MUM1/IRF4在滤泡性淋巴瘤中的表达及其临床病理意义

目的 探讨MUM1/IRF4在滤泡性淋巴瘤(FL)中的表达情况及临床病理意义.方法 对96例FL患者标本进行MUM1、CD10、bcl-2、bcl-6、Ki-67免疫组织化学染色,并与患者的临床资料和病理学特征比较.结果 MUM1在96例FL中总的阳性率为59.2%(58/96),其中1～2级组阳性率为36.2%(19/51),3级组阳性率为86.4%(39/45)(x2=24.406,P<0.001).68.9%伴有弥漫成分的FL患者MUM1阳性(x2=8.161,P=0.004).MUM1和CD10的表达呈负相关,83.3%的CD10阴性病例表达MUM1(x1=12.649,P<0.001).MUM1阳性者核分裂和Ki-67标记指数高于MUM1阴性者(t=-3.852、t=-4.610,P<0.001).结论 MUM1可作为FL分型的标志物.MUM1阳性的FL可能为类似非生发中心B细胞分化特征的高度恶性淋巴瘤.     

原发性骨淋巴瘤的影像学及临床病理特征

原发性骨淋巴瘤(PLB)为非霍奇金淋巴瘤(NHL),是一类罕见的结外淋巴瘤,占所有NHL的1%、结外淋巴瘤的5%、原发于骨的恶性肿瘤的7%.目前公认的PLB诊断标准为:肿瘤局限于单骨,临床和影像学检查未发现有其他系统病灶;病理组织学上确诊骨病灶为淋巴瘤;就诊时只有局部浸润,或至少在原发灶出现6个月后才有远处骨骼和其他部位的转移.由于PLB表现的多样性和异质性,且发病率较低,导致诊断困难,现分析归纳其临床病理及影像学特征,以提高认识,降低误诊和漏诊率.     

原发系统性间变性大细胞淋巴瘤临床病理特征及免疫表型分析

目的 分析原发系统性间变性大细胞淋巴瘤( ALCL)的临床病理特征和免疫组织化学特点,提高诊治水平。方法选取22例ALCL患者,均进行分期、国际预后指数(IPI)、乳酸脱氢酶(LDH)检测,应用免疫组织化学SP法检测间变性淋巴瘤激酶(ALK)、Ki-67、Caspase-3、CD30、EMA、Granzyme B等,回顾性分析患者临床、病理形态学资料、免疫表型及生物学特性,并进行预后分析。结果22例均为原发系统性ALCL,ALK+ 15例(68.2％),ALK-7例(31.8％);AILK+患者发病年龄、Ki-67增殖指数较ALK-患者低,Caspase-3表达率高,差异有统计学意义(x2 =4.618,P= 0.032);15例ALK+ALCL均表达CD30和EMA。ALCL中ALK的表达与Ki-67、Caspase-3的表达呈负相关(r= -0.581,P= 0.006;r=0.458,P=0.032)。ALK+病例较ALK-病例GranzymeB(x2=0.11,P=0.74)、TIA-1( x2= 0.01,P=0.92)的表达率高,但差异无统计学意义(P＞0.05)。有效率为54.5％(12/22),其中完全缓解率为18.2％(4/22);全组中位生存期12个月,1年生存率为59.1％( 13/22),2年生存率为50.0％(11/22)。Ann Arbor分期、LDH及IPI与疾病预后相关。结论ALK+较ALK-ALCL患者核增殖低,恶性程度低,临床特征和免疫表型具有一定的特征性;ALK、Ki-67、Caspase-3、分期、血清LDH及IPI对预测ALCL患者的生存和指导治疗有帮助。     

原发性纵隔大B细胞淋巴瘤研究进展

原发性纵隔大B细胞淋巴瘤(PMBCL)是弥漫大B细胞淋巴瘤(DLBCL)的一种特殊类型,具有独特的临床表现及病理学、分子生物学特征.目前尚无标准的治疗方案,回顾性分析表明第三代的化疗方案优于CHOP方案,利妥昔单抗的应用缓解了这种差异,是否需要接受联合放疗尚无定论.未来将脱氧葡萄糖-正电子发射计算机断层显像(FDG-PET)用于PMBCL的疗效评估,如果能提供可靠的预后信息,就可以减轻治疗强度.     

