In situ eosinophil activation in 26 primary cutaneous T-cell lymphomas with blood eosinophilia

Blood and tissue eosinophils can be associated with Hodgkin and non-Hodgkin lymphomas in that they have prognostic value. Tissue eosinophils in T-cell lymphoma patients with blood eosinophilia have not been systematically assessed. The objective of this research was to study the presence, density, and activation of tissue eosinophils in patients with primary cutaneous T-cell lymphomas (CTCLs) with blood eosinophilia and a possible relationship between features of the disease and prognosis. With skin biopsy specimens from 26 CTCL patients with blood eosinophilia, tissue eosinophils were studied with electron microscopy, extracellular eosinophil peroxidase deposits, and interleukin-5 expression. Tissue eosinophils, found in 22 of 26 cases, were constantly activated. Both density and activation of tissue eosinophils were significantly related to disease progression. The state of activation of tissue eosinophils in CTCL might reflect inflammatory flare-ups associated with aggressive lymphomas. Further studies are needed to confirm the value of eosinophil density as a simple and reliable marker of CTCL progression.     

C-KIT expression in primary cutaneous T-cell lymphomas

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.     

Ichthyosiform eruptions in association with primary cutaneous T-cell lymphomas

Background  Malignant lymphoma is occasionally complicated by ichthyosiform eruptions.
Objectives  To analyse histopathologically the ichthyosiform eruptions associated with cutaneous lymphomas.
Methods  We reviewed the files of patients with malignant lymphoma seen in our dermatology department between January 2001 and May 2006 to search for patients with ichthyosiform eruptions.
Results  In our series, nine of 106 patients with malignant lymphomas had ichthyosiform eruptions during their clinical courses, including three (30%) of 10 patients with anaplastic large cell lymphoma (ALCL) and six (14%) of 44 patients with mycosis fungoides (MF). None of the 18 patients with cutaneous B-cell lymphoma had ichthyosiform eruptions. The three patients with ALCL had ichthyosiform eruptions histopathologically consistent with acquired ichthyosis (AI) in which packed horny layers and thin granular layers were present without lymphocytic infiltration. In contrast, four of the six patients with MF (stages Ib and IIb) had ichthyosiform eruptions with epidermotropic infiltration of atypical lymphocytes, as observed in ichthyosiform MF (IMF). Of the remaining two patients, one showed histopathological features overlapping AI and IMF, and the other had AI alone. These two patients (stages IVa and IIb) had tumours composed of CD30+ cells. Filaggrin expression was markedly diminished in both AI and IMF-like eruptions, similar to that of inherited ichthyosis vulgaris.
Conclusions  Ichthyosiform eruptions are often associated with ALCL and MF and can be classified into three groups: AI associated with ALCL and MF expressing CD30, IMF, and their overlap.     

原发性皮肤T细胞淋巴瘤T细胞受体基因重排检测

Southern印迹分析（SBA）和取和合酶链反应（PCR）法检测早期（IA）和组织学上未确诊的蕈样肉芽肿（MF）皮肤损害的T细胞受体基因重排（TCRGR）阳性率分别为50％以上和19％,有助于诊断。IIA期MF患者特别是伴浅表淋巴结肿大（组织学上大都是反应性增生）的外周血中TCRGR阳性率较高（65％－80％）,支持MF早期即为一系统性疾病的理论,但外周血中克隆T细胞和预后相关性则难于确定。Sezary综合征（SS）的TCRGR的发生率在皮肤、淋巴结和外周血中分别为70％、100％和86％。非MF／SS皮肤T细胞淋巴瘤的皮肤 损害和外周血中TCRGR亦较常见。淋巴瘤样丘疹病的皮肤损害和外周血中也可见TCRGR。     

Treatment of cutaneous T-cell lymphomas

Primary cutaneous T-cell lymphomas (CTCL), representing a heterogeneous group of non-Hodgkin's lymphomas (NHL), can be defined as clonal proliferation of skin-infiltrating T lymphocytes primarily presenting in the cutaneous compartment. They show a considerable variation in clinical presentation, histology, immunophenotype, and prognosis, which is best reflected by the proposal of the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer (EORTC). Due to the heterogeneity of CTCL and the lack of curative therapy regimens, multiple strategies have been proposed for the management of the different CTCL entities. This includes topical application of corticosteroids, nitrogen mustard or carmustine (BCNU), radiotherapy, including total skin electron beam irradiation, photo(chemo)therapy, biological response modifiers, cytostatic chemotherapy, and combined regimens. More recently, fusion proteins and peptide vaccines have been introduced in the management of CTCL. Classification, staging, and treatment modalities are discussed in detail and summarized in a stage-adapted therapy regimen for CTCL.     

