Search Results (19)

Artificial intelligence (AI) is rapidly transforming diagnostic approaches in different fields of medical sciences, demonstrating an emerging potential to revolutionize dermatopathology due to its capacity to process large amounts of data in the shortest possible time, both for diagnosis and research purposes. Different AI models have been applied to neoplastic skin diseases, especially melanoma. However, to date, very few studies have investigated the role of AI in dermatoses. Herein, we provide an overview of the key aspects of AI and its functioning, focusing on medical applications. Then, we summarize all the existing English-language literature about AI applications in the field of non-neoplastic skin diseases: superficial perivascular dermatitis, psoriasis, fungal infections, onychomycosis, immunohistochemical characterization of inflammatory dermatoses, and differential diagnosis between the latter and mycosis fungoides (MF). Finally, we discuss the main challenges related to AI implementation in pathology. Full article

Angiogenesis, the formation of new blood vessels from pre-existing ones, is a crucial process in the progression and metastasis of melanoma. Recent research has highlighted the significant role of epigenetic modifications in regulating angiogenesis. This review comprehensively examines the current understanding of how epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, influence angiogenic pathways in melanoma. DNA methylation, a key epigenetic modification, can silence angiogenesis inhibitors such as thrombospondin-1 and TIMP3 while promoting pro-angiogenic factors like vascular endothelial growth factor (VEGF). Histone modifications, including methylation and acetylation, also play a pivotal role in regulating the expression of angiogenesis-related genes. For instance, the acetylation of histones H3 and H4 is associated with the upregulation of pro-angiogenic genes, whereas histone methylation patterns can either enhance or repress angiogenic signals, depending on the specific histone mark and context. Non-coding RNAs, particularly microRNAs (miRNAs) further modulate angiogenesis. miRNAs, such as miR-210, have been identified as key regulators, with miR-9 promoting angiogenesis by targeting E-cadherin and enhancing the expression of VEGF. This review also discusses the therapeutic potential of targeting epigenetic modifications to inhibit angiogenesis in melanoma. Epigenetic drugs, such as DNA methyltransferase inhibitors (e.g., 5-azacytidine) and histone deacetylase inhibitors (e.g., Vorinostat), have shown promise in preclinical models by reactivating angiogenesis inhibitors and downregulating pro-angiogenic factors. Moreover, the modulation of miRNAs and lncRNAs presents a novel approach for anti-angiogenic therapy. Full article

DICER1 syndrome, a rare autosomal dominant genetic disorder, stems from mutations in the DICER1 gene, disrupting RNA interference and leading to various tumors. These tumors, affecting organs like the lung, kidney, ovaries, and brain, pose diagnostic challenges due to diverse presentations. Understanding DICER1-associated tumors, including pleuropulmonary blastoma, ovarian Sertoli–Leydig cell tumors, and others, is vital for early detection and management. Surgical resection, chemotherapy, and targeted therapies are primary treatment modalities, with genetic counseling playing a crucial role. Multidisciplinary care is essential for optimal management, offering hope for improved outcomes in affected individuals. Full article

Lignans, a class of secondary metabolites found in plants, along with their derivatives, exhibit diverse pharmacological activities, including antioxidant, antimicrobial, anti-inflammatory, and antiangiogenic ones. Angiogenesis, the formation of new blood vessels from pre-existing ones, is a crucial process for cancer growth and development. Several studies have elucidated the synergistic relationship between angiogenesis and inflammation in various inflammatory diseases, highlighting a correlation between inflammation and vascular endothelial growth factor (VEGF)-induced angiogenesis. Thus, the identification of novel molecules capable of modulating VEGF effects presents promising prospects for developing therapies aimed at stabilizing, reversing, or even arresting disease progression. Lignans often suffer from low aqueous solubility and, for their use, encapsulation in a delivery system is needed. In this research, a bioinspired benzoxantene has been encapsulated in solid lipid nanoparticles that have been characterized for their pharmacotechnical properties and their thermotropic behavior. The effects of these encapsulated nanoparticles on angiogenic parameters and inflammation in VEGF-induced angiogenesis were evaluated using human brain microvascular endothelial cells (HBMECs) as a human blood–brain barrier model. Full article

Since its introduction in the early 2000s, liquid-based cytology (LBC) has been increasingly used for gynecologic and non-gynecologic cytology, and its multiple advantages have been widely recognized. The aim of this study was to investigate the use of a new fixative and pre-analytical method for morphological diagnosis in cytological samples. In particular, we evaluated the effect of a novel preservative solution on the preparation of diagnostic slides by comparing it with the standard reference used globally in cytology laboratories. This study included both gynecological (n = 139) and non-gynecological (n = 183) samples. Several morphologic variables were then identified and evaluated. Using this approach, we were then able to demonstrate the suitability of the new system, with improved safety, to be integrated within current pathology clinical practice. Overall, using a safer preservative solution, the study shows no statistical difference (and then non-inferiority) in the new fixation protocol compared with the standard reference used in routine practice in terms of diagnostic adequacy, evaluated both in clinically relevant gyn and non-gyn datasets. Full article

