胰岛素样生长因子-Ⅰ对高氧致新生鼠慢性肺疾病Ⅰ型胶原表达的影响

目的研究collagen Ⅰ在高氧致新生鼠慢性肺疾病中的表达、作用及IGF-Ⅰ对collagenⅠ表达的影响。方法将足月新生大鼠144只随机分为高氧组和空气组，分别于实验1d，3d，7d，10d，14d和21d应用免疫组化染色分别检测collagenⅠ和IGF～Ⅰ蛋白表达，并将IGF—Ⅰ和collagenⅠ蛋白表达进行相关分析。结果高氧组在3d～10d IGF—Ⅰ和collagenⅠ蛋白表达与空气组相比较明显降低（P〈0．05）；14d和21d IGF—Ⅰ和collagenⅠ蛋白表达与空气组相比较明显增加（P〈0．05），IGF—Ⅰ和collagenⅠ表达呈正相关。结论collagenⅠ与CLD时肺泡发育受阻和肺纤维化发生有关，IGF—Ⅰ是影响collagenⅠ合成的重要生长因子之一。     

转化生长因子β与组织器官纤维化

胶原的合成和沉积是人体组织器官纤维化的病理基础,转化生长因子β（TGF-β）与胶原代谢关系最为密切,它可以通过刺激胶原基因过度表达及其自分泌调控等多种机制在纤维化病变过程中发挥关键作用。TGF-β的生物学作用也是通过与其高亲和力的表面膜受体特异性结合而产生的,本文就其作用方式及作用机制作一综述。     

转化生长因子-β1和结缔组织生长因子在慢性心力衰竭大鼠心肌纤维化中的动态表达

目的:探讨慢性心力衰竭心肌内转化生长因子-β1(TGF-β1)及结缔组织生长因子(CTGF)的表达及意义.方法:采用肾上腹主动脉缩窄法制作雄性Wisstar大鼠慢性心衰模型,随机分为心衰1、7、14d组,另取假手术组作为对照.观察和比较成模后心衰各组和假手术组血流动力学参数及左心室肌质量指数,用Masson染色法和透射电镜观察左室心肌组织形态的改变.用免疫组织化学方法检测各组大鼠左室心肌组织中TGF-β1、CTGF的表达水平.结果:心衰模型各组TGF-β1、CTGF的蛋白表达高于假手术组,且随着心力衰竭程度的加重而表达增高.结论:TGF-β1、CTGF可能参与了大鼠压力负荷性心肌纤维化的发生和发展,其水平的高低与慢性心力衰竭的严重程度密切相关.     

腺病毒介导hTGF-β1基因体内转染兔椎间盘对髓核细胞Ⅰ型、Ⅱ型胶原的影响

目的观察腺病毒载体介导外源性人转化生长因子(Ad/CMV-hTGF-β1)对兔椎间盘髓核细胞Ⅰ型、Ⅱ型胶原的影响.方法纯种成年新西兰大白兔20只,随机分为实验组和对照组,每组10只.于实验组兔腰3、4椎间盘髓核内注射Ad/CMV-hTGF-β1(6×106pfu),注射量为20μl,对照组则注射20μl磷酸盐缓冲液(PBS).术后3周取出椎间盘,免疫组织化学方法观察椎间盘髓核细胞中Ⅰ型、Ⅱ型胶原的表达情况,并用VIDAS图像分析系统进行半定量分析.结果免疫组织化学染色显示实验组椎间盘髓核细胞Ⅰ型胶原的表达比对照组低;而Ⅱ型胶原的表达则比对照组高,差别有统计学意义(P＜0.05).结论体内转染腺病毒介导的hTGF-β1基因能降低椎间盘髓核细胞Ⅰ型胶原的表达、提高Ⅱ型胶原的表达,提示hTGF-β1可以抑制椎间盘的退变.     

