Late post-treatment radiographic changes 3 years following chemoradiation for glioma: the importance of histopathology

Abstract

Treatment-related changes can mimic brain tumor progression both clinically and radiographically. Distinguishing these two entities represents a major challenge in neuro-oncology. No single imaging modality is capable of reliably achieving such distinction. While histopathology remains the gold standard, definitive pathological criteria are also lacking which can further complicate such cases. We report a patient with high-grade glioma who, after initially presenting with histopathologically confirmed pseudoprogression 10 months following treatment, re-presented 3 years following concurrent chemoradiation with clinical and radiographic changes that were most consistent with progressive disease but for which histopathology revealed treatment effects without active glioma. This case highlights the potential late onset of treatment-related changes and underscores the importance of histopathologic assessment even years following initial therapy.

Keywords: DWI; MRI; MRS; PET; brain cancer; diagnostic challenge; high-grade glioma; neuro-oncology; post-treatment changes; pseudoprogression; radiation necrosis; radiation therapy.

Figure 1.. Radiographic history of a patient with high-grade glioma, from diagnosis to confirmed late post-treatment changes.

MRI, FDG-PET and MRP imaging methods were utilized to assess patient's progression throughout time. (A) On diagnosis (month 0), increased hyperintensity in the left frontal lobe was seen, and histopathology diagnosed Grade III infiltrating astrocytoma with oligodendroglial features. (B) A total of 10 months following chemoradiation, surveillance MRI revealed increased contrast enhancement in the left frontal lobe, and craniotomy yielded a histopathologic evaluation consistent with prominent treatment effect and no active tumor cells. (C) Following second surgery, 19 months post-treatment, MRI continued to demonstrate an area of contrast enhancement around the intervention region, in the left frontal lobe, while 18-F-FDG PET showed decreased tracer uptake in the same location. (D) The radiographic improvement seen on month 38 indicates that the imaging changes from month 19 were probably treatment related. (E) In December 2014, 40 months after chemoradiation, MRI examination displayed increased contrast enhancement in the left frontal gyri associated with a markedly increased T2/FLAIR hyperintense signal and increased perfusion involving the same region, highly concerning for disease progression. However, histopathological examination was consistent with late post-treatment changes, showing no evidence of active tumor (Figure 2). (F) During the 7 months following the third craniotomy, imaging continued to progressively worsen until, 46 months post RT, MRI demonstrated an increase in the size of the contrast-enhancing area which, in term, was consistent with a hypermetabolic focus on 18-F-FDG PET. (G) By December 2015, the patient's neurologic exam had significantly improved, and neuroimaging showed a significant decrease in the size of the contrast-enhancing area on MRI, returning to baseline prior to his late decline in November 2014. FDG: Fluorodeoxyglucose; MRP: Magnetic resonance perfusion; RT: Radiotherapy.

Figure 2.. Histological features of treatment effect occurring 40 months post radiation.

In December 2014, 40 months after chemoradiation, although the results of MRI examination were again highly concerning for disease progression, histopathological investigation was consistent with post-treatment changes showing the presence of hyalinized vessels and a macrophage infiltrate in the absence of active tumor cells.