儿童皮下脂膜炎样T细胞淋巴瘤临床病理特点及其与EB病毒关系的研究

目的：研究儿童皮下脂膜炎样T细胞淋巴瘤（SPTCL）的临床和病理特点及与EB病毒感染的关系。方法：选用CD20、CD5RO．CD68．CD30、CD56、TIA—1等抗体作免疫组织化学ABC法染色；应用EBER1／2原位杂交检测EB病毒，结果：13例SPTCL占同期观察的皮肤非何杰金淋巴瘤的36．1％，其中男8例，女5例；发病年龄平均4．8岁；主要表现为下肢、躯干无症状性结节或肿块，常伴发热和肝脾肿大。组织学特点为肿瘤花皮下脂肪内呈脂膜炎样浸润，瘤细胞大小不等、形态各异，瘤内可见上皮样肉芽肿、多核巨细胞、豆袋细胞、小片坏死。免疫表型：TIA—1抗体表达12例，13例CD5RO均为阳性，CD20、CD30、CD56均为阴性；EB病毒EBER1／2原位杂交阳性率38．5％。13例中随访10例，死亡5例，其中4例合并噬血细胞综合征（HPS），4例中EBER阳性3例。结论：SPTCL在儿童皮肤非何杰金淋巴瘤中并不少见．儿童SPICL可能与EB病毒潜伏感染有一定的相关性。与EB病毒相关的SPTCL具有更大的侵袭性，常伴有HPS．预后较差。     

原发性皮肤CD30~+间变性大细胞淋巴瘤

报告1例原发性皮肤CD30~+间变性大细胞淋巴瘤(PC-ALCL)。患者女,58岁。左侧大腿暗红斑及斑块1年余,背部红斑及斑块伴溃疡3个月余。背部皮损组织病理检查:表皮部分坏死,真皮至皮下大量胞质丰富的大淋巴样细胞成片浸润,细胞核呈间变性,其间可见中性粒细胞和嗜酸性粒细胞浸润。免疫组化示大淋巴样细胞强阳性表达CD30,阳性表达CD2、CD3、CD4和多发性骨髓瘤原癌基因(MUM)-1,部分表达CD5和T细胞内抗原(TIA)-1,Ki-67阳性率95%;而不表达CD8、CD20、CD79α、CD56、EB病毒编码RNA(EBER)和间变型淋巴瘤激酶(ALK)。结合临床及组织病理改变,诊断为PC-ALCL。     

Epstein-Barr病毒感染及相关皮肤疾病

EB病毒是一种人类疱疹病毒,其原发感染多无临床症状或导致传染性单核细胞增多症。原发感染后,EB病毒终身潜伏于健康人体的B淋巴细胞。但是,部分感染者发展为慢性活动性EB病毒感染,或者出现一些EB病毒相关的恶性疾病,如Burkitt's淋巴瘤、鼻咽癌、霍奇金淋巴瘤、牛痘样水疱病样淋巴细胞增生性疾病、NK/T细胞淋巴瘤、皮下脂膜炎样T细胞淋巴瘤、血管免疫母细胞T细胞淋巴瘤。本文将详述EB病毒感染的特点、机制,并讨论EB病毒相关皮肤疾病的临床、病理特征。     

皮肤淋巴瘤第六讲非MF/SS皮肤恶性淋巴瘤及其治疗原则

阐述非蕈样肉芽肿/Sézary综合征皮肤恶性淋巴瘤包括原发性皮肤淋巴增殖性疾病(淋巴瘤样丘疹病、原发性皮肤CD30阳性大T细胞淋巴瘤)、CD30阴性皮肤大T细胞淋巴瘤、多形小/中等大T细胞淋巴瘤、皮下脂膜炎样T细胞淋巴瘤、鼻和鼻型自然杀伤/T细胞淋巴瘤以及原发性皮肤滤泡中心细胞性淋巴瘤、原发性皮肤边缘区淋巴瘤和小腿大B细胞淋巴瘤、富于T细胞的B细胞淋巴瘤与血管内大B细胞淋巴瘤的治疗。     

儿童皮下脂膜炎样T细胞淋巴瘤的研究

目的 探讨儿童皮下脂膜炎样T细胞淋巴瘤(SPTL)的临床病理、免疫表型、基因重排及EB病毒(EBV)感染情况。方法 将收集的5例儿童SPTL作临床病理和免疫组化分析,采用PCR检测TCRγ、IgH基因重排,运用EBER1/2原位杂交检测EBV感染。结果 男4例、女1例,年龄9～13岁,主要表现为无症状的结节、斑块或肿块。组织学上肿瘤在皮下脂肪内呈脂膜炎样浸润,细胞大小不等、异形性明显,瘤内可见豆袋细胞、上皮样肉芽肿和小片状坏死。瘤细胞表达T细胞标记βF1、CD2、CD3、CD8、CD45RO和细胞毒颗粒相关蛋白标记TIA-1、粒酶B,不表达CD4、CD20。4例检出单克隆性TCRγ基因重排,未检出IgH基因重排。EBER1/2原位杂交阳性2例。获随访的3例中1例死于本病,该例EBER1/2阳性。结论 儿童SPTL面部易受累,全身症状多见,噬血细胞综合征发生率与死亡率较高。伴有EBV感染者可能预后较差。     

