Increased expression of a novel early activation surface membrane receptor in cutaneous T cell lymphoma cells

Using a newly generated monoclonal antibody we identified the 96 kDa transmembrane receptor SC5 expressed simultaneously on a human Sezary cell line and a minor T cell subset in normal individuals. SC5 antigen was detected mostly on CD45RO+ lymphocytes from both CD4+ and CD8+ subsets as well as on natural killer and B lineage cells. SC5 surface expression increased very early after polyclonal stimulation of CD3+ cells due to the transfer of intracellular SC5 molecules to the cell membrane. Engagement of SC5 receptor by its monoclonal antibody inhibited the anti-CD3-induced proliferation and cytokine secretion of peripheral blood T cells and cell clones, whereas SC5 monoclonal antibody did not affect the cytotoxic activity of CD8+ T cell clones. Extensive phenotypic analysis revealed that the percentage of SC5+ CD4+ circulating lymphocytes in Sezary syndrome patients was significantly increased in comparison with controls (p < 0.01) and correlated with the morphologically detected percentage of Sezary syndrome cells in peripheral blood (p < 0.001). In one patient we clearly demonstrated that the circulating malignant T cells coexpress SC5 molecules. Importantly, ligation of SC5 receptor in a cutaneous T cell lymphoma cell line profoundly inhibited the anti-CD3-induced proliferation. Consequently, the expression of SC5 receptor in the peripheral blood of Sezary syndrome patients may serve not only to detect the presence of circulating malignant CD4+ cells but also as a target for immunotherapy.     

Increased risk of secondary cancers in patients with primary cutaneous T cell lymphoma

As putative etiologic factors of primary cutaneous T cell lymphomas may have a general cancerogenic effect, we wanted to assess the risk of secondary malignancies in 319 patients diagnosed with histopathologically verified cutaneous T cell lymphomas and reported to the Finnish Cancer Registry during the years 1953-95. Standardized incidence ratios were defined as the ratio of observed to expected numbers of cases. To obtain the expected numbers of cancer, age-, sex-, and period-specific Finnish incidence rates were applied to the appropriate person-years under observation. Ninety-five percent confidence intervals were calculated assuming a Poisson distribution. For the whole period, we detected 36 secondary cancers whereas 26 were expected (standardized incidence ratios 1.4, 95% confidence intervals 1.0-1.9). The overall risk of lung cancer was significantly increased (standardized incidence ratio was 2.7, 95% confidence intervals were 1.4-4.8); and in particular small-cell lung cancer showed high standardized incidence ratios (standardized incidence ratio was 8.5, 95% confidence intervals were 2.8-20). Also, the risk of lymphomas was elevated (standardized incidence ratios for Hodgkin and non-Hodgkin lymphomas combined were 7.0, 95% confidence intervals were 1.9-18). The incidence of other cancers was similar to the national ratios. An increased risk of secondary cancers and in particular small-cell cancer of the lung and lymphomas among patients with primary cutaneous T cell lymphoma is demonstrated. In clinical practice, lung cancer and lymphomas must be kept in mind when following up patients with cutaneous T cell lymphomas.     

Serological immunomarkers in cutaneous T cell lymphoma

INTRODUCTION: As serological immunomarkers like neopterin, beta2-microglobulin, soluble IL-2 receptor (sIL-2R) and IL-6 have been described to be elevated in various malignancies, the aim of this study was to investigate whether they would be of diagnostic and prognostic value for leukemic and non-leukemic cutaneous T cell lymphoma (CTCL). PATIENTS AND METHODS: Forty-one CTCL patients from the lymphoma clinics of the Department of Dermatology, University of Zurich, were tested for the serum levels of the above-mentioned immunomarkers at several time points, and clinical status and clinical outcome were recorded. Thirty-nine patients with CBCL and T cell inflammatory diseases served as controls. RESULTS: The study revealed that neopterin, beta2-MG and sIL-2R are significantly elevated in Sezary syndrome, whereby sIL-2R seemed to be the most sensitive marker and is typically increased in Sezary syndrome. Moreover, there is a correlation between tumor burden index values and serum parameters. Concerning the outcome of the disease (progression versus non-progression), only neopterin showed a significant prognostic value in non-leukemic CTCL patients. CONCLUSION: Serological immunomarkers are helpful tools in determining the tumor burden in CTCL and thus might be useful for disease monitoring during treatment. They may have prognostic value for predicting the clinical course.     

