WHO-EORTC classification for cutaneous lymphomas 汇报者：权晟

introduction The term “primary cutaneous lymphoma” refers to cutaneous T-cell lymphomas (CTCLs) and cutaneous B-cell lymphomas (CBCLs) that present in the skin with no evidence of extracutaneous disease at the time of diagnosis. Primary cutaneous lymphomas often have a completely different clinical behavior and prognosis from histologically similar systemic lymphomas, which may involve the skin secondarily, and therefore require different types of treatment.

Primary cutaneous lymphomas are currently classified by the European Organization for Research and Treatment of Cancer (EORTC) classification or the World Health Organization (WHO) classification, but both systems have shortcomings. During recent consensus meetings representatives of both systems reached agreement on a new classification, which is now called the WHO-EORTC classification.

Mycosis Fungoides (MF) MF is a commonly epidermotropic CTCL characterized by a proliferation of small- to mediumsized T lymphocytes with cerebriform nuclei. 蕈样霉菌病(MF) 蕈样霉菌病是一种常见嗜表皮性的皮肤T细胞淋巴瘤（CTCL），特点是增生的小至中等大小的T淋巴细胞，有“脑回样”的核。MF是最常见的皮肤T细胞淋巴瘤，约占所有皮肤原发性淋巴瘤的50%。

Clinical features MF has an indolent clinical course with slow progression over years or sometimes decades, from patches to more infiltrated plaques and eventually to tumors . 临床特征： MF多发在成人，有惰性的临床病程、进展缓慢，从斑块到浸润的斑块最后到肿瘤经时数年，有时可达十几年。在部分病人，淋巴结和内脏器官可能会在疾病的晚期被累及。肿块期的MF病人可特征性地同时出现斑点、斑块和瘤块，后者多出现溃疡。

组织病理学： MF的早期斑块状的病损表现为表浅的“条带样”或“苔藓样”浸润，主要成份是淋巴细胞和组织细胞。异型的瘤细胞数量不多，细胞小至中等大小、有“脑回状”的核，多数局限在表皮（嗜表皮性）。肿瘤细胞特征性地沿表皮的基底层生长，呈“晕环状”或“线状”的排列。出现表皮间的异型淋巴细胞的聚集（Pautrier微脓肿）是一种特征性的特点，但仅可见于一小部分病例。

Immunophenotype The neoplastic cells in MF have a mature CD3, CD4, CD45RO, CD8 memory T-cell phenotype. Demonstration of an aberrant phenotype (loss of pan–T-cell antigens such as CD2, CD3, and CD5) is often seen and is an important adjunct in the diagnosis of MF. 免疫表型： MF中的肿瘤细胞有成熟型的CD3+、CD4+、CD45RO+、CD8－的T记忆细胞的免疫表型。出现奇异的表型（如丢失全T细胞抗原CD2、CD3、CD5等）常见，可作为诊断MF的参考指标。

Genetic features. Clonal T-cell receptor gene rearrangements are detected. Many structural and numerical chromosomal abnormalities have been described, but MF-specific chromosomal translocations have not been identified. 遗传学特征： 克隆性的T细胞受体基因重排见于多数病例。许多染色体的结构和数目的异常已有描述，尤其是进展期的MF，但恒定的MF特异的染色体异位还未发现。10号染色体长臂的缺失和P15、P16、P53肿瘤抑制基因的异常可见于多数的MF患者。

Prognosis and predictive factors. The prognosis of patients is dependent on stage. In recent studies, 10-year disease-specific survivals were 97-98% for patients with limited patch/plaque disease, 83% for patients with generalized patch/plaque disease, 42% for patients with tumor stage disease. 预后及预测因素： MF患者的预后取决于分期。局限性的斑片/斑块期的MF患者，10年生存率是97~98%；弥漫的斑片/斑块期的MF患者是83%；肿块期的是42%。

Sézary综合症 (SS) Sézary syndrome (SS) Sézary syndrome is defined historically by the triad of erythroderma, generalized lmphadenopathy, and the presence of neoplastic T cells (Se´zary cells) in skin, lymph nodes, and peripheral blood. Sézary综合症 (SS) Sézary综合症包括了既往的“红皮病”、泛发的淋巴结病和在皮肤、淋巴结及血液中出现肿瘤性T细胞（Sézary细胞）的三联症。

