LMNA::NTRK1 and PRDX1::NTRK1 Atypical Spitz Tumor: A Report of Two Additional Cases With Histological, Immunohistochemical, and Molecular Insights.

ABSTRACT: Over the past decade, advancements in molecular biology have contributed to changes in the diagnostic classification of Spitz neoplasms, including Spitz nevi, atypical Spitz tumors, and Spitz melanomas. The recent World Health Organization classification of skin tumors identifies fusion kinases, including NTRK1, NTRK2, and NTRK3, as critical drivers of these lesions. New fusion genes have continued to expand the spectrum of known molecular alterations, particularly within the category of Spitz NTRK-rearranged lesions. We present 2 new cases of NTRK-rearranged Spitz lesions: an atypical Spitz tumor with common LMNA::NTRK1 fusion and an atypical Spitz tumor with a rare PRDX1::NTRK1 fusion. Clinical, histopathological, immunohistochemical, and molecular analyses were performed to diagnose these patients. This report adds to the growing body of knowledge on NTRK-rearranged Spitz lesions and underscores the importance of integrating molecular findings with morphological and immunohistochemical data for the accurate classification and understanding of these neoplasms.

The Impact of Cesarean Section Delivery on Intestinal Microbiota: Mechanisms, Consequences, and Perspectives-A Systematic Review.

The relationship between cesarean section (CS) delivery and intestinal microbiota is increasingly studied. CS-born infants display distinct gut microbial compositions due to the absence of maternal birth canal microorganisms. These alterations potentially link to long-term health implications like immune-related disorders and allergies. This correlation underscores the intricate connection between birth mode and the establishment of diverse intestinal microbiota. A systematic literature review was conducted on the PubMed, Scopus, and Web of Science databases by analyzing the articles and examining the intricate interactions between CS delivery and the infant's intestinal microbiota. The analysis, based on a wide-ranging selection of studies, elucidates the multifaceted dynamics involved in CS-associated shifts in the establishment of fetal microbiota. We also explore the potential ramifications of these microbial changes on neonatal health and development, providing a comprehensive overview for clinicians and researchers. By synthesizing current findings, this review contributes to a deeper understanding of the interplay between delivery mode and early microbial colonization, paving the way for informed clinical decisions and future investigations in the field of perinatal medicine.

Are Whiplash-Associated Disorders and Temporomandibular Disorders in a Trauma Related Cause and Effect Relationship? A Review.

Background: Whiplash is associated with a wide variety of clinical manifestations, including headache, neck pain, cervical rigidity, shoulder and back pain, paresthesia, vertigo, and temporomandibular disorders (TMDs). Previous studies reported that TMDs are more common in individuals with chronic whiplash-associated disorders (WAD) than in the general population; however, the pathophysiology and mechanism of this relationship are still not well understood. Methods: A PubMed and Ovid EMBASE review was performed to identify all studies addressing the trauma related cause and effect relationship between WAD and TMDs from January 2003 to March 2023. Results: After screening for eligibility and inclusion criteria, a total of 16 articles met the selection criteria. The various included studies discussed different aspects of the association between WDA and TMDs, including changes in the coordination and amplitude of jaw opening, the severity of the associated symptoms/signs in cases of WAD, the degree of fatigue and psychological stress, difficulty in feeding, cervical and myofascial pain, changes in the MRI signal at various muscle points, muscle tenderness, and quality of life. Conclusions: In this review, we summarized the clinical evidence of any trauma related cause and effect relationship between whiplash and TMDs. An accurate screening of the previous literature showed that, in conclusion, the relationship between whiplash and TMDs is still unclear.

Kinase Fusions in Spitz Melanocytic Tumors: The Past, the Present, and the Future.

