[Treatment of rare cutaneous T­cell lymphoma and blastic plasmacytoid dendritic cell neoplasm]. / Therapie seltener kutaner T­Zell-Lymphome und der blastären plasmazytoiden dendritischen Zellneoplasie.

Among the group of primary cutaneous lymphomas several subtypes have very low incidence rates. Based on the revision of the WHO classification for lymphoid neoplasms (2016), an overview of rare cutaneous T­cell lymphoma (CTCL) subtypes is given and therapeutic approaches are detailed. The prognosis of the different subtypes is highly variable underlining the importance of adequate stage and subtype adapted treatment. In cases of indolent subtypes topical treatment, e. g. topical corticosteroids or UV phototherapy are often sufficient. For aggressive variants, early discussion of more aggressive systemic treatment options is warranted.

Primary cutaneous follicular helper T-cell lymphoma: diagnostic pitfalls of this new lymphoma subtype.

The recently proposed entity of cutaneous follicular helper T (T(FH)) cell lymphoma (CT(FH)CL) harbors distinct clinical and histopathologic features. Here, diagnostic pitfalls are exemplified in a case report and by review of the literature. A 45-year-old patient developed rapidly growing nodules and plaques on upper arms and buttocks, which were initially misdiagnosed as primary cutaneous follicle center B-cell lymphoma (CFCL). Consequently, systemic therapy with rituximab failed and consecutive skin biopsies revealed CT(FH)CL (CD3+CD4+CD10+PD-1+bcl6+ICOS+CXCL13+). Interestingly, the prima vista PD-1-positive and CD10-positive tumor cells lost PD-1 expression in follow-up biopsies while retaining CD10, ICOS and CXCL13 expression. All biopsy specimens displayed an identical clonal T-cell population. Initially, nodules were controlled by local radiotherapy and oral psoralen combined with ultraviolet A (PUVA) therapy. However, disease recurred and progressed rapidly with disseminated nodules. Treatment with bexarotene, methotrexate and polychemotherapy failed to stop disease progression. Finally, modified total skin electron beam radiation resulted in complete remission. Disease stabilized on maintenance therapy with bexarotene in combination with ultraviolet A (UVA) therapy. The case highlights that because of concomitant B-cell stimulation, CT(FH)CL clinicopathologically is prone to be mistaken for CFCL. Importantly, CT(FH)CL might lose PD-1 while retaining CD10 expression in later stages, which may lead to confusion in distinguishing CT(FH)CL from CFCL.

Bexarotene in the treatment of cutaneous T-cell lymphoma.

Primary cutaneous T-cell lymphomas encompass a spectrum of non-Hodgkin's lymphomas that are characterised by clonal proliferation of skin-homing malignant T lymphocytes. Mycosis fungoides and the leukaemic variant Sézary syndrome, collectively referred to as cutaneous T-cell lymphomas, are the most common entities. No curative therapy exists and patients ultimately develop advanced or relapsed disease that is refractory to standard treatment options. Therefore, there is a great need for the development of novel emerging therapies. Bexarotene is the first synthetic nuclear retinoid X receptor-selective retinoid approved by the FDA for the treatment of refractory cutaneous T-cell lymphoma in all stages, as both an oral capsule and a topical gel formulation. Bexarotene was found to induce apoptosis in a variety of preclinical in vitro and in vivo models including cutaneous T-cell lymphoma cells, and has shown efficacy in two multi-centre, open-label Phase II - III clinical trials for early and advanced stages of cutaneous T-cell lymphoma in patients who have failed or were refractory to standard therapies. New insights into the immunomodulatory function of bexarotene have indicated opportunities for combined treatment with IFN-alpha, denileukin diftitox or phototherapy. This article reviews the biological properties, pharmacokinetics, clinical efficacy, safety and role of bexarotene in the treatment of cutaneous T-cell lymphoma.

Systemic and primary cutaneous anaplastic large cell lymphomas.

Anaplastic large cell lymphoma (ALCL) is a neoplasm of activated lymphocytes, commonly expressing T-cell antigens and cytotoxic proteins. Histopathology reveals distinctive infiltration of sinuses and paracortical T-cell-rich regions of lymph nodes by tumor cells which have abundant cytoplasm and large irregular/convoluted nuclei, and which are frequently multinucleated with prominent nucleoli. ALCL often presents in advanced clinical stages with B symptoms; extranodal disease occurs in 40% of patients. The pathogenesis of systemic ALCL is linked to phosphorylation of a tyrosine kinase (ALK) resulting in unregulated growth of affected lymphoid cells. ALK is activated through chromosomal translocations/inversions with any of several partner genes, most commonly nucleophosmin (NPM). Downstream signal transduction pathway(s) are not fully defined but appear to involve phospholipase Cgamma, phosphatidylinositol (PI)3K/Akt, and STAT-3 and STAT-5 proteins. Primary cutaneous ALCL appears to have a different pathogenesis and better prognosis than does systemic ALCL, presenting as one or more skin tumors, usually localized. Excision or local irradiation is usually effective treatment. A clinically benign variant of primary cutaneous ALCL is lymphomatoid papulosis (LyP), characterized by recurrent crops of papules/nodules up to 2 cm in diameter which undergo spontaneous regression. LyP is managed by observation, ultraviolet light therapy, or low-dose methotrexate. LyP patients have a predisposition to develop malignant lymphomas, including Hodgkin's lymphoma, mycosis fungoides, and non-Hodgkin's lymphoma, by as yet unknown mechanisms. The prognosis for patients with LyP is otherwise excellent.

