Semin Cutan Med Surg
· 2018 Jun · PMID 30040090
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Immunotherapy for the treatment of advanced melanoma has become a primary treatment in the clinic. Current therapies include systemic cytokines, immune checkpoint inhibitors, and localized intratumoral therapies. Checkpo...Immunotherapy for the treatment of advanced melanoma has become a primary treatment in the clinic. Current therapies include systemic cytokines, immune checkpoint inhibitors, and localized intratumoral therapies. Checkpoint inhibitors block natural pathways that dampen or inhibit an immune response to stimulus. These pathways include programmed cell death 1 receptor/programmed death-ligand 1 and cytotoxic T lymphocyte antigen-4. Systemic immunotherapies have proven to be effective in clinical trials both as monotherapy and in combination therapy. Oncolytic viruses are used to treat tumor locally and induce an effective immune response. Although some immune-mediated adverse events have been shown to occur with immunotherapy and may cause disease through systemic immune activation, most symptoms are mild to moderate. Overall immunotherapy in advanced melanoma has provided effective and durable responses to treat patients with advanced melanoma.
Johnson DB, Chon J, Johnson MR
… +1 more, Balko JM
Semin Cutan Med Surg
· 2018 Jun · PMID 30040089
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Immune checkpoint inhibitors have dramatically transformed melanoma treatment options. However, intrinsic and acquired resistance remain fundamental limitations to extending the benefits to all patients. Understanding mo...Immune checkpoint inhibitors have dramatically transformed melanoma treatment options. However, intrinsic and acquired resistance remain fundamental limitations to extending the benefits to all patients. Understanding molecular and clinical features that correlate with response to treatment (biomarkers) may unravel therapeutic resistance, assist in treatment decision-making, and facilitate drug development. An intensive effort to characterize these biomarkers is underway. Herein, we highlight promising molecular biomarkers involving the tumor microenvironment, host immune response, and microbiome. We particularly focus on anti-programmed death-1 (PD-1) therapy but will also briefly cover anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) and novel combination therapies.
Semin Cutan Med Surg
· 2018 Jun · PMID 30040088
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Over the past 10 years of remarkable development of both molecularly targeted and immune-targeted therapy for the treatment of melanoma, a clear preference of immunotherapy over molecularly targeted therapy has emerged a...Over the past 10 years of remarkable development of both molecularly targeted and immune-targeted therapy for the treatment of melanoma, a clear preference of immunotherapy over molecularly targeted therapy has emerged among melanoma treatment providers. Still, the clinical data remain remarkable for patients with BRAF-mutant stage III and IV melanoma, and there seems to be a clear benefit of BRAF-targeted therapy for these patients. The key, then, is to identify the best way to use BRAF-targeted therapy. In this review, the clinical data of molecular-targeted therapy are summarized, mechanisms of resistance to single-agent BRAF and combined BRAF with mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) inhibitor are discussed, and strategies to overcome this resistance are presented; then, we review a number of clinical dilemmas that influence the decision-making of using targeted therapy over immunotherapy, and viceversa, and help define the specific role of targeted therapy in the immunotherapy era.
Semin Cutan Med Surg
· 2018 Jun · PMID 30040087
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Melanoma is an aggressive cancer that arises from melanocytes that can both locally invade surrounding tissues as well as metastasize systemically. If detected early, melanoma can be curable with surgical resection. Howe...Melanoma is an aggressive cancer that arises from melanocytes that can both locally invade surrounding tissues as well as metastasize systemically. If detected early, melanoma can be curable with surgical resection. However, despite complete removal, high-risk resected melanomas have a significant rate of both local and distant recurrence. Curative treatment options are typically limited for patients who develop distant recurrence after resections of their primary melanoma. Therefore, adjuvant therapy is typically given after complete resection of high-risk melanomas to try and reduce the risk of recurrent disease. Adjuvant therapy for high-risk resected melanoma has changed considerably over the past couple of years due to the availability of new melanoma therapies that are active in the metastatic setting. Here, we review the new treatment options and ongoing clinical research for adjuvant therapy.
