原发中枢神经系统淋巴瘤的脑脊液细胞学诊断

  目的  研究脑脊液细胞学方法对原发中枢神经系统淋巴瘤(primary central nervous system lymphoma, PCNSL)的诊断意义。  方法  回顾性分析21例脑脊液细胞学阳性的PCNSL患者的临床资料, PCNSL的诊断综合应用脑脊液细胞学、脑脊液免疫细胞化学、脑脊液淋巴细胞基因分析和流式细胞分析等方法。  结果  21例患者临床-神经影像学分型包括脑脊膜型13例, 实质型4例, 室管膜(下)型3例, 眼型1例。脑脊液细胞学检查21例均见淋巴瘤细胞或异型淋巴细胞。脑脊液免疫细胞化学检查17例呈B淋巴细胞优势, 符合B淋巴细胞来源淋巴瘤, 10例Ki67阳性细胞比例在40%~60%。7例流式细胞分析中5例以B细胞为主, B细胞比例66%~87%;1例以NK/T细胞为主。脑脊液淋巴细胞基因重排检测3例为IgH单克隆, 1例为T细胞受体单克隆。最终6例行脑活检并确诊PCNSL。综合上述结果, 21例确诊PCNSL, 其中B细胞型19例, T细胞型2例。  结论  综合应用脑脊液细胞学、免疫细胞化学、细胞基因重排检测和流式细胞分析的脑脊液学方法, 是诊断PCNSL的重要途径。     

Titin抗原决定簇在正常胸腺、胸腺瘤和胸腺癌组织中的表达

  目的  探讨在正常胸腺、胸腺瘤、胸腺癌组织中titin抗原决定簇的表达及其与重症肌无力(myastheniagravis, MG)临床表现的关系。  方法  选取4例MG伴胸腺瘤患者的胸腺瘤、1例胸腺癌、1例MG伴胸腺瘤患者胸腺瘤旁增生的胸腺组织以及1例正常胸腺组织标本, 对所有标本作连续冰冻切片, 分别进行HE染色、细胞角蛋白(cytokeratin, CK)和titin抗原的免疫组化染色, 同时测定MG伴胸腺瘤患者血清titin抗体的浓度。  结果  免疫组化染色结果显示, titin在胸腺瘤中表达呈强阳性, 其分布与胸腺瘤上皮细胞的分布一致, 胸腺瘤内淋巴细胞和其他结构titin染色呈阴性; 在胸腺癌组织内titin染色呈阴性; 在正常胸腺中titin染色位于胸腺小体, 呈弱阳性, 其他结构未见着色。4例MG伴胸腺瘤患者中有3例血清titin抗体阳性。  结论  MG伴胸腺瘤患者的胸腺瘤组织中有titin抗原决定簇的表达, 且仅表达于胸腺瘤上皮细胞, 而正常胸腺组织中titin表达于胸腺小体, 提示伴MG的胸腺瘤中发生了免疫微环境的变化。     

宫颈腺样囊性癌临床病理特征及免疫组织化学表型

  目的  探讨宫颈腺样囊性癌(adenoid cystic carcinoma, ACC)临床病理及免疫组化特征。  方法  收集北京协和医院2003年1月至2013年12月病理数据库及会诊数据库中诊断为宫颈腺样囊性癌病例共4例; 并采用免疫组化方法对石蜡组织标本进行检测, 总结其临床病理特征、治疗及预后。  结果  4例宫颈腺样囊性癌患者平均年龄61.5岁, 多为绝经后妇女(3/4), 就诊主要症状为阴道流血(3/4), 肿瘤类型多为外生性肿物(3/4)。病理学特征方面, 3例患者表现为宫颈腺样囊性癌合并侵袭性鳞癌, 1例为宫颈腺样囊性癌单一组分; 腺样囊性癌的主要生长方式为筛状; 免疫组织化学表达方式支持其导管腺上皮及肌上皮两种组成成分:CK7在导管腺上皮中阳性表达, P63、SMA在肌上皮中阳性表达; 腺样囊性癌特征性标志物C-MYB在所有病例中均强阳性表达。3例患者完全切除子宫, 1例患者行宫颈锥切, 临床分期均为Ⅰ期; 术后均行放射治疗, 2例患者同时行化学治疗; 4例患者平均随访时间为21.25个月, 均为无病生存状态。  结论  宫颈腺样囊性癌是一种罕见的特殊类型腺癌, 常合并其他类型的宫颈肿瘤, 免疫组化表型与其他部位的腺样囊性癌相同, 但预后相对较差, 术后可辅以放疗及化疗, 早期发现并治疗可以提高患者生存率。     

