皮肤淋巴瘤分类的进展

世界卫生组织(WHO)淋巴瘤分类工作组和欧洲癌症研究与治疗组织(Eoropean Organization for Researchand Treatment of Cancer,EORTC)为获得一个临床医生与病理医生都能接受、对临床医疗和病理诊断都有指导价值的皮肤淋巴瘤分类方案,结合各自的经验和研究成果,将2001年WHO淋巴造血组织肿瘤的病理学和遗传学分类1与EORTC关于原发性皮肤淋巴瘤的分类相结合,于2005年推出了WHO-EORTC皮肤淋巴瘤分类2。2006年WHO皮肤肿瘤病理学和遗传学分类3直接引入了WHO-EORTC皮肤淋巴瘤分类,个别内容稍有补充。新的分类,有助于深入了解皮肤淋…     

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     

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。     

TCR基因重排在皮肤T细胞淋巴瘤中的应用

T细胞在成熟过程中通过T细胞表面受体基因重排,从而具有特异性识别抗原的能力,在这一过程中的任何失调都会导致疾病。皮肤T细胞淋巴瘤是由于单个淋巴细胞的恶性增殖所导致的,病变组织表现出T细胞受体基因重排克隆性。蕈样肉样肿和Sézary综合征为最常见的皮肤T细胞淋巴瘤。T细胞受体基因重排的检测在皮肤T细胞淋巴瘤的发病机制研究、分类、诊断、判断预后上有重要的作用。     

淋巴瘤样丘疹病1例

2005年,世界卫生组织(WHO)与欧洲癌症研究治疗组织(EORTC)共同推出的皮肤淋巴瘤的分类,将淋巴瘤样丘疹病归类于原发性皮肤CD30+淋巴增殖性疾病.该病免疫表型主要表现为CD3+,CD4+,CD8-,CD30+.现报道免疫表型为CD3+,CD4-,CD8+,CD30+的淋巴瘤样丘疹病1例如下.     

皮肤假性淋巴瘤石蜡包埋组织克隆性基因重排检测

皮肤假性淋巴瘤系指在组织学上类似皮肤恶性淋巴瘤,而临床表现为良性生物学行为,不完全符合皮肤淋巴瘤的诊断标准.区分淋巴细胞的良性反应性增生和恶性增生(淋巴瘤)一直是临床病理诊断的难题^[1].淋巴细胞成熟过程中免疫球蛋白和T细胞受体基因重排,为检测淋巴细胞的克隆性增生提供了理论基础^[2].     

原发性皮肤大B细胞淋巴瘤的研究进展

阐述原发性皮肤大B细胞淋巴瘤的分类、原发性皮肤富于T细胞的B细胞淋巴瘤、血管内大B细胞淋巴瘤和B-免疫母细胞性淋巴瘤的临床表现、组织病理变化、免疫组化、基因重排与诊断和鉴别诊断，以及皮肤大B细胞淋巴瘤的形态学变异的研究进展。     

原发性皮肤间变性大细胞淋巴瘤T细胞γ受体、IgH基因重排

目的：探讨原发性皮肤间变性大细胞淋巴瘤(C-ALCL)临床病理特点和基因诊断方法。方法：对6例C-ALCL的临床表现、病理形态学和免疫组化染色进行观察,并用PCR方法对石蜡标本进行T细胞γ受体(TCRγ)和重链免疫球蛋白(1gH)基因重排检测。结果：临床起病以孤立性结节多见,病情进展缓慢,个别可自行消退。5例患者经治疗病情稳定,1例死于淋巴结及肝脏转移。镜下以75％以上CD30^ 间变性大细胞弥漫浸润真皮及皮下脂肪组织为特点,多数瘤细胞表达T细胞免疫表型。5例标本TCRγ基因重排阳性。结论：C-ALCL是少见的原发皮肤的低度恶性T细胞性淋巴瘤,预后较好。综合临床表现、组织病理改变、免疫组化及基因重排检测有助于本病的正确诊断。     

皮肤淋巴瘤的现状与展望

皮肤淋巴瘤是指原发于皮肤的具明显异质性的淋巴增殖性疾病.病因及发病机制不明,可能为一种多因子作用于具有遗传缺陷的淋巴细胞诱发的累加效应和逐渐发展的过程.皮肤淋巴瘤的分类和分期需以阐明组织起源、判定生物行为并指导临床治疗为目的,经过不断完善后,现已形成最新的WHO/EORTC分类系统.尽管分子病理学对某些皮肤淋巴瘤的早期诊断和生物行为判断具有重要价值,但皮肤淋巴瘤的确定诊断,还需要结合临床、组织病理、免疫表型和分子特征等的综合资料.皮肤淋巴瘤的标准化治疗方案可能难以统一,治疗方法的选择需以分期为基础,各种新的实验性生物学治疗方法正不断应用于临床.     

