New Diagnostic Strategy for Atypical Pituitary Adenomas: Clinical and Histopathological Score

  • Francisco Tortosa Centro Hospitalar Lisboa Norte, EPE - Hospital Santa Maria (Lisbon)
  • Susan M Webb Universitat Autònoma de Barcelona (UAB), (Barcelona)
Keywords: Diagnosis, pituitary neoplasm, prognosis


Background: Currently, prognosis remains the major challenge of the adenomatous pituitary pathology. According to the World Health Organization (WHO), pituitary tumors are classified into typical adenoma, atypical adenoma and carcinoma. Given that the prediction of the behavior of these tumors remains a major clinical and anatomo-pathological challenge, we propose a new diagnostic strategy to orient prognosis and therapy of these tumors, based on a multiparameter system, as well as a simple clinico-laboratory and radio-histopathologic diagnostic algorithm.Methods: To validate the method, we have applied it retrospectively to a series of 243 pituitary adenomas (diagnosed according to the 2004 WHO classification on tumors of endocrine organs), operated by transsphenoidal via between 2004 and 2014, at Centro Hospitalar Lisboa Norte, the largest reference center in Portugal.Result: A hundred twenty nine had a follow-up of at least 5 years in order to evaluate recurrences. While 6.2% of typical adenomas recurred, among the atypical the recurrence rate was 68.8%.Conclusion: With this work we intend to provide a more specific differentiating system of possible malignancy, to early identify probable cases of poor evolution, which could be very useful in clinical practice.

Author Biographies

Francisco Tortosa, Centro Hospitalar Lisboa Norte, EPE - Hospital Santa Maria (Lisbon)
Department of Pathology, Hospital Santa Maria
Susan M Webb, Universitat Autònoma de Barcelona (UAB), (Barcelona)
Department of Medicine / Endocrinology, Hospital Sant Pau, IIB-Sant Pau


1. Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, et al. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States 2006-2010. Neuro-Oncol. 2013;15(2):ii1-ii56.

2. Sanno N, Oyama K, Tahara S, Teramoto A, Kato Y. A survey of pituitary incidentaloma in Japan. Eur. J. Endocrinol. 2003;149:123-127.

3. Vernooij MW, Ikram MA, Tanghe HL, Vincent AJ, Hofman A, Krestin GP, et al. Incidental findings on brain MRI in the general population. N. Engl. J. Med. 2007;357:1821-1828.

4. Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, et al. The prevalence of pituitary adenomas: a systematic review. Cancer. 2004;101(3):613-619.

5. 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;91:4769-4775.

6. Fernandez A, Karavitaki N, Wass J. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin. Endocrinol. 2010;72:377-382.

7. Al-Brahim NY, Asa SL. My approach to pathology of the pituitary gland. J. Clin. Pathol. 2006;59:1245-1253.

8. Asa SL. Practical pituitary pathology: what does the pathologist need to know?. Arch. Pathol. Lab. Med. 2008;132:1231-1240.

9. Al-Shraim M, Asa SL. The 2004 World Health Organization classification of pituitary tumors: What is new? Acta Neuropathol. 2006;111(1):1-7.

10. 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;126:123-135.

11. Lloyd RV, Kovacs K, Young Jr WF, Farrel WE, Asa SL, Trouillas J, Kontogeorgos G, Sano T, Scheithauer B, Horvath E. Tumours of the pituitary gland. In: DeLellis RA, Lloyd RV, Heitz PU, Eng C, editors. World Hearth Organization Classification of Tumours. Pathology and genetics of tumours of endocrine organs. Lyon: IARC Press; 2004. 9-47.

12. Pernicone PJ, Scheithauer BW. Invasive pituitary adenoma and pituitary carcinoma. In: Thapar K, Kovacs K, Scheithauer BW, Lloyd RV, editors. Diagnosis and management of pituitary tumors. Totowa NJ: Humana Press; 2001. 369-386.

