CHAPTER 1
Introduction
Primary cutaneous lymphomas represent distinct clinical and histopathologic subtypes of extranodal lymphomas. They can be defined as neoplasms of the immune system, characterized by a proliferation of either T, natural killer (NK), or B lymphocytes, which show a particular tropism for the skin. By definition, primary cutaneous lymphomas show no evidence of extracutaneous manifestations at presentation. Besides malignant lymphomas, the skin may be the primary site of onset of other hematological malignancies such as myeloid leukemia (“aleukemic leukemia cutis”) and blastic plasmacytoid dendritic cell neoplasm; although staging investigations may be negative at presentation, these disorders should be better regarded as a secondary cutaneous manifestation of an undiscovered malignant hematological disease, and treated accordingly.
Primary cutaneous lymphomas should be separated from secondary skin manifestations of extracutaneous (usually nodal) lymphomas and leukemias, which represent metastatic disease characterized usually by a worse prognosis, and requiring different treatments. Since the histopathology of primary and secondary cutaneous lymphomas may be similar or identical, in many cases complete staging investigations are needed to establish this distinction (early mycosis fungoides representing the most important, but not the only exception to this rule).
Besides cutaneous lymphomas, many diseases that simulate them either clinically, histopathologically, or both, are a daily source of diagnostic problems (cutaneous pseudolymphomas). Criteria for diagnosis and differential diagnosis of these benign lymphoproliferative conditions are discussed in Chapter 31 of this book.
Finally, besides infiltration by neoplastic lymphocytes, the skin may present with several specific or nonspecific signs and symptoms related to extracutaneous lymphomas, some of which are highly suggestive of specific conditions. A discussion of non‐neoplastic cutaneous manifestations of systemic lymphomas and leukemias is provided in Chapter 29.
Classification of cutaneous lymphomas
Regrettably, as in past times, different classifications for lymphomas and leukemias are again in use. A Clinical Advisory Committee (CAC) together with world leading hematopathologists published the International Consensus Classification (ICC) of Myeloid and Lymphoid Neoplasms in 2022 [1] (the ICC book has been subsequently published in 2025) [2]. On the other hand, the World Health Organization (WHO), prepared in 2022 the 5th revision of the Classification of Haematolymphoid Tumours [3, 4] (the WHO book has been subsequently published in two volumes in 2024) [5]. However, the ICC and WHO schemes differ only in some parts, and there is no major discrepancy for what concerns skin lymphomas; the entities relevant for the skin are listed in Table 1.1. For what concerns cutaneous lymphomas, the ICC and WHO schemes are based on the seminal work made by the European Organization for Research and Treatment of Cancer (EORTC) – Cutaneous Lymphomas Task Force, which in 1997 published the first comprehensive classification of cutaneous lymphomas [6], subsequently revised together with a WHO panel in 2005 and 2018, and updated in 2024 (Table 1.1) [7]. In fact, in contrast to previous editions, in the last edition of the WHO Classification of Haematolymphoid Tumours published in 2024, primary cutaneous T‐cell lymphomas are listed as a distinct group (most primary cutaneous B‐cell lymphomas are referred to as specific entities in the context of other extracutaneous B‐cell lymphomas) [3]. Curiously enough, however, Sézary syndrome has not been included in the group of cutaneous T‐cell lymphomas in the WHO classification. The recognition of cutaneous lymphomas as a distinct group (after decades of disregard by most hematopathologists) is mainly due to the work done in the past by the Dutch and Austrian groups, particularly by Rein Willemze and Helmut Kerl.
Despite the presence of an accepted frame for classification of primary cutaneous lymphomas, in many publications obsolete terminology such as “cutaneous T‐cell lymphoma” is still used. Under this term cases of mycosis fungoides and Sézary syndrome (and sometimes of other T‐cell lymphomas arising in the skin as well) are lumped together, thus hindering any meaningful analysis of the published data. In order to compare data, it is paramount that physicians in different countries and centers classify cutaneous lymphomas in a repeatable way.