蚊咬超敏与儿童皮肤T/NK细胞淋巴瘤

儿童发生的皮肤T/NK细胞淋巴瘤在发生前可有蚊咬超敏现象,蚊咬超敏、慢性EBV感染、T/NK细胞淋巴瘤形成一个临床三联征,称之为HMB-EBV-NK病或Tokura-Ishihara病,属于儿童EBV阳性T细胞淋巴增殖性疾病。EB病毒慢性感染是蚊咬超敏和T/NK细胞型淋巴增殖性疾病共同的病因。在慢性EB病毒感染的基础上,蚊唾液腺变应原刺激CD4阳性T细胞反应,诱导EB病毒癌基因活化,进展为儿童皮肤T/NK细胞淋巴瘤。蚊咬超敏和儿童皮肤T/NK细胞淋巴瘤是EBV阳性T细胞淋巴增殖性疾病这一疾病谱系的不同阶段。     

儿童皮下脂膜炎样T细胞淋巴瘤并发噬血细胞综合征一例

正皮下脂膜炎样T细胞淋巴瘤(subcutaneous panniculitis-like T-cell lymphoma,SPTCL)是一种原发于皮肤的外周T细胞淋巴瘤,主要累及皮下脂肪组织。本病临床少见,常伴噬血细胞综合征(hemophagocytic syndrome,HPS),预后差。笔者收治1例长期随访的皮下脂膜炎样T细胞淋巴瘤并先后两次在EB病毒感染活动期出现噬血细胞综合征的     

皮下脂膜炎样T细胞淋巴瘤研究进展

皮下脂膜炎样T细胞淋巴瘤是指主要累及皮下脂肪细胞且与脂膜炎相似的一种原发于皮肤的外周T细胞淋巴瘤。本文对其临床特点、组织病理学特点、实验室检查、组织学来源,与EB病毒感染的关系、治疗及预后、诊断及鉴别诊断综述如下。     

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。     

皮下脂膜炎样T细胞淋巴瘤的EB病毒感染和P53蛋白表达的关系

目的探讨皮下脂膜炎样T细胞淋巴瘤(SPTL)中EB病毒(EBV)的潜伏感染情况及其与P53蛋白表达的关系。方法采用EBER1/2原位杂交检测20例SPTL组织中的EBV感染;用免疫组化LSAB法检测P53蛋白表达。结果20例SPTL中5例(25%)EBER1/2原位杂交阳性,6例(30%)的P53阳性。统计学分析,二者具有相关性(r= 0.533,P<0.05)。结论部分SPTL病例伴EBV潜伏感染,伴有EBV感染的SPTL患者可能预后较差。SPTL组织中P53蛋白表达可能与EBV的感染有关。     

Unlikely role of Epstein-Barr virus in the pathogenesis of primary cutaneous CD30+ anaplastic large cell lymphoma

BACKGROUND: Primary cutaneous CD30+ anaplastic large cell lymphoma (ALCL) is a rare subset of cutaneous lymphoma, with a much better prognosis than its nodal counterpart. The pathogenesis of both nodal and primary cutaneous CD30+ ALCL is largely unknown but experimental data support the hypothesis that the Epstein-Barr virus could play a role in the nodal subset. OBJECTIVE: To evaluate the involvement of Epstein-Barr Virus (EBV) in primary cutaneous CD30+ ALCL by searching for both nucleic acids and EBV proteins in cutaneous lesions. SETTING: Two University Hospitals in Southern France (secondary referral hospitals). PATIENTS: Eight consecutive patients with typical primary cutaneous CD30+ anaplastic large cell lymphoma were studied. METHODS: Search for the presence of DNA, RNA and EBV proteins in cutaneous lesions by PCR, in situ hybridization and immunohistochemistry. RESULTS: EBV DNA and RNA was identified in only one lesion of primary cutaneous CD30+ ALCL and in none of the normal adjacent skin samples. In situ hybridization and immunohistological studies were consistently negative in all samples. Conclusion: These results do not support an early role of EBV in the oncogenetic pathogenesis of primary cutaneous CD30+ ALCL.     

