非霍奇金氏淋巴瘤骨髓微小病灶检测的临床意义

目的：探讨微小病灶非霍金氏淋巴瘤中的检测对病人疗效、预后的影响。方法：采有ＰＣＲ方法扩增Ｔ细胞受体γ链（ＴＣＲγ）和免疫球蛋白重链（ＩgＨ）基因重排，对１３例骨 髓形态学检查正常的Ｔ，细胞非霍奇金氏淋巴瘤（Ｔ－ＮＨＬ）和１７例Ｂ细胞非霍奇金氏淋巴瘤（Ｂ－ＮＨＬ）病人治疗前骨髓标本进行微小病灶（ＭＲＤ）检测。结果：其中７例Ｔ－ＮＨＬ病人发生ＴＣＲγ基因重排，检出率为５３．８％，１１例Ｂ－ＮＨＬ病人发生     

吉林省与日本秋田县非何杰金淋巴瘤的免疫分型与临床关系（附219例报告）

对吉林省与秋田县２１９例非何杰金淋巴瘤（ＮＨＬ）的免疫分型与临床进行了对比分析，结果发现：吉林省Ｂ－ＮＨＬ的发生率高，Ｂ、Ｔ－ＮＨＬ之比为５．１：１，其病理类型以弥漫大细胞性居多。秋田县以免疫母细胞性居多。两地区低度恶性者均占少数。Ｂ－ＮＨＬ的完全缓解（ＣＲ）率及生存期明显优于Ｔ－ＮＨＬ（Ｐ＜０．０５）。     

吉林省与日本秋田县非何杰金淋巴瘤的免疫分型与临床关系：附2…

对吉林省与秋田县２１９例非何杰金淋巴瘤（ＮＨＬ）的免疫分型与临床进行了对比分析，结果发现：吉林省Ｂ－ＮＨＬ的发生率高，Ｂ、Ｔ－ＮＨＬ之比为５．１：１，其病理类型以弥漫大细胞性居多。秋田县以免疫母细胞性居多。两地区低度恶性者均占少数，Ｂ－ＮＨＬ的完全缓解（ＣＲ）率及生存期明显优于Ｔ－ＮＨＬ（Ｐ〈０．０５）。     

抗凋亡蛋白Bcl—2在非霍奇金淋巴瘤中的表达,分布及其临床意义

研究抗凋亡蛋白Ｂｃｌ－２在非霍奇金淋巴瘤（ＮＨＬ）中的表达、分布及其临床意义。方法采用４重ＰＡＰ免疫组织化学法,对比分析了１２例反应性淋巴滤泡增生与７１例ＮＨＬ的常规石蜡包埋淋巴结组织中Ｂｃｌ－２蛋白的表达与分布。结果（１）９３．０％Ｔ、Ｂ淋巴细胞性ＮＨＬＢｃｌ－２蛋白阳性。（２）８／９例滤泡中心起源的弥漫型ＮＨＬ中,Ｂｃｌ－２蛋白局限于中心细胞,而中心母细胞多为阴性。（３）５／１０例呈浆细胞样分化趋势的弥漫性大Ｂ细胞ＮＨＬ,Ｂｃｌ－２蛋白表达增强。（４）７例滤泡型ＮＨＬ中,Ｂｃｌ－２蛋白主要定位于瘤性滤泡中央,而其周围则相对稀疏。相反,生理性淋巴滤泡中,Ｂｃｌ－２蛋白则主要分布于套区,生发中心均为阴性。结论Ｔ、Ｂ淋巴细胞ＮＨＬ均能表达Ｂｃｌ－２;Ｂｃｌ－２表达可能与ＮＨＬ分化水平相关;Ｂｃｌ－２蛋白免疫组化染色有助于鉴别反应性淋巴滤泡增生过长与滤泡型淋巴瘤。     