Semin Cutan Med Surg
· 2018 Jun · PMID 30040086
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Surgery remains one of the key treatment modalities for melanoma. Wide excision of the primary site with sentinel lymph node biopsy for selected patients has been recognized as the standard surgical approach for patients...Surgery remains one of the key treatment modalities for melanoma. Wide excision of the primary site with sentinel lymph node biopsy for selected patients has been recognized as the standard surgical approach for patients with early-stage disease. Controversies persist regarding margin width, indications for sentinel lymph node biopsy, and surgical management of regional nodal basins. Additionally, new therapies such as intralesional therapies as well as new systemic therapies are changing the role for surgery in patients with recurrent local-regional as well as metastatic disease. In this chapter, we discuss the current recommendations as well as the topics of debate in the surgical management of melanoma.
Semin Cutan Med Surg
· 2018 Jun · PMID 30040085
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Recent advances in techniques for pathologic evaluation of melanocytic neoplasms, updates in staging, and novel treatment and prognostic assays have brought pathologists to the forefront of the care of the melanoma patie...Recent advances in techniques for pathologic evaluation of melanocytic neoplasms, updates in staging, and novel treatment and prognostic assays have brought pathologists to the forefront of the care of the melanoma patient. Specimen procurement, handling, and evaluation are all key to the production of a pathology report that guides the clinician to the proper treatment of the patient. Recent, relevant changes in the pathologic analysis of melanocytic neoplasms, highlighting the AJCC 8th edition guidelines, and pathologic changes related to therapy are discussed herein. Also included is a discussion of molecular assays used to aid in diagnosis of challenging lesions, predict clinical outcome, and predict response to targeted therapy.
Baldwin HE, Stein Gold LF, Gordon KB
… +3 more, Green JB, Leonardi CL, Sengelmann RD
Semin Cutan Med Surg
· 2018 Jun · PMID 30016379
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Updates on managing some of the most common dermatologic conditions for which patients seek care illuminated presentations at the Skin Disease Education Foundation's 42nd Annual Hawaii Dermatology Seminar®. This educatio...Updates on managing some of the most common dermatologic conditions for which patients seek care illuminated presentations at the Skin Disease Education Foundation's 42nd Annual Hawaii Dermatology Seminar®. This educational supplement summarizes the highlights of clinical sessions presented during this CME/CE conference. Treatment of psoriasis has continued to advance, with three interleukin (IL)-17 antagonists approved by the US Food and Drug Administration (FDA) and a fourth in phase 3 trials. An authority on the use of biologics in psoriasis presents current data on the safety and efficacy of these therapies. Tumor necrosis factor (TNF) inhibitors also retain a place in the management of psoriasis, with records of long-term safety. A fourth TNF inhibitor awaits FDA approval for use in psoriasis, offering data on transmission during pregnancy and lactation. An expert on the use of this drug class presents the evidence. Topical therapies remain the cornerstone of care for many patients with psoriasis as well as those with rosacea. Our faculty update readers about new and investigational topical therapies for moderate or severe psoriasis, as well as for acne and rosacea. The current literature on monitoring patients receiving isotretinoin also is summarized. Aesthetic and cosmetic dermatology services form a sizable portion of some practices. Our faculty review data on safety of topical and procedural therapies for cellulite as well as safe injection of facial fillers.
Semin Cutan Med Surg
· 2018 Mar · PMID 29719024
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Cutaneous T-cell lymphoma (CTCL) is a group of malignancies derived from skin-homing T cells. Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common CTCL variants. In recent years, the genetic landscape of S...Cutaneous T-cell lymphoma (CTCL) is a group of malignancies derived from skin-homing T cells. Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common CTCL variants. In recent years, the genetic landscape of SS/MF has been characterized using genome-wide nextgeneration sequencing approaches. These studies have revealed that genes subjected to oncogenic mutations take part in cell cycle regulation, chromatin modification, Janus kinase (JAK)-signal transducer and activator of transcription protein (STAT) signaling, T-cell receptor (TCR)/ nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, and microtubule associated protein kinase (MAPK) signaling, which suggests that deregulation of these cellular processes underlies lymphomagenesis. These studies provide the groundwork for functional and clinical studies that will lead to better risk assessment and more effective therapeutic approach in CTCL patients.
