Update in Diagnosis and Management of Primary Cutaneous B-Cell Lymphomas

Amanda Krenitsky; Skylar Klager; Leigh Hatch; Carlos Sarriera-Lazaro; Pei Ling Chen; Lucia Seminario-Vidal

Disclosures

Am J Clin Dermatol. 2022;23(5):689-706. 

In This Article

Abstract and Introduction

Abstract

Primary cutaneous lymphomas are a rare group of diseases, with an estimated incidence of 0.5–1 case per 100,000 people per year. Primary cutaneous B-cell lymphomas (pCBCLs) represent 25–30% of all primary cutaneous lymphomas. There are three main subtypes of pCBCL: primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma, and primary cutaneous diffuse large B-cell lymphoma, leg type. Cutaneous B-cell lymphomas have a broad spectrum of clinical presentations, which makes diagnostic and therapeutic strategies challenging. To date, treatment recommendations for cutaneous B-cell lymphomas have been largely based on small retrospective studies and institutional experience. Recently, the pharmacotherapeutic landscape has expanded to include drugs that may modify the underlying disease pathology of pCBCLs, representing new therapeutic modalities for this rare group of diseases. Novel therapies used for other systemic B-cell lymphomas show promise for the treatment of pCBCLs and are being increasingly considered. These new therapies are divided into five main groups: monoclonal antibodies, immune checkpoint inhibitors, small-molecule inhibitors, bispecific T-cell engaging, and chimeric antigen receptor T cell. In this review, we discuss the clinical, histopathological, molecular, and cytogenetic features of the most common pCBCL subtypes with a focus on current and innovative therapeutic developments in their management. These emerging treatment strategies for B-cell lymphomas and cutaneous B-cell lymphomas may represent novel first-line options for the management of these rare diseases.

Introduction

Primary cutaneous B-cell lymphomas (pCBCLs) constitute a heterogeneous group of extra-nodal B-cell non-Hodgkin lymphomas (B-NHLs). Defined as being present only in the skin at the time of diagnosis, pCBCLs are a rare entity, representing only 25–30% of all primary cutaneous lymphomas.[1] Incidence is estimated at < 1 per 100,000 persons/year and increases with age.[2]

The 2018 update of the World Health Organization-European Organization for Research and Treatment of Cancer classifies pCBCL into three major subtypes: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle center lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT). Primary cutaneous follicle center lymphoma and PCMZL portend an indolent clinical course with 5-year survival rates of over 90% and up to 98%, whereas PCDLBCL, LT is a more aggressive variant with associated 5-year survival between 20 and 70%.[3] Intravascular large B-cell lymphoma is a rare and aggressive subtype of large B-cell lymphoma with a 3-year survival rate of 56% in patients with only cutaneous manifestations and 22% in those with disseminated disease. Primary cutaneous diffuse large B-cell lymphoma not otherwise specified, and Epstein–Barr virus-positive mucocutaneous ulcer are very rare pCBCL subtypes. Primary cutaneous diffuse large B-cell lymphoma not otherwise specified has a 5-year survival around 90% and Epstein–Barr virus-positive mucocutaneous ulcer portends an indolent self-limited course.[1,2,4]

An accurate pathologic diagnosis of the subtype is the most important first step in the management of pCBCLs. Basic clinicopathologic evaluation is the same for each subtype, although some further evaluation may be useful in certain circumstances to clarify a particular diagnosis. To appropriately confirm the diagnosis of pCBCL, systemic involvement must be ruled out. As such, a thorough work-up is necessary and includes a detailed history and physical examination, tissue sampling, molecular studies, and laboratory studies. Cytogenetics and flow cytometry of the blood and/or lesional tissue are helpful in certain conditions[5–7]

Management of pCBCL is complex and requires coordination of a multidisciplinary care team comprising dermatologists, pathologists, hematology-oncologists, and radiation oncologists. There is a scarcity of large randomized trials in pCBCL, and current therapeutic guidelines are based on small retrospective studies.[3,8–10] This review aims to describe the pathophysiological, epidemiological, clinicopathological, immunohistochemical, molecular, and cytogenetic features of the most common pCBCL subtypes with a focus on current and innovative therapeutic developments in their management.

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