WHO淋巴组织肿瘤新分类的学习与思考

1 WHO淋巴组织肿瘤新分类的产生及特点 人类对恶性淋巴瘤的认识经历了漫长曲折的过程.二十多年来,恶性淋巴瘤的分类从主要反映细胞形态的多种病理分类到临床实用的工作公式,长期以来争论不休,褒贬不一,难以建立起被国际接受的分类计划,使众多临床肿瘤和病理医生陷入极大困惑.     

Clinicopathological study of primary gastric lymphoma

OBJECTIVE: To present a histopathologic and immunohistochemical analysis of primary gastric lymphomas that was reclassified according to the new World Health Organization classification of lymphoid neoplasms. METHODS: We reviewed the morphological and immunohistochemical features of 28 patients with gastric lymphomas, diagnosed in the Department of Pathology at the University Hospital of Tishreen University, Lattakia, Syria, during the period 1994-2003. Specimens were obtained from endoscopic and surgical biopsies. The immunohistochemical study was performed to analyze the immunophenotype of these lymphomas. RESULTS: Patients were aged 17-71 years. There was a slight predominance of females (male to female ratio, 13:15). Seventeen of the patients had tumors mainly located in the gastric antrum. Histologically, the most common lymphoma was of mucosa-associated lymphoid tissue (MALT) type (20 patients), also with diffuse large B-cell lymphoma (7 patients), and anaplastic large cell lymphoma (one patient). CONCLUSION: Our study demonstrates the different patterns of gastric lymphomas in Lattakia, Syria during a 10-year period in 28 Syrian patients, and reveals that the most primary gastric lymphomas are B-cell MALT lymphomas.     

Spectrum of malignant lymphoma in Queen Elizabeth Hospital, Sabah

Lymphomas, ranked twelve among all cancers world-wide in the 1990s, in which it is more prevalent in males compared to females. A previous study on lymphomas in East Malaysia for a period of 3 years from 1981-1983 showed that the pattern of lymphomas conformed to the general pattern observed in Asia. Current study reviews lymphoma cases from the Department of Pathology, Queen Elizabeth Hospital, Sabah between 1997 and 1999, with the aim of investigating if the spectrum and pattern in Sabah has since changed, a decade later. A total of 91 confirmed lymphoma cases were phenotyped with a panel of antibodies and classified using the new WHO proposed list of lymphoid neoplasms. The 1981-1983 series was reviewed and cases reclassified accordingly for comparison. There are 83 (91.2%) NHL and 8 (8.8%) HL cases in this series, a ratio of NHL to HL of 9:1. Of the 83 cases of NHL, 66 (79.5%) were confirmed B-cell type, 13 (15.7%) T-phenotype, 1(1.2%) null cell type and one case unclassified. Diffuse large B-cell lymphoma is the most prevalent, (65.1%), followed by Burkitt's lymphoma and follicular lymphoma, (10.6%) each. Lymphoma pattern concurs with the previous series from Sabah, with higher prevalence of diffuse large cell lymphoma and lower incidence of follicular lymphoma and HL, as seen elsewhere in Asia. There is an overall increase in the number of cases of NHL in the 1990s. However, the proportion of T-NHL is reduced when compared to the series in the 1980s.     

黏膜相关淋巴组织淋巴瘤分子生物学机制研究进展

黏膜相关性淋巴组织(mucosa-associated lymphoid tissue,MALT)淋巴瘤是非霍奇金淋巴瘤中边缘带淋巴瘤的一种,它通常作为一种局灶性病灶位于胃、唾液腺、甲状腺及眼眶附属器中, 目前正逐渐从临床、病理及分子遗传学的角度得到认识.本文对MALT淋巴瘤发病的分子生物学机制研究进展做一综述.     

