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Purpose : To report a case of bilateral retinal inflammation under long-term therapy with dabrafenib/trametinib for metastatic cutaneous melanoma. Methods : Retrospective chart review. Results : A 59-year-old patient with metastatic cutaneous melanoma diagnosed in 2004 under treatment with dabrafenib/trametinib since 2014 presented to our department with intraretinal hemorrhage and extrafoveal macula edema on the right eye and optic disc swelling on the left eye. The patient did not report visual complaints. After cessation of dabrafenib/trametinib and subconjunctival and intravitreal corticosteroid injections, optic disc swelling on the left eye recovered after 6 months. The macula edema on the right eye was treated with one intravitreal anti-VEGF (vascular endothelial growth factor) injection after encroaching upon the fovea 10 months after initial presentation. The final visual acuity was 20/20 on both eyes. Conclusion : Even after years of treatment with low dose dabrafenib/trametinib, ocular toxicity can develop. Such cases can respond well to intravitreal corticosteroids.

We prospectively performed a longitudinal analysis of circulating tumor DNA (ctDNA) from 149 plasma samples and CT scans in Stage III and IV metastatic melanoma patients ( n = 20) treated with targeted agents or immunotherapy using two custom next-generation sequencing (NGS) Ion AmpliSeq™ HD panels including 60 and 81 amplicons in 18 genes, respectively. Concordance of matching cancer-associated mutations in tissue and plasma was 73.3%. Mutant allele frequency (MAF) levels showed a range from 0.04% to 28.7%, well detectable with NGS technologies utilizing single molecule tagging like the AmpliSeq™ HD workflow. Median followup time of the tissue and/or plasma positive cohort ( n = 15) was 24.6 months and median progression-free survival (PFS) was 7.8 months. Higher MAF ≥ 1% at baseline was not significantly associated with a risk of progression (Odds Ratio = 0.15; p = 0.155). Although a trend could be seen, MAF levels did not differ significantly over time between patients with and without a PFS event ( p = 0.745). Depending on the cell-free DNA amount, NGS achieved a sensitivity down to 0.1% MAF and allowed for parallel analysis of multiple mutations and previously unknown mutations. Our study indicates that NGS gene panels could be useful for monitoring disease burden during therapy with ctDNA in melanoma patients.

Introduction: Cutaneous melanoma is one of the most aggressive forms of skin neoplasms and represents a major cause of neoplastic or cancer death in Europe. Without adequate therapy, the 5-year survival rate is 15% when the disease metastasizes to distant organs. The objective of our study was to evaluate the status quo of the current treatment standards in stage IV melanoma and rationale for therapy decisions in Germany and Austria between January 2016 and September 2018., Methods: In this retrospective, anonymized registry, data of male and female patients with unresectable advanced/metastatic BRAF-positive cutaneous melanoma treated in the first, second, and third line with registered substances were analyzed using descriptive statistics., Results: Ninety-nine patients (50.5% male) received a total of 172 treatment lines. The first (99 patients), second (56 patients), and third (17 patients) treatment lines were documented. Within the 80.8% of patients with stage IV melanoma, targeted therapy (TT) was more frequently administered as a first-line treatment than immunotherapy (IO) with checkpoint inhibitors (59.6% TT vs. 40.4% IO). Across all lines, patients received TT in 54.7% and IO in 43.0% of the cases. As targeted agents, dabrafenib plus trametinib was predominantly prescribed (72.3%), whereas the monotherapy with anti-programmed cell death protein 1 and anti-cytotoxic T lymphocyte-associated protein 4 antibodies or their combination was prescribed similarly often (50.0% vs. 47.3%). Most commonly, the treatment type was switched from TT to IO or vice versa upon disease progression. The most frequent rationales for prescribing either TT or IO were remission pressure (72.9%) or physician's preference (45.0%), respectively. Disease progression was a more frequent cause of treatment discontinuation than undesired events., Conclusion: Patients in Germany and Austria with unresectable advanced or metastatic BRAF-mutant melanoma predominantly receive guideline-recommended treatments. TT was more frequently administered than IO while the rationale for prescribing a specific treatment type differed between the two.