Topical imiquimod as treatment for different kinds of cutaneous lymphoma

Imiquimod as a topical immune response modifier leads to a localized production of interferon and other cytokines. Apart from its use for genital warts it has therefore been used as treatment for different cutaneous neoplasms, including a few cases of cutaneous T-cell lymphoma. We treated 8 patients (4 with mycosis fungoides, 1 with CD30+ anaplastic large cell lymphoma and 3 with primary cutaneous B-cell lymphoma) with topical imiquimod. Therapy was started three times per week, in cases without response, the frequency was increased to a daily application. Two patients with mycosis fungoides and the patient with the CD30+ anaplastic large cell lymphoma had a complete clinical remission, the other two patients with mycosis fungoides did not show a response to imiquimod. Of the patients with cutaneous B-cell lymphoma, two reached a partial remission, one did not respond to therapy. Two patients had side effects such as erythema and pruritus which disappeared when the frequency of therapy was reduced. Our preliminary data show that imiquimod might be effective in some cases with therapy resistant lesions of cutaneous T-cell lymphoma as well as of cutaneous B-cell lymphoma, but more controlled studies are needed.     

Evidence for polyclonal infection of Epstein-Barr virus in a patient with primary cutaneous anaplastic large cell lymphoma

We report a case of CD30 + primary cutaneous anaplastic large cell lymphoma. The lymphoma cells were shown to express the Epstein-Barr virus (EBV)-encoded small RNAs by in situ hybridization and to have EBV genomes by PCR, whereas no monoclonal band was detected by Southern blot analysis using the EBV terminal repeat probe. These data suggested polyclonal infection by EBV, which provides evidence that EBV plays little part in the pathogenesis of this tumour even in the infected cases.     

Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathological,immunophenotypic and molecular analysis of six patients

BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma of the skin. In the World Health Organization classification of T-cell and natural killer cell lymphoma it is listed as an example of extranodal lymphoma. In practice, however, it is most likely to present to a dermatologist. OBJECTIVES: To describe the clinicopathological, immunophenotypic and molecular features of six U.K. patients with SPTCL. METHODS: The clinical, histological and immunophenotypic features were reviewed. T-cell receptor (TCR) gene analysis was performed on blood and tissue samples using polymerase chain reaction/single-strand conformational polymorphism analysis of the TCR-gamma gene using consensus primers. In situ hybridization was performed on lesional skin to detect mRNA for Epstein-Barr virus (EBV). RESULTS: All patients presented with subcutaneous nodules, plaques or ulceration, and three had systemic symptoms. All biopsies exhibited an infiltrate of medium to large pleomorphic cells involving the subcutis with characteristic rimming of fat spaces. Five showed areas of necrosis, but only one showed marked cytophagia. In three cases the neoplastic cells did not express TCR-beta. One was strongly p53 positive, and the other two were CD56 positive. Both these patients showed epidermal involvement with lichenoid changes histologically, and both developed the haemophagocytic syndrome. The other three cases were TCR-beta positive, CD8 positive and CD56 negative. All cases were positive with pan T-cell markers and also for the cytotoxic granule protein T-cell intracellular antigen-1 and granzyme B. All cases were EBV negative both by immunostaining (latent membrane protein-1) and by in situ hybridization (EBV-encoded mRNA). TCR gene analysis revealed a T-cell clone in four of five cases; two of these patients had an identical T-cell clone in the peripheral blood. The median survival was 16 months. However, two of the three TCR-beta-negative patients have died, whereas none of the TCR-beta-positive patients has died. CONCLUSIONS: This is the first series of SPTCL patients to be reported in the U.K. and the data support the view that there are two subsets of SPTCL: those derived from gammadelta T cells which carry a poor prognosis, and are usually CD56 positive, and a more indolent group derived from alphabeta T cells.     

Skin is the frequent site for involvement of peripheral T-cell and natural killer cell lymphomas in Korea

We have studied the clinicopathological features of 19 Korean cases of peripheral T-cell and natural killer (NK) cell lymphomas, not including mycosis fungoides. Primary cutaneous involvement was demonstrated in eight of these 19 cases, and we recognized four clinicopathologic subtypes among these eight patients: nasal type NK/T cell lymphoma, three cases; primary cutaneous CD30 positive anaplastic large cell lymphoma, two cases; subcutaneous panniculitis-like T-cell lymphoma, one case; lymphoma with hydroa vacciniforme-like cutaneous lesions, two cases. We did not, however, encounter any cases of HTLV-associated adult T-cell lymphoma/leukemia, which is common in Taiwan and Japan. EBV-associated lymphoma is the most prominent type of peripheral T-cell and NK cell neoplasm involving the skin in Korea.     

