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Progestin-related WHO grade II meningiomas behavior—a single-institution comparative case series

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Abstract

WHO grade II progestin-related meningiomas have been reported in recent series but we found no previous study describing their long-term outcome. Our study aimed to evaluate patients operated on for high-grade intracranial meningioma and who underwent long-term exposure to high dose of cyproterone acetate, nomegestrol acetate, and chlormadinone acetate. Our study retrospectively included 9 patients with high-grade progestin-related intracranial meningioma between December 2006 and September 2021. In each patient, clinico-radiological follow-up was performed every 6 months after diagnosis and treatment withdrawal recommendation. The mean progestative exposure was 11.4 years. Edema existence or absence of cleft sign on MRI were the key factors for surgical indication. All patients underwent surgery. Adjuvant radiotherapy was indicated in 1 patient, and Gamma Knife radiosurgery was proposed in 2 other patients for a second location of meningioma. Six patients harbored a grade II chordoid meningioma subtype with 100% PR expression and 3 patients a grade II atypical meningioma subtype with lower PR expression. The mean follow-up was 8.1 years and none of the 9 patients presented with a recurrence. Patients with grade II progestin-related meningiomas have less tumor recurrence after surgery than patients with sporadic grade II meningiomas, especially after progestin withdrawal. The presence/appearance of peri-meningioma edema and the absence of cleft sign before volumetric change should suggest the existence of an underlying WHO grade II meningiomas. In these cases, surgical resection may immediately be considered and adjuvant radiotherapy should be reserved for proven recurrence cases.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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References

  1. AbiJaoude S, Marijon P, Roblot P, Tran S, Cornu P, Kalamarides M, Peyre M (2021) Sustained growth of intraosseous hormone-associated meningiomas after cessation of progestin therapy. Acta Neurochir (Wien). https://doi.org/10.1007/s00701-021-04781-8

    Article  Google Scholar 

  2. Aboukais R, Baroncini M, Zairi F, Reyns N, Lejeune JP (2013) Early postoperative radiotherapy improves progression free survival in patients with grade 2 meningioma. Acta Neurochir (Wien) 155:1385–1390; discussion 1390. https://doi.org/10.1007/s00701-013-1775-0

  3. Aboukais R, Zairi F, Le Rhun E, Lejeune JP, Devos P, Reyns N (2015) Radiation-associated grade 2 meningiomas: a nine patient-series and review of the literature. Clin Neurol Neurosurg 136:10–14. https://doi.org/10.1016/j.clineuro.2015.05.022

    Article  PubMed  Google Scholar 

  4. Aboukais R, Zairi F, Lejeune JP, Le Rhun E, Vermandel M, Blond S, Devos P, Reyns N (2015) Grade 2 meningioma and radiosurgery. J Neurosurg 122:1157–1162. https://doi.org/10.3171/2014.9.JNS14233

    Article  PubMed  Google Scholar 

  5. Apra C, Roblot P, Alkhayri A, Le Guerinel C, Polivka M, Chauvet D (2020) Female gender and exogenous progesterone exposition as risk factors for spheno-orbital meningiomas. J Neurooncol 149:95–101. https://doi.org/10.1007/s11060-020-03576-8

    Article  CAS  PubMed  Google Scholar 

  6. Bernat AL, Oyama K, Hamdi S, Mandonnet E, Vexiau D, Pocard M, George B, Froelich S (2015) Growth stabilization and regression of meningiomas after discontinuation of cyproterone acetate: a case series of 12 patients. Acta Neurochir (Wien) 157:1741–1746. https://doi.org/10.1007/s00701-015-2532-3

    Article  Google Scholar 

  7. Bernat AL, Bonnin S, Labidi M, Aldahak N, Bresson D, Bouazza S, Froelich S (2018) Regression of giant olfactory groove meningioma and complete visual acuity recovery after discontinuation of cyproterone acetate. J Ophthalmic Vis Res 13:355–358. https://doi.org/10.4103/jovr.jovr_21_17

    Article  PubMed  PubMed Central  Google Scholar 

  8. Botella C, Coll G, Lemaire JJ, Irthum B (2015) Intra cranial meningiomas and long term use of cyproterone acetate with a conventional dose in women. A report of two cases of tumor decrease after treatment withdrawal. Neurochirurgie 61:339–342. https://doi.org/10.1016/j.neuchi.2015.05.002