喉非霍奇金淋巴瘤临床病理学观察

目的对喉非霍奇金淋巴瘤（ＬＮＨＬ）这一罕见病变临床病理学特点进行观察，并对其病理诊断、起源组织及与ＥＢＶ感染的关系作一初步探讨。方法复习１８ａ间９例喉ＮＨＬ病理存档资料及临床资料，用免疫组化方法进行病理分型及观察。结果９例均表现为渐进性声嘶伴憋气，６例以呼吸困难急症入院。组织学上多形Ｔ细胞淋巴瘤５例，Ｂ细胞淋巴瘤４例，其中淋巴浆细胞样型和小细胞性各２例。２例Ｂ淋巴瘤作ＥＢＶ免疫组化染色，结果均为阳性。９例中５例确认为喉原发淋巴瘤，２例为上呼吸道多灶病变。结论ＬＮＨＬ中高度恶性的多形Ｔ淋巴瘤超过半数，区分ＬＮＨＬ免疫亚型并探讨其播散方式及与ＥＢＶ感染的关系很有必要。     

44例儿童恶性淋巴瘤的免疫病理分类及临床病理分析

本文对４４例儿童恶性淋巴瘤进行免疫病理分类和临床病理分析。结果表明，临床主要表现浅表淋巴结肿大，消溲，苍白，发热及腹腔肿块，非何杰金氏淋巴瘤３３例，全部为弥漫 型，其中Ｂ淋巴瘤１８例，裂，无裂细胞性和无裂细胞性各７例；Ｔ淋巴瘤１４例，大部分为淋巴母细胞性；组织细胞性１例。     

乳腺恶性淋巴瘤形成及免疫组织化学研究

目的：研究乳腺非霍奇金淋巴瘤（ＮＨＬ）的组织形态特点及免疫表型。方法：对１７例乳腺ＮＨＬ作形态学分析，其中１１例进行了免疫学标记，结果：１３例为原发性，４例为继发性，８例（４７．０６％）见“淋巴上皮病变”，１３例（７６．４７％），见肿瘤浸润脉管，４例（２３．５３％）伴有“淋巴细胞性乳腺病”，３例（１７．６５％）见局部瘤细胞呈靶环样排列，免疫组化示１６例（９４．１２％）为Ｂ细胞ＮＨＬ，其中２例（１２．５０％）ＫＰ１阳性，１例（６．２５％）ＵＣＨＬ－１阳性，结论：（１）大多数乳腺原发性ＮＨＬ为ＭＡＬＴ型淋巴瘤，（２）淋巴细胞性乳腺病可能是一些乳腺ＮＨＬ的前驱病变；（３）少数Ｂ细胞ＮＨＬ能与ＫＰ１或ＵＣＨＬ－１发生交叉反应。     

恶性淋巴瘤的超微病理学研究

应用进射电镜对４２例恶性淋巴瘤（ＭＬ）的超微结构进行了观察分析，其中３４例（８１％）的电镜亚型分类结果与病理分类一致，其中６例非霍奇金淋巴瘤（ＮＨＬ）的亚型分类以电镜更为正确，另２例由于电镜取材不适，将霍奇金病（ＨＤ）误诊为ＮＨＬ，复查病理后修正了电镜诊断。本组病理分类准确率为８５％，而结合电镜观察其亚型分类准确率达９５％。研究结果认为病理分类、免疫分型及电镜观察三者结合应用，可提高ＭＬ的诊断及亚型分类准确性，有助于ＭＬ的临床诊治及其深入研究。     

恶性淋巴瘤的超微病理学研究

应用透射电镜对４２例恶性淋巴瘤（ＭＬ）的超微结构进行了观察分析，其中３４例（８１％）的电镜亚型分类结果与病理分类一致，其中６例非霍奇金淋巴瘤（ＮＨＬ）的亚型分类以电镜更为正确，另２例由于电镜取材不适，将霍奇金病（ＨＤ）误认为ＮＨＬ，复查病理后修正了电镜诊断。本组病理分类准确率为８５％，而结合电镜观察其亚型分类准确率高９５％。研究结果认为病理分类、免疫分型及电镜观察三者结合应用，可提高ＭＬ的诊断及亚     

