Intriguing Case: Myxoid Meningioma

A mucosubstance-rich myxoid meningioma that recurred twice is reported. This rare form of meningioma is a potential source of confusion with other myxoid neoplasms such as metastatic adenocarcinoma or chordoma. In addition to the usual stigmata of meningial cell differentiation, ultrastructural examination revealed spaces delineated by a network of cellular processes and enclosing loose granular and fibrillar material. This neoplasm is probably linked to the so-called microcystic meningioma but has an overt production of acid muco-substance.     

Rhabdoid meningioma: intraoperative diagnosis using smear preparation

Tumors with rhabdoid morphology were first described by Beckwith and Palmer in 1978 as aggressive renal tumors in very young children. Subsequently, rhabdoid tumors and tumors with rhabdoid features have been described in many other organ systems and all tend to have a poor outcome no matter what the histogenesis of the original tumor. Rhabdoid cells are plump, with abundant eosinophilic fibrillary to hyaline cytoplasm and peripheral, vesicular, variably pleomorphic nuclei. Nucleoli are invariably present. While their morphology is well recognized in processed biopsy material, their presence on a smear preparation can be quite startling. A case is presented to highlight the appearance of rhabdoid cells on an intraoperative smear preparation of a rhabdoid meningioma. An accompanying secretory component added to the complex picture.     

MIB-1 labeling indices in benign, aggressive, and malignant meningiomas: A study of 90 tumors

Predicting tumor behavior in meningiomas based on histology alone has been problematic. This study retrospectively compares histology and MIB-1 (cell proliferation marker) labeling indices (LI) in benign, aggressive, and malignant meningiomas. Six histological features, including mitoses, necrosis, loss of pattern, hypervascularity/ hemosiderin deposition, prominent nucleoli, and nuclear pleomorphism, were compared in 90 meningiomas (Fisher's exact test). Tumors with two or more of the above features were designated as aggressive meningiomas. Malignant meningiomas were characterized by brain invasion or metastasis. The MIB-1 Us (% positive tumor cell nuclei) were compared between the three groups (Kruskal-Wallis test, Wilcoxon two-sample test). Of the benign meningiomas (n = 37; mean age, 54 years), 41% had one of the six histological features, with nuclear pleomorphism (n = 10) being the most frequent. The aggressive tumors (n = 29; mean age, 61 years) were characterized by nuclear pleomorphism (n = 28), mitoses (n = 20), necrosis (n = 16), loss of pattern (n = 16), prominent nucleoli (n = 6), and hypervascularity/hemosiderin deposition (n = 5). Malignant tumors (n = 24; mean age, 59 years) were characterized by nuclear pleomorphism (n = 22), mitoses (n = 21), loss of pattern (n = 21), necrosis (n = 21), nucleoli (n = 17), and hypervascularity/hemosiderin deposition (n = 3). Significant differences were found between the aggressive and malignant groups with regard to loss of pattern, necrosis, and nucleoli (P = .0043, .011, and .00029, respectively). Mean MIB-1 LIs for the benign, aggressive, and malignant groups were 1.0% (range, 0 to 5.5%), 5.5% (range, 0.1 to 32.5%), and 12.0% (range, 0.3 to 32.5%), respectively. Differences in the mean MIB-1 LI between groups were statistically significant, with P values of <.0001 (benign v aggressive) and .0012 (aggressive v malignant). Mean MIB-1 LIs for recurrent versus nonrecurrent tumors were 7.1% (range, 0 to 32.5%) versus 3.8% (range, 0 to 20.9%) (P = .32). The mean MIB-1 LI for patients who were alive with or without tumor was 6.2% (range, 0 to 32.5%) versus a mean MIB-1 LI of 14.2% (range, 2.8% to 32.5%) for patients who died of or with tumor (P = .0013). In conclusion, (1) There is a statistically significant difference in the increasing MIB-1 LI means between benign, aggressive, and malignant meningiomas and between patients who were alive versus those who died; (2) there is some overlap in MIB-1 LI ranges between groups, which warrants caution in interpreting an individual MIB-1 LI in a given tumor.     

