以环形红斑为初发表现的T淋巴母细胞性淋巴瘤的临床研究

目的 的降雨 例罕见的以环形红斑为初发表现的成人T淋巴母细胞性淋巴瘤。方法 对其临床,组织病理,免疫组化,分子生物学和各种特殊的实验室检查进行研究。结果 颈部,腹股沟肿大数10个淋巴结,全身百余个环形红斑,胸部CT示;前上纵隔占位性淋巴瘤表现。胸水中找到异形细胞。骨髓片示;淋巴瘤累及骨髓,外周血中未发现瘤细胞。淋巴结结构破坏,瘤细胞弥漫分布,呈“满天星”图像。部分瘤细胞浸润,部分向表皮性,可见Pautrier微脓肿,少数淋巴样细胞细胞核呈曲核型,与淋巴结的瘤细胞相似;免疫组化示：LCA,CD43,UCHL-1均阳性,TdT阴性,原位杂交示EBER1/2在淋巴结组织中呈最性;皮肤组织中呈阴性。结论 此例为首例报告罕见的以环形红斑为初发表现的T淋巴母细胞性淋巴瘤。     

皮肤恶性淋巴瘤的一些命名和概念的混乱与澄清

阐明了皮肤恶性淋巴瘤的一些命名和概念如皮肤T细胞淋巴瘤、原发性皮肤滤泡中心细胞性淋巴瘤、淋巴结滤泡性淋巴瘤（滤泡中心细胞性淋巴瘤）、血管中心性淋巴瘤、血管中心性免疫增殖性病变、原发性皮肤免疫细胞瘤的混乱与澄清。     

结外皮肤NK/T细胞淋巴瘤一例

患者，男，77岁。全身散发皮肤肿块1个月。组织病理示：表皮变薄，真皮全层大量淋巴样细胞弥漫浸润，部分区域具有亲表皮性，部分细胞胞体大,可见核分裂像。诊断：结外皮肤NK/T细胞淋巴瘤。患者确诊后转至肿瘤科，给予P-Gemox方案化疗。     

多脏器累及的亲表皮CD8~+ T细胞淋巴瘤1例

患者男,46岁,全身渗出性红斑、头皮脓肿9月。入院检查发现累及肺、肝脏,皮肤组织病理示:表皮海绵水肿,真皮弥漫淋巴细胞,异型细胞具亲表皮性,免疫组化示:LCA(+),CD8(+),TIA(+),TCR基因重排阳性,诊断:亲表皮CD8+皮肤T细胞淋巴瘤。予以2次CHOP化疗,无效死亡。本病在国内首次报道,具有独特临床病理特点,早期累及皮外,侵袭性高,无有效治疗方法,预后差。     

间变性淋巴瘤激酶阴性的间变性大细胞淋巴瘤泛发性皮肤侵犯一例

患者男,37岁,入院前7个月无明显诱因右大腿出现一鹅蛋大小肿物,无明显不适,肿物逐渐增大,右大腿、臀部出现弥漫性、非凹陷性肿胀,入院前2个月全身皮肤出现暗红色丘疹、结节、斑块,部分斑块渐出现大小不一的糜烂、溃疡。实验室检查：白蛋白降低,乳酸脱氢酶显著升高。B超示浅表淋巴结肿大、融合,彩色多普勒示淋巴结内部较丰富的树枝样血流信号。CT显示右大腿及会阴部广泛淋巴结肿大伴软组织水肿,上腹部广泛淋巴结肿大,纵膈内淋巴结肿大。皮损组织病理：真皮全层致密分布单一核细胞,部分有异形性及不典型核分裂;免疫组化：CD3、CD8、CD30（阳性细胞占80%）、CD4、CD45RＯ、粒酶B 阳性,CD56、间变性淋巴瘤激酶（ＡＬＫ）、T细胞胞质内抗原1阴性。淋巴结病理：淋巴结结构完全破坏,肿瘤弥漫成片生长,肿瘤细胞比一般的大细胞淋巴瘤瘤细胞大,胞质丰富,嗜碱性或嗜双色性,细胞核偏位,呈马蹄形、肾形或分叶状,核染色质稀疏,可见单个或多个嗜碱性小核仁;免疫组化：CD2、CD4、CD3、粒酶B、上皮膜抗原（EMA）、Ki-67、CD30阳性,CD8、CD56、T细胞胞质内抗原（TIA）-1、ＡＬＫ均为阴性。诊断：间变性淋巴瘤激酶阴性的原发系统型间变性大细胞淋巴瘤泛发性皮肤侵犯。     

原发性皮肤CD4^＋多形性小/中T细胞淋巴瘤一例

报告1例原发性皮肤CD4^＋多形性小/中T细胞淋巴瘤.患者男,19岁.全身多发暗红色斑块和小结节2年.皮损组织病理检查示,真皮内血管及附属器周围有致密小到中等大,胞质空亮,核扭曲的淋巴样细胞浸润,可见核分裂像.未见亲表皮性,但有浸润毛囊现象.免疫组化检查显示,CD3阳性、CD4阳性、CD8阴性、CD30阴性和CD20阴性,Ki-67阳性率约为25%.诊断：原发性皮肤CD4＋多形性小/中T细胞淋巴瘤.     

