伴全身弥漫性红斑的结外NK/T细胞淋巴瘤1例

患者女,26岁。反复出现发热、皮下结节和红斑半年,全身红斑水肿加重半月。皮肤组织病理示:表皮细胞有变性坏死,基底细胞液化变性,真皮浅层较多慢性炎症细胞浸润,皮下脂肪局部变性。鼻中甲黏膜活检示:黏膜间质淋巴细胞异型增生,核大扭曲;LCA+,CD3+,UCHL-1+,CD4-,CD8+,CD56+,TIA+,GranzymeB+。诊断:结外NK/T细胞淋巴瘤。全身弥漫性水肿性红斑,皮下结节损害是一种副肿瘤综合症的表现,对患者全面筛查有助于早期发现潜在恶性肿瘤。     

鼻部NK/T细胞淋巴瘤累及皮肤

为了探讨鼻部NK／T细胞淋巴瘤累及皮肤的临床表现、病理、免疫表型及EB病毒相关性。通过临床表现及病程，分析原发及累及部位。通过UCHL－1，CD56,多克隆CD3，CD8，CD20，TIA－1，粒酶B（GrB）等对肿瘤细胞免疫表型进行研究，EBV－EBER探针原位杂交检测肿瘤细胞阳性率分析其病因及发病。结果本例皮肤及鼻部取材组织病理表现为坏死及中等大小的异型性肿瘤细胞增生浸润，UCHL－1＋，CD56＋，CD3＋，CD8－，CD20－，TIA－1＋，granzyme B ,为NK／T细胞淋巴瘤表型。EBV瘤细胞阳性率达60％，进一步证实为鼻部NK／T细胞淋巴瘤，EBV相关性。支持鼻部NK／T细胞淋巴瘤是具有特殊免疫表型，与EB病毒有高度相关性的独立疾病，临床进展迅速，病程短，提示为高度侵袭性。     

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。     

结外鼻型NK/T细胞淋巴瘤4例及临床与病理分析

目的探讨结外鼻型NK/T细胞淋巴瘤的临床及组织病理学特点。方法分析4例患者的皮疹特点、实验室检查和组织病理等临床资料。结果4例患者中男1例,女3例,平均年龄52.5岁,皮损表现为溃疡、肿块和紫癜等,其中3例患者皮损均发生于面部,1例患者皮损发生于下颌及双下肢,组织病理检查示瘤细胞的弥漫性浸润,细胞大小不等,瘤细胞异型性明显;免疫组织化学显示瘤细胞表达CD56、CD3ε、粒酶B,EBER1/2原位杂交阳性。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,皮损临床表现、常规实验室检查亦对诊断有提示意义。     

Intravascular Cytotoxic T-Cell Lymphoma in a Young Immunocompetent Woman

Intravascular lymphoma (IVL) is a rare disorder characterized by the presence of large neoplastic lymphoid cells restricted to the lumens of small vessels with a predilection for the skin and the central nervous system. While the vast majority of cases involving IVL are of B-cell lineage, the disease rarely affects the T-cell, the histiocytes, and the natural killer cells. We report a case of intravascular T-cell lymphoma (IVTL) associated with Epstein-Barr virus (EBV). A 23-year-old healthy woman presented with tender indurated erythematous patches with overlying telangiectasia on her right breast, abdomen, both the upper and the lower extremities and the back for 3 months. The pathology revealed an infiltration of dermal and subcutaneous vessels by large and atypical lymphoid cells with immunohistochemical features of the T-cell lineage with a cytotoxic phenotype (CD3+, CD8+, granzyme B+, TIA-1+, CD4-, CD5-, CD20-, CD56-). Interestingly, the DNA extracted from the skin biopsies demonstrated evidence of a monoclonal immunoglobulin heavy chain gene rearrangement, but no T-cell receptor gene rearrangement was found. In situ hybridization study for EBV-encoded RNA was positive. She was diagnosed with an EBV-associated IVTL. The patient''s skin lesions were refractory to the combination of chemotherapy and autologous stem cell transplant, and she expired. The findings in the present case may highlight the unique clinicopathologic aspects of EBV-associated cytotoxic IVTL that occurred in a young, immunocompetent woman.     

