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PubMed This is a summary of 17 peer-reviewed journal articles Updated
Endocrinology · Pituitary Neuroendocrine Tumor

Pathology: Decoding Your Pituitary Tumor (PitNET) Report

At a Glance

A pituitary pathology report for Cushing disease identifies the tumor's specific characteristics, now officially called a PitNET. Key markers like T-PIT confirm the tumor's origin, while the Ki-67 index and USP8 mutation status help doctors predict tumor behavior and plan future treatments.

When your neurosurgeon removes the tumor causing your Cushing disease, the tissue is sent to a laboratory where a pathologist examines it under a microscope. This examination results in a Pathology Report, which is the final word on what was growing in your pituitary gland.

The New Name: PitNET

You may notice a change in how your tumor is described. In 2022, the World Health Organization (WHO) updated the official name for pituitary tumors from “Pituitary Adenoma” to Pituitary Neuroendocrine Tumor, or PitNET [1][2].

  • Why the change? The term “adenoma” implies a simple, harmless growth. Doctors moved to “PitNET” to recognize that these tumors are biologically active and can vary in how they behave—some are very quiet, while others are more persistent [3].
  • Is it cancer? For the vast majority of patients, the answer is no. While “tumor” is a scary word, the “PitNET” label is used to help doctors better predict how the tumor might grow or respond to treatment, rather than to label it as a malignancy [4][1].

Key Markers to Look For

A modern pathology report uses immunohistochemistry (staining the cells with special dyes) to identify the specific “fingerprint” of your tumor [5].

1. T-PIT: The Lineage Marker

This is the most important “identity” marker for Cushing-related tumors. T-PIT is a transcription factor—a protein that acts like a master switch to turn a cell into a “corticotroph” (an ACTH-producing cell) [6]. If your tumor is T-PIT positive, it confirms the tumor belongs to the family of cells that causes Cushing disease [7].

2. ACTH Staining

This confirms the tumor was actively producing Adrenocorticotropic Hormone (ACTH) [8]. In some cases, a tumor may be “silent,” meaning it is T-PIT positive but not actually pumping ACTH into your blood [9].

3. Crooke’s Hyaline Change

You might see this unusual phrase on your report. Crooke’s hyaline change is a glass-like appearance that happens to normal pituitary cells when they are exposed to very high levels of cortisol [10].

  • What it means: Finding this change in the normal tissue next to the tumor is actually a good sign—it proves that your body was indeed under “cortisol stress” and that the surgeon likely found the right spot [11].

Molecular Insights: The USP8 Mutation

Recent research has discovered that about half of all ACTH-secreting tumors have a specific genetic mutation called USP8 [12].

  • The “Good” Mutation: If your tumor has a USP8 mutation, it is often associated with smaller, less invasive tumors and a higher chance of achieving full remission after surgery [13][14].
  • Treatment Clues: Tumors with this mutation may also respond better to specific medications, such as pasireotide, if the disease ever returns [15].

Your Completeness Checklist

When you review your report with your doctor, ensure these four elements are present to have a complete picture of your diagnosis [5][16]:

  1. Lineage Confirmation: Does it mention T-PIT or Corticotroph lineage?
  2. Proliferation Index: Does it list a Ki-67 percentage? (Lower than 3% is usually considered less aggressive) [17].
  3. Invasion Status: Does the pathologist mention if the tumor was growing into nearby structures like the cavernous sinus?
  4. Hormone Profile: Does it confirm ACTH positivity?

By understanding these markers, you and your medical team can move from “guessing” how your body will recover to having a data-driven plan for your long-term health.

Common questions in this guide

Why is my pituitary tumor now called a PitNET instead of an adenoma?
The term PitNET stands for Pituitary Neuroendocrine Tumor. Doctors use this updated name rather than 'adenoma' to recognize that these tumors are biologically active and vary in how they behave, helping them better predict future growth or treatment responses.
What does T-PIT positive mean on my pathology report?
T-PIT is a specific protein that acts as a master switch for cells that produce ACTH. A T-PIT positive result confirms that your tumor belongs to the family of cells responsible for causing Cushing disease.
What is Crooke's hyaline change?
Crooke's hyaline change is a glass-like appearance in normal pituitary cells caused by exposure to high cortisol levels. Seeing this in the normal tissue around your tumor confirms your body was under cortisol stress and that the surgeon removed tissue from the correct area.
What does a USP8 mutation mean for my pituitary tumor?
About half of ACTH-producing tumors have a USP8 genetic mutation. Tumors with this mutation are often smaller, less invasive, and have a higher chance of full remission after surgery, as well as a better response to certain medications if the disease returns.
Why is the Ki-67 index important on my pathology report?
The Ki-67 index measures how fast the tumor cells are multiplying. A lower Ki-67 percentage, typically under three percent, usually indicates a slower-growing and less aggressive tumor.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does the report mention 'T-PIT' or 'ACTH' staining, and what do those results tell us about the tumor's origin?
  2. 2.What was the Ki-67 labeling index for my tumor, and how does that affect my risk of recurrence?
  3. 3.Is there any evidence of 'invasion' mentioned in the report that didn't show up on my MRI?
  4. 4.Does my tumor show 'Crooke’s hyaline change,' and is that a sign that the remaining pituitary is functioning normally?
  5. 5.Was my tumor tested for the USP8 mutation, and does that help us predict how I might respond to future medications if needed?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (17)
  1. 1

    From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal.