13. Yildirim AE, Divanlioglu D, Nacar OA, Dursun E, Sahinoglu M, Unal T, et al. Incidence, Hormonal Distribution and Postoperative Follow Up of Atypical Pituitary Adenomas. Turk. Neurosurg. 2013;23(2):226-231.

14. Tortosa F, Webb SM. Atypical pituitary adenomas: 10 years experience in a reference centre of Portugal. Neurología. 2015;

15. Kovacs K, Horvath E, Vidal S. Classification of pituitary adenomas. J. Neurooncol. 2001;54:121-127.

16. Pernicone PJ, Scheithauer BW, Sebo TJ, Kovacs KT, Horvath E, Young WF Jr, et al. Pituitary carcinoma: A clinicopathological study of 15 cases. Cancer. 1997;79:804-812.

17. Ragel BT, Couldwell WT. Pituitary Carcinoma: A Review of the Literature. Neurosurg. Focus. 2004;16(4):E7.

18. Borrecho G, Ortiz S, Tortosa F. Estudo da actividade proliferativa com Ki67 em adenomas hipofisários: O homem e a máquina. XIII Congresso Técnico de Anatomia Patológica; 2012 May 25-27; Figueira da Foz, Portugal: Associação Portuguesa de Técnicos de Anatomia Patológica.

19. Miermeister CP, Petersenn S, Buchfelder M, Fahlbusch R, Lüdecke DK, Hölsken A, et al. Histological criteria for atypical pituitary adenomas - data from the German pituitary adenoma registry suggests modifications. Acta Neuropathol Commun. 2015; doi: 10.1186/s40478-015-0229-8.

20. Nosé V, Ezzat S, Horvath E, Kovacs K, Laws ER, Lloyd R, et al. Protocol for the examination of specimens from patients with primary pituitary tumors. Arch. Pathol. Lab. Med. 2011;135:640-646.

21. 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;156:203-216.

22. Zada G, Woodmansee WW, Ramkissoon S, Amadio J, Nose V, Laws RE. Atypical pituitary adenomas: Incidence, clinical characteristics, and implications. J. Neurosurg. 2011;114:336-344.

23. Thapar K, Kovacs K, Scheithauer BW, Stefaneanu L, Horvath E, Pernicone PJ. Proliferative activity and invasiveness among pituitary adenomas and carcinomas: An analysis using the MIB-1 antibody. Neurosurgery. 1996;38:99-107.

24. Amar AP, Hinton DR, Krieger MD, Weiss MH. Invasive pituitary adenomas: significance of proliferation parameters. Pituitary. 1999;2:117-212.

25. Aranda FI, Niveiro de Jaime M, Peiró G, Alenda C, Picó A. Adenoma hipofisario: estudio de la actividad proliferativa con Ki-67. Rev. Esp. Patol. 2007;40(4):225-231.

26. 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;96:2665-2669.

27. Mamelak AN, Carmichael JD, Park P, Bannykh S, Fan X, Bonert HV. Atypical pituitary adenoma with malignant features. Pituitary. 2011;14:92-97.

28. Pasquel FJ, Vincentelli C, Brat DJ, Oyesiku NM, Ioaquimescu AG. Pituitary carcinoma in situ. Endocr. Pract. 2012;19(3):69-73.

29. Heaney AP. Clinical review: Pituitary carcinoma: difficult diagnosis and treatment. J. Clin. Endocrinol. Metab. 2011;96:3649-3660.

30. Scheithauer BW, Gaffey TA, Lloyd RV, Sebo TJ, Kovacs KT, Horvath E, et al. Pathobiology of pituitary adenomas and carcinomas. Neurosurgery. 2006;59:341-353.

31. Lopes MBS. Diagnostic controversies in pituitary tumor pathology. ANNP Companion Meeting. USCAP; 2013 March 2-8; Baltimore, USA: United States & Canadian Academy of Pathology.

32. Pizarro CB, Oliveira MC, Coutinho LB, Ferreira NP. Measurement of Ki-67 antigen in 159 pituitary adenomas using the MIB-1 monoclonal antibody. Braz. J. Med. Biol. Res. 2004;37:235-243.
Original Article