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Haematologica 2019 Volume 104(2):226-235
CD30-positive primary cutaneous lymphoproliferative disorders: molecular alterations and targeted therapies
Lucia Prieto-Torres,1 Socorro M. Rodriguez-Pinilla,2,3 Arantza Onaindia,4 Mariano Ara,5 Luis Requena1 and Miguel Á. Piris2,3
Departments of 1Dermatology, 2Pathology, Hospital Universitario Fundación Jiménez Díaz, Madrid; 3 Hospital Universitario Fundación Jiménez Díaz, Madrid, CIBERONC, Madrid, 4Pathology, Hospital Universitario Marques de Valdecilla, Santander and 5Dermatology Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
ABSTRACT
Primary cutaneous CD30-positive T-cell lymphoproliferative disor- ders are the second most common subgroup of cutaneous T-cell lymphomas. They include two clinically different entities with some overlapping features and borderline cases: lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma. Molecular studies of primary cutaneous anaplastic large cell lymphoma reveal an increasing level of heterogeneity that is associated with histological and immunophenotypic features of the cases and their response to specific therapies. Here, we review the most significant genetic, epigenetic and molecular alterations described to date in primary cutaneous CD30-pos- itive T-cell lymphoproliferative disorders, and their potential as therapeu- tic targets.
Introduction
CD30+ primary cutaneous T-cell lymphoproliferative disorders are the second most common subgroup of cutaneous T-cell lymphomas after mycosis fungoides (MF), accounting for approximately 30% of cases.1 These cutaneous lymphomas have customarily been classified on the basis of their clinical presentation into lym- phomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (pcALCL) and borderline cases. In recent years, genomic analysis has become important for the diagnosis and clinical management of patients affected by sys- temic and cutaneous hematologic malignancies.2 Systemic anaplastic large cell lym- phoma (ALCL) is defined by mutually exclusive rearrangements of ALK, DUSP22/IRF4 and TP63, which have prognostic and survival implications and must be taken into account in the management of patients.2 pcALCL have histopathological and immunophenotypic similarities with systemic ALCL, but have a more indolent behavior. Chromosomal translocations described in systemic ALCL can also be seen in pcALCL, although they have different clinical implica- tions. Thus, there are some ALK+ pcALCL, and some cases of LyP and pcALCL share a DUSP22-IRF4 locus translocation. Bearing all this in mind, we have reviewed the molecular alterations in CD30+ primary cutaneous T-cell lymphopro- liferative disorders, describing the various molecular alterations and considering their clinical and therapeutic implications.
Lymphomatoid papulosis
LyP is an enigmatic disease that follows the course of a chronic skin condition and has the histology of a lymphoma. It typically has a recurrent, self-healing course, with an excellent prognosis.3 Clinical features of all types of LyP are similar and consist of papular, papulonecrotic and/or nodular skin lesions at different stages of evolution. The number of lesions is, however, highly variable, ranging from only a few lesions to hundreds. Likewise, there is great variability in the dura- tion of lesions, which may be present for a few weeks or persist for decades. Lyp
Correspondence:
lucia14_prie@msn.com
Received: September 19, 2018. Accepted: December 7, 2018. Pre-published: January 10, 2019.
doi:10.3324/haematol.2018.197152
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/2/226
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