Differential Profile of Primary and Recurrent Ameloblastomas Among Afro-descendants and Non-Afro-descendants-a Systematic Review.

Ameloblastoma is an aggressively growing jaw tumor with high recurrent properties. Reports on global and racial distribution of ameloblastoma are variable and inconclusive. The role of race and ethnicity on ameloblastoma growth characteristics, genetic mutational profile, and recurrence is also still unclear. The primary aim of this systematic review was to assess genetic, racial, and ethnic distribution of primary and recurrent ameloblastoma from published literature. The secondary aim was to assess potential correlations between ethnicity, genetic mutation, and disparities in ameloblastoma treatment outcomes in Afro-descendants and non-Afro-descendants. Twenty-three eligible articles were selected based on preferred reporting items for systematic review and meta-analysis (PRISMA), and a total of 169 ameloblastoma cases were evaluated. Data on patient demographics, ameloblastoma growth characteristics, and genetic status were collected for quantitative analysis. Among a total of 169 ameloblastoma cases, Afro-descendant patients had higher primary and recurrent ameloblastomas at 15.5% and 4.7% respectively compared to non-Afro-descendant at 10.7% and 1.8% respectively. Additionally, BRAF V600E was positively associated with 48.8% of all ameloblastomas and strong predilection for Afro-descendants. Despite the paucity of information on genetic profile of ameloblastomas in the Afro-descendant patient cohort, this ethnic group still accounted for 2.95% of all BRAF V600E-positive tumors. These suggest that Afro-descendants are understudied regarding ameloblastoma characteristics, genetic profile, and recurrence profile. Mutational analysis of ameloblastoma tumors in Afro-descendants should be promoted.

Treatment options for advanced ameloblastoma in the era of precision medicine: A brief review.

Although complete excision is the standard of care for ameloblastoma, a subset of recurrent and/or metastasizing ameloblastomas are difficult to treat surgically. Over the past decade, several recurrent mutations in the mitogen-activated protein kinase pathway genes have been identified in ameloblastoma, based on which the efficacy of targeted therapy has been investigated. However, most of the literature has focused on BRAF V600E mutations, the most common oncogenic mutations in ameloblastoma. Hence, this study aims to review the current knowledge of targetable genetic alterations in ameloblastoma from a broader perspective. In addition, the therapeutic potential of immunotherapy for ameloblastoma will be briefly discussed in the context of tumoral PD-L1 expression and the tumor immune microenvironment.

Parathyroid carcinoma: molecular therapeutic targets.

Parathyroid carcinoma (PC) is an extremely rare malignant tumor of the parathyroid glands, accounting for less than 1% of primary hyperparathyroidism, commonly characterized by severe and unmanageable hypercalcemia, aggressive behavior, high metastatic potential, and poor prognosis. PC manifests prevalently as a sporadic tumor and only occasionally it is part of congenital syndromic and non-syndromic endocrine diseases. Molecular pathogenesis of this form of parathyroid tumor is not fully elucidated and it appears to be caused by multiple genetic and epigenetic drivers, differing among affected patients and not yet clearly stated in distinguishing PC from the benign parathyroid adenoma (PA). Congenital forms of PC have been prevalently associated with germline heterozygous loss-of-function mutations of the CDC73 tumor suppressor gene, both in the context of the hyperparathyroidism jaw-tumor syndrome (HPT-JT) and of the isolated familial hyperparathyroidism (FIPH). Currently, surgical en bloc resection of affected gland(s) and other involved structures is the elective therapy for both primary and recurrent PC. However, it usually results ineffective for advance and metastatic disease, and a high percentage of post-operative recurrence is reported. Targeted medical therapies for surgically untreatable PC, based on the molecular profile of PC samples, are, therefore, needed. The characterization of genetic and epigenetic alterations and deregulated pathways in PC samples will be of fundamental importance to tailor treatment for each patient. Here, we reviewed main findings on molecular pathogenetic aspects of PC, and the current state of the art of therapies.

Bioengineering the ameloblastoma tumour to study its effect on bone nodule formation.

Ameloblastoma is a benign, epithelial cancer of the jawbone, which causes bone resorption and disfigurement to patients affected. The interaction of ameloblastoma with its tumour stroma drives invasion and progression. We used stiff collagen matrices to engineer active bone forming stroma, to probe the interaction of ameloblastoma with its native tumour bone microenvironment. This bone-stroma was assessed by nano-CT, transmission electron microscopy (TEM), Raman spectroscopy and gene analysis. Furthermore, we investigated gene correlation between bone forming 3D bone stroma and ameloblastoma introduced 3D bone stroma. Ameloblastoma cells increased expression of MMP-2 and -9 and RANK temporally in 3D compared to 2D. Our 3D biomimetic model formed bone nodules of an average surface area of 0.1 mm2 and average height of 92.37 [Formula: see text] 7.96 µm over 21 days. We demonstrate a woven bone phenotype with distinct mineral and matrix components and increased expression of bone formation genes in our engineered bone. Introducing ameloblastoma to the bone stroma, completely inhibited bone formation, in a spatially specific manner. Multivariate gene analysis showed that ameloblastoma cells downregulate bone formation genes such as RUNX2. Through the development of a comprehensive bone stroma, we show that an ameloblastoma tumour mass prevents osteoblasts from forming new bone nodules and severely restricted the growth of existing bone nodules. We have identified potential pathways for this inhibition. More critically, we present novel findings on the interaction of stromal osteoblasts with ameloblastoma.