In recent years, particular interest has developed in molecular biology applied to the field of dermatopathology, with a focus on nevi of the Spitz spectrum. From 2014 onwards, an increasing number of papers have been published to classify, stratify, and correctly frame molecular alterations, including kinase fusions. In this paper, we try to synthesize the knowledge gained in this area so far. In December 2023, we searched Medline and Scopus for case reports and case series, narrative and systematic reviews, meta-analyses, observational studies-either longitudinal or historical, case series, and case reports published in English in the last 15 years using the keywords spitzoid neoplasms, kinase fusions, ALK, ROS1, NTRK (1-2-3), MET, RET, MAP3K8, and RAF1. ALK-rearranged Spitz tumors and ROS-1-rearranged tumors are among the most studied and characterized entities in the literature, in an attempt (although not always successful) to correlate histopathological features with the probable molecular driver alteration. NTRK-, RET-, and MET-rearranged Spitz tumors present another studied and characterized entity, with several rearrangements described but as of yet incomplete information about their prognostic significance. Furthermore, although rarer, rearrangements of serine-threonine kinases such as BRAF, RAF1, and MAP3K8 have also been described, but more cases with more detailed information about possible histopathological alterations, mechanisms of etiopathogenesis, and also prognosis are needed. The knowledge of molecular drivers is of great interest in the field of melanocytic diagnostics, and it is important to consider that in addition to immunohistochemistry, molecular techniques such as FISH, PCR, and/or NGS are essential to confirm and classify the different patterns of mutation. Future studies with large case series and molecular sequencing techniques are needed to allow for a more complete and comprehensive understanding of the role of fusion kinases in the spitzoid tumor family.

Stem Cells: Present Understanding and Prospects for Regenerative Dentistry.

Regenerative medicine in dentistry focuses on repairing damaged oral tissues using advanced tools like stem cells, biomaterials, and tissue engineering (TE). Mesenchymal stem cells (MSCs) from dental sources, such as dental pulp and periodontal ligament, show significant potential for tissue regeneration due to their proliferative and differentiative abilities. This systematic review, following PRISMA guidelines, evaluated fifteen studies and identified effective strategies for improving dental, periodontal, and bone tissue regeneration through scaffolds, secretomes, and bioengineering methods. Key advancements include the use of dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) to boost cell viability and manage inflammation. Additionally, pharmacological agents like matrine and surface modifications on biomaterials improve stem cell adhesion and promote osteogenic differentiation. By integrating these approaches, regenerative medicine and TE can optimize dental therapies and enhance patient outcomes. This review highlights the potential and challenges in this field, providing a critical assessment of current research and future directions.

The Role of Curcumin in Oral Health and Diseases: A Systematic Review.

Curcumin (Curcumin) belongs to the polyphenol family. It is extracted by drying the root of a plant of Asian origin, belonging to the Zingiberaceae family. The best-known species is Curcumincuma Longa. Curcumin has been recognized as having great therapeutic powers since ancient times. Studies on curcumin have since confirmed its powerful antioxidant properties, preventing both the formation of free radicals and their neutralization, having anti-inflammatory, antibacterial, immunological, and neuroprotective properties, as well as being a regulator of the intestinal microbiota with beneficial effects on the clinical manifestations of metabolic syndrome. Our study aimed to highlight how all these therapeutic aspects could benefit oral health, both preventing and improving the course of pathological processes. The effect of mouthwashes, and curcumin-based gels on the regulation of bacterial plaque and in the control of gingivitis, was largely comparable to that of using 0.20% chlorhexidine, with fewer side effects. Being a highly hydrophobic substance, it has a high permeability to cross the cell membrane. Bioavailability increases when combined with liposoluble substances (e.g., olive oil) and piperine, which improves absorption. Curcumin also has a negligible degree of toxicity, making it an excellent alternative to the use of gold standard products for oral disinfection.

Mast cell density in Merkel cell carcinoma and its correlation with prognostic features and MCPyV status: a pilot study.

