Necrosis is a consistent factor to recurrence of meningiomas: should it be a stand-alone grading criterion for grade II meningioma?


The purpose of this study was to evaluate spontaneous necrosis as a possible isolated factor for progression and recurrence in grade I meningiomas classified according to the current World Health Organization (WHO) classification. Meningiomas are the most frequently reported primary intracranial tumours, accounting for more than 35%. The 2016 WHO classification of central nervous system tumors stratifies meningiomas in grades I (benign), II (atypical), and III (malignant), according to histopathological aspects and the risk of progression or recurrence. Among 110 patients with intracranial meningiomas, 70 were WHO grade I meningiomas with no findings of atypia (G1WON), 15 were WHO grade I with necrosis (G1WN), 21 were WHO grade II (G2), and 4 were WHO grade III (G3). The mean follow-up was 5.9 ± 0.2 years. High performance scale (KPS ≥ 80) was different (p < 0.001) between WHO grade I meningiomas without (81.4%) and with (60%) necrosis. The 5-year mortality rate was 1.4, 6.7 and 5.9% for G1WON, G1WN and G2, respectively, with significant difference (p = 0.011) related to the presence of necrosis. The risk of recurrence was 3.7 times higher in G1WN than in G1WON (p = 0.017), and 4.2 times in G2 (p = 0.010). Progression-free survival (PFS) was clearly higher in patients with G1WON compared to G1WN and G2 (p = 0.002 and p < 0.001, respectively). There was no significant difference in PFS between G1WN and G2 (p = 0.692). Retreatment was also superior in meningioma with necrosis. Our findings provide clear statistical data to consider that patients with benign meningiomas and histologic findings of spontaneous necrosis are at increased risk of progression and recurrence compared to those with benign lesion without atypical features. Statistical analysis curves also suggest that these lesions behave more similarly to those currently classified as WHO grade II meningioma.

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  1. 1.

    Ostrom QT, Gittleman H, Fulop J et al (2015) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro Oncol 17(Suppl 4):iv1–iv62

    Article  Google Scholar 

  2. 2.

    Louis DN, Perry A, Reifenberger G et al (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820

    Article  Google Scholar 

  3. 3.

    Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO Classification of Tumours of the Central Nervous System. Acta Neuropathol 114(2):97–109.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Perry A, Stafford SL, Scheithauer BW, Suman VJ, Lohse CM (1997) Meningioma grading: an analysis of histologic parameters. Am J Surg Pathol 21:1455–1465

    CAS  Article  Google Scholar 

  5. 5.

    Backer-Grøndahl T, Moen BH, Torp SH (2012) The histopathological spectrum of human meningiomas. Int J Clin Exp Pathol 5(3):231–242

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Jaaskelainen J, Haltia M, Laasonen E, Wahlstrom T, Valtonen S (1985) The growth rate of intracranial meningiomas and its relation to histology. Surg Neurol 24:165–172

    CAS  Article  Google Scholar 

  7. 7.

    Chen WYK, Liu HC (1990) Atypical (anaplastic) meningiorna: relationship between histological features and recurrence-clinicopathological study. Clin Neuropathol 9:74–81

    CAS  PubMed  Google Scholar 

  8. 8.

    Christensen D, Laursen H, Klinken L (1983) Prediction of recurrence in meningiomas after surgical treatment. Acta Neuropathol 63:130–134

    Article  Google Scholar 

  9. 9.

    McLean CA, Jolley D, Cukier E, Giles G, Gonzales MF (1993) Atypical and malignant meningiomas: importance of micronecrosis as a prognostic indicator. Histopathology 23:349–353

    CAS  Article  Google Scholar 

  10. 10.

    Ironside JW, Moss TH, Louis DN, Lowe JS, Weller RO (2002) Meningiomas. In: Ironside JW, Moss TH, Louis DN, Lowe JS, Weller RO (eds) Diagnostic pathology of nervous system tumours. Churchill Livingstone, Edinburgh, pp 344–382

    Google Scholar 

  11. 11.

    Ho DM, Hsu CY, Ting LT, Chiang H (2002) Histopathology and MIB-1 labeling index predicted recurrence of meningiomas: a proposal of diagnostic criteria for patients with atypical meningioma. Cancer 94:1538–1547

    Article  Google Scholar 

  12. 12.