表现为神经淋巴瘤病的外周T细胞淋巴瘤一例

31岁男性患者,全身反复出现红斑、结节伴肢端麻木感8年。体格检查:全身皮肤散在直径1～5 cm淡红至紫红色斑片和结节。双侧颈部及腹股沟可触及数个直径1 cm的淋巴结。双手尺侧及双足深浅感觉减退,双下肢腱反射减弱。四肢肌电图检查示:获得性多灶性感觉运动神经病。PET-CT提示淋巴瘤。右肘尺神经组织病理示:弥漫增生的淋巴样细胞;免疫组化染色示:肿瘤细胞CD3、CD5、TIA-1均阳性,Ki-67约40%～70%阳性。TCR克隆性基因重排阳性。左小腿皮肤结节组织病理:表皮和真皮浅层、皮肤附属器及部分血管周围较多异形淋巴样细胞浸润;免疫组化染色示:CD3、CD5、GrB、TIA-1均阳性,Ki-67约40%阳性。诊断为:(1)非霍奇金淋巴瘤IVB期;(2)外周T细胞淋巴瘤,非特指型;(3)神经淋巴瘤病。治疗:先后采取吉西他滨+培门冬酶、DICE、CHOP、EPOCH+来那度胺、BECOP+西达苯胺等化疗方案,目前口服西达苯胺治疗,原皮损逐渐消退,但双小腿仍有新发结节,总体病程缓慢进展。     

滤泡树突状细胞肉瘤并发副肿瘤性天疱疮

报告1例滤泡树突状细胞肉瘤并发副肿瘤性天疱疮.患者男,49岁.因全身红色风团反复发作5个月、口腔黏膜疼痛性溃疡2个月、间擦部位水疱并进行性加重1个月就诊.皮肤科检查:全身散在红色风团,口腔黏膜溃疡,间擦部位水疱.皮损组织病理检查显示表皮内角质形成细胞灶性坏死、棘层松解、基底细胞液化变性.皮损直接免疫荧光显示基膜带及棘细胞间IgG沉积.患者血清以大鼠膀胱为底物间接免疫荧光显示移行上皮细胞间荧光阳性.腹部B超及CT检查示腹膜后占位性病变.手术切除肿瘤后经组织病理学及免疫组织化学证实为滤泡树突状细胞肉瘤.手术切除肿瘤20 d后患者死于呼吸衰竭.     

以皮肤浸润性斑块为首发表现的B细胞淋巴瘤1例

报告 1例皮肤B细胞淋巴瘤。患儿男 ,9岁 ,全身皮肤淡红色浸润性斑块 1月。骨穿示淋巴瘤细胞浸润性骨髓 ,组织病理示淋巴瘤性细胞浸润 ,免疫组化证实为B细胞淋巴瘤。     

胫前大疱性表皮松解症并发落叶型天疱疮1例

报告胫前大疱性表皮松解症并发落叶型天疱疮1例。患者男,64岁。全身红斑、瘙痒1年,出现松弛性水疱、糜烂、结痂5个月。患者自10岁始四肢出现瘙痒性疱疹,渐形成红色瘢痕,并持续至今。皮损组织病理检查：大疱处示棘层上部大疱,疱中有嗜酸性纤维蛋白网、大量中性粒细胞及棘层松解细胞;胫前处皮损示表皮下裂隙性水疱,较多成纤维细胞和结缔组织。间接免疫荧光检查抗表皮细胞间基质抗体（＋）,滴度为1：40。     

A Case of Paraneoplastic Pemphigus as a Preceding Manifestation of Underlying Follicular Lymphoma Treated with R-CHOP

Paraneoplastic pemphigus is a rare, life-threatening disorder associated with an underlying neoplasm, which presents with painful stomatitis and polymorphous skin lesions. Successful diagnosis of paraneoplastic pemphigus can lead to the diagnosis and treatment of the underlying malignancy. However, involvement of the respiratory system is typically unresponsive to treatment. Herein, we report the case of a 44-year-old female diagnosed with paraneoplastic pemphigus with underlying follicular lymphoma treated with a chemotherapy regimen including rituximab. Her skin lesions and underlying lymphoma responded to treatment, but bronchiolitis obliterans continued to progress and resulted in fatal respiratory failure.     

