以皮肤损害为首发表现的结外鼻型NK/T细胞淋巴瘤1例及文献复习

目的:报道1例皮肤结外鼻型NK/T细胞淋巴瘤,分析其临床表现、组织病理特点及治疗和预后,以提高皮肤科临床医生对本病的诊治水平.方法:通过临床表现、组织病理分析,结合免疫组化染色、EB病毒原位杂交确诊.结果:颈后皮损组织病理示真皮浅中层血管附属器周围几大灶淋巴样细胞浸润,细胞核大,胞浆透明,异型性明显.瘤细胞表达CD2、CD3、CD5、CD7、CD8、GranzymeB、Ki-67,而不表达CD56,EB病毒( + ).诊断为皮肤的结外鼻型NK/T细胞淋巴瘤.结论:结外鼻型NK/T细胞淋巴瘤具有独特的组织病理及免疫组化特征,恶性度高、易误诊、预后差.     

皮肤的结外鼻型NK/T细胞淋巴瘤1例

对1例皮肤的结外鼻型NK/T细胞淋巴瘤临床病理结合免疫组化染色、EB病毒原位杂交及T细胞受体基因重排进行分析.右胫后多发结节,组织病理特征为肿瘤组织在真皮及皮下组织内弥漫性浸润,肿瘤组织具有血管中心性及血管破坏性特点,肿瘤细胞具有异型性.瘤细胞表达CD2,CD56,颗粒酶B,EBER阳性,未检测到TCR克隆性基因重排.诊断为皮肤的结外鼻型NK/T细胞淋巴瘤.皮肤的结外鼻型NK/T细胞淋巴瘤恶性度高、预后差;诊断有赖于组织病理及免疫表型检测及EBER原位杂交技术.     

皮肤的结外鼻型NK/T细胞淋巴瘤1例及文献复习

目的报道1例皮肤结外鼻型NK/T细胞淋巴瘤,以引起临床和病理医师对此病的关注。方法通过临床病理分析结合免疫组化染色、EB病毒原位杂交及T细胞受体基因重排的PCR检测分析确诊。结果左膝内后方皮损初次活检诊断为结节性脂膜炎,1个月内再次活检示真皮和皮下脂肪内肿瘤大片坏死,瘤细胞异型性明显,血管中心性浸润和血管坏死。瘤细胞表达CD2,CD8,CD45RO,CD56,TIA-1,GranzymeB和LMP-1,EB病毒(+);未检测到TCR-γ的克隆性基因重排。诊断为皮肤的结外鼻型NK/T细胞淋巴瘤。结论皮肤的结外鼻型NK/T细胞淋巴瘤恶性度高、易误诊、预后差;诊断有赖于常规组织病理结合分子病理技术。     

CD56^＋皮肤淋巴瘤

CD56+皮肤淋巴瘤(CL)是以肿瘤细胞表达CD56分子为特征的一组CL,主要包括结外NK/T细胞淋巴瘤,鼻型、母细胞性天然杀伤(NK)细胞淋巴瘤、CD56+急性髓系白血病,一些皮肤T细胞淋巴瘤也可共表达CD56.CD56+CL多具有极高的侵袭性.     

皮肤结外鼻型NK/T细胞淋巴瘤1例

鼻型NK/T细胞淋巴瘤大部分来源于NK细胞,部分病例来源于NK样T细胞.2001年淋巴造血系统肿瘤新WHO分类已将其命名为"结外NK/T细胞淋巴瘤,鼻型(extranodal NK/T-cell, nasal type)".1以往曾称为中线恶性网织细胞增生症或致死性中线肉芽肿等.主要发生于结外,是指原发于皮肤、呼吸道或消化道以外的NK/T细胞淋巴瘤,以区别于原发于鼻部的鼻NK/T细胞淋巴瘤,占全部恶性淋巴瘤的2%～10%.     

累及皮肤的结外鼻型NK/T细胞淋巴瘤

报告1例累及皮肤的结外鼻型NK/T细胞淋巴瘤.患者男,72岁.确诊结外鼻型NK/T细胞淋巴瘤8年后,鼻根部出现红肿、破溃.根据皮损、组织病理检查和免疫组化染色结果确诊.     