B cells often infiltrate the microenvironment of human tumors. B cells can both positively and negatively regulate antitumor immune responses. In several human cancers, higher numbers of CD20(+) TAB are associated with a favorable prognosis, whereas in human primary melanomas, this association is contentious. In this study, we determined the association of TAB numbers in cutaneous primary melanoma tissue samples and patients' overall survival. The CD20 immunohistochemistry on archival nonmetastasized and metastasized cutaneous primary melanoma tissues from 2 independent patient cohorts was performed. One cohort was used in class comparison for metastasis, the most important prognostic factor for overall survival, and the other cohort for a subsequent survival analysis. Survival association was further validated with RNA data from a third independent cohort. Whole tissue sections were read automatically via quantitative digital imaging and analysis. Survival data were analyzed by Cox proportional hazard modeling. We discovered that cutaneous primary melanomas without metastasis contain significantly more TAB than primary melanomas that had metastasized. At time of first diagnosis, a higher number of TAB is associated with a significantly better overall survival in patients with cutaneous primary melanomas of >1 mm Breslow depth. Also, higher CD20/CD19 tumor mRNA levels are correlated with a significantly better overall survival. Thus, our data support TAB numbers as a prognostic biomarker in cutaneous primary melanoma patients with a tumor of >1 mm Breslow depth. For a survey in larger studies, whole tissue section analysis seems to be key to accurate assessment of TAB numbers., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The significance of the histological visualization of hemophagocytosis in tissues depends on the context, varying from a nonspecific phenomenon to a characteristic or diagnostic feature for certain disease entities. Hemophagocytosis is also one of the key features of macrophage activation syndrome (MAS) (hemophagocytic syndrome) a potentially life-threatening complication of underlying conditions such as infections, malignancy, and autoimmune disorders. Clinical manifestations of MAS are high fever, pancytopenia, liver dysfunction, and coagulopathy. These clinical symptoms are due to an abnormal activation of the immune system in a strong association with the cytokine milieu. The diagnosis of MAS may be easily missed; it is usually detected in the bone marrow, lymph node, liver, and spleen. Only few reports exist in the literature with histological description of cutaneous hemophagocytosis as a sign for MAS in patients with lymphoma and infection. In this report, the authors present the clinicopathological and immunohistochemical features of 3 patients with cutaneous hemophagocytosis, specifically erythrophagocytosis, associated with autoimmune disease, and discuss the relevance of these findings., Observation: The authors report 3 patients who developed cutaneous hemophagocytosis during the course of an underlying autoimmune disorder. One patient suffered from dermatomyositis, the other 2 patients from systemic lupus erythematosus, whereby one of them was a 3-month old girl with neonatal lupus erythematosus. The patient with dermatomyositis developed MAS according to the current diagnostic criteria. Although the 2 other patients had an acute flare of their autoimmune disease with histological signs of cutaneous hemophagocytosis, they did not fulfill the complete criteria for a diagnosis of MAS. Histiocyte proliferation and activation with increase of cytokines could be demonstrated by immunohistology., Conclusions: This report is the first to describe hemophagocytosis in cutaneous biopsies of patients with autoimmune diseases, associated with a complete or incomplete constellation of MAS. Key players in this process are histiocytes/macrophages engaged in phagocytosis of erythrocytes. Hemophagocytosis observed in skin biopsies may be a diagnostic clue for MAS and an indicator for a potentially aggressive course of the underlying disease.