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.

Synovial sarcoma of the hard palate: The third case in the medical literature.

Synovial sarcoma is a high-grade soft tissue sarcoma that rarely arises in the head and neck region. It affects the parapharyngeal space and the hypopharynx most commonly and it has different presentations based on the affected site. In extremely rare occasions, it involves the hard palate such as in our case where a 24-year-old female patient presented with a mass lesion involving the left hard palate, which was identified clinically and by imaging studies. The histopathological assessment confirmed that it was a monophasic synovial sarcoma which was also confirmed with further molecular studies. The patient underwent surgical excision and postoperative radiotherapy. Her close follow up over a 6-year period that followed her curative treatment has demonstrated no evidence of disease recurrence or distant metastasis. Surgical excision is the mainstay of treatment for synovial sarcoma and adjuvant radiotherapy is advised. Long-term follow up is recommended because of the remote possibility of late recurrence of the tumor.

Risk factors and prognosis for the primary intraosseous carcinoma of the jaw.

Primary intraosseous carcinoma (PIOC) is a rare but aggressive type of odontogenic tumour arising within the jawbone. Diagnosis criteria and treatment strategy remain difficult and controversial. The present study aimed to clarify the clinicopathological features and determine prognostic factors in management of PIOC. A retrospective study of 30 patients with PIOC, treated at the Hospital of Stomatology of Sun Yat-sen University between 2009 and 2017, was conducted. Clinical, histopathological and treatment modality data were collected. Follow-up data were recorded to determine prognostic factors. There were 19 males and 11 females with a mean age of 52.3 years. The most common location of the tumour was the mandible (90%). Having a history of tooth extraction or tooth mobility was the major characteristic symptom (63.3%), jaw swelling coming in second (53.3%). Half of the patients underwent surgery alone. The estimated 2-year overall survival rate (OS) and recurrence-free survival rate (RFS) were 61.3% and 40.1%, respectively. Higher histological grade was an independent risk factor for poor OS (hazard ratio (HR) 0.233 [0.059-0.915], P=0.037), while at pN+ stage for RFS, HR=5.627 [1.199-26.409], P=0.029. Because of its rarity and intrabony site, the classification, staging and treatment guidelines for PIOC should be further studied and established.

Melanotic neuroectodermal tumour of infancy of the jaws: an analysis of diagnostic features and treatment.

The purpose of this study was to integrate the available published data on melanotic neuroectodermal tumour of infancy (MNTI) of the jaws into a comprehensive analysis of its clinical/radiological features, with emphasis on the predictive factors associated with recurrence. Eligibility criteria included publications with sufficient clinical/radiological/histological information to confirm the diagnosis. A total of 288 publications reporting 429 MNTI cases were included. MNTIs were slightly more prevalent in males and markedly more prevalent in the maxilla. Most of the lesions were asymptomatic, presenting cortical bone perforation and tooth displacement. Nine lesions were malignant, with metastasis in five cases. Enucleation was the predominant treatment (67.2%), followed by marginal (18.4%) and segmental resection (6.1%). Eighty-one of 356 lesions (22.8%) recurred. Recurrence rates were 61.5% for curettage, 25.3% for enucleation alone, 16.2% for enucleation+curettage, 20.0% for enucleation+peripheral osteotomy, 11.3% for marginal resection, 10.0% for segmental resection, 30.0% for chemotherapy, and 33.3% for radiotherapy. Enucleation and resection presented significantly lower recurrence rates in comparison to curettage. Curettage appears not to be the best form of treatment, due to its high recurrence rate. As resection (either marginal or segmental) is associated with higher morbidity, enucleation with or without complementary treatment (curettage or peripheral osteotomy) would appear to be the most indicated therapy.

Radical vs conservative treatment of intraosseous ameloblastoma: Systematic review and meta-analysis.

OBJECTIVES: The aim of the present study was to assess the outcomes of radical and conservative treatment approaches of solid/multicystic and unicystic ameloblastoma in terms of recurrence rates. MATERIAL AND METHODS: A systematic review and meta-analysis was conducted based on the PRISMA statement. Search was performed using PubMed, Embase, SCOPUS, and Web of Science for articles published from January 1969 until March 2018. Quality assessment of the selected articles was conducted using the Quality Appraisal of Case Series Studies Checklist. The meta-analysis was performed using the MedCalc program. RESULTS: The search strategy yielded 6,984 articles; 20 studies met the eligibility criteria and were included in the meta-analysis. The pooled recurrence rate of solid/multicystic ameloblastomas following radical treatment was 8%, while conservative treatment caused recurrences in 41%. For unicystic ameloblastomas, these values were 3% and 21%, respectively. The risk of recurrences in both types of ameloblastomas following radical treatment was lower than following conservative treatment. CONCLUSIONS: The present study showed statistically significant differences in recurrence favoring radical treatment for both unicystic and solid/multicystic ameloblastoma. The solid/multicystic type showed more recurrences than the unicystic type. Unfortunately, since only retrospective studies were available, the evidence is less strong as wished for.

