微囊型脑膜瘤临床病理、超微结构和免疫组化研究

对１３例颅内微囊型脑膜力的临床病理，超微结构和免疫组化三个方面进行了研究。结果表明：本岛无固定部位，颅底多发。光镜下肿瘤胞浆空泡状或囊状扩张，梭形细胞间质有毛细胞血管。电镜下，肿瘤胞质突起相互分隔成囊腔，囊内可见束状胶原纤维丝。免疫体化，Ｖｉｍｅｎｔｉｎ和ＥＭＡ染色阳性。电镜和免疫组化有助于该病的诊断。     

脑膜瘤CT、MR 表现与病理-超微结构和免疫组化对照研究

 目的　提高 CT、MR对脑膜瘤的诊断水平。方法　 5 2 9例经 CT检查 5 1 5例 ,MR检查78例 ,均经手术病理证实。按 1 990年 WHO脑膜瘤新分类进行光镜分类 ,配合 JEM- 1 0 0透射电镜观察超微结构 ,作 6种肿瘤的免疫组织化学检测波形蛋白 ( Vimentin) ,胶质纤维酸性蛋白( GFAP) ,角蛋白 ( Keratin) ,S- 1 0 0蛋白 ,上皮膜抗原 ( EMA) ,黑色素瘤抗原 ( HMB45 )。结果　对CT显示混合密度、囊性低密度区 ;MR呈长 T1、长 T2等信号与电镜所见瘤细胞空泡状 ,突起交织形成囊状超微结构的微囊型脑膜瘤为密切关系。其它良、恶性脑膜瘤的 CT、MR表现与电镜显示肿瘤超微结构均为密切关系。对病理分类的 1 2种良、恶性脑膜瘤检测显示 Vimentin和 EMA均为阳性。结论　对 CT、MR可疑脑膜瘤和电镜较难确诊者 ,应配合电镜进行肿瘤超微结构观察和肿瘤免疫组化检测确诊.     

微囊型脑膜瘤2例临床病理学特征分析并文献复习

背景与目的：微囊型脑膜瘤是脑膜瘤的罕见亚型,国内外报道较为少见,且多以个案报道为主。本研究旨在探讨微囊型脑膜瘤的临床病理学特点及鉴别要点。方法：回顾分析2例微囊型脑膜瘤的临床表现、组织学形态及免疫组织化学表型,并复习相关文献。结果：2例均为中年患者,男性和女性各1例,男性患者因外伤引起脑出血就诊;女性患者因头痛就诊,病变分别位于左侧额部和右侧额部,最大径分别为5.75和5.47 cm。影像学改变均示“脑外肿瘤”。镜下瘤细胞排列疏松,形成大小不等的微囊,腔内含粉染之浆液,肿瘤细胞具有空泡状细胞质和细长的细胞质突起,典型的漩涡状结构和砂粒体少见。免疫组织化学示,波形蛋白（vimentin）、上皮膜抗原（epithelial membrane antigen,EMA）和孕激素受体（progesterone receptor,PR）均呈阳性表达,S-100、胶质纤维酸性蛋白（glial fibrillary acidic protein,GFAP）、CD34和肌酸激酶（creatine kinase,CK）均呈阴性表达,Ki-67阳性率达3%~5%。2例患者均行手术治疗,术后均随访观察,随访时间为5~6个月,截至2018年1月,2例患者一般情况良好,均未见肿瘤复发。结论：微囊型脑膜瘤为脑膜瘤的特殊亚型,依据病理组织学形态及免疫组织化学可明确诊断。目前治疗主要以手术治疗为主,预后良好。     

平滑肌肉瘤的临床病理研究：——病理组织学,免疫组化及超微结构分析

本文报告对２６例全身多个部位的平滑肌肉瘤（ＬＭＳ）的病理组织学、ＲＨＦ３５及Ｄｅｓｍｉｎ免疫组化及部分病例还进行了超微结构特征研究。结果表明ＬＭＳ具有较典型的组织学特征：瘤细胞呈杆状，平行排列，胞浆内有肌原纤维。低分化的ＬＭＳ细胞异型性大，但仍具有上述特征。Ｄｅｓｍｉｎ标记ＬＭＳ的阳性率是６５％，ＨＨＦ３５的阳性率是９６％。两者有显著性差异。其它对照的多种梭形细胞肉瘤中，除恶性纤维组织细胞瘤中可有     