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. Full article

Falls are the most frequent adverse events recorded in healthcare facilities. By employing a multifaceted strategy to ensure prevention interventions that are specific to the patient type and environmental risk management, risk factor evaluation may help to reduce falls in the hospital setting. Patient falls are one of the main causes of lawsuits against hospitals, which has led to the development of validated instruments that are beneficial in treating the patient after the incident and effective in minimizing the frequency of falls. The aim of our study is to evaluate compensation claims asserting healthcare culpability in situations where a patient fell in a hospital setting. The collected data relate to judgments issued in Italy until December 2022 regarding 30 episodes of falls that occurred between 2003 and 2018. Our research revealed that approximately 50% of Italian healthcare organizations lose the case in court when a patient falls in a hospital setting and dies or is injured. In half of these cases, the failure of the medical staff to use protective equipment against falls is what led to the court’s acceptance of the compensation claim. In order to improve the quality of healthcare services, fall prevention techniques must continue to be implemented. Full article

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. Full article

T cell immunoglobulin and mucin domain 3 (TIM-3) is an inhibitory immunocheckpoint that belongs to the TIM gene family. Monney et al. first discovered it about 20 years ago and linked it to some autoimmune diseases; subsequent studies have revealed that some tumours, including melanoma, have the capacity to produce inhibitory ligands that bind to these receptor checkpoints on tumour-specific immune cells. We conducted a literature search using PubMed, Web of Science (WoS), Scopus, Google Scholar, and Cochrane, searching for the following keywords: “T cell immunoglobulin and mucin-domain containing-3”, “TIM-3” and/or “Immunocheckpoint inhibitors” in combination with “malignant melanoma” or “human malignant melanoma” or “cutaneous melanoma”. The literature search initially turned up 117 documents, 23 of which were duplicates. After verifying eligibility and inclusion criteria, 17 publications were ultimately included. A growing body of scientific evidence considers TIM-3 a valid inhibitory immuno-checkpoint with a very interesting potential in the field of melanoma. However, other recent studies have discovered new roles for TIM-3 that seem almost to contradict previous findings in this regard. All this demonstrates how common and valid the concept of ‘pleiotropism’ is in the TME field, in that the same molecule can behave completely or partially differently depending on the cell type considered or on temporary conditions. Further studies, large case series, and a special focus on the immunophenotype of TIM-3 are absolutely necessary in order to explore this highly promising topic in the near future. Full article

Malignant melanoma is a cutaneous malignancy resulting from the uncontrolled proliferation of melanocytes and poses a challenge diagnostically because neoplastic lesions can mimic benign lesions, which are much more common in the population. Doctors, when they suspect the presence of melanoma, arrange for its removal and the performance of a histological examination to ascertain its diagnosis; in cases where the dermatoscopic examination is indicative of benignity, however, after the lesion is removed, histological examination is not always performed, a very dangerous occurrence and a harbinger of further medico-legal problems. The authors present a court litigation case of an “alleged” failure to diagnose malignant melanoma in a patient who died of brain metastases from melanoma in the absence of a certain location of the primary tumor: the physician who had removed a benign lesion a few months earlier was sued, and only thanks to the presence of photographic documentation was the health care provider able to prove his extraneousness. The aim of this paper is to formulate a proposal for a dermatological protocol to be followed in cases of excisions of benign skin lesions with a twofold purpose: on the one hand, to be able to prove, in a judicial context, the right action on the part of the sanitarians; on the other hand, to avoid the rise of so-called “defensive medicine”. Full article

Purpose: To evaluate the usefulness of studying vital injuries at the sternal head insertion of the sternocleidomastoid muscle in the medico-legal assessment of death by hanging. Materials and Methods: Study material was obtained from eight bodies of people who died from hanging. The control group included as many specimens collected from people who died from traumatic causes other than hanging (precipitation from medium to large heights and traffic accidents). The structures under study were examined histologically with a BX-51 light microscope (Olympus). An analysis of the extravasated erythrocytes was performed by counting the number per mm² in the histologic section on 10 HPF (400×), and Student’s t-test for a comparison of the averages was applied for all parametric values. The authors noted that the key finding, indicative of the subject’s viability at the time of discontinuation, was the presence of recent hemorrhagic infiltrate (in the absence of hemosiderin) at the tendon insertion of the sternocleidomastoid muscle and the proximal part of the muscle itself. Results: All specimens tested were positive for the presence of hemorrhagic infiltrate at the portions tested in a statistically significant manner. In contrast, in the control cases there was no or, where present, no statistically significant (p < 0.05) presence of recent hemorrhagic infiltrate. The limitation of the study is the low number of samples examined. In any case, the results obtained are strongly indicative of the possibility of using this type of forensic pathological investigation in cases where there is a doubt in terms of a differential diagnosis between hanging (suicidal type) and suspension of a corpse in a simulation of hanging. Full article

