Primary Cutaneous T-cell Lymphoma (primary + cutaneous_t-cell_lymphoma)

Distribution by Scientific Domains


Selected Abstracts


Epigenetic changes in cancer,

APMIS, Issue 10 2007
KIRSTEN GRŘNBĆK
A cancer develops when a cell acquires specific growth advantages through the stepwise accumulation of heritable changes in gene function. Basically, this process is directed by changes in two different classes of genes: Tumor suppressor genes that inhibit cell growth and survival and oncogenes that promote cell growth and survival. Since several alterations are usually required for a cancer to fully develop, the malignant phenotype is determined by the compound status of tumor suppressor genes and oncogenes. Cancer genes may be changed by several mechanisms, which potentially alter the protein encoding nucleotide template, change the copy number of genes, or lead to increased gene transcription. Epigenetic alterations, which, by definition, comprise mitotically and meiotically heritable changes in gene expression that are not caused by changes in the primary DNA sequence, are increasingly being recognized for their roles in carcinogenesis. These epigenetic alterations may involve covalent modifications of amino acid residues in the histones around which the DNA is wrapped, and changes in the methylation status of cytosine bases (C) in the context of CpG dinucleotides within the DNA itself. Methylation of clusters of CpGs called "CpG-islands" in the promoters of genes has been associated with heritable gene silencing. The present review will focus on how disruption of the epigenome can contribute to cancer. In contrast to genetic alterations, gene silencing by epigenetic modifications is potentially reversible. Treatment by agents that inhibit cytosine methylation and histone deacetylation can initiate chromatin decondensation, demethylation and reestablishment of gene transcription. Accordingly, in the clinical setting, DNA methylation and histone modifications are very attractive targets for the development and implementation of new therapeutic approaches. Many clinical trials are ongoing, and epigenetic therapy has recently been approved by the United States Food and Drug Administration (US FDA) for use in the treatment of myelodysplastic syndrome (MDS) and primary cutaneous T-cell lymphoma (CTCL). [source]


Identification of the testis-specific protein 10 (TSGA10) as serologically defined tumour-associated antigen in primary cutaneous T-cell lymphoma

BRITISH JOURNAL OF DERMATOLOGY, Issue 3 2005
S.M. Theinert
Summary Background, The number of identified tumour-associated antigens for cutaneous lymphoma is still very restricted, which limits the elucidation of the tumour immunology of these malignancies and the development of specific immunotherapies and immunodiagnostics. Objectives, To identify new serologically defined antigens associated with cutaneous lymphoma. Methods, A phage expression library of the human testis transcriptom was established and immunoscreened with sera from 100 patients with cutaneous lymphoma and nine with parapsoriasis, and 81 age-matched control donors. Positive expression clones were sequenced to identify the respective antigen. Results, The testis-specific protein 10 (TSGA10) was identified as an antigen recognized by sera of two patients with Mycosis fungoides but not by sera from healthy donors. By reverse transcription,polymerase chain reaction analysis, TSGA10 was found expressed in all cutaneous lymphoma samples tested, various tumour cell lines, testis, peripheral blood mononuclear cells, skin, isolated lymphocytes, keratinocytes and fibroblasts. TSGA10 overexpression had previously been reported for other cancers. Conclusions, TSGA10 is a new tumour-associated antigen of cutaneous lymphoma. [source]


Molecular cytogenetic analysis of cutaneous T-cell lymphomas: identification of common genetic alterations in Sézary syndrome and mycosis fungoides

BRITISH JOURNAL OF DERMATOLOGY, Issue 3 2002
X. Mao
Summary Background Data on genome-wide surveys for chromosome aberrations in primary cutaneous T-cell lymphoma (CTCL) are limited. Objectives To investigate genetic aberrations in CTCL. Methods We analysed 18 cases of Sézary syndrome (SS) and 16 cases of mycosis fungoides (MF) by comparative genomic hybridization (CGH) analysis, and correlated findings with the results of additional conventional cytogenetics, fluorescent in situ hybridization (FISH) and allelotyping studies. Results CGH analysis showed chromosome imbalances (CIs) in 19 of 34 CTCL cases (56%). The mean ±,SD number of CIs per sample was 1·8 ± 2·4, with losses (1·2 ± 2·0) slightly more frequent than gains (0·6 ± 1·0). The most frequent losses involved chromosomes 1p (38%), 17p (21%), 10q/10 (15%) and 19 (15%), with minimal regions of deletion at 1p31p36 and 10q26. The commonly detected chromosomal gains involved 4/4q (18%), 18 (15%) and 17q/17 (12%). Both SS and late stages of MF showed a similar pattern of CIs, but no chromosomal changes were found in three patients with T1 stage MF. Of the 18 SS cases also analysed by cytogenetics, seven showed clonal chromosome abnormalities (39%). Five cases had structural aberrations affecting chromosomes 10 and 17, four demonstrated rearrangement of 1p and three revealed an abnormality of either 6q or 14q consistent with CGH findings. FISH analysis showed chromosome 1p and 17q rearrangements in five of 15 SS cases, and chromosome 10 abnormalities in four SS cases consistent with both the G-banded karyotype and the CGH results. In addition, allelotyping analysis of 33 MF patients using chromosome 1 markers suggested minimal regions of deletion at D1S228 (1p36), D1S2766 (1p22) and D1S397 (1q25). Conclusions These findings provide a comprehensive assessment of genetic abnormalities in CTCL and a rational approach for further studies. [source]