种痘水疱病样皮肤T细胞淋巴瘤

报告1例长期复发的种痘水疱病样皮肤T细胞淋巴瘤.患者女,47岁.从2岁开始反复发作水肿性红斑、水疱、坏死及痘疮样萎缩性瘢痕形成,冬轻夏重,主要累及面部和四肢.组织病理示真皮层内可见较多淋巴样细胞灶状和散在浸润,可见核分裂象.免疫组化检测显示淋巴样细胞CD2、CD3、CD4、CD5阳性,CD7、CD8少数细胞阳性,CD2...     

Treatment of cutaneous T cell lymphoma

Primary cutaneous T cell lymphomas encompass a wide variety of lymphomas that are characterized by a distinct clinical presentation. Advanced biological techniques have allowed a more precise classification in recent years. Stage-adapted therapy is at present the best approach to treat cutaneous T cell lymphoma.     

种痘水疱病样皮肤T细胞淋巴瘤

种痘水疱病样淋巴瘤是近年来认识到的一种皮肤T细胞淋巴瘤,儿童多见,主要累及面部和四肢,表现为水肿性红斑、水疱、结痂和坏死,可伴有高热、肝脾大等全身症状。与EB(Epstein-Barr)病毒感染有关。组织病理显示肿瘤细胞侵犯血管和脂膜。该文报告1例该病患者。     

第四讲 皮肤淋巴瘤皮肤T细胞淋巴瘤向大细胞淋巴瘤转化

阐述皮肤T细胞淋巴瘤向大细胞淋巴瘤转化的临床表现、组织病理、免疫组织化学染色、分子生物学特征、诊断和鉴别诊断与治疗。     

Human leukocyte antigens in cutaneous T cell lymphoma

Mycosis fungoides (MF) and Sézary syndrome (SS) are malignant non-Hodgkin's lymphomas, characterized by the proliferation of helper type T lymphocytes with a predilection for the skin. Because of the similarities in cytologic, histologic, cytogenetic, immunologic, and functional aspects of the malignant cells, as well as overlapping clinical features, these disorders are currently classified as cutaneous T cell lymphoma (CTCL). Though the etiology of these disorders remains obscure, environmental factors as well as viral infection have been implicated. In this study, seventy-six white patients with CTCL were typed for human leukocyte antigen (HLA)-A, -B, and -C to assess genetic susceptibility as determined by the major histocompatibility complex. An increase in the frequency of B8 and Bw35 was seen in SS patients but not in MF patients.     

Gene expression profiles of cutaneous B cell lymphoma

We studied gene expression profiles of 17 cutaneous B cell lymphomas that were collected with 4-6 mm skin punch biopsies. We also included tissue from two cases of mycosis fungoides, three normal skin biopsies, and three tonsils to create a framework for further interpretation. A hierarchical cluster algorithm was applied for data analysis. Our results indicate that small amounts of skin tissue can be used successfully to perform microarray analysis and result in distinct gene expression patterns. Duplicate specimens clustered together demonstrating a reproducible technique. Within the cutaneous B cell lymphoma specimens two specific B cell differentiation stage signatures of germinal center B cells and plasma cells could be identified. Primary cutaneous follicular and primary cutaneous diffuse large B cell lymphomas had a germinal center B cell signature, whereas a subset of marginal zone lymphomas demonstrated a plasma cell signature. Primary and secondary follicular B cell lymphoma of the skin were closely related, despite previously reported genetic and phenotypic differences. In contrast primary and secondary cutaneous diffuse large B cell lymphoma were less related to each other. This pilot study allows a first glance into the complex and unique microenvironment of B cell lymphomas of the skin and provides a basis for future studies, which may lead to the identification of potential histologic and prognostic markers as well as therapeutic targets.     

Clinical implications of immunologic phenotyping in cutaneous T cell lymphoma

The composition of cutaneous lesions from 158 patients with confirmed cutaneous T cell lymphoma, 91 patients with suspected cutaneous T cell lymphoma, and 145 patients with lymphoid disorders other than cutaneous T cell lymphoma was quantitated in situ with the use of commercially available murine monoclonal antibodies that identify the Pan T, T-helper/inducer (Th), T cytotoxic/suppressor (Ts), and Pan B lymphocyte subsets. On average, cutaneous infiltrates of confirmed cutaneous T cell lymphoma were found to contain significantly more Th and less Ts or Pan B cells compared to benign lymphoid disorders. Moreover, when analyzed in terms of the type of lesion examined by biopsy, the absolute amount of Th cells progressively expands with increasing magnitudes of infiltrate in the dermis while the amount of Ts and Pan B cells remains relatively constant among lesions. A useful diagnostic criterion (anti-Leu 1/4 greater than or equal to 70% and anti-Leu 3a/anti-Leu 2a ratio greater than or equal to 6) correctly discriminated between cutaneous T cell lymphoma and non-cutaneous T cell lymphoma in 87.5% of cases. A positive immunodiagnostic result also may be useful for the prediction of subsequent histopathologic confirmation of cutaneous T cell lymphoma in patients who have suspect lymphoid infiltrates, such as alopecia mucinosis or idiopathic generalized erythroderma, when first seen. With the use of multivariate analysis, stage and possibly the percentage of Th cells within the T cell component in cutaneous infiltrates were covariates with significant relationships to survival in patients with confirmed cutaneous T cell lymphoma. In addition, Ts cells in infiltrates did not correlate significantly with observed responses to topical treatment and subsequent course in pretumorous mycosis fungoides. These results indicate that Ts cells play little biologic role in modifying the natural history of cutaneous T cell lymphoma.     

