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。     

中枢神经系统血管内ALK阳性间变性大细胞淋巴瘤一例并文献复习

目的 报道1例血管内间变性大细胞淋巴瘤激酶阳性(ALK+)间变性大细胞淋巴瘤(ALCL),提高对血管内淋巴瘤(IVL)的认识.方法 分析1例中枢神经系统血管内ALK+ALCL的临床资料、组织病理学特点和免疫表型,并结合文献进行复习.结果 患者女性,41岁.CT示右侧顶枕叶不规则低密度灶,增强扫描壁结节及边缘明显强化;磁共振(MRI)示右顶枕叶斑片状不规则异常信号影,累及右侧胼胝体压部,增强扫描呈斑片状不规则强化.血常规示单核细胞比例增高,红细胞压积减少.光学显微镜下观察:脑实质小血管管腔内多量明显异型性大单核细胞,肿瘤细胞胞质丰富嗜伊红,核圆形或不规则,可见马蹄形或肾形核,核仁清楚.免疫组织化学:肿瘤细胞LCA(+)、CD,(+)、ALK-1(+)、EMA(+)、粒酶B(+)、CD20(-)、CD79a(-)、CD30(-)、CD56(-)、GFAP(-)、AE1/AE3(-)、HMB45(-),血管内皮细胞CD31(+)、CD34(+).患者手术后8个月死亡,未行放化疗.结论 血管内ALK+ ALCL是IVL的一种罕见亚型,细胞形态特点及免疫表型类似于淋巴结或结外ALCL,临床症状无特异性,预后差,确诊主要依靠组织病理学检查.     

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.     

无骨髓及血液累及的皮肤原发B淋巴母细胞淋巴瘤一例并文献复习

目的 提高对不伴有外周血及骨髓累及的皮肤原发B淋巴母细胞淋巴瘤(B-LBL)的认识.方法 报道1例罕见的无骨髓血液累及的皮肤原发B-LBL病例的诊断和鉴别诊断过程,并结合文献复习讨论.结果 患者经手术切除行病理组织学活检和免疫组织化学检测示瘤细胞TdT+、CDd+79a、PAX5+,确诊B-LBL;遂榆杳外周血及骨髓,提示均无异常改变.诊断为皮肤原发的B-LBL.结论 皮肤原发B-LBL可不伴有外周血和骨髓病变,易造成临床误诊,需引起病理医生和外科医生的重视.     

侵袭性自然杀伤细胞白血病14例临床分析

目的 加深对侵袭性自然杀伤细胞白血病(ANKL)临床与实验室特点的认识.方法 回顾性分析14例ANKL患者的临床资料.结果 ANKL临床多表现为高热,热峰≥38.6℃,肝、脾大,淋巴结肿大;血细胞减少,肝功能及凝血功能异常;血清铁蛋白、乳酸脱氢酶水平升高.骨髓中可发现一群免疫表型为CD+2、CD+56、HLA-DR(+)、CD-3的异常细胞;疾病在诊断时多已累及全身,短期内出现全身多系统、多脏器衰竭至死亡.结论 ANKL是一组临床进展迅速的恶性血液系统疾病,预后差,死亡率高.骨髓异常细胞免疫表型检测有助于诊断.     

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.     

急性白血病患者造血干细胞P-选择素表达的研究

目的 研究急性白血病(AL)患者骨髓白血病干细胞表面分子P-选择素(CD62P)的表达情况及其临床意义.方法 采用流式细胞术(FCM)检测56例初治AL患者骨髓CD62P的表达情况,以15例健康成年人骨髓标本为对照.结果 38例急性髓系白血病(AML)患者干细胞(CD+45CD+34CD-38)中CD62P平均表达水平为(6.72±7.64)%,12例急性B淋巴细胞白血病(B-ALL)患者干细胞(CD+45CD+34CD+19)为(3.46±2.51)%,6例急性T淋巴细胞白血病(T-ALL)患者干细胞(CD+45 CD+34CD+7)为(6.23±4.95)%,均明显高于健康对照组[(1.04±1.23)%](t值分别为2.847、3.284、3.091,P＜0.01).经过正规方案治疗后,完全缓解组患者CD62P表达与健康对照差异无统计学意义(t=0.397,P＞0.05).另外CD+62P的AML及T-ALL患者白细胞计数、血红蛋白及血小板计数均明显高于CD-62P患者(t值分别为4.153、8.095、8.289、7.235、8.692、9.832,P＜0.05);而CD+62P与CD-62P的B-ALL患者无明显差异(t值分别为0.340、1.142、0.019,P＞0.05).结论 CD62P是血小板活化的标志物之一,在不同类型的AL中有不同程度的表达.AL骨髓造血干细胞中CD62P可能作为白血病造血干细胞的标志,以及临床疗效观察预后判断的指标之一.     

