原发性皮肤B细胞淋巴瘤的研究进展(一)

本文阐述原发性皮肤B细胞淋巴瘤的概念、病因、发病机制、命名、分类以及原发性皮肤滤泡中心细胞淋巴瘤的临床表现、组织病理、鉴别诊断、治疗和预后.     

原发性皮肤弥漫性大B细胞淋巴瘤（腿型）二例并文献复习

弥漫性大B细胞淋巴瘤（腿型）是皮肤B细胞淋巴瘤的一个罕见亚型，具有特征性的临床、病理、免疫组化及演变特征。本文报道2例原发性皮肤弥漫性大B细胞淋巴瘤（腿型）并复习相关文献。     

皮肤B细胞淋巴瘤的研究进展

 皮肤B细胞淋巴瘤是一组以皮肤损害为主要表现的成熟B细胞增殖性疾病，各亚型在临床表现、组织病理、免疫表型及遗传学特征具有异质性。其中原发性皮肤边缘区淋巴瘤和原发性皮肤滤泡中心淋巴瘤属于惰性淋巴瘤，原发性皮肤弥漫大B细胞淋巴瘤，腿型和血管内大B细胞淋巴瘤更具侵袭性，而EBV阳性皮肤黏膜溃疡呈惰性、自限性过程。惰性皮肤B细胞淋巴瘤首选局部治疗，侵袭性皮肤B细胞淋巴瘤首选利妥昔单抗联合化疗方案。本文从皮肤B细胞淋巴瘤的分类、临床表现、组织病理、免疫表型、遗传学特征、治疗和预后进行综述。     

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。     

成人T细胞白血病／淋巴瘤与皮肤淋巴瘤的鉴别

伴皮肤损害的成人Ｔ细胞白血病／淋巴瘤（ＡＴＬＬ）与皮肤Ｔ细胞淋巴瘤有极相似的临床病理和免疫分型，为了区别两者，对４例伴皮肤损害的ＡＴＬＬ和１８例皮肤淋巴瘤进行临床病理、免疫学分型及嗜人Ｔ淋巴细胞病毒Ｉ型（ＨＴＬＶ－Ｉ）前病毒ＤＮＡ的比较性研究，２例光线性类网织细胞增多症和２例皮肤淋巴细胞浸润症为阴性对照。结果：４例ＡＴＬＬ出现皮肤损害的同时表现系统症状如：广泛的浅淋巴结肿大，乳酸脱氢酶和白介素２受     

皮肤淋巴瘤第五讲 B细胞-皮肤淋巴样增生

阐述B细胞-皮肤淋巴样增生的命名、临床表现、组织病理、免疫组织化学染色及其与B-小淋巴细胞性淋巴瘤/慢性淋巴细胞性白血病、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等鉴别诊断和治疗。     

原发性皮肤边缘区B细胞淋巴瘤1例并文献复习

原发性皮肤边缘区B细胞淋巴瘤为原发性皮肤B细胞淋巴瘤中最常见的一种,属低度恶性淋巴瘤,国内关于该病的临床病例报道较少,该病临床上难与其他皮肤B细胞淋巴瘤及淋巴组织增殖性疾病相鉴别。现报道原发性皮肤边缘区B细胞淋巴瘤1例并对该病的相关文献进行复习。     

面部原发性皮肤弥漫性大B细胞淋巴瘤1例

原发性皮肤弥漫性大B 细胞淋巴瘤(primary cutaneous diffuselarge B-cell lymphomas,PCLBCL)是原发性皮肤淋巴瘤中比较少见的类型,被认为来源于生发中心或后生发中心,组织病理改变以中心母细胞和免疫母细胞浸润为主,见于老年患者的头、颈、躯干和四肢.国内文献报道发生于下肢的腿型PCLBCL相对多见, 而发生于头面部的PCLBCL 少见, 近期我科诊治1例,报告如下.     