Allelic losses at 1p, 9q, 10q, 14q, and 22q in the progression of aggressive meningiomas and undifferentiated meningeal sarcomas

Meningiomas are usually benign tumors; however, they can recur after surgical resection and occasionally show histological progression to a higher malignancy grade. Five such rare cases of aggressively recurring meningiomas were present in our departmental cohort of 923 primary meningeal neoplasms operated over a 17-year period. Four other aggressively recurring meningeal tumors with a very similar clinical and histomorphological appearance (three undifferentiated meningeal sarcomas, one hemangiopericytoma) were also included in this study. We investigated whether disease progression can be traced by genetic alterations and whether a pattern of genetic alterations is specific for meningiomas. A total of 40 specimens from primary tumors and multiple recurrences of the nine patients were analyzed with 26 polymorphic allelic markers for deletions on 1p, 1q, 9q, 10q, 14q, and 22q. Loss of heterozygosity (LOH) at 22q was observed in all meningiomas cases at the earliest time point analyzed. Allelic loss at 1p was seen in the original tumor in two cases and upon meningioma recurrence in two others. Deletion on 10q occurred during tumor progression in two cases, and on 9q and 14q in one case. While allelic loss at 22q appears to be an early event in aggressive meningioma disease, there is a clear correlation of further deletions on chromosome arms 1p, 9q, 10q, and 14q with histopathological and clinical progression, as shown in these intraindividual trackings. None of these genetic findings were present in the non-meningiomatous meningeal tumors, indicating that meningothelial cells have their own lineage-specific genetic pathways towards clinical malignancy.     

Molecular neuropathology of brain‐invasive meningiomas

Invasion of brain tissue by meningiomas has been identified as one key factor for meningioma recurrence. The identification of meningioma tumor tissue surrounded by brain tissue in neurosurgical samples has been touted as a criterion for atypical meningioma (CNS WHO grade 2), but is only rarely seen in the absence of other high‐grade features, with brain‐invasive otherwise benign (BIOB) meningiomas remaining controversial. While post‐surgery irradiation therapy might be initiated in brain‐invasive meningiomas to prevent recurrences, specific treatment approaches targeting key molecules involved in the invasive process are not established. Here we have compiled the current knowledge about mechanisms supporting brain tissue invasion by meningiomas and summarize preclinical models studying targeted therapies with potential inhibitory effects.     

Temporal bone secretory meningioma presenting as a middle ear mass

A 44-year-old woman presented with a history of increasing left hypoacusis and sporadic vertigo. CT scan revealed a tumor occupying the mastoid, middle ear, and external auditory canal. After surgical removal, a typical secretory meningioma was diagnosed. The histological hallmark and the immunohistochemical profile of secretory meningiomas are reviewed. The differential diagnosis of this tumor in this location is also commented on. As far as we know, primary temporal bone meningiomas with secretory histology have not been previously reported in the medical literature.     

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.     

Cytomorphology of Recurrent Osseous Extracranial Meningioma of Right Pubic Ramus:

Meningiomas are well‐recognized neoplasms of the central nervous system. Primary extracranial meningiomas (ECMs) are extremely rare and arise in various anatomic sites. We present a 56‐year‐old female with 13‐year history of primary grade I meningothelial meningioma of right pubic symphysis, orthotopic heart transplant, and right total hip arthroplasty, who presented with progressive right hip pain for 3 weeks. Primary intracranial, intraspinal and other tumors were excluded. Imaging revealed a destructive lytic lesion at right superior and inferior pubic rami and body, associated with extensive bone destruction and soft tissue mass. Touch imprint (TI) cytology of computed tomography (CT)‐guided core biopsy from the right pubic ramus (PRA) lesion showed a spindle cell neoplasm, with classical syncytial, lobular, and whorling cellular arrangement, composed of spindle, oval or round nuclei with occasional pseudoinclusions, consistent with known history of osseous meningioma. Tumor was further characterized by histopathology as grade 1 meningioma with meningothelial features. To our knowledge, primary osseous ECM arising specifically at the PRA has not been reported previously. ECM at this site may pose a diagnostic challenge for cytologists as its features may resemble other more commonly observed lesions. Accurate diagnosis requires awareness of occurrence of ECM at PRA and recognition of its characteristic cytomorphology. TI cytological features of our case are presented and previously described cytology of ECMs and diagnostic pitfalls are reviewed. Diagn. Cytopathol. 2016;44:618–622. © 2016 Wiley Periodicals, Inc.     

Atypical and malignant meningiomas: importance of micronecrosis as a prognostic indicator

Twenty-eight patients with a diagnosis of either atypical or malignant meningioma, according to the World Health Organisation (WHO) classification, were followed up to relate histopathological features with times to recurrence and death. Five year disease-free survival was 41% with a median disease free survival of 27 months. Micronecrosis was the only histopathological feature associated with increased risk of recurrence (rate ratio, 3.73; 95% confidence interval 1.03–13.6). At 36 months, 32% of patients with micronecrosis were alive compared with 71% of patients without micronecrosis. Brain invasion was not associated with disease-free survival. After recurrence, median survival was 7 months and was not correlated with any histopathological feature. The prevalence of micronecrosis was estimated from random samples of benign, atypical and malignant meningiomas to be 8%, 42% and 71% respectively. The relevance of these findings and the current WHO classification is discussed.     

