Adult T-Cell Leukemia/Lymphoma and Cutaneous T-Cell Lymphoma Are They Related?

Comparative studies were performed on clinical and laboratory features of four patients with different types of T-cell lymphoma of the skin; adult T-cell leukemia/lymphoma (ATLL), Sézary syndrome, mycosis fungoides, and Ki-1-positive lymphoma. All neoplastic cells studied showed a helper-inducer T-cell phenotype. A Ki-1-positive lymphoma is distinct from other types of cutaneous lymphomas because of unique morphologic and phenotypic features. Clonal proliferation of lymphocytes infected by human T-cell lymphotrophic virus (HTLV)-1 distinguishes ATLL from other T-cell lymphomas of the skin, especially in the endemic area of ATLL. From the pathogenic point of view, ATLL should not be included in a group with mycosis fungoides and Sézary syndrome.     

Alemtuzumab in Sézary syndrome: efficient but not innocent

Mycosis fungoides is the most common form of cutaneous T-cell lymphomas. The related Sézary syndrome is a more aggressive form in which the skin is diffusely affected and the peripheral blood is involved. Although easily managed during its early phases, late-stage mycosis fungoides/Sézary syndrome is usually difficult to treat and becomes refractory to chemotherapy. Recently, promising case-based results have been obtained with alemtuzumab, a humanized immunoglobulin G1 monoclonal antibody that binds to CD52 cell surface antigens, in the treatment of advanced stage mycosis fungoides/Sézary syndrome. We report a case of Sézary syndrome treated successfully with alemtuzumab but who died of treatment-related infection.     

Leucoderma associated with flares of erythrodermic cutaneous T-cell lymphomas: four cases. The French Study Group of Cutaneous Lymphomas

We describe four patients with erythrodermic cutaneous T-cell lymphomas (two with erythrodermic mycosis fungoides, and two with Sézary syndrome) who presented with extensive hypopigmented lesions that occurred during flares of their cutaneous disease. These cases must be distinguished from previously described hypopigmented mycosis fungoides where hypopigmented lesions were the sole manifestation of the lymphoma. In two cases a biopsy was performed on hypopigmented skin, showing an infiltrate of atypical lymphocytes with epidermotropism and absence of melanocytes, as in vitiligo. It is suggested that the hypopigmentation could be due to the cytotoxicity of tumour or reactional lymphocytes directed against melanocytes.     

Macrophage inhibitor factor (MIF) in cutaneous lymphoproliferative diseases

Macrophage migration inhibitor factor (MIF) activity in the sera of patients with mycosis fungoides, Sézary syndrome, and cutaneous lymphoma was observed in the sera of eight of the ten patients with stage II (infiltrative) mycosis fungoides, but in only one of the eight patients with stage I and in neither of the two patients with stage III mycosis fungoides. Two of the three patients with Sézary syndrome had MIF in the serum. No MIF was observed in cutaneous lymphoma. These data support the concept that Sézary syndrome and mycosis fungoides are T-cell diseases, and transitional, prelymphomatous diseases.     

Cutaneous T‐cell lymphoma and atopy: is there an association?

BACKGROUND: Case reports have suggested a relationship between atopic diatheses and Sézary syndrome, pre-Sézary syndrome or mycosis fungoides. However, Sézary and pre-Sézary syndromes are rare entities, and this association has never been analysed in greater detail for specific subtypes of cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To evaluate the prevalence of atopy in subjects with Sézary syndrome, pre-Sézary syndrome or mycosis fungoides, and to compare the rates with the reported prevalence of atopy in the general population. METHODS: We retrospectively reviewed the records of 157 patients with the diagnosis of Sézary or pre-Sézary syndrome seen between 1965 and 2000, and 102 patients with the diagnosis of mycosis fungoides evaluated from 1994 to 2000 at Mayo Clinic. RESULTS: Of 157 subjects with Sézary or pre-Sézary syndrome and 102 subjects with mycosis fungoides, 18 and 12, respectively, were identified as having a history of atopic dermatitis, asthma or allergic rhinitis. The prevalence rates of atopy in Sézary or pre-Sézary syndrome and mycosis fungoides were 11.5% (95% confidence interval 6.9-17.5%) and 11.8% (6.2-19.7%), respectively. CONCLUSIONS: No significant difference exists in the prevalence of atopy in Sézary or pre-Sézary syndrome compared with that in mycosis fungoides (chi2-test, P = 1.00). Furthermore, the rates of atopy in Sézary or pre-Sézary syndrome and mycosis fungoides are not significantly different from the prevalence of atopy in the general population (17-40%). On the basis of these observations, no evidence currently implicates a causal association of CTCL with atopy.     