淋巴瘤样丘疹病1例

2005年,世界卫生组织（WHO）与欧洲癌症研究治疗组织（EORTC）共同推出的皮肤淋巴瘤的分类,将淋巴瘤样丘疹病归类于原发性皮肤CD30＋淋巴增殖性疾病.该病免疫表型主要表现为CD3＋,CD4＋,CD8-,CD30＋.现报道免疫表型为CD3＋,CD4-,CD8＋,CD30＋的淋巴瘤样丘疹病1例如下.     

World Health Organization classification of hematopoietic and lymphoid tissues: implications for dermatology

The new World Health Organization (WHO) classification of hematopoietic and lymphoid malignancy represents the first worldwide consensus document on the classification of lymphoma/leukemia. Its aim is to supercede all existing classification systems, including the Revised European American Classification (REAL), and the organ-based classification of cutaneous lymphoma proposed in 1997 by the European Organization for Research and Treatment of Cancer (EORTC) cutaneous lymphoma project group. This article compares the REAL, EORTC, and WHO classifications with particular reference to cutaneous lymphoma. It identifies those entities that have been adopted from the EORTC classification, and illustrates important new entities in the category of cytotoxic T-/NK-cell lymphomas that characteristically present in the skin or subcutaneous tissue. However, WHO is not an organ-based classification and some categories (eg follicular B-cell lymphoma and peripheral T-cell lymphoma) include both cutaneous and systemic diseases, and these may have very different prognoses. It is, therefore, important that cancer registries are capable of recording sites of involvement for both B- and T-cell lymphomas so that the incidence and prognosis of cutaneous lymphomas can be established from national data sets in future years.     

Non‐mycosis fungoides cutaneous T‐cell lymphoma: reclassification according to the WHO‐EORTC classification

Background: Non‐mycosis fungoides (non‐MF) primary cutaneous T‐cell lymphomas (PCTCL) are heterogeneous and divided into subgroups by the World Health Organization‐European Organization for Research and Treatment of Cancer (WHO‐EORTC) classification of cutaneous lymphomas. We report the first North American series to examine the applicability of the classification, compare our findings with the predominant European literature and confirm the significance of separation into the indolent and aggressive groups. Methods: Forty‐four non‐MF PCTCL cases with available tissue for phenotyping, adequate clinical staging information and follow‐up were reclassified according to the WHO‐EORTC classification. Results: Non‐MF PCTCL had a longer overall survival (OS) (13.8 years) compared with secondary cutaneous T‐cell lymphoma (SC‐TCL) (2.5 years). Primary cutaneous anaplastic large cell lymphoma (PC‐ALCL) had the most favorable outcome (OS 14.1 years), whereas secondary and primary peripheral T‐cell lymphoma, unspecified had the shortest OS (2.5 and 2.4 years, respectively). Primary cutaneous CD4+ small/medium‐sized pleomorphic T‐cell lymphoma (CTLCD4) appeared to have a favorable course. Conclusions: Most non‐MF PCTCL can be classified according to the WHO‐EORTC classification. The relative frequencies are similar to European experience. Non‐MF PCTCL is a heterogeneous group with a favorable outcome compared to SC‐TCL, especially PC‐ALCL and CTLCD4. Separation of non‐MF PCTCL into indolent and aggressive groups appears clinically significant and may provide direction for therapeutic decisions. Weaver J, Mahindra AK, Pohlman B, Jin T, His ED. Non‐mycosis fungoides cutaneous T‐cell lymphoma: reclassification according to the WHO‐EORTC classification.     

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.     

Cutaneous Lymphomas: from Morphology to Chip Technology

Cutaneous lymphomas represent a heterogenous group of malignant lymphoid diseases with particular tropism for the skin. Prognosis and treatment depend on the type of lymphoma, thus precise diagnosis and classification are of paramount importance. Classification of cutaneous lymphomas relies on a synthesis of all available information, including clinical history and presentation, histopathology, immunophenotype, and molecular data. Thanks to the efforts of the lymphoma groups of both the World Health Organization (WHO) and the European Organization for Research and Treatment of Cancer (EORTC), a joint WHO-EORTC classification for primary cutaneous lymphomas has been proposed in 2005. The WHO-EORTC classification has been adsorbed with minor changes in the 2008 WHO classification of tumours of haematopoietic and lymphoid tissues, thus including for the first time primary cutaneous lymphomas as distinct subtypes of extranodal lymphomas in a general classification of lymphomas.     

