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Sunday, February 17, 2013

Array-CGH Analysis of Cutaneous Anaplastic Large Cell Lymphoma.


Array-CGH Analysis of Cutaneous Anaplastic Large Cell Lymphoma.


2013

Source

Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.

Abstract

This chapter describes a study in which the pattern of numerical chromosomal alterations in cutaneous anaplastic large cell lymphoma (C-ALCL) tumor samples was defined using array-based comparative genomic hybridization (CGH). First, the array-based CGH technique applied is outlined in detail. Next, its application in the analysis of C-ALCL tumor specimens is described. This approach resulted in the identification of highly recurrent chromosomal alterations in C-ALCL that include gain of 7q31 and loss on 6q16-6q21 and 13q34, each affecting 45% of the patients. The pattern characteristic of C-ALCL differs markedly from chromosomal alterations observed in other CTCL such as mycosis fungoides and Sézary syndrome and yielded several candidate genes with potential relevance in the pathogenesis of C-ALCL.

Friday, February 8, 2013

Indolent course of cutaneous gamma-delta T-cell lymphoma.


Indolent course of cutaneous gamma-delta T-cell lymphoma.


Feb 2013

Source

College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA.

Abstract

Cutaneous gamma-delta T-cell lymphoma  is a rare malignancy that typically displays an aggressive clinical course. We present an unusual case of a 57-year-old woman with a 3-year history of lower extremity nodules. Histopathologic, immunophenotypic and molecular genetic studies revealed a clonal, predominantly pannicular gamma-delta T-cell infiltrate, leading to a diagnosis of cutaneous lymphoma. The clinical course was characterized by rapid improvement within months of starting systemic corticosteroids, with relapse in ulcerations but no new lesions more than 3 years after onset of disease. Our case and seven previously reported patients with indolent and relatively localized cutaneous lymphoma provide evidence that not all cases of this entity carry a poor prognosis. This indolent subset adds complexity to treatment of cutaneous lymphoma.

Friday, February 1, 2013

The antihistamines clemastine and desloratadine inhibit STAT3 and c-Myc activities and induce apoptosis incutaneous T-cell lymphoma cell lines.


The antihistamines clemastine and desloratadine inhibit STAT3 and c-Myc activities and induce apoptosis in cutaneous T-cell lymphoma cell lines.


Feb 2013

Source

Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.

Abstract


Mycosis fungoides and its leukaemic counterpart Sézary syndrome are the most frequent cutaneous T-cell lymphomas (CTCL), and there is no cure for these diseases. We evaluated the effect of clinically approved antihistamines on the growth of CTCL cell lines. CTCL cell lines as well as blood lymphocytes from patients with Sézary syndrome were cultured with antihistamines, and the cell were analysed for proliferation, apoptosis and expression of programmed death molecules and transcription factors. The two antihistamines clemastine and desloratadine, currently used for symptom alleviation in allergy, induced potent reduction of the activities of the constitutively active transcription factors c-Myc, STAT3, STAT5a and STAT5b in mycosis fungoides and Sézary syndrome cell lines. This inhibition was followed by apoptosis and cell death, especially in the Sézary syndrome-derived cell line Hut78 that also showed increased expression of the programmed death-1 (PD-1) after clemastine treatment. In lymphocytes isolated from Sézary syndrome patients, the CD4-positive fraction underwent apoptosis after clemastine treatment, while CD4-negative lymphocytes were little affected. Because both c-Myc and STAT transcription factors are highly expressed in proliferating tumours, their inhibition by clemastine, desloratadine and other inhibitors could complement established chemotherapies not only for cutaneous T-cell lymphomas but perhaps also other cancers.

TCR-γ Expression in Primary Cutaneous T-cell Lymphomas.


TCR-γ Expression in Primary Cutaneous T-cell Lymphomas.


Jan 2013


Source

*CNIO Lymphoma Group Departments of †Pathology ‡‡‡Dermatology, Fundación Jiménez Díaz Departments of ‡Dermatology §§§Pathology, Hospital Universitario 12 de Octubre §Pathology Department, Hospital de Torrejón de Ardoz Departments of **Dermatology ∥∥Pathology, Hospital Universitario Gregorio Marañón ***Dermatology Department, Hospital Universitario de Getafe, Getafe †††Immunohistochemistry Unit, Biotechnology Programme, CNIO, Madrid ∥Dermatology Department, Hospital Universitario Juan Canalejo, La Coruña ¶Dermatology Department, Hospital de San Juan, Alicante #Dermatology Department, Hospital Universitario Reina Sofía, Córdoba ††Dermatology Department, Hospital Universitario Virgen del Rocío, Sevilla §§Pathology Department, Hospital Universitario Marqués de Valdecilla, Santander ¶¶Dermatology Department, Hospital Virgen del Castillo, Murcia ##Dermatology Department, Hospital Santiago Apostol, Vitoria, Spain ‡‡UCSD Moores Cancer Center, La Joya, CA ∥∥∥Department of Dermatology, Research Unit Dermatopathology, Medical University of Graz, Graz, Austria.

Abstract


Primary cutaneous γδ T-cell lymphomas (PCGD-TCLs) are considered a subgroup of aggressive cytotoxic T-cell lymphomas (CTCLs). We have taken advantage of a new, commercially available antibody that recognizes the T-cell receptor-γ (TCR-γ) subunit of the TCR in paraffin-embedded tissue. We have analyzed a series of 146 primary cutaneous T-cell lymphomas received for consultation or a second opinion in the CNIO Pathology Department. Cases were classified according to the World Health Organization 2008 classification as mycosis fungoides (MF; n=96), PCGD-TCLs (n=5), pagetoid reticulosis (n=6), CD30 primary cutaneous anaplastic large cell lymphomas (n=5), primary cutaneous CD8 aggressive epidermotropic CTCLs (n=3), primary cutaneous CTCL, not otherwise specified (n=4), and extranodal nasal-type NK/T-cell lymphomas primarily affecting the skin or subcutaneous tissue (n=11). Sixteen cases of the newly named lymphomatoid papulosis type D (LyP-D; n=16) were also included. In those cases positive for TCR-γ, a further panel of 13 antibodies was used for analysis, including TIA-1, granzyme B, and perforin. Clinical and follow-up data were recorded in all cases. Twelve cases (8.2%) were positive for TCR-γ, including 5 PCGD-TCLs, 2 MFs, and 5 LyP-Ds. All 5 PCGD-TCL patients and 1 MF patient died of the disease, whereas the other MF patient and all those with LyP-D were alive. All cases expressed cytotoxic markers, were frequently CD3/CD8, and tended to lose CD5 and CD7 expressions. Eight of 12 and 5 of 11 cases were CD30 and CD56, respectively. Interestingly, 5/12 TCR-γ-positive cases also expressed TCR-BF1. All cases analyzed were negative for Epstein-Barr virus-encoded RNA. In conclusion, TCR-γ expression seems to be rare and is confined to cytotoxic primarycutaneous TCLs. Nevertheless, its expression is not exclusive to PCGD-TCLs, as TCR-γ protein can be found in other CTCLs. Moreover, its expression does not seem to be associated with bad prognosis by itself, as it can be found in cases with good and bad outcomes.