前列腺素E2抑制转化生长因子-β1诱导的人胚肺成纤维细胞转分化及胶原合成

目的：研究前列腺素E₂（PGE₂）对转化生长因子-β₁（TGF-β₁） 诱导人胚肺成纤维细胞（HLF）转分化及促胶原(COL)合成作用的干预。方法： HLF 细胞生长至融合后分为 ①对照组、②TGF-β₁组、③TGF-β₁+PGE₂组、④TGF-β₁+吲哚美辛组，给予干预24 h后用细胞免疫荧光及Western blotting法观察发生转分化为肌成纤维细胞的标志蛋白 α-平滑肌动蛋白（α-SMA）的表达，用RT-PCR法检测结缔组织生长因子（CTGF）mRNA和Ⅰ型胶原（COLⅠ）mRNA的水平，用免疫细胞化学法检测CTGF蛋白表达，比色法检测培养上清中羟脯氨酸含量。结果: TGF-β₁ 可将HLF转分化为 α-SMA 阳性表达的肌成纤维细胞，PGE₂则能抑制这种转分化作用；PGE₂ 可显著减低TGF-β₁ 致肌成纤维细胞、CTGFmRNA与蛋白水平（P<0.05）和COLⅠmRNA 水平升高（P<0.05）； 吲哚美辛升高TGF-β₁ 致HLF肌成纤维细胞CTGF与COLⅠ的表达； 放线菌酮预处理肌成纤维细胞3 h后再加入TGF-β₁＋PGE₂，其COLⅠmRNA 水平明显低于TGF-β₁ 处理组水平（P<0.05）。结论: PGE₂可抑制TGF-β₁ 对成纤维细胞的转分化及促胶原合成作用, 且可通过依赖CTGF和非依赖2种方式下调COLⅠ的转录。     

结缔组织生长因子在单侧输尿管梗阻大鼠肾脏中的表达及其意义

目的：观察结缔组织生长因子（CTGF）在单侧输尿管梗阻（UUO）大鼠模型中的动态表达,探讨CTGF在肾小管间质纤维化中的作用机制。方法：将48只Wistar大鼠随机分为UUO组和假手术（SO）组,采用左输尿管结扎术复制UUO模型,于术后1、3、7、14d分别处死2组大鼠取左肾。采用Masson染色评定肾小管间质损伤程度;逆转录-聚合酶链式反应(RT-PCR)方法检测肾组织转化生长因子-β1（TGF-β1）、CTGF、Ⅰ型胶原（ColⅠ）和纤溶酶原激活物抑制物-1（PAI-1）mRNA表达;免疫组织化学方法测定TGF-β1、CTGF、ColⅠ、PAI-1表达;Westernblotting方法检测CTGF蛋白表达量的变化。结果:UUO术后1d,梗阻肾TGF-β1mRNA表达开始升高,第3-14d时升高更显著（P<0.01）,CTGF、ColⅠ、PAI-1mRNA水平随之逐渐升高。免疫组织化学染色发现,UUO大鼠肾小管和间质区域CTGF表达随病程进展逐渐增强;相关分析显示,UUO术后第7d,CTGF表达量与肾小管间质损伤指数、肾小管间质TGF-β1、ColⅠ、PAI-1表达强度均呈正相关,相关系数（r）分别为0.62、0.85、0.78和0.76（均P<0.01）。Westernblotting结果显示,CTGF蛋白水平在术后第3d开始上升,随病程进展更显著。结论:CTGF可通过促进细胞外基质产生和抑制细胞外基质降解双重途径诱导肾小管间质纤维化的发生和进展。     

脾脏硬化性血管瘤样结节性转化5例临床病理分析

目的 探讨脾脏硬化性血管瘤样结节性转化(sclerosing angiomatoid nodular transformation,SANT)的临床病理表现、诊断及鉴别诊断要点.方法 对5例SANT的临床、组织病理学形态及免疫组化特征进行形态学观察并文献复习.结果 5例中只有1例有临床症状.眼观脾脏SANT多为孤立性病灶,与周围脾组织界清,中心为白色瘢痕样外观.镜下呈多结节表现,结节中心为多个裂隙样或不规则型富含红细胞的血管腔隙,内衬肥胖的上皮细胞.结节周围靶环状紧密排列梭型、卵圆形细胞,间质内有淋巴细胞、浆细胞及组织细胞浸润.免疫组化显示血管样腔隙呈现3种不同的免疫表型:CD34-/CD31+/CD8+、CD34+/CD31+/CD8-和CD34-/CD31+/CD8-.结节周围梭型、卵圆形细胞呈现不同程度的SMA、CD31、CD68均(+).结论 SANT是源自脾脏红髓的具有独特形态学特点的血管瘤样病变,易与炎性假瘤、血管瘤等相混淆,临床呈良性表现.     