Cutaneous lymphomas other than mycosis fungoides in Singapore: a clinicopathological analysis using recent classification systems

BACKGROUND: Cutaneous lymphomas other than mycosis fungoides (MF) are a heterogeneous group with wide variations in clinical presentation, biological behaviour and prognosis. New classification systems have been designed or proposed in recent years, with well-defined disease entities and emphasis on the importance of site. OBJECTIVES: This study aims to analyse a series of non-MF lymphomas in an institution-based dermatological setting in Singapore, based on the European Organization for Research and Treatment of Cancer (EORTC) classification and the World Health Organization (WHO) classification. A secondary objective is to highlight the clinical utility of both classification systems. PATIENTS AND METHODS: Forty cases diagnosed over a 12-year period were examined by immunohistochemistry with antibodies targeting CD3, CD4, CD5, CD8, CD20, CD30, CD43, CD45RO, CD56 and CD68 in paraffin-embedded specimens. The immunohistological diagnosis was correlated with the clinical presentation and staging investigations for the final diagnosis and the course of disease recorded. RESULTS: Non-MF T-cell lymphomas presenting in the skin comprised 31 cases (78%) and were 3(1/2) times more common than B-cell lymphomas, which comprised nine cases (22%). The common subtypes were lymphomatoid papulosis, CD30+ large cell cutaneous T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma. The commonly ascribed B-cell pattern with infiltrates in the mid and deep dermis and perivascular spaces was seen in 60% of T-cell lymphomas. Overall, there were equal numbers of primary cutaneous T-cell lymphomas and those due to concurrent or secondary cutaneous lymphoma. Five of six cases of subcutaneous panniculitis-like T-cell lymphoma had concurrent cutaneous and systemic involvement and their median survival was 7 months. CONCLUSIONS: The predominance of cutaneous T-cell lymphomas in this case series closely matched that reported from east Asia; cutaneous B-cell lymphomas are much less common than in Europe. The EORTC classification, which is designed only for primary cutaneous lymphomas, should be used in conjunction with the WHO classification because of the high prevalence of cutaneous lymphomas as the secondary site of disease from systemic lymphoma. In addition, subcutaneous panniculitis-like T-cell lymphoma is a primary cutaneous lymphoma where systemic involvement is common at initial presentation. We propose full immunophenotyping and complete clinical evaluation with staging investigations for all patients presenting with cutaneous lymphomas other than MF.     

EORTC classification for primary cutaneous lymphomas: the best guide to good clinical management. European Organization for Research and Treatment of Cancer.

In 1997 the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer (EORTC) published a proposal for a classification for the group of primary cutaneous lymphomas (1). The EORTC classification is the first and only classification that is designed exclusively for the group of primary cutaneous lymphomas. It is also the only classification that has been clinically validated for this group of diseases. As illustrated by this special issue, this classification has resulted not only in the discussion of the definition and terminology of some types of cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma (CBCL), but also in a discussion of whether organ-based classification schemes (separate from existing hematopathologic classification schemes for non-Hodgkin lymphomas) should be used. This article explains why it was necessary to create a separate classification for the group of primary cutaneous lymphomas. A short introduction on the history of the classification of cutaneous lymphomas is provided. Next, the basic principles of the EORTC classification are presented. Finally, controversies between the EORTC classification versus the REAL classification (2) and the proposed WHO classification (3), which still impede the usage of one common classification system, are discussed.     

Relative frequency of the different types of cutaneous T cell and natural killer cell lymphomas in Korea based on the proposed WHO classification and the EORTC classification

