Skip to main content
SpringerLink
Log in

Definition and diagnosis of aggressive pituitary tumors

  • Published:
Reviews in Endocrine and Metabolic Disorders Aims and scope Submit manuscript

Abstract

Pituitary adenomas are considered benign tumors, but approximately 10% of them can have an aggressive behavior and more rarely (0.2%) can present metastasis, being classified as pituitary carcinomas. Aggressive adenomas are generally large and invasive tumors that present unusually rapid growth and/or that grow irrespective of conventional treatment with surgery, medical therapy and radiotherapy. Nevertheless, large tumors, as well as invasive tumors are not always aggressive, with this definition being possible only after clinical follow-up of these tumors, with growth rate and response to therapies being key points to its diagnosis. The correct identification and diagnosis of aggressive adenomas is of great importance as they are associated with great morbidity and increased mortality.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Lloyd RV, Osamura R, Kloppel G, Rosai J. Pathology and genetics of Tumours of endocrine organs. IARC WHO classification of Tumours. Lyon: IARC Press; 2017.

    Google Scholar 

  2. Asa SL, Casar-Borota O, Chanson P, Delgrange E, Earls P, Ezzat S, et al. From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an international pituitary pathology Club proposal. Endocr Relat Cancer. 2017;24(4):C5–8. https://doi.org/10.1530/ERC-17-0004.

    Article  CAS  PubMed  Google Scholar 

  3. Hall WA, Luciano MG, Doppman JL, Patronas NJ, Oldfield EH. Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population. Ann Intern Med. 1994;120(10):817–20. https://doi.org/10.7326/0003-4819-120-10-199405150-00001.

    Article  CAS  PubMed  Google Scholar 

  4. Molitch ME. Nonfunctioning pituitary tumors and pituitary incidentalomas. Endocrinol Metab Clin N Am. 2008;37(1):151–71, xi. https://doi.org/10.1016/j.ecl.2007.10.011.

    Article  Google Scholar 

  5. Freda PU, Beckers AM, Katznelson L, Molitch ME, Montori VM, Post KD, et al. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(4):894–904. https://doi.org/10.1210/jc.2010-1048.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Levy A, Lightman S. Molecular defects in the pathogenesis of pituitary tumours. Front Neuroendocrinol. 2003;24(2):94–127. https://doi.org/10.1016/s0091-3022(03)00012-8.

    Article  CAS  PubMed  Google Scholar 

  7. Raverot G, Burman P, McCormack A, Heaney A, Petersenn S, Popovic V, et al. European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas. Eur J Endocrinol. 2018;178(1):G1–G24. https://doi.org/10.1530/EJE-17-0796.

    Article  CAS  PubMed  Google Scholar 

  8. McCormack A, Dekkers OM, Petersenn S, Popovic V, Trouillas J, Raverot G, et al. Treatment of aggressive pituitary tumours and carcinomas: results of a European Society of Endocrinology (ESE) survey 2016. Eur J Endocrinol. 2018;178(3):265–76. https://doi.org/10.1530/EJE-17-0933.

    Article  CAS  PubMed  Google Scholar 

  9. Losa M, Bogazzi F, Cannavo S, Ceccato F, Curto L, De Marinis L et al. Temozolomide therapy in patients with aggressive pituitary adenomas or carcinomas. J Neurooncol. 2015. doi:https://doi.org/10.1007/s11060-015-1991-y.

  10. Heaney A. Management of aggressive pituitary adenomas and pituitary carcinomas. J Neuro-Oncol. 2014;117(3):459–68. https://doi.org/10.1007/s11060-014-1413-6.

    Article  CAS  Google Scholar 

  11. Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab. 2006;91(12):4769–75. https://doi.org/10.1210/jc.2006-1668.

    Article  CAS  PubMed  Google Scholar 

  12. Fernandez A, Karavitaki N, Wass JA. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol. 2010;72(3):377–82. https://doi.org/10.1111/j.1365-2265.2009.03667.x.

    Article  Google Scholar 

  13. Fernandez-Balsells MM, Murad MH, Barwise A, Gallegos-Orozco JF, Paul A, Lane MA, et al. Natural history of nonfunctioning pituitary adenomas and incidentalomas: a systematic review and metaanalysis. J Clin Endocrinol Metab. 2011;96(4):905–12. https://doi.org/10.1210/jc.2010-1054.

    Article  CAS  PubMed  Google Scholar 

  14. Raverot G, Dantony E, Beauvy J, Vasiljevic A, Mikolasek S, Borson-Chazot F, et al. Risk of recurrence in pituitary neuroendocrine tumors: a prospective study using a five-tiered classification. J Clin Endocrinol Metab. 2017;102(9):3368–74. https://doi.org/10.1210/jc.2017-00773.