Paraneoplastic pemphigus associated with CD20-positive follicular non-Hodgkin's lymphoma treated with rituximab: a third case resistant to rituximab therapy

Paraneoplastic pemphigus is an IgG-mediated disease characterized clinically by a polymorphous blistering eruption with severe mucosal involvement associated with an underlying or occult malignancy. It is associated with high mortality, and response to treatment is generally poor. Potent immunosuppression is often necessary to control progression of the disease. Three case reports have documented successful treatment of paraneoplastic pemphigus with rituximab, an anti-CD20 monoclonal antibody. However, two previous reports have noted that rituximab was unsuccessful in halting progression of PNP. We report a third case of paraneoplastic pemphigus associated with follicular non-Hodgkin's lymphoma in which rituximab was not effective. Whether rituximab is an effective and novel treatment for paraneoplastic pemphigus remains undecided.     

Paraneoplastic pemphigus: a pustular form during chronic lymphoid leukemia]

BACKGROUND: Paraneoplastic pemphigus is an autoimmune disease of the skin and mucosa described in 1990. The condition is generally associated with lymphoma or chronic lymphoid leukemia. Lesions are often misleading, masquerading as polymorphous erythema or lichen. We report a case of paraneoplastic pemphigus with pustulous skin lesions. CASE REPORT: A 52-year-old man developed over a few weeks time erosive lesions of the oral cavity and lips associated with papulous skin lesions. Secondarily, large-sized pustules, sometimes a hypopion, were observed associated with bullae. The diagnosis of paraneoplastic pemphigus was confirmed by direct immunofluorescence that evidenced IgG deposits within the keratinocytes and along the basal membrane and by indirect immunofluorescence on rat bladder that evidenced circulating antibodies. This paraneoplastic pemphigus was the inaugural sign of chronic lymphoid leukemia. DISCUSSION: Skin lesions described in paraneoplastic pemphigus include: erosion, vesicles, bullae, and psoriasiform, lichen-like, plate-like or vegetative formations. To our knowledge, this is the first report of a pustulous form; clinically similar to Hallopeau pustulous pemphigus.     

Case of paraneoplastic pemphigus with immunoglobulin (Ig)G and IgA antibodies to various antigens

A 63‐year‐old Japanese man with non‐Hodgkin B‐cell lymphoma presented with erythematous skin lesions on his entire body, with oral, ocular and anal mucosal lesions. The patient was diagnosed with paraneoplastic pemphigus. Immunofluorescence showed both immunoglobulin (Ig)G and IgA antibodies to keratinocyte cell surfaces. Various immunoblot and enzyme‐linked immunosorbent assays showed both IgG and IgA antibodies to various autoantigens, including desmogleins, desmocollins, envoplakin, periplakin and bullous pemphigoid antigens. This was a unique case with a very rare autoantibody profile in paraneoplastic pemphigus.     

Rituximab as a dual therapeutic option for pemphigus and primary cutaneous B‐cell lymphomas: Two case reports

It is known that individuals with immune dysregulation have an increased risk of non‐Hodgkin lymphoma. This association has been proven for pemphigus as well as for other autoimmune disease. We describe the development of cutaneous B‐cell lymphoma in two patients affected by long‐standing pemphigus vulgaris and pemphigus foliaceus (i.e., characterized by histological and immunopathological features different from those of paraneoplastic pemphigus). In both cases, a therapy with rituximab allowed to achieve the complete remission for the lymphoproliferative disease (never recurred at follow up) and a substantial long‐term improvement of the clinical manifestations of pemphigus, although persistent to serological disease and occasional recurrences. We suggest that clinicians should consider that patients with long‐standing pemphigus, both vulgaris and foliaceus, may develop primary cutaneous B‐cell lymphomas, as shown in our report, and in these cases the treatment with rituximab is elective, providing a therapeutic option for both low‐grade or follicular, CD20‐positive, B‐cell non‐Hodgkin lymphomas and pemphigus. Nevertheless, as shown in our cases, a constant surveillance for pemphigus is necessary.     

