gms | German Medical Science

K27M midline gliomas are defined by point mutations within the chromatin modifiers H.3, display a huge histological variability and are represented as a new entity in the new version of the WHO classification. They are associated with poor clinical outcome, but it is unclear, whether malignant tumor progression as observed for other types of diffuse gliomas contributes to disease progression. We investigated 14 patients with K27M glioma longitudinally (median age 21 years; WHO grades II-IV), either by MRI, O-(2-¹⁸F-fluoroethyl)-L-tyrosine PET (¹⁸F-FET-PET), and/or histology. H.3 K27M mutation was assessed by immunohistochemistry using mutation-specific antibodies on paraffin-embedded tumor material. Features considered as signs for malignant tumor progression were an increase (>20%) of maximal tumor-to-background ratio (TBR_max) in ¹⁸F-FET-PET as well as increased nuclear pleomorphism (np), cell density (cd), mitotic figures (mf), Ki67-index, vessel proliferation (vp), necrosis (nc), or nuclear accumulation of p53 (na p53). During the median follow-up of 36.3 months, 5 patients died (median survival 28.6 months). PET scans were acquired in 10/14 patients (8/10 with ≥2 scans). At first scan, TBR_max (mean 2.8; range 1.0-4.2) did neither correlate with the WHO grade nor predict patient’s outcome. However, TBR_max served as non-invasive marker of tumor aggressiveness during the course: TBR_max increased in 6/8 patients, 4 of them deceased shortly afterwards (median 3.7 months), 1 is currently in the hospice and 1 was lost to follow-up. The 2/8 patients without TBR_max progression are still alive. Nine patients had multiple surgeries, 8/9 patients displayed a progression in histology: increase in np (n=4), cd (n=7), vp (n=6), nc (n=5), mf (n=4), Ki67 (n=7) and/or na p53 (n=4). The 1 patient without histological progression did not show PET progression either and is still alive. K27M midline gliomas underlie malignant tumor progression that can be visualized by PET-imaging and histology. An increase of TBR_max and histological progression imply a change in tumor characteristics and indicate a poor prognosis with important implications for treatment regimens that may need to be adjusted in a relapse situation.