Guideline for the diagnosis and management of marginal zone lymphomas: A British Society of Haematology Guideline

SCOPE

The objective of this guideline is to provide healthcare professionals with clear guidance on the diagnosis and management of patients with marginal zone lymphoma (MZL).

METHODOLOGY

These guidelines were compiled according to the BSH process: https://b-s-h.org.uk/media/16732/bsh-guidance-development-process-dec-5-18.pdf.

The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org.

Recommendations are based on a review of the literature using Medline/Pubmed. Search terms included: marginal zone, MZL, extranodal MZL, MALT, nodal, splenic, treatment, randomised, clinical trial, radioimmunotherapy, hepatitis C, Helicobacter pylori. The search was limited to English language publications and conference abstracts from 1 January 1998 to 20 September 2022. Titles/abstracts obtained were curated and manually reviewed by the writing group, which conducted additional searches using subsection heading terms.

The manuscript was reviewed by the BSH Guidelines Haemato-oncology Task Force, the BSH Guidelines Executive Committee and the haemato-oncology sounding board of the BSH.

INTRODUCTION

The MZLs are a group of clinically indolent mature B-cell lymphomas derived from memory B cells of the ‘marginal’ zones of secondary lymphoid tissues. Marginal zone B cells are at the centre of inflammation, autoimmunity and malignant transformation through the coordination of innate and adoptive immunity. MZLs, especially extranodal marginal zone lymphomas (EMZL), frequently arise in the context of chronic infection or autoimmune disease, and, while the various subtypes share many biological, diagnostic and clinical features, they manifest subtype-specific features, resulting in a multisystem presentation.

The 5th World Health Organization (WHO) classification of tumours of haematopoietic and lymphoid tissues recognises distinct MZL subtypes according to the microenvironment of involved tissue1—EMZL of mucosa-associated lymphoid (MALT) tissue, splenic marginal zone lymphoma (SMZL) and nodal marginal zone lymphoma (NMZL).2, 3 Paediatric marginal zone lymphoma and primary cutaneous MZL, originally included under NMZL and EMZL/MALT, respectively, are now classified as separate entities.

MZL is the third most common lymphoma,4 comprising up to 15% of non-Hodgkin Lymphoma (NHL) in the Western World. Over 60% are EMZL/MALT (which can arise from any site following chronic antigenic stimulation), 20% are SMZL and <10% are NMZL. Incidence increases with age, suggesting cumulative exposure to risk factors. Age-adjusted incidence has increased by 1.1% per year5 with a current UK incidence of 2.62 per 100 000 and a male-to-female ratio of 1.6.4