Background: After the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma was published in 1983 with its subsequent recognition by the FDA for its refractory forms, the technology has shown significant promise in the treatment of other severe and refractory conditions in a multi-disciplinary setting. Among the major studied conditions are graft versus host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection and inflammatory bowel disease., Materials and Methods: In order to provide recognized expert practical guidelines for the use of this technology for all indications the European Dermatology Forum (EDF) proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task., Results and Conclusion: These guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion., (© 2013 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background & Aims: New treatment approaches are needed for patients with pancreatic adenocarcinoma. Carcinoembryonic antigen (CEA) is highly expressed on the surface of pancreatic adenocarcinoma cells; we investigated the effects of cytolytic T cells that recognize CEA in a mouse model of pancreatic carcinoma., Methods: Immune-competent mice that expressed the CEA transgene (CEAtg) in the intestinal and pulmonary tracts were given intrapancreatic injections of Panc02 CEA(+) cells (express CEA and click beetle luciferase) and tumors were grown for 10 days. Mice were then given single intravenous injections of T cells engineered to express a chimeric antigen receptor (CAR) with high specificity, but moderate affinity, for CEA and a luminescence marker., Results: Injection of the anti-CEA CAR T cells reduced the size of pancreatic tumors to below the limit of detection in all mice and produced long-term tumor eradication in 67% of mice. T cells also eradicated CEA(+) fibrosarcoma cells injected 45 days later. Bioluminescence imaging revealed the accumulation and persistence of the T cells at the tumor site. The efficacy of the T cells did not require lymphodepletion and was not reduced by soluble CEA. Mice developed some noninflammatory infiltrations of CAR(+) T cells in intestine and lung, but there was no evidence of destruction of CEA(+) healthy tissues., Conclusions: Injection of T cells that target CEA can eradicate tumors grown from CEA(+) pancreatic carcinoma cells in the pancreas of CEAtg mice without autoimmune effects., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Computerized analysis of pigmented skin lesions may help to increase diagnostic accuracy for melanoma, help to avoid unnecessary procedures and reduce health care costs., Objectives: We evaluated both the patient acceptance and diagnostic utility of such an analysis tool in a real clinical setting., Methods: Two hundred nine consecutive patients (median age: 34 years, range: 2-73 years), who were concerned about a pigmented skin lesion, answered a questionnaire about their attitude towards computerized analysis and their confidence in the resulting findings. Using a dermoscopy analyser, their skin lesions (n = 219) were then grouped into the categories, benign, suspicious and malignant, and results were compared with those obtained by in-person examination of dermato-oncologic experts., Results: More than half of the patients (n = 114) would accept the use of computer analysis for melanoma screening; although 16 (14.0%) patients would accept this method solely, 98 (86.0%) patients would prefer an additional in-person examination by a dermatologist. Of the 219 pigmented skin lesions, the dermoscopic experts rated 171 (78.1%) as benign, 36 (16.4%) as suspicious and 12 (5.5%) as malignant, whereas computer analysis revealed 102 (46.6%) benign, 78 (35.6%) suspicious and 39 (17.8%) malignant lesions. At the expense of specificity (48.8%), the sensitivity of computerized analysis was excellent (100%) and equal to that of in-person examination., Conclusions: Most patients would accept computer analysis for melanoma screening, some of them even without reservations. However, due to a high rate of false positive computer assessments, it cannot be recommended as a screening tool at this time., (© 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.)

Objective: To better characterize the dermoscopic patterns of mucosal lesions in relation to the histopathologic characteristics., Design: Retrospective and observational study., Setting: Fourteen referral pigmented lesion clinics in 10 countries., Patients: A total of 140 pigmented mucosal lesions (126 benign lesions, 11 melanomas, 2 Bowen disease lesions, and 1 metastasis) from 92 females (66%) and 48 males (34%) were collected from October 2007 through November 2008., Main Outcome Measures: Scoring the dermoscopic patterns (dots, globules, or clods, circles, lines, or structureless) and colors (brown, black, blue, gray, red, purple, and white) and correlation with the histopathologic characteristics., Results: Based on univariate analysis and 2 diagnostic models, the presence of structureless zones inside the lesions with blue, gray, or white color (the first model) had a 100% sensitivity for melanoma and 92.9% sensitivity for any malignant lesion, and 82.2% and 83.3% specificity for benign lesions in the group with melanoma lesions and the group with malignant lesions, respectively. Based on the colors (blue, gray, or white) only (the second model), the sensitivity for the group with melanoma was 100% and for the group with any malignant lesion was 92.9%, and the specificity was 64.3% and 65.1%, respectively. Patients with malignant lesions were significantly older than patients with benign lesions (mean [SD] ages, 60.1 [22.8] years vs 43.2 [17.3] years, respectively)., Conclusion: The combination of blue, gray, or white color with structureless zones are the strongest indicators when differentiating between benign and malignant mucosal lesions in dermoscopy.

