Zalaudek I.,Dermatology and Skin Cancer Unit |
Zalaudek I.,Medical University of Graz |
Kittler H.,Medical University of Vienna |
Hofmann-Wellenhof R.,Medical University of Graz |
And 11 more authors.
Journal of the American Academy of Dermatology | Year: 2013
Background: Spitz nevi and early melanomas lacking significant pigmentation exhibit overlapping dermoscopic patterns of regularly arranged dotted vessels over a pink background. Although white network has been described in both tumors, little is known about the frequency of this pattern in both tumors. Objective: We sought to compare the frequency of white network in Spitz nevi and early melanomas lacking significant pigmentation and to correlate this feature with histopathology. Methods: Two independent dermoscopists scored the presence of white network in a series of retrospectively collected images of histopathologically diagnosed cases of Spitz nevi and melanomas, dermoscopically typified by dotted vessels. Results: A total of 65 cases including 39 melanomas (median thickness 0.4 mm) and 26 Spitz nevi were analyzed. Patients with Spitz nevi were significantly younger compared to patients with melanoma (mean age: 26.8 vs 51.2 years, respectively; P <.001). The 2 observers scored white network being present in 23 (88.5%) and 24 (92.3%) Spitz nevi compared with 10 (25.6%) and 8 (20.5%) cases of 39 melanomas, respectively (P <.001). Interobserver agreement for white network was good (kappa = 0.67; 95% confidence interval 0.44-0.90). Histopathologically, elongated rete ridges were observed in 22 (88.5%) Spitz nevi and 11 (36.7%) melanomas (P <.001). Limitations: We did not evaluate other dermoscopic-histopathologic correlates commonly seen in Spitz nevi and melanomas in our study. Conclusion: Although white network occurs at significantly higher frequency among hypopigmented/amelanotic Spitz nevi compared with early melanoma, it is not exclusively seen in Spitz nevi. Thus, excision of melanocytic tumors showing this pattern is mandatory. © 2012 by the American Academy of Dermatology, Inc.
PubMed | Hospital Sant Joan Of Deu, Melanoma Unit and Hospital Clinic Of Barcelona
Type: Journal Article | Journal: Clinical and experimental dermatology | Year: 2016
Blue naevi may present rarely as multiple lesions grouped in a circumscribed area, described as agminated blue naevi. This clinical presentation may mimic metastatic malignant melanoma. We present two cases of agminated cellular blue naevi of the penis, with dermoscopy, reflectance confocal microscopy and histopathological correlation. Dermoscopy of the area showed multiple grouped lesions of homogeneous dark-brown to blue colour. Using reflectance confocal microscopy, focusing on the bluish areas, predominantly bright dendritic cells were visible at the dermoepidermal junction and papillary dermis, while in the brownish areas the presence of dendritic and bright cells predominated in the basal layer. Our patients are of special interest as they are the first cases, to our knowledge, reported of agminated blue naevi on the penis, studied by both dermoscopy and confocal microscopy, confirming the diagnosis with histopathological correlation. Moreover, one case represented a divided or kissing blue naevus of the penis.
Hore T.,North Shore Hospital |
Robinson E.,University of Auckland |
Martin R.C.W.,North Shore Hospital |
Martin R.C.W.,Melanoma Unit |
Martin R.C.W.,University of Auckland
World Journal of Surgery | Year: 2010
Background: Although cutaneous melanoma (CM) is rare among dark-skinned populations, it has been found that dark-skinned patients diagnosed with CM tend to have greater Breslow thickness and therefore a worse prognosis. Methods: Data was obtained from the New Zealand Cancer Registry pertaining to CM ICD-10 codes from 2000 to 2004. This data was used to compare different ethnicities. We compared New Zealand Europeans with those identifying themselves as Maori. Incorrect or absent data, benign nevi, and melanoma in situ were all excluded from analysis. Only one data entry was accepted per patient to avoid the inclusion of metastases. Results: Overall, 9004 patients were registered as being diagnosed with CM during 2000-2004, and 7120 with complete ethnicity data were analyzed. A total of 69 cases were identified as Maori. The incidence of CM among Maori is 2.7 per 100,000. Maori had significantly greater Breslow thickness compared with New Zealand Europeans (1.3 vs. 0.80 mm, P < 0.0001). There were differences in type of CM between the two groups (P < 0.00001); in particular, Maori had more acral CM (2.9% vs. 0.8%). Conclusions: Cutaneous melanoma is much less common among Maori than among New Zealand Europeans, but Maori have a greater Breslow depth and therefore have a worse prognosis. Increased awareness on behalf of these groups and health care practitioners should assist in ensuring early detection, thereby improving the overall outcome in Maori. © 2010 Société Internationale de Chirurgie.
