Transcription Factor Immunohistochemistry in the Classification of Pituitary Neuroendocrine Tumor/Adenoma: Proposal in a Limited-Resource Setting

Arch Pathol Lab Med. 2024 Feb 1;148(2):178-189. doi: 10.5858/arpa.2021-0479-OA.


Context.—: Pituitary neuroendocrine tumors/adenomas are common intracranial tumors that require accurate subtyping because each tumor differs in its biologic behavior and response to treatment. Pituitary-specific transcription factors allow for improved lineage identification and diagnosis of newly introduced variants.

Objective.—: To assess the usefulness of transcription factors and design a limited panel of immunostains for classification of pituitary neuroendocrine tumors/adenoma.

Design.—: A total of 356 tumors were classified as per expression of pituitary hormones and transcription factors T-box family member TBX19 (TPIT), pituitary-specific POU-class homeodomain (PIT1), and steroidogenic factor-1 (SF-1). The resultant classification was correlated with patients' clinical and biochemical features. The performance and relevance of individual immunostains were analyzed.

Results.—: Reclassification of 34.8% (124 of 356) of pituitary neuroendocrine tumors/adenoma was done after application of transcription factors. The highest agreement with final diagnosis was seen using a combination of hormone and transcription factors. SF-1 had higher sensitivity, specificity, and predictive value compared with follicle-stimulating hormone and luteinizing hormone. On the other hand, TPIT and PIT1 had similar performance and Allred scores compared with their respective hormones.

Conclusions.—: SF-1 and PIT1 should be included in the routine panel for guiding the classification. PIT1 positivity needs to be followed by hormone immunohistochemistry, especially in nonfunctional cases. TPIT and adrenocorticotropin can be used interchangeably as per availability of the lab.

MeSH terms

  • Adenoma* / pathology
  • Adrenocorticotropic Hormone
  • Humans
  • Immunohistochemistry
  • Neuroendocrine Tumors* / diagnosis
  • Pituitary Neoplasms* / metabolism
  • Transcription Factors


  • Transcription Factors
  • Adrenocorticotropic Hormone