组织芯片检测淋巴瘤中活化的细胞毒性细胞

目的：运用组织芯片及常规病理切片检测活化的细胞毒性细胞在各型淋巴瘤中的表达分布情况，为临床治疗和判断预后提供依据。方法：运用免疫组化方法检测60份淋巴瘤标本制成的组织芯片中穿孔素、颗粒酶B的表达和分布情况，同时选择10份鼻自然杀伤细胞（NK）／T细胞淋巴瘤常规标本与组织芯片进行比较研究，10份淋巴组织反应性增生标本作为对照。结果：在60份淋巴瘤组织芯片中，发生在淋巴结内者48份，淋巴结外者12份。B细胞淋巴瘤42份，T细胞淋巴瘤16份（外周T细胞淋巴瘤10份、NK／T细胞淋巴瘤2份、T淋巴母细胞瘤2份及问变性大细胞淋巴瘤2份），2份霍奇金淋巴瘤。42份B细胞淋巴瘤的瘤细胞均不表达穿孔素和颗粒酶B。10份外周T细胞淋巴瘤中8份表达穿孔素，9份表达颗粒酶B，阳性表达细胞均为非肿瘤细胞。芯片中的2份和常规10份鼻NK／T细胞淋巴瘤中均见穿孔素和颗粒酶B过度表达。T、B细胞淋巴瘤与NK／T细胞淋巴瘤比较有显著性差异（P〈0．01）。结论：穿孔素和颗粒酶B是鉴定活化的细胞毒性细胞的免疫标志物，可作为NK／T细胞淋巴瘤的诊断性标志物；其在T细胞淋巴瘤中的表达反映了机体的抗肿瘤免疫反应机制。组织芯片技术具有高信息量、简捷、高效、实验误差小、重复性好等优点，可作为研究淋巴瘤的有用工具。     

自身免疫性疾病转为恶性淋巴瘤12例临床分析

目的 探讨自身免疫性疾病与恶性淋巴瘤的关系.方法 回顾性分析20年来先发生自身免疫性疾病后被诊断为恶性淋巴瘤的12例患者的临床资料并复习相关文献.结果 12例中,原发干燥综合征(pSS)6例,其中4例有反复腮腺肿大、浅表淋巴结及肝脾肿大,4例炎症指标持续升高,发生淋巴瘤时以非霍奇金淋巴瘤(NHL)B细胞型为主;类风湿关节炎(RA)2例,均有严重的关节病变和炎性指标增高,淋巴瘤均为NHL弥漫大B细胞型;系统性红斑狼疮(SLE)2例,抗SSA、抗SSB均呈阳性,分别转为T和B细胞型NHL;皮肌炎和银屑病关节炎各1例,后均诊断为NHL B细胞型.结论 自身免疫性疾病患者恶性淋巴瘤的发病率较高,尤以原发干燥综合征、类风湿关节炎、系统性红斑狼疮为多.这些患者具有一定的特征性表现,转化的恶性淋巴瘤以B细胞型为主.     

当今淋巴瘤分类

恶性淋巴瘤是一组高度异质性疾病,有关其分类研究过去一直是仁见、智见智,数种分类（Ｒａｐｐａｐｏｒｔ,Ｌｕｋｅｓ－Ｃｏｌｌｉｎｓ,ＷＦ及Ｋｉｅｌ等）也各持所长、各抒己见。近年证实,各型淋巴瘤均是独立的疾病实体,其准确定义除了依赖病理形态与免疫表型外,尚需考虑其遗传特性与临床表现。在此基础上,“淋巴组织肿瘤欧美修改分类（ＲＥＡＬ）”与“淋巴造血组织肿瘤世界卫生组织分类（ＷＨＯ）”也应运而生。作就     

Marginal zone B-cell lymphoma of the uterus: a case report and review of the literature

We report here a case of a 52-year-old female in whom immunohistological studies of the uterus established a diagnosis of extranodal marginal zone B-cell lymphoma. Malignant lymphoma arising from mucosa-associated lymphoid tissue (MALT) of uterus is extremely rare. Accurate histologic interpretation of uterine lymphoma is essential, as treatment options and prognosis vary based on the histological grade of such lymphomas. Patients with primary uterine lymphoma generally have intermediate or high-grade lymphoma and poorer prognosis.     