Semin Cutan Med Surg
· 2018 Mar · PMID 29719023
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Dermatopathology reporting can be both exact and inexact. Exact reporting represents the use of terminology that corresponds to a disease sui generis, such as discoid lupus erythematosus or disseminated superficial porok...Dermatopathology reporting can be both exact and inexact. Exact reporting represents the use of terminology that corresponds to a disease sui generis, such as discoid lupus erythematosus or disseminated superficial porokeratosis. Inexact reporting can vary greatly amongst various practitioners-both in terms of the exact semantics used and also stylistically-and can be used habitually by pathologists as a means to provide cover for diagnostic uncertainty or inexperience. This article explores the use of descriptive (inexact) reporting as it applies to cutaneous lymphoma and its differential diagnosis. A collection of practical descriptive diagnostic categories that will be of use to both dermatologists and dermatopathologists is included.
Charli-Joseph Y, Toussaint-Claire S, Lome-Maldonado C
… +2 more, Montante-Montes de Oca D, Ortiz-Hidalgo C
Semin Cutan Med Surg
· 2018 Mar · PMID 29719022
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The histopathological diagnosis of dermal-based lymphoid infiltrates and proliferations is often challenging due to the vast list of biologically diverse entities that archetypally or occasionally center in the mid-dermi...The histopathological diagnosis of dermal-based lymphoid infiltrates and proliferations is often challenging due to the vast list of biologically diverse entities that archetypally or occasionally center in the mid-dermis, especially because significant overlap exists in their clinical, histopathologic, and immunophenotypic features. The differential diagnosis includes reactive infiltrates in common and rare inflammatory dermatoses, benign conditions that may mimic lymphoid neoplasms (pseudolymphomas), and true clonal proliferations arising either primarily in the skin or rarely in extracutaneous tissues with secondary cutaneous dissemination. While numerous histopathological and immunophenotypic features have been reported to support a definitive diagnosis, no single ancillary test is sufficient for their distinction. Therefore, in this review we advocate a stepped histopathological approach for dermalbased lymphoid infiltrations, employing as key elements the general lymphocytic composition (relative B- versus T-cell ratio), coupled with the predominant cytomorphology (cell size) present. Following this strategy, the relative incidence of cutaneous involvement by each disease should always be considered, as well as the notion that a definitive diagnosis must be founded on a multiparameter approach integrating all clinical, histopathologic, immunophenotypic, and-in selected cases-molecular features.
Semin Cutan Med Surg
· 2018 Mar · PMID 29719021
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Mycosis fungoides is the most common and therefore quintessential cutaneous lymphoma and is typically characterized by an epidermotropic infiltrate of atypical monoclonal CD4+ lymphocytes. Classical histopathologic findi...Mycosis fungoides is the most common and therefore quintessential cutaneous lymphoma and is typically characterized by an epidermotropic infiltrate of atypical monoclonal CD4+ lymphocytes. Classical histopathologic findings include epidermotropism, lymphocytes with convoluted nuclear contours and surrounding perinuclear "halos," and papillary dermal fibrosis. Atypical lymphocytes may occasionally form Pautrier's microabscesses with tagging of lymphocytes along the basal keratinocytes. Unfortunately, a variety of benign inflammatory infiltrates, as well as other cutaneous lymphomas, may demonstrate some similar histopathologic findings. Herein, we review the wide array of epidermotropic T-cell lymphomas and discuss distinguishing features between these entities. We also offer an algorithmic approach utilizing histopathologic, immunophenotypic, and molecular techniques that can be used for analyzing an epidermotropic T-cell infiltrate in order to render a specific diagnosis.