    Article  CAS  PubMed  Google Scholar 

  9. Bouillot P, Pellissier JF, Devictor B, Graziani N, Bianco N, Grisoli F, Figarella-Branger D (1994) Quantitative imaging of estrogen and progesterone receptors, estrogen-regulated protein, and growth fraction: immunocytochemical assays in 52 meningiomas. Correlation with clinical and morphological data. J Neurosurg 81:765–773. https://doi.org/10.3171/jns.1994.81.5.0765

    Article  CAS  PubMed  Google Scholar 

  10. Cea-Soriano L, Blenk T, Wallander MA, Rodríguez LA (2012) Hormonal therapies and meningioma: is there a link? Cancer Epidemiol 36:198–205. https://doi.org/10.1016/j.canep.2011.08.003

    Article  CAS  PubMed  Google Scholar 

  11. Cebula H, Pham TQ, Boyer P, Froelich S (2010) Regression of meningiomas after discontinuation of cyproterone acetate in a transsexual patient. Acta Neurochir (Wien) 152:1955–1956. https://doi.org/10.1007/s00701-010-0787-2

    Article  Google Scholar 

  12. Champagne PO, Passeri T, Froelich S (2019) Combined hormonal influence of cyproterone acetate and nomegestrol acetate on meningioma: a case report. Acta Neurochir (Wien) 161:589–592. https://doi.org/10.1007/s00701-018-03782-4

    Article  Google Scholar 

  13. Champeaux-Depond C, Weller J, Froelich S, Sartor A (2021) Cyproterone acetate and meningioma: a nationwide-wide population based study. J Neurooncol. https://doi.org/10.1007/s11060-020-03672-9

    Article  PubMed  Google Scholar 

  14. Champeaux-Depond C, Weller J, Froelich S, Sartor A (2021) Cyproterone acetate and meningioma: a nationwide-wide population based study. J Neurooncol 151:331–338. https://doi.org/10.1007/s11060-020-03672-9

    Article  CAS  PubMed  Google Scholar 

  15. Cheriyan S, Santoreneos S, Wells AJ (2020) Rapid growth of an atypical meningioma in association with cyproterone acetate use: Case report. J Clin Neurosci 82:268–270. https://doi.org/10.1016/j.jocn.2020.09.053

    Article  CAS  PubMed  Google Scholar 

  16. Gazzeri R, Galarza M, Gazzeri G (2007) Growth of a meningioma in a transsexual patient after estrogen-progestin therapy. N Engl J Med 357:2411–2412. https://doi.org/10.1056/NEJMc071938

    Article  CAS  PubMed  Google Scholar 

  17. Gil M, Oliva B, Timoner J, Maciá MA, Bryant V, de Abajo FJ (2011) Risk of meningioma among users of high doses of cyproterone acetate as compared with the general population: evidence from a population-based cohort study. Br J Clin Pharmacol 72:965–968. https://doi.org/10.1111/j.1365-2125.2011.04031.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gill CM, Loewenstern J, Rutland JW, Arib H, Francoeur N, Wang YC, Fishman N, Pain M, Umphlett M, Kinoshita Y, McBride RB, Bederson J, Donovan M, Smith M, Sebra R, Shrivastava RK, Fowkes M (2020) Recurrent IDH mutations in high-grade meningioma. Neuro Oncol 22:1044–1045. https://doi.org/10.1093/neuonc/noaa065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Goffin J (1986) Estrogen- and progesterone-receptors in meningiomas. Review article. Clin Neurol Neurosurg 88:169–175. https://doi.org/10.1016/s0303-8467(86)80024-5

    Article  CAS  PubMed  Google Scholar 

  20. Gonçalves AM, Page P, Domigo V, Méder JF, Oppenheim C (2010) Abrupt regression of a meningioma after discontinuation of cyproterone treatment. AJNR Am J Neuroradiol 31:1504–1505. https://doi.org/10.3174/ajnr.A1978

    Article  PubMed  PubMed Central  Google Scholar 

  21. Gruber CJ, Huber JC (2003) Differential effects of progestins on the brain. Maturitas 46(Suppl 1):S71-75. https://doi.org/10.1016/j.maturitas.2003.09.021

    Article  CAS  PubMed  Google Scholar 

  22. Huntoon K, Toland AMS, Dahiya S (2020) Meningioma: a review of clinicopathological and molecular aspects. Front Oncol 10:579599. https://doi.org/10.3389/fonc.2020.579599

