Simultaneous trigonal and spinal meningioma with varied histology: A rare case report

Background: Meningioma is one of the most common neoplasms of the central nervous system. Multiple meningiomas without neurofibromatosis are not a usual occurrence. Intraventricular meningioma with spinal meningioma is rare and not been reported in the literature. Case Description: We report a case of a 63-year-old male with the left trigonal and spinal meningioma. Both the meningiomas were resected in different settings. The histological examination of tumors revealed to be of varied histology, that is, meningothelial and atypical meningioma, respectively. Conclusion: Although various cases with multiple cranial and spinal meningiomas are described, this is the first case of an intraventricular and spinal meningioma. With varied histology, the case also reaffirms the theory of polyclonal origin of multiple meningiomas.

Multiple meningiomas

Multiple meningiomas are rare conditions that refer to the presentation of two or more meningiomas, simultaneous or not, without the association of neurofibromatosis. We report a case of a 83-year-old woman with a clinical presentation of loss of right visual acuity. After imaging exams, she was diagnosed with three meningiomas, located in the olfactory groove, left temporal-parietal convexity and parasagittal. In addition, a comprehensive review of the literature on pathophysiology, histology, risk factors, clinical presentation, and treatment of multiple meningiomas was carried out, in order to highlight the peculiarities of this condition and to associate it with our reported case. Therefore, this article made it possible to compare the characteristics presented in this patient with general aspects of the conditions reported in the literature review.

Multiple meningiomas in different neuroaxial locations: report of a rare case

We report a rare case of multiple meningiomas in a 74 year old female who was brought to the hospital with spastic paraparesis and MRI of spine and brain revealed multiple enhancing meningiomas in brain and spines. The spinal intradural extramedullary (IDEM) meningioma at C7-D1 level was excised which had caused paraparesis and postoperatively patient became symptom free. We will discuss about the incidence, symptomatology, investigations and management of multiple meningiomas in different neuroaxial compartments at the same period of time and will review the literature.

PATH-40. SPORADIC NF2 WILD-TYPE MULTIPLE MENINGIOMAS HARBOR DISTINCT DRIVER MUTATIONS

OBJECTIVE Multiple meningiomas (MM) are rare and present a unique management challenge. While the mutational landscape of single meningiomas has been extensively studied, understanding the molecular pathogenesis of sporadic MM remains incomplete. The objective of this study is to elucidate the genetic features of sporadic MM. METHODS We identified nine patients with MM (n=19) defined as ≥2 spatially separated synchronous or metachronous meningiomas. We profiled genetic changes in these tumors using next-generation sequencing (NGS) assay that covers a large number of targetable and frequently mutated genes in meningiomas including AKT1, KLF4, NF2, PIK3CA/PIK3R1, POLR2A, SMARCB1, SMO, SUFU, TRAF7, and the TERT promoter. RESULTS Most of MM were WHO grade 1 (n= 16, 84.2%). Within individual patients, no driver mutation was shared between separate tumors. All but two cases harbored different hot spot mutations in known meningioma-driver genes like TRAF7 (n= 5), PIK3CA (n= 4), AKT1 (n= 3), POLR2A (n=1) and SMO (n= 1). Moreover, individual tumors differed in histologic subtype in 8/9 patients. The low frequency of NF2 mutations in our series stands in contrast to previous studies that included hereditary cases arising in the setting of neurofibromatosis type 2 (NF2). CONCLUSIONS Our findings provide evidence for genomic inter-tumor heterogeneity and an independent molecular origin of sporadic NF2 wild-type MM. Furthermore, these findings suggest that genetic characterization of each lesion is warranted in sporadic MM.