Semin Cutan Med Surg
· 2018 Mar · PMID 29719020
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Cutaneous B-cell lymphomas (CBCLs) are a heterogeneous group of diseases that can have variable presentations, prognoses, and treatments. The proper identification of a CBCL hinges on proper histopathologic and clinical...Cutaneous B-cell lymphomas (CBCLs) are a heterogeneous group of diseases that can have variable presentations, prognoses, and treatments. The proper identification of a CBCL hinges on proper histopathologic and clinical evaluation. Comprising 25% to 30% of the primary cutaneous lymphomas, incident cases of CBCL are rare. Given the variable natural history of the CBCL, proper classification is critical so that patients are treated appropriately. CBCLs can be divided into 2 main groups: indolent and aggressive. Indolent CBCLs include primary cutaneous follicle center lymphoma and primary cutaneous marginal zone lymphoma. These subtypes usually do not affect a patient's lifespan but can lead to substantial symptomatology, prompting the need for treatment. The aggressive subtypes of CBCL include diffuse large B-cell lymphoma leg type and intravascular large B-cell lymphoma. These are treated as systemic lymphomas, and their prognoses are not as good. In this article, we discuss the clinical features, differential diagnoses, histopathologic features, and treatment options for each of the 4 types of CBCL. The proper categorization of these diseases can allow physicians to properly treat a patient with CBCL, including the avoidance of unnecessary therapy.
Semin Cutan Med Surg
· 2018 Mar · PMID 29719019
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Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder usually presents as a slow-growing and asymptomatic solitary lesion in the form of a nodule or tumor in the head and neck region. By definition, it...Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder usually presents as a slow-growing and asymptomatic solitary lesion in the form of a nodule or tumor in the head and neck region. By definition, it is histologically characterized by small- to medium-sized CD4+ lymphocytes involving the dermis in a dense and either nodular or diffuse pattern. Epidermotropism should be absent or minimal. Tumor cells are accompanied by numerous reactive B cells, plasma cells, histiocytes, and eosinophils. This lymphoproliferative disorder is characterized by the expression of follicular helper T-cell markers, particularly B-cell lymphoma 6 (BCL-6), programmed cell death protein 1 (PD-1), and C-X-C motif chemokine ligand 13 (CXCL-13), while CD10 is usually negative. Molecular studies show a clonal rearrangement of T-cell receptor genes in more than 60% of cases. Management of disease includes surgical excision, radiation therapy, and steroids (topical or intralesional). Patients with this diagnosis have an excellent prognosis, with a clinical course that is invariably indolent.
Semin Cutan Med Surg
· 2018 Mar · PMID 29719018
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The cytotoxic lymphomas of the skin constitute a heterogeneous group of rare lymphoproliferative diseases that are derived from mature T cells and natural killer (NK) cells that express cytotoxic molecules (T-cell intrac...The cytotoxic lymphomas of the skin constitute a heterogeneous group of rare lymphoproliferative diseases that are derived from mature T cells and natural killer (NK) cells that express cytotoxic molecules (T-cell intracellular antigen- 1, granzyme A/B, and perforin). Although frequently characterized by an aggressive course and poor prognosis, these diseases can have variable clinical behavior. This review delivers up-to-date information about the clinical presentation, histopathologic features, differential diagnosis, and therapy of extranodal NK/T-cell lymphoma, nasal type, primary cutaneous gamma delta T-cell lymphoma, and primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma.