平滑肌肉瘤的临床病理研究─—病理组织学、免疫组化及超微结构分析

本文报道对２６例全身多个部位的平滑肌肉瘤（ＬＭｓ）附病理组织学、ＨＨＦ３５及Ｄｅｓｍｉｎ免疫组化及部分病例还进行了超微结构特征研究。结果表明ＬＭＳ具有较典型的组织学特征：瘤细胞呈杆状，平行排列，胞浆内有肌原纤维。低分化的ＬＭＳ细胞异型性大，但仍具有上述特征。Ｄｅｓｍｉｎ标记ＬＭＳ的阳性率是６５％，ＨＨＦ３５的阳性率是９６％。两者有显著性差异。其它对照的多种梭形细胞肉瘤中，除恶性纤维组织细胞瘤中可有少数、单个的细胞呈ＨＨＦ３５阳性外，其它均不表达ＨＨＦ３５和Ｄｅｓｍｉｎ。因此ＨＨＦ３５是标记ＬＭＳ的敏感性高、特异性强的抗体。透射电镜观察ＬＭＳ具有特征性的密体和密斑存在。透射电镜观察也是确诊ＬＭＳ的途径之一。     

4种少见脑膜瘤的临床病理观察

报告４种少见的脑膜瘤亚型：分泌型、微囊型、脂肪瘤和黄色瘤型。临床表现主要有头痛、恶心、轻度呕吐、眼底水肿和肢体功能障碍。形态学：分泌型脑膜瘤以散在多个嗜酸性近圆形包含体为特征，包含体对ＣＥＡ、ＥＭＡ呈特异性表达；微囊性脑膜瘤含微小囊腔状如海绵，囊内含粉染浆液，囊壁由疏松和涡漩状排列之瘤细胞组成；脂肪瘤和黄色瘤型脑膜瘤分别在其瘤组织中含有大量脂肪细胞或泡沫细胞为特征。文中讨论了肿瘤形成机制及鉴别要点。     

胃癌细胞内微囊超微结构的研究

本文通过一组胃癌病例描述了细胞内微囊的超微结构及其诊断意义。全组75例胃癌中17例在癌细胞中发现微囊。电镜下,微囊乃细胞浆内的一种特殊结构,为与外界不相通的孤立囊腔,内表面披以微绒毛,囊腔内含有低电子密度的颗粒状物质。关于微囊的组织来源,作者推测可能来自二级溶酶体。由于微囊常见于胃癌而在其他癌瘤中罕见,故对胃癌的诊断具有一定的意义。     

脊索样脑膜瘤四例临床病理分析

目的 作为脑膜瘤的一种罕见亚型,脊索样脑膜瘤因不具备典型脑膜瘤的病理特征,常难以同脊索瘤及其他肿瘤区分,易造成误诊.本研究旨在通过探讨脊索样脑膜瘤临床病理特征、免疫表型及MRI特征表现,进一步提高对该亚型脑膜瘤的认识.方法 收集兰州大学第二医院2010-10-01-2015-10-25经手术后病理确诊的4例脊索样脑膜瘤患者临床资料,分析临床病理特征及影像资料,结合相关文献进行对比研究.结果 光镜下,4例HE染色示组织学类似脊索瘤,瘤组织排列成束状或小梁状分布于黏液样基质中,瘤细胞胞质丰富,嗜酸,并可见胞质内空泡,部分区域为典型脑膜瘤漩涡状、束状、编织状结构,2例瘤组织间可见少量淋巴细胞、浆细胞浸润.免疫表型示,瘤细胞EMA(+)、Vimentin(+)、CKp(-)、S-100(-)、GFAP(-),Ki-67阳性细胞数平均为8％.MRI示,4例均为单发病灶,3例位于顶叶,1例位于额颞叶;2例为实性类圆形,1例呈不规则团块状,1例为囊实性,实性呈结节状附壁生长;2例病灶界限不清,2例边界清晰;4例瘤周水肿明显,邻近脑组织均有不同程度受累;T1WI 4例呈等、略低信号;T2WI 3例呈等、略高信号,1例呈等、略低信号.结论 诊断脊索样脑膜瘤,应结合形态学、相应的免疫组化染色及具有一定表现特征的影像学检查,以有效降低误诊率.     

透明细胞型脑膜瘤的临床病理特征

透明细胞型脑膜瘤（clear cell meningioma,CCM）是一种少见的脑膜瘤亚型,好发于脊柱、桥脑小脑部位,患者发病年龄较轻,因肿瘤细胞的胞浆富含糖原呈透明状而得名。CCM的组织学结构特征为玻璃样变性的胶原混杂于温和的肿瘤细胞间,虽然组织学形态和善,但可呈侵袭性生长,具有较高的复发率,并可通过脑脊液播散[1],因此,在2000年,世界卫生组织(WHO)将CCM归为Ⅱ级神经系统肿瘤。本研究中,我们分析了3例CCM的临床病理特点、鉴别诊断和预后等,现将结果报告如下。     

