淋巴瘤骨髓浸润的磁共振成像定性和定量诊断价值

 【摘要】　目的　探讨磁共振成像（MRI）对淋巴瘤患者骨髓浸润的定性及定量诊断价值。方法　回顾性分析28例确诊淋巴瘤骨髓浸润的患者,MRI定性分析脊柱骨髓浸润的影像特征,定量测量病变骨髓与脑脊液在T1加权图像上的信号强度比（SIR1）。以31例正常脊柱骨髓为对照组。结果　定性诊断：27例患者脊柱骨髓MRI见异常信号,1例假阴性,MRI诊断的敏感度为96.4 %;淋巴瘤骨髓浸润的脊柱MRI表现主要有4种类型,分别为局灶型21.4 %（6／28）,多灶型53.6 %（15／28）,斑驳型14.3 %（4／28）,弥漫型7.1 %（2／28）。定量诊断：淋巴瘤组骨髓的SIR1（1.251±0.253）明显低于对照组（2.625±0.434）,两组差异有统计学意义（t＝15.022,P＜0.001）;轻、中、重度骨髓浸润SIR1值（分别为1.390±0.172、0.982±0.790、0.908±0.122）与对照组比较,差异均有统计学意义（均P＝0.000）,骨髓浸润轻度与中度组间、轻度与重度组间SIR1值差异有统计学意义（LSD法,P＝0.012,P＝0.025）,中度与重度组间的SIR1值的差异无统计学意义（LSD法,P＝0.757）;淋巴瘤骨髓浸润的骨髓SIR1值与骨髓中浸润的瘤细胞百分比呈负相关（r＝-0.765,P＜0.001）。结论　MRI无创、直观,能够展示骨髓全貌,对淋巴瘤骨髓浸润诊断敏感度高,定量分析能一定程度区分骨髓浸润程度,并反映骨髓中瘤细胞负荷量。     

白血病骨髓磁共振成像的定量测定

背景与目的:国内外对白血病骨髓磁共振成像(MRI)及MRI与临床实验室指标的相关性进行了大量的研究,但将淋巴细胞性白血病(lymphoidleukemia,LL)与髓细胞白血病(myeloidleukemia,ML)分开研究的不多。本研究分别测量LL与ML脊柱骨髓MRI信号强度比(signalintensityratio,SIR),探讨MRI定量测量在白血病组织学定性诊断(LL与ML)及肿瘤负荷评价中的作用。方法:对初诊的20例LL,10例ML进行脊柱骨髓MRI检查,全部白血病的诊断均经骨髓细胞学检查证实。脊柱骨髓MRI检查使用0.5T超导型磁共振成像系统,进行自旋回波(spinecho,SE)序列T1加权像(T1WI)及快速自旋回波(turbospinecho,TSE)序列T2加权像(T2WI),在T1WI上测量白血病骨髓SIR,同时进行外周血常规检查及髂骨骨髓细胞学检查。结果:20例LL和10例ML脊柱骨髓SIR分别为0.72±0.11、0.73±0.11,LL与ML之间SIR无统计学差异(P=0.836)。LL中脊柱骨髓SIR与骨髓内淋巴系幼稚细胞比均呈负相关(r=-0.836,P=0.000)。ML脊柱骨髓SIR与骨髓内粒系幼稚细胞比呈负相关(r=-0.673,P=0.033)。结论:SIR不能区分LL、ML,其组织学定性诊断价值有限,但SIR可评价白血病的肿瘤负荷。     

急性淋巴细胞白血病患者 ASB2和 Jak3基因mRNA 表达的研究

目的：研究急性淋巴细胞白血病（ALL）患者骨髓中锚蛋白重复序列和抑制细胞因子信号盒蛋白2（ASB2）和 Janus 激酶3（Jak3）mRNA 的表达及其两者的相关性。方法收集初诊的48例 ALL患者（37例 B 细胞 ALL,11例 T 细胞 ALL）和34例非白血病患者（对照组）骨髓,采用实时荧光定量 PCR检测骨髓中 ASB2和 Jak3 mRNA 表达情况。结果B 细胞 ALL 和 T 细胞 ALL 患者骨髓中 ASB2 mRNA表达量相对于对照组分别升高了32．7倍和68．5倍,差异均有统计学意义（t ＝20．1,P ＜0．01;t ＝23．1, P ＜0．01）,Jak3 mRNA 表达量较对照组分别升高了2336．3和7131．5倍（t ＝70．2,P ＜0．01;t ＝90．4, P ＜0．01）。ASB2和 Jak3 mRNA 表达量具有相关性（r ＝0．523,P ＜0．001）。结论ASB2和 Jak3在 ALL患者骨髓中异常表达,且具有正相关性,两者可能共同参与白血病细胞的恶性增殖和异常分化。     