Extranodal diffuse non hodgkin lymphoma in the thigh

Diffuse large B-cell lymphoma usually starts as a rapidly growing mass in an internal lymph node and can grow in other areas such as the bone or intestines. About 1/3 of these lymphomas are confined to one part of the body when they are localized. In the case of a 78-year-old man, an extensive tumour was located on the right thigh. Biopsies of the tumour revealed diffuse proliferation of large lymphoid cells which have totally affected the normal architecture of striated muscle. The patient received multimodality treatment including chemotherapy of the CHOP regimen and adjuvant radiotherapy. Despite this being a fast growing lymphoma, about 3 out of 4 people will have no signs of disease after initial treatment, and about half of all people with this lymphoma are cured with therapy.     

Primary thyroid lymphoma: report of two cases

Primary thyroid lymphoma is a rare disease. Most of the patients have a history of Hashimoto's thyroiditis. Main histopathologic subtypes are either mucosa-associated lymphoid tissue (MALT) or diffuse large cell lymphomas. Treatment options are surgical resection in localised, low-grade MALT lymphomas or systemic chemotherapy in aggressive, diffuse large cell lymphomas. But, sometimes other histopathologic subtypes can be seen and therapeutic approaches must be done. We report two patients who have primary thyroid lymphoma. There was no history of Hashimoto's thyroiditis in either case, and neither of them had MALT histologic subtype. First patient a sixty four year old woman, admitted to hospital because of bilateral thyroid nodules. Histological subtype was B cell follicular lymphoma. Subtotal thyroidectomy was performed and radiotherapy was administered to the entire neck region. Second patient, a 50 year old man, presented with complaints of a left thyroid mass and dyspnoea. Total thyroidectomy was carried out and chemotherapy was given. Histological diagnosis was diffuse large B cell lymphoma. Thyroid lymphomas had heterogenous histological and clinical characteristics. In localised, non-aggressive subtypes, surgical treatment must be considered. Postoperative chemotherapy or radiotherapy may be necessary in some patients.     

间变性大细胞淋巴瘤的临床病理分析

目的探讨间变性大细胞淋巴瘤的临床病理特点、免疫表型及鉴别诊断。方法对8例淋巴结及皮肤的间变性大细胞淋巴瘤组织学观察及免疫组化染色（ABC法），并复习相关临床资料。结果8例间变性大细胞淋巴瘤患者男性5例，女性3例，年龄12—53（平均34）岁。6例发生于淋巴结，2例发生于皮肤。组织学特征：部分或全部淋巴结受累，瘤细胞有成巢或沿淋巴窦内生长现象，发生于皮肤者肿瘤组织弥漫成片分布，瘤细胞高度异型、多形，核分裂象多见。免疫表型：8例瘤细胞均表达CD30，6例表达CD3或CD45RO，而CD15和CD20均阴性。结论间变性大细胞淋巴瘤是一种形态学高度异形、免疫表型特异，而临床预后相对较好的淋巴瘤。组织学上需与转移癌、恶性黑色素瘤及霍奇金淋巴瘤相鉴别。CD30免疫组织化学标记在鉴别诊断中具有重要价值。     

35例胃肠道B细胞淋巴瘤的临床病理分析

目的:探讨胃肠道B细胞淋巴瘤的临床特点和病理诊断。方法:对35例胃肠道B细胞淋巴瘤分别进行HE染色和免疫组织化学染色。临床病理学观察内容包括患者年龄、性别、肿瘤发生部位、肿瘤的组织形态学等。免疫组织化学染色采用EliVision plus法。结果:35例胃肠道B细胞淋巴瘤的男女之比为1.3∶1;发病年龄25～83岁,平均59岁。诊断为弥漫性大B细胞淋巴瘤19例(54%);黏膜相关组织边缘区B细胞淋巴瘤(MALT淋巴瘤)7例(20%);套细胞淋巴瘤7例(20%);不能分类2例(6%)。发生于胃18例(51%);发生于小肠7例(20%);发生于结肠6例(17%);发生于回盲部、阑尾、肛管、吻合口各1例。免疫组织化学标记:所有病例均表达CD20和CD79a,不表达CD3,不同类型淋巴瘤不同程度表达CD10、bcl-6、MuM1、CyclinD1等。结论:胃肠道B细胞淋巴瘤主要分为弥漫性大B细胞淋巴瘤和小B细胞淋巴瘤两大类;胃肠道小B细胞淋巴瘤以MALT淋巴瘤和套细胞淋巴瘤多见;对胃肠道B细胞淋巴瘤中的诊断进行了分析和总结。     