乳腺非何杰金淋巴瘤8例临床病理及免疫表型分析

本文对６例原发及２例继发乳腺ＮＨＬ进行报道分析，临床易误诊为乳腺癌，在部分病例镜下可见到淋巴上皮病损。本组组织学类型大多为高度恶性，免疫组化示：原发组６例中４例为Ｂ细胞性，１例为Ｔ细胞性，１例未定，继发２例均为Ｂ细胞性。本研究示；原发与继发乳腺ＮＨＬ主要靠临床区别，组织学形态难以鉴别，以至少部分乳腺ＮＨＬ与粘膜相关淋巴组织有关，年轻妇女乳腺ＮＨＬ预后差。     

Incidence of hematological malignancies in Martinique, French West Indies, overrepresentation of multiple myeloma and adult T cell leukemia/lymphoma.

A registry of hematological malignancies is held in the unit of cytology of the University Hospital of Martinique. Human T cell lymphotropic virus type-1 (HTLV1) is endemic in this island. We determined the incidence and epidemiological features of hematological malignancies from the 715 new cases diagnosed between 1990 and 1998 among the adult population. Incidence rates per year were steady during this period. The most frequent hematological malignancies were multiple myeloma (MM) (34%), followed by non-Hodgkin's lymphoma (NHL) (23%). Among the cases of NHL with an immunohistological study, 57% had a T cell phenotype. Among these 61% were adult T cell leukemia/lymphoma. Epidemiological data on hematological malignancies in the West Indies has not been previously reported. There are two striking differences with other population-based registries: a high incidence of MM (5/100000) and a high proportion of T cell NHL among NHL (57%). The high proportion of T cell NHL is probably due to the high incidence of ATL. A low incidence of B cell NHL might also contribute to this effect. The increased incidence of MM in West Indies had not been previously reported. A similar high incidence of MM has been reported among Afro-Americans in the USA.     

The Polymerase Chain Reaction in Diagnosis of Small B-Cell Non-Hodgkin Lymphomas

Background: Small B-cell non-Hodgkins lymphoma (NHL) is difficult to be distinguished from non-neoplastic reactive processes using conventional haematoxylin-eosin (HE) staining due to different interpretations among pathologists with diagnosis based on morphologic features. Ancillary examinations such as immunohistochemical (IHC) staining are essential. However, negative or doubtful results are still sometimes obtained due to unsatisfactory tissue processing or IHC technique. The polymerase chain reaction (PCR) as a molecular diagnostic technique is very sensitive and specific. Clonality detection of heavy chain immunoglobulin (IgH) gene rearrangement has been widely used to establish diagnosis of B-cell NHL. Aims: To elaborate interobserver variation in small B-cell NHL diagnosis based on morphologic features only and to confirm sensitivity and specificity of the PCR technique as an ancillary method. Materials and Methods: A toptal of 28 samples of small B cell NHL and suspicious lymphoma were interpreted by 3 pathologists in Sardjito General Hospital based on their morphology only. The reliability of assessment and the coefficient of interobserver agreement were calculated by Fleiss kappa statistics. Interpretation results were confirmed with IHC staining (CD20, CD3, Bcl2). PCR was performed to analyze the clonality of IgH gene rearrangement. Results: Interobserver agreement in morphologic evalution of small B cell NHL and chronic lymphadenitis revealed kappa coefficient 0.69 included in the substantial agreement category. The cases were divided into 3 groups based on morphology and IHC results; lymphoma, reactive process and undetermined group. PCR analysis showed 90% sensitivity and 60% specificity. Conclusions: The present study revealed a substantial agreement among pathologists in small B-cell NHL diagnosis. For difficult cases, PCR is useful as complementary method to morphologic and IHC examinations to establish definitive diagnosis.     