恶性淋巴瘤患者血清瘦素及一氧化氮水平变化

目的 探讨恶性淋巴瘤患者血清瘦素及一氧化氮（NO）的水平变化。方法 采用RIA法，硝酸还原法对30例恶性淋巴瘤患者和30例正常对照进行瘦素及NO测定。结果 30例初治恶性淋巴瘤患者瘦素低于正常水平（P＜0．05），早晚期有明显差异（P＜0．05），缓解后瘦素水平上升，但仍低于正常对照（P＜0．05）；NO水平明显高于正常对照（P＜0．05），早晚期无明显差异（P＞0．05）。治疗缓解后NO与正常对照组无明显差异（P＞0．05）。结论 瘦素及NO可能与恶性淋巴瘤发病有关，并可能作为其临床分期及疗效判断的有效指标。     

增殖细胞核抗原和p53蛋白在胆囊癌中的表达

本文应用PCNA和p53抑癌基因蛋白的免疫络化方法，对11例胆囊上皮良性病变和33例胆囊癌进行了研究，结果发现胆囊良性病变和胆囊癌的平均PCNA指数分别为：良性病变为24．1％（n＝11．x±24．6），高分化癌为48．0％（n＝13，x±12．8），中分化癌为49．5％（n＝11，x±15．4）．低分化癌为76．4％（n＝9，x±18．1）；高分化胆囊癌平均PCNA指数明显高于良性病变（P＜0．05）；低分化癌的平均PCNA指数明显高于高分化癌（P＜0．05）；11例胆囊上皮良性病变均无p53蛋白阳性表达；33例胆囊癌p53阳性表达12例（36．4％），高分化癌p53阳性率为15．4％（2／13）．中分化癌45．5％（5／11）．低分化癌55．6％（5／9）：各组阳性率比较无显著性差异（P＞0．05）；PCNA指数≥50％的胆囊癌其p53蛋白阳性率明显高于PCNA指数＜50％的胆囊癌（P＜0．05）。结果提示：PCNA指数与胆囊癌的分化程度有关．PCNA及p53蛋白的免疫组化染色对胆囊上皮良、恶性病变的鉴别论断有帮助。本文还就胆囊癌p53蛋白表达与PCNA指数的关系进行了讨论。     

多肿瘤抑制基因MTS1 mRNA和蛋白在胃癌及癌前病变中的表达及意义

目的：探讨多肿瘤抑制基因（MTS1）在胃癌发生、发展中的意义和临床应用价值。方法：应用原位分子杂交技术、免疫组织化学技术分别检测210标本中MTS1基因mRNA及其蛋白的表达规律。结果：正常胃粘膜、轻、中度异型增生及小肠型肠化间差异无显著性（P＞0．05），但与重度异型增生、结肠型肠化及胃癌组织间差异有显著性（P＜0．01），而后三者相互间差异则无显著性（P＞0．05）。正常胃粘膜与轻、中度异型增生之间MTS1蛋白表达的阳性率及强阳性率差异无显著性（P＞0．05）；正常胃粘膜与重度异型增生之间MTS1蛋白阳性率差异无显著性（P＞0．05），而强阳性率间差异则有显著性（P＜0．01）。正常胃粘膜与两型肠化及胃癌组织间的阳性率、强阳性率差异均有显著性（P＜0．05，P＜0．01），重度异型增生、两型肠化与胃癌组织间的阳性及强阳性差异均无显著性（P＞0．05）；MTS1蛋白阴性表达患者五年生存率与阳性表达者差异无显著性（P＞0．05），而两者与强阳性表达者的差异则有显著性（P＜0．01）。结论：MTS1基因变异在胃癌的发生、发展中具有重要意义。MTS1基因mRNA及其蛋白表达的检测有助于胃癌的早期诊断和治疗；其蛋白的功能异常与患者预后密切相关。     

