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Pituitary

, Volume 22, Issue 5, pp 514–519 | Cite as

Clinical, pathologic, and imaging characteristics of pituitary null cell adenomas as defined according to the 2017 World Health Organization criteria: a case series from two pituitary centers

  • Joao Paulo Almeida
  • Corbin C. Stephens
  • Jennifer M. Eschbacher
  • Michelle M. Felicella
  • Kevin C. J. Yuen
  • William L. White
  • Michael A. Mooney
  • Anne Laure Bernat
  • Ozgur Mete
  • Gelareh Zadeh
  • Fred Gentili
  • Andrew S. LittleEmail author
Article
  • 155 Downloads

Abstract

Purpose

The 2017 World Health Organization classification of pituitary tumors redefined pituitary null cell adenomas (NCAs) by restricting this diagnostic category to pituitary tumors that are negative for pituitary transcription factors and adenohypophyseal hormones. The clinical behavior of this redefined entity has not been widely studied, and this is a major shortcoming of the classification. This study evaluated the imaging and clinical features of NCAs from two pituitary centers and compared them with those of gonadotroph adenomas (GAs).

Methods

Imaging, pathologic, and clinical characteristics of NCAs and GAs were retrospectively reviewed. Tumor immunohistochemistry was performed to confirm absence of adenohypophyseal hormones and pituitary transcription factor expression.

Results

Thirty-one NCAs were compared with 38 GAs. NCAs were more likely to invade the cavernous sinus (15/31 [48%] vs. 5/38 [13%], P = .003) and had a higher proliferative index (i.e., MIB-1 > 3%, 11/31 [35%] vs. 5/38 [13%], P = .04). Gross total resection was less likely in the NCA group (19/31 [61%] vs. 33/38 [87], P = .02). Progression-free survival was worse in the NCA cohort (5-year progression-free survival, 0.70 vs. 1.00; P = .011, by log-rank test).

Conclusions

Compared with GAs, NCAs are more invasive at the time of presentation and have a more aggressive clinical course. This study provides evidence that NCAs represent a distinct clinicopathologic entity with behavior that differs adversely from that of GAs. This may inform clinical decision-making, including frequency of postoperative tumor surveillance and timing of adjunctive treatments.

Keywords

Gonadotroph adenoma Gonadotroph tumors Null cell adenoma Null cell pituitary tumor pituitary 

Abbreviations

GA

Gonadotroph adenoma

NCA

Null cell pituitary adenoma

WHO

World Health Organization

T-Pit

T-box family member that is the product of TBX19

SF-1

Steroidogenic factor 1

PIT-1

Pituitary-specific POU class homeodomain transcription factor 1

Notes

Acknowledgements

The authors thank the Neuroscience Publications office at Barrow Neurological Institute for assistance with manuscript preparation.

Author contributions

Dr. ASL and Dr. WLW contributed to the study design. Dr. WLW, Dr. ASL, Dr. JME, Dr. MMF, Dr. GZ, Dr. JPA, Dr. FG, Dr. OM, Dr. KCJY, Dr ALB, and Mr. CCS participated in manuscript preparation and critical review. Dr. JPA, Dr. ASL, and Mr. CCS participated in data collection. All authors contributed to data interpretation

Funding

Barrow Neurological Foundation, Phoenix, Arizona, USA.

Compliance with ethical standards

Conflict of interest

Dr. Little is a stockholder in Kogent Surgical, LLC, and has stock options in SPIWay, LLC. Dr. Yuen is a consultant for Pfizer, Novo Nordisk, Sandoz, Aeterna Zentaris, Novartis, Corcept Therapeutics, and Strongbridge. Drs. White, Mooney, Felicella, Zadeh, Almeida, Gentili, Mete, Bernat, Eschbacher, and Mr. Stephens have no disclosures.

Supplementary material

11102_2019_981_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 13 kb)
11102_2019_981_MOESM2_ESM.docx (16 kb)
Supplementary material 2 (DOCX 17 kb)