225例大肠腺瘤癌变的临床病理、免疫组化及其超微结构

目的：探讨大肠腺瘤及其癌变的临床病理、免疫组织化学及其超微结构。方法：随机选择我院近5年间纤维肠镜1804人次，检出大肠腺瘤225枚，其中91例行CEA组织化学染色，15例行电镜观察。结果：腺瘤肠镜检出率为12．47％（225／1804），癌变33例，癌变率为14．67％（33／225），其中管状腺瘤癌变4例，绒毛管状腺瘤癌变8例，绒毛状腺瘤癌变21例。有蒂的管状腺瘤异型程度轻、癌变率低、预后好；宽蒂、无蒂的扁平型、凹陷型、绒毛状腺瘤，异形程度重，癌变率高，浸润深，预后差。CEA染色阳性率：腺瘤癌变者93．33％（14／15），绒毛状腺瘤78．95％（15／19），绒管状腺瘤70．50％（12／17），管状腺瘤67．5％（27／40）。电镜观察显示绒毛状腺瘤部分腺上皮细胞突破基底膜向间质伸长，可出现异形细胞，核大核沟深，常染色质丰富核仁明显，癌变者可见淋巴细胞溶解癌细胞膜现象。结论：大肠腺瘤为癌前病变，不同类型的大肠腺瘤其治疗及预后不同。     

Adenoid cystic carcinoma of the tracheobronchial tree: clinicopathology and immunohistochemistry

Adenoid cystic carcinoma of the tracheobronchial tree in five patients was treated surgically and the clinicopathologic manifestations and histogenesis were examined in detail. Symptoms such as cough, dyspnea, hemoptysis, and atelectasis on chest X-ray were present in four patients, and the other patient was asymptomatic. Histologically, growth patterns were classified as tubular, cribriform, and solid. The solid pattern was the most aggressive with extensive perineural invasion. Immunohistochemically, secretory component, lactoferrin, and epithelial membrane antigen were present in the cells lining the gland-like lumen of tissues with the tubular and cribriform patterns, but was rare in those with a solid pattern. Desmin and S-100 protein were detected in the nonlining cells of tissues with all three patterns. These findings suggest that this tumor originates from the myoepithelial cells of the bronchial gland and that the solid pattern was the most poorly differentiated form.     

Solitary malignant Schwannoma: clinical aspects, immunohistochemistry and ultrastructure

Solitary malignant Schwannoma is a rare tumor derived from cells of the nerve sheath, the Schwann cells. During the past 6 years we have treated six patients with this tumor, four males and two females ranging in age from 18 to 69 years. Five of them had their tumors located on the trunk, which is associated with a bad prognosis. In four of the six patients ultrastructural examination played an important role in making the diagnosis of malignant Schwannoma. Light microscopy alone is insufficient because the spindle-shaped cells growing in fascicles often closely resemble other sarcomatous tumors. Ultrastructural typical findings of Schwannomas are cytoplasmic processes, intercellular junctions and basal lamina. Surgery was the sole treatment in three patients. One patient only received chemotherapy because of disseminated disease. The other two were treated with surgery combined with radiotherapy. Four patients developed distant metastases for which chemotherapy was given, but all patients died within 3 years after their initial treatment. Only two patients are free of disease 56 and 72 months after treatment. Solitary malignant Schwannoma is a tumor with a grave prognosis, for which ultrastructural and immunohistochemical examination plays an important role in order to establish the diagnosis.     

Dental X-rays and the risk of intracranial meningioma: a population-based case-control study

BACKGROUND: Ionizing radiation is a likely cause of intracranial meningioma. The authors determined whether the risk of intracranial meningioma was associated with past dental X-rays-specifically, posterior bitewings, full-mouth series, and lateral cephalometric and panoramic radiographs. METHODS: The authors conducted a population-based case-control study of residents of King, Pierce, and Snohomish counties in western Washington State. Case patients (n = 200) had an incident intracranial meningioma that was confirmed histologically during life between January 1995 and June 1998. The authors used random-digit dialing and Medicare eligibility lists to identify two control subjects to be matched to each case patient based on age and gender. Exposures were determined during an in-person interview. The authors compared self-report and dental records in a subset of study participants. RESULTS: Of the 4 dental X-ray procedures evaluated, only the full-mouth series (specifically, > or = 6 over a lifetime) was associated with a significantly increased risk of meningioma (odds ratio, 2.06; 95% confidence limits, 1.03-4.17). However, evidence for a dose-response relation was lacking (P for trend = 0.33). The risk was elevated with the aggregate number of full-mouth series in 10-year periods from approximately 15-40 years before diagnosis, with significant elevations in the 10-year periods beginning 22-30 years before diagnosis. The risks in these analyses were even greater when only women were considered. CONCLUSIONS: Dental X-rays involving full-mouth series performed 15-40 years ago, when radiation exposure from full-mouth series was much greater than it is now, were associated with an increased risk of meningioma. The authors did not observe an increased risk with bitewings, lateral cephalometric, and panoramic radiographs.     