子宫肌瘤与腺肌瘤组织及患者外周血白细胞ER、PR测定

本文对子宫肌瘤及腺肌瘤与雌、孕激素的关系进行对比研究，结果子宫肌瘤及腹肌瘤组织雌激素受体（ER）阳性率均明显高于正常子宜肌层组织（P＜0．01及P＜0．·05），孕激素受体（PR）阳性年仅腺肌瘤组织显著低于正常子宫肌层组织（P＜0．05）；子宫肌瘤、像肌瘤患者与正常对照组外周血白细胞均存在ER、PR，三组之间无显著性差异（P＞0．05）；子宫肌瘤及腺肌瘤患者增生早期血清雌二醇（E2）明显高于正常人群（P＜0．05），肌瘤患者血清孕酮（P）明显低于正常人群（P＜0．05），提示血清激素水平失调及瘤组织中激素作用的不平衡性，可能与肌瘤及腺肌瘤的发生、发展有一定关系。血清E2增高及瘤组织中可能存在的高E2环境，抑制机体免疫功能，也可影响肌瘤及腺肌瘤的发生、发展。     

根治术前后肿瘤细胞在骨髓中播散的自动显微图像研究

目的对比研究泌尿系肿瘤患者根治术前后骨髓中散在的微转移肿瘤细胞。方法术前及术后采集肾癌、前列腺癌和尿道膀胱癌共102例患者的骨髓标本,应用细胞角蛋白的免疫细胞化学方法及自动显微图像对比检测分析。结果根治术前后骨髓中微转移肿瘤细胞检出率密切相关（P＜0．005）,术前肿瘤细胞总检出率为31．4％,术后为34．3％,无显著性差别（P＝0．65）;三种泌尿肿瘤患者根治术前后检出率比较亦均无明显差别（P＝0．70P＝0．10P＝0．59）但术后检出的肿瘤细胞数多于术前者（总数分别为64和44）,3个以上阳性细胞仅在术后出现,两次阳性的细胞数均值分别为1．31±0．48和1．95±1．02（P＝0．0099）12例患者手术8天后检出细胞数（22）明显多于术前者（7）,P＝0．01。结论免疫细胞化学方法可作为检测骨髓中隐蔽的微转移肿瘤细胞的敏感标准方法,根治术前后检出率虽无明显改变,但术后及手术8天以后检出细胞数明显多于术前者,提示手术可能会促使肿瘤细胞在骨髓中的播散。     

COBDP方案和改良的INBDP方案治疗非霍奇金淋巴瘤

目的 探讨COBDP方案和改良后的INBDP联合化疗方案在治疗非霍奇金霍奇金淋巴瘤中的临床近期疗效和毒副反应。方法 以异环磷酰胺,诺维本分别替代COBDP联合化疗方案中的环磷酰胺和长春新碱。两种方案共治疗非霍奇金淋巴瘤73例进行疗效比较,以χ^2和P值检验。结果 INBDP方案组CR摔79．3％,优于CDBDP方案组的56．9％,（χ^2＝3．926,P＜0．05）。INBDP方案组RR率93．1％高于COBDP方案组81．8％,（χ^2＝1．883,P＜0．05）。两组方案的副反应均表面在骨髓抑制,INBDP方案组比COBDP明显。     

结直肠癌组织中B细胞集落增强因子基因表达水平及其临床意义

目的：探讨前 B 细胞集落增强因子（PBEF）基因在结直肠癌中的表达情况,分析其与结直肠癌临床病理特征的关系以及诊断和预后价值。方法采用免疫组织化学 SP 法,检测68例结直肠癌组织标本及其癌旁正常组织中 PBEF 的表达水平,分析 PBEF 表达水平与肿瘤病理特征及预后之间的相关性。结果结直肠癌组织和正常肠黏膜组织中 PBEF 的表达阳性率分别为80．9％（55／68）和29．4％（20／68）,两组间差异有统计学意义（χ2＝36．41,P ＜0．05）。结直肠癌组织中 PBEF 表达水平与患者年龄（χ2＝0．11,P ＞0．05）、性别（χ2＝0．39,P ＞0．05）、组织学类型（χ2＝0．54,P ＞0．05）、是否穿透浆膜（χ2＝1．55,P ＞0．05）无关,但与分化程度（χ2＝6．29,P ＜0．05）、淋巴结转移（χ2＝4．32,P ＜0．05）、远处转移（χ2＝4．16,P ＜0．05）及临床分期（χ2＝7．58,P ＜0．05）有关。PBEF 蛋白表达阳性、阴性患者的5年生存率分别为73．3％、81．8％,两组差异无统计学意义（χ2＝0．315,P ＞0．05）。结论PBEF 异常高表达可能与结直肠癌的发生、发展密切相关。     