Merkel cell carcinoma (MCC) is a rare, highly aggressive, primitive neuroendocrine carcinoma of the skin, the origin of which is not yet fully understood. Numerous independent prognostic factors have been investigated in an attempt to understand which are the most important parameters to indicate in the histological diagnostic report of MCC. Of these, mast cells have only been studied in one paper before this one. We present a retrospective descriptive study of 13 cases of MCC, received at the Department of Pathology over a 20-year period (2003-2023 inclusive) on which we performed a study using whole-slide (WSI) morphometric analysis scanning platform Aperio Scanscope CS for the detection and spatial distribution of mast cells, using monoclonal anti-tryptase antibody and anti-CD34 monoclonal antibody to study the density of microvessels. In addition, we analyzed MCPyV status with the antibody for MCPyV large T-antigen (Clone CM2B4). We found statistically significant correlation between mast cell density and local recurrence/distant metastasis/death-of-disease (p = 0.008). To our knowledge, we firstly reported that MCPyV ( -) MCC shows higher mast cells density compared to MCPyV ( +) MCC, the latter well known to be less aggressive. Besides, the median vascular density did not show no significant correlation with recurrence/metastasis/death-of-disease, (p = 0.18). Despite the small sample size, this paper prompts future studies investigating the role of mast cell density in MCC.

The Effectiveness of Curcumin in Treating Oral Mucositis Related to Radiation and Chemotherapy: A Systematic Review.

Chemotherapy (CT) and radiation therapy (RT), while effective against cancer, often cause severe side effects, such as oral mucositis and other oral diseases. Oral mucositis, characterized by inflammation and ulceration of the oral mucosa, is one of the most painful side effects that can reduce quality of life and limit cancer treatment. Curcumin, a polyphenol from Curcuma longa, has garnered attention for its anti-inflammatory, antioxidant, and anti-carcinogenic properties, which protect the oral mucosa by reducing oxidative stress and modulating inflammation. This study reviews the therapeutic potential of curcumin in preventing and managing oral mucositis caused by CT and RT. Clinical trials show curcumin's effectiveness in reducing the incidence and severity of oral mucositis. Although curcumin supplementation appears to be a promising and cost-effective approach for mitigating oral complications in cancer patients, further clinical trials are needed to confirm its efficacy and optimize dosing strategies.

Diagnosis and Orthodontic Treatment of Obstructive Sleep Apnea Syndrome Children-A Systematic Review.

Obstructive sleep apnea syndrome (OSAS) is a respiratory illness that is associated with recurrent episodes of either partial or full obstruction of the upper airways, or apnea, among other sleep disorders. This study aims to analyze, through a literature review, whether orthodontic treatment can be a good treatment strategy for this type of disorder. We performed a database search on Scopus, Web of Science, and Pubmed with the keywords OSA(S) and orthodontics to select the papers under evaluation. The criteria for inclusion were articles related to OSA(S) children undergoing an orthodontic treatment and clinical studies or case series, excluding systematic reviews, narrative reviews, meta-analyses, adult studies, animal models, and in vitro studies. The screening phase ended with the selection of 16 publications for this work. RME, or rapid maxillary expansion, turned out to be the preferred orthodontic treatment in cases of pediatric OSAS. The goal of this orthodontic procedure is to increase the hard palate's transverse diameter by reopening the mid-palatal suture. Children with maxillary contraction and dental malocclusion typically undergo such a procedure and have excellent results. However, OSAS is a multifactorial disorder; it does not seem related to the morphology of the oral cavity, and therefore, it is not always possible to cope with this problem exclusively through orthodontic treatment.

Cutaneous Sarcoidosis-like Eruption Following Second Dose of Moderna mRNA-1273 Vaccine: Case or Relationship?

Various adverse reactions to SARS-CoV-2 vaccines have been described since the first months of the vaccination campaign. In addition to more frequent reactions, rare reactions, such as sarcoidosis-like, rashes have been reported. We present a case of a 23-year-old woman with a rash on the chin and peribuccal region, which developed approximately 3 weeks after the administration of the second dose of the Moderna mRNA-1273 vaccine. We briefly discuss other reports in the literature.

Artificial Intelligence Applied to a First Screening of Naevoid Melanoma: A New Use of Fast Random Forest Algorithm in Dermatopathology.