Clinical features SS is a rare disease and occurs exclusively in adults. It is characterized by erythroderma, which may be associated with marked exfoliation, edema, and lichenification, and which is intensely pruritic. Lymphadenopathy, alopecia, onychodystrophy,and palmoplantar hyperkeratosis are common findings. 临床特征： SS是一种罕见病，毫无例外地发生在成人。特征性地表现为红皮病，可相关性地出现明显褪皮、水肿和“苔藓样”硬化，这会造成奇痒。淋巴结病、秃头、甲床萎缩和掌柘部位角化亢进是常见的症状。

组织病理学： SS最主要的特征与MF的特征类似。然而SS中的浸润细胞成分更单一，可无“嗜表皮现象”。累及淋巴结时可特征性地出现出弥漫、单一的Sézary细胞浸润，伴有淋巴结正常结构的破坏。 免疫表型： 肿瘤性的T细胞呈CD3+、CD4+、CD8－的表型。血循环中的Sézary细胞常表现出CD7和CD26的丢失。

Genetic features. T-cell receptor genes are clonally rearranged. Recurrent chromosomal translocations have not been detected in SS, but complex karyotypes are common. Several studies have identified a consistent pattern of identical chromosomal abnormalities in SS, which was almost identical to that in MF, suggesting that both conditions represent parts of the same spectrum of disease with a similar pathogenesis。 遗传学特征： T细胞受体基因呈现克隆性的重排。在周围血中出现克隆性的T细胞是重要的诊断依据。特定的染色体异常尚未在SS中发现，但复杂的核型常见。有研究证实在SS中的一个与MF的几乎相同的特征性的染色体结构异常。提示这两类疾病代表同一疾病谱不同部分、有相似的病因。

Prognosis and predictive factors. The prognosis is generally poor, with a median survival between 2 and 4 years, depending on the exact definition used. Most patients die of opportunistic infections that are due to immunosuppression. 预后及预测因素： 预后通常不佳，中位生存时间约2~4年，与诊断界定有关。多数病人死于由免疫抑制引起的机会性感染。

原发性皮肤CD30阳性的淋巴增殖性疾病（LPD） LPD是第二种最常见的皮肤T细胞淋巴瘤，大约占CTCL的30%。这组中包括原发性皮肤间变性大细胞淋巴瘤（C-ALCL）、淋巴瘤样丘疹病（LyP）和交界病例。现在普遍认为C-ALCL和LyP形成一种疾病的谱系。 “交界性病变” 是指那些尽管仔细分析临床病理的相关性仍不能准确区分C-ALCL和LyP的病例。通过临床进一步随访检查病人将最终确诊病人为C-ALCL还是LyP。

Primary cutaneous anaplastic large-cell Lymphoma (CALCL) CALCL is composed of large cells with an anaplastic, pleomorphic, or immunoblastic cytomorphology and expression of the CD30 antigen by the majority (more than 75%) of tumor cells. There is no clinical evidence or history of LyP, MF, or another type of CTCL. 原发性皮肤间变性大细胞淋巴瘤 CALCL由大细胞构成，细胞具有间变样、多形性或免疫母细胞样形态，而且大于75%肿瘤细胞表达CD30抗原。没有LyP、MF或其它CTCL的临床证据或病史。

临床特征 C-ALCL主要发生在成人，大多数病人表现为孤立的或局限的结节或肿块，有时为丘疹，常伴有溃疡。在大约20%的病人中可见到多灶性皮肤病变。病变可以类似于LyP表现为部分或全部自发消退。这些淋巴瘤在皮肤经常复发。大约10%的病人有皮肤外的播散，主要累及局部淋巴结。

组织病理学 密集成片的CD30阳性的肿瘤性大细胞弥漫、非嗜表皮性浸润。大多数病例肿瘤细胞具有间变细胞的形态学特点。少部分病例（20%-25%）无间变表现。反应性的淋巴细胞经常出现在病变的周边部。溃疡性病变可以表现为LyP样的组织学特征。

Immunophenotype The neoplastic cells generally show an activated CD4 T-cell phenotype with variable loss of CD2, CD5, and/or CD3, and frequent expression of cytotoxic proteins (granzyme B, TIA-1, perforin). Some cases (less than 5%) have a CD8 T-cell phenotype. CD30 must be expressed by the majority (more than 75%) of the neoplastic T cells. 免疫表型 肿瘤细胞通常表现为活化的CD4+T细胞表型，常不表达CD2、CD5和/或CD3，表达细胞毒性蛋白（粒酶B、TIA-1、穿孔素）。少数病例表现为CD8+T细胞表型。CD30必须表达大于75%肿瘤性T细胞。