应用世界卫生组织淋巴组织肿瘤新分类对304例恶性淋巴瘤的重新评估

目的 研究世界卫生组织(WH0)淋巴组织肿瘤新分类法的适用性,观察淋巴瘤不同类型的发生率以及淋巴瘤类型分布的地域人群特点。方法 对已经病理证实的304例恶性淋巴瘤(ML),复习其组织学、免疫组化标记和临床特点,按WH0新分类标准进行了重新评估。结果 304例中霍奇金淋巴瘤占6．6％,非霍奇金淋巴瘤(NHL)为93．4％,其中发生于淋巴结者41．8％,结外为58．2％。284例NHL中B细胞肿瘤60．2％,T和NK细胞肿瘤39．1％;前6位最常见类型为弥漫性大B细胞淋巴瘤、鼻型结外NK／T细胞淋巴瘤(NK／T-L)、非特殊型外周T细胞淋巴瘤、MALT型结外边缘区B细胞淋巴瘤、血管免疫母细胞性T细胞淋巴瘤和滤泡性淋巴瘤(FL),共占NHL的88．03％。本组与欧美等地区发病相比,NK／T-L和外周T细胞淋巴瘤明显较高,而B-小淋巴细胞性淋巴瘤和FL明显较低。结论 使用新分类使ML病理诊断变得较为简便易行,大多类型依据临床、组织病理学和免疫标记特征即可作出相应诊断。     

根据WHO(2008)新分类对371例蒙古族患者恶性淋巴瘤的临床病理分析

目的:探讨蒙古族患者恶性淋巴瘤的临床病理特点和WHO(2008)新分类的实用性。方法:复查371例既往经病理诊断为恶性淋巴瘤的病例,观察其形态学、免疫组化及临床特点,按WHO(2008)新分类标准进行重新定性和分类,对其中126例有随访的病例进行生存率分析。结果:317例中,319例NHL(85.98%),其中B细胞肿瘤67.08%,T和NK细胞肿瘤32.9%,52例(14.0%)为CHL。前六位最常见类型为弥漫大B细胞淋巴瘤(DLBCL),非特指性周围T细胞淋巴瘤(PT-un)、结外黏膜相关组织边缘区淋巴瘤(MALT)、滤泡性淋巴瘤(FL)、T淋巴母细胞性白血病/淋巴瘤(T-LBL)、慢性淋巴细胞性白血病/小淋巴细胞性淋巴瘤(CLL/SLL)、青少年中最常见为LBL、DLBCL淋巴瘤。不同类型NHL的生存情况在总体上差别有统计学意义(P<0.01),其中边缘区B细胞淋巴瘤(MZL)与SLL的预后最佳,LBL与PT-un的预后最差,DLBCL与FL介于前两者之间。结论:WHO(2008)新分类实用性强、便于掌握,各亚型的形态学、免疫学指标可靠,结合临床能较好应用于淋巴瘤的诊断和预后。     

突变型p53在弥漫性大B细胞淋巴瘤中作用的研究进展

弥漫性大B细胞淋巴瘤(DLBCL)是一种异质性的血液系统恶性肿瘤,约占非霍奇金淋巴瘤的三分之一,具有多种临床、形态学和分子特征。p53是重要的肿瘤抑制基因,通过诱导细胞周期阻滞、DNA修复和细胞凋亡及调控多种信号转导途径抑制肿瘤的发生发展。p53突变导致的细胞周期失调及信号转导通路失活是多种恶性肿瘤发生及进展的因素。本文就突变型p53在DLBCL中作用以及可能的机制进行综述。     

