We reported a case of 73-year-old male with multiple pulmonary nodules and cavities. The patient was admitted with a chief complaint of "dry cough with shortness of breath for 3 months". Chest CT showed multiple irregular masses, nodules, and patchy lesions in both lungs, accompanied by the formation of cavities. He also had anemia and renal dysfunction. Despite given empirical anti-infective and anti-tuberculosis treatments, the pulmonary nodules progressed, and the cavities enlarged. Anti-neutrophil cytoplasmic antibodies (ANCA) were negative twice. Bronchoscopic biopsy was performed. The mucosal pathology of the right middle lobe lesion showed little necrosis, focal granulomatous structure formation, and relevant vasculitis and remaining vessel wall structure in the necrosis lesions by elastic fiber staining. A clinical diagnosis of ANCA-negative necrotizing granulomatous polyangiitis was made and the patient was treated with glucocorticoids and cyclophosphamide. The nodules and cavities shrank, and some lesions were absorbed.

目的 总结单形性嗜上皮性肠道T细胞淋巴瘤(monomorphic epitheliotropic intestinal T-cell lymphoma,MEITL)的临床特征、诊治过程及预后.方法 回顾性分析2014年5月～2021年5月我院11例MEITL临床资料.男10例,女1例.年龄27～69岁,中位年龄58岁.病变位于小肠7例,结直肠1例,同时累及小肠和结肠1例,小肠和食管1例,结肠和肺1例.8例经手术确诊,手术指征为肠穿孔5例,肠梗阻1例,小肠占位1例,食管占位1例,行小肠部分切除吻合术5例,小肠肿瘤切除、远端旷置、近端造瘘术1例,腹腔镜小肠部分切除吻合术1例,食管癌根治术1例,术后均接受化疗,术后首周期化疗均未发生严重的腹腔感染或手术伤口感染.3例内镜病理确诊,接受化疗,其中1例接受自体造血干细胞移植,1例化疗中肠梗阻行小肠部分切除吻合.结果 10例死亡,中位生存期14.5月(3～25月),1例随访70个月生存.结论 MEITL起病隐匿,常以急腹症为首诊症状,治疗以化疗为主,外科手术在辅助明确诊断及肠道并发症的治疗方面具有重要作用.

Objective:To explore the clinical application of NanoString fluorescent barcode technology in the molecular subtyping of diffuse large B-cell lymphoma (DLBCL), and to analyze the correlation between the cell-of-origin subtype and prognosis of patients.Methods:The tumor tissue samples of 12 patients with DLBCL at the Third People's Hospital of Datong of Shanxi Province and 8 patients with DLBCL at Peking University, Health Science Center between January 2014 and December 2019 were collected. According to Hans algorithm, all patients were divided into 1 case of germinal center-derived B-cell (GCB) type and 19 cases of non-GCB type. NanoString platform was used to analyze the expression level differences of 15 genes-related to Lymph2Cx molecular subtyping of all samples at mRNA level. Hierarchical clustering was used to subgroup 20 DLBCL cases and to contrast the prognosis in different subgroups according to the subtyping.Results:NanoString fluorescent barcode technology was used to detect samples of 20 DLBCL cases and hierarchical clustering analysis was performed, and then subtyping results showed that 11 cases were GCB-like type and 9 cases were activated B cell (ABC)-like type. Based on Hans algorithm, 10 GCB-like cases were non-GCB type. According to the survival analysis, GCB-like group had a better overall survival compared with that in ABC-like group ( P=0.019). Conclusion:NanoString fluorescent barcode technology can be successfully applied to the cell-of-origin subtyping of DLBCL, and the molecular subtyping strategy can effectively predict the prognosis of patients.

