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Modern diagnostic procedures, such as three-dimensional total body photography (3D-TBP), digital dermoscopy (DD), and reflectance confocal microscopy (RCM), can improve melanoma diagnosis, particularly in high-risk patients. This study assessed the benefits of combining these advanced imaging techniques in a three-step programme in managing high-risk patients. This study included 410 high-risk melanoma patients who underwent a specialised imaging consultation in addition to their regular skin examinations in outpatient care. At each visit, the patients underwent a 3D-TBP, a DD for suspicious findings, and an RCM for unclear DD findings. The histological findings of excisions initiated based on imaging consultation and outpatient care were compared. Imaging consultation detected sixteen confirmed melanomas (eight invasive and eight in situ) in 39 excised pigmented lesions. Outpatient care examination detected seven confirmed melanomas (one invasive and six in situ) in 163 excised melanocytic lesions. The number needed to excise (NNE) in the imaging consultation was significantly lower than that in the outpatient care (2.4 vs. 23.3). The NNE was 2.6 for DD and 2.3 for RCM. DD, 3D-TBP, or RCM detected melanomas that were not detected by the other imaging methods. The three-step imaging programme improves melanoma detection and reduces the number of unnecessary excisions in high-risk patients.
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BACKGROUND: Cutaneous manifestations of drug-induced type IV reactions vary widely, with symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) being a less common presentation. Corticosteroids (CS), primarily known for their anti-inflammatory effects, rarely induce hypersensitivity reactions. OBJECTIVE: The aim of this case series is to report four cases of SDRIFE following systemic prednisolone therapy and to review existing CS classification proposals to better understand cross-reactivity of CS. PATIENTS/METHODS: Patients recruited at a German dermatology centre underwent allergologic evaluation including prick and patch testing with various CS. Positive cases underwent oral challenge testing with alternative agents. The classification systems of Coopman et al. and Baeck et al. were taken into account. DISCUSSION: Despite a paucity of literature, CS-induced type IV reactions do occur, including SDRIFE. Classification systems based on chemical structure provide insight into cross-reactivity patterns. Provocation tests with alternative CS highlight the complexity of managing CS hypersensitivity. CONCLUSION: SDRIFE may develop following systemic prednisolone therapy. Classification systems are helpful in understanding cross-reactivity and help in the selection of alternative preparations but are not always reliable. Individualised assessment is crucial for managing CS hypersensitivity, with consideration of alternative agents and emergency use of CS when necessary.
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Erupciones por Medicamentos , Exantema , Prednisolona , Humanos , Femenino , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/diagnóstico , Exantema/inducido químicamente , Persona de Mediana Edad , Prednisolona/uso terapéutico , Prednisolona/administración & dosificación , Masculino , Adulto , Reacciones Cruzadas , Anciano , Pruebas del Parche , Glucocorticoides/uso terapéutico , Glucocorticoides/administración & dosificaciónRESUMEN
BACKGROUND: Treatment decisions in metastatic melanoma (MM) are highly dependent on patient preferences and require the patients' involvement. The complexity of treatment options with their individual advantages and disadvantages is often overwhelming. We therefore developed an online patient decision aid (PtDA) to facilitate shared decision making (SDM). METHODS: To evaluate the PtDA we conducted a two-armed, twocenter, prospective, open randomized controlled trial with MM patients who were facing a decision about first-line treatment. The patients were allotted randomly in a 1:1 ratio to an intervention group (IG) with access to the PtDA before discussion with a physician or to a control group (CG) without access to the PtDA. The primary endpoint was knowledge about the options for first-line treatment (multiple-choice test, 10 items, range 0-40 points). The secondary endpoints were the SDM (third-party ratings of audio recordings of the treatment discussions) and satisfaction with the decision at the follow-up visit. RESULTS: Of the 128 randomized patients, 120 completed the baseline questionnaire and were analyzed (59% male, median age 66 years). The primary endpoint, i.e., the mean difference in knowledge after discussion with a physician, differed significantly between the IG and the CG (-3.22, 95% CI [-6.32; -0.12], p = 0.042). No differences were found for the secondary endpoints, SDM and satisfaction with the decision. The patients in the IG rated the PtDA as very useful. CONCLUSION: The PtDA improved the knowledge of patients with MM about the options for treatment. Both groups were highly satisfied with their treatment decisions. However, additional physician training seems necessary to promote SDM.