Pleomorphic T-cell lymphoma and large-cell anaplastic lymphoma of the skin. A morphological, immunophenotypical, and ultrastructural study of two typical cases

Pleomorphic T-cell lymphoma and large-cell anaplastic lymphoma are recently defined lymphoma types that both occur in the skin. This report outlines the characteristics of these lymphomas and describes the clinical, histological, immunological, and ultrastructural features as seen in two typical case histories. Cutaneous T-cell lymphomas other than mycosis fungoides and Sézary syndrome are heterogeneous; they deserve further scientific attention to obtain data about their natural history and their response to therapy.     

Characterization of skin infiltrating cells in adult T-cell leukaemia/lymphoma (ATLL): clinical, histological and immunohistochemical studies on eight cases

Eight cases of adult T-cell leukaemia/lymphoma (ATLL) with cutaneous involvement were studied. The clinical and histological features of these cases were recorded and immunohistochemistry carried out using a panel of monoclonal antibodies to T-cell differentiation antigens. Patients with ATLL showed distinct differences from patients with mycosis fungoides (MF) and Sézary syndrome (SS). Patients tended to have papulonodular and purpuric skin eruptions with pleomorphic lymphoid infiltrates, and often a degree of vasculitis. There was a high level of expression of activated T-cell antigens, CD25, CD30, CD38, T9 and Leu 8.     

Intraepidermal localization of the clone in cutaneous T-cell lymphoma.

BACKGROUND: No immunohistologic techniques are currently available to demonstrate clonality of T-cell lymphomas. Monoclonal antibodies to the variable region of the T-cell receptor (TCR) have been produced that identify minor populations of normal peripheral blood T lymphocytes. OBJECTIVE: We investigated the expression of TCR V-region genes in cutaneous lymphomas to determine whether immunostaining with these antibodies may be a simple method to detect clonal T-cell proliferations and help to distinguish benign lymphoid infiltrates from malignant lymphoma. METHODS: Cutaneous samples were obtained from 18 cutaneous T-cell lymphomas (14 mycosis fungoides, 1 Sézary syndrome, 2 pleomorphic T-cell lymphoma, and 1 large cell anaplastic lymphoma) and 8 benign lymphoid infiltrates. Frozen sections were incubated with monoclonal antibodies and stained by the alkaline phosphatase-antialkaline phosphatase technique. Staining was performed with a panel of 7 anti-TCR V-region antibodies, 6 T-cell markers, 1 anti-beta chain antibody, and 1 anti-delta chain antibody. RESULTS: Clonality could be demonstrated in 2 of 18 cutaneous lymphomas. We observed the strictly intraepidermal localization of clonal proliferation in one case of early-stage mycosis fungoides. CONCLUSION: Anti-TCR V-region antibodies may identify a strictly epidermotropic clone in early mycosis fungoides. However, the panel of antibodies currently available stains only a minority of cutaneous T-cell lymphomas. The usefulness of these antibodies as a clonotypic marker needs to be reevaluated when a larger panel of antibodies becomes available.     