系统疾病的皮肤表现

980529 成人T细胞白血病/淋巴瘤与皮肤淋巴瘤的鉴别/汪晨（北京中日友好医院）…//中华皮肤科杂志.-1997,30（4）.-237 对4例伴皮肤损害的成人T-细胞白血病/淋巴瘤（ATLL）和18例皮肤T-细胞淋巴瘤（CTCL）进行了临床病理、免疫学分型及嗜人T淋巴细胞病毒1型（HTLV-1）前病毒DNA的比较性研究,结果:4例ATLL出现皮肤损害同时有系统症状如:广泛的浅淋巴结肿大,乳酸脱氢酶和白介素2受体异常增高,外周血有花瓣样细胞和骨髓异常,其外周血、骨髓、皮肤和淋巴结的HTLV-1前病毒DNA均阳性,而18例CT-CL均阴性。2例光线性点网织细胞增多症和2例皮肤淋巴细胞浸润均为阴性对照。足资鉴别。参6 （贾泰元）     

原发性皮肤T细胞淋巴瘤

原发性皮肤T细胞淋巴瘤属结外非霍奇金淋巴瘤 ,以皮肤内辅助T细胞的单克隆扩增为特征。他与有相同组织学亚型的累及皮肤的原发性淋巴结淋巴瘤在临床及组织学特征、生物学行为及预后都明显不同。如今最常用的原发性皮肤T细胞淋巴瘤分类是EORTC分类 ,HTLV -Ⅰ可能与原发性皮肤T细胞淋巴瘤相关 ,有待进一步验证。原发性皮肤T细胞淋巴瘤有较为独特的免疫表型 ,T细胞受体基因重排检测有助于其早期诊断及疾病的转归和预防的判断     

Primary cutaneous B cell lymphoma: Clinical features,diagnosis and treatment

Primary cutaneous B cell lymphoma(PCBCL) is defined as B cell lymphomas that presents in the skin without any evidence of extra-cutaneous involvement at diagnosis. They are the second most common type of primary cutaneous lymphomas accounting for 25%-30%. Since the prognosis and treatment differ from systemic lymphomas involving the skin, differential diagnosis is very important. PCBCL is a heterogeneous group of disease comprising different B cell lymphomas with distinct treatment and prognosis. PCBCL is divided into 5 subclasses according to World Health Organization and European Organization of Research and Treatment of Cancer classification. Primary cutaneous marginal zone lymphoma and primary cutaneous follicle centerlymphoma are indolent forms and often confined to skin at presentation and during the course of the disease. But primary cutaneous diffuse large B cell lymphoma, leg type and intravascular large B cell lymphoma are more aggressive forms that may disseminate to extra-cutaneous tissues. There is not a treatment consensus since they are rare entities. Local therapies like radiotherapy, surgery or intralesional steroids are options for localized disease in indolent forms. More disseminated disease may be treated with a systemic therapy like single agent rituximab. However combination chemotherapies which are used in systemic lymphomas are also required for aggressive PCBCL. Although indolent forms have relatively better prognosis, early relapses and disseminated diseases are mostly observed in aggressive form with a consequent poor prognosis.     

Primary cutaneous B‐cell lymphoma in Nottinghamshire U.K.: prognosis of subtypes defined in the WHO‐EORTC classification

Background Primary cutaneous B‐cell lymphomas (PCBCL), with the exception of large B‐cell lymphoma of leg type and intravascular large B‐cell lymphoma, are associated with an excellent prognosis. These lymphomas have become much better understood in recent years leading to the publication in 2005 of the World Health Organization–European Organisation for Research and Treatment of Cancer classification. Objectives To determine the relative frequency of occurrence of subtypes of PCBCL in a defined population, and the survival of patients with these subtypes. Methods During the period 1987–2009, 61 consecutive patients with PCBCL were identified from the Nottingham Lymphoma Registry (population 1·1 million). After histological review, the number of patients with each subtype was as follows: marginal zone, 18; follicle centre, 14; diffuse large B cell, leg type, 16; diffuse large B cell, other sites, 12; and intravascular large B cell, one. Results The 5‐ and 10‐year lymphoma‐specific survival for patients with marginal zone lymphoma was 100%. The only patient with intravascular large B‐cell lymphoma died from widespread disease in spite of chemotherapy. The 4‐year lymphoma‐specific survival for follicle centre cell lymphoma was 90%. Patients with the other subtypes had the following 5‐year lymphoma‐specific survival rates: diffuse large B cell, leg type, 61% and diffuse large B cell, other, 40%. The median age at diagnosis for patients with diffuse large B‐cell lymphoma, leg type was 82 years and as a consequence the 5‐year overall survival was only 15%. There was a 3·4‐fold increase in the incidence of PCBCL from the period 1987–1997 to the period 1998–2009. Conclusions PCBCL is a rare disease (incidence around three per million population per year). It is, in our view, essential that it is diagnosed by a pathologist with an interest in cutaneous lymphoma and that the very different prognosis of the individual subtypes is appreciated by the treating clinician.     