Ancient melanocytic nevus (AN) is an unusual but distinctive melanocytic neoplasm within the spectrum of simulators of malignant melanoma. This report describes 13 patients with AN where a long follow-up information was available. Histopathology is characterized by 2 populations of melanocytes, namely, one with large pleomorphic cells and the other with small melanocytes. A few mitotic figures may be present exceptionally. MIB-1 (Ki67) proliferation marker reveals an overall low nuclear labeling index. Additional important findings are stromal degenerative changes. AN must be especially differentiated from dermal melanoma arising in a nevus.

This work displays the bridging of two fields - namely dermatopathology and art. What is astonishing is that structures one sees through the microscope reveal aesthetic and artistic aspects and sometimes resemble in a startling way the designs of certain artists. Specific examples are illustrated to enhance the joy and appreciation of morphologic images., (© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.)

We describe two exceptional collision tumors, namely: a 63-year-old woman revealing a melanocytic tumor within a trichoblastoma and a 71-year-old woman with a squamous cell carcinoma colonized by dendritic cells of a melanoma. Both neoplasms showed two different tumor components with intimate relationship. The lesions are labeled in a "playful" way with the acronyms METRO (MElanocytic tumor +TRichOblastoma) and CAMEL (CArcinoma +MELanoma) to facilitate memorization.

Skin infections after transplantation are frequent and of special importance because they may be quite severe. The spectrum of dermatologic infections in transplant recipients includes bacterial, mycotic and viral diseases. Pyoderma, herpes virus 6/7, herpes simplex virus, varicella-zoster virus, cytomegalovirus and candida infections predominate. Rare pathogens must be also considered. Cutaneous infections can be divided into three phases following transplantation. Diagnosis and adequate early therapy together with specific prophylaxis and follow-up of transplant patients should be strived for to avoid life-threatening complications.

Background: Facial lentigo maligna (LM) and lentigo maligna melanoma (LMM) may be difficult to diagnose clinically and dermoscopically. Reflectance confocal microscopy (RCM) enables the in vivo assessment of equivocal skin lesions at a cellular level., Objectives: To assess cytomorphological and architectural RCM features of facial LM/LMM., Methods: Four women and eight men aged 58-88 years presenting with facial skin lesions suspicious of LM/LMM were included. In total, 17 lesion areas were imaged by RCM before biopsy. The histopathological diagnosis of LM was made in 15 areas; the other two were diagnosed as early LMM., Results: A focal increase of atypical melanocytes and nests surrounding adnexal openings, sheets of mainly dendritic melanocytes, cord-like rete ridges at the dermoepidermal junction (DEJ) and an infiltration of adnexal structures by atypical melanocytes were found to be characteristic RCM features of facial LM/LMM. Areas with a focal increase of atypical melanocytes and nests surrounding adnexal openings were observed at the basal layer in three cases. The remaining cases displayed these changes at suprabasal layers above sheets of mainly dendritic melanocytes. Cord-like rete ridges at the DEJ and an infiltration of adnexal structures by atypical melanocytes were observed in all cases. Previously described criteria for RCM diagnosis of melanoma, such as epidermal disarray, pleomorphism of melanocytes and pagetoid spreading of atypical melanocytes, were additionally observed., Conclusions: We observed a reproducible set of RCM criteria in this case series of facial LM/LMM.

We present a new concept on the nosology of parapsoriasis lichenoides (= parakeratosis variegata) and show that this parapsoriasis type is not a separate entity. It represents different diseases: a large number of cases presenting as reticular parapsoriasis are mycosis fungoides, another group represents reticular variants of the parapsoriasis guttata group (pityriasis lichenoides acuta et chronica). Further, cases exist that can be classified as lichen planus reticularis or other diseases (e. g. keratosis lichenoides).