    Article  PubMed  PubMed Central  Google Scholar 

  23. Jenkinson MD, Javadpour M, Haylock BJ, Young B, Gillard H, Vinten J, Bulbeck H, Das K, Farrell M, Looby S, Hickey H, Preusser M, Mallucci CL, Hughes D, Gamble C, Weber DC (2015) The ROAM/EORTC-1308 trial: radiation versus observation following surgical resection of atypical meningioma: study protocol for a randomised controlled trial. Trials 16:519. https://doi.org/10.1186/s13063-015-1040-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Karsy M, Azab MA, Abou-Al-Shaar H, Guan J, Eli I, Jensen RL, Ormond DR (2018) Clinical potential of meningioma genomic insights: a practical review for neurosurgeons. Neurosurg Focus 44:E10. https://doi.org/10.3171/2018.2.FOCUS1849

    Article  PubMed  Google Scholar 

  25. Maas SLN, Stichel D, Hielscher T, Sievers P, Berghoff AS, Schrimpf D, Sill M, Euskirchen P, Blume C, Patel A, Dogan H, Reuss D, Dohmen H, Stein M, Reinhardt A, Suwala AK, Wefers AK, Baumgarten P, Ricklefs F, Rushing EJ, Bewerunge-Hudler M, Ketter R, Schittenhelm J, Jaunmuktane Z, Leu S, Greenway FEA, Bridges LR, Jones T, Grady C, Serrano J, Golfinos J, Sen C, Mawrin C, Jungk C, Hanggi D, Westphal M, Lamszus K, Etminan N, Jungwirth G, Herold-Mende C, Unterberg A, Harter PN, Wirsching HG, Neidert MC, Ratliff M, Platten M, Snuderl M, Aldape KD, Brandner S, Hench J, Frank S, Pfister SM, Jones DTW, Reifenberger G, Acker T, Wick W, Weller M, Preusser M, von Deimling A, Sahm F, German Consortium on Aggressive M (2021) Integrated molecular-morphologic meningioma classification: a multicenter retrospective analysis, retrospectively and prospectively validated. J Clin Oncol:JCO2100784. https://doi.org/10.1200/JCO.21.00784

  26. Malaize H, Samoyeau T, Zanello M, Roux A, Benzakoun J, Peeters S, Zah-Bi G, Edjlali M, Tauziede-Espariat A, Dezamis E, Parraga E, Chrétien F, Varlet P, Plu-Bureau G, Oppenheim C, Pallud J (2021) Evolution of the neurosurgical management of progestin-associated meningiomas: a 23-year single-center experience. J Neurooncol. https://doi.org/10.1007/s11060-021-03696-9

    Article  PubMed  Google Scholar 

  27. Mancini I, Rotilio A, Coati I, Seracchioli R, Martelli V, Meriggiola MC (2018) Presentation of a meningioma in a transwoman after nine years of cyproterone acetate and estradiol intake: case report and literature review. Gynecol Endocrinol 34:456–459. https://doi.org/10.1080/09513590.2017.1395839

    Article  PubMed  Google Scholar 

  28. Omulecka A, Papierz W, Nawrocka-Kunecka A, Lewy-Trenda I (2006) Immunohistochemical expression of progesterone and estrogen receptors in meningiomas. Folia Neuropathol 44:111–115

    CAS  PubMed  Google Scholar 

  29. Passeri T, Champagne PO, Bernat AL, Hanakita S, Salle H, Mandonnet E, Froelich S (2019) Spontaneous regression of meningiomas after interruption of nomegestrol acetate: a series of three patients. Acta Neurochir (Wien) 161:761–765. https://doi.org/10.1007/s00701-019-03848-x

    Article  Google Scholar 

  30. Peyre M, Kalamarides M (2018) Molecular genetics of meningiomas: Building the roadmap towards personalized therapy. Neurochirurgie 64:22–28. https://doi.org/10.1016/j.neuchi.2014.06.007

    Article  CAS  PubMed  Google Scholar 

  31. Peyre M, Gaillard S, de Marcellus C, Giry M, Bielle F, Villa C, Boch AL, Loiseau H, Baussart B, Cazabat L, Raffin-Sanson ML, Sanson M, Kalamarides M (2018) Progestin-associated shift of meningioma mutational landscape. Ann Oncol 29:681–686. https://doi.org/10.1093/annonc/mdx763

