胰腺实性-假乳头状肿瘤和神经内分泌肿瘤中Claudin5和Claudin7的表达及意义

目的探讨Claudin5和Claudin7在胰腺实性-假乳头状肿瘤(solid-pseudopapillary neoplasm,SPN)、神经内分泌肿瘤(neuroendocrine tumor,NET)中的表达及意义。方法采用免疫组化En Vision法检测20例SPN和23例NET中β-catenin、CD10、CK、vimentin、CD99、NSE、Syn、PR、Claudin5和Claudin7的表达。结果 (1)在SPN和NET中β-catenin、CD10、CK、vimentin、CD99、NSE、Syn、PR呈不同程度阳性表达。其中,β-catenin和CD10在SPN和NET中的阳性率差异有统计学意义(P0.05),β-catenin诊断SPN的敏感性为90.0%,特异性为52.2%;CD10诊断SPN的敏感性为80.0%,特异性为69.6%。其余6种标志物差异无统计学意义(P0.05)。(2)Claudin5在SPN中的阳性率为100%(20/20),明显高于NET(13.0%,3/23),差异有统计学意义(P0.05);其诊断SPN的特异性(100%)和敏感性(87.0%)均高于β-catenin和CD10。(3)Claudin7在胰腺NET中的阳性率为100%(23/23),而在所有SPN中均不表达;其诊断NET的特异性和敏感性均为100%。结论 Claudin5和Claudin7分别在SPN和NET中呈肿瘤细胞胞膜阳性表达模式,是两者的免疫组化特征。联合检测Claudin5、β-catenin、CD10和Claudin7有助于诊断和鉴别诊断SPN和NET。     

联合运用BCL-10和Trypsin在胰腺腺泡细胞癌诊断和鉴别诊断中的作用

目的探讨联合运用BCL-10和Trypsin在胰腺腺泡细胞癌(pancreatic acinar cell carcinoma, PACC)、胰腺神经内分泌肿瘤(pancreatic neuroendocrine tumors, PNET)及胰腺实性假乳头肿瘤(solid pseudopapillary neoplasm, SPN)中的诊断和鉴别诊断作用。方法收集安徽医科大学第一附属医院病理科2014～2018年已确诊的46例胰腺肿瘤相关病例,其中7例PACC来自复旦大学附属中山医院病理科及皖南医学院弋矶山医院病理科,采用免疫组化EnVision两步法检测BCL-10、Trypsin、CD10、β-catenin、CgA、Syn在PACC、PNET和SPN中的表达。结果 BCL-10、Trypsin在PACC中的阳性率分别为80.0%和70.0%,在SPN中均阴性;BCL-10在PNET中均阴性,Trypsin在PNET中的阳性率为18.8%。CgA、Syn在PNET中的阳性率分别为100.0%和93.7%,在PACC和SPN中的阳性率较低(0～40.0%)。在SPN中CD10阳性率和β-catenin核阳性率分别为95.0%和100.0%,β-catenin在另外两种肿瘤中主要呈散在胞膜弱阳性,胞核阳性率较低(10.0%～25.0%)。BCL-10和Trypsin在PACC中的敏感性分别为80.0%、70.0%,特异性分别为94.7%、91.7%。联合使用BCL-10和Trypsin的敏感性和特异性分别为90.0%、97.1%。结论与传统指标Trypsin相比,BCL-10对PACC的诊断具有较高的敏感性和特异性,联合运用BCL-10和Trypsin对PACC、PNET及SPN的鉴别诊断具有重要价值。     

胰腺实性-假乳头状肿瘤中TFE3的表达及意义

目的探讨胰腺实性-假乳头状瘤(solidpseudopapillary neoplasms,SPN)的临床病理学特征、免疫表型及TFE3表达的意义。方法回顾性分析22例胰腺SPN的临床病理特点,采用免疫组化EnVision法检测TEF3在22例胰腺SPN中的表达;选取15例原发胰腺的其他肿瘤作为对照,5例胰腺SPN行FISH检测TFE3基因状态。结果 21例胰腺SPN显示TFE3不同程度的核阳性,胰腺其他肿瘤TFE3呈阴性,FISH检测未发现TFE3基因改变。结论胰腺SPN是好发于年轻女性的低度恶性肿瘤,除β-catenin外,TFE3亦可作为诊断胰腺SPN的有用指标。     