Metastatic meningioma detected in pleural fluid

Meningiomas with both malignant cytologic features and clinical behavior are rare. A 39-yr-old man with recurrent meningioma developed a pleural effusion which, on cytologic examination, contained metastatic meningioma. The diagnosis was subsequently confirmed histologically and ultrastructurally. In conclusion, metastatic meningiomas can retain meningotheliomatous cytologic features which may allow a diagnosis to be made of clinically unanticipated tumor spread. Diagn. Cytopathol. 1998;18:453–457. © 1998 Wiley-Liss, Inc.     

Primary orbital meningioma: a study of six cases at a single institution

Primary orbital meningioma is a rare tumor of the anterior visual pathway and constitutes approximately 2% of all orbital tumors and 1-2% of all meningiomas. The differentiation from secondary orbital meningioma of intracranial origin is sometimes difficult on image. As the tumor often leads to visual loss if left untreated and surgical intervention inevitably causes morbidity, the timing and modality of treatment are very important. We carried out the study involving six cases (mean age: 42.7 years, male to female ratio: 1:5) of primary orbital meningioma to further elucidate its behavior. The clinical signs and symptoms, diagnosis, treatment strategies, and follow-up information are recorded for all cases. The most frequent initial symptoms were visual complaints (100%) and proptosis (67%). In five cases, the diagnosis was based on pathologic findings and the tumors were all grade I meningiomas. In one case, however, the diagnosis was based on radiographic and clinical findings, lacking histologic confirmation. Five patients were operated on, four underwent tumor removal, and one received eyeball exenteration. One patient was treated with Novalis radiotherapy. The mean follow-up period was 8.8 years (range from 9 months to 15 years). All patients experienced loss of vision during the course without exception. No recurrent tumor was found in five cases during follow-up. In case 5, whose eyeball was exenterated, developed recurrent meningioma 7 years later. She received radiotherapy but the tumor was out of control. She expired 8 years after eyeball exenteration. The primary orbital meningioma is aggressive in behavior despite its benign histopathologic features. Loss of vision is frequently seen even after treatment. The tumor could be fatal if surgery and radiotherapy fail to control its intracranial extension.     

Introduction to the mini‐symposium “molecular neuropathology of meningioma”

Progress of molecular meningioma characterization (*courtesy of Ralf Ketter, Homburg, Germany).     

TERT promoter mutations in primary and secondary WHO grade III meningioma

Purpose: TERT promoter mutation (TERTp^Mut) has a strong association to recurrence and has been suggested to act as a driver mutation for malignant transformation of WHO grade I and II meningiomas. TERTp^Mut has been investigated in selected high‐grade meningioma samples. The existence of TERTp^Mut across recurrent tumors in a population‐based cohort needs to be investigated in order to identify when TERTp^Mut emerges across recurrent samples and to validate prognostic impact among WHO grade III tumors. Methods: We gathered material from a consecutive single‐center cohort of 40 patients with malignant meningioma (WHO grade III) treated between 2000 and 2018, including specimens from primary and secondary malignant meningiomas with the corresponding earlier benign specimens and later malignant recurrences. In total 107 tumor samples were studied by Sanger sequencing for TERT promoter mutational status. Results: Seven of 40 patients (17.5%) harbored TERTp^Mut thus validating the incidence of TERTp^Mut in previous non‐population‐based cohorts. In 6/7 patients, the TERTp^Mut was present at initial surgery (WHO grade I–III) while in one patient the TERTp^Mut was found de novo when the meningioma became malignant. The incidences were 2/1.000.000/year for TERTp^Mut WHO grade III meningioma and 8/1.000.000/year for TERTp^wt WHO grade III meningioma in our catchment area. We found a 1.7 times higher recurrence rate (CI 95% 0.65–4.44) and a 2.5 higher mortality rate per 10 person‐years (CI 95% 1.01–6.19) for TERTp^Mut compared to TERTp^wt. Conclusion: TERTp^Mut can occur independently of malignant progression in meningioma and was most often present from the first tumor sample across recurring tumors. TERTp^Mut in WHO grade III may represent a marker of an aggressive subset of tumors.     