Malignant melanoma (MM) is traditionally known as the “great mime” of human pathology, as it is potentially capable of imitating the most disparate neoplasms. It is known that in addition to the more classic histotypes of MM, there are also rare forms, including angiomatoid MM. Similarly, it has been amply demonstrated in the literature that MM is capable of dedifferentiating, losing melanocytic lineage markers, constituting a diagnostic challenge for the pathologist. Although 5 cases of primary angiomatoid MM have been described in the literature, to the best of our knowledge, no cases of dedifferentiated melanoma with pseudo-angiomatoid aspects have ever been described. In this paper, we present a very rare case of partially dedifferentiated MM in which the most dedifferentiated component lost melanocytic lineage immunohistochemical markers and assumed a pseudo-angiomatous morphology. Given the rarity of the case, we carried out a literature review of similar cases described, trying to draw new future perspectives not only about this particular variant of MM but also about the widest field of dedifferentiation/undifferentiation of MM. Full article

Background: In recent years, great research interest has been directed to the diagnostic, therapeutic and marker role of Preferentially expressed Antigen in Melanoma (PRAME) in the setting of various human neoplasms. Although it has been extensively studied mainly in the differential diagnosis setting of melanocytic pigmented lesions, still very few papers have analyzed the usefulness or otherwise of PRAME in the context of other non-melanoma skin cancers (NMSC). (2) Methods: In this paper, we report the data of our experience of 21 cases of sebaceous carcinoma (SC) classified in the three WHO grade and collected in the period between January 2005 and 31 October 2022, on which immunostaining for PRAME was performed; Non-parametric Mann–Whitney test for non-normally distributed values was performed. A comparison was made of the means between the three study groups (grade I, II and III). A value of p ≤ 0.05 was set as statistically significant (3) Results: Only seven cases (33.3%) were positive with an immunoscore of 2+/3+ for intensity and 1+/2+ for percentage cells positivity, while 14 cases (66.6%) were totally or nearly totally negative for PRAME with a few of sebaceous-like cells positive with an immunoscore of 1+. Eight cases of SC grade I were immunostaining for PRAME, a level of the cytoplasm of foci of sebaceous differentiation with a significant statical value (p < 0.0001) with respect to ten cases of SC grade II; furthermore, the eight cases of grade I were positive for PRAME in the same areas respect the 3 cases of SC grade III (p = 0.0303). There were no statistical significance between the 10 cases of grade II and 3 cases of grade III (p = 0.2028); (4) Conclusions: PRAME not seems to add particular information in the case of histopathological diagnostics of SC where other markers, including adipophylline, can be quite indicative. It seems, on the other hand, that PRAME can be useful in the subclassification setting of sebaceous carcinoma in grades I–II–III according to the directives of the latest WHO 2018, highlighting the foci of mature sebaceous differentiation most present in grades 1–2 and almost completely absent in grade 3 of the SC. Full article

Malignant melanoma (MM) is known to be the great mimic in dermatopathology. Over time, several variants have been described, not all of which have repercussions on the clinical/oncological management of the affected patient. The existence, however, of these alternative forms of MM is of great interest to the pathologist, as they are potentially capable of inducing diagnostic errors affecting the diagnostic-therapeutic care pathway (PDTC). In this paper, we present a very rare case of polymorphic MM, in which five different morphological aspects coexisted in the same lesion, confirmed by immunohistochemical investigation and by RT-PCR for mutation of the BRAF gene and discuss the importance of correct recognition of these different morphological features to avoid misdiagnosis. Full article

Angiomatoid fibrous histiocytoma (AFH) is a rare neoplasm described for the first time by Enzinger in 1979, and classified by World Health Organization 2020 as intermediate malignant potential neoplasm. It mostly occurs in the subcutis and is characterized by varying proportions of epithelioid, ovoid and spindle cells in a nodular and syncytial growth pattern, with some hemorrhagic pseudovascular spaces. In this paper, we report the clinical case of a 62-year-old man who presented with AFH on the right arm, and relapsed three years after first surgical excision. After a further three years, the patient presented with an intramuscular localization of AFH, and 12 months after this, a pulmonary metastasis of AFH was diagnosed. Given the rarity of the spreading of AFH, we performed Fluorescence In Situ Hybridization (FISH) and we detected EWSR1::CREB1 gene fusion. Full article