The consistency of neuropathological diagnoses in patients undergoing surgery for suspected recurrence of glioblastoma

J Neurooncol. 2019 Jan;141(2):347-354. doi: 10.1007/s11060-018-03037-3. Epub 2018 Nov 9.


Purpose: Clinical factors and neuro-imaging in patients with glioblastoma who appear to progress following standard chemoradiation are unable to reliably distinguish tumor progression from pseudo-progression. As a result, surgery is commonly recommended to establish a final diagnosis. However, studies evaluating the pathologists' agreement on pathologic diagnoses in this setting have not been previously evaluated.

Methods: A hypothetical clinical history coupled with images of histological sections from 13 patients with glioblastoma who underwent diagnostic surgery for suspected early recurrence were sent to 101 pathologists from 50 NCI-designated Cancer Centers. Pathologists were asked to provide a final diagnosis (active tumor, treatment effect, or unable to classify) and to report on percent active tumor, treatment effect, and degree of cellularity and degree of mitotic activity.

Results: Forty-eight pathologists (48%) from 30 centers responded. In three cases > 75% of pathologists diagnosed active tumor. In two cases > 75% diagnosed treatment effect. However, in the remaining eight cases the disparity in diagnoses was striking (maximum agreement on final diagnosis ranged from 36 to 68%). Overall, only marginal agreement was observed in the overall assessment of disease status [kappa score 0.228 (95% CI 0.22-0.24)].

Conclusions: Confidence in any clinical diagnostic assay requires that very similar results are obtained from identical specimens evaluated by sophisticated clinicians and institutions. The findings of this study illustrate that the diagnostic agreement between different cases of repeat resection for suspected recurrent glioblastoma can be variable. This raises concerns as pathological diagnoses are critical in directing standard and experimental care in this setting.

Keywords: Glioblastoma; Progression; Pseudo-progression; Radiation necrosis; Treatment effect.

MeSH terms

  • Brain Neoplasms / pathology*
  • Brain Neoplasms / surgery
  • Diagnosis, Differential
  • Disease Progression
  • Glioblastoma / pathology*
  • Glioblastoma / surgery
  • Humans
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Recurrence, Local / surgery
  • Observer Variation