Explore the vast range of titles available.

Almost 17% of Western patients affected by non-small cell lung cancer (NSCLC) have an activating epidermal growth factor receptor (EGFR) gene mutation. Del19 and L858R are the most-common ones; they are positive predictive factors for EGFR tyrosine kinase inhibitors (TKIs). Currently, osimertinib, a third-generation TKI, is the standard first-line therapy for advanced NSCLC patients with common EGFR mutations. This drug is also administered as a second-line treatment for those patients with the T790M EGFR mutation and previously treated with first- (erlotinib, gefitinib) or second- (afatinib) generation TKIs. However, despite the high clinical efficacy, the prognosis remains severe due to intrinsic or acquired resistance to EGRF-TKIs. Various mechanisms of resistance have been reported including the activation of other signalling pathways, the development of secondary mutations, the alteration of the downstream pathways, and phenotypic transformation. However, further data are needed to achieve the goal of overcoming resistance to EGFR-TKIs, hence the necessity of discovering novel genetic targets and developing new-generation drugs. This review aimed to deepen the knowledge of intrinsic and acquired molecular mechanisms of resistance to EGFR-TKIs and the development of new therapeutic strategies to overcome TKIs’ resistance.

Lichen amyloidosis (LA) is a type of cutaneous amyloidosis characterized by brownish hyperkeratotic and itchy papules on the lower leg, back, forearm, or thigh. It is associated with itching and atopic dermatitis (AD) according to an etiopathogenetic mechanism that has not yet been fully elucidated. Currently, the available therapies for this condition include oral antihistamines, laser, cyclosporine, topical corticosteroids, and phototherapy, but, in light of the overlap with AD, Dupilumab may also be indicated. We report the case of a female, 52 years old, who had been suffering from AD and LA for about 27 years. She had lesions attributable to both diseases on the trunk and lower limbs associated with severe itching and had proved resistant to cyclosporine therapy. It was decided to opt for Dupilumab with the induction of 2 fl of 300 mg and maintenance with 1 fl every other week. The therapy proved to be effective, returning a total resolution of both diseases one year after the beginning of the treatment. Dupilumab demonstrated efficacy and safety in the LA related to AD and led to clinical and quality of life improvements in this patient. Therefore, Dupilumab should be considered when treating LA. Further studies should be conducted focusing on the efficacy of the drug on LA (whether or not related to AD), changes in the skin lesions after discontinuation, and the safety of long-term application.

Tumid lupus erythematosus (TLE) has been the subject of heated debate regarding its correct nosographic classification. The definition of TLE has changed over time, varying according to the different studies performed. In this review, we address the initial definition of TLE, the changes that have taken place in the understanding of TLE, and its placement within the classification of cutaneous lupus erythematosus (CLE), with a focus on clinical, histopathological, immunophenotypical, and differential diagnosis aspects.

Bullous dermatoses encompass a group of disorders marked by blister formation on the skin and/or mucosa with diverse etiologies. This case report aims to describe a rare occupationally induced bullous dermatosis in a worker exposed to polyvinyl chloride (PVC) welding fumes, and to highlight the need for improved protective measures in industrial environments. A 48-year-old male employed in a PVC manufacturing plant developed recurrent bullous skin lesions on the hands, face, and neck after operating a PVC film-welding machine without personal protective equipment. Clinical evaluation was supported by histopathology, direct and indirect immunofluorescence, serologic testing (ELISA for anti-desmoglein-1, anti-desmoglein-3, BP230, and BP180), and a porphyrin screen. Patch tests and autoimmunity screening were also performed. Direct immunofluorescence revealed linear C3 and IgG deposits along the basement membrane zone, consistent with a bullous pemphigoid-like pattern, while other autoimmunity markers were negative. Complete remission of lesions occurred after cessation of exposure and job reassignment, without the need for ongoing pharmacologic treatment. A clear \"stop-restart\" relationship between exposure and symptoms supported a causal association. This report describes the first documented case of bullous dermatosis triggered by occupational exposure to PVC welding fumes. The findings emphasize the relevance of occupational assessment in unusual dermatologic presentations and support the implementation of adequate protective measures and exposure monitoring in high-risk settings.

