CD30 +Lymphoproliferative Disorders of the Skin

Primary cutaneous CD30 ⁺lymphoproliferative disorders encompass lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (pcALCL), and indeterminate cases. LyP is a benign disorder characterized by recurrent crops of red or violaceous papulonodules. Patients with LyP are at an increased risk of a secondary malignancy. pcALCL is characterized by a solitary red to violaceous nodule or tumor larger than 20 mm. LyP is benign, is limited to the skin, and self-resolves, with a 5-year survival rate of 100%; pcALCL is limited to the skin and responsive to directed therapies, with a 5-year survival rate of over 95%. Aggressive chemotherapeutic regimens should be avoided.

Key points

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Primary cutaneous CD30 ⁺lymphoproliferative disorders encompass a spectrum of benign to malignant phenotypes including lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (pcALCL) and borderline cases.
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LyP is characterized by recurrent crops of several to hundreds of red to violaceous papulonodules measuring up to 20mm, usually on the trunk and extremities, while pcALCL presents with a solitary or localized red to violaceous nodulotumor greater than 20mm that may occur anywhere on the body.
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Patients with LyP are at increased risk of secondary malignancy, most often mycosis fungoides or ALCL, may be diagnosed before, during or after the diagnosis of LyP and should undergo ongoing surveillance.
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Patients presenting with cutaneous ALCL should be worked-up to ensure it is primary cutaneous and not secondary cutaneous involvement of systemic ALCL.
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LyP is benign, limited to the skin and self-resolving with a 5-year survival rate of 100%, while pcALCL is usually limited to the skin and responsive to directed therapies, with a 5-year survival of over 95%; aggressive systemic or multi-agent chemotherapeutic regimens should be avoided.

Introduction

Cluster of differentiation 30 (CD30), a 120-kDa type I transmembrane glycoprotein of the tumor necrosis factor receptor superfamily member 8 (TNFRSF8) gene and previously known as Ki-1 antigen, is a cell surface cytokine receptor present on activated T and B cells. Upon T-cell activation, CD28 and other costimulatory receptors, including CD30, are upregulated. CD30 expression requires CD28 or interleukin-4 receptor signaling and, when CD30 is activated, downstream signaling augments T-cell proliferation at low levels and regulates T-cell survival.

CD30 interacts with CD30 ligand (CD30L, CD153, TNFSF8), a 40-kDa type II membrane-associated glycoprotein belonging to the TNF family that is expressed on activated T cells, primarily CD4 T cells of both T helper 1 and 2 (Th1 and Th2) phenotypes, as well as on a subset of accessory cells and B cells. CD30 signaling ultimately leads to nuclear factor-κB activation through both TNFR-associated factor 2-dependent and TNFR-associated factor 2-independent pathways that can inhibit effector cell activity, promote apoptosis, or promote survival depending on the cell type and different intracellular signaling pathways activated. For example, ligation of CD30 signals can downregulate the cytotoxic effector molecules Fas ligand, perforin, and granzyme B, and inhibit cytotoxicity. CD30 signaling also promotes apoptosis by strongly inhibiting the expression of the oncogene c-myc and upregulating Fas (TNFRSF6), death receptor 3 (TNFRSF25), and TNF-related apoptosis-inducing ligand (TNFSF10, TRAIL). In addition to increasing the cell’s susceptibility to apoptosis, CD30 signaling strongly upregulates chemokine receptor 7, a homing molecule that enhances the cell’s ability to home to lymphoid organs. A variety of causes have been implicated in the induction of CD30 expression in human cutaneous reactive and neoplastic lymphocytic processes including infectious, exogenous, inflammatory, and lymphoproliferative disorders (LPD; Table 1 ).

Table 1

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