目的 探讨单形性亲上皮性肠道T细胞淋巴瘤(MEITL)的临床病理特点、免疫表型及分子遗传学改变.方法 选择新乡医学院第一附属医院及北京大学第三医院收治的16例MEITL患者,采用免疫组织化学、原位杂交及T细胞受体(TCR)基因克隆性重排检测等方法检测其组织病理学,分析患者的临床病理学特点.结果 16例MEITL患者中男女比例为9:7,中位发病年龄为54岁.13例患者病变部位位于小肠,1例位于升结肠近回盲部,1例位于降结肠,1例位于乙状结肠;临床表现以腹胀、腹痛、腹泻为主,部分出现腹部肿块及肠穿孔,无特异性改变;镜下肿瘤细胞形态较单一,小至中等大,细胞质淡染,核圆形、核仁不明显,染色质细腻;可见"亲上皮现象",核分裂象及坏死易见.免疫组织化学检测结果显示,CD3、CD8、CD56、T细胞胞内抗原1(TIA-1)、B淋巴细胞瘤-2(Bcl-2)呈阳性表达,CD5、Granzyme B呈阴性表达,Ki-67增殖指数50％ ～90％;原位杂交结果显示,EB病毒编码的小RNA阴性.TCR重排检测阳性14例,阴性2例.结论 METCL是罕见的原发胃肠道的高侵袭性淋巴瘤,多位于小肠,无特异性的临床表现,肿瘤细胞形态较单一,可见"亲上皮现象",核分裂象及坏死易见,CD3、CD8、CD56、TIA-1、Bcl-2呈阳性表达,CD5、Granzyme B呈阴性表达,Ki-67增殖指数及TCR重排检测阳性率较高.

Objective: To investigate the incidence of high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement in Chinese diffuse large B-cell lymphoma (DLBCL) . Methods: From January 2013 to August 2020, 922 DLBCL cases were collected. C-MYC and BCL2 protein expression levels were analyzed by immunohistochemistry staining. Fluorescence in situ hybridization was used to detect the structural abnormalities of MYC, BCL2, and BCL6, including gene breaks and copy number changes. Results: MYC and BCL2 and/or BCL6 gene breaks were found in 29 out of 922 DLBCL cases (3.15%) , including 25 cases of double-hit lymphoma (DHL; 14 cases involving MYC and BCL2 rearrangements and 11 cases involving MYC and BCL6 rearrangements) and four cases involving MYC, BCL2, and BCL6 rearrangements, referring to triple-hit lymphoma. According to the threshold of C-MYC ≥40% and BCL2 ≥50%, 541 cases (58.68%) overexpressed C-MYC and BCL2 proteins, including 22 DHL cases. Moreover, according to the threshold of C-MYC ≥70% and BCL2 ≥50%, 52 cases (5.64%) overexpressed C-MYC and BCL2 proteins, including nine DHL cases. The P53 protein expression was detected by immunohistochemistry staining. The mutant P53 expression pattern was shown in 101 out of 709 cases (14.25%) , whereas 13 cases (1.83%) were negative, likely indicating P53 gene fragment deletion. Conclusion: The incidence of high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements was low in DLBCLs, and no significant correlation between gene abnormality and protein overexpression was shown. The correct diagnosis of DHL depends on molecular genetic detection.

目的:探讨CD38表达在侵袭性B细胞淋巴瘤诊断和鉴别诊断中的意义.方法:应用多参数流式细胞术检测102例初发侵袭性B细胞淋巴瘤[主要包括弥漫大B细胞淋巴瘤(DLBCL) 73例、Burkitt淋巴瘤7例和高级别B细胞淋巴瘤22例]患者淋巴结或骨髓标本中流式免疫标记物的表达情况,比较CD38在各组患者肿瘤细胞上表达水平的差异,分析其在侵袭性B细胞淋巴瘤鉴别诊断中的特点.结果:3组患者肿瘤细胞膜表面CD5、CD19dim、CD20dim和CD45dim表达水平差异无统计学意义(均P＞0.05),CD10表达水平以及缺乏免疫蛋白轻链表达差异有统计学意义(P=0.029,P=0.043);将DLBCL分为MYC-R+和MYC-R-患者,CD38+、CD38++和平均荧光强度在DLBCL MYC-R+、DLBCL MYC-R-、Burkitt淋巴瘤和双重/三重打击淋巴瘤4组患者肿瘤细胞表达水平差异有统计学意义(均P＜0.05),CD38+在诊断这4组侵袭性B细胞淋巴瘤时除DLBCL MYC-R+外特异性可达100％,但敏感性较低;CD38++诊断DLBCL MYC-R+时特异性可达100％,敏感性低至13％,而诊断Burkitt淋巴瘤和双重/三重打击淋巴瘤时敏感性则明显升高(分别为86％和79％).结论:CD38不同表达水平在侵袭性B细胞淋巴瘤鉴别诊断中具有重要作用,尤其CD38高表达可以及时准确地早期诊断双重/三重打击淋巴瘤,对临床治疗具有指导意义.