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Melanoma , Humanos , Melanoma/secundario , Melanoma/terapia , Masculino , Femenino , Anciano , Persona de Mediana Edad , Técnicas de Apoyo para la Decisión , Participación del Paciente/estadística & datos numéricos , Participación del Paciente/métodos , Neoplasias Cutáneas/terapia , Alemania , Estudios Prospectivos , Adulto , Satisfacción del Paciente/estadística & datos numéricos , Educación del Paciente como Asunto/métodosRESUMEN
Dermatomyositis (DM) is a rare autoimmune disease with involvement of skin and muscle that is classified as an idiopathic inflammatory myopathy. In addition to cutaneous lesions as well as weakness and atrophy of muscles, the heart and lungs are the major affected organs. DM occurs in association with malignant tumors in 20% of affected adults. The pathogenesis of the disease is not completely understood. DM is a multifactorial disease influenced by genetic, environmental and immunological factors. The immune response is characterized by activation of innate and adaptive immune mechanisms and a strong activation of the type I interferon pathway. Myositis-specific antibodies are characteristic of DM and allow differential diagnosis. Therapies include corticosteroids, antimalarials, immunoglobulins, biologics such as rituximab or JAK inhibitors. Early diagnosis and treatment are essential for the prognosis.
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Dermatomiositis , Miositis , Adulto , Humanos , Dermatomiositis/diagnóstico , Miositis/diagnóstico , Piel , Corticoesteroides/uso terapéutico , AnticuerposRESUMEN
INTRODUCTION: Non-melanoma skin cancer (NMSC) is a cause of significant morbidity and mortality in high-risk individuals. Total body photography (TBP) is currently used to monitor melanocytic lesions in patients with high risk for melanoma. The authors examined if three-dimensional (3D)-TBP could be useful for diagnosis of NMSC. METHODS: Patients (n = 129; 52 female, 77 male) with lesions suspicious for NMSC who had not yet had a biopsy underwent clinical examination followed by examination of each lesion with 3D-TBP Vectra®WB360 (Canfield Scientific, Parsippany, NJ, USA) and dermoscopy. RESULTS: The 129 patients had a total of 182 lesions. Histological examination was performed for 158 lesions; the diagnoses included basal cell carcinoma (BCC; n = 107), squamous cell carcinoma (SCC; n = 27), in-situ SCC (n = 15). Lesions were located in the head/neck region (n = 138), trunk (n = 21), and limbs (n = 23). Of the 182 lesions examined, 12 were not visible on 3D-TBP; reasons for not being visible included location under hair and on septal of nose. Two lesions appeared only as erythema in 3D-TBP but were clearly identifiable on conventional photographs. Sensitivity of 3D-TBP was lower than that of dermoscopy for BCC (73% vs. 79%, p = 0.327), higher for SCC (81% vs. 74%, p = 0.727), and lower for in-situ SCC (0% vs. 33%, p = 125). Specificity of 3D-TBP was lower than that of dermoscopy for BCC (77% vs. 82%, 0.581), lower for SCC (75% vs. 84%, p = 0.063), and higher for in-situ SCC (97% vs. 94%, p = 0.344). Diagnostic accuracy of 3D-TBP was lower than that of dermoscopy for BCC (75% vs. 80%), lower for SCC (76% vs. 82%), and lower for in-situ SCC (88% vs. 89%). Lesion location was not associated with diagnostic confidence in dermoscopy (p = 0.152) or 3D-TBP (p = 0.353). If only lesions with high confidence were included in the calculation, diagnostic accuracy increased for BCC (n = 27; sensitivity 85%, specificity 85%, diagnostic accuracy 85%), SCC (n = 10; sensitivity 90%, specificity 80%, diagnostic accuracy 83%), and for in-situ SCC (n = 2; sensitivity 0%, specificity 100%, diagnostic accuracy 95%). CONCLUSION: Diagnostic accuracy appears to be slightly lower for 3D-TBP in comparison to dermoscopy. However, there is no statistically significant difference in the sensitivity and specificity of 3D-TBP and dermoscopy for NMSC. Diagnostic accuracy increases, if only lesions with high confidence are included in the calculation. Further studies are necessary to determine if 3D-TBP can improve management of NMSC.
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Carcinoma Basocelular , Melanoma , Neoplasias Cutáneas , Humanos , Femenino , Masculino , Dermoscopía/métodos , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patología , Melanoma/diagnóstico por imagen , Melanoma/patología , Carcinoma Basocelular/diagnóstico por imagen , Carcinoma Basocelular/patología , FotograbarRESUMEN
Cutaneous cystic lesions (nâ¯= 35) were examined with optical coherence tomography. Cysts were visible as a hyporeflective roundish area with a clear margin; in some cases, the epidermis was thinned. Epidermal cysts, trichilemmal cysts, and hidrocystomas had a linear margin representing the epithelium of the cyst, whereas mucoid pseudocysts showed no linear margin. Trichilemmal and epidermal cysts presented with hyperreflective content that corresponds to keratin. By visualizing the margin and the content of the cyst, it was possible to differentiate between different types of cysts.
