Clinical Insights and Emerging Strategies in Managing Cutaneous T-Cell Lymphoma
May 2017 | Volume 16 | Issue 5 | Original Article | 405 | Copyright © May 2017
Christina C. Patrone BAa and Larisa J. Geskin MD FAADb
aColumbia University College of Physicians & Surgeons, New York, NY bDepartment of Dermatology, Columbia University Medical Center, New York, NY
Mycosis Fungoides and Sézary Syndrome, the two most common types of Cutaneous T-Cell Lymphoma (CTCL), present many management challenges for dermatologists. Here, we provide a comprehensive review of up-to-date literature, guidelines, and expert clinical insights. We highlight the updates in the World Health Organization Classification of Cutaneous Lymphomas; we summarize the epidemiology, including a recently observed stabilization of increasing incidence of CTCL in the past decade and increased incidence in males, blacks, and veterans; we also provide the most recent updates on prognostic factors for CTCL. Utilization of Next-Generation Sequencing and other novel technologies has shed light on pathogenic mechanisms of CTCL, including immune dysregulation, antigen stimulation, and genomic alterations. CTCL management still remains a significant challenge due to lack of standardization of therapies for every stage of the disease. We provide a straightforward approach to clinical evaluation, diagnostic workup via immunophenotyping and molecular studies, staging guidelines, and select treatment strategies in Mycosis Fungoides and Sézary Syndrome. CTCL patients require individualized, holistic, and multidisciplinary care, for whom addressing management in different skin types and prioritizing quality of life issues are essential.
J Drugs Dermatol. 2017;16(5):405-412.
Cutaneous T-Cell Lymphoma (CTCL) is a heterogeneous group of Non-Hodgkin’s lymphomas arising from mature T-cells. CTCL is a rare but important entity for all dermatologists to become familiar with in order to facilitate diagnosis and management. This review will focus on the two most common types of CTCL, Mycosis Fungoides (MF), and Sézary Syndrome (SS), summarizing the latest evidence-based guidelines, including classification, epidemiology, clinical presentation, diagnosis, pathophysiology, and treatment strategies. We will highlight management of CTCL in patients with Fitzpatrick skin types IV-VI and issues affecting quality of life. CTCL represents a unique intersection of dermatology, immunology, and oncology, and requires multidisciplinary management. Classification The term Mycosis Fungoides was first coined in 1806 to describe a patient with cutaneous patches that progressed into plaques and tumors.1 Sézary Syndrome was first documented in 1933 as a syndrome of pruritus, generalized erythroderma, and abnormal hyperconvoluted lymphoid cells in the blood.2 The distinction between primary cutaneous and primary systemic lymphomas was first made in 19753; prior to that time cutaneous lymphomas were managed in the same manner as their nodal counterparts. In 2005, the World Health Organization (WHO) and the European Organization for Research and Treatment of Cancer (EORTC) published a collaborative WHO-EORTC Classification of Cutaneous Lymphomas,4 for the first time attempting to unify these entities to optimize diagnosis, therapy and clinical investigation in these diseases. The WHO integrated these entities in its 2008 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, Fourth Edition.5 These definitions are accepted world-wide by dermatologists, oncologists, pathologists, and dermatopathologists. The latest WHO classification was recently revised and the official monograph is currently pending. Notable updates include adding “Primary cutaneous acral CD8+ T-cell lymphoma” as a provisional entity and changing “Primary cutaneous CD4+ small/medium T-cell lymphoma” to “primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder” to reflect its indolent behavior and favorable prognosis.6 About 50% of cutaneous lymphoma cases classified by the WHO-EORTC are Mycosis Fungoides (MF) (44%) and its variants, Folliculotropic MF (4%), Pagetoid Reticulosis (<1%), and Granulomatous Slack Skin (<1%). MF is defined as an epidermotropic proliferation of small to medium sized T lymphocytes with cerebriform nuclei, characterized by the evolution of patches, plaques, and tumors.4 3% of CTCL cases are Sézary Syndrome, classically defined by the triad of erythroderma, generalized lymphadenopathy, and the presence of neoplastic Sézary cells circulating in the peripheral blood.7 Whether MF and SS are distinct diseases or exist on a spectrum is controversial, but SS is officially classified as a separate disease