CD56 expression in a case of primary cutaneous CD30+ anaplastic large cell lymphoma

We describe clinicopathological features of an unusual case of CD30+/CD56+ T-cell lymphoma in a 58-year-old Korean man who presented with disseminated nodules, papules and hyperpigmented patches. Coexpression of CD30 and CD56 in T-cell lymphoma is very rare. Our patient did not respond to an intensive chemotherapy regimen, in contrast to the previously reported cases of primary cutaneous CD30+ anaplastic large cell lymphoma. Coexpression of CD56 might therefore identify a subset of CD30+ lymphomas with more aggressive features.     

Primary "cutaneous" T-cell anaplastic large cell lymphoma, CD30+, neutrophil-rich variant with subcutaneous panniculitic lesions, in a post-renal transplant patient: report of unusual case and literature review

Posttransplantation lymphoproliferative disorders (PTLD) presenting clinically in the skin are rare and usually of B-cell phenotype. Only 7 cases of cutaneous T-cell PTLD have been previously reported, mostly mycosis fungoides type, with no known cases of "cutaneous" presentation by CD30 (Ki-1) anaplastic large cell lymphoma (ALCL).The case reported is a 59-year-old male who developed multiple skin nodules on the right leg, 6 years following renal transplantation. Initial biopsy showed ALCL involving the dermis with a background rich in neutrophils. The neoplastic cells were of T-cell phenotype, strongly CD30 with typical staining, and BCL-2 positive, but P53 negative. No EBV was detected by IHC, ISH, or DNA analysis. One year later, he developed painful subcutaneous nodules with surrounding erythema, resembling deep pustules or panniculitis, which on biopsy showed preferential involvement of the subcutaneous fat and prominent component of neutrophils. Twenty-two months following diagnosis, he died of cardiac failure with terminal myocardial infarct. There was however no clinical evidence of systemic spread of the lymphoma.This report adds to the clinical and morphologic spectrum of these rare "cutaneous" lymphomas of T-cell lineage arising in the posttransplantation setting, and suggests that EBV does not play a role in their pathogenesis.     

A Case with an Indolent Course of Subcutaneous Panniculitis-Like T-Cell Lymphoma Demonstrating Epstein-Barr Virus Positivity and Simulating Dermatitis Artefacta

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of cytotoxic T-cell lymphoma. The disease has a poor prognosis in patients with the complication of hemophagocytic syndrome, especially in those with Epstein-Barr virus (EBV) positivity.A 20-year-old woman presented with multiple, itchy, purplish nodules and excoriations on both of her upper limbs. The histopathologic, immunohistochemical staining, and clonal T-cell receptor gene rearrangement examinations of skin lesions revealed the diagnosis of SPTCL. In situ hybridization performed for EBV was positive. There were no findings suggesting systemic involvement of SPTCL, or hemophagocytic syndrome. The lesions improved with systemic corticosteroid therapy and radiotherapy, with no recurrence.We present a patient with a protracted course of SPTCL in whom EBV positivity was demonstrated. This apparent conflict may be explained by geographic and ethnic variations in EBV infection. Further studies may shed light on the real relationship between EBV-RNA and the course of SPTCL.     

Human herpesvirus 8-associated lymphoma mimicking cutaneous anaplastic large T-cell lymphoma in a patient with human immunodeficiency virus infection

Primary effusion lymphoma, a human herpesvirus 8 (HHV8)-associated lymphoma, is uncommon, and it is usually seen in human immunodeficiency virus (HIV)-infected patients. It presents as a body cavity-based lymphomatous effusion, but several cases of the so-called solid primary effusion lymphoma presenting as solid tumors without associated lymphomatous effusion have been reported. They have similar clinical, histopathological and immunophenotypical features. Most of them have a B-cell genotype. This suggests the solid variant may represent a clinicopathological spectrum of primary effusion lymphoma. We report a case of HHV8-associated lymphoma histopathologically and immunophenotypically mimicking cutaneous anaplastic large cell lymphoma. The patient was a 31-year-old HIV-seropositive man presenting with skin nodules over his right thigh. Biopsy of the nodules showed anaplastic large cells infiltrating the dermis. These malignant cells strongly expressed CD3, CD30 and CD43. Cutaneous anaplastic large T-cell lymphoma was initially diagnosed, but further tests, including immunoreactivity for HHV8 protein and clonal rearrangements of immunoglobulin genes, confirmed the diagnosis of HHV8-associated B-cell lymphoma with aberrant T-cell marker expression. This case provides an example of solid primary effusion lymphoma mimicking cutaneous anaplastic large T-cell lymphoma and highlights the importance of HHV8 immunohistochemistry and molecular tests in the diagnosis of HHV8-associated lymphoma with a cutaneous presentation.