, 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



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).


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.


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).


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.


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



Gonadotroph adenoma


Null cell pituitary adenoma


World Health Organization


T-box family member that is the product of TBX19


Steroidogenic factor 1


Pituitary-specific POU class homeodomain transcription factor 1



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


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)


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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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