Macroglossia in endocrine and metabolic disorders: current evidence, perspectives and challenges.

Macroglossia is an uncommon condition characterized by chronic, painless and abnormal enlargement of the tongue. A multitude of medical conditions can cause macroglossia. Major endocrine and metabolic disorders associated with macroglossia include genetic, congenital and acquired conditions, such as mucopolysaccharidoses; acquired and congenital hypothyroidism and myxedema; transient neonatal diabetes mellitus; acromegaly and amyloidosis. Macroglossia is often associated (~57-60%) with all types of mucopolysaccharidoses, particularly type I (Hurler syndrome) and type II (Hunter syndrome), being a prominent feature of the disorder. It may also occur in patients with acquired and congenital hypothyroidism and myxedema, being a common sign of congenital hypothyroidism with an approximate prevalence of 12-25% at the time of diagnosis. Macroglossia is a predominant oral finding in subjects with transient neonatal diabetes mellitus (~44%), acromegaly (54-69%) and amyloidosis (10-25%), particularly AL amyloidosis (20-40%) whereas is considered a hallmark of the disease. Secondary to macroglossia various disturbances may occur, such as difficulty in speech or eating, orthodontic anomalies or even more serious conditions including upper airway obstruction or obstructive sleep apnea. Until now, no comprehensive review has been conducted focusing on macroglossia in endocrine and metabolic disorders. The objective of this review is to summarize literature on the etiology and epidemiology of macroglossia in major endocrine and metabolic disorders. It highlights key aspects such as pathophysiology, clinical presentation, diagnostic evaluation, management and prognosis of macroglossia in the context of endocrine and metabolic disorders.

Survival Rates of Short Dental Implants (≤6 mm) Used as an Alternative to Longer (>6 mm) Implants for the Rehabilitation of Posterior Partial Edentulism: A Systematic Review of RCTs.

Short dental implants have been proposed as an alternative treatment option to bone regeneration procedures for the rehabilitation of resorbed alveolar ridges. The aim of this paper was to systematically review randomized controlled trials (RCTs) comparing short implants (≤6 mm) and longer implants (>6 mm) in atrophic alveolar ridges in terms of implant survival rates, peri-implant marginal bone loss (MBL), prevalence of peri-implantitis and technical complications. A thorough electronic search was performed until September 2023. RCTs with follow-up of at least 1-year post-loading comparing short implants with rough surfaces to longer implants in the posterior jaws of systemically and periodontally healthy, partially edentulous adults were considered. Studies with incomplete information on the number of patients, follow-up or definition of "short implants" were excluded. The revised Cochrane risk-of-bias tool for randomized trials was used for Risk of bias assessment. Fixed-effects meta-analysis of the selected studies was applied to compare the outcome variables. Random-effect meta-analysis was performed, on the basis of within-study comparisons. In total, 16 articles were selected for meta-analysis and incorporated 408 short implants and 475 longer implants inserted in 317 and 388 patients, respectively. The survival rates of longer implants in pristine or augmented bone were significantly increased compared to short implants (95%CI: 2-5%, p < 0.001). Standard-length implants displayed increased, although non-statistically significant MBL (95%CI: -0.17-0.04, p > 0.05), and prevalence of peri-implantitis (95%CI: 0-5%, p > 0.05). No statistically significant differences were observed between short and long implants in terms of technical complications (implant-level 95%CI: -4-6%, p > 0.05). Short implants represent a promising alternative treatment option for the rehabilitation of posterior jaws to avoid additional bone augmentation procedures. Nonetheless, they should be selected cautiously due to a potentially limited survival rate compared to longer implants. A major limitation of this study is the variability in the included studies regarding sample size, patient profile, type of bone, loading protocol, definition of peri-implantitis, among others. This study received no external funding. The study protocol was registered in PROSPERO (CRD42023485514).

Lymphoepithelial Subtype of Oral Squamous Cell Carcinoma: Report of an EBV-Negative Case and Literature Review.