MTAP、CDKN2A和CDKN2B在弥漫大B细胞淋巴瘤中的表达及其临床意义

目的 研究弥漫大B细胞淋巴瘤(DLBCL)MTAP、CDKN2A和CDKN2B基因的表达及其临床意义.方法 以实时定量聚合酶链反应(PCR)方法检测40例DLBCL及19例淋巴结反应性增生组织中MTAP、CDKN2A和CDKN2B基因的表达情况,结合临床特征进行分析,并进行随访.结果 DLBCL组MTAP、CDKN2A和CDKN2B基因表达水平较淋巴结反应性增生组降低,差异有统计学意义(P值分别为0.024、0.044和0.047);三者表达均与Ann Arbor临床分期相关(P值分别为0.004、0.001和0.027);与患者的性别、年龄、淋巴结外病变累及、ECOG体力评分、骨髓累及、血清乳酸脱氢酶水平均无明显相关(均P＞0.05).其中MTAP与CDKN2A基因表达情况还与B症状(P值分别为0.003和0.028)和国际预后指数(IPI)相关(P值分别为0.001和0.011).此外,生存分析结果显示,MTAP、CDKN2A和CDKN2B基因表达水平与患者总生存期相关(P值分别为0.022、0.019和0.042).结论 MTAP、CDKN2A和CDKN2B基因在DLBCL中呈低水平表达,与疾病进展和患者预后有关,可作为反映其生物学行为和评估患者临床疗效的分子标志物.     

以附件浸润为首发的急性髓系白血病一例并文献复习

目的 报道1例以子宫附件浸润为首发的急性髓系白血病(AML),评价预后并进行文献复习.方法 采用MICM标准确诊.形态学包括骨髓涂片、细胞化学染色、组织活检、免疫组织化学,流式细胞术分析免疫表型和RHG显带技术进行细胞遗传学分析.结果 该例患者确诊为AML-M2型.结论 AML可能有特殊的临床表现和细胞遗传学改变.     

芯针穿刺活检在恶性淋巴瘤诊断中的应用

目的:探讨芯针穿刺活检诊断恶性淋巴瘤的临床应用价值,阐明其有效性.方法:采用HE和免疫组织化学染色方法,对88例芯针穿刺活检诊断为恶性淋巴瘤及淋巴组织非典型增生的病例进行回顾性研究,观察芯针穿刺活检诊断的准确率.结果:本组患者穿刺活检诊断恶性淋巴瘤的准确率为87.5%(77/88),恶性淋巴瘤90%(70/77)可区分组织类型.诊断为淋巴组织非典型增生11例,其中5例通过手术切除活检确诊为恶性淋巴瘤,6例不能明确诊断.在住院患者中,恶性淋巴瘤诊断的准确率为91%(53/58).结论:芯针穿刺活检是诊断恶性淋巴瘤可靠的方法,绝大多数患者可得到明确的分类.     

Cerebral cortex regional blood flow and tissue oxygen tension during the trigeminal depressor response in rabbits

The paradox of pancytopenia despite cellular bone marrows (BM) was investigated in 120 patients with myelodysplastic syndromes (MDS). Detailed cell cycle kinetics were examined following in vivo infusions of iodo--and/or bromodeoxyuridine (IUdR/BrdU), while the incidence of apoptosis was measured by in situ end labeling (ISEL) of fragmented DNA. Results showed that MDS are highly proliferative disorders with an equally high incidence of apoptotic intramedullary cell death accounting for the paradox of cellularity/cytopenia. By double-labeling BM biopsy sections for ISEL/BrdU we found the peculiar situation of "signal antonymy" where S-phase cells were frequently apoptotic, a phenomenon so far only seen in MDS biopsies. The cause-effect relationship of this excessive proliferation/apoptosis is discussed at length.     

Bone marrow involvement in lymphoblastic lymphoma and small non-cleaved cell lymphoma: the role of trephine biopsy

Trephine biopsy (TB) combined with bone marrow aspiration (BMA) is the most common method for evaluating bone marrow (BM) involvement in non-Hodgkin's lymphomas. Nevertheless, the role of TB in high-grade lymphomas remains controversial. We reviewed the results of 42 consecutive BMAs and TBs performed simultaneously in 29 patients with lymphoblastic lymphoma (LL) and small, non-cleaved cell lymphoma (SNCL). In LL, 8M involvement was documented in 35.4% of the cases by BMA and 22.5% of the cases by TB. In SNCL it was documented in 45.4% of the cases by BMA and 36.3% by TB. There were no statistically significant differences (p > 0.05) in the rates of BM involvement found by TB or BMA in the two types of lymphoma, although BMA appeared to be more sensitive than TB. These observations suggest that routine TB may not be necessary in assessing BM involvement in patients with LL and SNCL.     