Expression of the T-cell regulatory marker FOXP3 in primary cutaneous large B-cell lymphoma tumour cells

Background Primary cutaneous B‐cell lymphomas (PCBCL) are subdivided into the aggressive form, primary cutaneous diffuse large B‐cell lymphoma, leg type (PCLBCL, LT) and two subtypes of indolent behaviour (primary cutaneous follicle centre lymphoma and primary cutaneous marginal zone B‐cell lymphoma). The difference in clinical behaviour can be explained by the tumour cell itself, or the lymphoma microenvironment including the antitumour immune response. Objectives To investigate the presence of regulatory T cells (Treg), CD4+CD25+FOXP3+, in the microenvironment of PCBCL in correlation with clinical outcome. Methods Tumour specimens of 55 consecutive cases of PCBCL were blinded and analysed for FOXP3, CD4 and CD25 expression by immunohistochemistry. Confocal images were taken with a Leica SP5. Statistical analyses were performed to determine significance. The test was considered significant when P < 0·05. Results The CD4 and FOXP3 expression as well as the CD4/FOXP3 ratio were significantly increased in PCBCL of indolent behaviour in contrast to PCLBCL, LT (P = 0·0002 for CD4, P < 0·0001 for FOXP3 and P = 0·0345 for FOXP3/CD4 ratio). CD25 expression did not differ in the three groups (P = 0·9414). Within the group of patients with PCLBCL, LT we identified a subgroup with FOXP3+ tumour cells as demonstrated by CD20/FOXP3 double stainings. Patients with FOXP3+ PCLBCL, LT tumour cells showed a better prognosis on Kaplan–Meier analysis. Conclusion High numbers of Treg in the lymphoma microenvironment correlate with a better prognosis in PCBCL. In PCLBCL, LT the presence of FOXP3+ tumour cells is beneficial for prognosis suggesting that FOXP3 expression of PCLBCL, LT tumour cells might serve as a tumour suppressor.     

Primary cutaneous medium and large cell lymphomas other than mycosis fungoides. An immunohistological and follow-up study on 54 cases

Summary Primary cutaneous medium and large cell lymphomas (MLCL) other than mycosis fungoides (MF) are rare, and their prognosis and treatment are controversial. The clinical, immunohistological and follow-up data of 54 well-documented cases of primary cutaneous MLCL other than MF, seen in our institutions over a 14-year period, were retrospectively reviewed, in order to determine the prognostic factors related to these lymphomas, and to analyse the results obtained with different treatment regimens. Forty-six patients presented with a solitary tumour or with localized lesions. and eight had disseminated cutaneous lesions. According to the updated Kiel classification, 45 cases (83%) corresponded to B-cell lymphomas: centroblastic lymphomas, 32 cases; centroblastic-centrocytic lymphomas, 11 cases; immunoblastic lymphomas, two cases. Nine cases (17%) were classified as T-cell lymphomas: pleomorphic medium and large cell lymphomas, eight cases; anaplastic large cell lymphoma. one case. Four of eight patients with disseminated skin lesions had a T-cell lymphoma. whereas 41 of 46 patients with a solitary tumour had a B-cell lymphoma. Patients with disseminated skin lesions and elevated serum lactate dehydrogenase (LDH) levels had a poor prognosis. Comparison of patients' overall survival, depending on immunohistological subtype, showed that the median survival of patients with pleomorphic T-cell lymphoma was 2·5 years, whereas it was not reached at 12 years for patients with centroblastic centrocytic and centroblastic lymphoma. The eight patients with disseminated skin lesions were treated with polychemotherapy. Most patients with a solitary tumour or with localized lesions of low tumour bulk were treated by surgical excision or radiotherapy alone, and nine other patients with localized lesions of high tumour bulk were treated with initial polychemotherapy. Clinical presentation (i.e. solitary or disseminated lesions), serum LDH levels, and the immunohistological subtype, are important prognostic factors in cutaneous MLCL. Patients with disseminated skin lesions have a poor prognosis, and should be treated with intensive polychemotherapy regimens, whereas those with a solitary tumour, or with localized lesions of low tumour bulk, are adequately treated by radiotherapy.     