    Ng HK, Poon WS, Goh K, Chan MS (1996) Histopathology of post-embolized meningiomas. Am J Surg Pathol 20:1224–1230

    CAS  Article  Google Scholar 

  13. 13.

    Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    CAS  Article  Google Scholar 

  14. 14.

    Edwards JG, Swinson DE, Jones JL, Muller S, Waller DA, O’Byrne KJ (2003) Tumor necrosis correlates with angiogenesis and is a predictor of poor prognosis in malignant mesothelioma. Chest 124:1916–1923

    Article  Google Scholar 

  15. 15.

    Fisher ER, Anderson S, Redmond C, Fisher B (1993) Pathologic findings from the national surgical adjuvant breast project protocol B-06. 10-year pathologic and clinical prognostic discriminants. Cancer 71:2507–2514

    CAS  Article  Google Scholar 

  16. 16.

    Lam JS, Shvarts O, Said JW, Pantuck AJ, Seligson DB, Aldridge ME, Bui MH, Liu X, Horvath S, Figlin RA, Belldegrun AS (2005) Clinicopathologic and molecular correlations of necrosis in the primary tumor of patients with renal cell carcinoma. Cancer 103:2517–2525

    CAS  Article  Google Scholar 

  17. 17.

    Swinson DE, Jones JL, Richardson D, Cox G, Edwards JG, O’Byrne KJ (2002) Tumour necrosis is an independent prognostic marker in non-small cell lung cancer: correlation with biological variables. Lung Cancer 37:235–240

    Article  Google Scholar 

  18. 18.

    Stefansson IM, Salvesen HB, Akslen LA (2006) Vascular proliferation is important for clinical progress of endometrial cancer. Cancer Res 66:3303–3309

    CAS  Article  Google Scholar 

  19. 19.

    Helczynska K, Kronblad A, Jogi A, Nilsson E, Beckman S, Landberg G, Pahlman S (2003) Hypoxia promotes a dedifferentiated phenotype in ductal breast carcinoma in situ. Cancer Res 63:1441–1444

    CAS  PubMed  Google Scholar 

  20. 20.

    Vakkila J, Lotze MT (2004) Inflammation and necrosis promote tumour growth. Nat Rev Immunol 4:641–648

    CAS  Article  Google Scholar 

  21. 21.

    Sadri N, Zhang PJ (2013) Hypoxia-inducible factors: mediators of cancer progression; prognostic and therapeutic targets in soft tissue sarcomas. Cancers 5:320–333

    CAS  Article  Google Scholar 

  22. 22.

    Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140:883–899

    CAS  Article  Google Scholar 

  23. 23.

    Hockel M, Vaupel P (2001) Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 93:266–276

    CAS  Article  Google Scholar 

  24. 24.

    Sun SQ, Cai C, Murphy RK et al (2014) Management of atypical cranial meningiomas, part 2: predictors of progression and the role of adjuvant radiation after subtotal resection. Neurosurgery 75:356–363

    Article  Google Scholar 

  25. 25.

    Bredholt G, Mannelqvist M, Stefansson IM et al (2015) Tumor necrosis is an important hallmark of aggressive endometrial cancer and associates with hypoxia, angiogenesis and inflammation responses. Oncotarget 6(37):39676–39691

    Article  Google Scholar 

  26. 26.

    Koong AC, Chen EY, Giaccia AJ (1994) Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues. Cancer Res 54:1425–1430

    CAS  PubMed  Google Scholar 

  27. 27.

    Marciscano AR, Stemmer-rachamimov O, Niemierko A, Larvie M, Curry WT, Barker FG, Martuza RL, Mcguone D, Oh KS, Loeffler JS, Shih H (2016) Benign meningiomas (WHO Grade I) with atypical histological features: correlation of histopathological features with clinical outcomes. J Neurosurg 124:106–114

    Article  Google Scholar 

  28. 28.

    Jellinger K (1988) Histopathological features predicting recurrence of meningiomas after (sub)total resection. Clin Neuropathol 7:174

    Google Scholar 

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Correspondence to Pedro Góes.

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Góes, P., Santos, B.F.O., Suzuki, F.S. et al. Necrosis is a consistent factor to recurrence of meningiomas: should it be a stand-alone grading criterion for grade II meningioma?. J Neurooncol 137, 331–336 (2018).

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  • Meningioma
  • Necrosis
  • Atypical
  • Progression