J Neurol Surg B Skull Base 2021; 82(S 03): e94-e100
DOI: 10.1055/s-0040-1702219
Original Article

The Past, Present, and Future Statuses of Formerly Classified “Atypical Pituitary Adenomas”: A Clinicopathological Assessment of 101 Cases in a Cohort of More than 1,000 Pure Endoscopically Treated Patients in Single Center

Ercan Bal
1   Department of Neurosurgery, Ankara Yıldırım Beyazıt University School of Medicine, Ankara, Turkey
,
İbrahim Kulaç
2   Department of Pathology, Koç University Hospital, İstanbul, Turkey
,
Selim Ayhan
3   Departments of Neurosurgery and Electroneurophsiology, Vocational School of Health Sciences, Acibadem Mehmet Ali Aydınlar University, İstanbul, Turkey
,
Figen Söylemezoğlu
4   Department of Pathology, Hacettepe University School of Medicine, Ankara, Turkey
,
Mustafa Berker
5   Department of Neurosurgery, Hacettepe University School of Medicine, Ankara, Turkey
› Author Affiliations
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Abstract

Objective This study was aimed to assess the clinical aggressiveness of pituitary neoplasms that were previously defined as atypical adenomas.

Methods A total of 1,042 pituitary adenomas were included in the study and 101 of them were diagnosed as atypical adenoma. Demographic characteristics, radiological evaluations, and clinical information were obtained from a computer-based patient database. Cases were categorized as atypical or typical using the criteria listed in 2004 Classification of Tumors of Endocrine Organs.

Results The cure and reoperation rates did not show any statistically significant difference between the typical and atypical adenomas. However, a higher Ki-67 labeling index was found to be associated with a higher rate of reoperation (p = 0.008) in atypical adenomas. Of note, cavernous sinus invasion or parasellar extension was found to be associated with lower cure rates in patients with atypical pituitary adenomas (p < 0.001 and p = 0.001, respectively).

Conclusion Although atypical pituitary adenomas are known to be more invasive, this study demonstrated that the reoperation and cure rates are the same for typical and atypical adenomas. Our findings advocate for omitting the use of atypical adenoma terminology based solely on pathological evaluation. As stated in the 4th edition of the World Health Organization (WHO) classification, accurate tumor subtyping, evaluation of proliferation by means of mitotic count and Ki-67 labeling index, and radiological and intraoperative assessments of tumor invasion should be taken into consideration in the management of such neoplasms.

Note

All authors have read the manuscript and have agreed to submit it in its current form for consideration for publication in the Journal. This study is not supported by grants or contracts from federal agencies, nonprofit organizations, and/or commercial entities. E.B., İ.K., and S.A. were working in Hacettepe University, Ankara, Turkey, during the preparation of the this manuscript.


Ethical Approval

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




Publication History

Received: 07 June 2019

Accepted: 10 January 2020

Article published online:
20 February 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
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  • References

