ICML 2015 Report: Thirty years of progress in cutaneous lymphoma research

John Ultmann Memorial Lecture / by Maria Dalby.  Cutaneous lymphomas are rare conditions that require careful linking of clinical features with pathological findings for accurate diagnoses and effective treatments. Professor of dermatology Rein Willemze from Leiden in the Netherlands is fascinated by the challenges presented by cutaneous lymphoma in its many and varied forms in the clinic; as John Ultmann memorial lecturer at the ICML, Professor Willemze described how the classification of cutaneous lymphomas has changed over the last few decades and the ways patients have benefited from this.

For a long time after cutaneous lymphoma was first described in the medical literature in the early 1800s, mycosis fungoides (MF) and Sezary syndrome (SS) were the only known presentations of the condition. It was not until into the 1980s and the advent of advanced immunohistochemical methods using monoclonal antibody technology that cutaneous lymphomas could be classified based on their histological and phenotypical features as part of the Kiel classification.¹ This classification separated cutaneous lymphomas into B-cell and T-cell cutaneous lymphomas, and each of these into low-grade or high-grade disease. By correlating these features with clinical observations, dermatologists and pathologists were able to further define other types of cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma (CPCL), including primary cutaneous follicle centre cell lymphoma (PCFCL), cutaneous anaplastic large T-cell lymphoma (C-ALCL), and primary cutaneous large B-cell lymphoma (PCLBCL). In the European Organisation for Research and Treatment of Cancer (EORTC) classification which was published in 1997, cutaneous lymphomas were additionally classified according to their behaviour – indolent, aggressive or intermediate.² Over the next few years consensus was established between EORTC and the World Health Organisation (WHO) which resulted in the WHO-EORTC classification published in 2005³ and in the current WHO classification from 2008⁴ which is now the standard reference work for pathologists and oncologists all over the world.

The recognition of primary cutaneous lymphomas as distinct types of malignant lymphomas that may present on the skin without any evidence of extracutaneous disease and that display different clinical characteristics to histologically similar nodal lymphomas with secondary skin involvement, has led to considerable improvements in the diagnosis and treatment of these patients. Avoiding routine use of systemic chemotherapy in patients with, for example, C-ALCL or PCFCL has reduced the burden of treatment and improved the long-term outlook. C-ALCL typically appears as solitary lesions on adult skin which tend to resolve spontaneously; less than 10% of patients have nodal or systemic involvement at presentation and the five-year disease-specific survival (DSS) is around 96% . Skin relapses are common and readily treatable with radiotherapy. Another form of CD30-positive lymphoproliferative disorder of the skin is lymphomatoid papulosis which is self-healing; all lesions will resolve spontaneously, but the histological features are easily confused with more aggressive types of lymphoma.⁵ Similarly, less experienced haematopathologists may mistake PCFCL for diffuse large B-cell lymphomas for which CHOP plus rituximab is first-line therapy; radiotherapy has demonstrated excellent outcomes in PCFCL^{6, 7} and should be the treatment of choice except in very large tumours. Professor Willemze stressed the need for a multidisciplinary approach to diagnosing and treating cutaneous lymphomas; multidisciplinary teams involving dermatologists, pathologists, oncologists and radiologists were pioneered by the Dutch Cutaneous Lymphoma Group back in the mid-1980s and are now the standard approach in several countries.