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Abstract
Primary cutaneous T-cell lymphomas (CTCLs) comprise a constellation of heterogeneous lymphoproliferative disorders characterized by clonal accumulation of neoplastic T lymphocytes in the skin.
T-cell lymphomas consist of approximately 80% of all primary cutaneous lymphomas.
The most common of these are MF, which takes its name from the mushroom-shaped tumor nodules that result from the vertical proliferation of infiltrating cells, and Sézary syndrome (SS). MF is characterized by infiltration of the skin by neoplastic T lymphocytes with hyperconvoluted cerebriform nuclei (mycosis cells) that usually express a mature peripheral T-cell (CD4+) phenotype.
A suppressor phenotype (CD8+) may be seen infrequently.
Partial loss of pan-T-cell antigens such as CD7 and CD3 may be a feature of MF but is not pathognomic for the disease. Activation markers, including IL-2 receptor (CD25), can be demonstrated in approximately 60% of cases. Skin involvement can be manifest as patches, plaques or tumors, but patients may have more than one type of lesion simultaneously. The patch stage consists of erythematous macular lesions which occur most frequently over the trunk and extremities and are often associated with scaling or pruritis. In the plaque stage, lesions are oval or circular and well demarcated, with raised borders. Patches may coalesce into larger plaques or even give the appearance of patchy erythroderma.
Dermal thickening of the skin by T-cell infiltration may lead to an infrequent but classical appearance on the face known as ”leonine facies.” The differential diagnosis of plaque stage disease includes nonmalignant conditions such as eczema, psoriasis, and parapsoriasis. Tumor stage disease represents a vertical growth phase that presents clinically as expanding nodules, which may ulcerate.
The differential diagnosis for tumor stage cutaneous lymphoma includes lymphomatoid papulosis, anaplastic T-cell lymphoma of the skin, peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma, and other rare entities. The mechanism of recruitment of malignant T-cell clones to the skin is probably related to chemokine-chemokine receptor interactions.
Thymus and activation-regulated chemokine (TARC/CCL17) is a member of the CC chemokines. It is a ligand for CC chemokine receptor 4 (CCR4) and CC chemokine receptor 8 (CCR8) and serves for the recruitment and migration of these receptor-expressing cells.
In MF, it has been reported that CCR4 is strongly expressed in the lesional skin, especially in the advanced stage. Serum TARC levels in patients with the tumor stage of MF were excessively higher than those in the patch or plaque stage, and its serum level is significantly correlated with disease activity.
Our study was designated to elucidate the participation of TARC in each stage of MF to show the correlation between both serum and tissue levels of TARC in MF patients.
Thierty two patients with different stages of MF and ten controls were included in the study. Skin biopsies and blood samples were taken to evaluate both tissue and serum level of TARC by using ELISA method.
The results of our study revealed that: 1- In the tissue samples it was found that the TARC level was higher in the tumor stage (mean value = 19595) than the plaque stage (mean value = 8579.91) and the level in the plaque stage was higher than the patch stage (mean value = 2845.91). 2- It was also observed that the TARC level of each disease stage was correlated with the disease extent. The relation between tissue TARC level and disease extent was more obvious in the tumor stage and the plaque stage than in the patch stage.
3-Also tissue TARC level was found to be higher in the lesions with longer duration than that of the earlier lesions: 4- In serum samples it has been found that the TARC values were higher in tumor stage than in plaque stage and the patch stage, but the mean value of the patch stage was higher than the mean value of the plaque stage (mean value of tumor stage was 2377.5, for plaque stage was 720 and for patch stage was 1309.39). 5- It was also found that the TARC values in the serum correlated with the tumor extension like the tissue values but it was more obvious in the tumor stage and the patch stage more than the plaque stage. 6- Also serum TARC level was found to be higher in the lesions with longer duration than that of the earlier lesions