    Article  CAS  PubMed  Google Scholar 

  32. Peyre M, Gauchotte G, Giry M, Froehlich S, Pallud J, Graillon T, Bielle F, Cazals-Hatem D, Varlet P, Figarella-Branger D, Loiseau H, Kalamarides M (2018) De novo and secondary anaplastic meningiomas: a study of clinical and histomolecular prognostic factors. Neuro Oncol 20:1113–1121. https://doi.org/10.1093/neuonc/nox231

    Article  CAS  PubMed  Google Scholar 

  33. Pond JB, Morgan TG, Hatanpaa KJ, Yetkin ZF, Mickey BE, Mendelsohn DB (2015) Chordoid meningioma: differentiating a rare World Health Organization Grade II tumor from other meningioma histologic subtypes using MRI. AJNR Am J Neuroradiol 36:1253–1258. https://doi.org/10.3174/ajnr.A4309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Portet S, Naoufal R, Tachon G, Simonneau A, Chalant A, Naar A, Milin S, Bataille B, Karayan-Tapon L (2019) Histomolecular characterization of intracranial meningiomas developed in patients exposed to high-dose cyproterone acetate: an antiandrogen treatment. Neurooncol Adv 1:vdz003. https://doi.org/10.1093/noajnl/vdz003

  35. Portet S, Banor T, Bousquet J, Simonneau A, Flores M, Ingrand P, Milin S, Karayan-Tapon L, Bataille B (2020) New insights into expression of hormonal receptors by meningiomas. World Neurosurg 140:e87–e96. https://doi.org/10.1016/j.wneu.2020.04.168

    Article  PubMed  Google Scholar 

  36. Roux A, Tauziede-Espariat A, Zanello M, Gareton A, Malaize H, Benzakoun J, Zah-Bi G, Oppenheim C, Plu-Bureau G, Chretien F, Pallud J (2020) Symptomatic progestin-associated atypical grade II meningioma. A first case report Neurochirurgie 66:174–178. https://doi.org/10.1016/j.neuchi.2019.12.013

    Article  CAS  PubMed  Google Scholar 

  37. Sahm F, Schrimpf D, Stichel D, Jones DTW, Hielscher T, Schefzyk S, Okonechnikov K, Koelsche C, Reuss DE, Capper D, Sturm D, Wirsching HG, Berghoff AS, Baumgarten P, Kratz A, Huang K, Wefers AK, Hovestadt V, Sill M, Ellis HP, Kurian KM, Okuducu AF, Jungk C, Drueschler K, Schick M, Bewerunge-Hudler M, Mawrin C, Seiz-Rosenhagen M, Ketter R, Simon M, Westphal M, Lamszus K, Becker A, Koch A, Schittenhelm J, Rushing EJ, Collins VP, Brehmer S, Chavez L, Platten M, Hänggi D, Unterberg A, Paulus W, Wick W, Pfister SM, Mittelbronn M, Preusser M, Herold-Mende C, Weller M, von Deimling A (2017) DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis. Lancet Oncol 18:682–694. https://doi.org/10.1016/S1470-2045(17)30155-9

    Article  CAS  PubMed  Google Scholar 

  38. Samarut E, Lugat A, Amelot A, Scharbarg E, Hadjadj S, Primot C, Loussouarn D, Thillays F, Buffenoir K, Cariou B, Drui D, Roualdes V (2021) Meningiomas and cyproterone acetate: a retrospective, monocentric cohort of 388 patients treated by surgery or radiotherapy for intracranial meningioma. J Neurooncol. https://doi.org/10.1007/s11060-020-03683-6

    Article  PubMed  Google Scholar 

  39. Sievers P, Sill M, Blume C, Tauziede-Espariat A, Schrimpf D, Stichel D, Reuss DE, Dogan H, Hartmann C, Mawrin C, Hasselblatt M, Stummer W, Schick U, Hench J, Frank S, Ketter R, Schweizer L, Schittenhelm J, Puget S, Brandner S, Jaunmuktane Z, Küsters B, Abdullaev Z, Pekmezci M, Snuderl M, Ratliff M, Herold-Mende C, Unterberg A, Aldape K, Ellison DW, Wesseling P, Reifenberger G, Wick W, Perry A, Varlet P, Pfister SM, Jones DTW, von Deimling A, Sahm F, Meningiomas” GCA, (2021) Clear cell meningiomas are defined by a highly distinct DNA methylation profile and mutations in SMARCE1. Acta Neuropathol 141:281–290. https://doi.org/10.1007/s00401-020-02247-2