结外鼻型NK/T细胞淋巴瘤

报告1例结外鼻型NK/T细胞淋巴瘤.患者女,67岁.面部反复出现红斑、肿胀10年,头痛1周.体格检查T 37.6℃,左额部大片暗红色浸润性斑块,表面光滑,无鳞屑,有结痂脱落痕迹.斑块边界欠清,鼻根部肿胀.鼻腔内有较多痂皮及脓性分泌物,左鼻腔内充满坏死组织及新生物.免疫组化染色LCA、CD2、CD3、D45RO、CD56、粒酶B均( ).CD4、CD8、CD20均(-).组织病理诊断结外鼻型NK/T细胞淋巴瘤.     

结外NK/T细胞淋巴瘤2例并文献复习

例1男,65岁,确诊并治疗NK/T细胞淋巴瘤后1年,皮肤受侵。例2女,25岁,起初为局部病变,后广泛播散。2例组织病理表现均为血管中心性浸润及血管破坏,无亲表皮现象。免疫组化选择性表达CD3ε,CD56,CD3,ki-67和粒酶B。原位杂交EBER均(+),CD20(-)。诊断:结外NK/T细胞淋巴瘤。     

皮肤NK/T细胞淋巴瘤的临床病理及其与EB病毒关系的研究

目的探讨皮肤 NK/T细胞淋巴瘤的临床病理特点、免疫表型及与 EB病毒感染的关系。方法应用免疫组织化学染色,选用 CD45RO、 CD3ε、 TIA－ 1、 CD20、 Ki－ B5、 CD68和 LMP1等抗体;用 EBER1/2原位杂交检测 EB病毒编码的小分子 RNA。结果 5例皮肤 NK/T细胞淋巴瘤患者占同期皮肤恶性淋巴瘤的 5.68％;男 4例,女 1例,平均年龄 34岁,主要表现为皮肤无症状肿块, 2例有溃疡形成;组织学特征为肿瘤在真皮和皮下脂肪内,易形成血管浸润性和破坏性病变,瘤细胞大小、形态各异;瘤细胞表达 T细胞标记（ 5/5）和 NK细胞或细胞毒性 T细胞标记 TIA－ 1（ 4/4）, EBER1/2（ 3/4）。结论皮肤 NK/T细胞淋巴瘤具有临床病理独特性,与 EB病毒感染有较强的相关性。     

EB病毒感染相关性皮肤淋巴瘤

Epstein-BarrVirus（EBV）正常成年人群感染率达95%以上,其可以感染B细胞、T细胞、NK细胞以及上皮细胞,分为潜伏感染和增殖感染。EBV相关性皮肤病有NK/T细胞淋巴瘤,皮下脂膜炎样T细胞淋巴瘤,慢性活动性EB病毒感染,种痘样水疱病,种痘样皮肤T细胞淋巴瘤,蚊虫叮咬过敏症,传染性单核细胞增多症等,特别是鼻/鼻型结外NK/T细胞淋巴瘤、皮下脂膜炎样T细胞淋巴瘤和种痘样皮肤T细胞淋巴瘤较为严重,治疗效果不佳,死亡率高。     

Cutaneous peripheral T-cell lymphoma of cytotoxic phenotype mimicking extranodal NK/T-cell lymphoma

