Non-Dipg Patients Enrolled In The International Dipg Registry: Histopathologic Evaluation Of Central Neuro-Imaging Review

Abstract INTRODUCTION The role of diagnostic biopsy in diffuse intrinsic pontine glioma (DIPG) remains in question. Distinguishing radiographically between DIPG and other pontine tumors with more favorable prognosis and different therapy is critically important. METHODS Cases submitted to the International DIPG registry with histopathologic data were analyzed. Central imaging review was performed on diagnostic brain MRI (if available) by two neuro-radiologists; all cases with imaging features or histopathology suggestive of alternative diagnoses were re-reviewed. Imaging features suggestive of alternative diagnoses included non-pontine origin, < 50% pontine involvement (without typical DIPG pattern on follow-up), focally exophytic morphology, sharply-defined margins, or marked diffusion restriction throughout. RESULTS Among 294 patients with pathology from biopsy and/or autopsy available, 27 (9%) had histologic diagnoses not consistent with DIPG, most commonly pilocytic astrocytomas (n=11) and embryonal tumors (n=9). Of these 294 patients with biopsy and/or autopsy pathologic data, 163 also had diagnostic MRI available for central neuroimaging review and radiographic comparison. Among 81 patients classified as characteristic of DIPG, 80 (99%) had histopathology consistent with DIPG (diffuse midline glioma, H3K27M-mutant, glioblastoma, anaplastic astrocytoma, diffuse astrocytoma). Among 63 patients classified as likely DIPG, but with unusual imaging features, 59 (94%) had histopathology consistent with DIPG. Nineteen patients had imaging features suggestive of another diagnosis, including 13 with non-pontine tumor origin; the remaining 6 patients all had histopathology not consistent with DIPG (embryonal tumors [n=3, including 1 with medulloblastoma], pilocytic astrocytoma [n=1], and ganglioglioma [n=1]). Association between central imaging review and histopathology was significant (p < 0.001 by the Freeman-Halton Fischer Exact Probability Test). CONCLUSIONS The important role and accuracy of central neuroimaging review in diagnosing or excluding DIPG is demonstrated. In patients with pontine tumors for which DIPG is felt unlikely radiographically, biopsy may be considered to guide diagnosis, prognosis, and treatment.