直肠神经内分泌肿瘤的临床病理研究

目的 研究直肠神经内分泌肿瘤(NET)的临床病理因素与淋巴结转移及预后的关系,探讨手术方式的选择.方法 收集48例直肠NET切除术后患者的临床病理资料.分别采用卡方检验和Logistic回归法进行肿瘤临床病理因素与淋巴结转移关系的单因素和多因素分析.采用Kaplan-Meier方法进行预后单因素生存分析,以Log-rank检验进行生存率比较,采用Cox模型进行预后多因素生存分析.结果 单因素分析显示,与淋巴结转移相关的临床病理因素为肿瘤距肛缘≤6 cm、肿瘤最大径＞2 cm、有肌层浸润、有远处转移、组织学3级.多因素分析显示,组织学3级是淋巴结转移的独立相关因素[比值比(OR)=9.333,95％可信区间(CD:1.054～82.635,P=0.045].单因素生存分析显示,预后差的相关因素为肿瘤距肛缘≤6 cm、肿瘤最大径＞2 cm、有肌层浸润、有淋巴结转移、有远处转移、组织学3级.多因素生存分析显示,肿瘤距肛缘≤6 cm[风险比(HR)=0.215,95％CI:0.047～0.980,P=0.047]、有远处转移(HR=8.788,95％CI:2.612～29.571,P＜0.01)、组织学3级(HR=5.510,95％CI:1.692～17.944,P=0.005)是预后差的独立相关因素.结论 在无远处转移的情况下,对于组织学1级和2级的直肠NET患者,若肿瘤最大径＞2 cm或有肌层浸润,推荐其接受根治性手术;在无远处转移的情况下,组织学3级的直肠NET患者均推荐其接受根治性手术.     

直肠神经内分泌肿瘤35例临床病理特征分析

目的分析直肠神经内分泌肿瘤(neuroendocrine neoplasms,NENs)临床表现、内镜下特征、病理特点及其相关性.方法回顾性分析35例直肠NENs患者的临床及病理资料,并对肿瘤直径、浸润深度、肝及淋巴结转移、免疫组化标志物阳性与否、肿瘤病理分级等指标进行Spearman相关性分析.结果直肠NENs多位于距肛门4-10 cm处,肿瘤直径(≥2cm,P=0.038)、嗜铬粒素A(chromogranin A,CgA)阳性(P=0.019)、浸润深度(P=0.035)与淋巴结转移相关,肿瘤直径(≥2cm,P=0.03)、CgA阳性(P=0.019)、病理分级(P0.001)与肝转移相关.结论直肠NENs缺乏特异性临床表现,肿瘤直径及浸润深度是影响治疗方式及预后的重要因素,病理分级、免疫组化在疾病诊断及预测淋巴结、肝转移中起着重要作用,建议CgA阳性的患者,早期行腹部CT、腹部超声及浅表淋巴结超声等检查,以尽早评估淋巴结及肝转移情况.     

结直肠神经内分泌肿瘤25例临床分析

目的探讨结直肠神经内分泌肿瘤的临床特征、诊治方法及预后。 方法回顾分析湖北省肿瘤医院自2006年1月至2015年1月收治的25例结直肠神经内分泌肿瘤患者的临床资料。 结果肿瘤部位：阑尾3例,升结肠3例,乙状结肠2例,直肠17例。分级情况：NET（G1）11例,NET（G2）3例,NEC（G3）8例,MANEC 3例。免疫组织化学：Syn、CgA、NSE阳性表达率为96%,68%和92%。预后：结直肠神经内分泌肿瘤出现转移部位最多见为肝脏。9例Ⅰ期患者生存时间均长于5年。6例Ⅱ期患者,3年内死亡1例,5年内死亡3例,余1例仍在随访中。8例Ⅲ期患者,1年生存率75%,3年生存率50%,5年生存率25%。2例Ⅳ期患者,1例存活28月,另1例存活37月。 结论结直肠神经内分泌肿瘤缺乏特征性临床表现,主要通过内镜下活组织病理检查明确诊断。结直肠神经内分泌肿瘤治疗方法主要依靠手术治疗,早期预后良好,预后与分期和分级密切相关。     