伴淋巴上皮涎腺炎样特征的胸腺增生临床病理学观察

目的探讨伴淋巴上皮涎腺炎样特征的胸腺增生临床病理学特征、免疫组化表型及鉴别诊断。方法收集2例LESA样胸腺增生患者的临床病理学资料,通过光镜形态学观察、免疫组织化学染色、原位杂交、Ig基因重排检测,并复习相关文献。结果 2例患者中,男性1例,女性1例,发病年龄56和66岁(平均年龄61岁)。肿瘤最大径6 cm、13 cm。镜下:低倍镜下肿瘤呈分叶状结构,叶状结构周围为脂肪组织;具有生发中心的淋巴滤泡增多,滤泡间区可见浆细胞;胸腺上皮细胞增生,可见大量胸腺小体,胸腺上皮呈岛状、巢状,并相互汇合形成梁状结构;囊性变,囊壁内衬胸腺上皮,囊内见均质嗜酸性物及胆固醇裂隙,常伴异物巨细胞反应;淋巴细胞浸润胸腺上皮形成淋巴上皮病变。免疫组织化学CD20、CD79α示B细胞,CD3、CD5示T细胞,CK、CK19显示淋巴上皮病变,原位杂交EBER阴性,未检测到Ig基因发生单克隆重排。结论 LESA样胸腺增生类似于涎腺良性淋巴上皮病变,是胸腺增生的一种新病理学形态,镜下主要表现为淋巴样组织浸润和淋巴上皮病变,预后良好,手术切除后,无复发和转移。     

小肠淋巴瘤和小肠间质瘤的超声征象及鉴别诊断

  目的  探讨超声对小肠淋巴瘤与小肠间质瘤的诊断与鉴别诊断价值。  方法  回顾性分析2009年1月至2016年1月于中国医学科学院肿瘤医院就诊, 行超声检查并经病理证实的36例小肠淋巴瘤和69例小肠间质瘤患者资料, 分析比较其临床特征和超声征象。  结果  小肠淋巴瘤和小肠间质瘤在超声回声是否均匀、是否伴有无回声区、是否伴有气体回声以及超声分型方面差异存在统计学意义(P均 < 0.001), 而在临床特征、大小、边界、是否分叶等方面差异无统计学意义。小肠淋巴瘤多表现为回声均匀、病灶内部无囊变坏死区, 超声分型为浸润型和肿块型; 而小肠间质瘤多表现为回声不均匀, 病灶内部可见囊变坏死区, 超声分型均为肿块型。  结论  小肠淋巴瘤和小肠间质瘤的超声征象具有特征性表现并有一定差异, 有助于对两者进行诊断和鉴别诊断。     

静脉内平滑肌瘤病的临床病理

  目的  探讨静脉内平滑肌瘤病(intravenous leiomyomatosis, IVL)的临床病理学特征, 诊断特点及鉴别诊断。  方法  分析34例IVL患者的临床表现, 对其手术标本进行HE和免疫组织化学染色(EnVision)观察。  结果  患者年龄24~61岁, 平均年龄44.8岁。临床表现为下肢肿胀、腹胀、月经异常等盆腔相关症状, 累及下腔静脉及心脏患者可有呼吸困难、心悸、胸闷等心血管症状。病变大体表现:14例位于子宫内, 6例累及盆腔静脉, 5例累及下腔静脉, 9例生长入心房内; 镜下表现为梭行平滑肌细胞构成, 核分裂罕见; 免疫组化染色SMA、ER、PR、Desmin阳性, HMB45、CD10阴性, 4例CD34阳性, 余均为阴性, Ki-67阳性指数0.3%~2.7%。  结论  静脉内平滑肌瘤病为育龄期妇女少见疾病, 组织学表现良性但生物学行为恶性, 具有特定的大体表现和免疫组化特点。     