多发性骨髓瘤MRI骨髓浸润模式与血管生成关系的研究

目的:探讨多发性骨髓瘤MRI骨髓浸润模式与血管生成的相关性。方法:以25例初诊MM患者为研究对象,进行传统影像学、血清肌酐、血清蛋白、β2微球蛋白、乳酸脱氢酶等检测,并根据Durie-Salmon分期系统进行分期。对骨髓瘤患者在初诊及治疗之前行脊柱T1WI、STIR和常规的T1WI增强扫描,分析骨髓瘤细胞在骨髓内的浸润模式。对照组包括非恶性血液病患者10例,其骨髓涂片及活检检查均证实为正常骨髓象。对研究组和对照组患者均进行骨髓活检及病理检查,免疫组化测定微血管密度（MVD）,以CD34单抗标记微血管内皮细胞。另外,采集骨髓后分离上层血浆,采用ELISA法测定VEGF蛋白浓度,根据结果进行统计学分析。结果:初治MM患者骨髓上清VGEF水平及MVD高于健康对照组（P＜0.05）。MRI骨髓弥漫性浸润的MM患者骨髓上清VGEF水平及MVD高于MRI骨髓成像正常或局灶性浸润的患者（P＜0.05）。结论:MRI骨髓弥漫性浸润模式与血管生成密切相关。     

胃肠道淋巴瘤64排螺旋CT与MRI影像学特点分析

目的 探讨原发性胃肠道淋巴瘤(PGIL)64排螺旋CT和磁共振成像(MRI)的影像学特点.方法 选取41例原发性胃肠道淋巴瘤患者,包括23例胃淋巴瘤和18例肠道淋巴瘤;同时选取32例胃间质瘤患者和40例结肠癌患者作为对照.比较胃淋巴瘤与胃间质瘤、肠道淋巴瘤与结肠癌的CT、MRI影像学特点.结果 CT扫描显示,大部分浸润型胃淋巴瘤患者的胃黏膜完整,胃壁不规则增厚且多呈稍低密度或等密度影;常规增强扫描后,胃黏膜明显强化.MRI检查显示,肿瘤组织在T1WI上多呈稍低或等信号,在T2WI上多呈稍高或等信号.胃淋巴瘤门静脉期平均CT值和平均表观弥散系数(ADC)值分别为(65.02±21.15)Hu和(0.81±0.10)×10-3cm2/s,均低于胃间质瘤,差异均有统计学意义(P﹤0.05);胃淋巴瘤和胃间质瘤的发病部位(胃窦、胃体、胃底)比较,差异均有统计学意义(P﹤0.05).肠道淋巴瘤CT扫描显示,肠道管腔狭窄或扩张,肠道管壁增厚且多呈等密度影;常规增强扫描后,增厚肠道管壁均匀强化,在T1WI上呈稍低或等信号,在T2WI上呈稍高信号.肠道淋巴瘤平均ADC值为(0.89±0.17)×10-3cm2/s,低于结肠癌的(1.27±0.32)×10-3cm2/s,差异有统计学意义(P﹤0.05).结论 胃肠道淋巴瘤CT及MRI表现有一定的特征,其CT值及ADC值具有一定的诊断价值.     