    Article  CAS  PubMed  Google Scholar 

  40. Tang M, Wei H, Han L, Deng J, Wang Y, Yang M, Tang Y, Guo G, Zhou L, Tong A (2017) Whole-genome sequencing identifies new genetic alterations in meningiomas. Oncotarget 8:17070–17080. https://doi.org/10.18632/oncotarget.15043

    Article  PubMed  PubMed Central  Google Scholar 

  41. Touat M, Lombardi G, Farina P, Kalamarides M, Sanson M (2014) Successful treatment of multiple intracranial meningiomas with the antiprogesterone receptor agent mifepristone (RU486). Acta Neurochir (Wien) 156:1831–1835. https://doi.org/10.1007/s00701-014-2188-4

    Article  Google Scholar 

  42. Ülgen E, Bektaşoğlu PK, Sav MA, Can Ö, Danyeli AE, Hızal DB, Pamir MN, Özduman K (2019) Meningiomas display a specific immunoexpression pattern in a rostrocaudal gradient: an analysis of 366 patients. World Neurosurg 123:e520–e535. https://doi.org/10.1016/j.wneu.2018.11.201

    Article  PubMed  Google Scholar 

  43. Weill A, Nguyen P, Labidi M, Cadier B, Passeri T, Duranteau L, Bernat AL, Yoldjian I, Fontanel S, Froelich S, Coste J (2021) Use of high dose cyproterone acetate and risk of intracranial meningioma in women: cohort study. BMJ 372:n37. https://doi.org/10.1136/bmj.n37

    Article  PubMed  Google Scholar 

  44. Wolfsberger S, Doostkam S, Boecher-Schwarz HG, Roessler K, van Trotsenburg M, Hainfellner JA, Knosp E (2004) Progesterone-receptor index in meningiomas: correlation with clinico-pathological parameters and review of the literature. Neurosurg Rev 27:238–245. https://doi.org/10.1007/s10143-004-0340-y

    Article  PubMed  Google Scholar 

  45. Youngblood MW, Günel M (2020) Molecular genetics of meningiomas. Handb Clin Neurol 169:101–119. https://doi.org/10.1016/B978-0-12-804280-9.00006-8

    Article  PubMed  Google Scholar 

  46. Youngblood MW, Miyagishima DF, Jin L, Gupte T, Li C, Duran D, Montejo JD, Zhao A, Sheth A, Tyrtova E, Özduman K, Iacoangeli F, Peyre M, Boetto J, Pease M, Avşar T, Huttner A, Bilguvar K, Kilic T, Pamir MN, Amankulor N, Kalamarides M, Erson-Omay EZ, Günel M, Moliterno J (2020) Associations of meningioma molecular subgroup and tumor recurrence. Neuro Oncol. https://doi.org/10.1093/neuonc/noaa226

    Article  PubMed Central  Google Scholar 

  47. Zairi F, Aboukais R, Rhun ELE, Marinho P, Maurage CA, Lejeune JP (2017) Close follow-up after discontinuation of cyproterone acetate: a possible option to defer surgery in patients with voluminous intracranial meningioma. J Neurosurg Sci 61:98–101. https://doi.org/10.23736/S0390-5616.16.03243-4

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosurgery, Lille University Hospital, Hôpital Nord, Rue E. Laine, 59037, Lille cedex, France

    Antoine Devalckeneer, Rabih Aboukais, Philippe Bourgeois & Jean-Paul Lejeune

  2. Lille University, INSERM, CHU Lille, U1189-ONCO-THAI-Image Assisted Laser Therapy for Oncology, 59000, Lille, France

    Rabih Aboukais & Jean-Paul Lejeune

  3. Department of Radiology, Lille University Hospital, Hopital Nord, Lille, France

    Vannod-Michel Quentin

  4. Department of Pathology, Centre Biologie Pathologie, Lille University Hospital, Hopital Nord, Lille, France

    Maxime Faisant, Claude-Alain Maurage & Fabienne Escande

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  1. Antoine Devalckeneer
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Antoine Devalckeneer, Rabih Aboukais, and Jean-Paul Lejeune. The first draft of the manuscript was written by Antoine Devalckeneer and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Antoine Devalckeneer.

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Devalckeneer, A., Aboukais, R., Faisant, M. et al. Progestin-related WHO grade II meningiomas behavior—a single-institution comparative case series. Neurosurg Rev 45, 1691–1699 (2022). https://doi.org/10.1007/s10143-021-01708-w

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