转化生长因子βⅠ型受体对组织纤维化形成及发展的影响

目的探讨转化生长因子βⅠ型受体(TGFβR-Ⅰ)对组织纤维化的形成及发展的影响。方法采用RNA干扰技术阻断人成纤维细胞系HFL-Ⅰ细胞的TGFβR-Ⅰ表达,Western blot法检测RNA干扰前后TGFβR-Ⅰ的表达水平,MTT法分析干扰前后的细胞生长状态,采用动物模型结合HE染色观察RNA干扰阻断TGFβR-Ⅰ表达前后的中毒性肝纤维化模型大鼠的肝脏病理学变化。结果特异性TGFβR-Ⅰ干扰RNA能有效抑制TGFβR-Ⅰ蛋白质合成和成纤维细胞株HFL-Ⅰ细胞的生长,正常鼠肝组织处于纤维化S0期,中毒性肝纤维化模型鼠肝组织处于纤维化S2期,特异性TGFβR-Ⅰ干扰RNA治疗组模型鼠肝组织则呈现纤维化S1期特征。结论抑制TGFβR-Ⅰ的表达可明显减轻中毒性肝纤维化模型大鼠的肝纤维化程度,对进一步优化肝纤维化的预防和治疗策略具有重要意义。     

脾硬化性血管瘤样结节性转化6例临床病理分析

目的探讨脾硬化性血管瘤样结节性转化(sclerosing angiomatoid nodular transformation, SANT)的临床病理学特征、诊断及鉴别诊断。方法回顾性分析6例脾SANT的临床病理学特征、免疫表型等,并复习相关文献。结果 6例脾SANT中男女各3例,发病年龄19～50岁,中位年龄31.5岁。患者无明显症状,由体检或其他手术发现。影像学检查无特异性。眼观:肿瘤呈结节状,呈灰白色或灰红色,实性质中或质软,边界清楚,直径0.7～6.5 cm。镜检:多灶性肉芽肿样结节,结节由密集排列的裂隙样薄壁血管构成,内皮细胞肥胖。间质见增生的成纤维细胞及慢性炎细胞。免疫表型:血管内皮细胞CD34(6/6)、CD31(6/6)、CD8(3/6)和FⅧRAg(4/6)均阳性;血管壁平滑肌和间质纤维细胞SMA阳性;IgG4阳性的浆细胞<10个/400 HPF;6例原位杂交检测EBER均阴性。结论脾SANT为罕见良性的肿瘤样病变,发病隐匿,无临床特征,影像学表现仅能发现病变,未能做出准确的诊断,确诊需结合组织学形态和免疫表型并排除其他病变。     

肺硬化性血管瘤21例临床病理分析

目的 探讨肺硬化性血管瘤(sclerosing hemangioma of the lung,SHL)的临床病理特征.方法 对21例SHL进行HE染色及免疫组织化学染色,光镜观察.结果 本组男4例,女17例,年龄19～65岁,平均42.8岁.HE染色示:SHL主要由实性片块区、乳头状区、血管瘤样区和硬化区4种组织结构组成,瘤细胞有2种即被覆乳头表面、实性区裂隙及血管样腔面的立方细胞和实性区及乳头轴心大小形态一致的多角形细胞;免疫组化染色示:2种细胞均表达EMA和TTF-1,立方细胞表达CK;而多角形细胞弥漫表达vimentin、ER、PR,部分表达Syn、CsA和NSE.结论 SHL多见于中青年女性,发病率低,易误诊为肺癌.典型的组织形态特征结合TTF-1、EMA、CK、vimentin等免疫组化染色,是诊断和鉴别诊断SHL的主要方法;ER、PR的高表达可能与女性的高发病率密切相关.     

