Studies of Clinical Diagnosis and Treatment on Cutaneous T-Cell Lymphoma

(1)应用免疫组织化学ABP(亲和素-生物素-过氧化物酶复合体)法和PAP(过氧化物酶-抗过氧化物酶复合体)法对皮肤淋巴瘤组织中的表面标志物进行了研究。ABP法检测的T细胞淋巴瘤中，除ATL外，80%为辅助性/诱导性表型(Leu2a~+，Leu3a^+)，6%为抑制性/细胞毒性表型(Leu2a~+，Leu3a~+)，1例为诱导型，1例为Ki-1淋巴瘤。这些结果表明皮肤T细胞淋巴瘤具有异质性。换句话说，CTCL是一种类型，但代表了皮肤T细胞淋巴瘤的主要比例。(2)成人T细胞白血病/淋巴瘤是日本一种不同于皮肤T细胞淋巴瘤的重要疾病，通常表现为与CTCL相同的表型，即辅助性/诱导性T细胞表型，通常累及皮肤。临床上，CTCL和ATL在本质上都是异质性的。因此，我们演示了不同的…在临床和免疫病理细胞表面特征方面，CTCL和ATL之间有更多的ES。在ATL患者中，主要的临床表现是外周淋巴结受累、皮肤损害、肝脾肿大、白血病表现和侵袭性病程。相比之下，在CTCL患者中，只有皮肤病变在疾病开始时占主导地位，并显示出相对良好的预后。皮肤ATL的表型不均一，即CD4^-CD8^-、CD4^+CD8^-和CD4^-CD8^+。Leu8、CD7(Leu9)和CD45RA(2H4)在皮肤浸润性ATL细胞、外周血和淋巴结ATL细胞中的表达均高于皮肤浸润性CTCL细胞。皮肤浸润性CTCL细胞CD25(IL-2R)、CD71(OKT9)、HLADR、HLADQ高表达，CD45RO(UCHL-1)高表达。ATL细胞和CTCL细胞最显著的表型差异是细胞表面表达Leu8、CD7和CD25抗原，皮肤浸润性ATL细胞和CTCL细胞与外周血和淋巴结ATL细胞的主要表型差异是CD29和CD45RA的表达。这些结果证实了细胞表面抗原表达的差异可能反映了ATL和CTCL的临床特征，提示外周血和淋巴结ATL细胞的主要表型是幼稚、相对不成熟或活化的T细胞，而CTCL细胞是先前激活的(记忆)T细胞。换句话说，CTCL细胞与ATL细胞不是同一来源。这些观察结果支持ATL是一种有别于CTCL的疾病的概念。(3)应用免疫组织化学方法检测29例皮肤T细胞淋巴瘤和多种良性皮肤淋巴组织中PC(Ki-67)抗原、DNA聚合酶-α和转铁蛋白受体(OKT9：CD71)的表达。此外，与淋巴瘤的组织学分级和淋巴细胞上抗原表达的相关性：高级别类型，如免疫母细胞型，阳性率明显高于中级别类型，且明显高于低级别类型。(4)探讨T细胞淋巴瘤的治疗特点和预后，包括霉菌样肉芽肿、皮肤非霉菌样T细胞淋巴瘤和皮肤B细胞淋巴瘤。外周血淋巴细胞中CD3阳性细胞和CD4阳性细胞的百分比是最有价值的预后因素之一。CTCL的TNM分期和国际工作方案也是影响预后的重要因素。较少

(1) We studied surface markers presents in lymphoma of the skin by immunohistochemical staining, using the ABP (avidine-biotin-peroxidase complex) methods and PAP (peroxidase-anti-peroxidase complex) methods. 80 percent of T-cell lymphoma except ATL analyzed by the ABP methods showed a helper/inducer phenotype (Leu2a~, Leu3a^+), 6 percent showed a suppressor/cytotoxic phenotype (Leu2a^+, Leu3a~), one case showed an inducer phenotype, one case showed a phenotype of so-called Ki-1 lymphoma. These results showed that T-cell lymphoma of the skin is heterogeneous in nature. In other words, CTCL is one type but represents a major propotion of T-cell lymphomas of the skin. (2) An important disease entity distinct from cutaneous T-cell lymphoma in Japan is adult T-cell leukemia/lymphoma, which usually shows the same phenotype as CTCL, i. e., a helper/inducer T-cell phenotype, and usually involves the skin. Clinically, both CTCL and ATL are heterogeneous in nature. So, we demonstrated differenc … More es between CTCL and ATL in terms of clinical and immunopathologic cell surface features. In patients with ATL, the predominant clinical findings were peripheral lymph node involvement, skin lesions, hepatosplenomegary, leukemic manifestations, and an aggressive course. In patients with CTCL, by contrast, only skin lesions predominated at the onset of the disease and a relatively good prognosis was demonstrated. Phenotypic heterogeneity of ATL in the skin, i. e., CD4^-CD8^-, CD4^+CD8^-, and CD4^-CD8^+, was demonstrated. Expression of Leu8, CD7 (Leu9), and CD45RA (2H4) was high in both the skin-infiltrating ATL cells and peripheral blood and lymph node ATL cells compared with that in the skin-infiltrating CTCL cells. Expression of CD25 (IL-2R), CD71 (OKT9), HLA-DR, and HLA-DQ was high, and that of CD45RO (UCHL-1) was not significantly high in the skin-infiltrating CTCL cells compared with that in ATL cells. The most significant phenotype difference between ATL cells and CTCL cells was the expression of Leu8 (lymph node homing receptor), CD7 and CD25 antigens on the cell surface, and the main phenotypic difference between skin-infiltrating ATL and CTCL cells and peripheral blood and lymph node ATL cells was the expression of CD29 and CD45RA. These findings confirm that the difference in antigen expression on the cell surface might reflect the clinical features of ATL and CTCL, and suggest that the predominant phenotype of peripheral blood and lymph node ATL cells is that of naive, relatively immature or activated T-cells, and that CTCL cells are previously activated (memory) T-cells. In other words, CTCL cells do not share the same origin as ATL cells. These observations support the concept that ATL ia a disease distinct from CTCL. (3) The expression of PC (Ki-67) antigen, DNA polymerase-alpha and trasferrin receptor (OKT9 : CD71) were studied in 29 cases of cutaneous T-cell lymphomas and in a variety of benign cutaneous lymphoid infiltrates by immunohistochemistry. PCBeside, correlation with histologic grading of lymphomas and expression of those antigens on lymphoid cells was indicated : the high-grade types, e. g., immunoblastic type, exhibited greater positivity than intermediate grade types and much more than low-grade types. (4) We investigated the pretreatment characteristics and prognosis of T-cell lymphoma, including mycosis fungoids, T-cell lymphoma of the skin other than MF, and B-cell lymphoma of the skin. Percentage of CD3-positive cell and CD4-positive cell in the peripheral blood lymphocytes was one of the most useful prognostic factor. TNM staging of CTCL and international working formulation were also useful factor for prognosis. Less