Intracranial hemangiopericytoma: Case study with cytogenetics and genome wide SNP-A analysis

The tumor entity of hemangiopericytoma is not universally recognized as a nosological entity by pathologists, and there is a trend toward reassigning it to other categories gradually. However, hemangiopericytomas occurring in the nervous system are included in the new WHO classification of brain tumors, and are distinguished from both meningioma and fibrous tumors. Since there are few genetic studies, we performed a comprehensive cytogenetic analysis of an infratentorial hemangiopericytoma in a 55-year-old female. It was originally classified as a grade II tumor but recurred as a grade III tumor with a proliferation index of 20%. Using trypsin-Giemsa staining (GTG-banding) and multicolor fluorescence in situ hybridization (M-FISH), we could confirm the loss of chromosomal material 10q, which has been previously described in hemangiopericytoma, and we identified de novo chromosomal aberrations on chromosome 8. Applying genome-wide high-density single nucleotide polymorphism array (SNP-A) analysis, we detected segments with loss or gain, as well as clonal deletions or regions suggestive of segmental uniparental disomy. These findings, together with the results of conventional histological and immunohistochemical characterization, provide additional evidence for the nosological separation of hemangiopericytoma in the central nervous system as a biologically different entity.     

Genome-wide genetic characterization of an atypical meningioma by single-nucleotide polymorphism array-based mapping and classical cytogenetics

Most meningiomas, accounting for about 20% of intracranial tumors, can be cured by surgical removal. Yet, 8-22% of these tumors are classified as atypical or anaplastic (WHO grade II or III, respectively) presenting with a more aggressive behavior and a high relapse rate. We analyzed genomic alterations of an atypical meningioma using high-density single nucleotide polymorphism arrays (SNP-A) karyotyping combined with GTG-banding, multicolor fluorescence in situ hybridization (M-FISH), and locus-specific FISH.In accordance to recent studies applying SNP-A karyotyping in different malignancies we found that genomic lesions are present at a higher frequency than predicted by traditional cytogenetics. Most of these aberrations have not been described before. Additionally, we unveiled loss of heterozygosity (LOH) without copy number changes on chromosome regions 1p31.1, 2p16.1, 2q23.3, 6q14.1, 6q21, 9p21.1, 10q21.1, and 14q23.3, suggesting partial uniparental disomy (UPD). UPDs are currently considered to play an important role in the initiation and progression of different malignancies.Furthermore, we detected two de novo reciprocal translocations, t(8;19)(q24;q13) and t(10;16)(q22;q12.1). While GTG-banding and M-FISH data suggested balanced translocations, SNP-A analysis clearly demonstrated imbalances in the same region.     

应用单核苷酸多态性芯片研究单亲二体型来源及致病机制

 目的：探讨人类全基因组单核苷酸多态性芯片(single nucleotide polymorphism array, SNP array)在单亲二体型来源及致病机制研究和遗传咨询中的应用价值。方法：对具有唐氏综合征高风险、需行羊水胎儿细胞G 显带染色体核型分析的124例孕妇,应用SNP array对羊水中的胎儿细胞及父母双方的外周血细胞进行遗传学分析。结果：对羊水胎儿细胞进行SNP array分析发现,2例部分型16单亲二体型,1例位点为16p12.2～13.3和16q24.1～24.3,另1例位点为16q21～24.3。对胎儿双亲外周血细胞进行遗传学连锁分析发现,2例单亲二体型均为母源性。结论：16号染色体长、短臂末端可能分别存在导致胎儿生长受限的基因。 SNP array可探索单亲二体型的来源及致病机制,为产前遗传咨询提供帮助。     

Metastasis of lung adenosquamous carcinoma to meningioma: case report with literature review

The occurrence of metastasis of a systemic neoplasm to an intracranial tumor is a rare phenomenon. Meningiomas have been reported as the most common intracranial tumor to harbor a systemic metastasis, with breast and lung carcinomas being the most common sites of origination. Here, we report a case of an adenocarcinoma metastasis of an adenosquamous lung carcinoma found within a meningioma, resulting in the patient’s first clinical manifestations. We also review the literature for other cases of adenocarcinoma metastatic to a meningioma and suggest mechanisms that make meningiomas likely to harbor systemic metastases including increased vascularity, slow growth rate, increased hyaline content and expression of cell-cell adhesion molecules.     