Diagnóstico y tratamiento de los linfomas cutáneos primarios de células T / Diagnosis and treatment of primary cutaneous t-cell lymphoma

Los linfomas cutáneos primarios representan un heterogéneo grupo de linfomas no-Hodgkin con una amplia variedad desde el punto de vista clínico, histológico, inmunofenotípico y pronóstico. Esta variedad, junto al diferente comportamiento biológico que han demostrado los linfomas cutáneos respecto a sus homólogos sistémicos, ha llevado al desarrollo de sistemas de clasificación específicos para el linfoma cutáneo, como la clasificación de la EORTC de 1997. El diagnóstico del linfoma cutáneo precisa de la integración de la información clínica, histológica, inmunohistoquímica y genética. No obstante, a pesar de la aplicación de técnicas de biología molecular existe un porcentaje de linfomas cutáneos que no llegan a diagnosticarse y clasificarse correctamente. Debido al buen pronóstico del linfoma cutáneo en estadios iniciales y a la ausencia de tratamiento curativo han sido propuestos múltiples regímenes para el manejo de estos pacientes. El uso de corticoides tópicos, emolientes, mostazas nitrogenadas, carmustina, fototerapia, radioterapia (localizada, irradiación corporal total), agentes modificadores biológicos (interferón, bexaroteno), quimioterápicos (gemcitabina, pentostatina, etc) son algunas de las modalidades terapéuticas actualmente empleadas en estos pacientes. La elección adecuada de la modalidad más adecuada en cada caso debe tener en cuenta el tipo clínico de linfoma y especialmente el estadio clínico del mismo, además del perfil de seguridad y las tasas de respuestas conseguidas con cada uno de estos agentes. Las clasificaciones actuales de linfoma cutáneo, modalidades terapéuticas, así como los protocolos de actuación para el manejo del paciente con linfoma cutáneo de células T son descritos con detalle en este artículo (AU)

Linfoma cutáneo de células T (CTCL) / Lymphoma, T-Cell, cutaneous

Esta comunicación tiene por objeto informar a la comunidad médica sobre un caso sumamente infrecuente de linfoma cutáneo primario de céluas T (CTCL). Se trata de un CTCL pleomórfico de células pequeñas que, dentro de la clasificación de la EORTC corresponde al grupo considerado provisional. En este grupo se ubican todos los CTCL de los que se desconocen su evolución y pronóstico dado el número insuficiente de casos estudiados. Asimisno se realiza una revisión del tema de la que surgen las siguientes consideraciones: 1) los linfomas cutáneos primarios y los linfomas ganglionares no Hodgkin, son idénticos desde el punto de vista morfológico pero constituyen entidades diferentes tanto desde el punto de vista clínico cuanto biológico, 2) las clasificaciones de Kiel y REAL resultan insuficientes para tratar esta problemática, 3) la clasificación de la EORTC parece ser la más apropiada aunque aún no existe suficiente experiencia sobre algunos tipos de CTCL.

Linfoma cutáneo de células T (CTCL) / Lymphoma, T-Cell, cutaneous

Esta comunicación tiene por objeto informar a la comunidad médica sobre un caso sumamente infrecuente de linfoma cutáneo primario de céluas T (CTCL). Se trata de un CTCL pleomórfico de células pequeñas que, dentro de la clasificación de la EORTC corresponde al grupo considerado provisional. En este grupo se ubican todos los CTCL de los que se desconocen su evolución y pronóstico dado el número insuficiente de casos estudiados. Asimisno se realiza una revisión del tema de la que surgen las siguientes consideraciones: 1) los linfomas cutáneos primarios y los linfomas ganglionares no Hodgkin, son idénticos desde el punto de vista morfológico pero constituyen entidades diferentes tanto desde el punto de vista clínico cuanto biológico, 2) las clasificaciones de Kiel y REAL resultan insuficientes para tratar esta problemática, 3) la clasificación de la EORTC parece ser la más apropiada aunque aún no existe suficiente experiencia sobre algunos tipos de CTCL. (AU)