We report the case of a 77-year-old man affected by a poorly differentiated metastatic pulmonary adenocarcinoma who, after the first course of therapy with cisplatin-pemetrexed-pembrolizumab treatment, developed rupioid psoriasis. We decided to discontinue pembrolizumab for four weeks until lesions improved and to start therapy with apremilast (an oral small molecule phosphodiesterase (PDE)4 inhibitor) in combination with systemic methylprednisolone 16 mg/day with consequent tapering until discontinuation in a few weeks. After accomplishing three months of treatment with apremilast, the patient gained complete remission of the rupioid lesions. Pembrolizumab therapy was reintroduced, and cycles were carried out without exacerbating the clinical picture. During the fourth month of therapy with apremilast, it was attempted to stop the treatment despite continuing the therapy with pembrolizumab. As a result, there was a relapse of the erythematous scaling plaques. After the subsequent reintroduction of apremilast, a new remission of the clinical picture occurred despite the absence of interruption of pembrolizumab. As far as we know, this is the second case of rupioid psoriasis induced by immunotherapy with pembrolizumab. Still, while the previous case was undergoing therapy with acitretin and methylprednisone, our patient is the first case treated with apremilast with excellent and rapid remission even after discontinuation and re-administration of pembrolizumab without exacerbation of dermatitis. In addition, the appearance of psoriasis during immunotherapy can be properly treated, which does not contraindicate the continuation of the antineoplastic treatment.

Although immunotherapy has proved to be a very efficient therapeutic strategy for many types of tumors, the results for pancreatic cancer (PC) have been very poor. Indeed, chemotherapy remains the standard treatment for this tumor in the advanced stage. Clinical data showed that only a small portion of PC patients with high microsatellite instability/mismatch repair deficiency benefit from immunotherapy. However, the low prevalence of these alterations was not sufficient to lead to a practice change in the treatment strategy of this tumor. The main reasons for the poor efficacy of immunotherapy probably lie in the peculiar features of the pancreatic tumor microenvironment in comparison with other malignancies. In addition, the biomarkers usually evaluated to define immunotherapy efficacy in other cancers appear to be useless in PC. This review aims to describe the main features of the pancreatic tumor microenvironment from an immunological point of view and to summarize the current data on immunotherapy efficacy and immune biomarkers in PC.

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.

[...]GPP is a genetically and phenotypically distinct condition from plaque psoriasis, highlighting a potential unmet need for this specific patient population, as GPP requires tailored treatment strategies that address its unique characteristics. In the acute setting, patients with GPP complain of burning sensation in skin associated with some pain, usually without any triggering factor, and consequently with a severe impact on their quality of life [14]. Notably, the greater prevalence of anxiety and depression in patients with GPP indicates that they experienced a greater emotional burden compared with patient with plaque psoriasis. [...]patients with GPP may require a multidisciplinary strategy to manage both the psychological and physical manifestations of the disease [14]. Biologic agents that inhibit the IL-36 pathway have shown efficacy and a favorable safety profile in patients with GPP and thus represent novel potential therapeutic options for this patient population [12, 27, 28, 29, 30, 31–32].

Background/Objectives: The correlation between contact allergy (CA), atopic dermatitis (AD) and psoriasis is still debated. Therefore, the present study aims to retrospectively analyze the frequency of contact sensitization among patients with psoriasis and AD compared to controls, in order to further investigate the relationship between CA and the underlying immunological background. Methods: All data concerning patients who underwent patch testing from 2016 to 2022 in the dermatology clinic of a tertiary center in Southern Italy have been retrospectively collected. Only patients who underwent patch testing with the S.I.D.A.PA. standard series have been selected and divided into three groups: AD group, psoriasis group and control group. Acquired data were organized into database and underwent statistical examination. Results: A total of 2287 patients have been enrolled, including 377 AD patients, 127 psoriatic patients and 1783 controls. The most frequent allergens were nickel and balsam of Peru. Methylisothiazolinone (4.2% vs. 2.2%), paraben mix (0.3% vs. 0%) and neomycin (1.3% vs. 0.4%) significantly provided more positive reactions (PSR) in the AD group compared to the control one, and fragrance mix II displayed a higher rate of positivity in the atopic group compared to the psoriatic one (3.2% vs. 0%). Conclusions: Psoriasis turned out to be a possible protective factor for CA (odds ratio = 0.6), while AD seems to facilitate its development (odds ratio: 1.42). The limitations of this study mainly rely upon its retrospective nature which limited the acquisition of clinical relevance for PSR. Further studies are required to better investigate this topic.

This report discusses a female patient with longstanding discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE), refractory to multiple immunosuppressive and biologic treatments. Upon presenting with infiltrated, hypertrophic plaques in facial and décolletage regions, she was started on anifrolumab therapy after the histopathological confirmation of DLE. Following three infusions, significant clinical and dermoscopic improvements were observed, including the resolution of plaques and regression of scarring areas. This case highlights anifrolumab’s efficacy in severe lupus skin manifestations, emphasizing its potential to induce dermoscopic and histological remission. Additionally, it suggests that dermoscopy could be a valuable tool for monitoring therapeutic responses in DLE and cutaneous lupus erythematosus, warranting further investigation.