脂肪母细胞瘤44例临床病理分析

目的　探讨脂肪母细胞瘤的临床、病理及预后。方法　对 4 4例脂肪母细胞瘤临床资料、病理切片和随访结果进行分析。结果　脂肪母细胞瘤 ,手术切除时的平均年龄为 (2 0 8± 14 6 )个月 ,患儿最大 5岁 ,男性多于女性。病变多发生于四肢、头颈部、腰背部及腋部。复发率 18 2 % ,弥漫型明显多于局限型。肿瘤最大径多为 3～ 7cm ,切面比脂肪瘤灰白。镜下见未成熟和成熟的脂肪组织小叶由丰富毛细血管、小静脉的狭窄纤维间隔分割 ,伴不同程度的黏液样基质。结论　脂肪母细胞瘤需与黏液脂肪肉瘤、纤维脂肪肉瘤和婴儿纤维性错构瘤相鉴别。脂肪母细胞瘤生物学行为完全良性 ,虽有局部复发 ,但从无转移及恶变 ,治疗方法主要为局部切除     

Chronic sclerosing sialadenitis as one of the immunoglobulin G4-related diseases: a clinicopathological study of six cases from Central Europe

Laco J, Ryska A, Celakovsky P, Dolezalova H, Mottl R & Tucek L (2011) Histopathology 58 , 1157–1163 Chronic sclerosing sialadenitis as one of the immunoglobulin G4‐related diseases: a clinicopathological study of six cases from Central Europe Aims: Chronic sclerosing sialadenitis (CSS) has been proposed recently to be a member of the group of IgG4‐related diseases in Japanese and American series. The aim of our study was to validate these results in a cohort of European patients. Methods and results: Our CSS series included four females and two males, aged 32–76 years, all presenting with unilateral swelling of submandibular gland. Microscopically, all CSS‐cases showed similar morphology with preservation of lobular architecture accentuated by cellular fibrous bands, dense lymphoplasmacytic inflammation and varied acinar atrophy. Ductal lymphocytes were detected in three cases. In five cases, the presence of intraductal secretory material accompanied by parenchymal neutrophils was observed. Obliterative phlebitis was seen in three cases. The inflammatory infiltrate was composed of T and B lymphocytes and polyclonal plasma cells. The median number of IgG‐positive plasma cells per high‐power field (HPF) was 157; median number of IgG4‐positive plasma cells per HPF was 133. Median value of the IgG4:IgG ratio was 0.84. Conclusions: This is the first European series to demonstrate that CSS belongs to the family of IgG4‐related disease. Unlike previous studies, in CSS we found rarely described ductal lymphocytes and parenchymal neutrophils. CSS displays consistent morphology with increased numbers of IgG4‐positive plasma cells, and should be regarded as a member of the IgG4‐related disease group.     

"Ancient" (sclerosing) thymomas: a clinicopathologic study of 10 cases

We present 10 cases of "ancient" (sclerosing) thymomas in 4 women and 6 men (age range, 34-73 years; mean, 53.5 years). Clinically, 4 patients had a history of shortness of breath and chest pain of several weeks' duration, 1 had a history of myasthenia gravis, and 5 were asymptomatic (anterior mediastinal masses discovered on routine chest radiographs). All underwent complete surgical resection of the anterior mediastinal mass. The tumors were light tan and solid, without areas of hemorrhage or necrosis, and 5 to 10 cm in greatest diameter. Extensive areas of hyalinized fibroconnective tissue constituting about 85% to 90% of the tumor mass was the main tumor feature. Focal areas of conventional thymoma also were present in all tumors. Follow-up information was obtained for 8 patients. Of these 8 patients, 6 died, all of unrelated causes (congestive heart failure, renal insufficiency, and pulmonary edema), and 2 were alive 1 and 6 years after surgical resection. The present cases highlight an important histopathologic feature of thymomas, which can pose problems in diagnosis, namely when dealing with small mediastinoscopic biopsy specimens.     

Chronic sclerosing sialadenitis of the submandibular gland: an entity of IgG4-related sclerosing disease

Chronic sclerosing sialadenitis typically involves the submandibular gland. It usually occurs in the middle-aged and elderly adults with a slight male predominance. Recent evidences have suggested that it is an entity of IgG4-related sclerosing disease and has distinct histopathological features, such as a dense lymphoplasmacytic infiltrate, sclerosis and obliterative phlebitis. It is important to discriminate this entity from other diseases, trying to give effective treatment to the patients. In this report, we described a patient having chronic sclerosing sialadenitis in the submandibular gland.     