Prevalence and severity of pruritus in cutaneous T cell lymphoma

Background The most common types of cutaneous T cell lymphoma (CTCL) are mycosis fungoides (MF) and its leukemic variant, Sézary syndrome (SS). One of the hallmarks of MF and SS is pruritus that rarely responds to treatment. Little is known about the prevalence and severity of pruritus in MF and SS. Objectives A retrospective analysis was performed to assess the prevalence and severity of pruritus in MF and SS. Methods This study compared self‐reported pruritus in early‐stage (stage Ia–IIa) and late‐stage (stage IIb–IVb) disease, and in MF and SS, in patients presenting at our CTCL clinic between January 1, 2006, and June 30, 2010. Results Of the 551 eligible patients, 486 reported baseline pruritus values. Overall, 373 patients had early‐stage disease, 113 had late‐stage disease, and 72 had SS. The prevalence of pruritus was 66% in all patients, 62% in patients with early‐stage disease, 83% in those with late‐stage disease, 61% in those with MF, and 94% in those with SS. Mean pruritus values out of 10 were: 4.2 [standard error of the mean (SEM) = 0.18] in all patients; 3.4 (SEM = 0.19) in patients with early‐stage disease; 6.6 (SEM = 0.36) in those with late‐stage disease; 3.6 (SEM = 0.18) in MF patients, and 7.7 (SEM = 0.37) in SS patients. Differences between early‐ and late‐stage disease, and MF and SS, were statistically significant (P < 0.001). Conclusions Pruritus affects a large proportion of patients with CTCL and is significantly more severe in late‐ than in early‐stage disease and in SS than in MF. Little information exists on the full range of the symptom burden on the patient. This aspect of patient care requires further exploration.     

Central nervous system involvement by cutaneous T cell lymphoma

Central nervous system disease in cutaneous T cell lymphoma is uncommon and is usually not considered in standard therapeutic regimens. We report three patients who had cutaneous T cell lymphoma with involvement of the central nervous system and review the cases of 28 such patients reported in the literature. Potential risk factors, the reliability of various diagnostic tests, and potential therapeutic modalities are discussed.     

牛痘样水疱病样皮肤T细胞淋巴瘤

目的:根据3例种痘样皮肤T细胞淋巴瘤(hydroa vacciniforme-like CTCL)患者的临床表现、治疗及转归,进一步探讨该病的诊断和治疗.方法:分析3例hydroa vacciniforme-like CTCL患者的临床资料、实验室检查、治疗及转归.结果:3例患者均为幼年发病,皮损开始出现在曝光部位,反复发作,数月或数年后进展性或逐渐蔓延至非曝光部位,且伴有发热等全身症状.皮损组织病理显示真皮内致密的淋巴样细胞浸润达真皮下层甚至脂肪层,常侵犯血管;免疫组化组织病理显示浸润细胞以CD8(+)细胞为主;T细胞受体γ基因(TCRγ基因)呈单克隆性重排;EB(Epstein-Barr)病毒原位杂交(+).结论:该病与EB病毒感染有关.该病预后差,但干扰索治疗可改善症状.     

Syringotropic cutaneous T cell lymphoma treated with PUVA therapy

Syringotropic cutaneous T cell Lymphoma (SCTCL) is a rare localized variant of CTCL. It is characterized by erythematous papules that, at histological examination, show dense dermal infiltrates of atypical T cells, that are preferentially located around hyperplastic eccrine sweat glands and ducts, with absent or minimal epidermotropism. Its relationship with mycosis fungoides and other CTCLs is not clarified and is still under discussion. Several treatment approaches have been suggested, but therapeutic results are often disappointing. We report the case of a patient with typical clinical and histopathological features of SCTCL and an excellent response to PUVA therapy.