探讨肝原发性黏膜相关淋巴组织淋巴瘤的病理学特征

目的探讨肝原发性黏膜相关淋巴组织（MALT）淋巴瘤的临床病理特征、免疫表型和基因重排特点。方法对2例原发于肝黏膜相关淋巴组织淋巴瘤进行回顾性研究,包括临床病理观察、免疫组化检测及多聚酶链反应（PCR）检测基因重排。结果2例均为偶然发现肝占位性病变,肿瘤组织主要由中心细胞样B细胞和单核细胞样B细胞构成,均见肿瘤细胞侵犯胆管上皮、侵袭肝细胞索形成淋巴上皮病变,肿瘤细胞CD20、CD79α和Pax-5（＋）,T细胞标记（-）,IgH基因均呈单克隆重排。结论原发性肝MALT型淋巴瘤是一种惰性淋巴瘤,多为偶然发现的肝占位性病变,诊断及鉴别诊断需要结合病理形态、免疫组化标记及必要的基因重排检测。     

逆行胰胆管造影诊治肝包虫囊肿破入胆总管1例并文献复习

  目的  研究逆行胰胆管造影(endoscopic retrograde cholangiopancreatography, ERCP)对肝包虫囊肿破入胆总管的诊疗价值。  方法  报告1例肝包虫囊肿破入胆总管患者的ERCP诊治经过并复习文献。  结果  该患者临床表现类似急性化脓性胆管炎, 经ERCP确诊, 且治疗后好转。  结论  肝包虫病患者突发急性胆系感染, 应怀疑肝包虫囊肿破入胆道。围手术期ERCP对提高该病的诊治水平有重要价值。     

一例原发性肾性糖尿患者的临床与基因突变分析

  目的  探讨1例原发性肾性糖尿(primary renal glucosuria, PRG)患者的临床表现及其分子生物学基础。  方法  详细收集患者的临床资料、生化检查及影像学检查结果, 抽取外周静脉血, 提取基因组DNA, 聚合酶链反应(polymerase chain reaction, PCR)扩增SLC5A2基因的14个外显子及其与内含子的交界区, 测序确定突变情况。  结果  患者临床表现、实验室检查和影像学检查符合PRG诊断。基因突变分析显示, 患者SLC5A2基因cDNA序列的第877位腺嘌呤A突变为胸腺嘧啶G(c.877 A>G), 造成第293位氨基酸由丝氨酸改变为半胱氨酸(p.Ser293Cys), 该突变位于SLC5A2的第7外显子。蛋白序列的保守性分析和突变蛋白的功能分析均表明p.Ser293Cys为致病性突变。  结论  通过SLC5A2基因突变分析, 从分子遗传学方面证实患者PRG的诊断。临床上血糖正常的患者出现尿糖阳性且无其他近端肾小管功能障碍表现的患者应该考虑到该疾病可能, 基因分析有助于确诊。     

Fechtner综合征异常家系的临床与分子缺陷

  目的  分析一先天性血小板减少症家系的临床、实验室特点, 并探讨其分子发病机制。  方法  收集该家系成员的临床资料, 采集先证者及其家系成员的静脉血, 分别进行全自动及人工血小板计数; 显微镜下观察血小板形态; 流式细胞术分析血小板膜蛋白; 透射电镜观察中性粒细胞胞浆包涵体。聚合酶链反应扩增非肌性肌球蛋白重链9基因(non-muscle myosin heavy chain9gene, MYH9)的40个外显子, 分析PCR产物的核苷酸序列, 并直接测序确定突变位点。  结果  镜下观察外周血涂片巨大血小板占90%以上, 血小板膜糖蛋白(CD41、CD61、CD42a、CD42b)均在正常范围内, 血小板功能正常; 中性粒细胞胞浆透射电镜可见无包膜分隔的包涵体, MYH9基因38号外显子第5521位核苷酸存在G→A杂合突变(GAG→AAG), 从而导致其编码的非肌性肌球蛋白重链A(NMMHC2A)第1841位谷氨酸变为赖氨酸, 正常对照及该家系正常者未见此突变。  结论  MYH9基因点突变并伴有血小板减少及巨大血小板是Fechtner综合征的主要特征。     