    Asa SL, Casar-Borota O, Chanson P, et al.

    Endocrine-related cancer 2017; (24(4)):C5-C8 doi:10.1530/ERC-17-0004.

    PMID: 28264912
  2. 2

    Overview of the 2022 WHO Classification of Pituitary Tumors.

    Asa SL, Mete O, Perry A, Osamura RY

    Endocrine pathology 2022; (33(1)):6-26 doi:10.1007/s12022-022-09703-7.

    PMID: 35291028
  3. 3

    A clinicopathological study of non-functioning pituitary neuroendocrine tumours using the World Health Organization 2022 classification.

    Woo CS, Ho RS, Ho G, et al.

    Frontiers in endocrinology 2024; (15()):1368944 doi:10.3389/fendo.2024.1368944.

    PMID: 38756997
  4. 4

    Pituitary Neuroendocrine Tumor: Is It Benign or Malignant?

    Lee CH

    Brain tumor research and treatment 2023; (11(3)):173-176 doi:10.14791/btrt.2023.0015.

    PMID: 37550816
  5. 5

    Pituitary adenomas: biology, nomenclature and clinical classification.

    Ho KKY, Melmed S

    Reviews in endocrine & metabolic disorders 2025; (26(2)):137-146 doi:10.1007/s11154-025-09944-x.

    PMID: 39862335
  6. 6

    Overexpression of T-box Transcription Factor 5 (TBX5) Inhibits Proliferation and Invasion in Non-Small Cell Lung Carcinoma Cells.

    Ma R, Yang Y, Tu Q, Hu K

    Oncology research 2017; (25(9)):1495-1504 doi:10.3727/096504017X14883287513729.

    PMID: 28276311
  7. 7

    Transcription factor-based classification of pituitary adenomas / PitNETs: a comparative analysis and clinical implications across WHO 2004, 2017 and 2022 in 921 cases.

    Nasi-Kordhishti I, Hladik M, Kandilaris K, et al.

    Acta neuropathologica communications 2025; (13(1)):135 doi:10.1186/s40478-025-02050-8.

    PMID: 40579705
  8. 8

    Liver metastases from pituitary carcinomas mimicking visceral well-differentiated neuroendocrine tumors: a series of four cases.

    Venable ER, Kerr SE, Lopes MBS, et al.

    Diagnostic pathology 2020; (15(1)):81 doi:10.1186/s13000-020-00997-x.

    PMID: 32622369
  9. 9

    Delineating the Spectrum of Pituitary Adenoma Based on the WHO 2017 Classification.

    Paramita P, Shilpa R, Nandeesh BN, et al.

    Neurology India 2024; (72(1)):96-101 doi:10.4103/neuroindia.NI_913_20.

    PMID: 38443009
  10. 10

    USP8, USP48, and BRAF mutations differ in their genotype-phenotype correlation in Asian Indian patients with Cushing's disease.

    Abraham AP, Pai R, Beno DL, et al.

    Endocrine 2022; (75(2)):549-559 doi:10.1007/s12020-021-02903-x.

    PMID: 34664215
  11. 11

    Significance of Crooke's Hyaline Change in Nontumorous Corticotrophs of Patients With Cushing Disease.

    Akirov A, Larouche V, Shimon I, et al.

    Frontiers in endocrinology 2021; (12()):620005 doi:10.3389/fendo.2021.620005.

    PMID: 33815279
  12. 12

    PATHOGENESIS OF CUSHING DISEASE: AN UPDATE ON THE GENETICS OF CORTICOTROPINOMAS.

    Albani A, Perez-Rivas LG, Reincke M, Theodoropoulou M

    Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists 2018; (24(10)):907-914 doi:10.4158/EP-2018-0111.

    PMID: 30084690
  13. 13

    Relevance of mutations in protein deubiquitinases genes and TP53 in corticotroph pituitary tumors.

    Pękul M, Szczepaniak M, Kober P, et al.

    Frontiers in endocrinology 2024; (15()):1302667 doi:10.3389/fendo.2024.1302667.

    PMID: 38487343
  14. 14

    USP8 and TP53 Drivers are Associated with CNV in a Corticotroph Adenoma Cohort Enriched for Aggressive Tumors.

    Uzilov AV, Taik P, Cheesman KC, et al.

    The Journal of clinical endocrinology and metabolism 2021; (106(3)):826-842 doi:10.1210/clinem/dgaa853.

    PMID: 33221858
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    The USP8 mutational status may predict drug susceptibility in corticotroph adenomas of Cushing's disease.

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    European journal of endocrinology 2016; (174(2)):213-26 doi:10.1530/EJE-15-0689.

    PMID: 26578638
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    Clinical and Pathological Features of Pit1/SF1 Multilineage Pituitary Neuroendocrine Tumor.

    Wang X, Tang H, Bie Z, et al.

    Neurosurgery 2024; doi:10.1227/neu.0000000000002846.

    PMID: 38289085
  17. 17

    Preoperative prediction of granulation pattern subtypes in GH-secreting pituitary adenomas.

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This page explains PitNET and Cushing disease pathology terminology for educational purposes only. Always discuss your specific pathology report results with your neuroendocrinologist or neurosurgeon.

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