Semin Cutan Med Surg
· 2018 Mar · PMID 29719017
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Cutaneous CD30+ T-cell lymphoproliferative disorders (CD30+ LPD) are the second most common form of cutaneous T-cell lymphoma. CD30+ LPD include lymphomatoid papulosis, primary cutaneous anaplastic large-cell lymphoma, a...Cutaneous CD30+ T-cell lymphoproliferative disorders (CD30+ LPD) are the second most common form of cutaneous T-cell lymphoma. CD30+ LPD include lymphomatoid papulosis, primary cutaneous anaplastic large-cell lymphoma, and borderline lesions. Despite expression of CD30 by the neoplastic cells as the hallmark of these disorders, they differ in their clinical presentation and histological features as well as the course, the prognosis, and consecutively in the treatment. Diagnosis of CD30+ LPD and distinction from the broad spectrum of differential diagnoses essentially depends on clinicopathologic correlation as well as the results of staging examinations. Although the histological findings indicate a high-grade lymphoma, CD30+ LPD in most cases have a favorable prognosis. Recent advances in targeted therapy have led to new therapeutic approaches to CD30+ LPDs. This review describes the clinicopathologic features of CD30+ LPDs, their differential diagnoses, the treatment, and the role of CD30 as a diagnostic marker and therapeutic target.
Semin Cutan Med Surg
· 2018 Mar · PMID 29719016
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Sézary syndrome (SS) is a rare subtype of cutaneous T-cell lymphoma marked by erythroderma, circulating neoplastic T cells, and poor prognosis. Its low incidence has made the study of its etiology, immunologic/molecular...Sézary syndrome (SS) is a rare subtype of cutaneous T-cell lymphoma marked by erythroderma, circulating neoplastic T cells, and poor prognosis. Its low incidence has made the study of its etiology, immunologic/molecular pathways, and effective treatments difficult. Because histopathology may be nonspecific in SS, microscopic findings must be correlated with the clinical presentation and the results of blood evaluation in order to make the diagnosis. Treatments that preserve, rather than compromise, the immune system are preferred.
Semin Cutan Med Surg
· 2018 Mar · PMID 29719015
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Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, which typically presents with erythematous patches and plaques, histopathologically characterized by superficial infiltrates of small to medium...Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, which typically presents with erythematous patches and plaques, histopathologically characterized by superficial infiltrates of small to mediumsized atypical epidermotropic T cells. Apart from this classic type of MF, many clinical and/or histopathologic variants have been described. Correct diagnosis of these MF variants is important, but may be difficult, because they may mimic a wide variety of inflammatory skin diseases. In this review, clinical and histopathologic characteristics of distinct variants of MF are presented, and their differential diagnosis and therapeutic options are discussed.
Semin Cutan Med Surg
· 2018 Mar · PMID 29719014
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Mycosis fungoides (MF) is the most common type of cutaneous lymphoma. The term MF should be used only for the classical presentation of the disease characterized by the evolution of patches, plaques, and tumors or for va...Mycosis fungoides (MF) is the most common type of cutaneous lymphoma. The term MF should be used only for the classical presentation of the disease characterized by the evolution of patches, plaques, and tumors or for variants showing a similar clinical course. MF is divided into 3 clinical phases: patch, plaque, and tumor stage, and the clinical course is usually protracted over years or decades. Histopathologically, MF is characterized by an epidermotropic infiltrate of T lymphocytes that displays in most cases a helper phenotype. Cytotoxic variants are well described and do not have specific clinical, histopathological, or prognostic features. MF should be differentiated from other cutaneous epidermotropic lymphomas and from many inflammatory dermatoses with some similar clinicopathological features. The therapy of MF is planned mainly according to the stage and extent of the disease. In early phases, nonaggressive options represent the first-line strategy (eg, local corticosteroids, psoralen, and ultraviolet A [UV-A] irradiation, etc.). In patients with advanced disease, good results with potential for cure have been obtained with allogeneic stem cell transplantation, but toxicity is a serious limiting factor for this treatment. Conventional systemic chemotherapy and single-agent chemotherapy (eg, gemcitabine) give usually good results in advanced MF, but recurrences are the rule. Monoclonal antibodies directed against cluster of differentiation (CD)52 (alemtuzumab), CD30 (brentuximab vedotin), and chemokine receptor 4 (CCR4; mogamulizumab), as well as several other experimental therapies, have shown promising results and represent a valid alternative.