Skip to main content

Advertisement

Log in

Advances and controversies in the classification and grading of pituitary tumors

  • Short Review
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Background

Pituitary tumors are common lesions, and they represent the second most frequent primary brain tumor. Their classification has undergone several changes over time. The World Health Organization conducts periodic expert review/consensus meetings and publishes the results as recommendations for changes in classification, based on advances in molecular and genetic advances. This paper summarizes the results of the 2017 WHO Classification, which recommends several important changes.

Purpose

This paper provides a review of the major changes and issues leading to an understanding of the basis for a new pituitary tumor classification. They include the rejection and modification of prior conceptual and pathological characteristics of these neoplasms. There is also considerable concern related to invasive and recurrent pituitary tumors which follow a less benign course than the typical pituitary adenoma.

Methods

A review of the outcome data for the previously designated “atypical” pituitary tumor category revealed that the former criteria were not adequate to support their ability to predict with accuracy the clinical course of a given tumor. A similar review was accomplished regarding the role of the p53 tumor suppressor mutation. Again, there was no reliable contribution of p53 status to tumor aggressiveness. Other changes have occurred regarding the cytogenetic lineage of the various subtypes of pituitary adenoma. The transcription factors Pit-1, SF-1, and TPit play a major role in determining tumor subtypes and have become part of the classification criteria.

Results

These advances now help provide the background for more reliable and consistent classification of pituitary adenomas. Further definition of aggressive characteristics such as cavernous sinus and dural invasion remain to be considered in the quest to make more accurate prognostic projections based on histopathological analysis.

Conclusions

The 2017 WHO Classification of Pituitary Tumors provides a more solid basis for accurate and reliable prognostic assessment of these lesions. Further progress undoubtedly will be made as the recommendations of this update are incorporated in to routine use.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Gittleman H, Ostrom QT, Farah PD, Ondracek A, Chen Y, Wolinsky Y, Kruchko C, Singer J, Kshettry VR, Laws ER, Sloan AE, Selman WR, Barnholtz-Sloan JS (2014) Descriptive epidemiology of pituitary tumors in the United States, 2004–2009. J Neurosurg 121(3):527–535. https://doi.org/10.3171/2014.5.jns131819

    Article  PubMed  Google Scholar 

  2. Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C, Barnholtz-Sloan JS (2013) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neurooncology 15(Suppl 2):ii1–ii56. https://doi.org/10.1093/neuonc/not151

    Article  Google Scholar 

  3. Benda C (1901) Die mikroscopische Befunde bei vier Fallen von Akromegalie. Dtsch Med Wochenschr 27:537–539

    Google Scholar 

  4. Erdheim J (1903) Zur normalen und pathologischen Histologie der Glandula thyreoidea, parathyroidea und Hypophysis. Beitr pathol Anat 33:158–236

    Google Scholar 

  5. Loewenstein C (1907) Die Entwicklung der Hypophysisadenome. Ein Beitr Lehre Geschwülsten 188:44–65

    Google Scholar 

  6. Kovacs K, Scheithauer BW, Horvath E, Lloyd RV (1996) The World Health Organization classification of adenohypophysial neoplasms. A proposed five-tier scheme. Cancer 78(3):502–510. https://doi.org/10.1002/(sici)1097-0142(19960801)78:3<502:aid-cncr18>3.0.co;2-2

    Article  CAS  PubMed  Google Scholar 

  7. Thapar K, Kovacs K, Laws ER, Muller PJ (1993) Pituitary adenomas: current concepts in classification, histopathology, and molecular biology. Endocrinologist 3:39–57

    Article  Google Scholar 

  8. Trouillas J, Girod C (1996) Pathology of pituitary adenomas. In: Landolt AM, Vance M, Reilly PL (eds) Pituitary adenomas. Churchill Livingstone, New York, pp 27–46

    Google Scholar 

  9. Asa SL, Bamberger AM, Cao B, Wong M, Parker KL, Ezzat S (1996) The transcription activator steroidogenic factor-1 is preferentially expressed in the human pituitary gonadotroph. J Clin Endocrinol Metab 81(6):2165–2170. https://doi.org/10.1210/jcem.81.6.8964846

    Article  CAS  PubMed  Google Scholar 

  10. Asa SL, Casar-Borota O, Chanson P, Delgrange E, Earls P, Ezzat S, Grossman A, Ikeda H, Inoshita N, Karavitaki N, Korbonits M, Laws ER Jr, Lopes MB, Maartens N, McCutcheon IE, Mete O, Nishioka H, Raverot G, Roncaroli F, Saeger W, Syro LV, Vasiljevic A, Villa C, Wierinckx A, Trouillas J, and the Attendees of 14th Meeting of the International Pituitary Pathology Club AFN (2017) From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal. Endocr Relat Cancer 24(4):C5–C8. https://doi.org/10.1530/erc-17-0004

    Article  CAS  PubMed  Google Scholar 

  11. Friend KE, Chiou YK, Laws ER Jr, Lopes MB, Shupnik MA (1993) Pit-1 messenger ribonucleic acid is differentially expressed in human pituitary adenomas. J Clin Endocrinol Metab 77(5):1281–1286. https://doi.org/10.1210/jcem.77.5.8077322

    Article  CAS  PubMed  Google Scholar 

  12. Lloyd RV, Osamura RY (1997) Transcription factors in normal and neoplastic pituitary tissues. Microsc Res Tech 39(2):168–181. https://doi.org/10.1002/(sici)1097-0029(19971015)39:2<168:aid-jemt8>3.0.co;2-h

    Article  CAS  PubMed  Google Scholar 

  13. Mason ME, Friend KE, Copper J, Shupnik MA (1993) Pit-1/GHF-1 binds to TRH-sensitive regions of the rat thyrotropin beta gene. Biochemistry 32(34):8932–8938

    Article  CAS  PubMed  Google Scholar 

  14. Seltzer J, Ashton CE, Scotton TC, Pangal D, Carmichael JD, Zada G (2015) Gene and protein expression in pituitary corticotroph adenomas: a systematic review of the literature. Neurosurg Focus 38(2):E17. https://doi.org/10.3171/2014.10.focus14683

    Article  PubMed  Google Scholar 

  15. WHO Classification of tumours of endocrine organs (2017), vol 10, 4th edn. IARC Publications, Lyon

  16. Lopes MBS (2017) The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. Acta Neuropathol 134(4):521–535. https://doi.org/10.1007/s00401-017-1769-8

    Article  CAS  PubMed  Google Scholar 

  17. Mete O, Lopes MB (2017) Overview of the 2017 WHO classification of pituitary tumors. Endocr Pathol 28(3):228–243. https://doi.org/10.1007/s12022-017-9498-z

    Article  CAS  PubMed  Google Scholar 

  18. Shibuya M (2018) Welcoming the new WHO classification of pituitary tumors 2017: revolution in TTF-1-positive posterior pituitary tumors. Brain Tumor Pathol. https://doi.org/10.1007/s10014-018-0311-6

    Article  PubMed  Google Scholar 

  19. Cote DJ, Smith TR, Sandler CN, Gupta T, Bale TA, Bi WL, Dunn IF, De Girolami U, Woodmansee WW, Kaiser UB, Laws ER Jr (2016) Functional gonadotroph adenomas: case series and report of literature. Neurosurgery 79(6):823–831. https://doi.org/10.1227/neu.0000000000001188

    Article  PubMed  Google Scholar 

  20. Balogun JA, Monsalves E, Juraschka K, Parvez K, Kucharczyk W, Mete O, Gentili F, Zadeh G (2015) Null cell adenomas of the pituitary gland: an institutional review of their clinical imaging and behavioral characteristics. Endocr Pathol 26(1):63–70. https://doi.org/10.1007/s12022-014-9347-2

    Article  PubMed  Google Scholar 

  21. Raverot G, Vasiljevic A, Jouanneau E, Trouillas J (2015) A prognostic clinicopathologic classification of pituitary endocrine tumors. Endocrinol Metab Clin N Am 44(1):11–18. https://doi.org/10.1016/j.ecl.2014.10.001

    Article  Google Scholar 

  22. Trouillas J, Roy P, Sturm N, Dantony E, Cortet-Rudelli C, Viennet G, Bonneville JF, Assaker R, Auger C, Brue T, Cornelius A, Dufour H, Jouanneau E, Francois P, Galland F, Mougel F, Chapuis F, Villeneuve L, Maurage CA, Figarella-Branger D, Raverot G, Members of H, Barlier A, Bernier M, Bonnet F, Borson-Chazot F, Brassier G, Caulet-Maugendre S, Chabre O, Chanson P, Cottier JF, Delemer B, Delgrange E, Di Tommaso L, Eimer S, Gaillard S, Jan M, Girard JJ, Lapras V, Loiseau H, Passagia JG, Patey M, Penfornis A, Poirier JY, Perrin G, Tabarin A (2013) 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 126(1):123–135. https://doi.org/10.1007/s00401-013-1084-y

    Article  PubMed  Google Scholar 

  23. Thapar K, Kovacs K, Laws E (1995) The classification and molecular biology of pituitary adenomas. In: Advances and technical standards in neurosurgery. Springer, Wien, p 3–53

  24. Thapar K, Scheithauer BW, Kovacs K, Pernicone PJ, Laws Jr ER (1996) p53 expression in pituitary adenomas and carcinomas: correlation with invasiveness and tumor growth fractions. Neurosurgery 38(4):765–770; discussion 770–761

  25. Zada G, Woodmansee WW, Ramkissoon S, Amadio J, Nose V, Laws ER Jr (2011) Atypical pituitary adenomas: incidence, clinical characteristics, and implications. J Neurosurg 114(2):336–344. https://doi.org/10.3171/2010.8.jns10290

    Article  PubMed  Google Scholar 

  26. Selman WR, Laws ER, Scheithauer BW, Carpenter SM (1986) The occurrence of dural invasion in pituitary adenomas. J Neurosurg 64(3):402–407

    Article  CAS  PubMed  Google Scholar 

  27. Thapar K, Kovacs K, Scheithauer BW, Stefaneanu L, Horvath E, Pernicone PJ, Murray D, Laws Jr ER (1996) Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery 38(1):99–106; discussion 106–107

  28. Scheithauer BW, Kovacs KT, Laws ER Jr, Randall RV (1986) Pathology of invasive pituitary tumors with special reference to functional classification. J Neurosurg 65(6):733–744. https://doi.org/10.3171/jns.1986.65.6.0733

    Article  CAS  PubMed  Google Scholar 

  29. Meij BP, Lopes MB, Ellegala DB, Alden TD, Laws ER Jr (2002) The long-term significance of microscopic dural invasion in 354 patients with pituitary adenomas treated with transsphenoidal surgery. J Neurosurg 96(2):195–208. https://doi.org/10.3171/jns.2002.96.2.0195

    Article  PubMed  Google Scholar 

  30. Caimari F, Hernandez-Ramirez LC, Dang MN, Gabrovska P, Iacovazzo D, Stals K, Ellard S, Korbonits M, International Fc (2018) Risk category system to identify pituitary adenoma patients with AIP mutations. J Med Genet 55(4):254–260. https://doi.org/10.1136/jmedgenet-2017-104957

    Article  CAS  PubMed  Google Scholar 

  31. Daly AF, Tichomirowa MA, Petrossians P, Heliovaara E, Jaffrain-Rea ML, Barlier A, Naves LA, Ebeling T, Karhu A, Raappana A, Cazabat L, De Menis E, Montanana CF, Raverot G, Weil RJ, Sane T, Maiter D, Neggers S, Yaneva M, Tabarin A, Verrua E, Eloranta E, Murat A, Vierimaa O, Salmela PI, Emy P, Toledo RA, Sabate MI, Villa C, Popelier M, Salvatori R, Jennings J, Longas AF, Labarta Aizpun JI, Georgitsi M, Paschke R, Ronchi C, Valimaki M, Saloranta C, De Herder W, Cozzi R, Guitelman M, Magri F, Lagonigro MS, Halaby G, Corman V, Hagelstein MT, Vanbellinghen JF, Barra GB, Gimenez-Roqueplo AP, Cameron FJ, Borson-Chazot F, Holdaway I, Toledo SP, Stalla GK, Spada A, Zacharieva S, Bertherat J, Brue T, Bours V, Chanson P, Aaltonen LA, Beckers A (2010) Clinical characteristics and therapeutic responses in patients with germ-line AIP mutations and pituitary adenomas: an international collaborative study. J Clin Endocrinol Metab 95(11):E373–E383. https://doi.org/10.1210/jc.2009-2556