Malignant melanoma (MM) is the "great mime" of dermatopathology, and it can present such rare variants that even the most experienced pathologist might miss or misdiagnose them. Naevoid melanoma (NM), which accounts for about 1% of all MM cases, is a constant challenge, and when it is not diagnosed in a timely manner, it can even lead to death. In recent years, artificial intelligence has revolutionised much of what has been achieved in the biomedical field, and what once seemed distant is now almost incorporated into the diagnostic therapeutic flow chart. In this paper, we present the results of a machine learning approach that applies a fast random forest (FRF) algorithm to a cohort of naevoid melanomas in an attempt to understand if and how this approach could be incorporated into the business process modelling and notation (BPMN) approach. The FRF algorithm provides an innovative approach to formulating a clinical protocol oriented toward reducing the risk of NM misdiagnosis. The work provides the methodology to integrate FRF into a mapped clinical process.

Endocrine Mucin-Producing Sweat Gland Carcinoma: Case Presentation with a Comprehensive Review of the Literature.

(1) Background: Endocrine Mucin-Producing Sweat Gland Carcinoma (EMPSGC) is a rare, low-grade, neuroendocrine-differentiated, cutaneous adnexal tumor, officially recognized by the World Health Organization (WHO) Skin Tumors Classification in 2018 as a separate entity and homologue of endocrine ductal carcinoma in situ (eDCIS)/solid papillary carcinoma of the breast. Although it is more frequent in the female sex, between 60 and 70 years old, in the peri-orbital region, EMPSGC has also been described in the male sex, in subjects under 60 and over 80, and in extra-eyelid localizations (cheek, temple, scalp), but also in extra-facial localizations (chest and scrotum). (2) Methods: We present the clinical case of a 71-year-old woman with an undated lesion of the scalp, which presented as a nodule, skin-colored, and 2.5 cm in maximum diameter. We also conduct a comprehensive literature review from 1997 to the end of 2022, consulting PubMed, Scopus, Web of Science (WoS), and Google Scholar using the following keywords: "Endocrine mucin-producing sweat gland carcinoma" and/or "EMPSGC" and/or "skin" and "cutaneous neoplasms". In addition, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 253 patients were recorded; 146 were females (57.7%) and 107 were males (42.2%). The vast majority of the lesions were in the eyelids (peri-ocular region), and only a minority of cases involved the cheeks, supra-auricular, retro-auricular, and occipital region, with very rare cases in the scalp, to which the present is also added. (4) Conclusions: The morphological and immunophenotypical features are essential both for the correct diagnosis and to be able to classify this lesion among the corresponding eDCIS/solid papillary carcinoma of the breast, with neuroendocrine differentiation. Recent papers have attempted to shed light on the molecular features of EMPSGC, and much remains to be conducted in the attempt to subtype the molecular profiles of these entities. Future studies with large case series, and especially with molecular biology techniques, will be needed to further add information about EMPSGC and its relationship in the PCMC spectrum.

Immunohistochemical Expression of Programmed Cell Death Ligand 1 (PD-L1) in Human Cutaneous Malignant Melanoma: A Narrative Review with Historical Perspectives.

Programmed death-ligand 1 (PD-L1) is the primary ligand of the receptor programmed death-1 (PD-1) which is constitutively expressed or activated in myeloid, lymphoid (T, B and NK), normal epithelial cells, and cancer. The PD-1/PD-L1 interaction is crucial for the physiological development of immunological tolerance but also in the development of the cancer. Among these, malignant melanoma represents a tumour in which the immunohistochemical expression of PD-L1 is important to guide future therapeutic choices based on the presence/absence of expression. Various clones have been used over time for immunohistochemical determination, and different results and heterogeneity remain among the various studies in the literature. We perform a narrative review of the present studies in order to discuss and take stock of what certain achievements have been made in this field, what challenges remain, and what possible solutions can be found.

Oxidative Stress and Natural Products in Orthodontic Treatment: A Systematic Review.