Dermatomyositis Associated with Primary Intramuscular B Cell Lymphoma

A rare case of dermatomyositis associated with primary intramuscular malignant lymphoma is described. A 40-year-old Japanese woman noticed swelling of the right thigh during the treatment of dermatomyositis with prednisolone, azathioprine and cyclophosphamide. A biopsy specimen taken from the right quadriceps muscle revealed infiltration of lymphoma cells which were positive for CD20. We reviewed 12 cases of dermatomyositis associated with malignant lymphoma reported in Japanese literature between 1984 and 1996.     

种痘样水疱病样T细胞淋巴瘤伴发原发性皮肤CD30阳性大细胞淋巴瘤1例

患者女,17岁。全身反复起丘疹、水疱、坏死、凹陷状瘢痕伴瘙痒、发热15年,四肢起肿块2年。血清抗EBV-IgM(-),抗EBV-IgG(+)。肿块处皮损组织病理示真皮中下层和皮下组织见弥漫性致密的瘤细胞浸润,细胞核呈间变性;免疫组化示CD3(+),浸润的大细胞CD30(+),CD43(+),80%浸润细胞Ki-67(+)。水疱处皮损组织病理示表皮网状变性及多个水疱,真皮和皮下组织可见血管和附属器周围以淋巴细胞为主的、伴少量嗜酸粒细胞浸润,部分浸润细胞呈明显异形性;免疫组化示CD3(+),CD30(-),CD43(+),Ki-67(+)。诊断:种痘样水疱病样T细胞淋巴瘤伴发原发性皮肤CD30阳性大细胞淋巴瘤。确诊后建议患者转肿瘤科化疗,随访中。     

银屑病患者的自然杀伤细胞活性测定

本文用乳酸脱氢酶释放法测定了３０例银屑病患者和２８例正常人的ＮＫ细胞活性，结果发现患者的ＮＫ细胞活性明显低于正常人，而且进展期患者的ＮＫ细胞活性也明显低于稳定期患者，提示ＮＫ细胞的活性与银屑病的发生和发展有关。     

鼻型节外NK/T细胞淋巴瘤1例

患者女,46岁。双下肢相继出现红色结节及溃疡4月余,鼻部溃疡1个月。右大腿皮损组织病理示:大淋巴样细胞弥漫浸润;免疫组化染色:CD2,CD3,CD56,TIA-1,Grb和EBER均(+),CD20(-)。诊断:鼻型节外NK/T细胞淋巴瘤。     

Intravascular Lymphoma Presenting as Telangectasias: Response to Rituximab and Combination Chemotherapy

Background: Intravascular lymphoma is a rare and aggressive disease with abnormal lymphocytes confined within blood vessels. Cutaneous findings are common in the presentation of this disease. Objectives: The objectives of this article are (1) to describe a case of intravascular lymphoma treated with chemotherapy and rituximab and (2) to review the literature with respect to skin findings and outcomes of these patients after chemotherapy. Patient: Our patient had an unusual presentation of intravascular lymphoma characterized by tender, slightly indurated plaques composed of dense telangectatic vessels. Results: Our patient responded to combination chemotherapy with the addition of a partial course of rituximab (anti-CD20 monoclonal antibody). Conclusion: Intravascular lymphoma commonly presents with skin findings of tender indurated plaques and nodules. Although a number of clinical variations exist, telangectatic plaques are rarely described. Including our case, 50 patients have been reported after treatment with chemotherapy. Approximately 46% of treated patients exhibit either partial or complete response to chemotherapy. This is the first reported case of intravascular lymphoma treated successfully with the addition of rituximab. Overall, this malignancy remains an unusual and aggressive disease. Recognition of the cutaneous findings and early treatment with chemotherapy may alter the course of this disease. Rituximab may be an important addition to combination chemotherapy in treating intravascular lymphoma.