    Article  PubMed  Google Scholar 

  15. De Sousa SMC, McCormack AI. Aggressive pituitary tumors and pituitary carcinomas. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, Dungan K, Grossman A et al., editors. Endotext. South Dartmouth (MA) 2000.

  16. Di Ieva A, Rotondo F, Syro LV, Cusimano MD, Kovacs K. Aggressive pituitary adenomas--diagnosis and emerging treatments. Nat Rev Endocrinol. 2014;10(7):423–35. https://doi.org/10.1038/nrendo.2014.64.

    Article  CAS  PubMed  Google Scholar 

  17. Kovacs K, Rotondo F, Horvath E, Syro LV. Stress in the classification of pituitary tumors. Focus on aggressive pituitary adenomas. Ideggyogy Sz. 2014;67(3–4):126–7.

    PubMed  Google Scholar 

  18. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47. https://doi.org/10.1016/j.ejca.2008.10.026.

    Article  CAS  PubMed  Google Scholar 

  19. Imber BS, Lin AL, Zhang Z, Keshavamurthy KN, Deipolyi AR, Beal K, et al. Comparison of radiographic approaches to assess treatment response in pituitary adenomas: is RECIST or RANO good enough? J Endocr Soc. 2019;3(9):1693–706. https://doi.org/10.1210/js.2019-00130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sav A, Rotondo F, Syro LV, Di Ieva A, Cusimano MD, Kovacs K. Invasive, atypical and aggressive pituitary adenomas and carcinomas. Endocrinol Metab Clin N Am. 2015;44(1):99–104. https://doi.org/10.1016/j.ecl.2014.10.008.

    Article  Google Scholar 

  21. Hamidi O, Van Gompel J, Gruber L, Kittah NE, Donegan D, Philbrick KA, et al. Management and outcomes of Giant Prolactinoma: a series of 71 patients. Endocr Pract. 2019;25(4):340–52. https://doi.org/10.4158/EP-2018-0392.

    Article  PubMed  Google Scholar 

  22. Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(2):273–88. https://doi.org/10.1210/jc.2010-1692.

    Article  CAS  PubMed  Google Scholar 

  23. Micko AS, Wohrer A, Wolfsberger S, Knosp E. Invasion of the cavernous sinus space in pituitary adenomas: endoscopic verification and its correlation with an MRI-based classification. J Neurosurg. 2015;122(4):803–11. https://doi.org/10.3171/2014.12.JNS141083.

    Article  PubMed  Google Scholar 

  24. Wang F, Zhou T, Wei S, Meng X, Zhang J, Hou Y, et al. Endoscopic endonasal transsphenoidal surgery of 1,166 pituitary adenomas. Surg Endosc. 2015;29(6):1270–80. https://doi.org/10.1007/s00464-014-3815-0.

    Article  PubMed  Google Scholar 

  25. Briceno V, Zaidi HA, Doucette JA, Onomichi KB, Alreshidi A, Mekary RA, et al. Efficacy of transsphenoidal surgery in achieving biochemical cure of growth hormone-secreting pituitary adenomas among patients with cavernous sinus invasion: a systematic review and meta-analysis. Neurol Res. 2017;39(5):387–98. https://doi.org/10.1080/01616412.2017.1296653.

    Article  PubMed  Google Scholar 

  26. Antunes X, Ventura N, Camilo GB, Wildemberg LE, Guasti A, Pereira PJM, et al. Predictors of surgical outcome and early criteria of remission in acromegaly. Endocrine. 2018;60(3):415–22. https://doi.org/10.1007/s12020-018-1590-8.

    Article  CAS  PubMed  Google Scholar 

  27. Oruckaptan HH, Senmevsim O, Ozcan OE, Ozgen T. Pituitary adenomas: results of 684 surgically treated patients and review of the literature. Surg Neurol. 2000;53(3):211–9. https://doi.org/10.1016/s0090-3019(00)00171-3.

    Article  CAS  PubMed  Google Scholar 

  28. Lelotte J, Mourin A, Fomekong E, Michotte A, Raftopoulos C, Maiter D. Both invasiveness and proliferation criteria predict recurrence of non-functioning pituitary macroadenomas after surgery: a retrospective analysis of a monocentric cohort of 120 patients. Eur J Endocrinol. 2018;178(3):237–46. https://doi.org/10.1530/EJE-17-0965.

    Article  CAS  PubMed  Google Scholar 

  29. Selman WR, Laws ER Jr, Scheithauer BW, Carpenter SM. The occurrence of dural invasion in pituitary adenomas. J Neurosurg. 1986;64(3):402–7. https://doi.org/10.3171/jns.1986.64.3.0402.

    Article  CAS  PubMed  Google Scholar 

  30. Knosp E, Steiner E, Kitz K, Matula C. Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery. 1993;33(4):610–7; discussion 7-8. https://doi.org/10.1227/00006123-199310000-00008.