EPCO-29. GENOMIC PROFILING OF SPORADIC MULTIPLE MENINGIOMAS

INTRODUCTION In rare cases, sporadic meningiomas can occur as multiple tumors in the same patient without a known germline mutation. While the underlying mechanism that leads to the formation of these multiple lesions has been hypothesized to be monoclonal or independent, the genomic profiles to support these theories remain understudied. METHODS Patients with an absence of family history of meningioma and prior radiation history with multiple metachronous meningiomas were included. All tissue underwent whole exome sequencing and analysis of somatic single nucleotide variations (SNV), small insertion/deletion (INDEL) events together with copy number variations (CNV) was performed. The genomic findings were correlated with clinical data. RESULTS A cohort of 13 meningiomas and one dural specimen, from five individuals was studied. The majority (9/13 tumors) of tumors had NF2 mutation/Chr22 loss. Four out of 5 cases had a monoclonal origination, whereas one case displayed an independent clonal formation. The somatic profile of dura was unrevealing. In contrast to the current understanding, we found monoclonal formation of multiple meningiomas is not exclusive to NF2 driven cases, as non-NF2 mutated meningiomas can too display a monoclonal etiology. Moreover, multiple monoclonal-originating lesions did not always display a homogenous profile, but rather exhibited heterogeneity through branching evolution, where some lesions acquired genomic alterations associated with aggressive behavior. The histological characterization of multiple meningioma cases does not necessarily overlap with the genomic clustering. CONCLUSION To our knowledge, this is the first study to use unbiased comprehensive genomic methods to reveal the heterogeneity of multiple meningioma genomic profiles. Our extensive genomic characterization of this cohort revealed that monoclonal formation can be observed both in NF2 and non-NF2 mutant meningiomas and can introduce heterogeneity. Therefore, in order to understand the full scope of each individual’s disease, detailed genomic profiling of all lesions, when possible, should be performed.

NCOG-28. THE IMPACT OF MULTIPLE MENINGIOMAS ON PROGRESSION-FREE SURVIVAL: A 10-YEAR MULTI-CENTER STUDY

INTRODUCTION Multiple meningiomas (MM) occurs in up to 18% of meningioma patients and progression data are scarce. The objective of this study is to explore the influence of number of lesions and clinical characteristics on progression-free survival (PFS) and time to a second intervention (TTSI) in patients with WHO grade 1 meningiomas. METHODS We retrospectively reviewed records of all adults diagnosed with a meningioma at our three main sites from January 2009 to May 2020. Progression was considered as time from diagnosis until radiographic progression of the originally resected meningioma. A secondary analysis was carried to evaluate the time from diagnosis to time of a second intervention. Univariable and multivariable analyses were conducted to assess whether number of lesions or any associated variables (age, sex, race, radiation, location, and extent of resection) had a significant impact on PFS and TTSI. RESULTS 838 patients were included. Log-rank test evaluating PFS and TTSI between single and multiple lesions showed significantly shorter progression for MM (p< 0.001 and p< 0.001, respectively). Multivariable Cox regression showed significantly inferior PFS on MM vs. single lesion (HR 2.262 [CI 95%, 1.392-3.677], p=0.001) and a significantly inferior TTSI for patients with MM vs. single meningioma (HR 2.377 [CI 95%, 1.617 – 3.494], p=0.001). When input as a continuous variable, PFS was significantly inferior for each additional meningioma (HR 1.350 [CI 95% 1.074-1.698], p=0.010) and TTSI is significantly inferior as well (HR 1.428 [CI 95% 1.189 – 1.716], p< 0.001). African-Americans had an inferior PFS when compared to Non-Hispanic White patients (HR 3.472 [CI 95% 1.083-11.129], p=0.036). CONCLUSION The PFS of meningiomas is influenced by the number of lesions present. Patients with MM are more prone to undergo a second intervention for progressive disease. Hence, a closer follow-up may be warranted in patients who present with multiple lesions.

Regression of Multiple Meningiomas after Discontinuation of Chronic Hormone Therapy: A Case Report

Introduction Meningiomas are more common in females and frequently express progesterone and estrogen receptors. Recent studies have revealed a high incidence of meningiomas in situations in which estrogen/progesterone levels are increased such as pregnancy, gender reassignment therapy, and fertility treatment. While the relationship remains unclear and controversial, these findings suggest exposure to high levels of endogenous or exogenous hormones may increase the risk of developing a meningioma. Patients and Methods A 40-year-old female with a history of endometriosis treated with chronic progesterone therapy presented with a visual deficit and was found to have multiple meningiomas, which regressed after cessation of exogenous progesterone. Conclusion A history of chronic hormone therapy should be included when evaluating patients diagnosed with meningiomas, particularly at a younger age and with multiple meningiomas. Cessation of exogenous progesterone resulting in regression of meningiomas suggests a direct action of progesterone on growth. Future studies are warranted to better elucidate this relationship.