Lymphoepithelial carcinoma (LEC) of the oral mucosa is a rare histopathologic subtype of squamous cell carcinoma (SCC), which shares morphologic similarities with nasopharyngeal carcinoma (NPC), non-keratinizing undifferentiated subtype. The admixture of neoplastic epithelial tumor cells and a dense lymphoplasmacytic infiltrate makes microscopic diagnosis challenging. LEC etiopathogenesis has been variably associated with Epstein-Barr virus (EBV) infection, depending on the specific anatomic location and racial predilection, with a higher incidence in endemic populations. Although described in several subsites of the head and neck region, including the major salivary glands, the oral mucosa is considered an infrequent location for LEC development, deriving either from minor salivary glands (MSGs) or the surface epithelium. Herein, we report a rare case of an EBV-negative LEC arising from the oral surface epithelium, presenting as gingival swelling, and review the pertinent English-language literature, which revealed only 26 previously reported oral LECs. Our case is only the fourth oral LEC originating from the surface epithelium and the first one to affect the gingiva.

Impact of Epigenetic Alterations in the Development of Oral Diseases.

BACKGROUND: Epigenetic mechanisms alter gene expression and regulate vital cellular processes that contribute to the onset and progression of major dental diseases. Their reversible character may prove beneficial for therapeutic targeting. This review aims to provide an update on the main epigenetic changes that contribute to the pathogenesis of Oral Squamous Cell Carcinoma (OSCC), pulpitis and periodontitis as well as dental caries and congenital orofacial malformations, in an effort to identify potential therapeutic targets. METHODS: We undertook a structured search of bibliographic databases (PubMed and MEDLINE) for peer-reviewed epigenetic research studies focused on oral diseases in the last ten years. A qualitative content analysis was performed in screened papers and a critical discussion of main findings is provided. RESULTS: Several epigenetic modifications have been associated with OSCC pathogenesis, including promoter methylation of genes involved in DNA repair, cell cycle regulation and proliferation leading to malignant transformation. Additionally, epigenetic inactivation of tumor suppressor genes, overexpression of histone chaperones and several microRNAs are implicated in OSCC aggressiveness. Changes in the methylation patterns of IFN-γ and trimethylation of histone Η3Κ27 have been detected in pulpitis, along with an aberrant expression of several microRNAs, mainly affecting cytokine production. Chronic periodontal disease has been associated with modifications in the methylation patterns of Toll-Like Receptor 2, Prostaglandin synthase 2, E-cadherin and some inflammatory cytokines, along with the overexpression of miR-146a and miR155. Furthermore, DNA methylation was found to regulate amelogenesis and has been implicated in the pathogenesis of dental caries as well as in several congenital orofacial malformations. CONCLUSION: Strong evidence indicates that epigenetic changes participate in the pathogenesis of oral diseases and epigenetic targeting may be considered as a complementary therapeutic scheme to the current management of oral health.

Could the endocrine disruptor bisphenol-A be implicated in the pathogenesis of oral and oropharyngeal cancer? Metabolic considerations and future directions.

Bisphenol-A (BPA), a prototype endocrine disrupting molecule, has been associated with many disease entities such as diabetes mellitus, obesity, polycystic ovarian disease, cardiovascular disease, reproductive and neurodevelopmental disorders. BPA has also been associated mainly with not only hormone sensitive cancers such as breast, prostate, endometrial, ovarian, testicular and thyroid cancers but also non-hormonal sensitive cancers such as cervical and lung cancers, osteosarcoma and meningioma. Recent research has investigated the sources of contamination which are responsible for higher BPA concentrations in the oral cavity and oropharyngeal space, representing the first site of BPA exposure after ingestion. Besides growing awareness and case registration, the incidence and prevalence of oral (OC) and oropharyngeal cancer (OPC) have increased during the last decades correlating with the increased production of BPA worldwide. So far, no study in the medical literature has explored the association of BPA with OC and OPC. BPA may be linked to the etiopathogenesis of OC and OPC through a multitude of mechanisms encompassing and interconnecting genetic, epigenetic, inflammatory, immune, metabolic, hormonal and oxidative stress alterations as well as modulation of oral microbiome. Hence, it is not possible to rule out a potential role of BPA exposure in oral and oropharyngeal tissue carcinogenesis, especially knowing its potential to participate in other non-hormonal sensitive malignancies and to deregulate signaling pathways implicated in OC and OPC. This perspective aims at outlining evidence and proposing for the first time a potential link between BPA with OC and OPC, the most frequent subtypes of head and neck malignancies.