Die Therapie der primären kutanen B-Zell-Lymphome

BACKGROUND AND OBJECTIVE: Primary cutaneous B-cell lymphomas (PCBCL) represent a unique type of extranodal B-cell lymphomas. Recently, the "European Organization for Research and Treatment of Cancer (EORTC)-Cutaneous Lymphoma Study Group" classified PCBCL into two major groups: one with low-grade malignancy and excellent prognosis (follicle center cell lymphoma, immunocytoma/marginal zone B-cell lymphoma) and the other with intermediate malignancy and worse prognosis (large B-cell lymphoma of the leg). The clinical course and the prognosis of both groups clearly distinguish them from nodal lymphomas with similar morphological aspects, thus underlying the need for different treatment modalities. PATIENTS/METHODS: We investigated retrospectively the therapeutic data from 51 patients with PCBCL (40 low grade lymphomas, 11 large B-cell lymphomas). Several treatment modalities were used: total excision, radiotherapy, polychemotherapy, systemic corticosteroids, systemic antibiotics, as well as a variety of combination treatments. RESULTS: Recurrence, dissemination and/or death of the patients were not significantly related to any single treatment modality. CONCLUSIONS: In our opinion, the choice of treatment for PCBCL depends on the histologic classification, the number, spread and localization of the infiltrates, and on the general condition of the patient.     

Spindle B‐cell lymphoma: a rare variant of follicle center lymphoma

Primary cutaneous follicle center lymphoma (PCFCL) is a common subtype of primary cutaneous B‐cell lymphoma (PCBCL). The prognosis of this subtype is favorable and recurrence is observed in up to 50% of patients. The dissemination to lymph nodes or internal organs is rare. In this study, two cases of rare variant of PCFCL are reported. Both cases presented with multiple erythematous nodules, plaques and some annular configurations. Histopathological examination revealed dermal lymphocytic infiltrates consisting of admixed centrocytes and centroblasts. Interestingly, spindle‐shaped cells with elongated nuclei, dispersed chromatin and scant cytoplasm were also detected. Immunohistochemical analysis revealed that all cells including the spindle cells were positive for CD20 and negative for CD3, CD43, CD10, CD34, CD68 and CD138. They were also negative for desmin and S‐100. They consistently expressed nuclear bcl‐6, but did not express bcl‐2. The histopathological and immunohistochemical examination suggest a rare case of primary cutaneous spindle cell B‐cell lymphoma (PCSBCL). Although few data is published about this rare subtype, PCSBCL is recently considered as a rare subtype of PCFCL. The prognosis and the nature of this peculiar subtype are not yet cleared. This indicates a great need for more investigations.     

Solitary plaque on the scalp as a primary manifestation of Hodgkin lymphoma: a case report and review of the literature

Cutaneous Hodgkin lymphoma is infrequent and typically occurs after extensive involvement of the lymph nodes. The condition decreased significantly in incidence in the past two decades, likely owing to the new treatment protocols composed of chemotherapy, radiotherapy and stem cell transplantation. Nevertheless, recognition of this uncommon but significant disease manifestation is important from a prognostic and therapeutic perspective. We are sharing a recent case of Hodgkin lymphoma where the primary presentation appeared as a solitary plaque on the left side of the occipital scalp, clinically suspected to represent a ruptured follicular cyst. The patient underwent excisional biopsy. Histological assessment revealed Hodgkin lymphoma affecting the skin. Radiological studies showed no regional lymphadenopathy. However, two enlarged lymph nodes were identified in the mediastinum and were positron emission tomography avid. The patient underwent systemic treatment without further histopathological examination of these two lymph nodes. Not being clear if these enlarged two lymph nodes were related to his cutaneous disease or not, we cannot be sure if the patient was afflicted either by primary cutaneous Hodgkin lymphoma or by secondary cutaneous involvement because of hematogenous spread. In either case, primary or secondary cutaneous Hodgkin disease is an extreme rarity. The literature is critically reviewed.     

Clinical study of primary cutaneous B-cell lymphoma using both the European Organization for Research and Treatment of Cancer and World Health Organization classifications

Primary cutaneous B-cell lymphoma (PCBCL) is rare, with few series reported in the literature. Its classification and treatment remain controversial. Biopsy specimens of 13 patients with PCBCL were classified according to both the European Organization for Research and Treatment of Cancer (EORTC) and the new World Health Organization (WHO) classifications. Treatment and clinical outcomes were documented. Using the EORTC classification there were seven men and six women aged 32-85 years (mean = 51 years) with follicle centre cell (FCC) lymphoma (nine), immunocytoma (two) and primary cutaneous large B-cell lymphoma of the leg (PCLBCL-leg) (two). When the WHO classification was used, the nine patients with FCC were reclassified as follicle centre (five) and diffuse large B-cell lymphoma (four). Most patients had localized disease (12). Initial treatment consisted of radiotherapy alone (seven), combination chemotherapy alone (one), combined chemoradiotherapy (three) and surgery (two). Twelve patients achieved complete remission (median follow up 28 months, range 10-167 months). One patient with PCLBCL-leg died from progressive cutaneous disease. Most localized PCBCL lesions (except PCLBCL-leg) have a favourable prognosis. We recommend that clinicians be familiar with the important differences in the EORTC and WHO classifications. Further large prospective studies comparing the WHO and EORTC classifications are required to more clearly delineate the outcomes of the increasing number of patients who are classified as DLBCL by the WHO system.     