皮肤淋巴瘤与EB病毒潜伏感染的关系及病毒亚型的分析

目的 探讨EB病毒潜伏感染及其亚型与皮肤淋巴瘤的相关性.方法 标本来源于41例淋巴瘤患者的皮肤组织和38例健康成人咽部洗漱液.采用原位杂交、PCR、巢式PCR、Southern杂交方法检测EB病毒及其亚型.通过Southern杂交对5例自然杀伤/T细胞淋巴瘤病例中EB病毒末端重复序列进行分析.结果 8例自然杀伤/T细胞淋巴瘤、4例皮下脂膜炎型淋巴瘤、1例自然杀伤/T淋巴细胞增生症、1例血管免疫母细胞恶性淋巴瘤和1例组织细胞样淋巴瘤EB病毒原位杂交和PCR结果均阳性.38例正常人中有14例咽部携带有EB病毒.15例蕈样肉芽肿、5例Sézary综合征病例中,EB病毒原位杂交和EB病毒BMRF1基因PCR扩增均为阴性.除1例淋巴细胞增生症患者为EB病毒亚型1和2双重感染外,其它病例均为亚型1感染.正常人群咽部携带亚型1EB病毒.5例自然杀伤/T细胞淋巴瘤与EB病毒末端重复序列特异性探针杂交后,均只产生一条杂交带.结论 EB病毒潜伏感染与皮肤自然杀伤/T细胞淋巴瘤及皮下脂膜炎型淋巴瘤相关,但与蕈样肉芽肿和Sézary综合征无明显相关性.肿瘤细胞中的EB病毒与正常人群咽部所携带的病毒亚型相同,均为亚型1.肿瘤细胞单克隆增殖发生于EB病毒感染之后,此结论支持EB病毒在自然杀伤/T细胞淋巴瘤中的致病作用.     

Aneuploidy in cutaneous T-cell lymphoma

A new method is described which makes it possible using skin specimens to perform flow cytometric analysis of DNA content. DNA content analysis was performed on 28 skin specimens and 9 blood samples from 18 patients with mycosis fungoides and Sézary syndrome. The reproducibility was fair, with almost identical results in 6 cases (mycosis fungoides and Sézary syndrome) where two samples (skin specimens or blood samples) were taken 6 hours to 10 days apart. Hyperdiploidy was found in 7 of 11 skin specimens from patients with mycosis fungoides stage I with negative histology. In 13 skin specimens and 3 blood samples from patients with mycosis fungoides stages II and IV, abnormalities including hyperdiploidy, near-tetraploidy and near-hexaploidy were found in 8 of 13 skin specimens and in 2 of 3 blood samples. Four patients with Sézary syndrome were studied: 2 patients in remission showed normal DNA histograms (2 skin specimens, 3 blood samples) and 2 patients with active disease showed aneuploidy in the 2 skin specimens examined and in 1 of 3 blood samples. These studies demonstrate: 1) the importance of flow cytometry as a diagnostic tool for use on skin specimens in the early stages of mycosis fungoides where routine histology is non-diagnostic; 2) the diagnostic and prognostic aid of flow cytometry during the course of mycosis fungoides and Sézary syndrome in addition to the probability of measuring the effect of treatment.     

Histopathologic studies in Sézary syndrome and erythrodermic mycosis fungoides: a comparison with benign forms of erythroderma

Histologic sections from eleven patients with Sézary syndrome were reviewed and compared with those of four patients with erythrodermic mycosis fungoides and twenty-four patients with a benign form of erythroderma, including fifteen patients with chronic dermatitis, four with a generalized drug eruption, and five with an erythrodermic psoriasis. The most important discriminating histologic feature in patients with Sézary syndrome was the presence of a monotonous bandlike or perivascular infiltrate in the papillary dermis, mainly composed of large cerebriform-mononuclear cells, as seen in seven of eleven Sézary syndrome patients. Pautrier's microabscesses were observed in seven of eleven Sézary syndrome patients, two of four patients with erythrodermic mycosis fungoides, but not in any of the patients with a benign form of erythroderma; their presence was therefore considered a reliable criterion in differentiating erythrodermic cutaneous T cell lymphoma from benign forms of erythroderma. However, features of chronic dermatitis were often found superimposed on those of Sézary syndrome and were even predominating in four of eleven Sézary syndrome patients. Moreover, four patients with a benign form of erythroderma showed a histologic picture suggestive of cutaneous T cell lymphoma. Therefore, in dubious cases repeated skin biopsies, additional investigations of lymph nodes and peripheral blood, and careful follow-up are mandatory for the achievement of a correct diagnosis.     

