Seminars in Cutaneous Medicine and Surgery

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...

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...

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...

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...

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...

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...

No abstract text is available yet for this article.

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...

No abstract text is available yet for this article.

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...