肠道原发性非霍奇金淋巴瘤85例分析

目的了解不同细胞来源的肠道原发性非霍奇金淋巴瘤(PINHL)在临床特征、内镜表现、诊断及治疗、预后方面的差异。方法回顾性分析我院2003年1月~2010年12月间明确诊断的PINHL病例,分别统计B细胞来源与T细胞来源的PINHL在临床表现、内镜表现、诊断治疗,并随访预后。结果共纳入PINHL 85例,中位年龄52岁,男女比例为3.05∶1,B细胞来源58例(68.2%),T细胞来源27例(31.8%)。T细胞淋巴瘤较B细胞淋巴瘤具有发病年龄小(32岁vs 56岁,P<0.01);发热、便血、腹泻、盗汗多(P<0.05);病变以多部位弥漫性分布和肠镜下以溃疡及溃疡浸润性表现为主;确诊时间长(4月vs 2月,P<0.01);误诊率高(16/27 vs 12/58,P<0.01);预后差等特点;且T细胞淋巴瘤以结外NK/T淋巴瘤为主。结论我院PINHL中,T细胞来源淋巴瘤比例高,发病年龄更早,诊断困难,容易误诊,总体预后差,病理分型以结外NK/T淋巴瘤为主。     

NK and NK-related neoplasms

Owing to the immunological progress in recent years, differentiation and maturation process of NK cells or NK-related cells has been made clear. Also, their neoplastic counterparts, namely NK cell related lymphoma/leukemia have been characterized. In this paper, we will report NK cell neoplasms based on the new classification of malignant lymphomas. Among these, nasal lymphoma is one of the most clearly defined entities, followed by NK cell leukemia/lymphoma, and blastic/blastoid NK cell leukemia/lymphoma.     

B细胞淋巴瘤分子发病机制的研究进展

B细胞淋巴瘤(BCL)是一组包含多种不同，临床表现和分子生物学特征的肿瘤。根据分子发病机制的不同可分为低生长比率BCL和高生长比率BCL。低生长比率BCL的发病主要为凋亡调控异常致使细胞凋亡受抑，而并无明显的细胞增殖异常。与此相反，高增长比率BCL是因参与细胞周期调控的癌基因异常(如Bcl-6和c-myc)致细胞增殖增加所致。部分低或高增长比率BCL均可获得另外的分子异常，主要为周期素依赖激酶抑制剂异常，从而进展为高度侵袭性淋巴瘤。     

Retrovirus and malignant lymphoma in homosexual men

We report malignant lymphoma in 27 homosexual men, of whom 22 had high-grade lymphomas (B-cell immunoblastic sarcoma or small non-cleaved lymphoma) and five had low-grade disease. Antibody to human T-cell lymphotropic virus type III (HTLV-III) was present in 13 (87%) of 15 with high-grade lymphoma and in two (40%) of five with low-grade disease. In contrast, only one (9%) of 11 "control" heterosexual patients with high-grade lymphoma had antibody to HTLV-III, while such antibody was found in none of 40 asymptomatic heterosexual controls and in 17 (55%) of 31 asymptomatic homosexual men. Of the homosexual lymphoma patients, 85% presented with disease in extranodal sites, including the central nervous system and rectum, and 81% had reversed T-helper/suppressor ratios. Median survival, despite treatment, is eight months. The acquired immunodeficiency syndrome-related lymphomas in homosexual men are extranodal, high-grade, B-lymphoid tumors, associated with exposure to HTLV-III and unusual clinical characteristics.     

Primary oesophageal Ki (CD30)-positive ALK+ anaplastic large cell lymphoma of T-cell phenotype

Primary oesophageal lymphoma is a very rare entity, with fewer than 30 reported cases worldwide. It represents an important cause of dysphagia. Most of the oesophageal lymphomas are diffuse large B-cell type, with only one reported case of anaplastic large cell lymphoma (ALCL) of T-cell phenotype. Primary oesophageal lymphomas that are not associated with an immunocompromised state tend to affect elderly patients. We describe the first case of primary oesophageal Ki (CD30)-positive ALK+ALCL of T-cell phenotype in a 34-year-old immunocompetent woman, who presented with a two-year history of dysphagia. She was treated with chemotherapy and endoscopic oesophageal dilations and stenting, resulting in complete remission of the lymphoma and resolution of the dysphagia. She then underwent autologous peripheral blood haematopoietic stem cell transplantation and remained disease-free two years after the diagnosis.