Background: Most previous studies on melanocytic naevi have not distinguished between the different types of naevi, except for some studies trying to define atypical naevi. No large, population-based studies on papillomatous or Unna-type melanocytic naevi have been performed., Objectives: To investigate the dermoscopic and clinical features of papillomatous naevi and to study some of the factors which could potentially influence their development., Methods: Seven hundred and seven caucasians aged 1-82 years participated in a screening campaign at open-air recreation facilities in Austria. The volunteers underwent a total body examination by experienced dermatologists and answered a questionnaire. Clinical and dermoscopic images of one representative papillomatous naevus per person were taken., Results: Twenty-nine per cent of the volunteers exhibited papillomatous naevi, the highest frequency being found in young adults. No correlation between the frequency of papillomatous naevi and gender, skin type, sunburns, sunbed use or hormonal factors was found. Most lesions were brown papules (median diameter 5.0 mm), located on the trunk. Dermoscopy showed a predominance of homogeneous and globular pattern, multifocal hypo/hyperpigmentation and comma vessels. Of the papillomatous naevi, 9.8% showed suspicious scores with dermoscopic algorithms., Conclusions: The lack of exogenous influencing factors and the predominance of globular dermoscopic pattern strengthen the hypothesis that papillomatous naevi belong to the same spectrum as small congenital melanocytic naevi. As the role of papillomatous naevi as precursors of melanoma remains unclear and they are frequently not recognized by the patients, one should perform dermoscopy of papillomatous naevi during skin cancer screening.

This Macro-Micro-Dermatology-contribution with the theme innovative drugs and drug reactions illustrates two new observations of practical interest: 1. Follicular eruption after Everolimus and 2. Atrophy of sebaceous glands after Sirolimus.

Topical imiquimod (IQ) is an effective treatment for genital warts and various malignant tumors of the skin. IQ acts through the Toll-like receptor 7 leading to the production of cytokines and chemokines such as interferons, interleukins, and growth factors. We investigated the composition of the inflammatory cell infiltrate before, during, and after the treatment of 10 superficial cutaneous malignancies (melanoma in situ (n = 4), melanoma metastasis (n = 1), squamous cell carcinoma in situ (n = 4), and basal cell carcinoma (n = 1) with 5% IQ cream. Immunophenotyping revealed in all cases during treatment an increased population of T-lymphocytes positive for CD3, CD4 and CD8, as well as a considerable number of cytotoxic cells (TIA-1+, granzyme B+) and plasmacytoid dendritic cells (CD 123+). These findings further support previous investigations that the antitumor effects of IQ result from an enhanced cytotoxic T-cell mediated immune response and from the recruitment of plasmacytoid dendritic cells to the skin. The population of infiltrative inflammatory cells was similar in all patients irrespective of the type of tumor.

Background: Halo nevi (HN) are benign melanocytic nevi surrounded by a depigmented area (halo). This study aims to evaluate the dermoscopic features of HN and their changes during digital dermoscopic follow-up and to investigate the frequency of the halo phenomenon in a series of melanomas., Observations: In a retrospective study, digital dermoscopic images of HN from patients who attended the Pigmented Skin Lesions Clinic of the Department of Dermatology, Medical University of Graz, between October 1, 1997, and March 31, 2004, were reviewed and classified by dermoscopic morphologic criteria. For HN that were followed up with digital dermoscopy, the percentages of changes in the size of the nevus and halo components were calculated. In addition, digital dermoscopic images of histopathologically confirmed melanomas obtained from the same database were reviewed for the presence of an encircling halolike depigmentation. We classified 138 HN in 87 patients (mean age, 22.4 years). The most common dermoscopic structures were the globular and/or homogeneous patterns in more than 80% of HN. Follow-up of 33 HN revealed considerable size reduction of the nevus component, but this was not associated with significant structural changes. Of a total of 475 melanomas, only 2 revealed an encircling halo, but both displayed clear-cut melanoma-specific patterns according to dermoscopy., Conclusions: Halo nevi exhibit the characteristic dermoscopic features of benign melanocytic nevi, represented by globular and/or homogeneous patterns that are typically observed in children and young adults. Halo nevi reveal considerable changes of area over time during digital dermoscopic follow-up, albeit their structural patterns remain unchanged. For this reason and because melanoma with halolike depigmentation, despite being rare, additionally exhibits melanoma-specific dermoscopic criteria, the role of digital dermoscopic follow-up in the diagnosis of HN is insignificant.