A case of mucosa-associated lymphoid tissue lymphoma of the gastrointestinal tract showing extensive plasma cell differentiation with prominent Russell bodies

A 73-year-old Japanese woman was hospitalized for detailed examination of nausea, diarrhea and loss of appetite. Atypical erosion in the ileum was found on endoscopy. Biopsy of this erosion showed proliferation of cells containing numerous Russell bodies. Differential diagnoses considered were Russell body enteritis, crystal-storing histiocytosis, Mott cell tumor, immunoproliferative small intestinal disease (IPSID) and mucosa-associated lymphoid tissue (MALT) lymphoma. The cells containing prominent Russell bodies showed diffuse positivity for CD79a and CD138, but negative results for CD20, CD3, UCHL-1, CD38 and CD68. Russell bodies were diffusely positive for lambda light chain, but negative for kappa light chain, and immunoglobulin (Ig) G, IgA and IgM. Based on these findings, Russell body enteritis, crystal-storing histiocytosis and IPSID were ruled out. As the tumor formed no mass lesions and was restricted to the gastrointestinal tract, MALT lymphoma with extensive plasma cell differentiation was finally diagnosed. The patient showed an unexpectedly aggressive clinical course. The number of atypical lymphocytes in peripheral blood gradually increased and T-prolymphocytic leukemia (T-PLL) emerged. The patient died of T-PLL 7 mo after admission. Autopsy was not permitted.     

Sonographic appearances of mucosa-associated lymphoid tissue lymphoma of the submandibular gland confirmed with sonographically guided core needle biopsy

A 71-year-old man presented with mucosa-associated lymphoid tissue (MALT) lymphoma of the submandibular gland 52 months after initial diagnosis of MALT lymphoma of the lung. Ultrasonography showed a well-demarcated, markedly hypoechoic, heterogeneous solid mass with linear echogenic strands and hypervascularity. Ultrasound-guided core-needle biopsy demonstrated histological findings of MALT lymphoma. Sonographic features of MALT lymphoma of the submandibular gland are characteristic and ultrasound-guided core-needle biopsy may be a suitable replacement for surgical biopsy.     

Analytical detection of immunoglobulin heavy chain gene rearrangements in gastric lymphoid infiltrates by peak area analysis of the melting curve in the LightCycler System

Because it is difficult to differentiate gastric mucosa-associated lymphoid tissue (MALT) lymphoma from chronic gastritis in gastric lymphoid infiltrates, molecular detection of monoclonality through immunoglobulin heavy chain (IgH) gene rearrangements is commonly performed. However, heterogeneity in the performance and results obtained from IgH gene rearrangements has been reported. To improve the accuracy in the diagnosis of gastric lymphoid infiltrates, we developed an analytical approach based on one-peak area analysis of the melting curve in the LightCycler System. Using a training-testing approach, the likelihood ratio method was selected to find a discriminative function of 4.64 in the training set (10 gastric MALT lymphomas and 10 chronic gastritis cases). This discriminative function was validated in the testing set (five gastric MALT lymphomas, six abnormal lymphocytic infiltrates with subsequently demonstrated gastric MALT lymphomas, and six cases of chronic gastritis). All but one case of gastric MALT lymphoma, as well as abnormal lymphocytic infiltrates, clustered under 4.64, and all chronic gastritis cases clustered above 4.64. These results were validated by conventional electrophoreses confirming one or two sharp bands in cases of gastric MALT lymphomas and a smear of multiple bands in cases of chronic gastritis. Analytical detection of IgH gene rearrangement in gastric lymphoid infiltrates by one-peak area analysis correctly distinguishes gastric MALT lymphomas from chronic gastritis, even in cases with diagnosis of abnormal lymphocytic infiltrates.     