Objective To study the frequency of diffuse large B-cell lymphoma (DLBCL) with multi-genetic alteration, and its correlation with c-myc, bcl-2 and bcl-6 protein expression. Methods 50 cases diagnosed with DLBCL from January 2012 to December 2016 were collected. The expression of c-myc, bcl-2 and bcl-6 was analyzed by immunohistochemistry. Interphase fluorescence in situ hybridization (I-FISH) analysis was performed to identify the genetic alteration of c-myc, bcl-2 and bcl-6. Results In all cases, there were 27 males and 23 females with a median age of 50 years (range: 3-85 years). 23 (46.00 %) cases were defined as primary nodal DLBCL and 27 (54.00 %) cases were primary extra-nodal DLBCL, with gastrointestinal tract (48.15 %, 13/27) being the most common site of involvement. c-myc protein expression was detected in 94.00 % (47/50) cases, in which 82.00 % (41/47) cases exhibited high levels of c-myc expression with positive nuclear staining observed in over 40.00 % of tumor cells. The positive rate of bcl-2 protein was 84.00 % (42/50), 76 % (38/50) cases presented with high-level bcl-2 expression. Concurrent high expression of c-myc and bcl-2 were presented in 18 cases (36.00%). FISH analysis demonstrated c-myc gene rearrangement in 7 cases (14.00 %) and amplification in 2 cases (4.00 %). bcl-2 gene rearrangement was detected in 6 cases (12.00 %) and 4 cases (8.00 %) exhibited gene amplification. bcl-6 gene rearrangement was identified in 8 cases (16.00%), amplification in 3 cases (6.00%), and 1 case concomitantly harbored the rearrangement and amplification of bcl-6. Multi-genetic alterations were defined in 4 cases with 3 cases fulfilling the criteria for double-hit lymphoma (DHL) and 1 case for triple-hit lymphoma (THL). For the cases with concomitant high-level expression of c-myc and bcl-2 proteins, 3 cases (16.67 %) was detected with multi-genetic alterations, including 2 cases for DHL and 1 case for THL. Conclusions The proportion of DLBCL with multi-genetic alterations is 8.00 % in this study. The genetic alterations are not consistently correlated with the protein expression. The molecular genetic testing is reliable for the identification of DHL.

目的 总结我国报道的原发心脏淋巴瘤的临床表现、检查特点、治疗及预后.方法 检索1986年到2013年我国发表的原发性心脏淋巴瘤的个案报道,进行总结和分析.结果 我国的个案报道均未提及患者存在免疫缺陷,肿块最常见累及部位为右心房,心电图(electrocardiogram,ECG)最常见表现为房室传导阻滞,超声心电图(ultrasound cardiogram,UCG)为较好的检查方法,其中预后较好的病例均进行了化疗.结论 原发心脏淋巴瘤无典型症状,多数为晚期就诊,预后差,化疗为相对较好的治疗手段.