    Article  CAS  PubMed  Google Scholar 

  31. Chen Y, Wang CD, Su ZP, Chen YX, Cai L, Zhuge QC, et al. Natural history of postoperative nonfunctioning pituitary adenomas: a systematic review and meta-analysis. Neuroendocrinology. 2012;96(4):333–42. https://doi.org/10.1159/000339823.

    Article  CAS  PubMed  Google Scholar 

  32. Ratnasingam J, Lenders N, Ong B, Boros S, Russell AW, Inder WJ, et al. Predictors for secondary therapy after surgical resection of nonfunctioning pituitary adenomas. Clin Endocrinol. 2017;87(6):717–24. https://doi.org/10.1111/cen.13402.

    Article  CAS  Google Scholar 

  33. Honegger J, Zimmermann S, Psaras T, Petrick M, Mittelbronn M, Ernemann U, et al. Growth modelling of non-functioning pituitary adenomas in patients referred for surgery. Eur J Endocrinol. 2008;158(3):287–94. https://doi.org/10.1530/EJE-07-0502.

    Article  CAS  PubMed  Google Scholar 

  34. Trouillas J, Roy P, Sturm N, Dantony E, Cortet-Rudelli C, Viennet G, et al. A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up. Acta Neuropathol. 2013;126(1):123–35. https://doi.org/10.1007/s00401-013-1084-y.

    Article  PubMed  Google Scholar 

  35. Saeger W, Ludecke DK, Buchfelder M, Fahlbusch R, Quabbe HJ, Petersenn S. Pathohistological classification of pituitary tumors: 10 years of experience with the German pituitary tumor registry. Eur J Endocrinol. 2007;156(2):203–16. https://doi.org/10.1530/eje.1.02326.

    Article  CAS  PubMed  Google Scholar 

  36. Dudziak K, Honegger J, Bornemann A, Horger M, Mussig K. Pituitary carcinoma with malignant growth from first presentation and fulminant clinical course--case report and review of the literature. J Clin Endocrinol Metab. 2011;96(9):2665–9. https://doi.org/10.1210/jc.2011-1166.

    Article  CAS  PubMed  Google Scholar 

  37. Santos-Pinheiro F, Penas-Prado M, Kamiya-Matsuoka C, Waguespack SG, Mahajan A, Brown P, et al. Treatment and long-term outcomes in pituitary carcinoma: a cohort study. Eur J Endocrinol. 2019. https://doi.org/10.1530/EJE-18-0795.

  38. Yoo F, Kuan EC, Heaney AP, Bergsneider M, Wang MB. Corticotrophic pituitary carcinoma with cervical metastases: case series and literature review. Pituitary. 2018;21(3):290–301. https://doi.org/10.1007/s11102-018-0872-8.

    Article  CAS  PubMed  Google Scholar 

  39. Ben-Shlomo A, Cooper O. Silent corticotroph adenomas. Pituitary. 2018;21(2):183–93. https://doi.org/10.1007/s11102-018-0864-8.

    Article  CAS  PubMed  Google Scholar 

  40. Drummond J, Roncaroli F, Grossman AB, Korbonits M. Clinical and pathological aspects of silent pituitary adenomas. J Clin Endocrinol Metab. 2019;104(7):2473–89. https://doi.org/10.1210/jc.2018-00688.

    Article  PubMed  Google Scholar 

  41. Fountas A, Lavrentaki A, Subramanian A, Toulis KA, Nirantharakumar K, Karavitaki N. Recurrence in silent corticotroph adenomas after primary treatment: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2018. https://doi.org/10.1210/jc.2018-01956.

Download references

Author information

Authors and Affiliations

  1. Neuroendocrinology Research Center/ Endocrinology Division – Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Leandro Kasuki

  2. Neuroendocrinology Division, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil

    Leandro Kasuki

  3. Endocrinology Division, Hospital Federal de Bonsucesso, Rio de Janeiro, Brazil

    Leandro Kasuki

  4. “Groupement Hospitalier Est” Hospices Civils de Lyon, Endocrinology Department, Reference Center for Rare Pituitary Diseases HYPO, 59 Pinel Boulevard, 69677, Bron, France

    Gérald Raverot

  5. Université Lyon 1, 69100, Villeurbanne, France

    Gérald Raverot

  6. INSERM U1052, CNRS, UMR5286, Cancer Research Center of Lyon, 69372, Lyon, France

    Gérald Raverot

  7. Fédération d’Endocrinologie du Pôle Est, Groupement Hospitalier Est, 59 Bd Pinel, F-69677, Bron, France

    Gérald Raverot

Authors
  1. Leandro Kasuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gérald Raverot
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gérald Raverot.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kasuki, L., Raverot, G. Definition and diagnosis of aggressive pituitary tumors. Rev Endocr Metab Disord 21, 203–208 (2020). https://doi.org/10.1007/s11154-019-09531-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11154-019-09531-x

Keywords

Search

Navigation