Spain L.,Melanoma Unit |
Diem S.,Melanoma Unit |
Larkin J.,Melanoma Unit
Cancer Treatment Reviews | Year: 2016
Immune checkpoint inhibition with the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibodies nivolumab and pembrolizumab has improved survival in metastatic melanoma, lung cancer and renal cancer. Use of these agents holds promise in other malignancies. The augmented immune response enabled by these agents has led to a particular group of side effects called immune-related adverse events (irAEs). The main irAEs include diarrhea, colitis, hepatitis, skin toxicities and endocrinopathies such as hypophysitis and thyroid dysfunction. The anti-PD-1 antibodies have a different toxicity profile to ipilimumab with fewer high grade events. This article identifies the rates of common and uncommon irAEs associated with each immune checkpoint inhibitor (ICPI) and their timing of onset, focusing mainly on the experience in melanoma and lung cancer. An approach to management for each class of irAE is provided. © 2016 Elsevier Ltd.
Gonzalez-Alvarez T.,Melanoma Unit |
Armengot-Carbo M.,Melanoma Unit |
Armengot-Carbo M.,Hospital Arnau Of Vilanova |
Barreiro A.,Melanoma Unit |
And 8 more authors.
Dermatology | Year: 2014
The rosette structure is a dermoscopic sign visible under polarized light, characterized by 4 white points arranged as a 4-leaf clover. It has been mainly described in facial sun-damaged skin and actinic keratosis, although it has also been found in squamous and basal cell carcinomas, and in 2 cases of hypomelanotic melanomas. We describe 2 different cases of pigmented incipient melanomas with the presence of multiple rosettes and shiny white structures on dermoscopy. In the reflectance confocal microscope they exhibit a disarranged epidermal architecture with atypical and dendritic cells. Histological examination showed focal hyperkeratosis and a normal corneal layer presented alternatively. To our knowledge this is the first description of rosette structures in pigmented melanomas. Based on a proper dermoscopic- confocal-histopathological correlation, we hypothesize that rosettes could correspond to optic phenomena due to changes in the superficial epidermal reaction and in the acrosyringia. © 2013 S. Karger AG, Basel.
Sznol M.,Melanoma Unit
Seminars in Oncology | Year: 2012
Antibodies targeting ligandreceptor interactions that control activation and function of immune cell subsets such as dendritic cells (DCs) and in particular T cells have shown substantial promise for the treatment of unresectable or metastatic melanoma. The furthest in development, the antagonist antiCTLA-4 antibodies, which block a key negative regulator of T-cell activation, have been shown to produce durable clinical responses in a small subset of patients. One of these antibodies, ipilimumab, also prolonged overall survival in two randomized phase III studies, leading to regulatory approval for marketing by the US Food and Drug Administration (FDA). Consistent with its mechanism of action, the major adverse events from antiCTLA4 stem from immune-mediated inflammatory reactions. Paradigms for the administration of antiCTLA-4 and newer immunomodulatory agents have evolved to effectively manage the adverse events and also to consider unique patterns and kinetics of tumor response. Early clinical studies of another antagonist antibody, which blocks the co-inhibitory receptor PD-1 on activated T cells, also are showing promising activity in metastatic melanoma. The clinical efficacy of cancer vaccines, which in broad terms also includes intratumorally administered agents designed to increase tumor immunogenicity, is being investigated in ongoing phase III trials, and various new agents are in earlier development, including newer cytokines and T-cell or DC co-stimulatory antibodies, some of which have already demonstrated clinical activity in advanced disease. Current data suggest that focusing development on agents countering immune suppression in the tumor microenvironment or blocking regulatory checkpoints to T-cell activation may have the greatest clinical yield. Combinations of immunomodulatory agents also may improve clinical activity, although possibly at a cost of greater toxicity. A major challenge for the field will be to develop predictive biomarkers of response, and to identify mechanisms of resistance to existing agents that can be addressed in subsequent clinical trials. © 2012 Elsevier Inc.