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.

Craniofacial disorders.

The complexity of the craniofacial patient mandates the cooperation of a multidisciplinary team that can systematically evaluate each individual and ensure that a protocol-driven pathway is undertaken for the best patient care. Oral and maxillofacial surgeons contribute to surgical care in this setting with specific knowledge of growth and development of the face. This enables optimum timing for early skeletal correction where appropriate, and definitive surgery following the cessation of growth to maximize function and aesthetics. This chapter will describe the major principles in managing patients with specific craniofacial anomalies and provide examples of the outcomes possible.

Ameloblastoma-Clinical, radiological, and therapeutic findings.

Ameloblastoma are the most common odontogenic tumor. As they usually do not form metastasis, they are considered as benign tumors with a locally invasive growth pattern and destruction of the jaws and the surrounding tissue (Oral Diseases, 23, 2017, 199). This article focuses on clinical, radiological, and therapeutic findings, which may influence diagnosis and treatment of ameloblastoma in the future.

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.

Management of familial hyperparathyroidism syndromes: MEN1, MEN2, MEN4, HPT-Jaw tumour, Familial isolated hyperparathyroidism, FHH, and neonatal severe hyperparathyroidism.

While primary hyperparathyroidism (PHPT) generally represents a common endocrine disorder, being the more frequent cause of hypercalcemia in outpatients, familial forms of PHPT (FPHPT) account for no more than 2-5% of the overall PHPT. In the last decades, many technical progresses in both molecular and biochemical-radiological evaluation have been made, and substantial advancements in understanding these disorders have been reached. Differences both in the pathogenesis and clinical presentation exist among the various hyperparathyroid syndromic forms, and, since FPHPT is frequently associated to other endocrine, proliferative and/or functional disorders, as also non-endocrine tumours, with varying clinical spectrum of occurrence in each syndrome, its early clinically detection for appropriately preventing complications (i.e. kidney and bone disorders) is strictly advised. In this review, the clinical-biochemical features and diagnostic procedures of each FPHPT form will be summarized and a general overview on surgical and pharmacological approaches to FPHPT has been also considered.

Ameloblastic fibroma and ameloblastic fibrosarcoma: A systematic review.

PURPOSE: To integrate the available data published to date on ameloblastic fibromas (AF) and ameloblastic fibrosarcomas (AFS) into a comprehensive analysis of their clinical/radiological features. METHODS: An electronic search was undertaken in July 2017. Eligibility criteria included publications having enough clinical, radiological and histological information to confirm a definite diagnosis. RESULTS: A total of 244 publications (279 central AF tumours, 10 peripheral AF, 103 AFS) were included. AF and AFS differed significantly with regard to the occurrence of patients' mean age, bone expansion, cortical bone perforation and lesion size. Recurrence rates were as follows: central AF (19.2%), peripheral AF (12.5%), AFS (all lesions, 35%), primary (de novo) AFS (28.8%) and secondary AFS (occurring after an AF, 50%). Larger lesions and older patients were more often treated by surgical resections for central AF. Segmental resection resulted in the lowest rate of recurrence for most of the lesion types. AFS treated by segmental resection had a 70.5% lower probability to recur (OR 0.295; P = .049) than marginal resection; 21.3% of the AFS patients died due to complications related to the lesion. CONCLUSIONS: Very long follow-up is recommended for AF lesions, due to the risk of recurrence and malignant change into AFS. Segmental resection is the most recommended therapy for AFS.

Clinicopathological characteristics of desmoplastic ameloblastoma: A systematic review.

The aim of the present review was to systematically present the clinicopathological data of desmoplastic ameloblastoma (DA) from articles published in the literature. A comprehensive search of the databases (PubMed, Medline, SCOPUS, Web of Science, and Google Scholar) for published articles on DA was conducted. A total of 238 cases were identified and analyzed from 76 published papers. DA showed a slight male predilection (male: female=1.07:1) with a predominance in the fourth and fifth decades of life. Mandibular involvement (52.55%) was most commonly seen with a marked tendency for the anterior region (mandible: 40.9%, maxilla: 48.07%). The size of the lesion ranged from .5 cm to 20.4 cm, with the majority of cases measuring more than 3 cm in size (53.84%). Radiologically, most of the lesions presented mixed radiolucency and radiopacity (62%), and root resorption was observed in only seven cases. The majority of the lesions showed ill-defined margins upon radiographic examination (65.78%). Most of the cases were treated with resection (78.57%), and five of the 10 recurrent cases were treated by enucleation/curettage. DA is characterized by the unique presentation of clinicopathological parameters. It is not possible to comment on its aggressive/recurrent nature and best treatment modality due to inadequate follow-up data.