系统型间变性大细胞淋巴瘤30例临床分析

目的 探讨系统型间变性大细胞淋巴瘤(S-ALCL)的临床特征和预后相关因素.方法 回顾性分析30例S-ALCL患者的临床资料.30例患者均以联合化疗为主,配合局部病灶野放疗8例.化疗方案主要为CHOP、EPOCH、Hyper-CVAD,以CHOP方案为主.结果 30例S-ALCL患者中位年龄36岁,男女比例为1.5∶1,有B症状、Ⅲ～Ⅳ期和结外侵犯者分别占60.0%(18/30)、73.3%(22/30)和60.O%(18/30);乳酸脱氢酶(LDH)升高者占46.7%(14/30);间变性大细胞淋巴瘤激酶(ALK)+18例(60.0%),其发病年龄小于ALK-者(u=3.92,P=0.001).单因素分析显示ALKˉ及LDH升高是重要的预后不良因素.结论 S-ALCL患者发病年龄较轻,预后较好.但ALK-、LDH升高者预后不良.治疗以联合化疗为主,对于有不良预后因素的患者,大剂量治疗可能获益.     

经典型霍奇金淋巴瘤肿瘤细胞和背景淋巴细胞相关标记的表达

目的:探讨经典型霍奇金淋巴瘤中的肿瘤细胞和非肿瘤背景淋巴细胞蛋白表达的特征及差异性.方法:收集经典型霍奇金淋巴瘤68例,对诊断切片和免疫标记片重新复查,采用Envision法补做相关免疫组织化学标记,观察CD30、CD15及T/B表型等的表达.结果:肿瘤细胞和背景淋巴细胞CD30的表达率分别为86.76%(59/68)和20.59%(14/68),CD15的表达率分别为51.47%(35/68)和63.24%(43/68);肿瘤细胞表达T细胞表型的阳性率为45.59%(31/68),B细胞表型的阳性率为42.65%(29/68).成熟淋巴细胞以T细胞为主时,肿瘤细胞表达B细胞表型21例,表达T细胞表型28例;成熟淋巴细胞以非T细胞为主时,肿瘤细胞表达B细胞表型8例,表达T细胞表型3例(P>0.05).结论:CD30和CD15是非特异性标记物,在肿瘤细胞和反应性淋巴细胞中均可表达;肿瘤细胞表达T细胞的免疫表型高于表达B细胞的免疫表型;背景细胞以T淋巴细胞为主时,肿瘤细胞表达T和B表型阳性率无差异.     

艾滋病病毒感染合并口腔浆母细胞型淋巴瘤一例临床病理分析

目的 分析艾滋病病毒(HIV)合并口腔浆母细胞型淋巴瘤的形态学特点、免疫表型及鉴别诊断.方法 对1例HIV合并口腔浆母细胞型淋巴瘤进行形态学、免疫组织化学分析及文献复习.结果 免疫组织化学显示CD-20、CD-3、CD-45、CD-30、ALK(-)、EBV(+)、CD138灶(+)、Ki-67 90%(+)、EMA灶(+)、CD68组织细胞(+)、CDRB灶(+)、CD45RO个别(+)、CD-79a、CD-56、IgM、IgG、IgA、HMB45、bcl-2、CD5、cyclinD1、CD43、CD10、Desmin、MPO、CD15、MYOD1、CK均为(-).病理诊断弥漫大B细胞淋巴瘤浆母细胞型分化.结论 弥漫性大B细胞淋巴瘤病理类型多样,HIV合并口腔浆母细胞型较少见,掌握其形态学特征,熟悉各类型的免疫表型的异同点对诊断与鉴别诊断有重要意义.     

原发性结外淋巴瘤241例临床特点及误诊原因分析

目的 分析原发性结外淋巴瘤的发病及临床特点,总结应对误诊策略.方法 回顾分析2001年1月至2010年4月收治的241例原发性结外淋巴瘤的病例资料.结果 发病率最高的年龄段为51～60岁,男女比例为1.4∶1;前三位常见发病部位为消化道(50.62%),咽淋巴环(14.52%),脾(6.22%);最常见的病理类型为弥漫大B细胞型(58.91%);首发症状多表现为原发器官的肿大及原发部位肿物形成(67.63%).结论 原发性结外淋巴瘤临床表现不特异,应提高警惕,避免误诊.     