PCR-SSCP检测非霍奇金淋巴瘤患者骨髓克隆性T细胞受体基因重排及其临床意义

背景与目的：进一步了解非霍奇金淋巴瘤（non-Hodgkin‘s lymphoma,NHL)患者骨髓标本克隆T细胞受体（T cell receptor,TCR)基因重排情况及临床意义。方法：应用聚合酶链反应（polymerase chain reaction,PCR)联合单链构象多态性（single-strand conformation polymorphism,SSCP),分析43例NHL患者骨髓标本TCRVγI-Jγ基因重排情况。结果：43例NHL患者有26例（60．5％）存在克隆性TCRVγI－Jγ基因重排。16例骨髓形态学检查未发现淋巴瘤细胞浸润者中有3例（18．8％）发现克隆性TCRVγ－Jγ基因重排。此3例患者分别于4－9个月后行骨髓形态检查时发现淋巴瘤细胞浸润。27例骨髓形态学检查有淋巴瘤细胞浸润者有23例（85．2％）存在克隆性TCRVγI－Jγ基因重排阳性,26例PCR扩增阳性病例经SSCP分析发现7例（26．9）％存在寡／亚克隆重排。7例存在寡／亚克隆重排患者经3－11个月有5例（71．4％）发展为白血病,存在寡／亚克隆重排NHL患者1年内转化为白血病的发生率显著高于无寡／亚克隆重排患者（10．5％）（P＜0．005）。结论：应用PCR检测NHL患者骨髓标本克隆性TCRVγ－Jγ基因重排可较骨髓形态学检查更早发现NHL患者骨髓浸润微小病灶。具有寡／亚克隆NHL患者更易发展为白血病,还可发展为急性非淋巴细胞白血病。     

Determination of T cell monoclonality in non-Hodgkin's lymphoma by frozen section immunohistology. The SWOG Central Repository Members.

Monoclonal antibodies (mAb) reactive with seven distinct T cell receptor (TcR) alpha/beta variable region (V) families have become available. We investigated the potential utility of these mAb to establish T cell clonality (restrictive expression of one single V region family type) by frozen section immunohistology. We studied 40 non-Hodgkin's lymphomas (NHL) previously classified, immunophenotypically and genotypically by the South Western Oncology Group (SWOG) as 20 B and 20 T cell NHL. Frozen sections of each neoplasm were immunostained with the following mAb: beta-V5a, beta-V5b, beta-V6a, beta-V8a, beta-V12a, alpha/beta-Va and alpha-V2a. The large atypical lymphocytes of 18 of 20 T cell NHL showed no reactivity with the seven V region family mAb and only two showed exclusive immunoreactivity (one with anti-alpha V2a and the other with anti-beta V6a). All large atypical B cells in the 20 B cell NHL were non-reactive with the V region family mAb and each of the 40 neoplasms disclosed no or a trace reactivity in small host T cells. The results show that clonality can be determined in only a small percentage of T cell NHL (Sensitivity 10%, specificity 100%). Therefore, until new mAb become available, genotypic analysis remains the most sensitive and reliable method to establish T cell clonality.     

A prospective analysis of circulating saturated and monounsaturated fatty acids and risk of non‐Hodgkin lymphoma

Circulating saturated (SFA) and monounsaturated fatty acids (MUFA), which are predominantly derived from endogenous metabolism, may influence non‐Hodgkin lymphoma (NHL) risk by modulating inflammation or lymphocyte membrane stability. However, few biomarker studies have evaluated NHL risk associated with these fats. We conducted a prospective study of 583 incident NHL cases and 583 individually matched controls with archived pre‐diagnosis red blood cell (RBC) specimens in the Nurses’ Health Study (NHS) and Health Professionals Follow‐Up Study (HPFS). RBC membrane fatty acid levels were measured using gas chromatography. Using multivariable logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL and major NHL subtypes including T cell NHL (T‐NHL), B cell NHL (B‐NHL) and three individual B‐NHLs: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B‐cell lymphoma (DLBCL) and follicular lymphoma. RBC SFA and MUFA levels were not associated with NHL risk overall. However, RBC very long chain SFA levels (VLCSFA; 20:0, 22:0, 23:0) were inversely associated with B‐NHLs other than CLL/SLL; ORs (95% CIs) per standard deviation (SD) increase in level were 0.81 (0.70, 0.95) for 20:0, 0.82 (0.70, 0.95) for 22:0 and 0.82 (0.70, 0.96) for 23:0 VLCSFA. Also, both VLCSFA and MUFA levels were inversely associated with T‐NHL [ORs (95% CIs) per SD: VLCSFA, 0.63 (0.40, 0.99); MUFA, 0.63 (0.40, 0.99)]. The findings of inverse associations for VLCSFAs with B‐NHLs other than CLL/SLL and for VLCSFA and MUFA with T‐NHL suggest an influence of fatty acid metabolism on lymphomagenesis.     