Lateral ventricular meningioma presenting with intraventricular hemorrhage: a case report and literature review

Lateral ventricular meningiomas presenting with primary intraventricular hemorrhage are extremely uncommon. We report here a case of primary intraventricular hemorrhage attributable to a lateral ventricular meningioma. This case concerns a 46-year-old female patient who presented with sudden onset of headache. Computed tomography (CT), computed tomography angiography (CTA) and magnetic resonance imaging (MRI) examinations showed hemorrhage from a ruptured tumor mass, which was pathologically confirmed as a transitional meningioma. The patient underwent surgical treatment and had a good prognosis. A retrospective review of eight previous cases of hemorrhage from ruptured lateral ventricular meningiomas revealed that hemorrhage of lateral ventricular meningiomas and hemorrhage of meningiomas at other intracranial sites have similar causes. The clinical and pathological features of ruptured lateral ventricular meningiomas are consistent with those of unruptured lateral ventricular meningiomas. As this clinical entity is extremely rare, attention is called for while performing differential diagnosis.     

Methylation analysis in tongue tissue of BWS patients identifies the (EPI)genetic cause in 3 patients with normal methylation levels in blood

The Beckwith–Wiedemann syndrome is caused by disturbed imprinting of genes at 11p15.5. Routine diagnostic testing for Beckwith–Wiedemann syndrome (BWS) includes methylation analysis of the imprinting centers ICR1 and ICR2 in DNA extracted from lymphocytes. In approximately 15% of BWS patients the diagnosis cannot be molecularly confirmed. In this study we determined the methylation status in resected tongue tissue of 11 BWS patients and compared this to the genetic defects found by routine diagnostic screening of blood lymphocytes. In all three patients with normal methylation levels in blood, aberrant methylation patterns were found in tongue tissue. In two patients a UPD was detected and the third case had hypermethylation of ICR1. This result shows that tissue specific mosaic (epi)genetic changes, not present in blood, is the underlying defect in at least a subset of BWS patients without a molecular diagnosis after standard genetic testing.     

Primary clear cell meningioma of the orbit mimicking a metastatic carcinoma: usefulness of immunohistochemistry and cytogenetic analysis

Clear cell meningiomas (CCM) are rare tumors of the nervous system that usually occur in young patients and display high recurrence rates and potentially aggressive behavior. In this report, we describe a primary CCM of the orbit in an 84-year-old man with a previous history of a clear cell carcinoma of the kidney. Histologically, the tumor demonstrated a sheet-like proliferation of clear polygonal cells. Differential diagnosis includes metastasis of clear cell carcinomas. Immunohistochemistry, by showing that tumor cells expressed vimentin, epithelial membrane antigen, and progesterone antigens, and cytogenetic analysis, by identifying a monosomy 22, confirmed the diagnosis of CCM.     

颅外原发下颌骨脑膜瘤临床诊治一例报道并文献复习

目的 探讨颅外原发下颌骨脑膜瘤的临床病理和影像学特征,以及诊断和治疗方法。方法 回顾性分析2017年10月无锡市第二人民医院收治的1例57岁女性颅外原发下颌骨脑膜瘤患者的临床资料。在PubMed、中国知网、万方数据及维普数据库中,以“下颌骨(mandibular)”和“原发性脑膜瘤(primary meningioma)”为关键词,检索截至2017年10 月有关下颌骨原发性脑膜瘤的相关文献,共纳入7篇8例颅外原发下颌骨脑膜瘤的报道,均为英文文献;结合本例诊治过程,总结该病临床及影像学表现、组织学形态、免疫组织化学特征、治疗方法及临床预后特点。结果 本文1例中年女性下颌骨无痛性膨胀性病变,CT为境界清楚的透射影,组织学梭形肿瘤细胞伴有局部旋涡状结构,免疫组织化学瘤细胞上皮膜抗原(EMA)、波形蛋白(Vimentin)支持脑膜瘤的诊断;手术完整切除下颌骨肿瘤,术后随访9个月无复发。结合文献报道的8例共9例颅外原发下颌骨脑膜瘤,男2例、女7例,年龄20~74岁;多以下颌骨局部膨胀为主要临床表现;影像学为下颌骨境界清楚的溶骨性病变,多为透射影,也可透射和非透射混合影像;组织学同颅内脑膜瘤,为纤细梭形瘤细胞束状或旋涡状排列,细胞间丰富胶原,部分细胞多边形上皮样,胞界不清,片状分布,可见砂粒体,细胞无异形;免疫组织化学瘤细胞EMA、Vimentin均阳性,孕激素受体、广谱细胞角质蛋白、肌动蛋白结合蛋白、平滑肌肌动蛋白、结蛋白、S-100蛋白、β-微管蛋白-3、CD34、B淋巴细胞瘤-2和尤因肉瘤标记物均阴性,Ki-67增殖指数1%。治疗以肿块切除及下颌骨切除自体骨片移植为主要手术方式。组织学良性者预后好,手术切除可治愈。结论 颅外原发下颌骨脑膜瘤非常罕见,需结合临床及影像学、病理组织学进行鉴别诊断和诊断。手术完整切除肿块及下颌骨重建可治愈。     