In recent years, orthodontics, a specialized branch of dentistry, has evolved considerably in terms of both techniques and materials used. Aimed at correcting dental malocclusions and craniofacial anomalies, it improves the functionality and aesthetics of the face and oral cavity. However, orthodontic treatment, in its developmental stages, may induce oxidative stress (O.S.) phenomena, with an increase in the production of reactive oxygen species (ROS), damaging the dental and periodontal tissues involved, affecting the short-, medium- and long-term results. Studies on the antioxidant effects of natural products (e.g., resveratrol, green tea, turmeric, etc.) in the medical field have aroused considerable interest in recent years. A systematic literature review was conducted on the PubMed, Scopus, and Web of Science databases using natural products (N.P.s), O.S., and orthodontic as keywords. The study aims to consider the determinants of the increase in ROS occurring during orthodontic treatment and the possibility of natural products being able to control and neutralize biochemical phenomena by restoring the physiological process in which the balance between the production of ROS and the ability of the body's antioxidant system to neutralize them is in favor of the latter.

Advances in Preventive and Therapeutic Approaches for Dental Erosion: A Systematic Review.

This review discusses both preventive measures and clinically implemented therapy procedures that have been developed recently for the prevention and treatment of tooth erosion. METHODS: The databases PubMed, Scopus, and Web of Science were used for a thorough search. Studies on the prevention and treatment of dental erosion that were conducted in English and used in vitro were among the inclusion criteria. RESULTS: The search turned up 391 papers in total, with 34 of those publications matching the requirements for inclusion. Varnishes, toothpastes, and solutions containing fluoride and other substances were used as preventive measures. CONCLUSIONS: Dental erosion is a significant issue, and taking preventative steps is crucial to lessening the disease's spread and its effects. Interventions based on fluoride seem to be successful at halting erosion and encouraging remineralization. To effectively address severe tooth erosion, therapeutic methods, including composite restorations, prosthetic crowns, and veneers, are available. Dental erosion causes aesthetic and functional issues that are best addressed with less invasive treatments like direct composite restorations. To improve and broaden the range of available treatments for this common dental issue, additional research and development are required.

Application of Graphene Oxide in Oral Surgery: A Systematic Review.

The current review aims to provide an overview of the most recent research in the last 10 years on the potentials of graphene in the dental surgery field, focusing on the potential of graphene oxide (GO) applied to implant surfaces and prosthetic abutment surfaces, as well as to the membranes and scaffolds used in Guided Bone Regeneration (GBR) procedures. "Graphene oxide" and "dental surgery" and "dentistry" were the search terms utilized on the databases Scopus, Web of Science, and Pubmed, with the Boolean operator "AND" and "OR". Reviewers worked in pairs to select studies based on specific inclusion and exclusion criteria. They included animal studies, clinical studies, or case reports, and in vitro and in vivo studies. However, they excluded systematic reviews, narrative reviews, and meta-analyses. Results: Of these 293 studies, 19 publications were included in this review. The field of graphene-based engineered nanomaterials in dentistry is expanding. Aside from its superior mechanical properties, electrical conductivity, and thermal stability, graphene and its derivatives may be functionalized with a variety of bioactive compounds, allowing them to be introduced into and improved upon various scaffolds used in regenerative dentistry. This review presents state-of-the-art graphene-based dental surgery applications. Even if further studies and investigations are still needed, the GO coating could improve clinical results in the examined dental surgery fields. Better osseointegration, as well as increased antibacterial and cytocompatible qualities, can benefit GO-coated implant surgery. On bacterially contaminated implant abutment surfaces, the CO coating may provide the optimum prospects for soft tissue sealing to occur. GBR proves to be a safe and stable material, improving both bone regeneration when using GO-enhanced graft materials as well as biocompatibility and mechanical properties of GO-incorporated membranes.

Histopathological Patterns of Cutaneous Adverse Reaction to Anti-SARS-CoV-2 Vaccines: The Integrative Role of Skin Biopsy.