Hypoplastic myelodysplastic syndrome

Over a period of 8 years 11 of 64 patients seen at Loyola University Medical Center with the diagnosis of myelodysplastic syndrome (MDS) also exhibited bone marrow hypoplasia (marrow cellularity of 25% or less) at presentation. The other 53 had normocellular or hypercellular marrow. Clinical features, hemograms, chromosome analysis, incidence of progression to acute leukemia or aplastic anemia, and survival in each group were compared. Using the French-American-British (FAB) classification, there were seven patients with refractory anemia (RA), one refractory anemia with ringed sideroblasts (RARS), and three refractory anemia with excess blasts (RAEB) in the hypoplastic MDS group. Those with normocellular or hypercellular marrow included 22 with RA, nine with RARS, 12 with RAEB, three with chronic myelomonocytic leukemia, and four with RAEB in transformation; one had chronic diGuglielmo syndrome and two patients were not classified. Patients with hypoplastic MDS had lower hemoglobin levels (median, 8 g/dl versus 9 g/dl), more severe leucopenia (median 3100/microliter versus 4200/microliter) and thrombocytopenia (median, 28,000/microliter versus 75,000/microliter), and marked macrocytosis (mean corpuscular volume (MCV), 107 mu 3 versus 97 mu 3). Nine patients with hypoplastic MDS had a chromosome analysis of the bone marrow, and all were normal. In those with normocellular or hyperplastic bone marrow, 22 such analyses were done, and seven (23%) were abnormal. One patient (11%) from the hypoplastic group and 11 (23%) from the normocellular or hyperplastic MDS transformed into acute leukemia. None progressed to aplastic anemia. With a mean follow-up time of 33 months in the hypoplastic MDS, eight patients (72%) are alive. In the group with normal or hyperplastic MDS, the mean follow up was 47 months, and 27 patients (50%) have survived. The two groups differ significantly in leukocyte count (P less than 0.0015), platelet count (P less than 0.0001), and MCV (P less than 0.0023). There may be a possible difference between these groups related to abnormal karyotype, but it is not statistically significant (P = 0.06). Therapy with pyridoxine, folic acid, prednisone, anabolic steroids, retinoids, or low-dose cytosine arabinoside was not beneficial in hypoplastic MDS. Hypoplastic MDS appears to be a distinct clinicopathologic entity characterized by marrow hypoplasia, macrocytosis, severe leucopenia and thrombocytopenia, low incidence of progression to acute leukemia, and unresponsiveness to conventional therapy.     

The detection of bone marrow involvement by lymphoma using magnetic resonance imaging

We used magnetic resonance (MR) to image the bone marrow of 31 patients with lymphoma. Images were obtained of the femoral, pelvic, and vertebral marrow with a 0.15 tesla imaging system using a T1-weighted spin echo sequence (TR600/TE 40). With this pulse sequence, normal marrow produces a high intensity signal that reflects the presence of marrow fat (short T1 relaxation time). We previously reported MR imaging of patients with leukemia in relapse and found a diffusely and symmetrically decreased marrow signal intensity due to the replacement of normal marrow fat by cellular material with a long T1. Unlike leukemia, patients with lymphomatous marrow involvement often had patchy, often discrete, areas of low signal intensity, representing focal marrow infiltration. Five of six patients in this study with lymphoma detected by histologic examination also had marrow lesions seen on MR. An additional four patients had marrow lesions detected by MR that were not detected on initial marrow biopsies; two of these had marrow involvement proven on subsequent biopsies, one had disease isolated to the vertebrae that was never pathologically documented, and one had progression of disease in the marrow documented by MR without biopsy confirmation. These results indicate that marrow involvement with lymphoma can be detected by MR imaging and that MR can complement bone marrow biopsy.     

Low field strength magnetic resonance imaging of bone marrow in patients with malignant lymphoma

Detection of bone marrow infiltration by lymphoma with low field strength magnetic resonance imaging (MRI) has been assessed. Measurements of spin lattice relaxation time (T1) were made in 31 patients with lymphoma and compared with the results of bone marrow biopsy and with T1 measurements made on 90 healthy volunteers. The sensitivity of MRI was excellent in patients for whom the microscopic pattern of marrow infiltration was diffuse, but poor in those with microscopically focal infiltration.     