Hormonal exposures and the risk of intracranial meningioma in women: a population-based case-control study

Background  

The role of exogenous hormone exposures in the development of meningioma is unclear, but these exposures have been proposed as one hypothesis to explain the over-abundance of such tumors in women.     

Gamma knife radiosurgery of imaging-diagnosed intracranial meningioma

PURPOSE: To evaluate tumor control and outcome from radiosurgery of meningiomas diagnosed by imaging without pathologic verification. METHODS AND MATERIALS: A total of 219 meningiomas diagnosed by imaging criteria underwent gamma knife radiosurgery to a median marginal tumor dose of 14 Gy (range 8.9-20), a median treatment volume of 5.0 cm(3) (range 0.47-56.5), and a median maximal dose of 28 Gy (range 22-50). The median follow-up was 29 months (range 2-164). RESULTS: Tumor progression developed in 7 cases, 2 of which turned out to be different tumors (metastatic nasopharyngeal adenoid cystic carcinoma and chondrosarcoma). One tumor was controlled, but the development of other brain metastases suggested a different diagnosis. The actuarial tumor control rate was 93.2% +/- 2.7% at 5 and 10 years. The actuarial rate of identifying a diagnosis other than meningioma was 2.3% +/- 1.4% at 5 and 10 years. The actuarial rate of developing any postradiosurgical injury reaction was 8.8% +/- 3.0% at 5 and 10 years. No pretreatment variables correlated with tumor control in univariate or multivariate analysis. The risk of postradiosurgery sequelae was lower (5.3% +/- 2.3%) in patients treated after 1991 (with stereotactic MRI and lower doses; p = 0.0104) and tended to increase with treatment volume (p = 0.0537). CONCLUSION: Radiosurgery of meningioma diagnosed by imaging without tissue confirmation is associated with a high rate of tumor control and acceptable morbidity but carries a small risk (2.3%) of an incorrect diagnosis.     

Stereotactic radiosurgery and radiotherapy in benign intracranial meningioma

PurposeTo investigate the role of stereotactic radio surgery (SRS) and hypo-fractionated stereotactic radiotherapy (SRT) in treatment of benign intracranial meningioma.Patients and methodsBetween 2003 and 2010, 32 patients with a median age of 44 years (range 21–67 years) were treated with SRS (n = 19), and hypo-fractionated SRT (n = 13) for intracranial meningioma. Fourteen patients underwent SRS or SRT as their primary treatment, while 18 patients underwent post operative SRS or SRT (PORT). Cumulative progression free survival, overall cumulative survival, toxicity and symptomatology were evaluated.ResultsThe median follow up period was 39 months (range 6–72 months). The 5 year overall survival and progression free survival were 90 ± 5% and 94 ± 4% after SRT or SRS respectively.Symptoms were improved or stable in 94% of patients. Acute toxicity was mild, and was seen in 41% of patients. Clinically significant late morbidity or new cranial nerve palsies did not occur.ConclusionStereotactic radio surgery (SRS) and hypo-fractionated stereotactic radiotherapy (SRT) are effective and safe treatment modality for local control of meningioma with low risk of significant late toxicity. In case of large tumor size and adjacent critical structures, hypo-fractionated SRT is highly recommended.     

Newly established patient-derived organoid model of intracranial meningioma

BackgroundRecent comprehensive studies have revealed several molecular alterations that are frequently found in meningiomas. However, effective treatment reagents targeting specific molecular alterations have not yet been identified because of the limited number of representative research models of meningiomas.MethodsWe performed organoid cultures using meningioma cells and meningioma tumor tissues. Using immunohistochemistry and molecular analyses consisting of whole-exome sequencing, RNA-seq, and DNA methylation analyses, we compared the histological findings and molecular profiling of organoid models with those of parental tumors. Further, using these organoid models together with a public database of meningiomas, we explored molecular alterations, which are a potent treatment target for meningioma.ResultsWe established 18 organoid models comprising of two malignant meningioma cells (HKBMM and IOMM-Lee), 10 benign meningiomas, four malignant meningiomas, and two solitary fibrous tumors (SFTs). The organoids exhibited consistent histological features and molecular profiles with those of the parental tumors. Using a public database, we identified that upregulated forkhead box M1 (FOXM1) was correlated with increased tumor proliferation. Overexpression of FOXM1 in benign meningioma organoids increased organoid proliferation; depletion of FOXM1 in malignant organoids decreased proliferation. Additionally, thiostrepton, a FOXM1 inhibitor combined with radiation therapy, significantly inhibited the proliferation of malignant meningioma organoid models.ConclusionsAn organoid model for meningioma enabled us to elucidate the tumor biology of meningioma along with potent treatment targets for meningioma.