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Oncology · Pancreatic Neuroendocrine Tumor

Decoding Your Pathology Report

At a Glance

Your pancreatic neuroendocrine tumor (pNET) pathology report uses the Ki-67 index and mitotic rate to measure tumor growth and assign a WHO Grade (G1 to G3). These markers, along with cell differentiation, help your doctor understand how aggressive the tumor is and guide treatment decisions.

Your pathology report is the most important document in your medical folder. It is the “source of truth” that tells your care team exactly what kind of cells they are dealing with and how those cells are likely to behave. Understanding a few key terms will empower you to discuss your diagnosis more clearly with your specialist.

Measuring Growth: The Proliferation Markers

Pathologists use two main measurements to see how fast your tumor is growing. Think of these as a “speedometer” for your cancer:

  • Mitotic Rate: A pathologist looks under a microscope and physically counts how many cells are in the actual act of splitting (mitosis) within a specific area, measured as per 2 mm² (historically measured as 10 high-power fields) [1][2].
  • Ki-67 Index: This is a more sensitive test that uses a special stain to identify a protein (Ki-67) present in any cell that is preparing to divide [1][3]. It is expressed as a percentage—the higher the percentage, the more “active” the tumor [4].

The WHO Grading System

The World Health Organization (WHO) uses these “speed” measurements to assign a Grade (G1, G2, or G3). This grade helps predict how aggressive the tumor is [2].

Grade Ki-67 Index Mitotic Rate (per 2 mm²) Growth Description
Grade 1 (G1) Less than 3% Less than 2 Slow-growing (Indolent) [2]
Grade 2 (G2) 3% to 20% 2 to 20 Intermediate growth [2]
Grade 3 (G3) Greater than 20% Greater than 20 Fast-growing (Aggressive) [2]

The Critical Distinction: pNET G3 vs. pNEC

If your report mentions “Grade 3,” it is vital to know which category it falls into. These two types are treated very differently:

  • Well-Differentiated pNET G3: The cells still look somewhat like healthy pancreatic cells, even though they are dividing quickly [5]. These often have a better outlook and respond to different treatments than the alternative [5][6].
  • Poorly Differentiated pNEC (Carcinoma): The cells look very abnormal and messy under the microscope [5]. This is a much more aggressive form that typically requires intensive chemotherapy [7][8].

Confirming the Diagnosis: The “Stains”

To make sure the tumor is actually neuroendocrine, pathologists use immunohistochemistry (IHC)—stains that “light up” when they hit specific proteins found in neuroendocrine cells. Look for these names on your report:

  • Synaptophysin and Chromogranin A: These are the “gold standard” markers used to confirm the tumor is neuroendocrine [2][9].
  • INSM1: A newer, very reliable marker used to double-check the diagnosis [9].

Pathology Report Checklist

Check your report for these essential items. If they are missing, ask your doctor for a “supplemental” or “addendum” report:

  • [ ] Differentiation: Is it called “well-differentiated” or “poorly differentiated”? [5]
  • [ ] Ki-67 Index: Is there a specific percentage listed? [10]
  • [ ] Mitotic Rate: Is there a count of mitoses per 2 mm² (or 10 high-power fields)? [2]
  • [ ] IHC Markers: Are Synaptophysin or Chromogranin A mentioned as positive? [2]
  • [ ] Grade: Is it clearly labeled G1, G2, or G3? [2]