P04.14 Sporadic wild-type multiple meningiomas harbor distinct driver mutations

BACKGROUND Multiple meningiomas (MM) are rare and present a unique management challenge. While the mutational landscape of single meningiomas has been extensively studied, understanding of the molecular pathogenesis of sporadic MM remains incomplete. The objective of this study is to elucidate the genetic features of sporadic MM. MATERIAL AND METHODS We identified eight patients with MM (n=17) defined as ≥2 spatially separated synchronous or metachronous meningiomas. We profiled genetic changes in these tumors using a next generation sequencing (NGS) assay that covers a large number of targetable and frequently mutated genes in meningiomas including AKT1, KLF4, NF2, PIK3CA/PIK3R1, POLR2A, SMARCB1, SMO, SUFU, TRAF7, and the TERT promoter. RESULTS Most of MM were WHO grade 1 (n= 14, 82.3%). Within individual patients, no driver mutation was shared between separate tumors. All but two cases harbored different hot spot mutations in known meningioma-driver genes like TRAF7 (n= 5), PIK3CA (n= 3), AKT1 (n= 3) and SMO (n= 1). Moreover, individual tumors differed in histologic subtype in 7/8 patients. The low frequency of NF2 mutations in our series stands in contrast to previous studies that included hereditary cases arising in the setting of neurofibromatosis type 2 (NF2). CONCLUSION Our findings provide evidence for genomic inter-tumor heterogeneity and an independent molecular origin of sporadic NF2 wild-type MM. Furthermore, these findings suggest that genetic characterization of each lesion is warranted in sporadic MM.

Neurosarcoidosis resembling multiple meningiomas: A misleading presentation of the disease and diagnostic challenge

Sarcoidosis is characterized by the presence of noncaseating granulomatous inflammation in the affected organs. Neurosarcoidosis denotes the involvement of the nervous system and can be either isolated or coexisting with extraneural systemic inflammation. The diagnosis of isolated neurosarcoidosis may be challenging due to unspecific symptoms and similar appearances with other disease processes. This report presents an uncommon case of intracranial sarcoidosis mimicking multiple meningiomas. Familiarity with the spectrum of magnetic resonance imaging findings in neurosarcoidosis is crucial to prevent interpretive errors which may in turn lead to an inappropriate diagnosis and treatment.

Nomegestrol Acetate or Chlormadinone Acetate Progestative Treatment in Women: Meningioma Behavior at Treatment Discontinuation

Background: Associations between progestins and meningiomas is now well established. While the link between cyproterone acetate (CA) and meningioma was thoroughly studied, there is far less available data regarding the link between chlormadinone acetate (CHA) or nomegestrol acetate (NA) and risk of intracranial meningiomaMethods: We are presenting a series of 28 patients diagnosed with single or multiple meningiomas while treated with CHA-NA, in which the clinical and radiological course were analyzed after treatment discontinuation.Results: 28 women, with a mean age of 56 years old, were diagnosed with one or multiple meningioma while being treated with either CHA or NA. After stopping treatment, 89.3% showed either tumor shrinkage or tumor stabilization on follow-up MRIs. Multiple meningiomas were more likely observed in patients with long periods of treatment (>10 years, p 0.03) and seem to have a better clinical course (p 0.01). Most of the lesions were located on the skull base (55.4%). Four patients with multiple meningiomas showed discordant tumors evolution, with some tumors growing while others were decreasing. Most of the growing meningiomas were either convexity or midline lesions and more posteriorly located. Conclusion: Our study demonstrated a significant percentage of tumor diminution or stabilization after NA and CHA discontinuation. Therefore, treatment discontinuation with close monitoring should be the first measure taken if urgent surgery is not indicated. However, our results seem to be less encouraging than previously described in patients treated by CA, with more patients showing tumor growth despite treatment discontinuation. Further studies are needed to differentiate the effect of the different progestins treatment on meningiomas.