The advent of vaccines represented a milestone to allow the slowing down and then containing of the exponential increase in ongoing infections and deaths of COVID-19. Since the first months of the vaccination campaign in various continents, there has been a certain number of reports of adverse events, including skin reactions. We conducted a systematic review, searching on PubMed, Web of Science, Scopus, and Cochrane Library for the words: COVID vaccine, dermatopathology, skin, eruptions, rash, cutaneous, BNT162b2 (Pfizer-BioNTech), ChAdOX1 (AstraZeneca), and mRNA-1273 (Moderna). A total of 28 records were initially identified in the literature search of which two were duplicates. After screening for eligibility and inclusion criteria, 18 publications were ultimately included. Various clinical cutaneous manifestations and histopathological patterns following vaccination have been described in literature. The most frequent clinical-pathological presentations were erythematous maculo-papular eruptions in different way of distribution with histopathological pictures mostly represented by interface changes and mixed peri-vascular and peri-adnexal cell infiltrate. Other presentations included new onset of pemphigoid bullous disease (n = 15), delayed T-cell-mediated hypersensitivity reaction (injection site reactions) (n = 10), purpuric skin rash (n = 13), mostly localized on the legs bilaterally and symmetrically with histological pictures characterized by extravasation of erythrocytes in the superficial and middle dermis, and other types of reactions. New studies with large case series and further literature reviews are needed to improve the clinical management of patients and optimize the timeline for carrying out histological biopsy for confirmatory, supportive, and differential diagnosis purposes.

Benefits of Natural Antioxidants on Oral Health.

In recent years, special attention has been paid to the correlation between oxidation-reduction mechanisms and human health. The free radicals produced via physiological cellular biochemical processes are major contributors to oxidation phenomena. Their instability is the major cause of cellular damage. Free radical reactive oxygen species containing oxygen are the best-known ones. The body neutralises the harmful effects of free radicals via the production of endogenous antioxidants (superoxide dismutase, catalase, glutathione, and melatonin). The field of study of nutraucetics has found antioxidant capacity in substances such as vitamins A, B, C, E, coenzyme Q-10, selenium, flavonoids, lipoic acid, carotenoids, and lycopene contained in some foods. There are several areas of investigation that aim to research the interaction between reactive oxygen species, exogenous antioxidants, and the microbiota to promote increased protection via the peroxidation of macromolecules (proteins, and lipids) by maintaining a dynamic balance among the species that make up the microbiota. In this scoping review, we aim to map the scientific literature on oxidative stress related to the oral microbiota, and the use of natural antioxidants to counteract it, to assess the volume, nature, characteristics, and type of studies available to date, and to suggest the possible gaps that will emerge from the analysis.

Development of Flat Warts on the Cheeks after BioNTech-Pfizer BNT162b2 Vaccine: Is There a Correlation?

The SARS-CoV-2 pandemic has affected health systems across the globe, making the use of vaccines more urgent and topical than ever. Since the first months after the introduction of vaccinations, several reactions, both local and systemic, have been reported although they were mostly very mild and only rarely harbingers of more serious complications. We present a case of multiple flat warts onset over the cheeks in a patient after the second dose of mRNA BioNTech-Pfizer BNT162b2 vaccine, and we discuss the possible temporal association between the two events, also considering the patient's antibody status.

Balloon Cell Melanoma: Presentation of Four Cases with a Comprehensive Review of the Literature.

BACKGROUND: balloon cell melanoma represents less than 1% of all histological forms of malignant melanoma and represents a diagnostic challenge for the dermatopathologist. METHODS: in this paper we present our cases of BCM found in our daily practice from 1 January 2008 to 31 December 2021, and we conduct a review of the literature relating to this entity in the period from the first description, 1970, to early 2022. RESULTS: four cases of melanoma balloon cell have been extrapolated from our electronic database, while in the review of the literature we have identified 115 cases of patients with primary and/or metastatic BCM. CONCLUSIONS: we believe that future studies with numerous case series are essential not only to increase the knowledge of the pathophysiology of this neoplasm but also to correctly evaluate the response of BCM patients to new oncological therapies.