Immunohistochemical Approach to the Differential Diagnosis of Meningiomas and Their Mimics

Abstract

The differential diagnosis between meningioma and others tumors can be challenging. This study aimed to evaluate different immunohistochemical markers for the differential diagnosis between meningioma and their morphological mimics. Immunohistochemistry was performed on tissue microarray with antiepithelial membrane antigen (EMA), progesterone receptor, somatostatin receptor 2A (SSTR2A), CD34, STAT6, S100, SOX10, HMB45, MelanA, GFAP, inhibin, and BCL2 antibodies. One hundred and twenty-seven meningiomas, 26 solitary fibrous tumor/hemangiopericytomas (SFT/HPC), 39 schwannomas, 17 hemangioblastomas, 21 melanomas, 9 gliosarcomas, 5 neurofibromas, 9 peripheral primitive neuroectodermal tumors, 7 synovial sarcomas, and 5 malignant peripheral nerve sheath tumors were included in the microarray. SSTR2A was the most sensitive (95.2%) and specific (92%) marker of meningiomas. In combination, SSTR2A and/or EMA positivity reached maximal sensitivity (100%). Coexpression of SSTR2A and EMA was the most specific (94.8%) for the diagnosis of meningioma, regardless of the grade or subtype, with the exception of the differential diagnosis with synovial sarcoma. All synovial sarcomas were EMA-positive and 6/7 SSTR2A-positive. STAT6 showed optimum sensitivity and specificity (100%) for SFT/HPC. SOX10 was the most sensitive (94.3%) and specific (100%) marker to discriminate meningiomas from schwannomas. In conclusion, SSTR2A, STAT6, and SOX10 were the most sensitive and specific markers to distinguish meningiomas from their morphological mimics.

In situ characterization of stem cells-like biomarkers in meningiomas

“…Surprisingly, and in contrast to other studies, more cells positive for GFAP or BIIIT were detected in grade II/III meningiomas [ 75 ]. A form of GFAP that differs in the C-terminal domain was detected in the subventricular zone (SVZ) of the brain, suggesting that GFAP may not be an exclusive astrocytic differentiation marker [ 56 , 57 ].…”

MUC4 expression in meningiomas: under‐recognized immunophenotype particularly in meningothelial and angiomatous subtypes

“…Epithelial membrane antigen, vimentin and PgR have been traditionally used for the diagnosis of meningioma, but these markers are not specific. Although SSTR2A has been demonstrated recently as a highly specific and reliable diagnostic marker for meningioma, its reported sensitivity is variable, ranging from 72.5% to 100%, and it may also be expressed in schwannomas, MPNSTs and perineuriomas . According to our present study, 92.9% of meningiomas expressed MUC4, at least focally, with meningothelial and angiomatous tumour subtypes expressing this marker most diffusely.…”

Recent Advances in Meningioma Immunogenetics

“…Indeed, increasing tumor grade is associated with increased expression of VEGF, Ki67, TOP2, PD-1, and PDGFRB (17,48,53), while hypermethylation of RIZ1 and WNK2 leads to loss of protein expression in high grade meningioma (6,41). In addition, the methylation status of several T-box and Hox genes may also predict poor outcomes independent of gene expression (42,44), thus bolstering the support for methylation profiling as a means to predict recurrence in meningioma (44).…”

“…Another recent investigation used regression modeling to generate a methylation profile-based algorithm that could accurately predict 5 year PFS rates (44). Detailed characterization revealed hypermethylation of CPG sites in homeobox or T-box genes in recurrence-prone tumors, although this was not associated with expression level changes.…”

“…Detailed characterization revealed hypermethylation of CPG sites in homeobox or T-box genes in recurrence-prone tumors, although this was not associated with expression level changes. This group went on to generate a meningioma recurrence score, based on the methylome-predictor, extent of resection, and WHO grade that can be used clinically to assess recurrence risk across patients as well as to inform choices for follow-up scheduling and administration of adjuvant therapy (44).…”