(18)F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Findings in Mucosa-associated Lymphoid Tissue Lymphoma of the Larynx: a Case Report and Literature Review

Laryngeal mucosa-associated lymphoid tissue (MALT) lymphoma is rare, with only 25 cases reported in the literature. This report presents a case of laryngeal MALT lymphoma in a 35-year-old female with a 6-year history of progressively worsening hoarseness. MALT lymphoma was diagnosed based on biopsy and immunohistochemical analysis. The patient received two cycles of cyclophosphamide + epirubicin + vincristine + prednisone (CHOP) chemo therapy, which was ineffective. (18)F-fluoro deoxy glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) showed (18)F-FDG accumulation in the larynx only and identified stage IE lymphoma. CHOP chemotherapy was terminated and the patient was treated with radiotherapy. After 3 months (total radiation dose 27 Gy), (18)F-FDG PET/CT scan showed that the laryngeal lesion was in complete remission. A review of the literature on the MEDLINE(?)/PubMed(?) databases regarding laryngeal MALT lymphoma and the use of PET/CT found that radiotherapy is the firstline treatment for stage I and II MALT lymphoma.     

The possible involvement of micro-organisms other than Helicobacter pylori in the development of rectal MALT lymphoma in H. pylori-negative patients

It remains unclear whether lymphoma of the mucosa-associated lymphoid tissue (MALT) in the extragastric organs is related to Helicobacter pylori infection or not. This report describes three patients with rectal MALT lymphoma negative for H. pylori infection, all of whom showed disease regression after being treated with antibiotics. One patient had MALT lymphoma in both the descending colon and the rectum; the other two patients had rectal disease only. None of the patients had chronic gastritis which was detectable either endoscopically or histologically and H. pylori infection was completely ruled out by various methods, including a urease breath test. These patients received antibiotic therapy. In all the patients, regression of MALT lymphoma was observed endoscopically and histologically, and polymerase chain reaction revealed that a previously observed rearranged band of immunoglobulin heavy chain had also disappeared after antibiotic treatment. These cases therefore suggest involvement of micro-organisms other than H. pylori in the development of rectal MALT lymphoma.     

Laterally spreading tumor-like primary rectal mucosa-associated lymphoid tissue lymphoma: A case report

BACKGROUNDColorectal mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease, and only a few cases have been reported to date. It has no specific clinical presentations and shows various endoscopic appearances. There is no uniform consensus on its treatment. With the advancement of endoscopic technology, endoscopic treatment has achieved better results in individual case reports of early-stage patients.CASE SUMMARYWe report a case of rectal MALT in a 57-year-old Chinese man with no symptoms who received endoscopy as part of a routine physical examination, which incidentally found a 25 mm × 20 mm, laterally spreading tumor (LST)-like elevated lesion in the rectum. Therefore, he was referred to our hospital for further endoscopic treatment. Complete and curable removal of the tumor was performed by endoscopic submucosal dissection. We observed enlarged and dilated branch-like vessels similar to those of gastric MALT lymphoma on magnifying endoscopy with narrow-band imaging. And immunopathological staining showed hyperplastic capillaries in the mucosa. Histopathological findings revealed diffusely hyperplastic lymphoid tissue in the lamina propria, with a visible lymphoid follicle structure surrounded by a large number of diffusely infiltrated lymphoid cells that had a relatively simple morphology and clear cytoplasm. In addition, immunohistochemical analysis suggested strongly positive expression for CD20 and Bcl-2. Gene rearrangement results showed positivity for IGH-A, IGH-C, IGK-B, and IGL. Taking all the above findings together, we arrived at a diagnosis of extranodal marginal zone B-cell lymphoma of MALT lymphoma. Positron emission tomography-computed tomography examination showed no other lesions involved. The patient will be followed by periodic endoscopic observation.CONCLUSIONIn conclusion, we report a case of rectal MALT with an LST-like appearance treated by endoscopic submucosal dissection. Further studies will be needed to explore the clinical behavior, endoscopic appearance, and treatment of rectal MALT.     