胰腺神经内分泌肿瘤患者临床特征及预后影响因素分析

目的 探讨胰腺神经内分泌肿瘤(PNET)患者的临床特征及预后影响因素。方法 收集2012年3月-2019年4于上海交通大学附属第一人民医院病理确诊为PNET的54例患者临床资料,分析患者临床、病理、影像学特征及预后情况。计数资料组间比较采用χ2检验或Fisher精确检验。采用Kaplan-Merier法进行生存分析,并用log-rank进行组间差异检验。结果 54例PNET患者中,男19例(35.2%),女35例(64.8%);无功能性PNET 47例(87.0%),功能性PNET 7例(13.0%);TNMⅠ、Ⅱ、Ⅲ、Ⅳ期分别有17例(31.5%)、26例(48.1%)、9例(16.7%)、2例(3.7%);世界卫生组织病理分级G1、G2、G3期分别有24例(46.2%)、22例(42.3%)、6例(11.5%)。CT(χ2=8.250,P=0.010)和MRI(χ2=6.048,P=0.031)检查评估结果示肿瘤边界不清的患者术后复发和病死率更高。患者总生存期为1~86个月,5年生存率为92.0%,无病生存期为1~71个月。单因素分析结果显示,PNET患者TNM分期(χ2=9.572,P=0.023)、病理分级(χ2=7.506,P=0.023)、手术切缘侵犯(χ2=15.123,P<0.001)、淋巴结转移(χ2=4.716,P=0.030)及远处转移(χ2=5.534,P=0.019)与总生存期相关。结论 PNET CT和MRI提示肿瘤边界不清者预后较差。肿瘤TNM分期、病理分级、手术切缘侵犯、淋巴结转移及远处转移与PNET患者预后有密切关系。     

87例胃肠胰神经内分泌肿瘤的诊治分析

目的 探讨胃肠胰神经内分泌肿瘤(GEP-NEN)发生部位、临床症状、内镜及影像学表现、病理特点、诊断、治疗及预后。方法收集中山大学附属第一医院2000年1月至2010年6月间收治的87例GEP-NEN患者病历资料,通过对神经内分泌标记物突触素(Syn)和铬粒素A(CgA)的免疫组织化学染色确定肿瘤是否具有神经内分泌性质,按组织学和增殖活性明确肿瘤分级,将GEP-NEN分为神经内分泌瘤（G1和G2级）、神经内分泌癌（G3级）和混合性腺神经内分泌癌(G3级),探讨其临床特点及诊疗情况。结果 36例(41.4 ％)GEP-NEN发生在胰腺,其次为直肠18例(20.7％)、胃9例(10.3％)、十二指肠6例(6.9％)。87例GEP-NEN中65例(74.7％)为非功能性,多以各种消化道症状或肿瘤局部占位为首发症状,无一例出现类癌综合征,内镜及影像学表现主要为肿瘤占位病变。87例GEP-NEN中69例(79.7％)为神经内分泌瘤(NET)、13例(14.9％)为神经内分泌癌(NEC)、5例(5.4％)为混合性腺神经内分泌癌(MANEC);G1、G2和G3级肿瘤分别占64.9％、14.9％和20.2％。22例(47.8％) GEP-NEN患者就诊时肿瘤浸润肌层/浆膜层,18例(20.7％)出现淋巴结转移,18例(20.7％)出现远处转移,大部分转移至肝脏。CgA和Syn免疫组织化学染色阳性率分别为74.2％和88.1％。79例(90.8％)患者进行手术治疗。随访1年、3年和5年生存率分别为76.9％、54.2％和41.7％。结论GEP-NEN可发生于消化系统任何部位,临床表现多样,内镜和影像学检查是重要的诊断手段,确诊主要依赖病理,手术是主要的治疗手段,肿瘤病理分类、分级和远处转移情况等与其预后有关。     