OBJECTIVE:To study the clinicopathologic features, differential diagnosis and prognosis of primary bone anaplastic large cell lymphoma(ALCL).METHODS:Twelve patients diagnosed with primary bone ALCL were retrospectively reviewed. The clinicopathologic features, immunohistochemic findings and results of in situ hybridization for EB virus were analyzed.RESULTS:Of the 12 patients, the male-to-female was 7: 5 with a median age of 17.5 years (range from 9 to 64 years). Bone pain was the presenting symptom in all patients. Radiographic examination demonstrated solitary osteolytic lesion in 8 patients and multiple lesions in the rest 4 patients. Spine (7 cases) was the most common site to be involved, followed by ilium (5 cases), sacrum (2 cases), humerus (1 case) and collarbone (1 case). Ten patients were available with the follow-up data including 5 ALK-positive and 5 ALK-negative patients, and the follow-up time was 2 to 47 months. Interestingly, the 3 dead patients were ALK-negative whereas 5 of 7 ALK-positive patients achieved remission.CONCLUSIONS:Primary bone ALCL is a rare type of non-Hodgkin lymphoma and it more frequently involves the axial skeleton. Boys and young males are more commonly affected. Patients usually present at an early stage and have a relatively favorable prognosis. Expression of ALK protein may be associated with a favorable prognosis in primary bone ALCL.

Objective: This study aimed to investigate the clinical characteristics, treatment options, and prognosis of multiple myeloma (MM) patients complicated with extramedullary plasmacytoma (EMP). Methods:The case of MM concurrent with EMP are rare. During the period between June 2005 and June 2013, clinical experience, diagnosis, and treatment of MM with EMP cases were retrospectively analyzed. Results:Fourteen cases were diagnosed with MM complicated with EMP in the Third Hospital of Peking Uni-versity, Beijing, China. Among these 14 cases, seven were males and seven were females. The mean age of patients was 56.9 years (ranging from 40 to 80 years old). Nine of the cases were diagnosed with EMP during the preliminary diagnosis, and the remaining five cases developed EMP during the course of treatment. Among the 14 cases, six were solitary EMPs and eight were multiple EMPs. Among the multiple EMP cases, five died, one showed disease progression, and two demonstrated partial regression. Conclusion:The prognosis of MM complicated with EMP is poor. Thus, new treatment strategies should be further explored.

目的 探讨1例骨孤立性浆细胞瘤(SPB)进展为多发性骨髓瘤(MM)后发生弥漫大B细胞淋巴瘤(DLBCL)患者的临床特点.方法 分析该患者不同时间的临床特点、病理表现和治疗经过,并复习相关文献.结果 患者SPB确诊后2年内治疗有效,病情稳定;2年后进展为MM;1年后发生DLBCL,对化疗耐药.结论 SPB在治疗过程中部分可转化为MM,但也可发生其他肿瘤.因此,在病变治疗过程中,需要及时进行活组织检查,明确病变的性质及是否发生转化.

患者男,59岁,腰腿痛5年余,加重2个月,主要为双侧腰骶部、臀部及大腿后外侧,严重时放射至足背区.查体:四肢针刺觉及肌力无异常,双下肢膝腱反射及跟腱反射未引出,病理征阴性,下肢位置觉减退.实验室检查正常.MRI:L2～3节段椎管内见长圆形等T1稍长T2信号,约1.1 cm×1.1cm×4.4 cm,边缘清楚,增强后明显均匀强化,终丝受压推移.行椎管肿瘤摘除术,术中见L2、3节段椎管内椭圆形肿瘤,表面光滑,褐红色,质硬、脆,血供丰富,与神经粘连轻,肿瘤连接于终丝,终丝血管异常粗大;肿瘤左侧与L2水平神经根相连,不易分离.术后病理:上皮样细胞构成瘤实质,细胞形态均一、胞质多,核仁不明显,少见核分裂象,排列呈腺泡状;间质为血窦及少许纤维样分隔.免疫组化示瘤细胞CgA强阳性.病理诊断:L2、3节段椎管内副神经节细胞瘤.

患者女,32岁.发现右内踝无痛性包块1年半,缓慢增大,右足第1趾活动渐受限.查体:右内踝可触及约2.5 cm×4.5 cm包块,质中,与周围组织粘连,边界欠清,不可推移,有轻压痛;右踝活动可,局部皮色、皮温正常,右屈踇肌力4级,第五趾外展肌力1级.实验室检查正常.