T-cell receptor gene analysis in cutaneous T-cell lymphomas

An essential property of the immune system is its ability to generate diverse antibody and T-cell mediated responses to virtually any potential foreign particle, The basic molecular mechanisms responsible for producing this extensive diversity have now been elucidated. Each T cell expresses a unique membrane hound T-cell antigen receptor (TCR) which combines with specific antigenic peptides and major histocompatibility complex molecules. The characterization of TCR usage now represents a focal point for many studies of inflammatory and neoplastic disorders. Such studies are helping to clarify the pathogenesis of T-cell mediated diseases and provide the basis for the development of specific therapies. This paper will review several techniques used to identify neoplastic T-cell clones in cutaneous T-cell lymphoma. Similar methods may be used to analyse TCR gene usage in cutaneous inflammatory dermatoses.     

Herpes zoster-varicella in cutaneous T-cell lymphomas

The overall frequency of herpes zoster-varicella (HZV) infection in 221 patients with histologically confirmed cutaneous T-cell lymphoma was 10% (22 patients). The frequency of HZV infection and serious complications (viral dissemination, bacteremia) was relatively high in patients with evidence of extracutaneous involvement, especially in patients with Sézary syndrome. The major factors identified to account for this predisposition to HZV infection include intensive treatment with radiation therapy or drugs given for systemic effect and/or immunologic deficiency consequent to advanced disease. These observations are quite similar to those made in patients with Hodgkin's disease.     

Cytokines and cutaneous T-cell lymphomas

Abstract: Cytokines are considered to be of major importance for the pathogenesis of cutaneous T-cell lymphomas (CTCL). Their impact may result from autocrine, paracrine or endocrine effects. Several investigations demonstrated the overexpression of different cytokines in different CTCL entities. Interestingly, stage-dependent shifts in the cytokine pattern have been observed in mycosis fungoides (MF). There is evidence that the abnormal cytokine expression in CTCL might be responsible for tumor progression, resulting from an enhanced proliferation of the malignant cells and/or the depression of the anti-tumor immune response. Moreover, cytokine loops might explain phenomena like the epidermotropism of malignant cells or eosinophilia and increased plasma levels of IgE, which are present in advanced stages of CTCL. Analysis of the cytokine pattern in CTCL might give the basis for direct therapeutic intervention into the cytokine network as a new therapeutic approach. In this review, the current knowledge regarding cytokines in CTCL is summarized.     

Clonal disease in extracutaneous compartments in cutaneous T-cell lymphomas. A comparative study between cutaneous T-cell lymphomas and pseudo lymphomas

Extracutaneous involvement is a sign of poor prognosis in cutaneous T-cell lymphomas (CTCL). Unfortunately it becomes clinically and histologically manifest only late in the course of the disease. It was the purpose of this study to detect clonality in peripheral blood, lymph nodes and bone marrow samples at times when extracutaneous involvement cannot other-wise be demonstrated. In addition to skin biopsies, peripheral blood, lymph node and bone marrow samples from a total of 25 patients were analysed by Southern blotting for clonal gene rearrangement of the T-cell receptor β-chain. Six of the patients were suffering from mycosis fungoides (MF), four from non-MF CTCL (pleomorphic T-cell lymphomas), seven from Sézary syndrome (SS), eight from pseudolymphoma (insect bites) (PSL), and one from lymphomatoid papulosis (LP). Clonal TcR b gene rearrangements were found in patients with MF in four of five skin probes as well as in two of two lymph node samples and in one of two peripheral blood samples. In SS patients, all skin probes (seven of seven), lymph node samples (six of six), peripheral blood samples (six of six) and one bone marrow specimen had a clonal TcR β gene rearrangement. In patients with non-MF CTCL, two of four skin, zero of two peripheral blood and one of one bone marrow samples with clonal T cells were detected. All investigated patients showed exactly the same rearrangement pattern at extranodal sites and in the skin, which is proof for the same clone in all compartments. In contrast, no rearrangements were detected in LP and PSL (zero of eight skin probes, zero of two peripheral blood samples). Our results provide strong evidence for an early systemic spread of neoplastic cells in CTCL. However, an initial tumour burden has to be reached in order to lead to a clinically and prognostically relevant manifestation.     