Treatment of cutaneous T-cell lymphomas with TP-5. Evaluation of the clinical effect in 8 patients

Eight patients with cutaneous T-cell lymphomas (6 patients with mycosis fungoides, 1 patient with Sézary's syndrome, 1 patient with low-grade malignant lymphoma, unclassified) were treated with TP-5, a synthetic pentapeptide having the same biologic activity as the thymic hormone thymopoietin. TP-5 was administered three times weekly at a dosage of 50 mg subcutaneously in 6 patients, 50 mg intravenously in 1 patient, and 100 mg subcutaneously in 1 patient. Clinical evaluation at the end of the trial disclosed improvement in 4 patients (2 patients with mycosis fungoides, 1 patient with Sézary's syndrome, 1 patient with low-grade malignant lymphoma, unclassified), deterioration in 3 patients with mycosis fungoides and no change in 1 patient with mycosis fungoides. As TP-5 evidently exerts some effect on cutaneous T-cell lymphomas, further investigations of its therapeutic potential in this group of diseases seem worthwhile.     

Management of cutaneous T-cell lymphomas: Established and emergent therapies

Cutaneous T-cell lymphoma is an uncommon group of non-Hodgkin's lymphoma primarily affecting the skin. It is comprised of a variety of entities with different clinical behaviours and prognosis. Mycosis fungoides is the commonest subtype, and Sézary syndrome is a much rarer form of cutaneous T-cell lymphoma. At this stage, control rather than cure is the goal of therapy, with particular emphasis placed on preserving quality of life. Our review of the efficacy, safety profile and accessibility of treatment modalities for mycosis fungoides/Sézary syndrome is a tailored guide for the clinician treating these rare conditions.     

Immunophenotypic studies in cutaneous T-cell lymphomas: clinical implications

Examination of biopsies from 62 patients with, or suspected of having cutaneous T-cell lymphoma (CTCL) revealed 24 cases in which the neoplastic cells expressed aberrant or suppressor T-cell phenotypes. The clinical records of these patients were reviewed in an attempt to establish whether recognition of these phenotypes has any clinical implications. Twelve patients had mycosis fungoides (MF) with plaques (n=4) or tumours (n=8), four had Sézary syndrome, and eight had large-cell lymphomas of pleomorphic (n=6) or anaplastic subtype (n=2). Most of the large-cell lymphomas behaved aggressively, as might have been expected from their cytological appearance. Aggressive courses were also seen in Sézary syndrome, and in tumour lesions of MF, whereas the behaviour in cases of plaque lesions was indolent. Again, this might have been anticipated from the clinical staging and routine histological examination. It is suggested that the expression of aberrant or suppressor T-cell phenotypes in CTCL is not of independent prognostic significance, but that the stage and histology are more important. This issue is an important topic for a prospective analysis.     

Mycosis fungoides und Sézary-Syndrom – Überblick und Ausblick

Mycosis fungoides and Sézary syndrome are the most important representatives of the heterogeneous group of cutaneous T-cell lymphomas. The diseases are rare and the diagnosis, which always requires a clinical-pathological correlation, is often delayed, especially in early forms of mycosis fungoides. The prognosis of mycosis fungoides depends on its stage and is usually favorable in the early stages. Clinically relevant prognostic parameters are missing and their development is the subject of current clinical research. Sézary syndrome, characterized by initial erythroderma and blood involvement, is a disease with a high mortality rate, in which good responses can now be achieved in many cases with new treatment options. The pathogenesis and immunology of the diseases is heterogeneous, with recent results pointing primarily to changes in specific signal transduction pathways that may be suitable as future treatment targets. Current therapy for mycosis fungoides and Sézary syndrome is primarily palliative with topical and systemic options either used alone or in combination. Only with allogeneic stem cell transplantation durable remissions can be achieved in selected patients. Similar to other areas of oncology, the development of new therapies for cutaneous lymphomas is currently changing from relatively untargeted empiricism to disease-specific, targeted pharmacotherapy based on knowledge from experimental research.     

Sézary Cell Count in Exfoliative Dermatitis

Sézary cells were present in a number of less than 1000/mm3 in 52 of 78 cases of various benign diffuse dermatoses and mycosis fungoides. The count was higher than 1000/mm3 in two cases of Sézary syndrome in which the histopathology was that of mycosis fungoides and in six cases of exfoliative erythroderma of undetermined etiology with the histopathology of nonspecific chronic dermatitis. One of these six cases developed palmoplantar keratoderma, but abnormal cells were not present in the tissue. The diagnosis of Sézary syndrome in these cases of exfoliative erythroderma could not be established, even though the Sézary cell count was more than 1000/mm3, because the abnormal cells were absent in the skin biopsy specimen. It is concluded that the number of Sézary cells present is not significant for the diagnosis of Sézary syndrome. Our cases with the diagnosis of Sézary syndrome are an erythrodermic variant of mycosis fungoides rather than a progressive conversion from exfoliative erythroderma.     