A case of primary hepatic extranodal marginal zone B-cell mucosa-associated lymphoid tissue (MALT) lymphoma treated by radiofrequency ablation (RFA), and a literature review

Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is an extremely rare liver malignancy that usually lacks characteristic imaging findings and which is often misdiagnosed. We report a 63-year-old woman diagnosed with primary hepatic extranodal marginal zone B-cell lymphoma, MALT type. The patient underwent needle biopsy and radiofrequency ablation (RFA), and showed no signs of relapse during the 12-month postoperative follow-up. This case stresses the rarity of primary hepatic MALT-type lymphoma and the unique and effective treatment for this patient. Our patient received RFA, which showed good efficacy and which provides a new option for the treatment of hepatic MALT lymphoma. We also present our findings from a systematic review to improve the current understanding of this disease.     

T(11;18)及核bcl-10蛋白在胃肠MALT淋巴瘤中的表达

为了探讨t(11；18)(q21；q21)染色体易位及核bcl-10蛋白在胃肠粘膜相关淋巴组织淋巴瘤(MALT lymphoma)中的表达，用酸性酚氯仿法从石蜡组织中提取RNA；逆转录合成cDNA后用聚合酶链反应(PCR)扩增API2-MALT1融合基因；用免疫组织化学法检测石蜡切片中bcl—10蛋白的表达。结果表明：42例MALT淋巴瘤中，t(11；18)(q21；q21)染色体易位在低度恶性MALT淋巴瘤中的表达为14％，在伴高恶转化型MALT淋巴瘤中的表达为46％，在40例弥漫大B细胞淋巴瘤(diffuse 1arge B cell lymphoma，DLBCL)对照组中没有表达；43例MALT淋巴瘤中bcl-10蛋白在低度恶性MALT淋巴瘤的核表达为61％，在伴高恶转化型MALT淋巴瘤中的核表达为69％。结论：t(11；18)易位可能与高度进展MALT淋巴瘤有一定相关性，但与DLBCL无关;bcl-10蛋白的核表达在恶性程度不同的两组MALT淋巴瘤中无显著性差异，其原因有待进一步研究。     

Primary hepatic mucosa-associated lymphoid tissue lymphoma with HP and previous HBV infection: A case report and literature review

Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively rare disease with low malignancy, and its aetiology is unclear. A 65-year-old man presented with abdominal pain. Hepatitis virus examination revealed a previous hepatitis B virus (HBV) infection, and a carbon-13 urea breath test result was positive for the patient. Abdominal contrast-enhanced computed tomography revealed a patch of abnormal density in the right posterior lobe of the liver. The patient underwent VI segment hepatectomy and was pathologically diagnosed with hepatic MALT lymphoma. After the operation, he received quadruple anti-Helicobacter pylori (HP) therapy and refused other treatments. He has been followed up by telephone for 20 months after discharge and is now in a stable condition. In this study, we counted 105 cases of hepatic MALT lymphomas reported in English or Chinese since 1995 and summarised the clinical characteristics and concomitant diseases in this condition. Based on the literature review, we speculated that chronic infectious diseases, especially viral infections (including hepatitis C virus (HCV) and HBV) and HP infection, are associated with the pathogenesis of primary hepatic MALT lymphoma. In addition, autoimmune diseases might also play a role in this condition.     

Primary mucosa-associated lymphoid tissue lymphoma in the midbrain: A case report

BACKGROUNDPrimary non-dural central nervous system mucosa-associated lymphoid tissue (MALT) lymphoma is a rare indolent B-cell lymphoma, with only a few reported cases worldwide.CASE SUMMARYA 33-year-old man presented with a 5-mo history of left blepharoptosis and a 4-mo history of right limb numbness and weakness. Magnetic resonance imaging showed a significantly enhanced mass in the left midbrain. Subsequent positron emission tomography revealed that the lesion had increased glucose uptake. A stereotactic robotic biopsy supported a diagnosis of MALT lymphoma. Then he was treated with radiation therapy (30Gy/15F), which resulted in complete remission. We also review the literature on brain parenchymal-based MALT lymphoma, including the clinical presentation, treatment options, and outcomes.CONCLUSIONAlthough there is no consensus on the optimal treatment for this rare disease, patients can respond well when treated with radiotherapy alone.