Rare growth of a psammomatous meningioma in a mature ovarian Teratoma: A case report

The presence of meningothelial elements along with abundant psammoma bodies indicates the presence of a benign meningioma within a teratoma. Recognition of meningioma arising in the setting of a teratoma is of prognostic significance, depending on the nature of this component and its spread beyond the organ of origin.     

Intracranial Rosai-Dorfman disease mimicking isolated meningioma: a case report and review of the literature

Rosai-Dorfman disease is a rare malignant infirmity. Here, we present a case of a 57-year-old man with giddiness and unstable gait, as well as blurred vision in the left eye for four months. Radiologically the diagnosis before surgery was meningioma. The patient received a craniotomy, and the histopathologic diagnosis was Rosai-Dorfman disease. We reviewed the diagnosis, mechanism, and treatment of this disease.     

Clear cell meningioma with anaplastic features: Case report and review of literature

Clear cell meningioma (CCM) is an uncommon variant of meningioma, corresponding to WHO grade II. We present two cases of CCMs with anaplastic features in the intracranial and intraspinal region. The first case is a 65-year-old male who gradually developed changes in behavior over a period of 1 year. The second case is a 35-year-old female who presented with a 7-month history of posterior cervicothoracic pain and dysuria for 1 week. Magnetic resonance imaging revealed an intracranial lesion in the right frontal lobe in the male patient, and an intradural extramedullary lesion at C7 in the female patient. On histological examination, both tumors partly exhibited unusual anaplastic appearances with nuclear pleomorphism, high mitotic activity and necrosis, distinct from classical CCMs. Tumor cells were immunoreactive to epithelial membrane antigen (EMA) and vimentin, with a high MIB-1 index up to 40%. Total excision was performed. The male patient was found to have developed local recurrence and lateral ventricle metastasis 3 months after surgery. A diagnosis of CCM with anaplastic features was made (WHO grade III). Based on its aggressive behavior, we recommend postoperative adjuvant radiotherapy or chemotherapy even if total excision of the tumor has been performed, and MRI scans every 3–6 months during the first period of follow-up.     

A collision tumor of solitary fibrous tumor/hemangiopericytoma and meningioma: A case report with literature review

An intracranial collision tumor is a rare lesion composed of two histologically different neoplasms in the same anatomic location. Even more rare is the collision tumor of a solitary fibrous tumor/hemangiopericytoma (SFT/HPC) and meningioma. The patient was a 46-year-old woman who had a 40 × 35 × 30-mm mass in the vermis of the cerebellum. Histologically, the mass consisted of two different components. One component showed the morphology of meningioma (World Health Organization (WHO) grade I), and the other component exhibited small round cell proliferation with hypercellular density, which was revealed to be SFT/HPC (WHO grade III) based on STAT6 immunohistochemistry. STAT6 showed completely different immunohistochemistry results in these two components (nuclear-negative in meningioma and nuclear-positive in SFT/HPC). Since these two neoplasms are associated with different prognoses, they should be distinguished from each other. When meningioma and an SFT/HPC-like lesion are identified morphologically, it is important to recognize the presence of such a collision tumor composed of meningioma and SFT/HPC, and identify the SFT/HPC component by employing STAT6 immunohistochemistry.     

Expression of E-cadherin and catenins in meningioma: ubiquitous expression and its irrelevance to malignancy

