Dahiya, Sonika

Abstract Adult primary leptomeningeal gliomatosis (PLG) is a rare, rapidly progressive and fatal disease characterized by prominent leptomeningeal infiltration by a glial tumor without an identifiable parenchymal mass. The molecular profile of adult PLG has not been well‐characterized. We report the clinical, pathological, and molecular findings of six adult PLG patients (five males and one female), median age 58 years. All cases exhibited pathological leptomeningeal enhancement at presentation. Leptomeningeal biopsy was diagnostic in five (of six) cases, revealing infiltration by an astrocytic glioma with mitotic activity, lacking microvascular proliferation or necrosis. One case was diagnosed at autopsy. All tumors were IDH‐wildtype, with five harboring TERT promoter mutations. Additional mutations identified were PTEN in one case, TP53 in two cases, and NF1 in two cases. A chromosome profile with +7/−10 was found in four cases, whereas the remaining two showed either chromosome 7 or 7p gain only. Four cases showed chromosome 9p loss with CDKN2A/B homozygous deletion, one case showed hemizygous CDKN2A/B loss, and one case showed intact chromosome 9 and CDK4/GLI1 amplification. DNA methylation profiling was performed in four cases and revealed a match to glioblastoma (GBM) family and mesenchymal typical class with high confidence scores in two cases; the other two cases showed only suggestive combined scores for GBM family and mesenchymal atypical class. The molecular profile of all cases closely aligned with that of adult‐type GBM, IDH‐wildtype, CNS WHO grade 4. All patients succumbed to the disease. In five cases with extensive leptomeningeal disease at diagnosis, the course was rapid, with median survival of 24 days following palliative care. Only one case, with relatively localized disease at diagnosis, received chemoradiation therapy and survived 535 days, raising the possibility that early diagnosis and timely treatment could improve outcome. A detailed list of previously reported cases is provided in a supplementary table.

Abstract Meningiomas are the most frequent primary intracranial tumors. Hence, they constitute a major share of diagnostic specimens in neuropathology practice. The 2021 WHO Classification of Central Nervous System Tumors (“CNS5”) has introduced the first molecular grading parameters for meningioma with oncogenic variants in the TERT promoter and homozygous deletion of CDKN2A/B as markers for CNS WHO grade 3. However, after the publication of the new classification volume, clarifications were requested, not only on novel but also on long-standing questions in meningioma grading that were beyond the scope of the WHO “blue book.” In addition, more recent research into possible new molecular grading parameters could not yet be implemented in the 2021 classification but constitutes a compelling body of literature. Hence, the consortium to inform molecular and practical approaches to CNS tumor taxonomy-not official WHO (cIMPACT-NOW) Steering Committee convened a working group to provide such clarification and assess the evidence of possible novel molecular criteria. As a result, this cIMPACT-NOW update provides guidance for more standardized morphological evaluation and interpretation, most prominently pertaining to brain invasion, identifies scenarios in which advanced molecular testing is recommended, proposes to assign CNS WHO grade 2 for cases with CNS WHO grade 1 morphology but chromosomal arm 1p deletion in combination with 22q deletion and/or NF2 oncogenic variants, and discusses areas in which the current evidence is not yet sufficient to result in new recommendations.

Abstract Anaplastic meningiomas can have a sarcomatous appearance on histology but true sarcomatous (metaplastic) differentiation is rare. These tumors follow an aggressive clinical course with recurrence and poor clinical outcomes. Due to significant overlap in morphology and immunohistochemical profiles, distinguishing between sarcomatous transformation of a meningioma and a true sarcoma can be challenging. Here, we outline potential diagnostic pitfalls and the utility of ancillary molecular testing in 3 patients diagnosed with sarcomatous meningiomas. We report loss of typical meningothelial markers in sarcomatous meningiomas. Ancillary molecular testing can support the diagnosis of sarcomatous meningioma when a molecular signature consistent with meningioma is seen, such as inactivation of the NF2 gene. Recognition of this rare transformation in meningioma can prevent a misdiagnosis of a primary sarcoma, whether sporadic or radiation-induced from prior treatment of a more classic meningioma.