Table 1.1 Comparison of the International Consensus Classification of Myeloid and Lymphoid Neoplasms and the 5th edition of the WHO Classification of Haematolymphoid Tumours for entities relevant to the skin, and corresponding entities in the 2018 WHO‐EORTC Classification of Cutaneous Lymphomas
| International consensus classification | WHO 5ed | 2018 WHO‐EORTC classification of cutaneous Ly. |
| Mycosis fungoides and variants | Mycosis fungoides and variants | Mycosis fungoides and variants |
| Folliculotropic mycosis fungoides | Folliculotropic mycosis fungoides | Folliculotropic mycosis fungoides |
| Pagetoid reticulosis | Pagetoid reticulosis | Pagetoid reticulosis |
| Granulomatous slack skin | Granulomatous slack skin | Granulomatous slack skin |
| Sézary syndrome | Sézary syndrome | Sézary syndrome |
| Adult T‐cell leukemia/lymphoma | Adult T‐cell leukemia/lymphoma | Adult T‐cell leukemia/lymphoma |
| Cutaneous CD30+ lymphoproliferative disorders | Cutaneous CD30+ lymphoproliferative disorders | Cutaneous CD30+ lymphoproliferative disorders |
| Cutaneous anaplastic large cell lymphoma | Cutaneous anaplastic large cell lymphoma | Cutaneous anaplastic large cell lymphoma |
| Lymphomatoid papulosis | Lymphomatoid papulosis | Lymphomatoid papulosis |
| Subcutaneous panniculitis‐like T‐cell lymphoma | Subcutaneous panniculitis‐like T‐cell lymphoma | Subcutaneous panniculitis‐like T‐cell lymphoma |
| Extranodal NK/T‐lymphoma, nasal‐type | Extranodal NK/T‐lymphoma, nasal‐type | Extranodal NK/T‐lymphoma, nasal‐type |
| Cutaneous γ/δ T‐cell lymphoma | Cutaneous γ/δ T‐cell lymphoma | Cutaneous γ/δ T‐cell lymphoma |
| Cutaneous aggressive epidermotropic CD8+ CTCL | Cutaneous aggressive epidermotropic CD8+ CTCL | Cutaneous aggressive epidermotropic CD8+ CTCL (provisional) |
| pCSMPCD4+ T‐cell lymphoproliferative disorder | pCSMPCD4+ T‐cell lymphoproliferative disorder | pCSMPCD4+ T‐cell lymphoproliferative disorder (provisional) |
| Acral CD8+ T‐cell lymphoproliferative disorder | Acral CD8+ T‐cell lymphoproliferative disorder | Acral CD8+ T‐cell lymphoma (provisional) |
| EBV+ T/NK‐cell lymphoproliferative disorders of childhood | EBV+ T/NK‐cell LPs and lymphomas of childhood | Chronic active EBV infection |
| Peripheral T‐cell lymphoma, NOS | Cutaneous peripheral T‐cell lymphoma, NOS | Cutaneous peripheral T‐cell lymphoma, NOS |
| Cutaneous marginal zone lymphoproliferative disorder | Cutaneous marginal zone lymphoma | Cutaneous marginal zone lymphoma |
| Cutaneous follicle center lymphoma | Cutaneous follicle center lymphoma | Cutaneous follicle center lymphoma |
| Cutaneous diffuse large B‐cell lymphoma, leg‐type | Cutaneous diffuse large B‐cell lymphoma, leg‐type | Cutaneous diffuse large B‐cell lymphoma, leg‐type |
| Intravascular large B‐cell lymphoma | Intravascular large B‐cell lymphoma | Intravascular large B‐cell lymphoma |
| EBV+ mucocutaneous ulcer | EBV+ mucocutaneous ulcer | EBV+ mucocutaneous ulcer (provisional) |
| NK: natural killer; CTCL: cutaneous T‐cell lymphoma; pCSMPCD4 + : primary cutaneous small/medium pleomorphic CD4‐positive; NOS; not otherwise specified; LPs: lymphoid proliferations. |
Examination of patients
Primary cutaneous lymphomas represent a heterogeneous group of diseases with different clinicopathologic presentations and prognostic features. In order to classify patients correctly, it is crucial that a complete clinical history is obtained and integrated with...
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