Purpose: The combination of interferon alfa (IFNalpha) and isotretinoin has shown a direct antiproliferative effect on human melanoma cell lines, but it remained unclear whether this combination is more effective than IFNalpha alone in patients with metastatic melanoma. We evaluated safety and efficacy of IFNalpha and isotretinoin compared with IFNalpha alone as adjuvant treatment in patients with primary malignant melanoma stage IIA and IIB., Patients and Methods: In a prospective, randomized, double-blind, placebo-controlled trial, 407 melanoma patients in stage IIA (301 patients) and IIB (106 patients) were randomly assigned to either IFNalpha and isotretinoin (isotretinoin group; 206 patients) or IFNalpha and placebo (placebo group; 201 patients) after excision of the primary tumor. IFNalpha was administered three times a week at a dose of 3 million units subcutaneously for 24 months. Isotretinoin at a dose of 20 mg for patients < or = 73 kg, 30 mg for patients greater than 73 kg, or placebo daily for 24 months., Results: A scheduled interim analysis revealed no significant differences in survival rates, with the isotretinoin group and the placebo group showing 5-year disease-free survival rates of 55% (95% CI, 46% to 65%) and 67% (95% CI, 59% to 75%), respectively, and overall 5-year survival rates of 76% (95% CI, 67% to 84%) and 81% (95% CI, 74% to 88%), respectively. The trial was stopped for futility., Conclusion: The addition of isotretinoin to an adjuvant treatment of low-dose IFNalpha in patients with stage IIA and IIB melanoma had no significant effect on disease-free or overall survival and is therefore not recommended.

The increasing use of new drugs in cancer therapy, especially growth factors, hormones, and chemotherapies resulted in several reports of unusual skin eruptions. We studied a patient with erythroderma who had received erythropoietin because of myeloma with tumor anemia. The histological features were characterized by a lichenoid, focally granulomatous infiltrate with predominance of histiocytes. It is important for dermatopathologists to recognize this interesting pattern induced by erythropoietin.

Background: Rituximab is a genetically engineered antibody directed against the CD20 antigen. Intravenous administration of rituximab has been used for the treatment of patients with low-, intermediate-, and high-grade B-cell non-Hodgkin's lymphomas and is a registered treatment modality for this indication. Treatment of primary cutaneous B-cell lymphoma (CBCL) with intralesionally or systemically administered rituximab has been described only in a few cases., Objective: Our purpose was to assess the efficacy of rituximab in the treatment of CBCL., Methods: We performed a retrospective study on 9 patients with CBCL who were treated with intralesional or systemic administration of rituximab., Results: Two patients treated with systemic rituximab achieved complete remission. Complete remission could be observed in 6 of 7 patients after 1 to 8 cycles of intralesional treatment with rituximab. In one patient one of two lesions showed a partial remission after 4 cycles of treatment, whereas the second showed complete remission. A local recurrence was observed in one patient after 27 months of follow-up and in two patients recurrences developed at other body sites after 12 and 14 months of follow-up. No severe side effect occurred except for slight pain during intralesional injection., Conclusion: Rituximab therapy is a well-tolerated and effective treatment for primary CBCL. In comparison to intravenous administration, intralesional application of the drug allows the use of lower dosages. Intralesional therapy with rituximab deserves further investigation and comparison to systemic administration of the drug in controlled multicenter studies.

