Analysis of Major Histocompatibility Antigens and the Mononuclear Cell Infiltrate in Halo Nevi

A series of monoclonal antibodies was used to characterize the nevomelanocytes and the inflammatory infiltrate of 11 halo nevi in different stages of resolution, employing an immunoperoxidase technique. Three of the 11 halo nevi histologically showed signs of mild or moderate nevomelanocytic atypia. It was found that the vast majority of the nevomelanocytes in halo nevi with a dense inflammatory infiltrate markedly expressed HLA-A,B,C antigens, while expression was not demonstrable in nevocellular nests not adjacent to the mononuclear infiltrate. No difference in expression of HLA-A,B,C antigens was found between the 3 cases with mild or moderate nevomelanocytic atypia and the other eases lacking atypia. Expression of HLA-DR (Ia-like) antigens was found on few nevomelanocytes in only 2 of 11 lesions. The cellular composition of the mononuclear inflammatory infiltrate showed a predominance of T cells (80% or more) with a relatively high proportion of cytotoxic/suppressor T cells. Most of the T cells showed signs of activation as judged by staining for HLA-DR antigens. These results demonstrate that the expression of HLA- A,B,C antigens on the nevomelanocytes and the cellular composition of the mononuclear inflammatory infiltrate in halo nevi are very similar to that in malignant melanomas and dysplastic nevi. These findings also indicate that the expression of HLA-A,B,C antigens on nevomelanocytes is primarily dependent on the presence of T- cell immune response and not necessarily related to the presence of nevomelanocytic atypia

Deep-Sequencing Analysis Reveals that the miR-199a2/214 Cluster within DNM3os Represents the Vast Majority of Aberrantly Expressed MicroRNAs in Sézary Syndrome

Dermatology-oncolog

Generalized Molluscum Contagiosum Successfully Treated with Interferon-Alpha in a Patient with Folliculotropic Mycosis Fungoides

We present the case of a 50-year-old patient with folliculotropic mycosis fungoides (FMF) unresponsive to retinoids and the chemotherapeutic regimens CHOP, gemcitabine, and brentuximab-vedotin. During immunosuppressive therapy, the patient developed extensive progressive molluscum contagiosum. The mollusca did not respond to topical imiquimod but showed a swift complete response to interferon-alpha 2a (IFNa). Recently, the patient started with alemtuzumab as induction therapy for an allogenic stem cell transplantation and simultaneously continued IFNa therapy

Clinical, Histologic, and Molecular Characteristics of Anaplastic Lymphoma Kinase-positive Primary Cutaneous Anaplastic Large Cell Lymphoma

Unlike systemic anaplastic large cell lymphoma, the vast majority of primary cutaneous anaplastic large cell lymphomas (C-ALCL) do not carry translocations involving the ALK gene and do not express ALK. Expression of ALK protein therefore strongly suggests secondary cutaneous involvement of a systemic anaplastic large cell lymphoma. Recent studies described a small subgroup of ALK-positive C-ALCL, but information on frequency, prognosis, and translocation partners is virtually lacking. A total of 6/309 (2%) C-ALCL patients included in the Dutch registry for cutaneous lymphomas between 1993 and 2019 showed immunohistochemical ALK expression. Clinical and histopathologic characteristics, immunophenotype and disease course were evaluated. Underlying ALK translocations were analyzed with anchored multiplex polymerase chain reaction-based targeted next-generation sequencing. Median age at diagnosis was 39 years (range: 16 to 53 y). All patients presented with a solitary lesion. Treatment with radiotherapy (n=5) or anthracycline-based chemotherapy (n=1) resulted in complete responses in all 6 patients. Three patients developed a relapse, of whom 2 extracutaneous. After a median follow-up of 41 months, 5 patients were alive without disease and 1 patient died of lymphoma. Immunohistochemically, 3 cases (50%) showed combined nuclear and cytoplasmic ALK expression with underlying NPM1-ALK fusions, while 3 cases (50%) showed solely cytoplasmic ALK expression with variant ALK fusion partners (TRAF1, ATIC, TPM3). ALK-positive C-ALCL is extremely uncommon, has a comparable favorable prognosis to ALK-negative C-ALCL, and should be treated in the same way with radiotherapy as first-line treatment

European Organisation for Research and Treatment of Cancer consensus recommendations for the treatment of mycosis fungoides/Sezary syndrome - Update 2017

