Cell Lineage-Specific Differences in Clinical Behavior of Non-Functioning Pituitary Adenomas

The Journal of Clinical Endocrinology & Metabolism, vol. 110, pp. e2362–e2382

Abstract

CONTEXT: Immunohistochemistry (IHC) of cell lineage-specific transcription factors (TFs) has been added to the histopathological classification of pituitary adenomas since 2017, resulting in new histopathological subtypes of TF+/hormone-non-functioning pituitary adenomas (NFPAs) and a reduction in the prevalence of null cell adenomas (NCAs). OBJECTIVE: This work aimed to evaluate associations between expression of cell lineage-specific TFs by IHC and radiological invasion and prognosis of NFPAs. DATA SOURCES: A literature search in Medline, Embase, and CENTRAL was performed from inception up to July 11, 2023. STUDY SELECTION: Eligible studies were cohort studies reporting on radiological invasion, recurrence, and/or radiotherapy in patients with NFPAs who tested positive for one cell lineage-specific TF or negative for all 3. Finally, 27 out of 1985 studies were included. DATA EXTRACTION: Two authors independently extracted data and critically appraised risk of bias using the Quality In Prognostic Studies (QUIPS) tool. DATA SYNTHESIS: Random-effects inverse variance models were used to pool effect sizes. Prevalence rate ratios (PRRs) were calculated using the Mantel-Haenszel method. Cavernous sinus invasion was more prevalent in NCAs and TPIT+ NFPAs compared with SF1+ NFPAs (PRR 1.60; 95% CI, 1.22-2.08, I2 10%, 95% prediction interval [PrI] 1.23-2.06; P = .0036, and PRR 1.43; 95% CI, 1.21-1.70, I2 0%, 95% PrI 1.17-1.76; P = .0017, respectively), and in NCAs compared with PIT1+ (PRR 1.44; 95% CI, 1.01-2.06, I2 0%, 95% PrI 0.83-2.50; P = .0454). A limited number of studies precluded data syntheses of recurrence and radiotherapy. CONCLUSION: The use of cell lineage-specific TFs by IHC enables to detect histopathological subtypes of NFPAs with distinct clinical behavior.

Authors 8

1. Loren S van der Hoeven corresponding Aachen Department of Endocrinology and Metabolism

   Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers · Endo-ERN · Amsterdam Gastroenterology Endocrinology Metabolism · University of Amsterdam

   Affiliation as printed

   Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology and Metabolism (AGEM), 1105 AZ, Amsterdam, the  

   Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, Pituitary Center Amsterdam , 1105 AZ, Amsterdam ,

   European Reference Network on Rare Endocrine Conditions (Endo-ERN), Coordinated from Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, 1105 AZ, Amsterdam, the  

   Amsterdam Gastroenterology Endocrinology and Metabolism (AGEM), Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

   Department of Endocrinology and Metabolism, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

   European Reference Network on Rare Endocrine Conditions (Endo-ERN)

   Pituitary Center Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

2. Tessa N. A. Slagboom

   Amsterdam University Medical Centers · Amsterdam Gastroenterology Endocrinology Metabolism · University of Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam

   Affiliation as printed

   Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, Pituitary Center Amsterdam , 1105 AZ, Amsterdam ,

   Amsterdam UMC, Vrije Univerisiteit Amsterdam, Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology and Metabolism (AGEM) , 1084 HV, Amsterdam, the Netherlands

   Amsterdam Gastroenterology Endocrinology and Metabolism (AGEM), Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

   Department of Endocrinology and Metabolism, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands

   Pituitary Center Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

3. Arjan Malekzadeh

   Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers · University of Amsterdam

   Affiliation as printed

   Amsterdam UMC, University of Amsterdam, Medical Library , 1105 AZ, Amsterdam ,

   Amsterdam UMC location University of Amsterdam, Medical Library, Meibergdreef 9, Amsterdam, The Netherlands

4. Jantien Hoogmoed Aachen Department of Endocrinology and Metabolism

   Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers · Endo-ERN · University of Amsterdam

   Affiliation as printed

   Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, Pituitary Center Amsterdam , 1105 AZ, Amsterdam ,

   Amsterdam UMC, University of Amsterdam, Department of Neurosurgery , 1105 AZ, Amsterdam ,

   European Reference Network on Rare Endocrine Conditions (Endo-ERN), Coordinated from Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism , 1105 AZ, Amsterdam , the

   Department of Neurosurgery, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

   European Reference Network on Rare Endocrine Conditions (Endo-ERN)

   Pituitary Center Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

5. Madeleine L. Drent Aachen Department of Endocrinology and Metabolism

   Amsterdam University Medical Centers · Endo-ERN · Amsterdam Gastroenterology Endocrinology Metabolism · University of Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam

   Affiliation as printed

   Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, Pituitary Center Amsterdam , 1105 AZ, Amsterdam ,

   Amsterdam UMC, Vrije Univerisiteit Amsterdam, Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology and Metabolism (AGEM) , 1084 HV, Amsterdam, the Netherlands

   European Reference Network on Rare Endocrine Conditions (Endo-ERN), Coordinated from Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, 1105 AZ, Amsterdam, the  

   Amsterdam Gastroenterology Endocrinology and Metabolism (AGEM), Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

   Department of Endocrinology and Metabolism, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands

   European Reference Network on Rare Endocrine Conditions (Endo-ERN)

   Pituitary Center Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

6. Eleonora Aronica

   Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers · University of Amsterdam

   Affiliation as printed

   Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology , 1105 AZ, Amsterdam ,

   Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, Pituitary Center Amsterdam , 1105 AZ, Amsterdam ,

   Department of (Neuro)Pathology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

   Pituitary Center Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

7. Dirk Jan Stenvers Aachen Department of Endocrinology and Metabolism

   Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers · Endo-ERN · Amsterdam Gastroenterology Endocrinology Metabolism · University of Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam

   Affiliation as printed

   Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology and Metabolism (AGEM), 1105 AZ, Amsterdam, the  

   Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, Pituitary Center Amsterdam , 1105 AZ, Amsterdam ,

   Amsterdam UMC, Vrije Univerisiteit Amsterdam, Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology and Metabolism (AGEM) , 1084 HV, Amsterdam, the Netherlands

   European Reference Network on Rare Endocrine Conditions (Endo-ERN), Coordinated from Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, 1105 AZ, Amsterdam, the  

   Amsterdam Gastroenterology Endocrinology and Metabolism (AGEM), Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

   Department of Endocrinology and Metabolism, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

   Department of Endocrinology and Metabolism, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands

   European Reference Network on Rare Endocrine Conditions (Endo-ERN)

   Pituitary Center Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

8. Alberto M. Pereira Aachen Department of Endocrinology and Metabolism

   Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers · Endo-ERN · Amsterdam Gastroenterology Endocrinology Metabolism · University of Amsterdam

   Affiliation as printed

   Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology and Metabolism (AGEM), 1105 AZ, Amsterdam, the  

   Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, Pituitary Center Amsterdam , 1105 AZ, Amsterdam ,

   European Reference Network on Rare Endocrine Conditions (Endo-ERN), Coordinated from Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, 1105 AZ, Amsterdam, the  

   Amsterdam Gastroenterology Endocrinology and Metabolism (AGEM), Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

   Department of Endocrinology and Metabolism, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

   European Reference Network on Rare Endocrine Conditions (Endo-ERN)

   Pituitary Center Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands