免疫母细胞性淋巴结病样T细胞淋巴瘤伴皮肤损害1例

免疫母细胞性淋巴结病样Ｔ细胞淋巴瘤（ＩＢＬ－ＴＣ）是特殊类型的周围Ｔ细胞淋巴瘤。临床特征为发热;淋巴结、肝脾肿大;皮疹及高γ球蛋白血症。皮疹呈多种形态,随其发展主要为二型：丘疹结节型和红皮病型。淋巴结病理示淋巴结结构破坏,有异形淋巴样细胞、免疫母细胞和浆细胞样的所谓淡染细胞（ｐａｌｅｃｅｌｌｓ）浸润。免疫学示Ｔ细胞标记。     

Treatment of cutaneous T-cell lymphoma with extracorporeal photochemotherapy

Background Cutaneous T-cell lymphoma (CTCL) and its leukemic erythrodermic form (Sézary syndrome) are malignancies cies of CD4+ T lymphocytes. Extracorporeal photochemotherapy (ECP) selectively affects autoreactive as well as malignant T lymphocytes. The efficacy of ECP depends strongly upon adequate serum/buffy coat levels of the photosensitizer 8-methoxypsoralen (8-MOP). The resorption of orally applied 8-MOP vanes inter- and intraindividually within a broad range, meaning that adequate therapeutic drug levels cannot always he achieved. Therefore, since July 1994 we have exclusively used a liquid 8-MOP preparation which is added directly into the buffy coat fraction of the ECP circuit, resulting in constant high drug levels of approximately 190 ng/ml. Twelve CTCL-patients (six with Sézary syndrome, six with mycosis fungoides received between six and 25 ECP treatments. Some of them had undergone previous therapy without success. Results All patients with Sézary syndrome declared a distinct reduction in intensity of pruritus. Three patients who received liquid 8-MOP extracorporeally showed a partial remission on the basis of skin scores. Of the patients receiving 8-MOP orally, two remained clinically unchanged and one showed a progression of the disease. In these cases, subtherapeutic 8-MOP plasma levels were often found. Of the six mycosis fungoides patients one achieved complete and two partial remission: another two patients showed minor response. These five patients were treated with liquid 8-MOP. One patient showed no change in skin lesions; he had received 8-MOP orally and achieved subtherapeutic photosensitizer plasma levels. Conclusion Our treatment protocols confirm the beneficial effects of ECP on CTCL at any stage, but it seems that adequate ECP efficiency is ensured only when an 8-MOP solution is applied extracorporeally.     

Cutaneous T-cell lymphoma

Cutaneous T-cell lymphoma (CTCL) is a neoplasm of helper T cells whose first manifestations usually appear in the skin. The various forms of CTCL are distinguished by both clinical features and histopathology. Early on, the diagnosis may be difficult to establish because of its numerous, and often non-specific, clinical presentations. Further, the pathological findings of early lesions may lack the diagnostic features observed in well-developed or advanced disease. The diagnosis of CTCL must be considered in any patient with a chronic, therapy-resistant condition of the skin. In patients with non-specific histological findings, a high index of suspicion and multiple biopsies may eventually lead to a diagnosis of CTCL. Once the diagnosis of CTCL is established, accurate staging is essential both for its effect on treatment decisions and for its prognostic value. In general, CTCL is a chronic, slowly progressive disease with a long evolution. The development of tumours is a poor prognostic sign, as is erythroderma. The Sezary syndrome is a distinct form of erythrodermic CTCL that is characterized by exfoliative erythroderma, lymphadenopathy, lymphocytosis, intense pruritus, and circulating large, abnormal lymphocytes (Sezary cells). When death does occur, it is most often due to septicemia. Treatment of CTCL must be tailored to the individual patient. The most commonly employed treatment options are photochemotherapy and topical chemotherapy.     

Phototherapy for cutaneous T-cell lymphoma

Phototherapy has been utilized for decades in the treatment of various dermatologic conditions, including cutaneous T-cell lymphoma (CTCL). Currently, a number of light sources are available, and selection of the specific modality is based on a number of factors, the most important of which is disease stage. The efficacy of broadband ultraviolet B (UVB) is limited to the patch stage, while psoralen and ultraviolet A (PUVA) is capable of clearing plaques and, sometimes, early tumors. Narrowband UVB is also effective for early stages and has practical advantages over PUVA, but more studies are needed to more fully evaluate its role in CTCL. Long-wave ultraviolet A (UVA1) has likewise shown efficacy, supported by findings of apoptosis induction in UVA1-treated cells. Long-term remissions have been reported for PUVA, but in the majority of cases, maintenance therapy was necessary. Although beneficial as monotherapy for early stages of the disease, phototherapy is also a useful adjunct to other modalities such as interferons, retinoids and electron beam therapy. Studies are ongoing to refine protocols for combination therapy, with the goal of improving efficacy, while minimizing adverse effects.     

