Staging of Mycosis Fungoides and Sézary Syndrome: Time for an Update?

Abstract

Mycosis fungoides (MF) is the most common variant of cutaneous T cell lymphoma and frequently presents as early-stage disease with skin patches and plaques with an indolent course, but patients experience significant morbidity from itch and disfigurement. Around 30% of patients with MF present in the advance stages with skin tumours, erythroderma, and extensive nodal or visceral involvement. Sézary syndrome (SS) is the leukaemic cutaneous T cell lymphoma variant. The staging of MF or SS was revised in 2007 to include skin, nodal, visceral, and blood (tumour- node-metastasis-blood classification) to determine nine stages (IA–IVB). While most patients with early disease (Stages IA–IIA) have a good prognosis, 25% progress to advanced disease, with a poor life expectancy of around 3 years; however, some patients do survive for ≥10 years. Accurate staging is crucial since management strategies are stage-based, with skin-directed therapy recommended in early-stage disease and with no curative therapeutic options to improve symptoms and reduce skin tumour burden. In contrast, advanced-stage patients mostly require systemic therapy. Most treatments have only partial response rates, around 40%, and allogeneic bone marrow transplant may provide a more long-lasting therapeutic option for advanced patients. Relevant prognostic factors within the tumour-node-metastasis-blood classification are discussed in this review and their relevance to overall IA–IVB staging and outcomes are debated. Several important prognostic features have been identified that may be used alongside staging to give further prognostic information. These prognostic features include age >60 years at diagnosis, large cell transformation of the skin, and raised serum lactate dehydrogenase levels, which could be developed into a prognostic index to identify patients at risk of progression and requiring more aggressive therapy. The PROCLIPI study, a prospective cutaneous lymphoma international study, has been ongoing since 2015 to collect such data, with the aim of developing a prognostic index for MF and SS.