系统性间变性大细胞淋巴瘤骨髓累及的临床病理学研究

目的 探讨系统性间变性大细胞淋巴瘤(S-ALCL)骨髓累及的临床病理学特点、免疫学表型及临床生物学行为.方法 回顾性分析34例S-ALCL病例资料,进行骨髓活检(19例)或涂片(15例).其中ALK(+)24例,ALK(-)10例.HE染色、免疫组织化学染色观察病理形态及免疫表型,原位杂交法检测EB病毒.结果 6例(17.6%)S-ALCL存在骨髓累及,均经骨髓活检标本确定,15例患者骨髓涂片中均未见肿瘤累及.ALK(+)ALCL和ALK(-)ALCL骨髓累及的发生率分别为16.7%(4/24)和20.0%(2/10),差异无统计学意义(P=0.3555).与无骨髓累及病例比较,骨髓累及病例的年龄、性别分布差异无统计学意义(P值分别为0.8089和0.3085).骨髓累及者肿瘤细胞以间质性分布为主[83.3%(5/6)].生存分析统计提示伴有骨髓累及的患者预后明显差于无骨髓累及者(P=0.0407).结论 S-ALCL骨髓累及发生率低,与患者的发病年龄、性别及ALK蛋白的表达无相关性.伴有骨髓累及的S-ALCL患者临床预后差,骨髓活检在判断S-ALCL预后中有重要意义.     

鼻型自然杀伤-T细胞淋巴瘤31例临床分析

目的 分析结外鼻型自然杀伤(NK)-T细胞淋巴瘤的临床特点及治疗方案,提高对鼻型NK-T细胞淋巴瘤的认识.方法 对经病理证实的鼻型NK-T细胞淋巴瘤31例的临床资料进行回顾性的分析结果31例患者中,EB病毒(EBV)感染24例(77.42%).近期疗效结果显示,放疗、化疗、放疗+化疗差异无统计学意义(x2=3.61,P＞0.05).随访截至2010年10月,3l例患者中死亡24例,7例生存,其中4例无瘤生存.19例死于肿瘤复发或进展.全组中位生存时间为32个月.患者5年生存情况与临床分期、区域淋巴结受累、B症状、乳酸脱氢酶(LDH)水平、局部肿瘤浸润、EBV感染、早期治疗有 关(x2值分别为8.88、7.25、16.95、6.00、7.23、7.44、7.80,均P＜0.05).结论 放疗、化疗、放疗+化疗治疗鼻型NK-T细胞淋巴瘤疗效差异不大;患者的生存情况与临床分期、区域淋巴结受累、B症状、LDH水平、局部肿瘤浸润、EBV感染、早期治疗等临床特征有关.     

Management of follicular lymphoma

Despite the fact that a small proportion of patients with follicular lymphoma may be alive 20 years after the initial diagnosis, and that it is repeatedly, albeit usually only partially, responsive to relatively mild therapy, the disease remains stubbornly incurable for the majority. Therefore, the testing of several new therapeutic approaches is welcome. Interferon has been investigated in two settings: in combination with conventional therapy and as "maintenance" following chemotherapy. Prolongation of remission duration has been demonstrated and one study shows a survival advantage. The purine analogue fludarabine, having originally been shown to induce remissions in patients with chronic lymphocytic leukemia, is also effective in follicular lymphoma, although its precise role remains to be determined. Myeloablative therapy with autologous bone marrow transplantation (which has been the subject of much debate and controversy in the context of low-grade lymphoma), has been shown to prolong duration of remission, although presently, there is no survival advantage. Finally, radiolabeled antibody therapy is showing promise in patients in whom other treatment modalities have failed. The significance of "minimal residual disease" manifest as circulating t(14;18)-containing cells, as demonstrated by polymerase chain reaction analysis awaits clarification.     

Treatment of follicular lymphoma

Follicular lymphoma is one of the most common neoplastic lymphoproliferative diseases encountered in the western world. Intensive scientific scrutiny has led to detailed understanding of the nature of the malignant cell and the specific genetic abnormalities which are frequently encountered and likely to be etiologic. Clinical research focusing on the treatment of follicular lymphoma continues to reveal new insights into the natural history of the disease. Investigations reported during the past year have focused on a number of important issues with regard to the management of patients with the diseases.     

Histologic transformation in follicular lymphoma

Blood donors (n = 663) from the Novy Jicín district, Czech Republic, were examined for the presence of antibodies to Toxoplasma gondii. The indirect fluorescent antibody test was used to simultaneously detect IgM and IgG antibodies. Titres > or =20 were considered positive. The seroprevalence of IgM and IgG antibodies was 2.4% and 32.1%, respectively. Periods, for how long the blood donors were infected, are discussed.     