Spain L.,Melanoma Unit |
Julve M.,Melanoma Unit |
Larkin J.,Melanoma Unit
Expert Opinion on Pharmacotherapy | Year: 2016
Introduction: In the 40-50% of advanced melanoma patients with tumors harboring BRAF V600E and V600 K mutations, BRAF inhibitors such as dabrafenib are a highly effective treatment. However, most patients develop resistance after several months on treatment. The addition of a MEK inhibitor, such as trametinib, to BRAF inhibition mitigates one key pathway of resistance, further increasing response rates and improving survival.Areas covered: This article summarizes the mechanism of action of the combination of dabrafenib and trametinib, its evolution through Phase I, II and III clinical trials and discusses its current use in the management of patients with advanced melanoma.Expert opinion: Combination therapy with dabrafenib and trametinib improves response rate, progression-free survival and overall survival when compared to dabrafenib or vemurafenib alone. The addition of trametinib to dabrafenib changes the adverse event profile, making hyperkeratosis and cutaneous squamous cell carcinomas less common but side effects such as fever and nausea more common. How dabrafenib/trametinib is best sequenced with other effective treatments such as immune checkpoint blockade remains uncertain. © 2016 Informa UK Limited.
PubMed | Cancer Research UK Research Institute, Imperial College London, Melanoma Unit and Guys and St Thomas NHS Foundation Trust
Type: Journal Article | Journal: British journal of cancer | Year: 2015
The melanoma-specific graded prognostic assessment (msGPA) assigns patients with brain metastases from malignant melanoma to 1 of 4 prognostic groups. It was largely derived using clinical data from patients treated in the era that preceded the development of newer therapies such as BRAF, MEK and immune checkpoint inhibitors. Therefore, its current relevance to patients diagnosed with brain metastases from malignant melanoma is unclear. This study is an external validation of the msGPA in two temporally distinct British populations.Performance of the msGPA was assessed in Cohort I (1997-2008, n=231) and Cohort II (2008-2013, n=162) using Kaplan-Meier methods and Harrells c-index of concordance. Cox regression was used to explore additional factors that may have prognostic relevance.The msGPA does not perform well as a prognostic score outside of the derivation cohort, with suboptimal statistical calibration and discrimination, particularly in those patients with an intermediate prognosis. Extra-cerebral metastases, leptomeningeal disease, age and potential use of novel targeted agents after brain metastases are diagnosed, should be incorporated into future prognostic models.An improved prognostic score is required to underpin high-quality randomised controlled trials in an area with a wide disparity in clinical care.
PubMed | Radiology Unit and Melanoma Unit
Type: Journal Article | Journal: Cancer immunology, immunotherapy : CII | Year: 2016
The efficacy and potential toxicity of rechallenge with combination ipilimumab and nivolumab has not been described. Retreatment of patients with immune checkpoint inhibitors in the setting of prior significant toxicity lacks evidence-based guidance.We present the first three, consecutive patients who received re-treatment with combination ipilimumab and nivolumab for metastatic melanoma managed at our institution.Rechallenge with combination ipilimumab and nivolumab in the setting of prior grade 3 toxicity with initial combination therapy is feasible, and responses are seen. We highlight the fact that grade 3 toxicity is likely to recur, but if so, can be manageable.Retreatment with ipi+nivo may be considered an option in carefully selected, well-informed patients. More research is required to delineate the benefits and risks with this approach.
PubMed | Melanoma Unit
Type: | Journal: Cancer treatment reviews | Year: 2016
Immune checkpoint inhibition with the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibodies nivolumab and pembrolizumab has improved survival in metastatic melanoma, lung cancer and renal cancer. Use of these agents holds promise in other malignancies. The augmented immune response enabled by these agents has led to a particular group of side effects called immune-related adverse events (irAEs). The main irAEs include diarrhea, colitis, hepatitis, skin toxicities and endocrinopathies such as hypophysitis and thyroid dysfunction. The anti-PD-1 antibodies have a different toxicity profile to ipilimumab with fewer high grade events. This article identifies the rates of common and uncommon irAEs associated with each immune checkpoint inhibitor (ICPI) and their timing of onset, focusing mainly on the experience in melanoma and lung cancer. An approach to management for each class of irAE is provided.