Mycosis fungoides and Sézary syndrome: focus on the current treatment scenario

Cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative disorders, characterized by infiltration of the skin by mature malignant T cells. Mycosis fungoides is the most common form of cutaneous T-cell lymphoma, accounting for more than 60% of cases. Mycosis fungoides in the early-stage is generally an indolent disease, progressing slowly from some patches or plaques to more widespread skin involvement. However, 20% to 25% of patients progress to advanced stages, with the development of skin tumors, extracutaneous spread and poor prognosis. Treatment modalities can be divided into two groups: skin-directed therapies and systemic therapies. Therapies targeting the skin include topical agents, phototherapy and radiotherapy. Systemic therapies include biological response modifiers, immunotherapies and chemotherapeutic agents. For early-stage mycosis fungoides, skin-directed therapies are preferred, to control the disease, improve symptoms and quality of life. When refractory or in advanced-stage disease, systemic treatment is necessary. In this article, the authors present a compilation of current treatment options for mycosis fungoides and Sézary syndrome.     

Relative frequency of the different types of cutaneous T cell and natural killer cell lymphomas in Korea based on the proposed WHO classification and the EORTC classification

The R.E.A.L. classification was largely adopted recently by the proposed WHO classification. The usefulness of this classification in cutaneous T cell and natural killer (NK) cell lymphomas in Korea was evaluated compared to that of the European Organization for Research and Treatment of Cancer (EORTC) classification. Overall, 78 patients with cutaneous T cell and NK cell lymphomas were diagnosed in Asan Medical Center in the 1990's. The clinical records, slides of H&E and immunohistochemical stainings were reviewed. By the proposed WHO classification, mycosis fungoides (20 cases), lymphomatoid papulosis (13 cases), nasal type NK/T-cell lymphoma (10 cases), CD30+ anaplastic large cell lymphoma (8 cases), subcutaneous panniculitis-like T-cell lymphoma (6 cases), peripheral T-cell lymphoma, unspecified (3 cases), Sézary syndrome (1 case) and blastic NK cell lymphoma (1 case) comprised the primary cases. Secondary or undetermined cases included peripheral T-cell lymphoma, unspecified (10 cases), nasal type NK/T-cell lymphoma (5 cases), and angioimmunoblastic T-cell lymphoma (1 case). EORTC classification for cutaneous T cell and NK cell lymphomas did not include nasal and nasal type NK/T-cell lymphomas, unspecified non-pleomorphic T-cell lymphoma, undetermined cases among primary or secondary ones and some rare types of skin lymphomas which can be classified by WHO. The WHO classification is more useful for skin lymphomas in Korea since it encompassed all the various types of skin T cell and NK cell lymphomas in Korea.     

Increased anti–Epstein—Barr virus antibodies in epidermotropic cutaneous T–cell lymphoma: a study of 64 patients

Epstein—Barr virus (EBV) is often associated with non–Hodgkin's T–cell lymphomas and has recently been found in the lesions of mycosis fungoides and Sézary syndrome. We sought to determine whether the anti–EBV antibody profile was disturbed in mycosis fungoides and Sézary syndrome and whether there are particular profiles characteristic of disease stage. Anti–EBV antibodies (anti–VCA,–EA and –EBNA) were studied in the sera of 64 patients. An immunoenzymatic technique was used, and the results were compared with the same number of age– and sex–matched healthy controls. Patients with mycosis fungoides and Sézary syndrome developed higher anti–VCA antibody titres (median 1200) than controls (median 320). Thirty–seven patients had anti–VCA ≥ 1200 vs. 19 controls (P<0.01). These elevated anti–VCA antibody titres were associated with positive EA in 19 patients versus three controls. No differences were found between the illness stages. Anti–EBV antibodies were most often found in mycosis fungoides and Sézary syndrome when the serological profile was similar to that of cellular immune deficiencies and EBV–related non–Hodgkin's lymphoma. EBV could be involved, either directly on lymphocytes or, more likely, indirectly by chronic antigenic stimulation.