CD56+ lymphoma with skin involvement: clinicopathologic features and classification

BACKGROUND: Extranodal lymphomas expressing CD56 (neuronal cell adhesion molecule) are characterized by a high incidence of cutaneous involvement and a very aggressive clinical course. Knowledge about the prognosis and clinicopathologic features of CD56(+) lymphomas with skin involvement is very limited. OBJECTIVES: To determine survival and prognostic factors for extranodal CD56(+) lymphomas with skin involvement and to describe their clinicopathologic features. DESIGN: Retrospective literature survey and case studies. PATIENTS: A total of 181 patients with CD56(+) lymphoma involving the skin: 177 cases from the literature and 4 new cases. MAIN OUTCOME MEASURE: Survival and its dependence on the following putative prognostic factors: staging, histopathologic findings, lymphocyte markers, T-cell receptor gene rearrangement, Epstein-Barr virus infection, treatment modality. RESULTS: Three major subtypes of CD56(+) lymphoma in the skin were distinguished: blastic lymphoma, nasal-type natural killer-cell/T-cell lymphoma, and subcutaneous panniculitislike lymphoma. The disease disseminated readily, mainly to lymph nodes, bone marrow, the central nervous system, and the liver, but 45% of patients had a purely cutaneous disease at presentation. All subtypes had a very aggressive course with a median survival of 14 months. The main risk factors were age older than 55 years (hazard ratio [HR], 2.5; 95% confidence interval [CI], 1.8-3.2), systemic dissemination at presentation (HR, 2.0; 95% CI, 1.5-3.3), and lack of CD30 (HR, 3.8; 95% CI, 1.4-4.9) or CD4 expression (HR, 1.56; 95% CI, 1.06-2.57). The different treatment modalities did not improve survival. CONCLUSIONS: CD56(+) lymphomas involving the skin are rare and extremely aggressive regardless of their histologic presentation and the extent of skin involvement. No effective treatment is available. The risk of death is particularly increased in older patients with CD30(-)CD4(-) lymphomas.     

Molecular staging of lymph nodes from 60 patients with mycosis fungoides and Sézary syndrome: correlation with histopathology and outcome suggests prognostic relevance in mycosis fungoides

BACKGROUND: Histological evidence of lymph node involvement is associated with a poor prognosis in patients with cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To determine whether T-cell receptor (TCR) gene analysis is of prognostic relevance in CTCL. METHODS: TCR gene analysis was performed on lymph node specimens from 60 patients with mycosis fungoides (MF) and Sézary syndrome (SS) using a highly sensitive polymerase chain reaction (PCR)/single-strand conformational polymorphism analysis and results were correlated with skin, overall clinical and histological lymph node stages. RESULTS: The frequency with which a T-cell clone was detected in lymph node samples from patients with MF increased with skin stage, overall clinical stage and with the degree of histological involvement: six of 19 patients with uninvolved lymph nodes or limited histological involvement (LN0-2) and 13 of 14 patients with advanced histological involvement (LN3-4) had a detectable T-cell clone. In SS, 22 of 27 patients had a detectable lymph node T-cell clone. The clonal patients had a poorer prognosis than nonclonal patients (median survival from biopsy of > 72 months vs. 16 months for MF and 41.5 vs. 16.5 months for SS). Regression analysis confirmed that TCR gene analysis identifies a group of MF patients with a worse prognosis (P = 0.013). However, the molecular lymph node stage did not provide independent prognostic information in this cohort of patients in multivariate analysis. CONCLUSIONS: Molecular staging in MF and SS using a PCR-based method for TCR gene analysis provides additional information to histological examination. Specifically, this study identified a group of MF patients with early lymph node involvement with a poorer prognosis. However, a larger prospective study of patients with MF and early histological lymph node involvement is required to confirm whether molecular staging of lymph nodes provides independent prognostic information in a multivariate model.