胰腺神经内分泌肿瘤与胰腺实性假乳头状瘤中β-catenin、E-cadherin及CD10的鉴别诊断价值

目的探讨胰腺神经内分泌肿瘤(pancreatic neuro endocrine neoplasms,PNEN)与胰腺实性假乳头状瘤(solid-pseudopapillarytumor of pancreas,SPTP)的临床病理学特征,并分析联合应用免疫组化标记β-catenin、E-cadherin及CD10的鉴别诊断价值。方法收集2007年3月～2017年2月经明确诊断的53例PNEN和40例SPTP,回顾性分析其临床病理资料,采用免疫组化法观察免疫标志物β-catenin、E-cadherin、CgA、Syn、CD56、CD10、CK在两组肿瘤中的表达。结果 PNEN和SPTP的病理学形态有重叠,β-catenin在PNEN中均为细胞膜、细胞质阳性,而在SPTP中则为细胞核阳性;E-cadherin在PNEN中为细胞膜、细胞质阳性(100%),而在SPTP中均显示细胞膜表达丢失;CD10在SPTP中的阳性率为100%(40/40),在PNEN中不表达。CgA、Syn、CD56、CK在PNEN及SPTP均有不同程度表达。结论β-catenin、E-cadherin及CD10阳性对PNEN和SPTP的鉴别诊断具有特异性,是较有价值的免疫组化标志物。     

胰腺囊性肿瘤53例临床病理特征

目的 探讨胰腺囊性肿瘤(pancreatic cystic neoplasm, PCN)的临床病理学特征。方法 收集53例PCN的临床病理资料，行HE及免疫组化EnVision法检测，并复习相关文献。结果 53例PCN中浆液性囊性肿瘤(serous cystic neoplasm, SCN)22例，实性假乳头状肿瘤(solid pseudopapillary neoplasm, SPN)13例(伴高级别转化1例),黏液性囊性肿瘤(mucinous cystic neoplasm, MCN)12例(伴相关浸润性癌2例，伴高级别异型增生1例),导管乳头状黏液性肿瘤(intraductal papillary mucinous neoplasm, IPMN)6例(伴相关浸润性癌1例，伴原位癌2例)。免疫表型：(1)22例SCN:22例均表达上皮标志物CK、CK7、CK19,10例表达α-inhibin, 22例均不表达CgA、Syn、CD56、vimentin, Ki-67增殖指数均约1%;(2)13例SPN:13例均表达PR、CD10及β-catenin, 6例表达vimentin, 5例...     

胰腺透明细胞变异型实性-假乳头状肿瘤1例并文献复习

目的 探讨胰腺透明细胞变异型实性-假乳头状肿瘤(clear cell variant of solid pseudopapillary neoplasm, ccSPN)的临床病理学特征。方法 回顾性分析1例ccSPN的临床资料，采用免疫组化EnVision两步法检测CK、vimentin、CD10、β-catenin、CD56、Syn、CgA、E-cadherin、Ki-67的表达，分析蛋白表达与临床病理特征的关系，并复习相关文献。结果 患者女性，54岁，以腹部疼痛为首发症状，MRI示胰体尾部占位伴钙化。镜下见肿瘤界尚清，瘤细胞体积小，形态温和，呈巢状或小梁状排列，大部分胞质内含大小不等的空泡或胞质完全空泡化，细胞核圆形或卵圆形，核仁不明显，未见明确核分裂象。瘤组织被透明变的间质分隔，局部黏液样变。免疫表型：vimentin、CD10、β-catenin、CD56、Syn均阳性，CK、E-cadherin、CgA均阴性，Ki-67增殖指数约2%。结论 ccSPN是实性-假乳头状肿瘤的一种罕见变异型，行影像学检查，并尽早手术切除及长期随访是疾病诊治的关键。     

