Optimizing DMG Diagnosis with Biopsy Techniques, Biomarker Testing, and Pathology Coordination

Funding support provided by Chimerix/Jazz Pharmaceuticals. Content independently developed and published by OncLive.

When handling diffuse midline gliomas, one of the foremost priorities is conserving biopsy tissue, as tumors in areas such as the midbrain, pons, and brainstem are particularly difficult to access. Because tissue samples are often very limited, diagnostic strategies must balance immediate needs with long-term value. While immunohistochemical stains can provide insight into histone mutations or loss of trimethylation, overreliance on such tests risks exhausting scarce material. Instead, comprehensive next-generation sequencing (NGS) panels, which can evaluate hundreds of genes including common drivers of diffuse midline gliomas, are considered the most reliable approach. Advances in liquid biopsy are also expanding options, as cerebrospinal fluid samples can now be sequenced to detect pathognomonic histone mutations, offering a less invasive alternative in some patients.

Community practices face unique challenges in managing these samples, particularly when access to advanced molecular testing is limited. Establishing partnerships with academic centers or external sequencing companies is strongly recommended, and these collaborations should be developed proactively rather than in reaction to a new case. The responsibility for initiating molecular testing often falls on the pathologist, though neuro-oncologists or neurosurgeons may occasionally take the lead. Critically, tissue must be preserved for sequencing, as running through immunohistochemical stains such as GFAP, P53, or KI67 can leave too little DNA for NGS, ultimately compromising diagnostic accuracy. Clear communication between community and referral centers helps ensure precious biopsy material is used appropriately.

Even when small amounts of tissue are available, technological advances now allow sequencing with very low DNA inputs, sometimes as little as 30–40 nanograms. While many academic institutions have in-house molecular testing, community groups that cannot send full tissue blocks can still contribute unstained slides suitable for sequencing. These innovations help overcome logistical barriers and reduce the likelihood of non-diagnostic results. By conserving tissue, coordinating effectively with pathology labs, and leveraging modern sequencing platforms, both academic and community settings can achieve more timely and accurate diagnoses for patients with diffuse midline gliomas.