Genetic features. Most cases show clonal rearrangement of T-cell receptor genes. The (2;5)(p23;q35) translocation and its variants, which is a characteristic feature of systemic ALCL, is not or rarely found in C-ALCL. 遗传学特征 大多数病例表现为T细胞受体基因克隆性重排。t（2；5）（p23；q35）异位为系统性ALCL的特征表现，但在C-ALCL病例中没有或极少出现。

Prognosis and predictive factors. The prognosis is usually favorable with a 10-year disease-related survival exceeding 90%. Patients presenting with multifocal skin lesions and patients with involvement of only regional lymph nodes have a similar prognosis to patients with only skin lesions. No difference in clinical presentation, clinical behavior, or prognosis is found between cases with an anaplastic morphology and cases with a nonanaplastic (pleomorphic or immunoblastic) morphology. 预后和预测因素 预后通常较好，10年生存率超过90%。具有多灶皮肤病变病人和仅累及局部淋巴结病人预后与仅有皮肤病变病人相似。具有间变形态和无间变形态病例在临床表现、临床行为或预后方面没有差别。

Lymphomatoid papulosis (LyP) Lymphomatoid papulosis is defined as a chronic, recurrent, self-healing papulonecrotic or papulonodular skin disease with histologic features suggestive of a (CD30) malignant lymphoma. 淋巴瘤样丘疹病 淋巴瘤样丘疹病（LyP）定义为慢性的、反复发作的、自愈性丘疹坏死性或丘疹结节性皮肤病变，组织学特征提示为一种（CD30阳性）的恶性淋巴瘤。

临床特征 LyP通常发生在成年人，但也可发生在儿童。主要表现为躯干和四肢部位出现特征丘疹性、丘疹坏死性和/或结节性皮肤病变。皮肤病变一般在3-12周消退，可能留下表浅瘢痕。疾病的持续时间不同（几个月-40多年）。大约20%的LyP随后发生另一类型恶性（皮肤）淋巴瘤（一般为MF、C-ALCL或霍奇金淋巴瘤）。

组织病理学 LyP的组织学分三型（A、B、C），三种亚型之间有重叠。在A型中，分散的或小簇的大的（有时为多核或R-S样，CD30阳性）细胞夹杂着许多炎性细胞。C型病变表现为单一形态的细胞或成片的CD30阳性的大的T细胞，而夹杂的炎性细胞相对很少。LyP的B型不常见，其特征为嗜表皮性，浸润的细胞为类似于MF的脑回样核的异型小淋巴细胞。

Immunophenotype The large atypical cells in the LyP type A and type C lesions have the same phenotype as the tumor cells in C-ALCL. The atypical cells with cerebriform nuclei in the LyP type B lesions have a CD3, CD4, CD8 phenotype and do not express CD30 antigen. 免疫表型 LyP的A型和C型病变中的异型大细胞与C-ALCL中的肿瘤细胞具有相同的免疫表型。LyP的B型病变中脑回样核的异型细胞CD3+、CD4+、CD8-、 CD30-。

Genetic features Clonally rearranged T-cell receptor genes have been detected in approximately 60%-70% of LyP lesions. Identical rearrangements have been demonstrated in LyP lesions and associated lymphomas. The (2;5) (p23;q35) translocation is not detected in LyP. 遗传学特征 在大约60%-70%LyP可检测到T细胞受体基因克隆性重排。在LyP病变和相关的淋巴瘤中可证实同样的重排形式。LyP未检测到t（2；5）（p23；35q）异位。

Prognosis and predictive factors LyP has an excellent prognosis. In a recent study of 118 LyP patients only 5 (4%) patients developed a systemic lymphoma, and only 2 (2%) patients died of systemic disease over a median follow-up period of 77 months。 预后和预测因素 LyP预后极佳。最近一组118例LyP病人研究发现仅有5例（4%）病人发展为系统性淋巴瘤，仅2例（2%）病人在77个月的中期随访时死于系统性疾病。发展成系统性淋巴瘤的危险因素尚不清楚。

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