Treatment planning in cutaneous T-cell lymphoma

Effective long-term management of cutaneous T-cell lymphoma (CTCL) requires administration of skin-directed therapies such as topically applied nitrogen mustard or photochemotherapy to achieve a complete response in clinically early disease (patch and thin-plaque-phase mycosis fungoides, MF) and often the concomitant administration of well-tolerated drugs with systemic effects such as interferon alfa, bexarotene, methotrexate or extracorporeal photopheresis in more advanced, but not highly aggressive/nontransformed disease (thick plaque or tumor phase MF or erythrodermic CTCL). The author's approach is provided as a guide for dermatologists in private practice.     

Genotraumatic T cells and cutaneous T-cell lymphoma. A causal relationship?

Mycosis fungoides, or cutaneous T-cell lymphoma (CTCL), is a T-cell mediated chronic inflammatory skin disease, which can occasionally progress with a variable time course to a fatal lymphoma or to a leukaemic form called Sézary's syndrome. Extensive research into CTCL has not yet elucidated the primary pathophysiological mechanisms. Immunohistological studies are so far less helpful than expected in establishing early diagnosis and prognosis of the disease. The proposition that an exogenous virus is the cause of CTCL has not been substantiated. Karyotypic analysis of lymphocytes from the skin and blood of patients with CTCL have shown the existence of several genetically aberrant T-cell clones in the same patient. These changes are discussed as potential primary events for the development of CTCL. The hypothesis is put forward that the development of genotraumatic T lymphocytes is involved in the progression of the disease.     

Erythrodermic syringotropic cutaneous T-cell lymphoma

Syringotropic cutaneous T-cell lymphoma (CTCL) is a rare localized variant of CTCL, characterized histologically by eccrine gland and ductal hyperplasia surrounded by a dense syringotropic lymphocytic infiltrate. Previously reported only in men, we describe the first woman with syringotropic CTCL. Unusually, she presented with erythroderma, cutaneous nodules, poikilodermatous patches, widespread alopecia and lymphadenopathy.     

Mycosis fungoides associated with Mediterranean lymphoma

Summary Mycosis fungoides was observed in a 71-year-old male with mediterranean lymphoma, a B-cell malignancy. It is proposed that this association is not incidental since hypergammaglobulinaemia and even monoclonal gammopathies have repeatedly been described in cutaneous T-cell lymphomas. Mediterranean lymphoma might have resulted from (a) helper cell activities of tumor T-lymphocytes, (b) common antigenic stimuli, or (c) deranged T-B cooperation due to concomitant mycosis fungoides.     

Incidence of primary cutaneous T-cell lymphoma in Norway

Background  Studies from different countries have reported an increased incidence of primary cutaneous lymphomas over the last decades.
Objectives  To estimate the incidence rates of primary cutaneous T-cell lymphoma (CTCL) and mycosis fungoides (MF)/Sézary syndrome (SS) in Norway, and to compare these rates with those reported from other countries.
Methods  Data from the Cancer Registry of Norway on non-Hodgkin lymphomas during the period 1980–2003 were analysed.
Results  In total, 337 cases of CTCL were reported to the Cancer Registry during the study period, of which 262 cases were classified as MF/SS. The incidence rate of CTCL increased significantly ( P _trend < 0·001) from 0·16 (95% confidence interval, CI 0·11–0·20) per 100 000 person-years in 1980–84 to 0·29 (95% CI 0·22–0·36) per 100 000 person-years in 2000–2003. The incidence of MF/SS also increased during the same period ( P _trend = 0·05) from 0·15 (95% CI 0·10–0·19) per 100 000 person-years to 0·18 (95% CI 0·13–0·24) per 100 000 person-years.
Conclusions  The incidence of both CTCL and MF/SS increased in Norway during the period 1980–2003.     