Cutaneous peripheral T-cell lymphoma unspecified is a rare neoplasm that is infrequently associated with Epstein-Barr virus (EBV) infection. In contrast, extranodal natural killer (NK)/T-cell lymphoma, although also rare, is known to be strongly associated with EBV and occurs most commonly in the nasal region. We report the case of a 55-year-old male who presented with fever and an indurated cutaneous plaque with ulceration. This cutaneous neoplasm showed diffuse dermal lymphomatous infiltration and tumor necrosis, with neoplastic cells expressing CD2, cytoplasmic CD3 (CD3ε), CD8, CD16, CD30, T-cell intracellular antigen-1, and granzyme B but not CD56, BF1, or T-cell receptor (TCR) δ1. Furthermore, the tumor cells were noted to be diffusely positive for EBV by in situ hybridization. A monoclonal TCR gene rearrangement was demonstrated. The disease showed an aggressive clinical course, and the patient died within 3 weeks of diagnosis without complete staging or chemotherapy. According to the 2005 World Health Organization/European Organization for Research and Treatment of Cancer scheme for cutaneous lymphoma and the 2008 WHO classification for lymphoid neoplasms, our case would have been classified as a nasal type extranodal NK/T-cell lymphoma with T-cell lineage. However, the expressions of CD8 and CD16, in addition to a monoclonal TCR gene rearrangement, are unusual findings in NK/T-cell lymphoma, and we believe such a phenotype/genotype should be more appropriately classified as an EBV-positive peripheral T-cell lymphoma, unspecified with a cytotoxic phenotype. Detailed clinicopathologic and molecular studies of similar cases may shed light on the prognostic impact of NK vs. T-cell lineage on extranodal NK/T-cell lymphomas.     

原发皮肤结外NK/T细胞淋巴瘤一例并文献复习

报道1例原发皮肤结外NK/T细胞淋巴瘤,并复习文献。患者,女,42岁。全身皮肤瘀斑、皮下结节20余天,发热4 d。右股内侧皮损组织病理示:大量淋巴细胞及浆细胞呈弥漫性浸润。免疫组化结果:CD3、CD43、CD56、颗粒酶B(Granzyme B,GгB)、细胞毒性蛋白(TIA)-1均(+)、Ki-67 LI约60%阳性;原位杂交EBER(+)。本病恶性程度高,需尽早进行组织病理检查及免疫组化染色以帮助诊断。     

Rearranged T-cell receptor gene and positive Epstein-Barr virus-encoded nuclear RNA in an extranodal NK/T-cell lymphoma with cutaneous manifestation only: case study

Natural killer (NK)/cytotoxic T-cell lymphoma, a new type of cutaneous neoplasm, has been described recently in the World Health Organization/European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas. We report an 11-year-old boy who had had erythematous plaques and blisters on his face and hands for 4 years and infiltrating plaques and necrosis on his extremities for 4 months. Routine clinical and laboratory examinations found no primary nasal involvement. Biopsies taken from nasal mucosa and skin showed that the tumour only involved dermis and subcutaneous tissue, and the infiltrated lymphohistiocytic tumour cells were CD56+, TIA+, CD45RO+ and CD30+. In situ hybridization for EBV-encoded nuclear RNA was positive. Clonal T-cell receptor-gamma2 gene rearrangement was positive. A diagnosis of extranodal NK/T-cell lymphoma, nasal type, was made. This is a rare case, with slow course and survival for >51 months with the presentation only occurring in the skin.     

Cutaneous natural killer/T-cell lymphoma

Lymphomas are classified as either Hodgkin's or non-Hodgkin's. The 2 subtypes of non-Hodgkin's lymphoma that can present primarily in the skin are cutaneous T-cell lymphoma and cutaneous B-cell lymphoma, both of which tend to be low-grade malignant neoplasms. Recently another distinct subtype of lymphoma was discovered, the natural killer (NK)/T-cell lymphoma, which can involve the skin in a primary or secondary fashion. The NK/T-cell subtype of lymphoma is characterized by the expression of the NK-cell antigen CD56. These CD56(+) lymphomas are further subdivided into nasal NK/T-cell lymphomas that commonly present as midfacial destructive disease and non-nasal NK/T-cell lymphomas that often arise in extranodal locations, including the skin. We report a case of aggressive NK-cell leukemia/lymphoma with numerous secondary cutaneous lesions and review the clinical and histopathologic spectrum of non-nasal CD56(+) lymphomas, with an emphasis on the dermatologic findings.     