Background: Surgical excision is the treatment of choice for lentigo maligna (LM), or melanoma in situ. Topical application of imiquimod, a local immune response modifier, is a novel therapeutic approach that leads to LM tumor clearance. This pilot, open-label, nonrandomized study evaluates the efficacy of imiquimod in patients with LM and other systemic problems that make them poor surgical risks., Observations: Six biopsy-proven cases of LM from 5 patients (age range, 67-80 years) in whom standard surgical therapy was contraindicated were enrolled in the study. Five tumors were located on the face and 1 on the right shoulder. Imiquimod was used as a 5% cream once a day for a maximum of 13 weeks. Immediate clinical responses and follow-up, as well as histopathologic changes and immunohistologic parameters (in 2 patients), were analyzed. The complete response rate for all LM cases was 100%. Time to complete clearing varied from 5 to 13 weeks based on both clinical and histopathologic findings. The inflammatory infiltrate following imiquimod treatment consisted of T-helper lymphocytes mixed with a significant number of cytotoxic cells and monocytes or macrophages. These results indicate that imiquimod induces a cytotoxic T-cell-mediated immune response. In all patients, erythema and erosions occurred at the treated area 2 to 4 weeks after initiation of imiquimod therapy. The patients have been followed up for 3 to 18 months without evidence of recurrences., Conclusions: Topical imiquimod appears to be an excellent therapeutic option for LM. Close evaluation of patients, including posttherapy histopathologic investigation, is essential. Imiquimod can be added to the list of therapeutic approaches for carefully selected patients with LM.

The correct classification of locoregional metastases of malignant melanoma to skin is central to the planning of treatment. Local recurrence means persistence of neoplastic cells at the local site by virtue of incomplete excision of the primary melanoma. Standard treatment is excisional surgery. In contrast, locoregional metastases of malignant melanoma (satellites, in-transit metastases) are metastases around a primary melanoma or between a primary melanoma and regional lymph nodes. They represent intralymphatic or hematogenous spread of neoplastic cells. We present a variety of available treatment options and discuss especially topical imiquimod as a novel approach for the palliative treatment of locoregional cutaneous melanoma metastases in selected patients.

We performed a multicentre study to test the validity of teledermoscopy for diagnosing acral melanoma and to evaluate inter-observer agreement on the classification of acral melanocytic lesions. Dermoscopic images of 77 acral melanocytic lesions (71 common melanocytic naevi and 6 melanomas) were sent by email to 11 dermatologists with different degrees of experience in dermoscopy. The observers analysed the images on a computer monitor to diagnose acral melanoma or atypical lesions and to categorize all lesions. All 11 observers, regardless of their degree of experience, obtained high values for sensitivity (mean 0.91, SD 0.09) and specificity (mean 0.95, SD 0.04) with regard to the diagnosis of melanoma. The inter-observer agreement was good to excellent (kappa 0.49-0.88) for the categorization of acral melanocytic lesions. All six melanomas were correctly classified as 'atypical pattern' and all observers recommended surgical excision. Teledermoscopy represents a useful tool for the diagnosis of acral melanoma and for the categorization of patterns that suggest benign or potentially malignant acral melanocytic lesions.

Background: There is a need for better standardization of the dermoscopic terminology in assessing pigmented skin lesions., Objective: The virtual Consensus Net Meeting on Dermoscopy was organized to investigate reproducibility and validity of the various features and diagnostic algorithms., Methods: Dermoscopic images of 108 lesions were evaluated via the Internet by 40 experienced dermoscopists using a 2-step diagnostic procedure. The first-step algorithm distinguished melanocytic versus nonmelanocytic lesions. The second step in the diagnostic procedure used 4 algorithms (pattern analysis, ABCD rule, Menzies method, and 7-point checklist) to distinguish melanoma versus benign melanocytic lesions. kappa Values, log odds ratios, sensitivity, specificity, and positive likelihood ratios were estimated for all diagnostic algorithms and dermoscopic features., Results: Interobserver agreement was fair to good for all diagnostic methods, but it was poor for the majority of dermoscopic criteria. Intraobserver agreement was good to excellent for all algorithms and features considered. Pattern analysis allowed the best diagnostic performance (positive likelihood ratio: 5.1), whereas alternative algorithms revealed comparable sensitivity but less specificity. Interobserver agreement on management decisions made by dermoscopy was fairly good (mean kappa value: 0.53)., Conclusion: The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions.

