The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas

Abstract

Primary cutaneous lymphomas are a heterogeneous group of T- and B-cell lymphomas that present in the skin with no evidence of extracutaneous disease at the time of diagnosis. The 2005 World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) consensus classification has served as a golden standard for the diagnosis and classification of these conditions. In September 2018, an updated version of the WHO-EORTC was published in the fourth edition of the WHO Classification of Skin Tumours Blue Book. In this classification, primary cutaneous acral CD8⁺ T-cell lymphoma and Epstein-Barr virus positive (EBV⁺) mucocutaneous ulcer are included as new provisional entities, and a new section on cutaneous forms of chronic active EBV disease has been added. The term "primary cutaneous CD4⁺ small/medium T-cell lymphoma" was modified to "primary cutaneous CD4⁺ small/medium T-cell lymphoproliferative disorder" because of its indolent clinical behavior and uncertain malignant potential. Modifications have also been made in the sections on lymphomatoid papulosis, increasing the spectrum of histologic and genetic types, and primary cutaneous marginal zone lymphomas recognizing 2 different subtypes. Herein, the characteristic features of these new and modified entities as well as the results of recent molecular studies with diagnostic, prognostic, and/or therapeutic significance for the different types of primary cutaneous lymphomas are reviewed. An update of the frequency and survival of the different types of primary cutaneous lymphomas is provided.

Figure 1.

Sézary syndrome. Patient presenting with (A) erythroderma. (B) Band-like infiltrate of atypical lymphoid cells in superficial dermis with formation of intraepidermal (Pautrier) microabscesses. (C) Strong expression of CD279 (PD-1) by neoplastic T cells is a useful marker to differentiate Sézary syndrome from erythrodermic inflammatory dermatoses. Original magnification ×40 (B-C); hematoxylin and eosin (B) and immunoperoxidase (C) stain.

Figure 2.

Cutaneous anaplastic large cell lymphoma presenting with multiple skin lesions on the right lower leg. (A) Part disappeared spontaneously. (B) Histologic examination shows a diffuse infiltrate of large anaplastic cells, which are positive for CD30 (C) and show cytoplasmic staining for ALK (D). Staging was negative; initially, an expectant policy was followed. Twelve months after diagnosis, the patient developed systemic disease with involvement of the lungs and bone marrow. Treatment with multiagent chemotherapy was unsuccessful and she died 18 months after diagnosis. Original magnification ×400 (B-D); hematoxylin and eosin (B) and immunoperoxidase (C-D) stain.

Figure 3.

Primary cutaneous acral CD8⁺T-cell lymphoma. (A) Typical clinical presentation, with slowly progressive skin tumor on the right ear. (B) Diffuse proliferation of medium-sized pleomorphic cells in the dermis; the atypical cells strongly express CD8 (C) and TIA-1 (D). (E) CD68 shows a positive Golgi dot-like staining. Original magnification ×20 (B,E) and ×40 (C-D); hematoxylin and eosin (B) and immunoperoxidase (C-E) stain.

Figure 4.

Primary cutaneous CD4⁺small/medium T-cell lymphoproliferative disorder. (A) Patient presenting with a tumor on the left cheek. (B) Detail of atypical dermal infiltrate showing a predominance of small/medium lymphoid cells and scattered large lymphoid cells, which express CD4 (C). (D) Expression of CD279/PD-1 by medium-sized to large atypical T cells, partly arranged in clusters. Original magnification ×200 (B,D) and ×40 (C); hematoxylin and eosin (B) and immunoperoxidase (C-D) stain.

Figure 5.

Primary cutaneous diffuse large B-cell lymphoma, leg type. (A) Cohesive sheets of large transformed cells with prominent nucleoli. Strong expression of BCL2 (B), IgM (C), and MYC (D) may facilitate differentiation from PCFCL. Original magnification ×400 (A, hematoxylin and eosin stain) and ×200 (B-D, immunoperoxidase stain).