References

  1. 1.
    Vieira LN, Boguszewski CL, Araujo LA, Bronstein MD, Miranda PA, Musolino NR, Naves LA, Vilar L, Ribeiro-Oliveira AJ, Gadelha MR (2016) A review on the diagnosis and treatment of patients with clinically nonfunctioning pituitary adenoma by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism. Arch Endocrinol Metab 60(4):374–390.  https://doi.org/10.1590/2359-3997000000179 CrossRefGoogle Scholar
  2. 2.
    Kovacs K, Horvath E, Ryan N, Ezrin C (1980) Null cell adenoma of the human pituitary. Virchows Arch A Pathol Anat Histol 387(2):165–174CrossRefGoogle Scholar
  3. 3.
    International Agency for Research on Cancer (2017) WHO Classification of Tumours of Endocrine Organs, 4th ed. MedicineGoogle Scholar
  4. 4.
    Mete O, Cintosun A, Pressman I, Asa SL (2018) Epidemiology and biomarker profile of pituitary adenohypophysial tumors. Mod Pathol 31(6):900–909.  https://doi.org/10.1038/s41379-018-0016-8 CrossRefGoogle Scholar
  5. 5.
    Nishioka H, Inoshita N, Mete O, Asa SL, Hayashi K, Takeshita A, Fukuhara N, Yamaguchi-Okada M, Takeuchi Y, Yamada S (2015) The complementary role of transcription factors in the accurate diagnosis of clinically nonfunctioning pituitary adenomas. Endocr Pathol 26(4):349–355.  https://doi.org/10.1007/s12022-015-9398-z CrossRefGoogle Scholar
  6. 6.
    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 CrossRefGoogle Scholar
  7. 7.
    Lloyd RV, Osamura, RY, Klöppel G, Rosai J (2017) WHO classification of tumours of the endocrine organs, vol. 10, 4th ed. Medicine, vol. 10. International Agency For Research on Cancer, LyonGoogle Scholar
  8. 8.
    Nishioka K, Kontogeorgas G, Lloyd RV, Lopes MB, Mete O, Nose V (2017) Null cell adenoma. In: Lloyd RV, Osamura RY, Klöppel G, Rosai J (eds) WHO classification of tumours of the endocrine organs, vol 10. International Agency For Research on Cancer, Lyon Cedex, pp 37–38Google Scholar
  9. 9.
    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 CrossRefGoogle Scholar
  10. 10.
    McDonald WC, Banerji N, McDonald KN, Ho B, Macias V, Kajdacsy-Balla A (2017) Steroidogenic factor 1, Pit-1, and adrenocorticotropic hormone: a rational starting place for the immunohistochemical characterization of pituitary adenoma. Arch Pathol Lab Med 141(1):104–112.  https://doi.org/10.5858/arpa.2016-0082-OA CrossRefGoogle Scholar
  11. 11.
    Knosp E, Steiner E, Kitz K, Matula C (1993) Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery 33(4):610–617 discussion 617-618 Google Scholar
  12. 12.
    Donangelo I, Melmed S (2006) Implication of pituitary tropic status on tumor development. Front Horm Res 35:1–8.  https://doi.org/10.1159/000094259 Google Scholar
  13. 13.
    Cheung LY, Davis SW, Brinkmeier ML, Camper SA, Perez-Millan MI (2017) Regulation of pituitary stem cells by epithelial to mesenchymal transition events and signaling pathways. Mol Cell Endocrinol 445:14–26.  https://doi.org/10.1016/j.mce.2016.09.016 CrossRefGoogle Scholar
  14. 14.
    Vankelecom H, Gremeaux L (2010) Stem cells in the pituitary gland: a burgeoning field. Gen Comp Endocrinol 166(3):478–488.  https://doi.org/10.1016/j.ygcen.2009.11.007 CrossRefGoogle Scholar
  15. 15.
    Nishioka H, Inoshita N (2018) New WHO classification of pituitary adenomas (4th edition): assessment of pituitary transcription factors and the prognostic histological factors. Brain Tumor Pathol 35(2):57–61.  https://doi.org/10.1007/s10014-017-0307-7 CrossRefGoogle Scholar
  16. 16.
    Batista RL, Trarbach EB, Marques MD, Cescato VA, da Silva GO, Herkenhoff CGB, Cunha-Neto MB, Musolino NR (2018) Nonfunctioning pituitary adenoma recurrence and its relationship with sex, size, and hormonal immunohistochemical profile. World Neurosurg 120:e241–e246.  https://doi.org/10.1016/j.wneu.2018.08.043 CrossRefGoogle Scholar
  17. 17.
    Greenman Y, Stern N (2009) Non-functioning pituitary adenomas. Best Pract Res Clin Endocrinol Metab 23(5):625–638.  https://doi.org/10.1016/j.beem.2009.05.005 CrossRefGoogle Scholar
  18. 18.
    Mete O, Asa SL (2012) Clinicopathological correlations in pituitary adenomas. Brain Pathol 22(4):443–453.  https://doi.org/10.1111/j.1750-3639.2012.00599.x CrossRefGoogle Scholar
  19. 19.
    Asa SL (2008) Practical pituitary pathology: what does the pathologist need to know? Arch Pathol Lab Med 132(8):1231–1240.  https://doi.org/10.1043/1543-2165(2008)132%5b1231:pppwdt%5d2.0.co;2 Google Scholar
  20. 20.
    Young WF Jr, Scheithauer BW, Kovacs KT, Horvath E, Davis DH, Randall RV (1996) Gonadotroph adenoma of the pituitary gland: a clinicopathologic analysis of 100 cases. Mayo Clin Proc 71(7):649–656.  https://doi.org/10.1016/S0025-6196(11)63002-4 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Joao Paulo Almeida
    • 1
  • Corbin C. Stephens
    • 2
  • Jennifer M. Eschbacher
    • 3
  • Michelle M. Felicella
    • 3
  • Kevin C. J. Yuen
    • 4
  • William L. White
    • 2
  • Michael A. Mooney
    • 2
  • Anne Laure Bernat
    • 1
  • Ozgur Mete
    • 5
  • Gelareh Zadeh
    • 1
  • Fred Gentili
    • 1
  • Andrew S. Little
    • 2
    • 6
    Email author
  1. 1.Division of Neurosurgery, Toronto Western Hospital, University Health NetworkUniversity of TorontoTorontoCanada
  2. 2.Department of NeurosurgeryBarrow Neurological InstitutePhoenixUSA
  3. 3.Department of NeuropathologyBarrow Neurological InstitutePhoenixUSA
  4. 4.Department of NeuroendocrinologyBarrow Neurological InstitutePhoenixUSA
  5. 5.Laboratory Medicine Program, Department of Pathology, University Health NetworkUniversity of TorontoTorontoCanada
  6. 6.c/o Neuroscience PublicationsBarrow Neurological Institute, St. Joseph’s Hospital and Medical CenterPhoenixUSA

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