The expression of cell adhesion molecules in 107 meningiomas was analyzed with immunohistochemical methods using antibodies to epithelial (E)-cadherin and catenins (alpha, beta and gamma). According to the provided World Health Organization (WHO) grading, 84, 18 and five cases were classified as grade I, II and III, respectively. In addition, hemangioblastoma (15 cases) and hemangiopericytoma (four cases) were also evaluated. In most meningiomas, E-cadherin, alpha- and beta-catenins were expressed along the cell membrane or inside the cytoplasm. The tumor cells constituting whorls and glandular structures of secretory type showed a strong immunoreactivity. gamma-Catenin expression tended to be weak and infrequent in fibrous meningiomas, while other types exhibited diffuse stainings. Even in meningiomas of more than grade II, the expressions of cell adhesion molecules were detected in all cases. Hemangiopericytoma was positive for alpha- and beta-catenins, and hemangioblastomas were positive for beta-catenin alone, which was distinct from the expression pattern in meningiomas. Quantitatively, there were no correlations between the histological variants, Ki-67 indexes, or grades of meningiomas and the immunoreactive scores except for gamma-catenin scores of fibrous meningiomas. The present study demonstrates that cell adhesion molecules are ubiquitously expressed in all variants of meningioma and may be involved in the tumor morphogenesis. This result suggests that the expression of cell adhesion molecules is not a reliable indicator of malignancy in meningiomas. The present study also suggests that these markers may be useful for the differential diagnosis of meningioma.     

Angiomatous lesion and delayed cyst formation after gamma knife surgery for intracranial meningioma: case report and review of literatures

Gamma Knife has become a major therapeutic method for intracranial meningiomas, vascular malformations and schwannomas with exact effect. In recent years an increasing number of delayed complications after Gamma Knife surgery have been reported, such as secondary tumors, cystic changes or cyst formation. But angiomatous lesion and delayed cyst formation after Gamma Knife for intracranial lesion has rarely been reported. Here we report the first case of angiomatous lesion and delayed cyst formation following Gamma Knife for intracranial meningioma and discuss its pathogenesis.     

Intracranial benign fibrous histiocytoma mimicking parasagittal meningioma: report of two cases and review of literature

Primary benign fibrous histiocytoma involving the central nervous system is an exceedingly rare tumor with most cases originating from the dura or parenchymal tissue. Diagnosis of primary benign fibrous histiocytoma is difficult due to its confusing histopathological characteristics. Two cases of primary intracranial benign fibrous histiocytoma mimicking parasagittal meningioma are presented in this report. Both tumors were gross totally resected and the patients showed no evidence of recurrence at follow-up of 12 months. The clinical features and prognosis of this rare tumor that were reported previously in the literature were also reviewed. Histopathological examination coupled with immunohistochemical staining is proved to be the convincing diagnostic method for the primary benign fibrous histiocytoma. Surgical resection is the recommendation for the therapy of the tumor.     

Reticular angiomatoid "malignant" fibrous histiocytoma--a case report with cytogenetics and molecular genetic analyses

Angiomatoid "malignant" fibrous histiocytoma is a rare sarcoma of low malignant potential that occurs most commonly in the extremities of children and young adults. Herein, we present a case of angiomatoid malignant fibrous histiocytoma with unusual histologic features arising in the mediastinum of an 80-year-old man. The tumor exhibited a reticular growth pattern and myxoid stroma. The tumor cells expressed epithelial membrane antigen and desmin. Cytogenetic analysis revealed the translocation t(2;22)(q33;q12). Molecular genetic analysis confirmed the rearrangement of the EWSR1 locus and the presence of the EWSR1/CREB1 fusion. This report expands the clinicopathologic spectrum of angiomatoid malignant fibrous histiocytoma and underscores the value of integrating morphologic, immunophenotypic, and molecular findings in the identification of its unusual morphologic variants.     

Loss of SMARCE1 expression is a specific diagnostic marker of clear cell meningioma: a comprehensive immunophenotypical and molecular analysis

Clear cell meningioma (CCM) is a rare grade II histopathological subtype that usually occurs in young patients and displays high recurrence rate. Germline SMARCE1 mutations have been described in hereditary forms of this disease and more recently in small syndromic and sporadic CCM series. The diagnostic value of SMARCE1 in distinguishing between CCM and other meningioma variants has not been yet established. The aim of our study was to investigate the status of SMARCE1 in a series of CCMs and its morphological mimickers. We compared the performance of an anti‐SMARCE1 antibody and the molecular analysis of the SMARCE1 gene in a retrospective multicenter series of CCMs. All CCMs lossed SMARCE1 immunoexpression. Bi‐allelic inactivating events were found by NGS‐based sequencing in all of these cases, except for one, which was incompletely explored, but had a wild‐type sequence. We then validated the anti‐SMARCE1 antibody specificity by analyzing additional 305 pediatric and adult meningiomas of various subtypes and 15 non‐meningioma clear cell tumors by SMARCE1 immunohistochemistry. A nuclear immunostaining was preserved in all other meningioma variants, as well as non‐meningioma clear cell tumors. In conclusion, our series showed, for the first time, that SMARCE1 immunostaining is a highly sensitive biomarker for CCM, useful as a routine diagnostic biomarker.