Continuing Medical Education: Paraneoplastic pemphigus: a clinical,laboratorial, and therapeutic overview

Paraneoplastic pemphigus is a rare and severe autoimmune blistering disease characterized by mucocutaneous lesions associated with benign and malignant neoplasms. Diagnostic criteria include the presence of chronic mucositis and polymorphic cutaneous lesions with occult or confirmed neoplasia; histopathological analysis exhibiting intraepidermal acantholysis, necrotic keratinocytes, and vacuolar interface dermatitis; direct immunofluorescence with intercellular deposits (IgG and C3) and at the basement membrane zone (IgG); indirect immunofluorescence with intercellular deposition of IgG (substrates: monkey esophagus and simple, columnar, and transitional epithelium); and, autoreactivity to desmogleins 1 and 3, desmocollins 1, 2, and 3, desmoplakins I and II, envoplakin, periplakin, epiplakin, plectin, BP230, and a-2-macroglobulin-like protein 1. Neoplasias frequently related to paraneoplastic pemphigus include chronic lymphocytic leukemia, non-Hodgkin lymphoma, carcinomas, Castleman disease, thymoma, and others. Currently, there is no standardized treatment for paraneoplastic pemphigus. Systemic corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine, rituximab, cyclophosphamide, plasmapheresis, and intravenous immunoglobulin have been used, with variable outcomes. Reported survival rates in 1, 2, and 5 years are 49%, 41%, and 38%, respectively.     

Paraneoplastic pemphigus: a subset of patients with pemphigus and neoplasia

We reviewed the clinical, histologic, and immunofluorescence features of 20 patients with pemphigus and neoplasia and compared them will a control group of 17 patients with pemphigus without neoplasia. Patients with neoplasia were divided according to clinical, histologic, and immunofluorescence findings into those with paraneoplastic pemphigus syndrome (12 patients) and those with classic pemphigus vulgaris or pemphigus foliaceus with neoplasia (8 patients). The histologic findings in patients with paraneoplastic pemphigus included acantholysis, interface dermatitis, spongiosis, and satellite keratinocyte necrosis. Histologic findings in the 8 patients with classic pemphigus and neoplasia included acantholysis and spongiosis. Direct immunofluorescence in both paraneoplastic pemphigus and pemphigus with neoplasia showed IgG staining of cell-surface proteins (intercellular substance) and deposition of immunoglobulin at the basement membrane one. Indirect immunofluorescence with rat bladder substrate was used to differentiate paraneoplastic pemphigus from classic pemphigus. Circulating IgG anti-cell-surface protein antibodies were detected in 4 patients with paraneoplastic pemphigus syndrome; they were absent in 2 patients with pemphigus and neoplasia. Immunoprecipitation of sera from the 4 patients with epithelial staining showed the complex of bands identified in studies of paraneoplastic pemphigus syndrome. We conclude that paraneoplastic pemphigus syndrome has distinct clinical, histologic, and immunologic features that differentiate it from classic pemphigus with underlying neoplasia.     

副肿瘤性天疱疮1例

报告1例副肿瘤性天疱疮。患者女性，48岁，因多形皮肤粘膜损害1月伴发非霍奇金淋巴瘤2年余入院。皮肤病理活检示棘刺松解性大疱，直接免疫荧光棘细胞间及基底膜区免疫反应物沉积。其免疫组化示T细胞侵入表皮现象。     

Paraneoplastic pemphigus presenting as erythrodermic lichenoid dermatitis with concomitant features of pemphigus foliaceus

We describe a patient with paraneoplastic pemphigus who presented with erythrodermic lichenoid dermatitis, later developing blisters of pemphigus foliaceus type and oral erosive lesions. In addition to antibodies against the plakin family proteins, the patient's serum was positive for anti-desmoglein 1 antibodies without coexisting anti-desmoglein 3 activities by enzyme-linked immunosorbent assay, which is a very rare autoantibody profile in paraneoplastic pemphigus.     

Paraneoplastic pemphigus associated with Castleman tumor: a commonly reported subtype of paraneoplastic pemphigus in China

BACKGROUND: Castleman tumor, a rare lymphoproliferative disorder, is one of the associated tumors in paraneoplastic pemphigus. We analyzed the characteristics of a group of patients with Castleman tumor to clearly understand and to improve the prognosis of the disease. OBSERVATIONS: Ten cases of paraneoplastic pemphigus associated with Castleman tumor treated in the Department of Dermatology, Peking University First Hospital, Beijing, China, from May 1, 1999, to March 31, 2004, were analyzed for clinical aspects, characteristics and histologic features of the tumors, and computed tomographic findings. Literature was reviewed and data were compared with our cases. Castleman tumor was a frequently reported neoplasm in association with paraneoplastic pemphigus in China. The disease was found to be caused by an autoimmune reaction originating from the B lymphocytes in the Castleman tumor. CONCLUSIONS: Castleman tumor in association with paraneoplastic pemphigus is a commonly reported subtype of paraneoplastic pemphigus in China. Early detection and removal of the Castleman tumor are crucial for the treatment of this tumor-associated autoimmune disease.