网状纤维染色及P504S在胰腺实性假乳头状瘤鉴别诊断中的价值

目的探讨网状纤维染色和P504S在胰腺实性假乳头状瘤(solid-pseudopapillary tumor,SPTP)和胰腺内分泌肿瘤(pancreatic endocrine neoplasm,PEN)鉴别诊断中的价值。方法应用网状纤维Gomori法对10例SPTP和6例PEN进行染色;采用免疫组化En Vision两步法检测P504S、CD10、PR、vimentin、Cg A、CD56、Syn在二者中的表达。结果 SPTP组网状纤维染色显示假乳头纤维血管轴心阳性,勾勒出管腔扩张的小血管形态;PEN组网状纤维染色显示肿瘤细胞巢周围血窦分割阳性,勾勒出相互吻合的毛细血管网。P504S、vimentin、CD10、PR、Cg A、CD56、Syn诊断SPTP的敏感性分别为60%、100%、80%、90%、20%、80%、80%;特异性分别为100%、83.3%、83.3%、66.7%、33.3%、16.67%、16.67%。P504S、vimentin、CD10、PR在SPTP组中的阳性率均高于PEN组,组间比较差异均有统计学意义(P均0.05)。联合检测P504S、vimentin、CD10、PR在SPTP组阳性率亦显著高于PEN组,组间比较差异均具有统计学意义(P0.01)。Cg A、CD56、Syn在二者间阳性率比较,差异无统计学意义(P0.05)。结论网状纤维染色可以直观简便的鉴别两组肿瘤;联合检测P504S、vimentin、CD10、PR也可以有效的鉴别SPTP和PEN,且P504S诊断SPTP的特异性高。     

INSM1在胃肠胰神经内分泌肿瘤诊断中的价值

目的探讨胰岛素瘤相关蛋白1(insulinoma-associated protein 1,INSM1)在胃肠胰神经内分泌肿瘤(gastroenteropancreatic neuroendocrine neoplasms,GEP-NEN)中的表达及其在诊断中的应用价值。方法应用免疫组化En Vision法检测48例GEPNEN和40例胃肠胰非神经内分泌肿瘤中INSM1、Cg A、Syn和CD56的表达,并分析其与GEP-NEN临床病理特征的关系。结果48例GEP-NEN中,INSM1的阳性率为81. 3%,而Cg A、Syn和CD56的阳性率分别为50%(24/48)、89. 9%(43/48)和66. 7%(32/48),INSM1、Cg A、Syn和CD56在胃肠胰非神经内分泌瘤中的阳性率分别为0 (0/40)、10. 0%(4/40)、12. 5%(5/40)和10%(4/40),INSM1、Cg A、Syn和CD56在GEP-NEN中的表达均明显高于胃肠胰非神经内分泌瘤中的表达(P 0. 05);INSM1主要表达于食管、胰腺和结直肠神经内分泌肿瘤中,与Cg A、Syn和CD56表达不同,INSM1表达与GEP-NEN分级无关(P 0. 05)。INSM1对GEP-NEN诊断的灵敏度高于Cg A,特异度与Cg A、Syn和CD56差异无统计学意义(P 0. 05)。结论INSM1属于新的神经内分泌标志物,可与Cg A、Syn和CD56联合检测用于GEP-NEN的诊断。     

混合性肝细胞肝癌和神经内分泌癌5例临床病理分析

目的探讨混合性肝细胞肝癌和神经内分泌癌(mixed hepatocellular carcinoma and neuroendocrine carcinoma, mHNEC)的临床病理学特征。方法回顾性分析5例mHNEC的临床病理学及免疫表型特征并复习相关文献。结果 5例患者均为男性,年龄25～78岁,平均59岁,3例因腹痛、腹胀入院,4例有乙肝病史。眼观:mHNEC中肝细胞肝癌(hepatocellular carcinoma, HCC)成分灰黄色,质软;神经内分泌癌(neuroendocrine carcinoma, NEC)成分灰白、灰红色,可伴坏死或出血。镜检:mHNEC中HCC成分和NEC成分可呈碰撞或混合穿插生长,其中HCC呈细梁、粗梁状排列,肿瘤细胞胞质丰富,核圆形,核仁明显;NEC呈巢、团状生长,核呈卵圆形,核质比高,核分裂象易见。免疫表型:mHNEC中HCC成分Hep Par1阳性,CD56、CgA和Syn均阴性;NEC成分Hep Par1阴性,CD56、CgA和Syn均阳性。NEC成分Ki-67增殖指数高于HCC成分。5例均行部分肝切除术,4例术后辅以综合治疗。术后随访1～49个月,2例死亡。结论肝脏mHNEC少见,其临床表现缺乏特异性,确诊依赖于病理特征及免疫表型。治疗方式主要是手术切除联合化疗。     