Allogeneic CD34 selected peripheral stem cell transplant for Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI): rapid haemopoietic and biochemical reconstitution

AIM: To analyze the bone marrow (BM) infiltration in low-grade non-Hodgkin's lymphomas (LGNHL) and assess its association with the histopathology type, clinical behavior, and disease prognosis. METHOD: BM smears obtained by needle biopsy and stained by standard methods were analyzed in 60 patients with LGNHL using the Working Formulation. RESULTS: BM infiltration was observed in 57% of the lymphocytic lymphomas (A), in 48% of lymphoplasmocytic/ plasmocytoid lymphomas (AI), and in 31% of follicular lymphomas (follicular small cleaved cell and follicular mixed B and C). The difference was not significant. The 5-year survival rates for patients with and without bone marrow infiltration were 53% and 56% respectively, and 10-year survival rates were 31% and 45% (p>0.05). CONCLUSION: The presence of bone marrow infiltration at diagnosis did not significantly affect the prognosis of LGNHL.     

Population dynamics of the monogenean Anoplodiscus cirrusspiralis on the snapper, Pagrus auratus

Mobilized peripheral blood progenitor cells (PBPC) have been shown to differ qualitatively from bone marrow (BM) progenitors. The released progenitor cells are predominantly in G0/G1 and show a relatively high percentage of rhodamine dull cells. Within the BM these last two features are characteristic of the more primitive progenitors. Although the mobilized PB cells can give rise to long-term repopulation and thus contain stem cells, the frequency of stem cells is not much higher if long-term initiating cell (LTC-IC) assays are used. To determine whether quiescent stem cells are selectively released or the low-cycle status of PB progenitors is related to the release from the BM microenvironment, the cell cycle status and rhodamine content in the PB and BM during mobilization were studied and compared with steady-state BM. More differentiated and more primitive progenitors were separated based on differentiation markers and cloned in single cell assay. In mobilized PB 54% of the CD34+ cells (n=5) were rhodamine dull compared to 22% in steady-state BM (P=0.014) [n=6]. The percentage of CD34+ cells in the S/G2M phases of the cell cycle was 2.1% in the mobilized PB (n=11), and 18% in steady-state BM (n=11) [P=0.002]. During mobilization the fraction of cells in the S/G2M phase of the cell cycle was 16% in BM (n=7), similar to steady-state BM (P=0.34). The released progenitors represented a selection of BM progenitors, with significantly more primitive progenitors (CD34+/13+/33dim) and less lymphoid precursors (CD34+/19+). Within the more differentiated CD34+113+/33bright, myelomonocytic precursors, both in PB as well as in BM, the percentage S/G2M was relatively higher than in the CD34+/13+/33dim subfraction: in normal BM: median 18% vs 8% (P=0.006) [n=8]; in mobilized PB 3% vs 2% (P=0.03) [n=10]; and in BM during mobilization 24% vs 7% (P=0.01) [n=6]. The cycle status of mobilized PB progenitors was low both in the primitive and more differentiated subfractions. During the mobilization period the BM progenitors are cycling as in steady-state BM. The low-cycle status of the mobilized PB progenitors may be related to the loss of contact with the micro-environment.     

Bone marrow manifestations of Hodgkin's disease

Bone marrow trephine biopsies were performed on 107 previously untreated patients with Hodgkin's disease (HD). Fifteen patients (14%) exhibited bone marrow involvement. These consisted of two of three patients (67%) with lymphocyte depletion, six of 27 patients (22%) with mixed cellularity, five of 64 patients (8%) with nodular sclerosis, and two who were unclassified. Twelve patients manifested a diffuse pattern of involvement; three, a focal pattern. In eight patients more than 70% of the marrow biopsy was replaced by Hodgkin's tissue, in one patient 50% of the marrow biopsy was replaced, and in six patients less than 30% of the marrow biopsy was replaced. Typical Reed-Sternberg (RS) cells were found in the trephine biopsies in 13 of the 15 patients and mononuclear RS variants in two. Bone marrow involvement was the only evidence of stage IV disease in 10 of the 15 patients. In addition to the 15 patients with initial involvement with HD, 11 patients without marrow involvement exhibited granulomas (six) and benign lymphocytic aggregates (five) in their trephine sections. Hematological parameters were studied in all pretreatment patients. Only in the nodular sclerosis group were these parameters useful in differentiating patients with and without Hodgkin's involvement of the marrow. Seventeen additional patients who had been previously treated at the time HD was demonstrated in their bone marrow were also studied. Large areas of necrosis were frequently seen in previously treated patients and one patient demonstrated cryptococcosis in the bone marrow.     

