Cutaneous Lymphomas with Cytotoxic Phenotype

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Abstract

Primary cutaneous cytotoxic lymphomas are T-cell or natural killer–cell lymphomas that express 1 or more cytotoxic markers. These neoplasms constitute a spectrum of diseases. In this review, an overview of clinical, morphologic, and phenotypical features of each subtype is provided. Differential diagnosis is discussed with attention to scenarios in which diagnostic difficulties are most frequently encountered.

Section snippets

Overview

Primary cutaneous cytotoxic lymphomas (PCCLs) (Table 1) are T-cell or NK-cell lymphomas that present in the skin with no evidence of extracutaneous disease at the time of diagnosis and express 1 or more cytotoxic markers, such as T-cell intracellular antigen (TIA)-1, perforin, or granzyme B. Expression of TIA-1 is characteristic of cytotoxic cells regardless of their activation status, whereas expression of perforin and granzyme is highly increased in activated cytotoxic cells and correlates

Key points T-cell and natural killer cell subsets

Historically, the classification of lymphomas has been based on the presumed normal counterpart. Thus, some of the subtypes of primary cutaneous cytotoxic T-cell lymphomas (TCLs) reflect the putative cell of origin, for example, naive CD8+ αβ T cell versus memory CD8+ αβ T cell.

  • 1.

    T-cell sublineages are divided into 2 large classes—αβ and γδ T cells—which relate to the expression of an αβ T-cell receptor (TCR) or a γδ TCR and the intrathymic progression through the double-positive stage (CD4+/CD8+

Overview

SPTCL is a rare subset of cutaneous lymphoma with an indolent course and long survival, characterized by subcutaneous infiltration of neoplastic CD8+ CD56, and betaF1+ cytotoxic T cells. In the WHO–European Organisation for Research and Treatment of Cancer (EORTC) classification of cutaneous lymphomas in 2005,8 the term SPTCL was restricted to cases with an αβ T-cell phenotype. Prior to this definition, the term SPTCL was used to include all TCLs with a panniculitic-like pattern, thus making

Overview

Primary cutaneous CD8+ aggressive epidermotropic cytotoxic TCL (AECTCL) is a rare, provisional entity characterized by a proliferation of epidermotropic CD8+ cytotoxic T cells.3, 4 Since the first description by Berti and colleagues,26 fewer than 100 cases of this lymphoma have been reported in the literature.26, 27, 28, 29, 30, 31, 32 Probably some cases of CD8+ AECTCL were categorized in the past as generalized pagetoid reticulosis (PR), Ketron-Goodman type. Patients present de novo with

Overview

In the latest WHO classification, PCGDTCL is considered a distinct entity composed of a clonal proliferation of mature, activated γ/δ T-cells with expression of CD3, CD2, and CD56 and negativity for betaF1, CD4, and usually CD8.3, 4 Historically, the diagnosis of PCGDTCL could only be established with certainty in tissue samples by flow cytometry or frozen sections by immunohistochemistry. The diagnosis based on formalin-fixed paraffin-embedded (FFPE) material was basically a presumptive

Overview

Primary cutaneous acral CD8+ TCL has been included as a provisional entity in the recent 2016 revision of the WHO classification of lymphoid neoplasms.3 It is defined as a clonal disorder composed of CD8+ cells with an indolent clinical course and was described by Petrella and colleagues in 2007.58 Four patients with lesions restricted to the skin of the ear were described and the name, indolent CD8+ lymphoid proliferation of the ear, was proposed. Since the original description, 47 additional

Overview

MF and its variants represent the most common type of cutaneous TCLs (approximately 50% of all primary cutaneous lymphomas). According to the WHO-EORTC classification of these neoplasm, the term MF should be used only for the classic Alibert-Bazin type, characterized by the evolution of patches, plaques, and tumors, or for variants showing a similar clinical course.8 Usually, MF is derived from mature CD4+ memory T cells; however, as many as 20% of cases of early MF display a cytotoxic

Summary

In this review, the group of primary cutaneous cytotoxic TCLs is described. These lymphomas can be broadly divided into 2 groups. The first group includes CD8+ MF, primary acral CD8+ lymphoma, SPTCL, and CD30+ LPDs with cytotoxic phenotype. These are lymphoid neoplasm with indolent behavior. A second group characterized by dismal prognosis, comprises PCGDTCL, CD8+ AECTCL, and NK/T-cell LPDs. When dealing with cytotoxic lymphomas in particular and with cutaneous lymphomas in general, it is

Acknowledgments

We are very grateful to Dr Teresa Estrach Panella for providing the clinical images showed in this work.

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    Disclosure Statement: The authors have nothing to disclose.

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