患者女,51岁,胸片见"双肺多发结节",无咳嗽、咳痰、咯血、发热、呼吸困难等不适.体格检查无异常.常规实验室检查及肿瘤标记物、血沉、结核菌素抗体均正常.CT示双肺多发大小不等、边缘光滑的类圆形结节,增强后明显强化(图1),CT值约43 HU(平扫)、66 HU(增强).气管及主支气管通畅,纵隔肺门无肿大淋巴结,胸腔内无积液.超声未探及全身浅表淋巴结肿大.CT引导下穿刺活检取肺内病变两条,约1 cm,质软、色灰白,组织学检查显示为大小较一致的短梭形及少量淡染圆形细胞增生,细胞异型性不明显,未见核分裂象,其间为成纤维细胞和纤维组织;免疫组化:CK混表面细胞(+),SMA(-),CD117散在(+),HMB45(-),Melan-A(-),TTF-1表面细胞及圆形细胞均(+).病理诊断(图2):肺硬化性血管瘤(pulmonary sclerosing hemangioma,PSH).未予患者特殊治疗,嘱其定期复查.

OBJECTIVE:To investigate the clinicopathologic features of reactive hyperplasia of lymph nodes in maxillofacial regions.METHODS:Thirty-two patients with lymph node reactive hyperplasia (LRH) were analyzed clinicopathologically including pathomorphologic manifestation and immunohistochemical expression.RESULTS:Histopathology of 32 patients showed significant hyperplasia in folliculus lymphaticus, marginal zone lymph, paracortical area lymph, and seldom mixed hyperplasia. Immunohistochemical study showed that the hyperplastic lymphocytes were mainly composed of CD20 positive B cells positive in 23 cases(72%), CD3 positive T cell in 7 cases (22%), CD20 positive T cell and CD3 positive B cell partially as well as histiocytes in 2 cases (6%). Atypical hyperplasia was found in 10 cases.CONCLUSION:Hyperplastic lymphocytes in LRH of maxillofacial regions are mainly composed of B cells. Malignant transformation may occur in these patients with atypical hyperplasia. Regularity follow up is necessary for these patients.

In order to investigate the clinical manifestations, diagnosis, therapy and prognosis of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM), 16 patients with LPL/WM were analyzed retrospectively. The results showed that the average age of 16 patients with LPL/WM was 65.1 years old, the most common syndromes were anemia and hyperviscosity syndrome, bone marrows were composed of small lymphocyte, admixed with variable numbers of plasma cells and plasmacytoid lymphocytes. And lymph node biopsy revealed that most cells expressed B-cell-associated antigen. Among the 16 cases, complete remission was 25%, overall response rate (ORR) was 81.3%, overall survival time was 6 to 108 months. 3 patients died and survival rate was 81.3 %. It is concluded that the clinical course of LPL/WM is typically indolent. These patients can acquire remission in clinic, but can not be cured, some of them can transform into patients with more malignant lymphoma.

The aim of study was to investigate the synergetic effect of B7-1 and CD40L co-stimulating pathway in the immunotherapy for lymphoma and to explore the effective manner of tumor vaccine for treating lymphoma. The lymphoma cell line A20 cells were inoculated into BALB/c mice as to establish A20-bearing mice model, the B7-1 and CD40L expression vector were alone or in combination directly injected into lymphoma of mice model, the PBS, vector pcDM8 and pcDNA3.1 were selected as controls so as to observe tumor growth. The pathological section and HE staining of tumor tissue were performed to observe the histological characteristics and the cell infiltration of lymphoma, the CCK-8 detection kit was used to analysis the splenic CTL cytotoxicity. The results showed that the intratumor injection of B7-1 and CD40L resulted in reduction of tumor size. Morphological observation of tumor revealed inflammatory cell infiltration in the tumors, massive necrosis and localization of tumor. CCK-8 kit detection indicated significant enhancement of splenic CTL cytotoxicity, the effect of B7-1 combined with CD40L was stronger than that of B7-1 or CD40L alone. It is concluded that B7-1 and CD40L show immunotherapeutic effect on lymphoma, and the effect becomes stronger when they are combined in treating lymphoma. Meanwhile, the intratumor injection may be considered as a safe and effective way for tumor vaccine.