Primary extradural meningiomas in head: a report of 19 cases and review of literature

Primary extradural meningiomas (PEMs) in head were rare tumors. Here we analyzed 231 cases of PEMs in head (including our 19 cases) reported in the literature during the CT era. We found that PEMs in head accounted for 0.8%-1.8% of all meningiomas. The constituent ratio of male PEMs in head increases markedly. PEMs in head have bimodal distribution of ages. The most common presenting symptom was a mass in the region of the lesion. The average duration of symptom was 2.38 years. The skull convexities, paranasal sinuse and nasal cavity, and middle ear ranked as the top three of all sites of tumors. The most common type was Type II (calvarial or diploic). Among 231 cases, total, subtotal and partial removals of tumors were achieved in 89%, 5.5% and 3.1% respectively, and no death occurred perioperatively in all patients. 90% were benign, 5.6% atypical and 3.9% malignant in the 231 cases. The most common histopathological subtype was meningothelial meningioma. The recurrence and tumor-related death rates were 22.4% and 8.2% respectively during a mean 3.03-year follow-up. Our results demonstrate that PEMs in head have some marked clinical characteristics compared with primary intradural meningiomas. Total tumor removal together with a wide excision of all involved tissues followed by the reconstruction of tissue defects is the best surgical project. The prognoses are good in the benign cases after complete surgical resections.     

Lack of genetic and epigenetic changes in meningiomas without NF2 loss

Approximately 60% of sporadic meningiomas are caused by inactivation of the NF2 tumour suppressor gene. The causative gene for the remaining meningiomas is unknown. Previous studies have shown that these tumours have no recurrent karyotypic abnormalities. They differ from their NF2-related counterparts in that they are more often of the meningothelial subtype and are located preferentially in the anterior skull base. To gain more insight into the aetiology of these tumours, we studied genetic and epigenetic alterations in 25 meningiomas without NF2 involvement. We first established a genome-wide allelotype using 3 microsatellite markers per chromosome arm. Loss of heterozygosity (LOH) was detected at a low frequency and no indication for the location of putative tumour suppressor genes could be established. We next screened the subtelomeric regions by using 2-3 polymorphic markers close to each telomere. Again no evidence for LOH of a particular chromosome arm was obtained, and no LOH was found in the genomic regions containing the NF2-related ERM family members ezrin and radixin, DAL-1, protein 4.1R, and TSLC1. Mutations in the X-chromosome based family member, moesin, were analysed by SSCP and were not detected. Microsatellite instability was studied using 6 commonly used markers but none of these was altered in any meningioma. Methylation was detected in 5 of 16 genes (NF2, p14(ARF), CDH1, BRCA1, RB1) previously shown to be silenced in a variety of tumour types. However, methylation percentages for these genes were generally higher in a group of NF2-related meningiomas, with the exception of the BRCA1 gene. The NF2 gene was methylated in only 1 of 21 tumours. In conclusion, meningiomas with an intact NF2 gene have a normal karyotype and no obvious genetic or epigenetic aberrations, suggesting that the gene(s) involved in the pathogenesis of these tumours are altered by smaller events than can be detected with the techniques used in our study.     

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.     

Reduced Activity of CD13/Aminopeptidase N (APN) in Aggressive Meningiomas Is Associated with Increased Levels of SPARC

Meningiomas are the second most common brain tumors in adults, and meningiomas exhibit a tendency to invade adjacent structures. Compared with high-grade gliomas, little is known about the molecular changes that potentially underlie the invasive behavior of meningiomas. In this study, we examined the expression and function of the membrane alanyl-aminopeptidase [mAAP, aminopeptidase N (APN), CD13, EC3.4.11.2] zinc-dependent ectopeptidase in meningiomas and meningioma cell lines, based on its prior association with tumor invasion in colorectal and renal carcinomas. We found a significant reduction of APN mRNA and protein expression, as well as enzymatic activity, in high-grade meningiomas. While meningioma tumor cell proliferation was not affected by either pharmacologic APN inhibition or siRNA-mediated APN silencing, APN pharmacologic and siRNA knockdown significantly reduced meningioma cell invasion in vitro . Next, we employed pathway-specific cDNA microarray analyses to identify extracellular matrix and adhesion molecules regulated by APN, and found that APN-siRNA knockdown substantially increased the expression of secreted protein, acidic and rich in cysteine (SPARC)/osteonectin. Finally, we demonstrated that SPARC, which has been previously associated with meningioma invasiveness, was increased in aggressive meningiomas. Collectively, these results suggest that APN expression and enzymatic function is reduced in aggressive meningiomas, and that alterations in the balance between APN and SPARC might favor meningioma invasion.     

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.     

Fine-needle aspiration cytology of orbital meningiomas

Meningiomas are benign tumors derived from arachnoid cells. Most commonly they arise within the cranial cavity, but they may arise extracranially in various anatomic sites. We present four cases of orbital meningiomas diagnosed on fine‐needle aspiration cytology (FNAC) and confirmed on histopathology. All the cases are presented with orbital mass. FNAC smears showed classical whorling and syncytial pattern of cells, withround to oval nucleus, inconspicuous nucleoli and one eachcase showed intranuclear inclusion and psammoma bodies. FNAC diagnosis of such lesions is difficult, because cytological features may mimic other soft tissue lesions located in orbital region. Awareness of this entity and its cytological appearance is important to allow correct diagnosis. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.