A case of adult T-cell leukaemia/lymphoma characterized by multiplex-fluorescence in situ hybridization, comparative genomic hybridization, fluorescence in situ hybridization and cytogenetics

BRITISH JOURNAL OF DERMATOLOGY, Issue 1 2001
X. Mao
Adult T-cell leukaemia/lymphoma (ATLL) is a neoplasm of mature helper (CD4) T lymphocytes. Little is known, however, about the chromosome aberrations associated with the pathogenesis of this malignancy. Using molecular cytogenetic techniques we, therefore, investigated a 44-year-old man who had a 7-year history of ATLL with cutaneous involvement mimicking primary cutaneous T-cell lymphoma. Conventional cytogenetics revealed gross chromosomal changes with chromosome numbers ranging from 71 to 82. There were structural abnormalities of chromosomes 7 and 9, partial deletions of chromosomes 1, 3, 5 and 6, and loss of chromosomes 2, 4, 9, 11,14, 21 and 22. Multiplex-fluorescence in situ hybridization (M-FISH) identified two derivative chromosomes, der(6)t(6;7)(q16;q21) and der(7)t(6;7)(q16;q21)ins(6;12)(q2?;?), and a deletion of chromosome 1p. Conventional FISH confirmed the M-FISH findings. Comparative genomic hybridization of the blood revealed gains of DNA copy number at 1q12,25, 6p24,25, 9p23, 16p13,q13, 17q11,21, 19p13 and 20q13 and loss at 11p15 while lymph nodes showed gains at 3p22,24, 3q27,29, 7q36 and 15q26 and losses at 2p24,25, 2q37, 10p14,15, 11p15, 13q33,34 and 16p13.3. No DNA copy number changes were seen in a skin lesion. These results show the extent of genetic abnormalities within this malignancy. [source]


Mycosis fungoides and chronic lymphocytic leukaemia , composite T-cell and B-cell lymphomas presenting in the skin

BRITISH JOURNAL OF DERMATOLOGY, Issue 2 2000
P.R. Hull
Composite lymphomas involving cutaneous B-cell and T-cell lymphomas are very uncommon. We report here the unique circumstance of a patient with mycosis fungoides (primary cutaneous T-cell lymphoma) who later developed chronic lymphocytic leukaemia (B-cell lymphoproliferation, B-CLL), which presented in the skin (leukaemia cutis) as a composite lymphoma affecting an earlobe. The presence of both lymphoproliferative disorders was confirmed with immunophenotyping and the finding of both immunoglobulin gene rearrangements and T-cell receptor gene rearrangements in the ear and the same T-cell receptor gene rearrangement in a plaque lesion of mycosis fungoides on the arm. [source]


Non-mycosis fungoides cutaneous T-cell lymphoma: reclassification according to the WHO-EORTC classification

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 5 2010
Joshua Weaver
Background: Non-mycosis fungoides (non-MF) primary cutaneous T-cell lymphomas (PCTCL) are heterogeneous and divided into subgroups by the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification of cutaneous lymphomas. We report the first North American series to examine the applicability of the classification, compare our findings with the predominant European literature and confirm the significance of separation into the indolent and aggressive groups. Methods: Forty-four non-MF PCTCL cases with available tissue for phenotyping, adequate clinical staging information and follow-up were reclassified according to the WHO-EORTC classification. Results: Non-MF PCTCL had a longer overall survival (OS) (13.8 years) compared with secondary cutaneous T-cell lymphoma (SC-TCL) (2.5 years). Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) had the most favorable outcome (OS 14.1 years), whereas secondary and primary peripheral T-cell lymphoma, unspecified had the shortest OS (2.5 and 2.4 years, respectively). Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma (CTLCD4) appeared to have a favorable course. Conclusions: Most non-MF PCTCL can be classified according to the WHO-EORTC classification. The relative frequencies are similar to European experience. Non-MF PCTCL is a heterogeneous group with a favorable outcome compared to SC-TCL, especially PC-ALCL and CTLCD4. Separation of non-MF PCTCL into indolent and aggressive groups appears clinically significant and may provide direction for therapeutic decisions. Weaver J, Mahindra AK, Pohlman B, Jin T, His ED. Non-mycosis fungoides cutaneous T-cell lymphoma: reclassification according to the WHO-EORTC classification. [source]