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Quiste Epidérmico , Hidrocistoma , Neoplasias Cutáneas , Neoplasias de las Glándulas Sudoríparas , Humanos , Quiste Epidérmico/diagnóstico , Tomografía de Coherencia Óptica , Neoplasias Cutáneas/diagnóstico , Hidrocistoma/patología , Neoplasias de las Glándulas Sudoríparas/patologíaRESUMEN
Leptomeningeal disease (LMD) is a devastating complication of cancer with a particularly poor prognosis. Among solid tumours, malignant melanoma (MM) has one of the highest rates of metastasis to the leptomeninges, with approximately 10-15% of patients with advanced disease developing LMD. Tumour cells that metastasise to the brain have unique properties that allow them to cross the blood-brain barrier, evade the immune system, and survive in the brain microenvironment. Metastatic colonisation is achieved through dynamic communication between metastatic cells and the tumour microenvironment, resulting in a tumour-permissive milieu. Despite advances in treatment options, the incidence of LMD appears to be increasing and current treatment modalities have a limited impact on survival. This review provides an overview of the biology of LMD, diagnosis and current treatment approaches for MM patients with LMD, and an overview of ongoing clinical trials. Despite the still limited efficacy of current therapies, there is hope that emerging treatments will improve the outcomes for patients with LMD.
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Melanoma , Carcinomatosis Meníngea , Neoplasias Meníngeas , Neoplasias Cutáneas , Humanos , Carcinomatosis Meníngea/diagnóstico , Carcinomatosis Meníngea/secundario , Carcinomatosis Meníngea/terapia , Melanoma/diagnóstico , Melanoma/terapia , Melanoma/secundario , Encéfalo , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/terapia , Microambiente Tumoral , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: Recent advances in digital pathology have enabled accurate and standardised enumeration of tumour-infiltrating lymphocytes (TILs). Here, we aim to evaluate TILs as a percentage electronic TIL score (eTILs) and investigate its prognostic and predictive relevance in cutaneous melanoma. METHODS: We included stage I to IV cutaneous melanoma patients and used hematoxylin-eosin-stained slides for TIL analysis. We assessed eTILs as a continuous and categorical variable using the published cut-off of 16.6% and applied Cox regression models to evaluate associations of eTILs with relapse-free, distant metastasis-free, and overall survival. We compared eTILs of the primaries with matched metastasis. Moreover, we assessed the predictive relevance of eTILs in therapy-naïve metastases according to the first-line therapy. FINDINGS: We analysed 321 primary cutaneous melanomas and 191 metastatic samples. In simple Cox regression, tumour thickness (p < 0.0001), presence of ulceration (p = 0.0001) and eTILs ≤16.6% (p = 0.0012) were found to be significant unfavourable prognostic factors for RFS. In multiple Cox regression, eTILs ≤16.6% (p = 0.0161) remained significant and downgraded the current staging. Lower eTILs in the primary tissue was associated with unfavourable relapse-free (p = 0.0014) and distant metastasis-free survival (p = 0.0056). In multiple Cox regression adjusted for tumour thickness and ulceration, eTILs as continuous remained significant (p = 0.019). When comparing TILs in primary tissue and corresponding metastasis of the same patient, eTILs in metastases was lower than in primary melanomas (p < 0.0001). In therapy-naïve metastases, an eTILs >12.2% was associated with longer progression-free survival (p = 0.037) and melanoma-specific survival (p = 0.0038) in patients treated with anti-PD-1-based immunotherapy. In multiple Cox regression, lactate dehydrogenase (p < 0.0001) and eTILs ≤12.2% (p = 0.0130) were significantly associated with unfavourable melanoma-specific survival. INTERPRETATION: Assessment of TILs is prognostic in primary melanoma samples, and the eTILs complements staging. In therapy-naïve metastases, eTILs ≤12.2% is predictive of unfavourable survival outcomes in patients receiving anti-PD-1-based therapy. FUNDING: See a detailed list of funding bodies in the Acknowledgements section at the end of the manuscript.