Objective To study the expressions of anaplastic lymphoma kinase (ALK-1) and cytotoxic proteins in primary systemic anaplastic large cell lymphoma (S-ALCL) and their relationship with clinical outcome. Methods 51 S-ALCL cases were collected from Lymphoma Lab of Peking University Health Science Centre & Peking Children's Hospital. The morphologic characteristics were studied under routine microscope, and essential immunohistochemical stainings were performed and reviewed to confirm the diagnosis of S-ALCL. Immunohistochemical stainings for ALK-1 and cytotoxic proteins (TIA-1 & granzyme B) were performed using standard SP method. Patients related clinical data including follow-up materials were collected. Results Survival time of 44 cases with completely clinical follow up materials ranged from 0.5～66months. 36 out of 51 cases(37 %) was positive for ALK-1 protein. While 20 cases out of 47 S-ALCL cases ( 42.55 % ) positive for granzyme B and 22 out of 28 cases (81.48 %) were positive for TIA-1. The prognosis of patients with ALK-1 protein positive and granzyme B negative expression was better, but TIA-1 expression might have nothing to do with clinical outcome (P＞0.05). In addition, multivariate analysis confirmed that ALK-1 protein expression, granzyme B protein expression and Ann-Arbor stage system were possible for prognosis(P＜0.05), Conclusion Expression of ALK-1 and granzyme B protein expression may serve as two independent prognostic predictors in S-ALCL patients.

OBJECTIVE:To explore the relationship of clinic features, lab findings, the origin of tumor cell as well as prognosis in Chinese patients with diffuse large B-cell lymphoma( DLBCL).METHODS:Seventy four cases of primarily diagnosed DLBCL were analyzed. Immunohistochemistry stain was used to check the expressions of Bcl-6,CD10 and MUM1.RESULTS:Among the 74 patients, the average age was 58.5 years, the ratio of male to female was 1.64:1. 23.2% (16/69) cases developed in lymph node, 15.9% (11/ 69) in the extra node area. Among 55 follow-up cases, 13 (23.6%) died, and 12 (92.3%) died in the first year after diagnosis. The prognosis analysis showed that diagnosed at age > 65 years (P = 0.036), and the international prognostic index (IPI) (P = 0.009) were independent prognostic factors; origin of tumor cell had a trend to be a prognostic factor, but no statistic difference (P = 0.086). beta2-MG and Bcl-6 expression had no relation with the prognosis.CONCLUSION:The middle and old-aged male patients are the most common in DLBCL and the first-year mortality rate is higher. The age at diagnosis and IPI can predict the clinical outcome. The origin of tumor cell might suggest the prognosis.

Objective To determine the long-term outcome of the gastric mucosa-associated lymphoid tissue lymphoma(MALT lymphoma) after helicobacter pylori(Hp) eradication and the significance of bcl-10 in the tumor's response to the Hp eradication. Methods 12 patients with Hp-positive gastric MALT lymphoma were enrolled in this study. We used immunochemistry stain to detect bcl-10 expression in the tumors and performed endoscopic follow-up after Hp eradication. Results bcl-10 nuclear expression was detected in 4 of 6 cases which did not acquire complete regression(CR) after Hp eradication and none was detected in 6 CR patients, indicating that the tumor progression might not be related to Hp infection and Hp eradication may be not the first choice and the only therapy method for bcl-10 nuclear expression patients. The total CR rate was 50 % (6/12) after Hp eradication with a median follow-up of 17.5 months. The median time achieved CR was 1.5 months with the longest one of 6 months. By now, the median duration of CR was 14 months with the longest one of 2 years. bcl-10 nuclear expression was not detected in the 6 CR cases, but in 4 of 6 who did not reach CR. Conclusion bcl-10 nuclear expression is more likely related to the non-response to the Hp eradication in the tumor. Hp eradication results in CR in part of gastric MALT lymphoma patients. However, it needs more cases and longer follow-up to confirm.