---

Antécédents: Le lymphome intravasculaire est une maladie rare et agressive qui se caractérise par la présence dans les vaisseaux sanguins de lymphocytes anormaux. Les affections cutanées sont fréquentes. Objectifs: Lobjectif de cette étude est 1) de décrire un cas de lymphome intravasculaire traité par chimiothérapie et rituximab et 2) de passer en revue la littérature médicale afin de recenser les troubles dermatologiques associés à la chimiothérapie. Méthode: Le patient présentait un cas inhabituel de lymphome intravasculaire se caractérisant par des plaques de veines télangiectasiques densesm, légèrement endurées et sensibles. Résultats: Le patient a réagi à une chimiothérapie en combinaison et au rituximab (anticorps monoclonal anti-CD20). Conclusion: Le lymphome intravasculaire sassocie souvent à des manifestations dermiques de plaques et de nodules indurés et sensibles. Bien quun nombre de variations cliniques existe, les plaques télangiectasiques sont rarement décrites. En tout, 50 patients, y compris notre cas, ont été signalés à la suite de traitements de chimiothérapie. Environ 46% des patients traités guérissent complètement ou partiellement. Il sagit du premier cas signalé de traitement réussi du lymphome intravasculaire par ajout de rituximab. Il sagit dune maladie inhabituelle et agressive. Le diagnostic dune affection dermique et la chimiothérapie précoce pourraient altérer le cours de la maladie. Le rituximab serait un important ajout à la chimiothérapie en combinaison dans le traitement du lymphome intravasculaire.

     

Treatment of Cutaneous T Cell Lymphoma

The treatment of cutaneous T cell lymphoma (CTCL), which includes mycosis fungoides and Sezary syndrome, has been in a state of continual change over recent decades, as new therapies are constantly emerging in the search for more effective treatments for the disease. However, prognosis and survival of patients with CTCL remains dependent upon overall clinical stage (stage IA-IVB) at presentation, as well as response to therapy. Past therapies have been limited by toxicity or the lack of consistently durable responses, and few treatments have been shown to actually alter survival, especially in the late stages of disease. Even aggressive chemotherapy has not been shown to improve overall survival compared to conservative sequential therapy in advanced disease, and adds the risk of immunosuppressive complications. Over the last decade, extracorporeal photopheresis has been the only single treatment that has been shown to improve survival in patients with Sezary syndrome, although its true efficacy and place in combination therapy remain unclear. Much of the focus of current research has been on combinations of skin-directed therapies and biological response modifiers, which improve response rates. The results of various trials over the years have also brought into favor the use of post-remission maintenance therapy with topical corticosteroids, topical mechlorethamine (nitrogen mustard), interferon-alpha, or phototherapy to prevent disease relapse. Recent novel developments in CTCL therapy include oral bexarotene, a retinoid X receptor-selective retinoid that has activity in all stages of CTCL, and the topical gel formulation of bexarotene, which plays a role in treating localized lesions. US Food and Drug Administration (FDA)-approved, oral systemic bexarotene has the advantage of a 48% overall response rate at a dosage of 300 mg/m(2)/day, and avoids immunosuppression and risk of central line and catheter-related infectious complications that are associated with other systemic therapies. Monitoring of triglycerides and use of concomitant lipid-lowering agents and thyroid replacement is required in most patients. Also recently FDA-approved, denileukin diftitox is the first of a novel class of fusion toxin proteins and is selective for interleukin-2R (CD25+) T cells, targeting the malignant T cell clones in CTCL. Denileukin diftitox is associated with capillary leak syndrome in 20 to 30% of patients, which may be ameliorated by hydration and corticosteroids. Higher response rates are possible by combining bexarotene with "statin" drugs and active CTCL therapies. Studies are being conducted on combining bexarotene and denileukin diftitox with other modalities. Biological response modifier therapies that are in current or future investigational trials include topical tazarotene, pegylated interferon, interleukin-2, and interleukin-12. At the forefront of systemic chemotherapy development, pegylated liposomal doxorubicin, gemcitabine, and pentostatin appear to have the greatest potential for success in CTCL therapy. Bone marrow transplantation, which is currently limited by the risk of graft-versus-host disease, offers the greatest potential for disease cure. Further developments for CTCL may include more selective immunomodulatory agents, vaccines, and monoclonal antibodies.     

