Leading neuropathology expert Dr. Sebastian Brandner, MD, explains how advanced genetic testing detects early-stage glioblastoma when traditional pathology appears benign, enabling earlier aggressive treatment for better brain cancer outcomes through precise molecular diagnosis.
Mais de Diagnostic Detectives Network
Early Detection of Glioblastoma Through Molecular Genetic Testing
Jump To Section
- Case Presentation: When Benign Appearance Hides Malignancy
- Molecular Diagnosis Reveals Hidden Glioblastoma
- The Concept of "Early GBM" in Brain Tumor Evolution
- Advantages of Genetic Testing Over Traditional Pathology
- Critical Treatment Implications of Precise Diagnosis
- The Future of Integrated Brain Tumor Diagnosis
- Full Transcript
Case Presentation: When Benign Appearance Hides Malignancy
A 55-year-old male patient presented with weeks of seizures, leading to brain tumor biopsy at a referring hospital. Dr. Sebastian Brandner, MD, describes how initial pathology suggested a benign glioma, yet lacked key benign markers like IDH mutation and 1p/19q chromosomal co-deletion - creating diagnostic uncertainty that prompted advanced genetic testing.
Molecular Diagnosis Reveals Hidden Glioblastoma
Gene array testing performed by Dr. Brandner's team identified the tumor as glioblastoma multiforme (GBM) despite its benign microscopic appearance. This case demonstrates how molecular profiling detects malignancy 6-12 months before traditional pathology would show classic GBM features, allowing earlier intervention.
The Concept of "Early GBM" in Brain Tumor Evolution
Dr. Sebastian Brandner, MD, explains these transitional tumors as "early GBMs" or "glioblastomas in the making" - tumors already possessing GBM's molecular signature while still displaying benign histology. Some colleagues term them IDH wild-type astrocytomas, but Dr. Sebastian Brandner, MD, emphasizes the progressive nature captured by "early GBM" terminology.
Advantages of Genetic Testing Over Traditional Pathology
Modern neuroimaging catches brain tumors earlier in their evolution, creating diagnostic challenges when pathology and clinical presentation don't align. Dr. Sebastian Brandner, MD, highlights how molecular diagnostics provide objective data when:
- MRI shows suspicious enhancement patterns
- Seizures occur in middle-aged patients without other causes
- Microscopic appearance contradicts clinical progression
Critical Treatment Implications of Precise Diagnosis
Accurate early GBM identification transforms treatment decisions, as Dr. Sebastian Brandner, MD, explains. Molecular diagnosis guides:
- Aggressiveness of surgical resection
- Timing of adjuvant chemotherapy and radiotherapy
- Prognostic discussions with patients
- Clinical trial eligibility for novel therapies
The Future of Integrated Brain Tumor Diagnosis
While automated analysis advances, Dr. Sebastian Brandner, MD, emphasizes pathologists' irreplaceable role in integrating molecular data with clinical context and microscopic findings. This case exemplifies how combining traditional pathology expertise with cutting-edge genetic testing creates optimal diagnostic precision for improved glioblastoma outcomes.
Full Transcript
Dr. Sebastian Brandner, MD: This was a special clinical brain tumor case that was referred to us from another hospital. They operated on a 55-year-old gentleman who had a few weeks of history of seizures. The neurosurgeon went straight into the brain tumor biopsy.
The pathologists at the referring hospital saw a benign tumor under the microscope, but that didn't really fit the clinical situation. All the markers of benign brain glioma were not present there. These markers are IDH mutation and 1p/19q chromosomal co-deletion.
Dr. Anton Titov, MD: What could that brain tumor be?
Dr. Sebastian Brandner, MD: So they sent it to us. "Prof. Brandner, could you help us with the gene array to diagnose this brain tumor?" We did exactly that. The gene array diagnostic brain tumor test came back with the diagnosis of glioblastoma.
Dr. Anton Titov, MD: How does that fit? Because the tumor looks benign.
Dr. Sebastian Brandner, MD: But we know that glioblastoma is a malignant tumor. There we need to think back on the biology of brain tumors. It is increasingly clear that glioblastomas do not just come out of the blue as a fully malignant tumor.
Now that we have all these advanced brain scanning technologies, patients come and get early diagnosis. They have a seizure, patients go to the general physician. The GP thinks that seizure in a 55-year-old otherwise healthy person could be a brain tumor.
Dr. Sebastian Brandner, MD: The general practitioner sends a patient to an MRI. MRI shows a brain tumor with enhancement. It could be even a diffusely infiltrating brain tumor.
It is increasingly understood that these are "early GBMs" [glioblastoma multiforme]. I call them "early GBMs". Other pathologists call them "IDH wild-type astrocytomas". I prefer the term "early GBM (glioblastoma multiforme)" because that reflects that this brain tumor is a growing GBM. It is GBM in the making. The term signifies evolution of brain tumor.
Yes! So the molecular profile of the brain tumor already has a profile of glioblastoma, but the pathology is that of a more benign tumor. We would wait another half-year, then this brain tumor would histologically show the hallmarks of a malignant glioma.
Dr. Sebastian Brandner, MD: This is why these molecular diagnostics can help us so tremendously. This is why I think this is the future. It's also very reassuring that pathologists use the latest brain tumor diagnostic technology.
Dr. Anton Titov, MD: Many colleagues ask: "With all this automated algorithmic diagnosis, will we all be made redundant?"
Dr. Sebastian Brandner, MD: My answer is "No". You still need to put these findings in clinical and pathologic context. No bioinformatician can tell a neurosurgeon how this tumor looks under the microscope, how to read and put those things together.
The integrated brain tumor diagnosis will become a very important feature. It is a very important element of the glioma clinical treatment. We develop new diagnostic technologies for brain tumors. We keep track with all the developments. It is better for the patient, but it is also better for the development and future of pathology.
Dr. Sebastian Brandner, MD: The new glioblastoma case that you described is also very important. It is interaction between the patient and physician. Because new brain cancer diagnosis is a difficult situation - a newly diagnosed brain tumor.
Dr. Anton Titov, MD: Physician and neurosurgeon cannot rely only on their clinical experience to develop and discuss the treatment strategy. How aggressively to treat malignant brain tumor, whether to use adjuvant chemotherapy, radiotherapy, how to estimate prognosis.
Dr. Sebastian Brandner, MD: But they can rely on quantitative data that you can provide to establish very precise diagnosis of brain tumor. Yes. A 55-year-old man had seizures. He was found to have a small brain tumor. It looked benign under the microscope, but its molecular genetic profile on gene expression array suggested aggressive glioblastoma multiforme (GBM). It was "early GBM" or glioblastoma-in-the-making.