Nasopharyngeal adenocarcinomas: a clinicopathologic study of 44 cases including immunohistochemical features of 18 papillary phenotypes

Nasopharyngeal adenocarcinomas (NPACs) are uncommon neoplasms with a diverse histomorphology and clinical behavior. The purpose of our study was to better understand the clinicopathologic characteristics of NPACs and to identify the histologic and immunohistochemical features that distinguish the subtypes of papillary NPACs. We conducted a retrospective review of 44 cases of NPACs accessioned between 1985 and 2000. We obtained follow-up information for all patients. We identified 24 females and 20 males, ranging in age from 9 to 74 years (median, 50 years). There were 28 salivary gland type, 13 conventional low-grade papillary NPACs of surface origin, and 3 metastatic adenocarcinomas, 2 thyroid and 1 lung. We performed immunohistochemical studies in 18 papillary NPACs. Two of the low-grade papillary NPACs simulated thyroid carcinoma; they expressed CK7, CK19, and TTF-1 but were negative for thyroglobulin. Polymorphous low-grade papillary NPACs expressed diffuse reactivity to S-100, whereas low-grade papillary NPACs were negative or focally positive. All patients with low-grade NPACs were alive at 5 to 20 years. In contrast, 18 (64.2%) of the 28 patients with salivary gland-type NPACs had died of the disease or were living with disease at follow-up. Primary NPACs can be classified by their morphology and clinical behavior into 2 groups: surface origin type and salivary gland type. Papillary NPACs can be identified by their histology and selective immunohistochemical expression. Pathologist should distinguish the different types of NPACs because their treatment and prognosis differ.     

Chronic sclerosing sialadenitis of the submandibular gland associated with idiopathic retroperitoneal fibrosis

We report a case of a 57-year-old man who developed a fibrosclerosing lesion in the submandibular gland and idiopathic retroperitoneal fibrosis (IRF) involving the unilateral periureteral region within a year. Both lesions were resected surgically because of the suspicion of neoplasm. Pathologic examination revealed similar histologic and immunohistochemical features for both lesions, namely, fibrosclerosis with prominent hyalinizing collagen bundles and proliferation of myofibroblastic cells, and a non-neoplastic reactive nature. There was infiltration by lymphocytes with prominent lymph follicles, plasma cells and macrophages. The histologic and immunohistochemical findings suggest that the two lesions were of a similar pathogenesis, which was possibly mediated by macrophages. We think that the present case may be an unusual form of multifocal fibrosclerosis. Although sialolithiasis is thought to be a major pathogenic factor for chronic sclerosing sialadenitis of the submandibular gland, the present case suggests that certain cases might have an etiology similar to IRF.     

Liver transplantation for primary sclerosing cholangitis: a long-term clinicopathologic study

The course and outcome of patients after liver transplantation (LT) for primary sclerosing cholangitis (PSC) are still debated. Our purpose is to define retrospectively, the post-LT clinicopathologic findings seen in 51 PSC patients with a follow-up of 2 to 14 years. Of the total 51 patients, 16 with native liver hilar xanthogranulomatous cholangiopathy (XGC) had median graft and patient survival of 573 and 835 days, respectively compared with 2489 and 2794 days, respectively, in 35 patients without XGC. Perioperative complications resulted in 9 early deaths (day 0 to 52). Of the remaining 42 patients, 6 had recurrent PSC (R-PSC) with typical histologic and cholangiographic findings, 12 had autoimmune liver disease-not otherwise specified with histology of autoimmune hepatitis/overlap syndrome, 3 had chronic rejection, 4 had ischemic cholangiopathy, and 17 had no recurrence. The presence of inflammatory bowel disease, total ischemia time of > or =11 hours, recipient-donor ABO and HLA Class I and II matches, and the type of immunosuppression did not affect the post-LT outcome. Recipient-donor gender mismatch was more common in R-PSC than in the nonrecurrent group (P=0.045). Post-LT malignancies were significantly more common in the nonrecurrent cases compared with all others combined (P=0.031) and caused deaths in 4. The majority of deaths (11/13) in other groups were due to sepsis complicating graft dysfunction. In conclusion, allograft autoimmune liver disease was seen in 18 (43%) of 42 long-term post-LT PSC patients, with progression in 5 of 18 patients. Features of PSC were seen in 6 (33%) of 18. Native liver XGC negatively impacted post-LT graft and patient survival. Increased incidence of malignancies in the nonrecurrent group may reflect overimmunosuppression in those patients.     