Blastic natural killer cell and extranodal natural killer cell-like T-cell lymphoma presenting in the skin: report of six cases from the UK

BACKGROUND: Some lymphomas express natural killer (NK)-cell markers such as the neural cell adhesion molecule, which is recognized by the CD56 antibody. These lymphomas may present in the skin, but do not represent a homogeneous group. The new World Health Organization classification of lymphoma/leukaemia recognizes several types of NK/T-cell neoplasm, including blastic NK-cell lymphoma, which characteristically presents with cutaneous lesions. OBJECTIVES: To describe the clinical, pathological and molecular features in six cases of CD56+ lymphoma with cutaneous presentation. METHODS: The clinical, histopathological and immunophenotypic features of six patients were reviewed. In addition, in situ hybridization (ISH) to identify Epstein-Barr virus (EBV) mRNA, and polymerase chain reaction analysis to identify the presence of a clonal population of T cells or B cells were performed on lesional skin. RESULTS: All patients presented with widespread nodules and plaques, which in five cases were a characteristic purple colour. Four patients developed disseminated disease, three with neurological involvement. These four patients died between 14 and 46 months following diagnosis (median 30 months). In four of six cases the histopathological and immunohistological features were in keeping with a blastic NK-cell lymphoma. No clonal immunoglobulin heavy chain (IgH) or T-cell receptor (TCR) gene rearrangement was detected in the four cases consistent with an origin from NK cells. A further case fitted the criteria for an extranodal NK/T-cell lymphoma of nasal type and was also the only case to show evidence of EBV mRNA by ISH. A clonal T-cell population was identified in the final case. This patient also exhibited molecular evidence of a clonal B-cell population and a t(14;18) translocation confirmed by sequence analysis. CONCLUSIONS: Our data confirm that NK-cell lymphomas presenting in the skin are a heterogeneous group, and that in the U.K., blastic NK-cell lymphoma is more common than extranodal NK/T-cell lymphoma of nasal type. These lymphomas pursue an aggressive course, with rapid development of disseminated disease, and resistance to chemotherapy. Detailed immunophenotyping is needed to distinguish the different types. Our molecular data indicate that blastic NK-cell lymphoma cases lack clonal TCR/IgH gene rearrangements consistent with an NK-cell origin. Our ISH findings indicate that EBV plays a pathogenetic role only in extranodal NK/T-cell lymphoma of nasal type.     

原发皮肤的儿童结外NK/T细胞淋巴瘤-鼻外型1例及文献复习

目的报道1例原发皮肤的儿童结外NK/T细胞淋巴瘤,鼻外型,并回顾文献,学习该病的临床特征、组织病理、免疫组化及治疗预后特点,以提高临床医生对该病的认识。方法分析本例原发皮肤的儿童结外NK/T细胞淋巴瘤-鼻外型患者的临床表现、辅助检查、病理组化及治疗预后,并复习近年国内外相关文献。结果 11岁男性患儿表现为皮肤结节、斑块伴乏力,肝脾淋巴结明显肿大。实验室检查示白细胞和血小板降低,肝酶升高,乳酸脱氢酶升高,凝血时间延长,血液EBV-PCR高度复制。组织病理提示局部或弥漫大小不一淋巴细胞浸润,可见核碎裂,部分细胞核大深染。免疫组化:CD3(+)、CD20(-)、CD56(+++)、颗粒酶B(+)、T细胞胞浆内抗原-1(+)、Ki-67约30%~40%(+);EB病毒编码RNA原位杂交(+++)。诊断:原发皮肤的结外NK/T细胞淋巴瘤,鼻外型。告知病情后家属放弃治疗。结论不同于鼻型,本病的临床表现特异性不高,易误诊为脂膜炎等,多合并系统受累,确诊依靠组织病理、免疫组化、EBV病原学检验及结合临床表现。尽管采用强势化疗,本病仍预后不良。     

Nasal type natural killer/T-cell lymphoma with subcutaneous panniculitis-like involvement: Association with a poor prognosis

We report the case of a 23-year-old Japanese man with nasal type natural killer (NK)/T-cell lymphoma and subcutaneous panniculitis-like involvement in the skin. The neoplastic cells possessed the following characteristics of NK cells: expression of cytoplasmic CD3ϵ, CD56, T-cell intracellular antigen-1, azurophilic granules in the cytoplasm, Epstein-Barr virus-encoded small nuclear RNA, and germline configurations of T-cell receptor-β and immunoglobulin heavy chain J genes in the involved tissue. Despite multiple courses of several chemotherapeutic regimens, the cutaneous lesions as well as his general condition deteriorated, and he died of subarachnoidal bleeding. We gathered 14 available reported cases of NK/T-cell lymphoma with subcutaneous panniculitis-like involvement and reviewed the 15 cases, including our patient. They were all of Asian descent. Of the 15 patients (5 men, 10 women), the mean age was 47 years (range, 22-77 years). They had frequent common systemic symptoms: hepatosplenomegaly, weight loss, general weakness, and arthralgia. Twelve of the 15 patients died of disease. The mean duration from diagnosis to death was 9.5 months. NK/T-cell lymphoma with subcutaneous panniculitis-like involvement is associated with a poor prognosis.     