Background: Dermoscopy (dermatoscopy, epiluminescence microscopy) is increasingly employed for the preoperative detection of cutaneous melanoma; dermoscopic features of pigmented skin lesions have been previously defined using histopathology as the key to the code. In a preliminary study on 10 cases evaluated by nine dermoscopists and nine histopathologists, the authors experienced that when at least two dermoscopists disagree in evaluating a melanocytic lesion, even histopathologic consultations may give equivocal results., Methods: One hundred seven melanocytic skin lesions, consecutively excised because of equivocal clinical and/or dermoscopic features, were retrospectively examined by eight dermoscopists and eight histopathologists; the diagnostic interobserver agreement was calculated by means of the Schouten k statistics. After histopathologic consultations, all 107 lesions underwent unblinded dermoscopic re-evaluation in order to find which dermoscopic features had given rise to histopathologic diagnostic difficulties., Results: The interobserver ageement was good for both dermoscopy (k = 0.53) and histopathology (k = 0.74). Out of 48 cases evaluated by the dermoscopists in complete accordance, only 8 (16.7%) received at least one conflicting histopathologic diagnosis. Instead, among the remaining 59 cases with at least one disagreeing dermoscopic diagnosis, 21 (35.6%) received at least one disagreeing histopathologic diagnosis. The unblinded dermoscopic re-evaluation showed that five out of seven lesions with clear-cut regression structures were histopathologically controversial., Conclusions: At least for selected and reasonably difficult lesions, a diagnostic discrepancy among formally trained dermoscopists seems to be predictive for a diagnostic disagreement among histopathologists. Lesions showing clear-cut regression structures are prone to give some histopathologic disagreement., (Copyright 2002 American Cancer Society.)

Co-culturing of immunological effector cells with antigen-pulsed DC leads to an increase of cytotoxic activity against antigen-expressing tumour cells. Using this approach, we could detect up to 2.8% antigen-specific CTLs after co-culture with antigen-pulsed DC. However, the required high effector cell numbers remain a major obstacle in immunotherapy. In this study, we show an approach for generating activated and antigen-specific effector cells that enables us to decrease effector to target cell ratios. We used an interferon-gamma secretion assay to enrich activated effector cells after co-culture with antigen-pulsed dendritic cells (DC). Purified immunological effector cells lysed 58.3% of antigen-expressing tumour cells at an effector to target ratio of 1:1. Furthermore, using MHC-IgG complexes, we enriched effector cells expressing antigen-specific T-cell receptor after co-culture with DC. Performing ELISpot, flow cytometry and TCR analysis, we could show a significant increase of activated and specific TCR-expressing effector cells after co-culture with DC.

Objectives: To create a dermoscopic classification of atypical melanocytic nevi (Clark nevi) and to investigate whether individuals bear a predominant type., Design: Digital dermoscopic images of Clark nevi were classified according to structural features, ie, reticular, globular, or homogeneous patterns or combinations of these types. The nevi were also characterized as central hypopigmented or hyperpigmented, eccentric peripheral hypopigmented or hyperpigmented, or multifocal hypopigmented or hyperpigmented., Setting: Two pigmented skin lesion clinics., Patients: We examined 829 Clark nevi on 23 individuals., Main Outcome Measure: A reliable dermoscopic classification of Clark nevi and frequency of different dermoscopic types., Results: Using the dermoscopic classification, the 829 Clark nevi were classified as follows: 221 (26.7%) as reticular, 167 (20.1%) as reticular-homogeneous, 148 (17.9%) as globular-homogeneous, 112 (13.5%) as reticular-globular, 89 (10.7%) as homogeneous, 84 (10.1%) as globular, and 8 (1.0%) as unclassified. Most individuals were prone to a predominant type of Clark nevus. Seven individuals (30%) showed a single type of Clark nevus in more than 50% of their nevi and 5 (22%) in more than 40% of their nevi., Conclusions: The proposed dermoscopic classification of Clark nevi is easily applicable and allows a detailed characterization of the different dermoscopic types of Clark nevi. Knowledge of these dermoscopic types should reduce unnecessary surgery for benign melanocytic lesions. Exact classification of the different types of Clark nevi is a necessary prerequisite for further clinical, dermoscopic, and histopathologic studies, which will give new insights in the biology of acquired melanocytic nevi.