Cutaneous lymphomas - an update

Primary cutaneous lymphomas (CL) and lymphoproliferative disorders (LPD) are heterogeneous T- and B-cell neoplasms defined by integrated clinical, histopathological, immunophenotypic and genetic criteria. The 5th edition of the WHO classifications of haematolymphoid and skin tumours and the International Consensus Classification incorporate recent clinicopathological and molecular advances. Formerly provisional entities, including primary cutaneous small or medium CD4+ T-cell LPD, primary cutaneous gamma/delta T-cell lymphoma, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma and Epstein-Barr virus-positive mucocutaneous ulcer, are now established, whereas primary cutaneous CD8+ acral T-cell lymphoma has been renamed primary cutaneous CD8+ acral T-cell LPD because of its excellent prognosis. The WHO classification additionally recognizes primary cutaneous peripheral T-cell lymphoma, not otherwise specified and reactive T- and B-cell-rich lymphoid proliferations. This review summarizes current developments in mycosis fungoides, primary cutaneous CD30-positive LPD, other cutaneous T-cell lymphomas, cutaneous B-cell lymphomas and reactive lymphoid proliferations. Emphasis is placed on diagnostic pitfalls, clinicopathological correlation, emerging immunohistochemical and molecular markers, T-cell receptor sequencing, artificial intelligence-based diagnostic support and clinically relevant genetic alterations. Particular attention is given to the distinction of indolent lymphoproliferations from aggressive lymphoma and from reactive mimics, as this distinction directly influences staging, treatment intensity and patient counselling. Recent data on transformation, gamma/delta phenotypes, CD30 expression, cutaneous B-cell lymphoma biology and EBV-associated lesions are also integrated. The revised classifications underscore that diagnosis of CL should not rely on morphology, immunophenotype or molecular findings alone, but on synoptic integration of all available data to avoid overdiagnosis, underdiagnosis and unnecessary therapy.