    Article  PubMed  Google Scholar 

  32. Kasuki L, Vieira Neto L, Wildemberg LE, Colli LM, de Castro M, Takiya CM, Gadelha MR (2012) AIP expression in sporadic somatotropinomas is a predictor of the response to octreotide LAR therapy independent of SSTR2 expression. Endocr Relat Cancer 19(3):L25–L29. https://doi.org/10.1530/erc-12-0020

    Article  CAS  PubMed  Google Scholar 

  33. Oriola J, Lucas T, Halperin I, Mora M, Perales MJ, Alvarez-Escola C, de Paz MN, Diaz Soto G, Salinas I, Julian MT, Olaizola I, Bernabeu I, Marazuela M, Puig-Domingo M (2013) Germline mutations of AIP gene in somatotropinomas resistant to somatostatin analogues. Eur J Endocrinol 168(1):9–13. https://doi.org/10.1530/eje-12-0457

    Article  CAS  PubMed  Google Scholar 

  34. Zaidi HA, Cote DJ, Dunn IF, Laws ER Jr (2016) Predictors of aggressive clinical phenotype among immunohistochemically confirmed atypical adenomas. J Clin Neurosci 34:246–251. https://doi.org/10.1016/j.jocn.2016.09.014

    Article  CAS  PubMed  Google Scholar 

  35. Raverot G, Dantony E, Beauvy J, Vasiljevic A, Mikolasek S, Borson-Chazot F, Jouanneau E, Roy P, Trouillas J (2017) Risk of recurrence in pituitary neuroendocrine tumors: a prospective study using a five-tiered classification. J Clin Endocrinol Metab 102(9):3368–3374. https://doi.org/10.1210/jc.2017-00773

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  37. Oystese KA, Casar-Borota O, Normann KR, Zucknick M, Berg JP, Bollerslev J (2017) Estrogen receptor alpha, a sex-dependent predictor of aggressiveness in nonfunctioning pituitary adenomas: SSTR and sex hormone receptor distribution in NFPA. J Clin Endocrinol Metab 102(9):3581–3590. https://doi.org/10.1210/jc.2017-00792

    Article  PubMed  Google Scholar 

  38. Perez-Rivas LG, Reincke M (2016) Genetics of Cushing’s disease: an update. J Endocrinol Investig 39(1):29–35. https://doi.org/10.1007/s40618-015-0353-0

    Article  CAS  Google Scholar 

  39. Lopes MB, Scheithauer BW, Schiff D (2005) Pituitary carcinoma: diagnosis and treatment. Endocrine 28(1):115–121. https://doi.org/10.1385/endo:28:1:115

    Article  CAS  PubMed  Google Scholar 

  40. Scheithauer BW, Gaffey TA, Lloyd RV, Sebo TJ, Kovacs KT, Horvath E, Yapıcıer Ö, Young WF, Meyer FB, Kuroki T, Riehle DL (2006) Pathobiology of pituitary adenomas and carcinomas. Neurosurgery 59(2):341–353

    Article  PubMed  Google Scholar 

  41. Al-Gahtany M, Horvath E, Kovacs K (2003) Pituitary hyperplasia. Hormones 2(3):149–158

    Article  PubMed  Google Scholar 

Download references

Funding

No funding was required for completion of this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E. R. Laws Jr..

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest. The authors declare that they have no conflict of interest, either financial or non-financial.

Ethical approval

The article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

There is no identifying patient information present in this manuscript; therefore, informed consent is unnecessary.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Laws, E.R., Penn, D.L. & Repetti, C.S. Advances and controversies in the classification and grading of pituitary tumors. J Endocrinol Invest 42, 129–135 (2019). https://doi.org/10.1007/s40618-018-0901-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-018-0901-5

Keywords

Navigation