  • 1 DeLellis RA, Lloyd RV, Heitz PU, Eng C. Pathology and Genetics of Tumours of Endocrine Organs. 3rd ed. Lyon: IARC Press; 2004
  • 2 Scheithauer BW, Gaffey TA, Lloyd RV. et al. Pathobiology of pituitary adenomas and carcinomas. Neurosurgery 2006; 59 (02) 341-353
  • 3 Miermeister CP, Petersenn S, Buchfelder M. et al. Histological criteria for atypical pituitary adenomas - data from the German pituitary adenoma registry suggests modifications. Acta Neuropathol Commun 2015; 3: 50
  • 4 Saeger W, Lüdecke 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 (02) 203-216
  • 5 Zada G, Woodmansee WW, Ramkissoon S, Amadio J, Nose V, Laws Jr ER. Atypical pituitary adenomas: incidence, clinical characteristics, and implications. J Neurosurg 2011; 114 (02) 336-344
  • 6 Zaidi HA, Cote DJ, Dunn IF, Laws Jr ER. Predictors of aggressive clinical phenotype among immunohistochemically confirmed atypical adenomas. J Clin Neurosci 2016; 34: 246-251
  • 7 Tortosa F, Webb SM. Atypical pituitary adenomas: 10 years of experience in a reference centre in Portugal. Neurologia 2016; 31 (02) 97-105
  • 8 Saeger W, Honegger J, Theodoropoulou M. et al. Clinical impact of the current WHO classification of pituitary adenomas. Endocr Pathol 2016; 27 (02) 104-114
  • 9 Mete O, Ezzat S, Asa SL. Biomarkers of aggressive pituitary adenomas. J Mol Endocrinol 2012; 49 (02) R69-R78
  • 10 Mete O, Asa SL. Clinicopathological correlations in pituitary adenomas. Brain Pathol 2012; 22 (04) 443-453
  • 11 Yildirim AE, Divanlioglu D, Nacar OA. et al. Incidence, hormonal distribution and postoperative follow up of atypical pituitary adenomas. Turk Neurosurg 2013; 23 (02) 226-231
  • 12 Matsuyama J. Ki-67 expression for predicting progression of postoperative residual pituitary adenomas: correlations with clinical variables. Neurol Med Chir (Tokyo) 2012; 52 (08) 563-569
  • 13 Przhiialkovskaia EG, Abrosimov AIu, Grigor'ev AIu, Marova EI, Rozhinskaia LIa. [Prognostic value of of the expression Ki-67, CD31, and VEGF in somatotropinomas] (in Russian). Arkh Patol 2010; 72 (01) 35-38
  • 14 Chacko G, Chacko AG, Kovacs K. et al. The clinical significance of MIB-1 labeling index in pituitary adenomas. Pituitary 2010; 13 (04) 337-344
  • 15 Gejman R, Swearingen B, Hedley-Whyte ET. Role of Ki-67 proliferation index and p53 expression in predicting progression of pituitary adenomas. Hum Pathol 2008; 39 (05) 758-766
  • 16 Paek KI, Kim SH, Song SH. et al. Clinical significance of Ki-67 labeling index in pituitary macroadenoma. J Korean Med Sci 2005; 20 (03) 489-494
  • 17 Zornitzki T, Knobler H, Nass D, Hadani M, Shimon I. Increased MIB-1/Ki-67 labeling index as a predictor of an aggressive course in a case of prolactinoma. Horm Res 2004; 61 (03) 111-116
  • 18 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 (02) 235-243
  • 19 Trouillas J, Roy P, Sturm N. et al; members of HYPOPRONOS. 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 (01) 123-135
  • 20 Wolfsberger S, Knosp E. Comments on the WHO 2004 classification of pituitary tumors. Acta Neuropathol 2006; 111 (01) 66-67
  • 21 Lloyd ROsamura RY, Klöppel G, Rosai J. WHO Classification of Tumours of Endocrine Organs. 4th ed. Lyon: IARC Press; 2017
  • 22 Lopes MBS. The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. Acta Neuropathol 2017; 134 (04) 521-535
  • 23 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 (04) 610-617
  • 24 Berker M, Hazer DB, Yücel T. et al. Complications of endoscopic surgery of the pituitary adenomas: analysis of 570 patients and review of the literature. Pituitary 2012; 15 (03) 288-300
  • 25 Berker M, Işikay I, Berker D, Bayraktar M, Gürlek A. Early promising results for the endoscopic surgical treatment of Cushing's disease. Neurosurg Rev 2013. Doi: 10.1007/s10143-013-0506-6
  • 26 Akin S, Isikay I, Soylemezoglu F, Yucel T, Gurlek A, Berker M. Reasons and results of endoscopic surgery for prolactinomas: 142 surgical cases. Acta Neurochir (Wien) 2016; 158 (05) 933-942
  • 27 Hazer DB, Işık S, Berker D. et al. Treatment of acromegaly by endoscopic transsphenoidal surgery: surgical experience in 214 cases and cure rates according to current consensus criteria. J Neurosurg 2013; 119 (06) 1467-1477
  • 28 Thapar K, Kovacs K, Scheithauer BW. et al. Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery 1996; 38 (01) 99-106
  • 29 Thapar K, Scheithauer BW, Kovacs K, Pernicone PJ, Laws Jr ER. p53 expression in pituitary adenomas and carcinomas: correlation with invasiveness and tumor growth fractions. Neurosurgery 1996; 38 (04) 765-770
  • 30 Kitz K, Knosp E, Koos WT, Korn A. Proliferation in pituitary adenomas: measurement by MAb KI 67. Acta Neurochir Suppl (Wien) 1991; 53: 60-64
  • 31 Salehi F, Agur A, Scheithauer BW, Kovacs K, Lloyd RV, Cusimano M. Ki-67 in pituitary neoplasms: a review--part I. Neurosurgery 2009; 65 (03) 429-437
  • 32 de Aguiar PH, Aires R, Laws ER. et al. Labeling index in pituitary adenomas evaluated by means of MIB-1: is there a prognostic role? A critical review. Neurol Res 2010; 32 (10) 1060-1071
  • 33 Del Basso De Caro M, Solari D, Pagliuca F. et al. Atypical pituitary adenomas: clinical characteristics and role of ki-67 and p53 in prognostic and therapeutic evaluation. A series of 50 patients. Neurosurg Rev 2017; 40 (01) 105-114
  • 34 Chiloiro S, Doglietto F, Trapasso B. et al. Typical and atypical pituitary adenomas: a single-center analysis of outcome and prognosis. Neuroendocrinology 2015; 101 (02) 143-150
  • 35 Terzi A, Saglam EA, Barak A, Soylemezoglu F. The significance of immunohistochemical expression of Ki-67, p53, p21, and p16 in meningiomas tissue arrays. Pathol Res Pract 2008; 204 (05) 305-314
  • 36 Mengel M, von Wasielewski R, Wiese B, Rüdiger T, Müller-Hermelink HK, Kreipe H. Inter-laboratory and inter-observer reproducibility of immunohistochemical assessment of the Ki-67 labelling index in a large multi-centre trial. J Pathol 2002; 198 (03) 292-299
  • 37 Nishioka H, Inoshita N. New WHO classification of pituitary adenomas (4th edition): assessment of pituitary transcription factors and the prognostic histological factors. Brain Tumor Pathol 2018; 35: 57-61
  • 38 Inoshita N, Nishioka H. The 2017 WHO classification of pituitary adenoma: overview and comments. Brain Tumor Pathol 2018; 35 (02) 51-56