The R.E.A.L. classification was largely adopted recently by the proposed WHO classification. The usefulness of this classification in cutaneous T cell and natural killer (NK) cell lymphomas in Korea was evaluated compared to that of the European Organization for Research and Treatment of Cancer (EORTC) classification. Overall, 78 patients with cutaneous T cell and NK cell lymphomas were diagnosed in Asan Medical Center in the 1990's. The clinical records, slides of H&E and immunohistochemical stainings were reviewed. By the proposed WHO classification, mycosis fungoides (20 cases), lymphomatoid papulosis (13 cases), nasal type NK/T-cell lymphoma (10 cases), CD30+ anaplastic large cell lymphoma (8 cases), subcutaneous panniculitis-like T-cell lymphoma (6 cases), peripheral T-cell lymphoma, unspecified (3 cases), Sézary syndrome (1 case) and blastic NK cell lymphoma (1 case) comprised the primary cases. Secondary or undetermined cases included peripheral T-cell lymphoma, unspecified (10 cases), nasal type NK/T-cell lymphoma (5 cases), and angioimmunoblastic T-cell lymphoma (1 case). EORTC classification for cutaneous T cell and NK cell lymphomas did not include nasal and nasal type NK/T-cell lymphomas, unspecified non-pleomorphic T-cell lymphoma, undetermined cases among primary or secondary ones and some rare types of skin lymphomas which can be classified by WHO. The WHO classification is more useful for skin lymphomas in Korea since it encompassed all the various types of skin T cell and NK cell lymphomas in Korea.     

Characteristics of cutaneous lymphomas in Korea

The clinicopathologic characteristics of malignant lymphomas vary according to geography. The aim of this study was to determine the relative frequency of cutaneous lymphomas and to examine the clinical relevance of the WHO classification in Korean cases of cutaneous lymphoma. The Korean Dermatopathology Research Group conducted a clinicopathologic review of a nationwide collection of 80 cutaneous lymphomas, diagnosed at 23 institutes over a recent 3-year period. The clinical records, haematoxylin & eosin-stained slides and immunohistochemical stains from 80 patients with malignant lymphomas of the skin were reviewed. In our study, the most frequent cutaneous lymphoma was mycosis fungoides. Compared with Western countries, Korea had higher rates of NK/T cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma and a much lower rate of B-cell lymphoma. The occurrence rates for various subtypes of malignant lymphoma in Korea are distinct from those in Western countries. The EORTC classification is not fully appropriate in dealing with Korean cases of cutaneous lymphoma, because NK/T cell lymphoma is not included in the EORTC classification for cutaneous lymphoma.     

The new World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas: a practical marriage of two giants

Following consensus meetings of the two parent organizations, a new World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification for primary cutaneous lymphomas has recently been published. This important development will now end the ongoing debate as to which of these was the preferred classification. The new classification will facilitate more uniformity in diagnosis, management and treatment of cutaneous lymphomas. In particular, it provides a useful distinction between indolent and more aggressive types of primary cutaneous lymphoma and provides practical advice on preferred management and treatment regimens. This will thereby prevent patients receiving high-grade treatment for low-grade biological disease. This review focuses on those diseases which have found new consensus agreement compared with the original WHO and EORTC classifications. In cutaneous T-cell lymphomas, these include folliculotropic mycosis fungoides, defining features of Sézary syndrome, primary cutaneous CD30+ lymphoproliferative disorders (primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis and borderline lesions) and subcutaneous panniculitis-like T-cell lymphoma. Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma and cutaneous gamma/delta T-cell lymphoma are allocated provisional entry status and thereby afford better definitions for some cases of currently unspecified primary cutaneous peripheral T-cell lymphoma. In cutaneous B-cell lymphomas, diseases which have found new consensus agreement include primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicular centre lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type and primary cutaneous diffuse large B-cell lymphoma, other. CD4+/CD56+ haematodermic neoplasm (early plasmacytoid dendritic cell leukaemia/lymphoma) now appears as a precursor haematological neoplasm and replaces the previous terminology of blastic NK-cell lymphoma. Other haematopoietic and lymphoid tumours involving the skin, as part of systemic disease, will appear in the forthcoming WHO publication Tumours of the Skin. The new classification raises interesting new problems and questions about primary cutaneous lymphoma and some of these are discussed in this article. It is, however, a splendid signpost indicating the direction in which research in cutaneous lymphoma needs to go. In the interim, we have an international consensus classification which is clinically meaningful.     

Lymphomatoide Papulose bei einem 2?1/2-j?hrigen Jungen

Lymphomatoid papulosis (LyP) is a rare cutaneous lymphoproliferative disorder that has malignant histologic features and a benign clinical course. LyP is classified according to the WHO/EORTC classification for cutaneous lymphoma as a CD30-positive lymphoproliferative disorder. Few previous reports have detailed features of LyP in pediatric and adolescent patients, but LyP very rarely presents in early childhood. A 2 1/2-year-old boy presented with a 1-year history of recurrent papular and nodular lesions on the face and trunk. Clinical and histopathologic criteria lead to the diagnosis lymphomatoid papulosis.