胰腺神经内分泌肿瘤计算机断层扫描增强特征对术前病理分级的预测价值

目的探讨胰腺神经内分泌肿瘤(panNEN)计算机断层扫描(CT)增强特征预测术前病理分级的价值。方法回顾性分析2009年2月至2020年8月复旦大学附属中山医院经手术和病理确诊的136例panNEN患者的CT资料。根据2019年第5版世界卫生组织消化系统肿瘤分类标准将panNEN分为G1、G2、G3级神经内分泌瘤(NET)和神经内分泌癌(NEC), 比较不同病理分级病灶实性部分CT值和相关参数的差异。采用受试者操作特征曲线下面积(AUC)评价CT值和相关参数对不同病理分级panNEN的鉴别诊断价值。统计学分析采用非参数Kruskal-Wallis检验和卡方检验。结果在136例panNEN患者中, 共检出142个肿瘤病灶, 其中G1、G2、G3级NET和NEC病灶数分别为58、73、7、4个。随着病理分级的升高, panNEN病灶实性部分的CT强化程度呈逐渐下降趋势。G2级NET患者动脉期和静脉期的CT值、CT值差值、相对密度指数均低于G1级NET患者[动脉期:105 HU (46～251 HU)比126 HU (57～195 HU)、62 HU(6～212 HU)比81 HU(23～1...     

118例胃肠胰神经内分泌肿瘤临床病理特征及预后分析

目的探讨胃肠胰神经内分泌肿瘤(gastroenteropancreatic neuroendocrine neoplasms,GEP-NENs)的临床病理特征和患者生存预后的影响因素。方法回顾性分析118例GEP-NENs病例的发病特点、临床表现、病理特征、疾病生存预后及影响因素。结果 118例患者中男女比例为1.7∶1,高发年龄段为40～69岁,主要发病部位是直肠、胰腺和胃,常见临床表现为腹痛(25.4%)、便血(14.4%)、腹胀(11.9%),阳性体征患者46例(39.0%),主要以肛门指检肿物多见。患者1年、3年、5年总体生存率分别为90.5%、73.5%、67.3%,M分期是影响患者生存预后的独立危险因素(P=0.003)。结论 GEP-NENs发病率逐年增加,临床表现差异较大,早期诊断困难。生存预后方面,女性患者、年龄≤60岁、肿瘤直径2 cm、G1级、T1期、N0期、M0期、Ⅰ期、接受手术治疗的患者生存预后相对较好。     

胃神经内分泌肿瘤148例临床病理特征和预后分析

回顾性分析2008年2月至2018年12月由常熟市第二人民医院、苏州大学附属第一医院、南京医科大学第一附属医院病理检查确诊为胃神经内分泌肿瘤的148例患者的临床病理资料,其中男111例,女37例,发病年龄为(61.5±10.5)岁。22例患者发生进食哽噎,其中19例肿瘤原发于贲门。贲门或胃角神经内分泌肿瘤与其他部位神经内分泌肿瘤在胃镜下形态、病灶数目、肿瘤最大径、病理分级、N分期、M分期、临床分型等方面的差异均有统计学意义(χ2=19.179、12.070、14.880、36.972、13.865、8.262、39.730,P均<0.01),年龄≥60岁和TNM分期为进展期或晚期的患者预后较差。     

病理分级标准的差异对胰岛素肿瘤诊断的意义

目的探讨不同病理分级标准下胰岛素肿瘤(Insulinomas)临床分型与病理分级的差异及其与临床病理特点、预后的关系。方法以世界卫生组织消化系统肿瘤分类(2010)为基础,在中国胃肠胰神经内分泌肿瘤病理诊断共识(2011)、(2013)补充下对既往诊断的胰岛素肿瘤组织行HE染色和Cg A、Syn、insulin、Ki-67免疫组化检测,根据不同病理分级标准重新诊断,对比评估。结果共收集27例胰岛素肿瘤患者标本。Ki-67index以2%、20%为病理分级临界值时,27例患者诊断为NET G1期16例,NET G2期9例,NEC 2例;Ki-67index以5%、20%为病理分级临界值时,27例患者诊断为NET G1期21例、NET G2期4例、高增殖活性的NET 2例、NEC 0例。27例患者Insulin、Cg A、Syn阳性表达率依次为66.67%、74.07%、100%。肿瘤组织学类型与肿瘤大小、病程相关(χ2=8.834、32.693,P=0.026、0.008),与肿瘤远处转移、局部组织浸润、性别、年龄、民族、ABO血型无关(χ2=5.83、5.83、4.079、43.153、0.484、3.536,均P0.05);NET G1期、NET G2期两组患者生存时间比较差异无统计学意义(P0.05)。结论两种分级方案的诊断结果有所差异,中国共识提出的"高增殖活性的NET"能解决Ki-67index 20%~60%的非低分化肿瘤命名和归类混乱问题。     

CK19与胃肠胰神经内分泌肿瘤远处转移的相关性

[目的]探讨CK19与胃肠胰神经内分泌肿瘤(GEP NEN)远处转移的相关性。[方法]对确诊的GEP NEN患者225例相关石蜡切片的核分裂计数、Ki-67(MIB-1)、CgA、Syn、CD56和CK19等指标的免疫组化再次染色评估;按照不同部位,进行CK19与病理参数(分级、淋巴结转移、远处转移)的相关性分析及单因素生存分析。[结果]与CK19阴性相比,胰腺部位CK19阳性表达患者提示较高的远处转移率(P=0.0241),及较高的分期(P=0.036),其他部位未提示病理参数相关。单因素生存分析显示:胰腺、直肠、胃部位CK19阳性表达患者与阴性表达患者未提示预后差异性(P值分别为0.609 7、0.831 3、0.838 5)。[结论]CK19阳性仅在胰腺神经内分泌肿瘤提示较高的远处转移率和ENETS分期,CK19阳性与GEP NEN患者预后未提示相关性。     

Identification of tumor-associated,MHC class II-restricted phosphopeptides as targets for immunotherapy

The activation and recruitment of CD4⁺ T cells are critical for the development of efficient antitumor immunity and may allow for the optimization of current cancer immunotherapy strategies. Searching for more optimal and selective targets for CD4⁺ T cells, we have investigated phosphopeptides, a new category of tumor-derived epitopes linked to proteins with vital cellular functions. Although MHC I-restricted phosphopeptides have been identified, it was previously unknown whether human MHC II molecules present phosphopeptides for specific CD4⁺ T cell recognition. We first demonstrated the fine specificity of human CD4⁺ T cells to discriminate a phosphoresidue by using cells raised against the candidate melanoma antigen mutant B-Raf or its phosphorylated counterpart. Then, we assessed the presence and complexity of human MHC II-associated phosphopeptides by analyzing 2 autologous pairs of melanoma and EBV-transformed B lymphoblastoid lines. By using sequential affinity isolation, biochemical enrichment, mass spectrometric sequencing, and comparative analysis, a total of 175 HLA-DR-associated phosphopeptides were characterized. Many were derived from source proteins that may have roles in cancer development, growth, and metastasis. Most were expressed exclusively by either melanomas or transformed B cells, suggesting the potential to define cell type-specific phosphatome “fingerprints.” We then generated HLA-DRβ1*0101-restricted CD4⁺ T cells specific for a phospho-MART-1 peptide identified in both melanoma cell lines. These T cells showed specificity for phosphopeptide-pulsed antigen-presenting cells as well as for intact melanoma cells. This previously undescribed demonstration of MHC II-restricted phosphopeptides recognizable by human CD4⁺ T cells provides potential new targets for cancer immunotherapy.     