肾细胞癌的临床病理与免疫表型研究

目的 研究肾细胞癌的临床病理特征、预后及免疫表型特点.方法 复习114例肾细胞癌的临床病理资料、HE切片,按2004年WHO肾肿瘤分类标准重新分类、随访并进行免疫组织化学染色.结果 114例.肾细胞癌包括5个类型,肾透明细胞癌77例(67.5%)、乳头状肾癌11例(9.6%)、肾嫌色细胞癌14例(12.3%)、Xp11.2易位_/TFE3基因融合相关性肾癌10例(8.8%)、未能分类肾肿瘤2例(1.8%).免疫组织化学结果,肾透明细胞癌主要表达CK(93.5%,72/77)、CD10(93.5%,72/77)、波形蛋白(75.3%,58/77),乳头状肾癌主要表达α-甲酰基辅酶A消旋酶(AMACR,11/11),肾嫌色细胞癌主要表达CD117(11/14),Xp11.2易位/TFE3基因融合相关性肾癌TFE3、AMACR、CD10和CK的阳性率分别为10/10、10/10、9/10和7/10.结论 肾癌是一组形态学上各有特征的异质性肿瘤,在形态学基础上,CD10、波形蛋白、CD117、AMACR、CK7、TFE3有助于亚型的诊断.     

Solid pseudopapillary neoplasm (SPN) of the testis: Comprehensive mutational analysis of 6 testicular and 8 pancreatic SPNs

BackgroundRecently, we came with the theory of a possible relationship between a group of testicular and pancreatic tumors. We used one case of a pancreatic analogue solid pseudopapillary neoplasm of the testis composed partially of areas reminiscent of solid pseudopapillary neoplasm (SPN) of the pancreas and partially of structures identical to primary signet ring stromal tumor of the testis (PSRSTT) as a connecting link between these two entities. After demonstrating that PSRSTT and pancreatic analogue SPN of the testis share the same immunoprofile and genetic features characteristic for pancreatic SPN, we came to the conclusion that pancreatic analogue SPN of the testis and PSRSTT represent a morphological spectrum of a single entity and that both are related to the pancreatic SPN.DesignThe aim of this study is to present a series of 6 cases of testicular tumors, which lacked the signet ring cell component and were thus morphologically very similar to the SPN of the pancreas. The goal of this study is to compare the genetic background of these testicular tumors that are obviously related to the PSRSTT/pancreatic analogue SPN of the testis with the series of 8 pancreatic SPN.ResultsThe mutational analysis revealed an oncogenic somatic mutation in the exon 3 of the CTNNB1 (β-catenin) gene in all analyzable (5/6) testicular and all pancreatic (8/8) tumors. The immunoprofile (positivity with β-catenin, CD10, vimentin, NSE, CD56, and negativity with inhibin, calretinin, chromogranin) was identical in all testicular and pancreatic tumors.ConclusionThis study expanded the morphological spectrum of the PSRSTT/pancreatic analogue SPN of the testis by adding 6 cases without the signet ring cell component. Considering the obvious analogy of PSRSTT/pancreatic analogue SPN of the testis/SPN of the testis and their relationship to the pancreatic SPN we propose the collective term “solid pseudopapillary neoplasm of the testis” for these tumors. The mutational profile of the SPN of the testis and pancreas was the same in both groups of tumors which we consider as a final proof that SPN of the testis is identical to the SPN of the pancreas.     

Solid-pseudopapillary neoplasm of the pancreas with massive central calcification in an old man

Solid-pseudopapillary neoplasm (SPN) is a rare pancreatic tumor primarily affecting women in their twenties. It is characterized by a well-demarcated or encapsulated mass, indolent behavior and favorable prognosis. Capsular or punctate calcification is occasionally observed. Reported herein is a case of SPN of the pancreas with massive calcification in a 76-year-old Japanese man. Macroscopically, the pancreatic tumor appeared to be a simple calcified nodule, but histological examination revealed that it was an epithelioid tumor with massive calcification. The tumor cells, forming nests and cords, had eosinophilic cytoplasm and small eccentric nuclei. They were immunohistochemically positive for vimentin, CD56 and neuron-specific enolase. Nuclear accumulation of β-catenin protein and a point mutation of the β-catenin gene by genomic DNA sequencing confirmed that the tumor was SPN. This is a very rare case of pancreatic SPN with massive calcification in an old man.     

E-cadherin-negative acinar cell carcinoma of the pancreas: report of a case showing a solid pseudopapillary growth pattern

E-cadherin expression patterns in acinar cell carcinomas (ACCs) of the pancreas have not been well documented. Herein, we present a hitherto undescribed case of E-cadherin-negative ACC with a solid pseudopapillary growth pattern in a 65-year-old man. We used an antibody against the extracellular domain of E-cadherin. As a further unusual status in ACC, faint β-catenin expression was observed in the cytoplasm of carcinoma cells. Morphological distinction from a solid pseudopapillary neoplasm (SPN) of the pancreas might be problematic in such a case, because of their similarities concerned with the growth pattern and E-cadherin negativity. Without nuclear accumulation of β-catenin, a diagnosis of SPN was almost excluded. Immunoreactivity for trypsin and BCL10 made an accurate diagnosis of ACC to this case. The tumor recurred 10 months post-surgery as rapidly enlarging masses in the liver, presumably indicating the aggressiveness of the E-cadherin-negative phenotype among ACCs.     

Incidence of composite intestinal adenoma-microcarcinoid in 158 surgically resected polyps and its association with squamous morule

Composite intestinal adenoma-microcarcinoid (CIAM) is a rare colorectal lesion consisting of adenoma and small well-differentiated neuroendocrine cell clusters at its base. Its incidence is unknown. Benign squamous morule may demonstrate a neuroendocrine phenotype by immunohistochemistry. We investigated the incidence and clinicopathologic features of CIAM in endoscopically unresectable, surgically removed colorectal adenomas and evaluated its association with squamous morule.Archived pathology materials from 158 surgically resected colorectal adenomas were reviewed. 139 (88%) polyps were entirely submitted for microscopic examination. All lymph nodes were negative for adenocarcinoma and neuroendocrine tumor. CIAM was identified in 6 (3.8%) cases. The microcarcinoid (MC) was distributed over a mean of 5.8 mm (range < 1 to 12 mm), and was multifocal in 5 cases. The MC component was positive for synaptophysin in 6, CK5/6 in 4, and β-catenin in 3 cases. Two of 6 (33.3%) CIAM showed concurrent squamous morule, compared to 4.0% (6 of 152) of adenomas without MC (p < 0.05). At the end of the mean follow-up of 53 months, 4 were free of disease and one patient with previous history of pulmonary large cell neuroendocrine carcinoma (NEC) had a recurrence of NEC. One patient died of an unrelated disease.The incidence of CIAM in surgically removed colorectal adenomas is 3.8%, with an indolent clinical course. Frequent co-expression of CK5/6 and β-catenin in MC combined with common co-existence of squamous morule in the same polyp suggests shared pathogenesis of MC in CIAM and squamous morule, likely representing altered Wnt/β-catenin signaling pathway.     

Gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC): An immunohistochemistry study of 13 microsatellite stable cases

BackgroundMixed adenoneuroendocrine carcinoma (MANEC) is currently included in the category of neuroendocrine carcinomas but the therapeutically management is not yet defined.AimsTo present the immunohistochemical (IHC) features of the epithelial mesenchymal transition (EMT) of MANEC.Materials and methodsThe clinicopathological features of 13 consecutive cases of MANEC (6 gastric and 7 colorectal) were correlated with the IHC expression of the biomarkers E-cadherin, β-catenin, N-cadherin, vimentin, maspin, CD44 and S100. In all of the cases open surgery was performed.ResultsAll of the cases showed microsatellite stable status, expressed E-cadherin and membrane β-catenin in both components (neuroendocrine and adenocarcinoma) and were negative for N-cadherin, vimentin and S-100. The colorectal MANECs were negative for maspin. In gastric MANECs, maspin showed cytoplasm positivity in the neuroendocrine component and nuclear translocation in the adenocarcinoma cells. CD44 was positive in all of the cases, in both components. No tumor buddings were identified. Three of the 13 patients survived for at least 32 months, all of them showing lymphatic emboli but not lymph node metastases. Pure neuroendocrine lymph node metastases were seen in only four of the cases: one from stomach, two of the ascending colon and two cases of the upper rectum.ConclusionsGastrointestinal MANEC is a microsatellite stable tumor with nodular growth, which components might originate from a CD44-positive stem-like precursor cell. Lymph node status remains the most reliable prognostic parameter and agressivity seems to not be influenced by tumor budding degree or EMT-related features. The histologic aspect of metastatic component (neuroendocrine versus adenocarcinoma) should be included in the histopathological reports and might be used for establishing the proper-targeted therapy of MANEC.     

Solid-pseudopapilläre Neoplasien

Solid pseudopapillary neoplasms (SPN) of the pancreas represent a special tumor entity, both morphologically and biologically. They form large solitary tumors that occur predominantly in young women. Histologically, they show solid, pseudopapillary, and pseudocystic patterns. The tumor cells are monomorphous and typically express vimentin, neuron-specific enolase, nuclear beta-catenin, and the progesterone receptor. Complete resection cures the tumor in about 90% of the cases. However, because recurrences and even metastases may occur in a small number of cases, SPN are classified as low-grade malignant tumors. Predicting malignancy histologically is not yet possible. The most important differential diagnosis to consider is neuroendocrine tumor of the pancreas. The etiology and pathogenesis of SPN are obscure.     

Solid and papillary neoplasm of the pancreas.

In two cases of solid and papillary neoplasm of the pancreas (SPN), positive staining for argyrophil granules, chromogranin-A, neuron-specific enolase, chymotrypsin, alpha 1-antitrypsin, vimentin, cytokeratin, and estrogen receptors was present. Ultrastructurally, neurosecretory as well as zymogenlike granules were demonstrated. Measurements of mean nuclear volume and volume-corrected mitotic index discriminated between SPN and well-differentiated ductal adenocarcinoma of the pancreas, with notably lower values being seen in SPN. Silver-stained nucleolar organizer region counts showed wide overlaps. The results suggest that SPN is a tumor with mixed endocrine and exocrine features. Its low malignant potential compared to ductal adenocarcinoma is reflected in the mean nuclear volume and volume-corrected mitotic index. The presence of estrogen receptors may prove therapeutically useful.     

What's new? The 2010 WHO classification for tumours of the pancreas

The new WHO classification of tumours of the pancreas logically includes both exocrine and neuroendocrine neoplasms in one volume, thus differing from all previous editions. Ductal adenocarcinoma is still the most frequent and clinically the most relevant malignant tumour. Its subtypes and variants are described in detail, as are mixed tumours. Other ductal tumours [mucinous cystic neoplasms (MCN) and intraductal papillary mucinous neoplasms (IPNM)] are classified as neoplasms with various grades of dysplasia up to invasive carcinoma. A new subtype of IPNM, intraductal tubulopapillary neoplasm (ITPN), has been characterized and newly added to the IPMN group. Serous and acinar tumours are classified as neoplasms with varying grades of dysplasia. Solid pseudopapillary neoplasm (SPN) is regarded as malignant (low grade) as a matter of principle because of its inherent potential to metastasize. Neuroendocrine neoplasms are characterized as G1 or G2 neuroendocrine tumours (NET) and neuroendocrine carcinomas (NEC, highly malignant). Syndromatic NETs are described and named according to their hormone expression pattern. The problems of staging when applying either the TNM or AJCC/UICC (American Joint Committee on Cancer/Union Internationale Contre le Cancer) classifications, which apply equally to endocrine and exocrine tumors, are discussed.