Advances in diffuse glial tumors diagnosis

Abstract

In recent decades, there have been significant advances in the diagnosis of diffuse gliomas, driven by the integration of novel technologies. These advancements have deepened our understanding of tumor oncogenesis, enabling a more refined stratification of the biological behavior of these neoplasms. This progress culminated in the fifth edition of the WHO classification of central nervous system (CNS) tumors in 2021. This comprehensive review article aims to elucidate these advances within a multidisciplinary framework, contextualized within the backdrop of the new classification. This article will explore morphologic pathology and molecular/genetics techniques (immunohistochemistry, genetic sequencing, and methylation profiling), which are pivotal in diagnosis, besides the correlation of structural neuroimaging radiophenotypes to pathology and genetics. It briefly reviews the usefulness of tractography and functional neuroimaging in surgical planning. Additionally, the article addresses the value of other functional imaging techniques such as perfusion MRI, spectroscopy, and nuclear medicine in distinguishing tumor progression from treatment-related changes. Furthermore, it discusses the advantages of evolving diagnostic techniques in classifying these tumors, as well as their limitations in terms of availability and utilization. Moreover, the expanding domains of data processing, artificial intelligence, radiomics, and radiogenomics hold great promise and may soon exert a substantial influence on glioma diagnosis. These innovative technologies have the potential to revolutionize our approach to these tumors. Ultimately, this review underscores the fundamental importance of multidisciplinary collaboration in employing recent diagnostic advancements, thereby hoping to translate them into improved quality of life and extended survival for glioma patients.

Figure 1

Two examples of different glial neoplasms defined by molecular findings. The first case ( A-C ) is a hemispheric tumor from a 43-year-old male patient. The cells have typical astrocytic morphology ( A ), with immunohistochemistry positive for IDH1 R132H ( B ) and ATRX loss ( C ). These findings are consistent with astrocytoma, The second case ( D-F ) is a pontine tumor in a 8-year-old patient. Although morphology is also astrocytic ( D ), the loss of H3K27me3 expression ( E ) and positivity for H3K27M mutation ( F ) rendered this patient a “diffuse midline glioma, H3 K27-altered” diagnosis.

Figure 2

Low-grade adult-type gliomas. Astrocytoma, IDH-mutant in a 29-year-old woman ( A , B and C ). Axial T2( A ) shows a relatively homogenous hyperintense lesion on the right middle frontal gyrus. Axial FLAIR ( B ) shows a heterogeneous low signal intensity, except for a peripheral rim (arrows) of preserved hyperintensity (T2-FLAIR “mismatch” sign). Axial T1 post-gadolinium ( C ) shows no enhancement. Oligodendroglioma, IDH-mutant, 1p/19q co-deleted in a 58-year woman ( D , E , F and G ). Axial T2 ( D ) demonstrates a heterogeneous hyperintense lesion in the right frontal lobe, with indistinct margins and the sinuous wave-like intratumoral-wall sign, representing cortical thickening (arrows and dashed line) around a T2 heterogeneously hyperintense core. Axial FLAIR ( E ) demonstrates no significant signal suppression except for a small cyst (arrow). Axial T1 post-gadolinium ( F ) shows no significant lesion enhancement. Axial CT ( G ) shows a linear calcification within the lesion (arrow).

Figure 3

High-grade adult-type glioma. Common GBM presentation in a 52-year-old male ( A and B ). Axial FLAIR ( A ) shows a heterogeneous lesion involving the right parietal and occipital transition, with surrounding edema. Axial T1 post-gadolinium( B ) demonstrates thick, irregularly shaped enhancement with central necrosis. Uncommon GBM presentation in a 66-year-old female ( C , D , and E ). Axial FLAIR ( C ) shows an infiltrative lesion involving the right temporal lobe (arrows). Axial T1 post-gadolinium ( D ) shows no enhancement in the lesion (arrows). Axial DWI ( E ) demonstrates an area of restricted diffusion delineating the cortex (arrow). This patient presented with seizures and was initially treated for herpes encephalitis, but subsequent progression and pathology (not shown) confirmed a GBM. Grade 4 astrocytoma, IDH-mutant in a 34-year-old female ( F and G ). Axial T1 post-gadolinium ( F ) shows a left parietal lesion with contrast enhancement and necrosis (arrow), with a significant non-enhancing component (arrowheads). In the nonenhancing part of the lesion, FLAIR signal suppression is consistent with IDH mutation.

Figure 4

Pediatric type tumors. High grade. DMG in a 3-year-old boy ( A and B ). Axial T2 ( A ) shows an infiltrative lesion centered on ventral pons, extending anteriorly to “embrace” the basilar artery (arrow). Axial T1 post-gadolinium ( B ) shows ring enhancement at the right anterior portion of the tumor (arrow). Low Grade. Angiocentric glioma in a 17-year-old boy ( C and D ). Axial FLAIR ( C ) demonstrates a hyperintense lesion with cysts (arrow) on the left middle frontal and pre-central gyrus. Axial T1( D ) without gadolinium shows typical linear cortical hyperintensity (arrow). PLNTY in a 18-year-old girl ( E and F ). Axial CT ( E ) demonstrates a massively calcified lesion in the left occipital and temporal lobe transition (arrow). Axial T1 post-gadolinium ( F ) shows partial ring-like enhancement (arrow).

Figure 5

Neuroplasticity over 13 years. Axial T2 ( A ) shows an IDH-mutant astrocytoma in the right primary motor cortex (arrow). Axial FLAIR fused with fMRI ( B ) with left motor hand task shows BOLD signal in the expected location at the right pre-central gyrus, near the posterior and medial tumoral margin (arrow). Axial T2 ( C ) performed five months after near total resection demonstrated only slight hyperintensity at the medial border of the surgical cavity (arrows). Axial T2 ( D ), 13 years later, shows a progression of the astrocytoma, now infiltrating medially the pre-central gyrus, toward the hand motor knob area (arrow). At this time, fMRI ( E ) with left-hand motor activity shows little BOLD signal in the right pre-central gyrus (arrowhead) but a more extensive BOLD signal in left motor areas (arrow), indicating the recruitment of ipsilateral motor cortex due to neuroplasticity.