Low-grade fibromyxoid sarcoma: a clinicopathologic study of 18 cases, including histopathologic relationship with sclerosing epithelioid fibrosarcoma in a subset of cases

Low-grade fibromyxoid sarcoma (LGFMS) is an uncommon tumor with diverse histopathologic features. It has been found to be histopathologically and genetically related to hyalinizing spindle cell tumor with giant rosettes. Lately, sclerosing epithelioid fibrosarcoma (SEF) has been identified as another rare variant of fibrosarcoma. Very few studies have addressed the aspect of its histopathologic relationship with LGFMS. The present study was conducted to critically analyze the clinicopathologic features of a series of LGFMS cases, including identification of cases with histopathologic similarity with SEF. During a 7-year period, 18 LGFMS cases were diagnosed in 9 male and 9 female patients, had ages ranging from 10 to 69 years (median, 32.5 years), and were most commonly identified in the lower extremities (8 cases, or 44.4%). Most cases (16, 88.8%) showed “classic” features of LGFMS with mild (13 cases, or 72.2%) to moderate atypia (5 cases) and nil mitosis (12 cases, or 66.6 %). Variable features included whorling tumor growth pattern, small rosettes, perivascular hyalinization, and amianthoid-like collagen, along with epithelioid differentiation and nuclear pseudoinclusions within tumor cells. Four cases (22.2%) with large collagenous rosettes were diagnosed as hyalinizing spindle cell tumor with giant rosettes. Distinct SEF-like areas were observed in 6 cases (33.3%). On immunohistochemistry, consistent vimentin positively reinforced fibroblastic lineage of the tumor. Therapeutically, all 4 of 7 cases with available follow-up details, which underwent wide excisions, have been free of disease at 5 to 61 months. Eight excisions with unclear margins included 3 cases free of disease (24, 36, and 52 months) and 1 case with recurrence and metastasis. Two cases of marginal excision had tumor recurrences, including 1 case that recurred after 10 years. Low-grade fibromyxoid sarcoma is an uncommon sarcoma with diverse histopathologic features. Histopathologic relationship exists between LGFMS and SEF in a few cases. An LGFMS is optimally managed with surgical wide excision and follow-up.     

Diffuse sclerosing variant of papillary thyroid carcinoma. A clinicopathologic study of 10 cases

The clinico-pathologic features of ten cases of the diffuse sclerosing variant (DSV) of papillary carcinoma of the thyroid (PCT) are presented and compared with those of 259 common PCT diagnosed during the same period at the Instituto Português de Oncologia (Centro de Lisboa). The primary therapeutic approach was basically the same in every case and follow-up information was obtained in every patient. DSV comprises 3.4% of our series of PCT. Patients with DSV are suggestively younger (34.7 +/- 19.9), than those with common PCT (42.3 +/- 16.1) regional lymph node metastases and distant metastases are significantly greater in DSV (100.0% and 50.0%, respectively) than in common PCT (38.6% and 14.3%, respectively). No significant differences were found between the two groups with regard to sex-ratio, extrathyroid invasion and mortality rate. No differences were either found regarding the immunohistochemical results: neoplastic cells of both groups showed immunoreactivity with antisera for thyroglobulin, epidermal keratins, S-100 protein and NSE. Some foci of three DSV cases displayed histological and histochemical features resembling those of the so-called mucoepidermoid carcinoma. It is concluded that a) DSV is an exceptional example of PCT in which most of the usual morphologic features of this type of carcinoma are overexpressed; b) DSV is not exclusively found in young patients and, in older patients, merges with other variants of PCT; c) DSV is indeed a more aggressive tumor than common PCT and should therefore be treated accordingly regardless of the age of the patients.