Conservative management of follicular non-Hodgkin's lymphoma in childhood

Among 447 children with non-Hodgkin's lymphoma (NHL) on the childhood U.K. registry, seven children with follicular (NHL) were identified. Four were male and their age ranged from 4.25 to 13.5 years (median 7.5); all had localized disease, Murphy's stage I (n = 4) and II (n = 3). Sites involved at presentation were cervical lymph nodes and tonsils (n = 5), ileum (n = 1) and parotid gland (n = 1). Three had complete surgical excision only and four had complete (n = 1) or incomplete excision (n= 3) followed by a short multi-agent chemotherapy regimen (UKCCSG 9001 protocol). With a median follow-up of 1.5 years (range 0.25-5 years) from diagnosis, six are alive in complete remission (CR) including three who had no chemotherapy. These results confirm previous reports that follicular lymphomas in children are rare (1.5%) and tend to be localized at presentation. Their rarity makes it difficult to produce guidelines about treatment, but in localized cases a period of non-intervention may be justified.     

Recombinant interferon-alpha therapy in patients with follicular lymphoma

BACKGROUND: Advanced stage, follicular, non-Hodgkin's lymphoma (NHL) has no cure and no single standard of care. Remissions induced by standard chemotherapy regimens generally are not durable and, with the exception of selected patients with limited early stage disease, most patients with follicular NHL eventually die of their disease. Recombinant interferon-alpha (rIFN-alpha) has demonstrated activity against follicular NHL in clinical trials. METHODS: A comprehensive survey of current therapeutic options for follicular NHL patients was conducted with emphasis on the role of rIFN-alpha used in conjunction with chemotherapy regimens. RESULTS: Phase III studies have demonstrated that rIFN-alpha delays disease progression and may improve overall survival when administered either with chemotherapy or as maintenance therapy after induction treatment for follicular lymphoma. Adverse effects from combination or maintenance regimens are not significantly different from those from chemotherapy alone. CONCLUSIONS: Recombinant IFN-alpha is safe and effective when given in conjunction with standard chemotherapeutic regimens in selected patients with follicular NHL, and may especially benefit patients with minimal residual disease after induction chemotherapy.     

Incidence, predictive factors, and outcome of lymphoma transformation in follicular lymphoma patients

PURPOSE: To assess the incidence of lymphoma transformation in the natural history of follicular lymphoma (FL) patients and the factors that are predictive of this event. PATIENTS AND METHODS: Two hundred twenty patients with FL treated in our institution between 1975 and 1990, with a median follow-up duration of 9 years, were included in this retrospective analysis. RESULTS: Transformation was proven by histology in 34 patients or by cytology in 13 patients and was considered as highly probable on clinical arguments in five patients for an overall incidence of 24%. The probability of transformation was 22% at 5 years and 31% at 10 years and tended to plateau after 6 years. Predictive factors for transformation were nonachievement of complete remission (CR) after initial therapy (P < 10(-4), low serum albumin level (< 35 g/L) (P = .001), and beta 2-microglobulin level greater than 3 mg/L (P = .02) at diagnosis. In a multiparametric analysis, only beta 2-microglobulin level retained prognostic significance for freedom-from-transformation (FFT) survival (P = .04). Transformation accounted for 44% of deaths and was associated with a poor outcome, with a median survival time of 7 months. CONCLUSION: Transformation is an early event in the course of the disease and is mainly observed in patients with known adverse prognostic factors or those who do not achieve CR after initial treatment. These findings may be useful to select follicular lymphoma patients for intensive therapeutic approaches.     

Prognostic value of cellular proliferation and histologic grade in follicular lymphoma

The clinical usefulness of histologic grading in follicular lymphoma (FL) is controversial and is further compromised by the subjective nature and poor reproducibility of most systems in current use. Therefore, we decided to objectively evaluate the importance of cellular proliferation in FL, along with the current grading systems. We studied 106 patients with FL who were uniformly staged and aggressively treated. A proliferative index (PI) was determined quantitatively using an automated image analyzer and a new Ki-67 antibody that stains archival paraffin tissues. The cases were also subclassified according to the Berard, Rappaport, Luke-Collins, and Jaffe methods, and survival analysis was performed. Patients with a low PI (< 40%) had a significantly longer overall survival (OS) than those with a high PI (> or = 40%), but the PI did not predict failure-free survival (FFS). The mean PI correlated well with the subgroups in each of the various classifications. All four of the classification methods were predictive of OS, but only the Berard method appeared to predict FFS and suggest that a proportion of patients with FL may be curable. In multivariate analysis, histologic classification was the only independent predictor of OS (Berard method: relative risk, 3.1) and the International Prognostic Index was the only independent predictor of FFS (relative risk, 2.3). We conclude that the Berard method for grading of FL is clinically useful and, along with the International Prognostic Index, should be included in future clinical studies of FL. The measurement of cellular proliferation does not appear to add additional useful information in FL.