Denileukin diftitox and hyper-CVAD in the treatment of human T-cell lymphotropic virus 1-associated acute T-cell leukemia/lymphoma

We report a case of human T-cell lymphotropic virus 1 (HTLV-1)-associated adult T cell leukemia/lymphoma (ATL) in clinical remission > 1 year after therapy with denileukin diftitox and hyper-CVAD (hyperfractionated cyclophosphamide/doxorubicin/vincristine/decadron). The patient presented with leukocytosis, anemia, and thrombocytopenia, and bone marrow biopsy demonstrated extensive myelofibrosis and infiltration with leukemic T cells. Initial therapy with 4 cycles of denileukin diftitox resulted in restoration of normal hematopoiesis and a reduction in bone marrow myelofibrosis. After disease progression, 4 cycles of hyper-CVAD were administered and a complete clinical remission was achieved. The patient remains free of disease with normal hematopoiesis and has continued maintenance therapy with denileukin diftitox for 1 year. This case demonstrates clinical improvement of myelofibrosis and acute T-cell leukemia after denileukin diftitox administration, suggesting that denileukin diftitox may affect the paracrine secretion of HTLV-1-associated clinical manifestations of ATL.     

继发性骨淋巴瘤的18F-FDG PET/CT影像诊断及与骨髓活检诊断效能的比较

目的:分析继发性骨淋巴瘤的PET/CT影像特点,比较骨髓活检（bone marrow biopsy,BMB）及PET/CT诊断骨淋巴瘤各自的优势,探讨如何进一步提高骨淋巴瘤的检出率。方法:回顾性分析放化疗前在我院行PET/CT检查的68例继发性骨淋巴瘤影像及骨髓活检资料。所有病例均病理确诊为淋巴瘤。骨淋巴瘤病灶的诊断标准:BMB阳性或骨局灶性FDG代谢增高且治疗后代谢减低或消失。采用SPSS 16.0统计分析不同分组的SUVmax及诊断效能差异。结果:PET/CT与BMB诊断灵敏度比较:68例中63例行BMB。PET/CT的总体诊断灵敏度及对非惰性淋巴瘤的诊断灵敏度高于BMB（P＜0.05）,而对惰性淋巴瘤,BMB灵敏度略高于PET/CT(P＞0.05)。PET/CT表现与BMB结果:根据PET/CT所见分为骨质破坏组（18例）和骨髓浸润组（50例）,骨质破坏组的SUVmax明显高于骨髓浸润组（P＜0.01）。骨质破坏组以弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma,DLBCL）为主,PET/CT均阳性。骨髓浸润组PET/CT阳性41例,表现为局灶性增高、弥漫不均匀性增高和弥漫均匀性增高,弥漫均匀性增高组的SUVmax明显低于其它两组。BMB阴性21例,其中骨质破坏组8例,局灶性骨髓浸润13例。病理类型与PET/CT表现:31例DLBCL、10例其它侵袭性非霍奇金淋巴瘤（non-Hodgkin's lymphoma,NHL）及6例霍奇金淋巴瘤（Hodgkin's lymphoma,HL）均PET/CT阳性;18例惰性淋巴瘤PET/CT仅11例阳性。DLBCL的SUVmax明显高于惰性淋巴瘤（P＜0.05）。结论:继发性骨淋巴瘤骨髓浸润多于骨质破坏。骨质破坏和局灶性骨髓浸润多见于侵袭性骨淋巴瘤,而弥漫性骨髓浸润更多见于惰性淋巴瘤。PET/CT对骨质破坏、局灶性骨髓浸润的诊断优于BMB,而BMB对弥漫性骨髓浸润的诊断优于PET/CT。联合BMB和PET/CT才能更准确地诊断骨淋巴瘤。     

非霍奇金淋巴瘤患者血清CA125和VEGF水平与骨髓浸润的相关性研究

 目的　评价CA125和血管内皮生长因子（VEGF）作为预测非霍奇金淋巴瘤（NHL）患者骨髓浸润的血清学指标的价值。方法　97例经病理确诊的初治NHL患者,其中50例经骨髓活检或骨穿检查证实有骨髓浸润,46例骨髓正常者作为对照组。采用ELISA方法分别于化疗前检测血清CA125和VEGF水平。结果　97例NHL患者中,骨髓浸润者占51.5 %（50例）,骨髓正常者占45.5 %（47例）。有骨髓浸润组其血清CA125和VEGF水平明显高于无骨髓浸润组（P＜0.05）。VEGF水平与骨髓中肿瘤细胞所占百分比呈正相关（r＝0.498,P＝0.01）,CA125水平与其无明显相关。结论　NHL骨髓浸润者血清CA125和VEGF明显升高,而且VEGF水平与骨髓浸润程度呈正相关。