Grading of meningeal solitary fibrous tumors/hemangiopericytomas: analysis of the prognostic value of the Marseille Grading System in a cohort of 132 patients

Abstract

The finding that meningeal solitary fibrous tumors (SFTs) and meningeal hemangiopericytomas (HPCs) are both characterized by NAB2-STAT6 gene fusion has pushed their inclusion in the WHO 2016 Classification of tumors of the central nervous system (CNS) as different manifestations of the same entity. Given that the clinical behavior of the CNS SFT/HPC spectrum ranges from benign to malignant, it is presently unclear whether the grading criteria are still adequate. Here, we present the results of a study that analyzed the prognostic value of an updated version of the Marseille Grading System (MGS) in a retrospectively assembled cohort of 132 primary meningeal SFTs/HPCs with nuclear overexpression of STAT6. The median patient follow-up was 64 months (range 4-274 months); 73 cases (55%) were MGS I, 50 cases (38%) MGS II and 9 cases (7%) were MGS III. Progression-free survival (PFS) and disease-specific survival (DSS) were investigated using univariate analysis: the prognostic factors for PFS included MGS, extent of surgery, radiotherapy, chemotherapy and mitotic activity ≥5/10 high-power field (HPF). Moreover, MGS, radiotherapy, mitotic activity ≥5/10 HPF, and necrosis were the prognostic factors measured for DSS. In multivariate analysis, extent of surgery, mitotic activity ≥5/10 HPF, MGS I and MGS III were the independent prognostic factors measured for PFS while necrosis, MGS III and radiotherapy were the independent prognostic factors for DSS. In conclusion, our results show that assessing the malignancy risk of SFT/HPC should not rely on one single criterion like mitotic activity. Therefore, MGS is useful as it combines the value of different criteria. In particular, the combination of a high mitotic activity and necrosis (MGS III) indicates a particularly poor prognosis.

The impact of histopathology and NAB2–STAT6 fusion subtype in classification and grading of meningeal solitary fibrous tumor/hemangiopericytoma

“…Furthermore, incorporating necrosis into ST-G, i.e., classifying tumors based on mitotic rate and necrosis, seems to improve the outcome models when compared to mitotic rate alone. In their recent work from 2018, Macagno et al sought to validate an updated version of the Marseille Grading Scheme which segregated 132 tumors into three groups based on mitotic activity (≥ 5 mitotic figures/10 HPF) and necrosis [4, 15]. On univariate analysis, they found that extent of surgery, radiotherapy/chemotherapy, and mitotic rate were significant in predicting RFS, while radiation, mitotic rate, and necrosis were significant for disease-specific survival [15].…”

“…In their recent work from 2018, Macagno et al sought to validate an updated version of the Marseille Grading Scheme which segregated 132 tumors into three groups based on mitotic activity (≥ 5 mitotic figures/10 HPF) and necrosis [4, 15]. On univariate analysis, they found that extent of surgery, radiotherapy/chemotherapy, and mitotic rate were significant in predicting RFS, while radiation, mitotic rate, and necrosis were significant for disease-specific survival [15]. Extent of surgery and mitotic rate remained significant prognostic factors for RFS with multivariate analysis, while necrosis and radiotherapy were significant for disease-specific survival [15].…”

Solitary fibrous tumor of central nervous system masquerading as meninigioma: Report of a rare case

“…Michele et al advocated inclusion of high Ki-67 (i.e. > 5%) as an adverse prognostic parameter in assessing the prognosis of SFT of the CNS [ 11 , 12 ].…”

Prognostic significance of NAB2–STAT6 fusion variants and TERT promotor mutations in solitary fibrous tumors/hemangiopericytomas of the CNS: not (yet) clear

“…Grading of meningeal solitary fibrous tumors/hemangiopericytomas (SFTs/HPCs) of the central nervous system (CNS) is nowadays based on histologic criteria as described in the revised fourth edition of the WHO Classification of CNS tumors [10] or the more recently published, updated version of the Marseille Grading System (MGS) [11]. Histology based grading of CNS SFTs/HPCs allows for discriminating subgroups with significant differences in prognosis.…”

“…To evaluate the prognostic value of NAB2-STAT6 fusion variants and TERT promoter mutations for CNS SFTs/HPCs, we retrospectively analyzed these markers in a cohort of136 patients with STAT6 nucleopositive CNS tumors. All tumors were graded according to the most recent WHO classification [10] and the updated MGS [11] and were analyzed for type of NAB2-STAT6 fusion and the presence of TERT promoter mutation. For NAB2-STAT6 fusion analysis, we performed reverse transcriptase polymerase chain reaction (RT-PCR) after RNA extraction and cDNA synthesis using multiple primer sets finding the most common fusion variants which were subsequently grouped based on their hypothesized functional effects [3,15].…”