In order to provide a common standard for the treatment of mycosis fungoides (MF) and Sezary syndrome (SS), the European Organisation for Research and Treatment of Cancer-Cutaneous Lymphoma Task Force (EORTC-CLTF) published in 2006 its consensus recommendations for the stage-adapted selection of management options for these neoplasms. Since then, the understanding of the pathophysiology and epidemiology of MF/SS has advanced, the staging system has been revised, new outcome data have been published and novel treatment options have been introduced. The purpose of the present document is to update the original recommendations bearing in mind that there are still only a limited number of controlled studies to support treatment decisions for MF/SS and that often treatment is determined by institutional experience and availability. This consensus on treatment recommendations was established among the authors through a series of consecutive consultations in writing and a round of discussion. Recommended treatment options are presented according to disease stage, whenever possible categorised into first-and second-line options and supported with levels of evidence as devised by the Oxford Centre for Evidence-Based Medicine (OCEBM). Skin-directed therapies are still the most appropriate option for early-stage MF, and most patients can look forward to a normal life expectancy. For patients with advanced disease, prognosis is still grim, and only for a highly selected subset of patients, prolonged survival can be achieved with allogeneic stem cell transplantation (alloSCT). There is a high need for the development and investigation in controlled clinical trials of treatment options that are based on our increasing understanding of the molecular pathology of MF/SS. (C) 2017 The Authors. Published by Elsevier Ltd.Peer reviewe

Outcomes of rare patients with a primary cutaneous CD30(+) lymphoproliferative disorder developing extracutaneous disease

Contains fulltext : 218224.pdf (Publisher’s version ) (Open Access

Cell-of-origin classification using the Hans and Lymph2Cx algorithms in primary cutaneous large B-cell lymphomas

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) and primary cutaneous follicle center lymphoma with a diffuse population of large cells (PCFCL-LC) are both primary cutaneous B-cell lymphomas with large-cell morphology (CLBCL) but with different clinical characteristics and behavior. In systemic diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), gene-expression profiling (GEP) revealed two molecular subgroups based on their cell-of-origin (COO) with prognostic significance: the germinal center B-cell-like (GCB) subtype and the activated B-cell-like (ABC) subtype. This study investigated whether COO classification is a useful tool for classification of CLBCL. For this retrospective study, 51 patients with PCDLBCL-LT and 15 patients with PCFCL-LC were analyzed for their COO according to the immunohistochemistry-based Hans algorithm and the NanoString GEP-based Lymph2Cx algorithm. In PCFCL-LC, all cases (100%) classified as GCB by both Hans and Lymph2Cx. In contrast, COO classification in PCDLBCL-LT was heterogeneous. Using Hans, 75% of the PCDLBCL-LT patients classified as non-GCB and 25% as GCB, while Lymph2Cx classified only 18% as ABC, 43% as unclassified/intermediate, and 39% as GCB. These COO subgroups did not differ in the expression of BCL2 and IgM, mutations in MYD88 and/or CD79B, loss of CDKN2A, or survival. In conclusion, PCFCL-LC uniformly classified as GCB, while PCDLBCL-LT classified along the COO spectrum of DLBCL-NOS using the Hans and Lymph2Cx algorithms. In contrast to DLBCL-NOS, the clinical relevance of COO classification in CLBCL using these algorithms has limitations and cannot be used as an alternative for the current multiparameter approach in differentiation of PCDLBCL-LT and PCFCL-LC

Genetic Stability of Driver Alterations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type and Their Relapses:A Rationale for the Use of Molecular-Based Methods for More Effective Disease Monitoring

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare, aggressive cutaneous lymphoma with a 5-year disease-specific survival of only ~55%. Despite high response rates to initial immune-polychemotherapy, most patients experience a disease relapse. The genetic evolution of primary and relapsed/refractory disease has only scarcely been studied in PCDLBCL-LT patients. Therefore, in this retrospective cohort study, 73 primary/pre-treatment and relapsed/refractory biopsies of 57 patients with PCDLBCL-LT were molecularly characterized with triple FISH and targeted next-generation sequencing for 52 B-cell-lymphoma-relevant genes, including paired analysis in 16 patients. In this cohort, 95% of patients harboured at least one of the three main driver alterations (mutations in MYD88/CD79B and/or CDKN2A-loss). In relapsed/refractory PCDLBCL-LT, these oncogenic aberrations were persistently present, demonstrating genetic stability over time. Novel alterations in relapsed disease affected mostly CDKN2A, MYC, and PIM1. Regarding survival, only MYC rearrangements and HIST1H1E mutations were statistically significantly associated with an inferior outcome. The stable presence of one or more of the three main driver alterations (mutated MYD88/CD79B and/or CDKN2A-loss) is promising for targeted therapies addressing these alterations and serves as a rationale for molecular-based disease monitoring, improving response evaluation and early identification and intervention of disease relapses in these poor-prognostic PCDLBCL-LT patients

Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium

ABSTRACT Background Advanced-stage mycosis fungoides (MF)/Sezary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. Patients and methods This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). Results Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. Conclusion This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach