Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract

Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic tract.They are composed of a neuroendocrine(NE)and a non-NE compo-nent in at least 30%of each tumour.The non-NE component can include different histological combinations of glandular,squamous,mucinous and sarcomatoid phenotypes,and one or both of the components can be low-or high grade malignant.Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion,and the lack of specific clinical trials is the main reason why their management is difficult.The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data.It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that,due to their low incidence,will require long recruitment periods.

Solid pseudopapillary neoplasm of the pancreas

Solid pseudopapillary neoplasms are rare.This article reviews the clinical and pathologic features of solid pseudopapillary neoplasm of the pancreas,including the epidemiology,cytology,molecular pathology,differential diagnosis,treatment,and prognosis.Solid pseudopapillary neoplasms are low-grade malignant tumours of the pancreas characterized by poorly cohesive epithelial cells with solid and pseudopapillary patterns.Solid pseudopapillary neoplasms occur predominantly in young women.Although solid pseudopapillary neoplasms can occur throughout the pancreas,they arise slightly more frequently in the tail of the pancreas.The aetiology is unknown.Extremely rare cases have been reported in the setting of familial adenomatous polyposis.There are no symptoms unique to solid pseudopapillary neoplasms,however,the most common symptom is abdominal pain or discomfort.The features of solid pseudopapillary neoplasms on computed tomography imaging are indicative of the pathologic changes within the tumour.Typically,well-demarcated masses with variably solid and cystic appearances.Microscopically,these tumours are composed of epithelial cells forming solid and pseudopapillary structures,frequently undergoing haemorrhagic cystic degeneration.Typically,these tumours express nuclear and/or cytoplasmicβ-catenin.Almost all solid pseudopapillary neoplasms harbour mutations in exon 3 of CTNNB1,the gene encodingβ-catenin.The overall prognosis is excellent,and most patients are cured by complete surgical resection.

New insights in diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms

Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare epithelial neoplasms derived from pluripotent endocrine cells along the gastrointestinal tract and pancreas.GEP-NENs are classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas.Despite overlapping morphological features,GEP-NENs vary in molecular biology,epigenetic,clinical behavior,treatment response,and prognosis features and remain an unmet clinical challenge.In this review,we introduce recent updates on the histopathologic classification,including the tumor grading and staging system,molecular genetics,and systemic evaluation of the diagnosis and treatment of GEP-NENs at different anatomic sites,together with some insights into the diagnosis of challenging and unusual cases.We also discuss the application of novel therapeutic approaches for GEP-NENs,including peptide receptor radionuclide therapy,targeted therapy,and immunotherapy with immune checkpoint inhibitors.These findings will help improve patient care with precise diagnosis and individualized treatment of patients with GEP-NENs.

Gastroenteropancreatic neuroendocrine neoplasms:A clinical snapshot

Our understanding about the epidemiological aspects,pathogenesis,molecular diagnosis,and targeted therapies of neuroendocrine neoplasms(NENs)have drastically advanced in the past decade.Gastroenteropancreatic(GEP)NENs originate from the enteroendocrine cells of the embryonic gut which share common endocrine and neural differentiation factors.Most NENs are welldifferentiated,and slow growing.Specific neuroendocrine biomarkers that are used in the diagnosis of functional NENs include insulin,glucagon,vasoactive intestinal polypeptide,gastrin,somatostatin,adrenocorticotropin,growth hormone releasing hormone,parathyroid hormone-related peptide,serotonin,histamine,and 5-hydroxy indole acetic acid(5-HIAA).Biomarkers such as pancreatic polypeptide,human chorionic gonadotrophin subunits,neurotensin,ghrelin,and calcitonin are used in the diagnosis of non-functional NENs.5-HIAA levels correlate with tumour burden,prognosis and development of carcinoid heart disease and mesenteric fibrosis,however several diseases,medications and edible products can falsely elevate the 5-HIAA levels.Organ-specific transcription factors are useful in the differential diagnosis of metastasis from an unknown primary of well-differentiated NENs.Emerging novel biomarkers include circulating tumour cells,circulating tumour DNA,circulating micro-RNAs,and neuroendocrine neoplasms test(NETest)(simultaneous measurement of 51 neuroendocrine-specific marker genes in the peripheral blood).NETest has high sensitivity(85%-98%)and specificity(93%-97%)for the detection of gastrointestinal NENs,and is useful for monitoring treatment response,recurrence,and prognosis.In terms of management,surgery,radiofrequency ablation,symptom control with medications,chemotherapy and molecular targeted therapies are all considered as options.Surgery is the mainstay of treatment,but depends on factors including age of the individual,location,stage,grade,functional status,and the heredity of the tumour(sporadic vs inherited).Medical management is helpful to alleviate the symptoms,manage inoperable lesions,suppress postoperative tumour growth,and manage recurrences.Several molecular-targeted therapies are considered second line to somatostatin analogues.This review is a clinical update on the pathophysiological aspects,diagnostic algorithm,and management of GEP NENs.

Giant benign phyllodes breast tumour with pulmonary nodule mimicking malignancy:A case report

BACKGROUND Phyllodes tumours(PTs)are fibroepithelial breast tumours,which can be classified as benign,borderline or malignant,according to their histological characteristics.While various huge borderline or malignant PTs have been previously described,a benign PT with a pulmonary nodule mimicking malignancy has not yet been reported.In order that doctors may have a comprehensive understanding of super-giant benign PTs(≥20 cm),we also performed a literature review to summarize the clinical features,differential diagnosis,and treatment of this disease.CASE SUMMARY A 42-year-old woman with severe anaemia presented with a rapidly enlarging right breast mass,measuring approximately 30 cm×25 cm×20 cm that was first noticed 1 year previously.A region of skin ulceration and necrosis(20 cm×15 cm)was observed on the lateral side of the mass.Computed tomography(CT)of the chest revealed a pulmonary nodule,which initially suggested a diagnosis of metastasis.CT showed that the boundaries between the pectoralis major and the mass were blurred,which was presumed to be due to tumour invasion.However,two core needle biopsies of the mass showed no evidence of malignancy.Following these results,the tumour was removed by mastectomy of the right breast.Interestingly,postoperative pathology finally proved the diagnosis of a benign PT.After 1 year of follow-up,wedge resection of the small pulmonary nodule was performed,and it was confirmed that the lung nodule was actually adenocarcinoma rather than metastatic breast cancer.The patient recovered very well without any postoperative treatment.CONCLUSION This case is unique in that the giant breast mass initially mimicking a malignantclinical presentation was eventually pathologically confirmed to be a benign PT,which misled the diagnosis and complemented the atypical features of benign PTs.The pathological and immunohistochemical results were important in the differential diagnosis.In addition,total mastectomy should be recommended due to difficulty in the precise diagnosis of PTs,especially in large breast masses.In the literature,almost one-half of super-giant benign cases were thought to be malignant tumours before surgery.This finding is a reminder to consider all conditions in order to make an accurate diagnosis and avoid excessive treatment.

Evolution of breast cancer therapeutics: Breast tumour kinase's role in breast cancer and hope for breast tumour kinase targeted therapy

There have been significant improvements in the detection and treatment of breast cancer in recent decades. However, there is still a need to develop more effective therapeutic techniques that are patient specific with reduced toxicity leading to further increases in patients' overall survival; the ongoing progress in understanding recurrence, resistant and spread also needs to be maintained. Better understanding of breast cancer pathology, molecular biology and progression as well as identification of some of the underlying factors involved in breast cancer tumourgenesis and metastasis has led to the identification of novel therapeutic targets. Over a number of years interest has risen in breast tumour kinase(Brk) also known as protein tyrosine kinase 6; the research field has grown and Brk has been described as a desirable therapeutic target in relation to tyrosine kinase inhibition as well as disruption of its kinase independent activity. This review will outline the current "state of play" with respect to targeted therapy for breast cancer, as well as discussing Brk's role in the processes underlying tumour development and metas-tasis and its potential as a therapeutic target in breast cancer.

Surgical management of pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms are a rare and complex group of neoplastic lesions that develop from pancreatic islet cells.Their incidence has dramatically increased during the last two decades.Due to its complex nature and pathophysiological behaviour,surgical management continues to evolve.Surgery remains the cornerstone of treatment for most non-functional and functional pancreatic neuroendocrine tumours,while lymphadenectomy remains a controversial subject.Different techniques,such as pancreas-preserving and minimally invasive approaches,continue to evolve and offer the same overall outcomes as open surgery.This comprehensive review describes in detail the current and most up-todate classification and staging of pancreatic neuroendocrine tumours,explores the rationale for nonsurgical and surgical management,and focuses on surgical treatment and more specifically,on minimally invasive approaches.

牙源性始基瘤4例临床病理学观察

目的 探讨牙源性始基瘤(primordial odontogenic tumour, POT)的临床病理学特征、诊断和鉴别诊断。方法 收集4例颌骨POT的临床资料,采用影像学检查、HE和免疫组化EnVision两步法染色,分析其临床病理特征并复习相关文献。结果 4例患者发病年龄5~21岁;男女性各2例;发病部位于上、下颌骨各2例。临床表现为缓慢生长的无痛性肿块,切面呈灰黄、灰白色,周围多与1枚未萌牙牙冠相关。肿瘤由黏液样背景中散在疏松梭形或星形细胞组成,周边可见单层立方、柱状上皮被覆,部分区域可见乳头状反褶内陷,2例可见钙化。结论 POT是罕见的良性牙源性混合性肿瘤,好发于儿童和青少年。掌握其特征性的组织学表现可作出正确诊断,行完整切除者预后良好。

纤支镜活检诊断气管支气管良性肿瘤11例临床病理分析

目的分析11例气管支气管良性肿瘤的临床病理特征,加深对该类肿瘤的认识,提高确诊率。方法对11例经纤支镜活检诊断为气管支气管良性肿瘤的病例进行回顾性分析。结果 11例中男女比为9∶2,包括气管鳞状上皮乳头状瘤及血管球瘤各1例;支气管颗粒细胞瘤及多形性腺瘤各1例;支气管平滑肌瘤及腺性乳头状瘤各2例;支气管错构瘤3例。不同病理类型的肿瘤表达特异性的免疫组化标记物,影像学检查误诊率较高。结论原发性气管支气管良性肿瘤多见于男性,发生部位以支气管居多。该类肿瘤多数病理类型具有特征性的组织学改变及免疫组化标记物,故纤支镜活检为最可靠确诊手段。为避免误诊临床医师应提高取活检意识。

甲状腺透明变梁状肿瘤临床病理观察

目的探讨甲状腺透明变梁状肿瘤的病理特征。方法对1例甲状腺肿瘤的临床病理资料进行光镜、电镜和免疫组化标记检查,选用的抗体TTF1、Ki-67、Ki-67(MIB-1)、E-cadherin、calcitonin、CgA、TFE3、Syn、AFP、EMA、CKpan和p53,并复习文献。结果患者为青年男性,肿瘤位于甲状腺左叶。大体呈灰白色球形实性肿块;组织学见肿瘤细胞呈梁状、腺泡样排列,细胞呈多角形或梭形;核仁周围有空晕,易见核内包涵体,小梁内见透明变物质并与瘤细胞融合。免疫组化显示肿瘤细胞细胞膜MIB-1强(+)。电镜可见细胞质富含中间丝。结论甲状腺透明变梁状肿瘤中呈梁状结构的肿瘤细胞细胞膜具有特征性的MIB-1(+),该肿瘤形态易与甲状腺乳头状癌实体亚型和甲状腺髓样癌相混淆。现在认为,该肿瘤是一种低度恶性潜能的肿瘤。

乳腺叶状肿瘤的形态学和免疫组织化学研究

目的观察乳腺叶状肿瘤（phyllodes tumours,PTs）的形态学和免疫组织化学特征,并探讨其诊断标准。方法对21例PTs进行组织学观察和免疫组化SP法检测,并选取5例乳腺纤维腺瘤和5例乳腺腺病标本作为对照组。使用一抗包括CK-pan、EMA、SMA、p53、S-100蛋白、CD117、CD34、CD99、bc l-2、ER、PR、K i-67、CD10。结果21例PTs大体上均表现为界限清楚的肿块,且呈分叶状。肿瘤由具有双层排列的上皮成分以及过度生长的间质成分组成。根据间质的过度生长程度、细胞的异型程度、核分裂数、肿瘤边缘情况、有无异源性成分以及肿瘤性坏死等继发性改变将其分为良性、交界性和恶性3个级别。间质细胞免疫组化表达情况：CKpan：0/21、EMA：0/21、SMA：17/21、CD117：6/21、CD34：18/21、S-100蛋白：2/21、CD99：13/21、CD10：8/21、PR：5/21、ER：4/21、p53：18/21、K i-67：3%~10%、bc l-2：15/21。结论PTs的诊断主要依据组织学观察,免疫组化CD117、CD34、CD99、CD10、bc l-2的检测可以起到一定的辅助作用。

小汗腺汗孔瘤16例临床病理分析

目的:总结分析小汗腺汗孔瘤的临床及病理特点.方法:对16例小汗腺汗孔瘤的临床、病理及免疫病理资料进行回顾性研究.结果:小汗腺汗孔瘤常发生在肢端,临床表现多样,易于误诊,组织病理学特点为缺乏胞浆的立方细胞增生,细胞核呈圆形或卵圆形,与周围界限清楚.结论:发生在肢端红色或疣状结节,病史较长,临床如怀疑汗孔瘤诊断时,采取手术切除及病理活检的方式是最好的选择方法.

非小细胞肺癌免疫治疗进展

近年来,非小细胞肺癌(non-small cell lung cancer,NSCLC)在手术治疗、放疗、化疗及靶向治疗方面均取得了很大的进展,但晚期NSCLC患者的5年生存率仍然很低。免疫治疗利用免疫系统来控制和清除瘤细胞,已成为肿瘤治疗的一种重要手段。NSCLC的免疫治疗近期取得了突破性的进展,抗原特异性肿瘤疫苗、检查点阻滞剂等多种新型抗肿瘤免疫治疗药物已进行NSCLC治疗的临床试验,并在II期和III期临床试验中取得一定的成果。目前已完善了免疫治疗疗效评估标准,成为免疫治疗药物抗肿瘤评价标准。免疫治疗将成为NSCLC治疗的一种重要手段。

甲状腺透明变梁状肿瘤6例临床病理分析

目的探讨甲状腺透明变梁状肿瘤(hyalinizing trabecudar tumor,HTT)临床病理学特征、鉴别诊断及治疗。方法回顾分析6例HTT的临床表现、超声检查、组织病理学及免疫表型特征,并复习相关文献。结果组织病理学显示瘤细胞呈梁状、器官样排列,小梁间见透明变性的基膜样物质沉积,细胞呈多角形或梭形;胞质嗜酸,细颗粒状,胞核圆形或卵圆形,常见核沟及核内假包涵体。免疫组化标记瘤细胞TG、TTF-1、CD56呈阳性,CK19散在(+),Galectin-3(-/+),不表达Calcitonin、MC、CEA、Syn、CgA,Ki-67表达膜阳性或质弱阳性,p53低表达。该肿瘤需与甲状腺乳头状癌、甲状腺髓样癌和副神经节瘤等相鉴别。结论 HTT是一种罕见的甲状腺肿瘤,多表现为良性的形态学及生物学行为,准确的病理学诊断对其临床治疗及预后有极其重要的作用。

松果体区肿瘤的MRI诊断

目的分析松果体区肿瘤的MRI特征,以提高诊断准确率。资料与方法经手术病理证实的松果体区肿瘤23例,均行MR平扫及增强扫描。结果(1)不同的松果体区肿瘤,如:脑膜瘤、松果体实质肿瘤、生殖细胞肿瘤等各具有特征性的MRI表现;(2)某些肿瘤具有年龄和性别特征,如:神经母细胞瘤和松果体母细胞瘤患者发病年龄均<10岁,生殖细胞瘤多发于青少年男性等。结论松果体区肿瘤具有较特征性的MRI表现,结合患者临床和发病年龄、性别、部位等特点,可进一步提高其术前诊断准确率。

胸腺原发性神经内分泌肿瘤临床病理特征

目的探讨胸腺神经内分泌肿瘤(thymic neuroendocrine tumour,TNET)的临床病理学特征、诊断及鉴别诊断。方法收集16例TNET的临床资料,采用免疫组化EnVision两步法检测CK、CD56、Syn、CgA、Ki-67等的表达,分析其与临床病理特征的关系,并复习相关文献。结果患者年龄35~75岁,中位年龄56岁。临床症状和影像学表现无特异性,影像学显示为前中纵隔占位,为孤立类圆形性结节,边界不定,肿瘤最大径1.5~9.8 cm。病理诊断:1例经典型类癌,10例中级别非典型类癌,1例大细胞神经内分泌癌,4例小细胞癌。免疫表型:CK(16/16),神经内分泌标志物CD56(14/16)、Syn(13/16)和CgA(10/16)均阳性,Ki-67增殖指数为1%~95%。随访时间6~120个月,1例经典型类癌患者仍健在,3例中级别非典型类癌患者发生远处转移,5例高级别神经内分泌癌患者均发生转移而死亡。结论TNET是一类罕见的胸腺恶性肿瘤,具有异质性。TNET确诊依赖于组织病理学、免疫表型及分子表型;TNET精准病理诊断和临床病理分期具有重要意义。

甲状腺透明变梁状肿瘤

1临床资料例1，女，53岁，发现左颈前肿块1个月余，无疼痛不适，肿块逐渐增大就诊我院。体检：左颈前可触及5cm×4cm×3cm的肿块，质中，活动差，颈部未触及肿大淋巴结。彩超报告：甲状腺左侧叶内实质性肿块。外院穿刺活检病理报告：①甲状腺嗜酸性腺瘤；②甲状腺癌可疑。在我院行左甲状腺部分切除：左甲状腺组织6cm×3cm×2．5cm，切面见1个4．5cm×2．2cm的灰红色质实区，其间有1个直径1cm的囊性区域，

良性脊索细胞瘤临床病理观察

目的探讨良性脊索细胞瘤(BNCT)的临床病理特征、诊断与鉴别诊断。方法在临床资料及影像学所见基础上,分析1例BNCT的组织病理特征并复习相关文献。结果患者女性,48岁。下腰痛1年。CT扫描显示第4腰椎椎体软骨终板下占位性病变,具有清楚的硬化边,但无明显的皮质塌陷及骨质破坏。MRI示T2WI呈高信号,而T2WI呈低信号。行病灶彻底刮除及腰椎重建术。巨检:病变呈果冻样或貌似变性的骨髓脂肪。镜检:肿瘤主要由实性片层状脂肪样细胞或洋葱皮样细胞构成,肿瘤细胞马赛克样排列,胞膜清晰,胞质空泡状、泛白或轻度嗜酸性,核圆形、卵圆形,居中或偏位。不仅无显著的核异型及核分裂,同时缺乏分叶状结构、细胞外黏液样基质及丰富的血管网,也无松质骨浸润及坏死。病变中可见一些岛状分布的非肿瘤性骨髓组织。受累骨小梁硬化。免疫组化示CKpan和CK8/18(+),但CD68(-)。结论 BNCT是一种罕见的骨内脊索源性良性肿瘤,预后良好。

卵巢颗粒细胞瘤的诊疗进展

卵巢颗粒细胞瘤是相对少见的卵巢性索间质细胞肿瘤,因发病初期多有内分泌相关症状,而使得该肿瘤容易被早期发现。各种分子生物学指标在该病的诊断及随访中发挥着重要的作用。手术是其重要的治疗措施,化疗、放疗、激素治疗及分子生物靶向治疗也是重要的治疗方法。对这类患者采取合理的治疗手段,相对于其他的卵巢恶性肿瘤,可以达到较高的存活率。

重组人可溶性凋亡配体相关蛋白联合顺铂抑制肺癌裸鼠移植瘤的生长

目的:探讨重组人可溶性凋亡配体相关蛋白(rhTRAIL)和顺铂联用对抑制人肺腺癌细胞系A549裸鼠移植瘤的生长有无协同增效作用。方法:将24只荷人A549肺腺癌BALB/CA-nu裸鼠随机分成4组,(1)阴性对照组;(2)rhTRAIL组(1μg/mL,隔日1次×8次);(3)顺铂组(1.5mg/kg,每周2次×4次);(4)联合用药组(rhTRAIL1μg/mL,隔日1次×8次+顺铂1.5mg/kg,每周2次×4次)。分别测量瘤重、瘤体积,计算肿瘤生长指数和抑瘤率,并观察各组移植瘤组织的毒副作用和病理形态结构。结果:阴性对照组肿瘤生长指数为7.63±2.01,而rhTRAIL组和顺铂组分别为4.15±1.04和4.37±0.93,联合用药组则减低至1.69±0.37。rhTRAIL组、顺铂组的抑瘤率分别为36.8%和30.3%,联合用药组则增高达69.5%。rhTRAIL组、顺铂组和阴性对照组比较,差异具有显著性(P<0.05);联合用药组和其他3组比较差异均有显著性(P<0.01)。各组裸鼠的毒副作用轻微,治疗前后体重无明显变化。结论:rhTRAIL、顺铂均可抑制A549裸鼠移植瘤的生长,rhTRAIL和顺铂联用具有协同增效作用。rhTRAIL有望成为一种重要的生物制剂应用于肺癌的多学科综合治疗。