皮肤T细胞淋巴瘤表观遗传学研究进展

表观遗传学主要是研究在不改变DNA序列的情况下,发生的基因表达水平可遗传的变化,主要包括DNA甲基化、组蛋白修饰和非编码RNA调控.皮肤T细胞淋巴瘤是一组原发于皮肤的T淋巴细胞恶性增殖性疾病,蕈样肉芽肿和Sezary综合征是最常见的皮肤T细胞淋巴瘤.近年来研究表明,表观遗传学不仅在皮肤T细胞淋巴瘤的发生发展中起重要作用,而且可以通过改变表观遗传达到治疗皮肤T细胞淋巴瘤目的.     

Sézary syndrome with early immunoblastic transformation

Summary Two patients with clinical manifestations of Sézary syndrome are reported. In both cases from an early stage of the disease in addition to characteristic Sézary cells large numbers of immunoblasts were present in skin lesions and peripheral lymph nodes and in one case also in the blood. Their relationship to the characteristic Sézary cells was shown by morphological, cytochemical and immunological methods. The infiltrates in the skin were epidermotropic in one case and nonepidermotropic in the other. Lymph node structure was effaced by diffuse infiltration of abnormal lymphoid cells. These were found to proliferate in the skin as well as in lymph nodes. Cytogenetical studies of blood lymphocytes indicated an abnormal hypodiploid clone in both cases. Immunologically the tumour cells had properties of peripheral T-lymphocytes but whereas all abnormal cells exhibited inducer/helper cell characteristics in one case, only a minority of the lymphocytes revealed these characteristics in the other case. In this case the tumour cell population changed into a more pleomorphic type. The classification of the cases is discused.     

Interferon in the treatment of cutaneous T-cell lymphoma

Interferons are polypeptides with a broad range of in vivo effects that have shown efficacy in cutaneous T-cell lymphoma (CTCL). Particularly useful is alfa interferon (IFN) which, as a single agent, has shown partial remission rates of > 50% and complete responses of > 20%. Side-effects are predictable, generally well tolerated and dose-related. The efficacy of IFN has increased with combination therapy without any significant increase in attendant side-effects. An update on the specifics of the different IFN subtypes, their inherent biologic activity, pharmacokinetics, efficacy and safety in CTCL is presented in this paper.     

Follicular cutaneous T-cell lymphoma: a clinicopathological study of nine cases

Nine patients with follicular cutaneous T-cell lymphoma (CTCL), a recently described variant of lymphoma, are presented. On the basis of clinical manifestations and disease course, three groups of patients were distinguished: (i) two patients with follicular CTCL not associated with conventional lesions of mycosis fungoides (MF) and showing no evolution towards MF in follow-up periods of 3 and 6 years; (ii) one patient with follicular CTCL that evolved into conventional MF within 3 years; (iii) six patients showing conventional MF lesions either before or concurrently with the follicular lesions and thus representing follicular CTCL of the true MF type. The follicular lesions included hair-devoid patches or plaques with spiky hyperkeratotic papules (four patients), keratosis pilaris-like lesions (four), comedo-like lesions (four), follicular papules with alopecia (three) and milia-like lesions (three). Histopathological examination showed perifollicular and intrafollicular lymphocytes, without mucin deposition and with minimal or no involvement of the overlying epidermis. Significant syringotropism was also observed in three cases. Immunohistochemical analysis showed the predominance of CD4 + T cells, deletion of CD7 in some cases, Ki-67 + lymphocytes confined mainly to the follicular epithelium, and expression of keratinocyte intercellular adhesion molecule-1 exclusively in the hair follicle. T-cell receptor gamma gene rearrangement was positive in the one case studied from each group. Different treatment modalities were employed, the most commonly used as monotherapy being phototherapy: psoralen ultraviolet A in four patients, two of whom showed a complete clinical and histopathological remission, and ultraviolet B in one patient, who showed a complete remission (both clinical and histopathological). This study indicates that follicular CTCL is more common than reflected in the literature, has heterogeneous clinical manifestations, and is either an expression of or closely related to MF. The influence of the follicular involvement on the therapeutic response remains to be clarified. However, our therapeutic experience clearly suggests that some patients with follicular CTCL can benefit from phototherapy.     

MYCOSIS FUNGOIDES WITH FATAL BRAIN INVOLVEMENT

The clinical course, therapy and investigations in a man with lichenoid mycosis fungoides which resulted in fatal spread to the brain is described. Immunological studies revealed a significant reduction in T cell numbers. Brain lesions were confirmed by CT Scan and drill biopsy. The literature on the subject is discussed.