Obstruction of the pancreatic duct by a granular cell tumor

Summary A 31-year-old woman presented with constant epigastric pain. Obstruction of the pancreatic duct was observed by ultrasonography and CT scan and was further defined by ERCP. Surgical exploration of the pancreas revealed a tumor in the pancreatic head. Histologic and immunocytochemical examination revealed a benign granular cell tumor, a neoplasm not previously described as causing obstruction in the pancreas.     

Recurrent endobronchial inflammatory myofibroblastic tumors: Novel treatment options

Endobronchial inflammatory myofibroblastic tumors (IMTs) rarely occur in children younger than 10 years of age and have intermediate malignant potential. A 7‐year‐old girl initially presented with pneumonia. After failing outpatient treatment, she re‐presented in status asthmaticus. Computed tomography showed a left mainstem endobronchial mass which was resected bronchoscopically. Pathology was consistent with IMT. Surveillance bronchoscopy identified a recurrence. Despite a left upper lobectomy, recurrence led to further treatment with celecoxib and argon plasma coagulation. Follow‐up bronchoscopy revealed complete resolution. She remains disease and symptom‐free at her six‐year follow‐up.     

Circulating tumour cells: insights into tumour heterogeneity

Tumour heterogeneity is a major barrier to cure breast cancer. It can exist between patients with different intrinsic subtypes of breast cancer or within an individual patient with breast cancer. In the latter case, heterogeneity has been observed between different metastatic sites, between metastatic sites and the original primary tumour, and even within a single tumour at either a metastatic or a primary site. Tumour heterogeneity is a function of two separate, although linked, processes. First, genetic instability is a hallmark of malignancy, and results in ‘fixed’ genetic changes that are almost certainly carried forward through progression of the cancer over time, with increasingly complex additional genetic changes in new metastases as they arise. The second type of heterogeneity is due to differential but ‘plastic’ expression of various genes important in the biology and response to various therapies. Together, these processes result in highly variable cancers with differential response, and resistance, to both targeted (e.g. endocrine or anti‐human epithelial growth receptor type 2 (HER2) agents) and nontargeted therapies (e.g. chemotherapy). Ideally, tumour heterogeneity would be monitored over time, especially in relation to therapeutic strategies. However, biopsies of metastases require invasive and costly procedures, and biopsies of multiple metastases, or serially over time, are impractical. Circulating tumour cells (CTCs) represent a potential surrogate for tissue‐based cancer and therefore might provide the opportunity to monitor serial changes in tumour biology. Recent advances have enabled accurate and reliable quantification and molecular characterization of CTCs with regard to a number of important biomarkers including oestrogen receptor alpha and HER2. Preliminary data have demonstrated that expression of these markers between CTCs in individual patients with metastatic breast cancer reflects the heterogeneity of the underlying tumours. Future studies are designed to determine the clinical utility of these novel technologies in either research or routine clinical settings.     

Solitary concomitant endocrine tumor and ductal adenocarcinoma of pancreas

Pancreatic tumors with combined exocrine and endocrine features are rare.Most reported cases are classified as mixed exocrine and endocrine carcinoma of the pancreas.We report the first case of solitary concomitant endocrine tumor and ductal adenocarcinoma of the pancreas.A 58-year-old patient was admitted for uncontrolled diabetes mellitus and body weight loss.The tumor was fortuitously discovered in the pancreatic tail after a tumor survey panel.Grossly,the solitary tumor had a central fibrous band that c...     

Mucin-producing bile duct tumors: radiological–pathological correlation and diagnostic strategy

Mucin-producing bile duct tumors are characterized by intraductal papillary tumors producing large amounts of mucin. The tumor comprises macroscopically prominent intraductal papillary neoplastic epithelia and produces a large amount of viscid mucin, resulting in dilatation of the bile ducts. The surface of the tumor is frond-like, velvety, or serrated. The tumor exhibits five intraductal growth patterns; polypoid intraductal growth, mucosal spreading growth, cast-like intraductal growth, cystic tumor, and intraductal floating tumors. Imaging features reflect the interplay between the morphology of the tumor, the amount of mucin production, and biliary dilatation. This review article describes the radiological manifestations of the tumor, based on pathological-radiological correlation and biological behavior.     

