Background: Acral amelanotic melanomas (AAMs), a rare subset of melanomas located on acral sites such as the palms, soles, and subungual areas, are diagnostically challenging due to their lack of typical pigmentation and often benign clinical appearance. Misdiagnosis is common, leading to delays in treatment and potentially worse outcomes. This systematic review aims to synthesise evidence on cases of AAM initially misdiagnosed as other conditions, to better understand their clinical and epidemiological characteristics, diagnostic pitfalls, and management strategies. Methods: A comprehensive search of the MEDLINE/PubMed, EMBASE, and SCOPUS databases was conducted up to March 2024. Case reports and small case series of AAMs initially misdiagnosed as other conditions were included. Data on patient demographics, clinical presentation, and diagnostic methods were collected and analyzed. Results: Of the 152 records identified, 26 cases from 23 articles met the inclusion criteria. A demographic analysis revealed that the gender distribution appears to be perfectly balanced, with an age range of 38 to 91 years. Misdiagnoses included non-healing ulcers or traumatic lesions (37.5%), benign proliferative lesions (29.2%) and infectious lesions (20.8%). The foot was the most affected site (53.8%). Notably, a histological evaluation was performed in 50% of cases involving the upper extremities, in contrast to only 7.1% of cases involving the foot and 0% of cases of the heel. This discrepancy suggests a reluctance to perform biopsies in the lower extremities, which may contribute to a higher misdiagnosis rate in these areas. Conclusions: The underutilization of biopsy in the diagnosis of lower extremity lesions contributes significantly to the misdiagnosis and delay in treatment of AAMs. Especially when the clinical assessment and dermoscopy are inconclusive, biopsies of suspicious lesions are essential. Immunohistochemistry and markers such as PRAME are critical in differentiating melanoma from other malignancies such as clear cell sarcoma. This review highlights the need for increased vigilance and a proactive diagnostic approach to increase early detection rates and improve prognostic outcomes.

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.

BCC is the most prevalent form of skin cancer, characterized by diverse clinical and pathological subtypes ranging from indolent to highly aggressive forms. While the majority of BCC cases are treated effectively with surgery or local therapies, locally advanced BCC (laBCC) and metastatic BCC (mBCC) pose significant therapeutic challenges. Recent advances in HHIs and immunotherapy have transformed the treatment landscape in such cases. However, resistance and intolerance to these treatments necessitate alternative approaches, including chemotherapy. Platinum-based agents such as cisplatin and carboplatin have shown limited efficacy but remain viable options in rapidly progressive cases. Among the therapeutic innovations to be explored, further lines of immunotherapy as well as combination therapies involving immunotherapy and targeted therapy have been proposed. This review synthesizes the current understanding about BCC subtypes, risk stratification, and emerging treatments, with a particular focus on laBCC and mBCC.

During the last decade, a new therapeutic revolution has involved the management of hepatocellular carcinoma (HCC). This is made possible thanks to the documented efficacy of immunotherapy for this disease. In addition, new evidence has demonstrated the role of the gut–liver axis and gut microbiota in host homeostasis, tumor development, and response to therapies. In particular, intestinal dysbiosis can alter the tumor microenvironment, leading to the activation of intracellular signaling pathways that promote carcinogenesis. The composition of gut microbiota proved to influence the immune checkpoint inhibitors (ICIs) efficacy and drug toxicities. Therefore, this review aims to deepen knowledge about the immunomodulatory role of gut microbiota and its possible employment as diagnostic and predictive biomarkers in diagnosis and response to HCC immunotherapy, respectively. The research was conducted through the analysis of Pubmed and Web of Science (WoS) databases for literature studies on the relationship between gut microbiota and HCC from 2015 to 2025.

Background: Ocular-surface abnormalities are common in patients with moderate-to-severe atopic dermatitis and may predispose to dupilumab-associated ocular surface disease (DAOSD). We investigated early ocular-surface changes during dupilumab treatment and whether baseline-guided hyaluronic acid (HA) eye-drop use was associated with more favorable ocular outcomes. Methods: In this prospective single-center cohort study, patients with moderate-to-severe atopic dermatitis underwent ophthalmologic assessment before dupilumab initiation and after 4 months. HA 0.15% eye drops were prescribed to patients with at least one basal or reflex Schirmer value ≤15 mm and ocular symptoms. Ocular outcomes included tear break-up time (TBUT), basal and reflex Schirmer tests, meibography, and the Ocular Surface Disease Index (OSDI). Follow-up values were compared between HA users and non-users using baseline-adjusted models with false-discovery-rate correction. Results: Thirty-nine patients were included; 18 received HA eye drops and 21 did not. Twenty-seven patients (69.2%) had at least one baseline Schirmer value ≤15 mm. At 4 months, reflex Schirmer values were higher in HA users than in non-users after baseline adjustment (adjusted mean difference, 5.60 mm; 95% CI, 1.64–9.57; p = 0.007; q = 0.035). In the low-Schirmer subgroup, HA use was associated with higher reflex Schirmer (8.50 mm; 95% CI, 4.84–12.17; q < 0.001) and basal Schirmer values (5.07 mm; 95% CI, 1.41–8.73; q = 0.022). Among untreated patients with low baseline Schirmer values, reflex tear production decreased in eight of nine patients, despite OSDI scores remaining within the conventional normal range. Conclusions: HA supplementation at dupilumab initiation was associated with more favorable changes in tear production, particularly among patients with reduced baseline Schirmer measurements. Objective deterioration in tear production despite persistently low OSDI scores highlights the limitations of symptom-based assessment alone. These findings support baseline ophthalmologic evaluation and combined objective and symptom monitoring during dupilumab treatment. Larger controlled studies are needed to determine whether early, targeted HA eye-drop use can prevent clinically relevant dupilumab-associated ocular surface disease.