光疗在皮肤T细胞淋巴瘤中的应用进展

【摘要】 皮肤T细胞淋巴瘤（CTCL）是T细胞来源的恶性肿瘤,目前针对CTCL的治疗主要为了控制症状及长期缓解,光疗及其联合疗法是重要手段之一。应用于CTCL的光疗方法包括长波紫外线加补骨脂素、窄谱中波紫外线、宽谱中波紫外线、体外光化学疗法、光动力疗法、长波紫外线1、308 nm准分子激光等。光疗效果受多种因素影响,如疾病分期、皮损部位、皮肤光反应类型等。在临床应用中,光疗包括清除、巩固、维持阶段,但维持治疗能否控制复发仍存在争议。了解各种光疗的机制、适应证、临床疗效及不良反应有助于选择最佳治疗方案。     

Genotypic analysis of cutaneous T-cell lymphomas

The gene encoding the beta-chain of the T-cell antigen receptor (TCR) has been analyzed for evidence of rearrangement in skin, blood, and lymph node specimens from 23 cases of known or suspected cutaneous T-cell lymphoma (CTCL). Two cutaneous large cell lymphomas, 4 cases of Sézary syndrome, and 5 cases of advanced (tumor) stages of mycosis fungoides showed clonal rearrangement of the TCR beta-chain gene in all samples, including lymph nodes in which histologic examination revealed only dermatopathic lymphadenitis. These results indicate that DNA analysis provides a valuable means for improving the diagnosis of extracutaneous disease in advanced stages of CTCL. In contrast, the gene was in a germline configuration in all samples from 12 patients with plaque stages of mycosis fungoides or suspected early CTCL, suggesting that in these 2 conditions the T-cell proliferation is either polyclonal or contains very few monoclonal (i.e., neoplastic) cells.     

Carcinoma spinocellulare and cutaneous T-cell lymphomas

Two cases of squamous cell carcinoma in patients with cutaneous T cell lymphoma are presented, together with a survey of the rather sparse literature on this subject. The cases presented showed considerable differences in their course. The mutagenic effects of the therapies used against the lymphoma are claimed to be responsible for the development of squamous cell carcinoma in almost all the published reports. However, we think the disturbances of the immune system caused either by the lymphoma itself or by the therapy might be a decisive factor in the development of secondary tumors. This possibility is supported by a comparison of immunosuppressed renal transplant recipients, who frequently develop squamous cell carcinomas of the skin. Frequent clinical follow-up examination of patients with cutaneous T cell lymphomas and early biopsy of suggestive lesions seem mandatory for differentiation between squamous cell carcinomas and tumorous infiltrations of the primary lymphoma. Radical surgical excision, which allows histological examination of the tumor margins, is the therapy of choice for these frequently very aggressive squamous cell carcinomas.     

T-cell receptor variable region gene expression in cutaneous T-cell lymphomas

The cutaneus T-cell lymphomas (CTCL) arc a group of diseases characterized by malignant proliferations of CD4 positive T-cells having monoclonally rearranged T-cell receptor (TCR) genes. A recent study using monoclonal antibodies to two TCR β-chain variable (V) region gene products showed preferential expression of the Vβ8 gene product in these tumors. The finding of predominant usage of a single Vβ gene would imply that selection by antigen is important in the etiology of these tumors. We have studied eight cases of cutaneous T-cell lymphoma and one cell line derived from a patient with mycosis fungoides/Sezary syndrome, using an extended panel of antibodies to V region gene products. Contrary to the previous report, in our study expression of the Vβ8 gene product by tumor cells was not observed in any of the cases of CTCL or in the tumor cell line studied; preferential use of any of the variable region genes recognized by the antibodies in the panel was not observed.     

Leukapheresis in the treatment of cutaneous T-cell lymphomas

In six patients with cutaneous T-cell lymphomas (CTCL), the effect of leukapheresis (LPH) on the disease and on various immunological and haematological parameters was investigated. Enriched mononuclear cells were removed by continuous centrifugation leukapheresis from the peripheral blood of the patients. A profound and longlasting effect was seen in one patient with the Sézary variant; a moderate response was seen in two other Sézary patients. No benefit was observed in two patients with more aggressive leukaemic disease, and one patient with plaque stage MF responded on two occasions. No limiting side effects were recognized and no consistent changes of immunological or haematological parameters were observed after LPH.     

Diagnosis and therapy of cutaneous T-cell lymphomas

We report the observation of 16 cases of cutaneous T cell lymphoma consisting of 11 cases with mycosis fungoides and 5 cases with high-grade malignant lymphomas. A standardized clinical evaluation is proposed for patients with low-grade malignant lymphomas for whom we favor the use of non-aggressive therapeutic regimens. High-grade lymphomas need a more complete systemic exploration. Treatment of cutaneous T cell lymphomas should be started with the least aggressive antineoplastic therapy.     

Classification and prognosis of cutaneous T-cell lymphomas

Modern concepts on the classification and prognosis of cutaneous T-cell lymphomas are discussed in this paper. The full spectrum of cutaneous T-cell lymphomas is not yet known. A new classification of histomorphological types of mycosis fungoides and Sézary's syndrome in correlation with prognostic features is proposed.