A Case of Aggressive NK/T-cell Lymphoma/Leukemia with Cutaneous Involvement in Adolescence

NK/T-cell lymphoma (NKTCL) is characterized by the expression of the NK-cell antigen CD56. Non-nasal NK/T-cell lymphomas are subdivided into primary cutaneous and 4 subtypes of secondary cutaneous lymphomas; nasal type, aggressive, blastic (blastoid), and other specific NK-like cell lymphoma. Aggressive NK/T-cell lymphoma/leukemia is a rare leukemic variant of nasal type NKTCL. We herein report a rare case of aggressive NK/T-cell lymphoma/leukemia with cutaneous involvement in adolescence.     

Ki-1 Large Cell Lymphoma with Regressing Lesions in a Child

An 8-year-old boy was seen with a cutaneous Ki-1 anaplastic, large cell lymphoma with multiple lesions. Some of the lesions showed spontaneous regression. During more than seven years of disease no systemic involvement was observed, but recurrent, self-healing lesions did appear. Histopathologic examination of five lesions revealed a variety of findings, from an inflammatory infiltrate to a highly anaplastic pattern. The neoplastic cells expressed Ki-1 and leukocyte common antigens. Ultrastructurally, those cells showed ruffled indentations. The differential diagnosis includes microvillous malignant lymphoma. The patient has had a four-year follow-up without relapses.     

Oral Manifestations of Cutaneous T Cell Lymphoma

Oral manifestations of cutaneous T cell lymphoma (CTCL) have received little attention in the dermatologic literature. The authors report two patients with lingual lesions. The histologic features are similar to those of the glabrous skin. A review of the 22 previously reported cases indicate a shortened survival. A retrospective review of 82 patients with CTCL treated at the authors' medical center identified only three with oral involvement. Radiation therapy offers effective palliation for these lesions.     

Primary Cutaneous Natural Killer Cell Blastic Lymphoma

An 81 yo male presented with several asymptomatic firm 1–5 cm red purple plaques on the trunk and lower extremities associated with a mild pancytopenia. Histological examination revealed a diffuse, monotonous dermal infiltrate of atypical medium sized cells with fine chromatin and scanty cytoplasm. Immunoperoxidase staining demonstrated positivity for CD 45, CD43, CD4, Bcl‐2, and TdT; but was negative for cytokeratin, melan‐A, CD30 and hematopoietic lineage specific markers. A subsequent bone marrow aspirate demonstrated a dense population of cells that were morphologically consistent with blasts. Immunophenotyping by flow cytometry revealed lesional cells that expressed CD56, CD4, CD7, CD5, HLA‐DR and TdT. However, lineage specific markers for B‐cells (CD19, CD20, cCD79a, and CD10), T‐cells (sCD3 and cCD3), and myeloid cells (CD13, CD33, CD117, cCD13, CD14, CD41, CD61, myeloperoxidase, and alpha napthyl butyrate esterase) were not expressed. Molecular studies by PCR exhibited no evidence of T‐cell receptor or heavy chain gene rearrangements. Collectively, these findings are consistent with a primary cutaneous blastic natural killer cell lymphoma. Blastic natural killer cell lymphomas are characterized by a high incidence of cutaneous involvement and an aggressive clinical course. Our patient responded dramatically to one cycle of CHOP chemotherapy with resolution of his cutaneous tumors.     

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.     

多发性结外鼻型NK/T细胞淋巴瘤1例

患者男,60岁,藏族。全身斑块、结节及肿块6月,肿块破溃伴疼痛2月。皮损病理组织示:表皮变薄,基底层液化变性,瘤细胞在真皮及皮下脂肪层呈弥漫性浸润,瘤细胞形态不一,核深染,可见血管中心性浸润及凝固性坏死。免疫组化标记瘤细胞CD3,CD3ε,CD56,TIA-1,粒酶B均为(+),CD30约10%(+),CD8(-),CD79a(-),EBER1/2原位杂交(+)。TCR-γ重排未见明确克隆性重排条带。诊断:皮肤结外鼻型NK/T细胞淋巴瘤。