CD4+/CD56+造血皮肤肿瘤的临床与病理学研究

Clinicopathologic Study of CD4+/CD56+ Haematodermatic Neoplasm

目的:探讨CD4+/CD56+造血皮肤肿瘤(CD4+/CD56+HN)的临床病理学特点、诊断与鉴别诊断。方法:对5例按照2005年世界卫生组织-欧洲癌症治疗研究组织(WHO-EORTC)皮肤淋巴瘤有关诊断标准确诊的CD4+/CD56+HN患者进行研究。全部5例均行骨髓活检,同时3例行皮肤活检,4例行浅表淋巴结活检。组织标本经常规中性甲醛缓冲液固定、石蜡包埋切片、HE染色。Elivsion方法进行免疫组化检测。结果:男4例,女1例;中位年龄47(8～73)岁。就诊时3例为无症状性、多发性皮肤病损,表面呈淡红色至紫红色的斑疹、丘疹、斑块、皮下结节。2例无皮肤病损者以浅表淋巴结肿大就诊。病理组织学检查示皮肤侵犯(3例)以真皮为主,表皮未受累及,未见侵犯血管与坏死;淋巴结结构部分破坏(4例),主要侵犯髓质及滤泡间区,类似于白血病样侵犯模式;骨髓侵犯程度为中、重度(4例),呈灶性或弥漫性分布。镜下示瘤细胞胞体中等大小,核圆或轻度不规则,染色质细致。形态类似于原单核细胞或淋巴母细胞。免疫组化显示瘤细胞免疫表型为CD4+(80%,4/5)、CD56+(100%,5/5)、CD43+(100%,4/4)、CD45+(100%,3/3)、CD123(100%,2/2)、CD117-、MPO-、Lysozyme-、CD68-、PAX5-、CD20-、CD3-。2例行联合化疗,病情进展,病程分别为26、11个月。结论:CD4+/CD56+HN是一种非髓系、非淋系来源的高度侵袭性造血系统肿瘤,具有独特的临床与病理学特点。容易侵犯皮肤、骨髓及淋巴结。瘤细胞不表达淋系与髓系系别特异性标记,需要与多种髓系及淋系来源的肿瘤如皮肤淋巴瘤、髓系肉瘤、急性白血病鉴别。

Objective： To explore the clinicopathologic characterisitcs, diagnosis and differential diagnosis of CD4 ＋/ CD56＋ hematodermatic neoplasm （CD4＋/CD56＋ HN）. Methods： Data of the 5 patients who were diagnosed as CD4＋/ CD56 ＋ HN, based on the related criteria of 2005 WHO-European Organization for Research and Treatment of Cancer （WHO-EORTC） classification for cutaneous lymphomas, was investigated. Bone marrow biopsy was conducted in all 5 patients, skin biopsy was conducted in 3 patients, and superficial lymph node biopsies were conducted in 4 patients. Histological specimens were fixed using routine formalin neutral buffered solution and subsequently embedded in paraffin. Sections were stained with hematoxylin and eosin. Immunohistochemistry was conducted using Elivision methods. Results： There were 4 males and 1 female, with a median age of 47 years （range, 8 - 73）. Three of the 5 patients presented with asymptomatic multiple skin lesions that were salmon pink to mauve macules, papules, plaques or subcutaneous nodules. The other two patients presented with superficial lymphadenectasis without skin lesions. Histologically, tumour cells infiltrated the dermis in 3 cases, sparing the epidermis. Blood vessel destruction and necrosis were absent. The architecture of lymph nodes was partially destroyed in 4 cases. Tumor cells involved the interfollicular zone and medulla, similar to a pattern of leukemic infiltration. The degree of bone marrow involvement was moderate to severe （4 cases） with a pattern of focal or diffuse infiltration by the tumor cells. Microscopically the tumor cells were medium-sized and displayed a round or slightly irregular-shaped nucleus with dispersed chromatin. The morphology of the tumor cells was similar to lymphoblasts or monoblasts. The results of immunohistochemistry showed the following results： in the immunophenotypical characterization of the tumors, there was expression of CD4 （80%, 4/5）, CD56 （100%, 5/5）, CD43（100%, 4/4）, CD45 （100%, 3/3） and CD123 （100%, 2/2）, whereas CD117, MPO, Lysozyme, CD68, PAX5, CD20 and CD3 were not expressed. Two of the patients were treated with combined chemotherapy and died of progression of disease at 26 and 11 months after diagnosis. Conclusions ： CD4＋/CD56＋ HN is a highly aggressive, non-myeloid and non-lymphoid hematopoietic neoplasm with distinct clinicopathologic features. Tissue involvement generally includes skin, bone marrow and lymph node. The neoplastic cells are devoid of lymphoid and myeloid lineage specific markers and should be discriminated from various types of myeloid and lymphoid neoplasms such as cutaneous lymphoma, myeloid sarcoma and acute leukemia.