C-KIT expression in primary cutaneous T-cell lymphomas

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2004
Tilmann C. Brauns
Background:, Mutations of the stem cell factor receptor C-KIT play a major pathogenetic role in the development of different malignant diseases like human mastocytosis, myeloproliferative disorders, gastrointestinal stromal tumors, acute myelogenous leukemia, and sinonasal lymphomas. Furthermore, the expression of C-KIT has been described in Hodgkin's disease and nodal CD30+ anaplastic large cell lymphomas (ALCLs). As it is possible to inhibit C-KIT by innovative kinase inhibitors like STI571, it may be an attractive target for new therapeutical approaches. Therefore, we screened more than 50 different types of cutaneous T-cell lymphomas (TCLs) for the presence of C-KIT. Immunohistochemical stainings were performed on paraffin-embedded tissue sections using a polyclonal rabbit anti-human C-KIT antibody. Naphtol-ASD-chloroacetate esterase (NASDCE)-control stainings were performed on every positive sample to distinguish C-KIT-positive lymphoma cells from C-KIT-positive mast cells. Results:, We found weak expression of C-KIT in seven of 18 patients with primary cutaneous CD30+ ALCL, two of eight patients with primary cutaneous pleomorphic TCL, six of 18 patients suffering from mycosis fungoides, and three of five patients with Sezary's syndrome. Generally, only a very small population of the lymphoma cells expressed C-KIT. This finding indicates a difference to the systemic variant of CD30+ ALCL. The potential use of C-KIT targeting new therapeutical approaches is therefore discussed critically, because C-KIT expression is very rare in all investigated types of primary cutaneous lymphoma. [source]


Microsatellite instability and its relevance to cutaneous tumorigenesis

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 5 2002
Mahmoud R. Hussein
Increasing evidence suggests that human tumors sequentially accumulate multiple mutations that cannot be explained by the low rates of spontaneous mutations in normal cells (2,3 mutations/cell). The mathematical models estimate that for the solid tumors to develop, as many as 6,12 mutations are required in each tumor cell. Therefore, to account for such high mutation rates, it is proposed that tumor cells are genetically unstable, i.e. they have genome-wide mutations at short repetitive DNA sequences called microsatellites. Microsatellite repeats are scattered throughout the human genome, primarily in the non-coding regions, and can give rise to variants with increased or reduced lengths, i.e. microsatellite instability (MSI). This instability has been reported in an increasing number of cutaneous tumors including: melanocytic tumors, basal cell carcinomas and primary cutaneous T-cell lymphomas. Moreover, MSI has been observed in skin tumors arising in the context of some hereditary disorders such as Muir,Torre syndrome, Von Recklinghausen's disease and disseminated superficial porokeratosis. While MSI in some of these disorders reflects underlying DNA replication errors, the mechanism of instability in others is still unknown. Thus far, MSI is considered to be a distinct tumorigenic pathway that reveals surprising versatility. The ramifications for cutaneous neoplasms warrant further investigation. [source]


Joint British Association of Dermatologists and U.K. Cutaneous Lymphoma Group guidelines for the management of primary cutaneous T-cell lymphomas

BRITISH JOURNAL OF DERMATOLOGY, Issue 6 2003
S.J. Whittaker
These guidelines were commissioned by the British Association of Dermatologists guidelines and therapeutics subcommittee. Members of the committee are N.H.Cox (Chairman), A.S.Highet, D.Mehta, R.H.Meyrick Thomas, A.D.Ormerod, J.K.Schofield, C.H.Smith and J.C.Sterling. Members of the U.K. Cutaneous Lymphoma Group who have contributed include C.Benton, R.Cowan, C.Deardon, B.Hancock, H.Lucraft and D.Slater. Disclaimer These guidelines have been prepared for dermatologists on behalf of the British Association of Dermatologists and the U.K. Cutaneous Lymphoma Group (UKCLG) and reflect the best data available at the time the report was prepared. Caution should be exercised in interpreting the data; the results of future studies may require alteration of the conclusions or recommendations in this report. It may be necessary or even desirable to depart from the guidelines in special circumstances. Just as adherence to guidelines may not constitute defence against a claim of negligence, so deviation from them should not be necessarily deemed negligent. Summary These guidelines for the management of cutaneous T-cell lymphoma have been prepared for dermatologists on behalf of the British Association of Dermatologists and the U.K. Cutaneous Lymphoma Group. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation. [source]