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Aprendizaje Profundo , Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/patología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Pronóstico , Linfocitos Infiltrantes de Tumor/patología , Recurrencia Local de Neoplasia/patología , Melanoma Cutáneo MalignoRESUMEN
Despite remarkable advances in treating patients with metastatic melanoma, the management of melanoma brain metastases remains challenging. Recent evidence suggests that epigenetic reprogramming is an important mechanism for the adaptation of melanoma cells to the brain environment. In this study, the methylomes and transcriptomes of a cohort of matched melanoma metastases were evaluated by integrated omics data analysis. The identified 38 candidate genes displayed distinct promoter methylation and corresponding gene expression changes in intracranial compared with extracranial metastases. The 11 most promising genes were validated on protein level in both tumor and surrounding normal tissue using immunohistochemistry. In accordance with the underlying promoter methylation and gene expression changes, a significantly different protein expression was confirmed for STK10, PDXK, WDR24, CSSP1, NMB, RASL11B, phosphorylated PRKCZ, PRKCZ, and phosphorylated GRB10 in the intracranial metastases. The observed changes imply a distinct intracranial phenotype with increased protein kinase B phosphorylation and a higher frequency of proliferating cells. Knockdown of PRKCZ or GRB10 altered the expression of phosphorylated protein kinase B and decreased the viability of a brain-specific melanoma cell line. In summary, epigenetically regulated cancer-relevant alterations were identified that provide insights into the molecular mechanisms that discriminate brain metastases from other organ metastases, which could be exploited by targeting the affected signaling pathways.
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Neoplasias Encefálicas , Melanoma , Proteínas de Unión al GTP Monoméricas , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Melanoma/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Encéfalo/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas de Unión al GTP Monoméricas/metabolismoRESUMEN
Psoriasis is frequently associated with the metabolic syndrome and occurs more often in obese individuals. In order to understand innate immune mechanisms mediating this inflammatory pattern we investigated expression of the chemokine and lipid scavenger receptor CXCL16 in patients with psoriasis and associated comorbidities. CXCL16 expression was enhanced on all monocyte subsets in psoriatic patients compared with healthy controls and positively correlated with psoriasis activity and severity index, body mass index and the risk for cardiovascular disease indicated by PROCAM score. The intensity of CXCL16 expression on monocytes further correlated with their capability to phagocytose oxidized LDL indicating the possibility to transform into foam cells in atherosclerotic plaques. Patients with psoriasis and atherosclerosis or obesity displayed elevated numbers of innate lymphoid cells in blood with specific increase of the IFN-γ or IL-17 producing ILC1 and ILC3 subpopulations. The expression of the CXCL16 receptor, CXCR6, was increased in ILCs and co-expressed with CCR6 but not CCR7 indicating their migratory potential to psoriatic skin or adipose tissue that is characterized by strong CXCL16 and CCL20 expression. This hypothesis was supported by the finding that the percentage of CXCR6 expressing ILCs was alleviated in blood of psoriatic patients. Together these data link a strong expression of CXCL16 to metabolic syndrome in psoriasis and indicate a possible link to ILC activation and tissue distribution in obese psoriatic patients. These data contribute to the understanding of the complex interaction of innate immunity and metabolic state in psoriasis.
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Síndrome Metabólico , Psoriasis , Quimiocina CXCL16/metabolismo , Humanos , Inmunidad Innata , Linfocitos , Síndrome Metabólico/metabolismo , Monocitos , Obesidad/metabolismo , Regulación hacia ArribaAsunto(s)
Dermatomiositis , Inhibidores de las Cinasas Janus , Paniculitis , Azetidinas , Dermatomiositis/complicaciones , Dermatomiositis/tratamiento farmacológico , Humanos , Inflamación , Janus Quinasa 1 , Janus Quinasa 2 , Inhibidores de las Cinasas Janus/uso terapéutico , Paniculitis/tratamiento farmacológico , Paniculitis/etiología , Purinas , Pirazoles , SulfonamidasRESUMEN
This decade has brought significant survival improvement in patients with metastatic melanoma with targeted therapies and immunotherapies. As our understanding of the mechanisms of action of these therapeutics evolves, even more impressive therapeutic success is being achieved through various combination strategies, including combinations of different immunotherapies as well as with other modalities. This review summarizes prospectively and retrospectively generated clinical evidence on modern melanoma therapy, focusing on immunotherapy and targeted therapy with BRAF kinase inhibitors and MEK kinase inhibitors (BRAF/MEK inhibitors), including recent data presented at major conference meetings. The combination of the anti-PD-1 directed monoclonal antibody nivolumab and of the CTLA-4 antagonist ipilimumab achieves unprecedented 5-year overall survival (OS) rates above 50%; however, toxicity is high. For PD-1 monotherapy (nivolumab or pembrolizumab), toxicities are in general well manageable. Today, novel combinations of such immune checkpoint inhibitors (ICIs) are under investigation, for example with cytokines and oncolytic viruses (i.e., pegylated interleukin-2, talimogene laherparepvec). Furthermore, current studies investigate the combined or sequential use of ICIs plus BRAF/MEK inhibitors. Several studies focus particularly on poor prognosis patients, as e.g., on anti-PD-1 refractory melanoma, patients with brain metastases, or uveal melanoma. It is hoped, on the road to cure, that these new approaches further improve long term survival in patients with advanced or metastatic melanoma.