A case of coexisting malignant carcinoid tumor and adenocarcinoma in the papilla of vater

A 47-year-old Japanese woman in whom obstructive jaundice had already been diagnosed, was found to have a dome-shaped elevated tumor approximately 3 cm in diameter located in the area very close to the papilla of Vater on endoscopical and radiographical investigations. Histopathologically, the resected tumor was composed mainly of solid nests of atypical argyrophilic cells, and partially of an area of well differentiated tubular adenocarcinoma, showing mutual transition in the mucosal layer. Both immunohistochemical and ultrastructural analyses confirmed the difference in character of tumor cells between these two areas; neuroendocrine cell carcinoma and tubular adenocarcinoma of common type in the intestine. To the best of our knowledge, this is only the third case reported to be a coexisting malignant carcinoid tumor and adenocarcinoma arising in the periampullary region.     

Metastatic germ cell tumor to the heart presenting with syncope.

Malignant nonseminomatous germ cell tumors (NSGCT) rarely metastasize to the heart. The first such case presenting with syncope is described. Eight previously described cases of NSGCT with intracaval metastasis to the heart are reviewed and the literature to date is discussed. Transesophageal echocardiography is the diagnostic study of choice and treatment consists primarily of platinum-based chemotherapy followed by surgical resection of residual deposits.     

Calcified Amorphous Tumor of the Heart: Case Report and Review of the Literature

Calcified amorphous tumor of the heart (cardiac CAT) is a rare non-neoplastic cardiac mass that mimics malignancy on imaging and can cause symptoms due to flow obstruction or embolization of calcific fragments. We report a 57-year-old female with multiple medical problems affected by cardiac CAT. The echocardiogram showed a 2 x 1.7 cm right atrial mass. Under the clinical diagnosis of cardiac myxoma, a mass resection was performed. Microscopic examination of the resected mass showed nodular calcified amorphous debris with admixed degenerated fibrin and focal chronic inflammation. At the 1-year follow-up, the patient was free of disease.We performed a literature review of 16 previously reported cases. Histologically, a cardiac CAT consists of calcification and eosinophilic amorphous material in the background of dense collagenous fibrous tissue. A review of these cases shows a wide range of age at diagnosis and slight female predominance. The patients are either asymptomatic at presentation or complain of shortness of breath. The tumors have been found in all chambers of the heart, most commonly in the left ventricle. The sizes of the tumors range from 0.17 to 4 cm, with 62.5% of the tumors being mobile. Among the nine cases with documented follow-up study, all but one was free of disease and only one case of relapse was recorded. In conclusion, cardiac CATs are frequently asymptomatic at presentation, size is equal to or less than 4 cm, they can be located in all four chambers and are usually mobile, and they may relapse when not completely excised.     

Sulfiredoxin is an AP-1 target gene that is required for transformation and shows elevated expression in human skin malignancies

Previous studies have shown that a dominant negative form of c-Jun (TAM67) suppresses mouse skin carcinogenesis both in vitro and in vivo. The current study identifies Sulfiredoxin (Srx) as a unique target of activator protein-1 (AP-1) activation and TAM67 inhibition. Manipulation of Srx levels by ShRNA or over-expression demonstrates that Srx is critical for redox homeostasis through reducing hyperoxidized peroxiredoxins. In JB6 cells, knockdown of Srx abolishes tumor promoter-induced transformation and enhances cell sensitivity to oxidative stress. Knockdown of Srx also impairs c-Jun phosphorylation, implicating a role for Srx in the feedback regulation of AP-1 activity. Screening of patient tissues by tissue microarray reveals elevated Srx expression in several types of human skin cancers. Our study indicates that Srx is a functionally significant target of AP-1 blockade that may have value in cancer prevention or treatment.