Rimming of adipocytes by neoplastic lymphocytes: a histopathologic feature not restricted to subcutaneous T-cell lymphoma

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma of the skin presenting with histopathologic features simulating those of a lobular panniculitis. The presence of neoplastic T-lymphocytes forming a rim around the individual fat cells in the subcutaneous lobules, so-called "rimming" of adipocytes, is considered a characteristic morphologic feature of this type of cutaneous lymphoma. In this study we reviewed a series of 45 biopsy specimens of primary and secondary cutaneous B- and T-cell lymphomas and one of myeloid leukemia involving the subcutaneous tissues and showing rimming of adipocytes (subcutaneous panniculitis-like T-cell lymphoma: n = 16; mycosis fungoides, tumor stage: n = 3; aggressive epidermotropic CD8(+) T-cell lymphoma: n = 2; cutaneous gamma/delta T-cell lymphoma: n = 4; extranodal NK/T-cell lymphoma, nasal type: n = 4; cutaneous medium-large pleomorphic T-cell lymphoma, NOS: n = 5; CD4(+)/CD56(+) hematodermic neoplasm (blastic NK-cell lymphoma): n = 7; secondary cutaneous large B-cell lymphoma: n = 3; secondary cutaneous lymphoplasmacytic lymphoma: n = 1; specific cutaneous manifestations of acute myelogenous leukemia: n = 1). We could demonstrate that rimming of adipocytes by neoplastic cells can be recognized not only in subcutaneous panniculitis-like T-cell lymphoma, but also in several different entities of malignant lymphoma with skin involvement. Precise classification of cases with prominent involvement of the subcutaneous tissues can only be achieved upon precise correlation of clinicopathologic and phenotypic features. Rimming of adipocytes should not be considered specific of subcutaneous panniculitis-like T-cell lymphoma.     

牛痘样水疱病样皮肤淋巴瘤与慢性活动性EB病毒感染的关系

目的 报道6例牛痘样水疱病样皮肤淋巴瘤,并研究其与慢性活动性EB病毒感染的关系.方法 临床病理分析、皮损免疫组织化学染色、血清学分析、EB病毒编码RNA原位杂交、外周血EB病毒DNA测定.结果 6例患者皮损均为反复发作的丘疹、丘疱疹、坏死、痘疮样瘢痕,其中4例还伴有程度不同的颜面、手足水肿.所有患儿均有长期间断发热等症状.皮损病理可见表皮多房性水疱,真皮全层大量淋巴细胞浸润,细胞形态异形,可见病理分裂象.4例皮损病理免疫组化染色,可见大量CD56阳性细胞,散在的CD3和CD45RO阳性细胞,T细胞内抗原-1和粒酶B染色阳性,诊断为牛痘样水疱病样皮肤NK/T细胞淋巴瘤;2例组化染色CD3和CD45RO阳性,CD56阴性,诊断为牛痘样水疱病样皮肤T细胞淋巴瘤.6例皮损均可见EB病毒编码RNA原位杂交阳性肿瘤细胞,血清学检查EB病毒衣壳抗原IgG抗体滴度升高,其中2例滴度为1:5120,2例为1:2560,2例为1:1280;2例患者外周血EB病毒DNA拷贝数高于正常.6例患儿均证实患有慢性活动性EB病毒感染.结论 牛痘样水疱病样皮肤淋巴瘤主要表现为颜面手足肿胀、水疱、痘疮样瘢痕,病理表现主要为真皮异形淋巴细胞浸润和血管中心坏死,免疫表型以NK/T型多见.慢性活动性EB病毒感染与该型淋巴瘤发病密切相关.