Diagnostic discrepancies in malignant astrocytoma due to limited small pathological tumor sample can be overcome by IDH1 testing.
The accurate grading of malignant astrocytomas has significant prognostic and therapeutic implications. Traditional histopathological grading can be challenging due to regional tumor heterogeneity, especially in scenarios where small amounts of tissue are available for pathologic review. Here, we hypothesized that a critical tumor resection volume is needed for correct grading of astrocytomas by histopathology. For insufficient tissue sampling, IDH1 molecular testing can act as a complementary marker to improve diagnostic accuracy. Volumetric analyses were obtained using preoperative and postoperative MRI images. Histological specimens were gathered from 403 patients with malignant astrocytoma who underwent craniotomy. IDH1 status was assessed by immunohistochemistry and sequencing. Patients with >20 cubic centimeters (cc) of the total tumor volume resected on MRI have higher rate of GBM diagnosis compared to <20 cc [odds ratio (OR) 2.57, 95% confidence interval (CI) 1.6-4.06, P < 0.0001]. The rate of IDH1 status remained constant regardless of the tumor volume resected (OR 0.81, 95% CI 0.48-1.36, P < 0.43). The rate of GBM diagnosis is twofold greater for individual surgical specimen >10 cc than those of lower volume (OR 2.48, 95% CI 1.88-3.28, P < 0.0001). Overall survival for AA patients with >20 cc tumor resection on MRI is significantly better than those with <20 cc tumor resected (P < 0.05). No volume-dependent differences were observed in patients with GBM (P < 0.4), IDH1 wild type (P < 0.1) or IDH1 mutation (P < 0.88). IDH1 status should be considered when total resection volume is <20 cc based on MRI analysis and for surgical specimen <10 cc to complement histopathologic diagnosis of malignant astrocytomas. In these specimens, under-diagnosis of GBM may occur when analysis is restricted to histopathology alone.
Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. kim.betty@mayo.edu.|Department of Neurosurgery, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL, 32224, USA. kim.betty@mayo.edu.
Betty Y S
BYS
Kim
Stanford School of Medicine, 291 Campus Dr., Stanford, CA, 94305, USA.
Wen
W
Jiang
Department of Neurosurgery, University of Manitoba, 727 McDermot Ave., Winnipeg, MB, R3E 3P5, Canada.
Jason
J
Beiko
Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Sujit S
SS
Prabhu
Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Franco
F
DeMonte
Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Mark R
MR
Gilbert
Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Raymond
R
Sawaya
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Kenneth D
KD
Aldape
Department of Neurosurgery, Massachusetts General Hospital, 55 Fruit St., Boston, MA, 02114, USA.
Daniel P
DP
Cahill
Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. imccutch@mdanderson.org.
Ian E
IE
McCutcheon
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D003399:Craniotomy; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading / Q000379:methods; D055815:Young Adult
D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human