Clinical effects of TA-077 in non-Hodgkin's lymphomas

Ten patients with non-Hodgkin's lymphomas (NHL), six untreated and four with previous chemotherapy, were treated with TA-077, a new derivative of nitrosourea. Partial remission was observed in three untreated cases (30%) of NHL [Case 1: 71-year-old female with B cell lymphoma/diffuse small cell type, Case 2: 79-year-old male with T cell lymphoma/diffuse large cell type, and Case 3: 64-year-old female with adult T cell leukemia lymphoma (ATLL)]. Remission durations were as follows: Case 1; 33 days, Case 2; 38 days and Case 3; 14 days. Side effects were transient anorexia (40%), nausea & vomiting (30%), liver dysfunction (10%) and delayed hematological toxicities (80%). Hematological toxicities consisted of leukocytopenia (80%), thrombocytopenia (60%) and anemia (20%). Our study suggests that TA-077 is a useful agent as one of the drugs used in combination chemotherapy against NHL, since it was effective for refractory T cell malignancies such as ATLL.     

Peripheral T cells of patients with B cell non-Hodgkin's lymphoma show a shift in their memory status

BACKGROUND: Tumor-infiltrating T cells have a positive influence on the clinical course of B cell non-Hodgkin's lymphoma (NHL). T cells in the peripheral blood of patients with B cell NHL, however, have so far rarely been examined. METHODS: Using flow cytometry we examined lymphocyte subpopulations and numbers of na?ve/memory T cell subtypes among peripheral T cells of patients with B cell NHL (N=22), patients with metastasized solid tumors (N=27), and healthy controls (N=20). In addition, we analyzed the intracellular content of effector molecules granzyme B and perforin and expression of the T cell receptor zeta chain. RESULTS: We observed increased percentages of potentially highly cytotoxic CD8+CD56+ T cells in the peripheral blood of patients with NHL. Both, patients with NHL and patients with solid tumors showed a much higher expression of the chemokine receptors CCR4 and CCR5 on their T cells than healthy controls, suggesting a polarization of their T cells following stimulation with antigen and/or cytokines in vivo. Furthermore, patients with B cell NHL and patients with solid tumors had far lower percentages of na?ve CD45RA+CCR7+ T cells than healthy controls and, in the case of CD4+ T cells, patients with solid tumors. In contrast, patients with B cell NHL showed markedly increased levels of memory effector CD45RA-CCR7- CD4(+) T cells when compared to healthy controls and patients with metastasized solid tumors. Patients with NHL also showed elevated levels granzyme B within CD8(+) T cells, indicating that the increase in memory effector cells was of functional relevance. CONCLUSIONS: These findings indicate a marked shift in the composition of peripheral T cells of patients with B cell NHL from na?ve to memory effector-type cells.     

Hyper—CVAD／MA方案治疗28例中国人非霍奇金淋巴瘤的有效性及安全性

目的评估Hyper-CVAD／MA强化方案治疗28例中国人T细胞性和侵袭性／高度侵袭性B细胞性非霍奇金淋巴瘤患者的有效性和安全性。方法回顾性分析28例2005年1月至2008年9月用Hyper—CVAD／MA方案治疗的初治或复治的B细胞或T细胞非霍奇金淋巴瘤患者的有效性和安全性。结果在27例可评价疗效的包括T细胞和B细胞淋巴瘤的病例中,有效率是70．4％;在13例可评价疗效的B细胞淋巴瘤中,有效率是84．6％。27例患者均发生Ⅲ度或Ⅳ度的骨髓抑制,有2例治疗相关死亡。结论Hyper—CVAD／MA方案治疗中国人T细胞性和侵袭性／高度侵袭性B细胞性非霍奇金淋巴瘤,有效率高,但毒副作用也显著,剂量需要进一步摸索。