascendente da mandíbula, com limites expansivos, preservando a cortical basilar. O modo de tratamento mais utilizado foi conservador: curetagem associada à crioterapia. A taxa de recidiva encontrada não foi diferente das encontradas nos tratamentos radicais dessa lesão.

Estudo clínico-patológico de ameloblastomas: análise de casos / Clinicopathologic study of ameloblastomas: analysis of cases

Analisaram-se casos de ameloblastomas diagnosticados na Disciplina de Patologia Oral da UFRN entre 1970 e 2000, objetivando correlacionar o tipo clínico, os padrões histológicos e o tratamento realizado. O tipo multicístico ocorreu em 87,25 por cento dos casos, o unicístico em 8,5 por cento e o periférico em 4,25 por cento. O aspecto radiográfico foi multilocular em 52,5 por cento dos casos e unilocular em 47,5 por cento. Os padrões histológicos predominantes foram o plexoforme (31,71 por cento) o folicular (17,07 por cento) e o desmoplásico (9,75 por cento). Os tumores com padrão plexiforme acometeram pacientes mais jovens e exibiram menor índice de recidiva do que os foliculares quando tratados por técnicas cirúrgicas conservadoras, realizadas em 77,14 por cento dos casos

Osteossarcoma maxilo-mandibular / Osteosarcoma of the jaw

O osteossarcoma é neoplastia altamente maligna que acomete, na maioria dos casos, os ossos longos. Apenas pequena porcentagem desses tumores se origina na região crânio-facial, acometendo principalmente mandíbula e maxila. Foram estudados seis casos de osteossarcomas maxilo-mandibulares, entre 1978 e 1995. Dos pacientes, quatro eram do sexo feminino e dois, do sexo masculino, com idade entre 14 e 54 anos. Mandíbula e maxila foram acometidas em igual proporção. O padrão observado nos métodos de diagnóstico por imagem (radiografia simples, tomografia computadorizada) foi de lesão osteoblástica, sendo visto apenas um caso com reação periosteal em "raios de sol". Todos os diagnósticos foram confirmados por estudo anatomopatológico. A abordagem terapêutica foi cirurgia, quimioterapia exclusiva e quimioterapia mais radioterapia. Os autores concluem que o aspecto osteoesclerótico é predominante nos osteossarcomas maxilo-mandibulares, embora o tão descrito aspecto em "raios de sol" naõ seja achado frequente.

Sarcoma osteogênico dos maxilares: estudo retrospectivo de 21 casos / Maxillary osteogenic sarcoma: a retrospective study of 21 cases

Os autores realizam um estudo de 21 casos de sarcoma osteogênico dos ossos da face tratados no Hospital A. C. Camargo, num período de 33 anos. Onze casos ocorreram na terceira e quarta décadas. O paciente mais jovem tinha 11 anos e o mais idoso 60 anos. Näo houve diferença de acometimento entre os sexos. Em umc aso a etiologia estava relacionada com trtamento radioterápico prévio e, em outro, havia associaçäo com doença de Paget. Apenas três pacientes estavam vivos em cinco anos. Näo houve correlaçäo entre o tipo histológico e o tempo de sobrevida

Sarcomas of the jaw.

A retrospective analysis is made of 61 patients with clinical and histological diagnosis of pure sarcomas of the jaw treated between 1950 and 1984. Surgery was the treatment of choice in 41 cases. Biopsy or palliative treatment were undertaken in the remaining patients. Twenty-four cases relapsed before 12 months, and 12 relapsed before 3 years. Twenty-four died before 12 months, nine before 2 years, and three after 2 years. At present there is no evidence of disease in eight patients: three out of 25 fibrosarcomas (one more than 1 year, one more than 13 years, and one more than 14 years), three out of 15 chondrosarcomas (one more than 1 year, one more than 13 years, and one more than 14 years), and two out of 15 osteosarcomas (one more than 18 years). The prognosis is gloomy. However, an early diagnosis and radical surgery contribute to an improvement in the course of the disease.