Comparison between a lyse-and-then-wash method and a lyse-non-wash technique for the enumeration of CD34+ hematopoietic progenitor cells

The flow cytometric enumeration of CD34+ hemopoietic precursor cells (HPC) present in samples used for transplantation of HPC has proven to be the most powerful single parameter for prediction of engraftment. At present, several different methodological approaches are used for the flow cytometric enumeration of CD34+ HPC. In the present study we have compared two of these methods as regards enumeration of CD34+ HPC and their CD34+/CD19- and CD34+/CD19+ subsets: a lyse-non-wash procedure based on the use of a recently commercialized red cell lysing solution (Quicklysis, Cytognos, Salamanca, Spain) and a lyse-and-then-wash method in which the Becton Dickinson (San Jose, CA) FACS Lysing Solution was used. For that purpose a total of 52 samples corresponding to 20 G-CSF mobilized peripheral blood (PB) samples and 21 PB-derived leucapheresis products from patients undergoing autologous PB stem cell harvest, together with 11 bone marrow (BM) samples from healthy volunteers were analyzed. Our results show that for each of the three types of samples analyzed the use of the lyse-and-then-wash method is associated with significantly lower numbers of both total CD34+ HPC (P < or = 0.003) and its major CD34+/CD19- subset (P < or = 0.01) while no significant changes are detected in the number of CD34+/CD19+ HPC in BM samples (P > 0.05). The use of an internal standard (reference beads) added just prior to data acquisition, showed that the differences between both methods are due to a selective loss of CD34+ HPC and its major CD34+/CD19- subset in BM (P=0.002 and P=0.003), PB (P < 0.0001 and P < 0.0001) and PB-derived leucapheresis products (P < 0.0001 and P=0.0001). Finally, addition of a centrifugation and washing step to a group of 11 leucapheresis samples lysed with Quicklysis showed that they did not significantly affect the overall number of total CD34+, CD34+/CD19- and CD34+/CD19+ HPC obtained. In line with these findings elimination of centrifugation and washing steps when FACS Lysing Solution was used to lyse mature red cells almost corrected for the selective loss of CD34+ HPC. In spite of these differences a significant degree of correlation (r > 0.83 in all cases) was found between both methods regarding the total number of CD34+, CD34+/CD19- and CD34+/CD19+ HPC present in the BM, PB and PB-derived leucapheresis samples analyzed in this study.     

Clinical predictors of non-diabetic renal disease in patients with non-insulin dependent diabetes mellitus

BACKGROUND: Several studies had suggested that non-diabetic renal disease (NDRD) was common among non-insulin dependent diabetes mellitus (NIDDM) patients with renal involvement. METHODS: We prospectively studied the prevalence of NDRD among a Chinese NIDDM population. Renal biopsy specimens were evaluated with light-, immunohistological and electron-microscopy. The cohort consisted of 51 patients who had NIDDM and proteinuria > 1 g/24 h. RESULTS: Patients with both isolated diabetic nephropathy (DN, n = 34) and NDRD (n = 17) had comparable duration of DM, creatinine clearance, serum creatinine, albumin and glycosylated haemoglobin levels, as well as incidences of retinopathy, neuropathy and hypertension. Significantly more patients with NDRD had microscopic haematuria (P = 0.043) or non-nephrotic proteinuria (P = 0.004). IgA nephropathy accounted for 59% of the NDRD identified. CONCLUSIONS: In this study, microscopic haematuria and non-nephrotic proteinuria predicted the presence of NDRD among NIDDM patients presenting with renal disease.     

Antimicrobial substances produced by Staphylococcus aureus strains isolated from cattle in Brazil

Many studies have documented faster engraftment after transplantation with peripheral blood stem cells (PBSC) compared to bone marrow (BM) stem cells. Most comparisons, however, have been between unprimed BM and primed PBSC. We have collected engraftment data on 39 patients from 4 Danish centres and compared G-CSF primed BM with G-CSF primed PBSC in malignant lymphoma and solid tumours. In the lymphoma group 6 BM transplants were compared with 8 PBSC transplants, whereas in the testicular cancer group 16 BM transplants were compared with 9 PBSC transplants. In the lymphoma group, the time to platelet engraftment (platelets >20x10(9)/l unsupported) was median 15 d in PBSC transplants and median 34 d in BM transplants (p=0.003). In the solid tumour patients the difference in time to platelet engraftment was 11 and 18 d in PBSC and BM transplants, respectively (p<0.0001). In an attempt to explain this difference we performed CD34+ subset analysis of BM and PBSC. This analysis revealed a higher content of lineage restricted cells (CD34+CD61+ and CD34+GlyA+) in PBSC compared to BM. In conclusion, G-CSF mobilized PBSC seems to result in faster engraftment than G-CSF primed BM, which could be explained by an increased number of lineage specific progenitors in PBSC compared to BM.