Common questions in this guide

What does the Ki-67 index mean on my pNET pathology report?
The Ki-67 index is a percentage that shows how many tumor cells are actively preparing to divide. A higher Ki-67 percentage indicates a more active and faster-growing tumor, which helps doctors determine the official tumor grade.
How does the WHO grading system work for pancreatic neuroendocrine tumors?
The WHO grading system uses your tumor's Ki-67 index and mitotic rate to assign a grade from 1 to 3. Grade 1 tumors are slow-growing and indolent, while Grade 3 tumors are fast-growing and more aggressive.
What is the difference between a Grade 3 pNET and a pNEC?
A Grade 3 pNET is well-differentiated, meaning the cells look somewhat normal despite growing quickly, and often has a better outlook. A pNEC (carcinoma) is poorly differentiated, meaning cells look highly abnormal, and represents a much more aggressive cancer that requires intensive treatment.
What do positive Synaptophysin and Chromogranin A results mean?
Synaptophysin and Chromogranin A are specific proteins found in neuroendocrine cells. If your pathology report lists these stains as positive, it confirms the diagnosis that your tumor is indeed a neuroendocrine tumor.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What is my specific Ki-67 percentage and mitotic count?
  2. 2.Is my tumor classified as a Grade 3 pNET (well-differentiated) or a pNEC (poorly differentiated)?
  3. 3.Which neuroendocrine markers, like Chromogranin A or INSM1, were used to confirm the diagnosis?
  4. 4.Was there any evidence of lymphovascular invasion or positive margins in the sample?
  5. 5.Was the biopsy sample large enough to give a definitive grade, or do we need more tissue?

Questions For You

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References

References (10)
  1. 1

    Head-to-head: Should Ki67 proliferation index be included in the formal classification of pulmonary neuroendocrine neoplasms?

    Pelosi G, Travis WD

    Histopathology 2024; (85(4)):535-548 doi:10.1111/his.15206.

    PMID: 38728050
  2. 2

    A Clinicopathologic and Molecular Update of Pancreatic Neuroendocrine Neoplasms With a Focus on the New World Health Organization Classification.

    Fang JM, Shi J

    Archives of pathology & laboratory medicine 2019; (143(11)):1317-1326 doi:10.5858/arpa.2019-0338-RA.

    PMID: 31509453
  3. 3

    Key Biomarker Correlations in Cutaneous Melanoma: Implications for Diagnostic, Prognostic, and Therapeutic Strategies-A Retrospective Single-Centered Study.

    Costache M, Gheorghişan-Gălățeanu AA, Derewicz D, et al.

    Medicina (Kaunas, Lithuania) 2025; (61(10)) doi:10.3390/medicina61101733.

    PMID: 41155720
  4. 4

    Can CT Image Reconstruction Parameters Impact the Predictive Value of Radiomics Features in Grading Pancreatic Neuroendocrine Neoplasms?

    Tixier F, Lopez-Ramirez F, Blanco A, et al.

    Bioengineering (Basel, Switzerland) 2025; (12(1)) doi:10.3390/bioengineering12010080.

    PMID: 39851354
  5. 5

    Pancreatic neuroendocrine neoplasms: current state and ongoing controversies on terminology, classification and prognostication.

    Taskin OC, Clarke CN, Erkan M, et al.

    Journal of gastrointestinal oncology 2020; (11(3)):548-558 doi:10.21037/jgo.2020.03.07.

    PMID: 32655934
  6. 6

    Treatment Response and Outcomes of Grade 3 Pancreatic Neuroendocrine Neoplasms Based on Morphology: Well Differentiated Versus Poorly Differentiated.

    Raj N, Valentino E, Capanu M, et al.

    Pancreas 2017; (46(3)):296-301 doi:10.1097/MPA.0000000000000735.

    PMID: 27759713
  7. 7

    DNA methylation reveals distinct cells of origin for pancreatic neuroendocrine carcinomas and pancreatic neuroendocrine tumors.

    Simon T, Riemer P, Jarosch A, et al.

    Genome medicine 2022; (14(1)):24 doi:10.1186/s13073-022-01018-w.

    PMID: 35227293
  8. 8

    Pancreatic neuroendocrine neoplasms: Clinicopathological features and pathological staging.

    Lam AK, Ishida H

    Histology and histopathology 2021; (36(4)):367-382 doi:10.14670/HH-18-288.

    PMID: 33305819
  9. 9

    Neuroendocrine neoplasms of the pancreas: diagnosis and pitfalls.

    Konukiewitz B, Jesinghaus M, Kasajima A, Klöppel G

    Virchows Archiv : an international journal of pathology 2022; (480(2)):247-257 doi:10.1007/s00428-021-03211-5.

    PMID: 34647171
  10. 10

    Ki-67 prognostic and therapeutic decision driven marker for pancreatic neuroendocrine neoplasms (PNENs): A systematic review.

    Pezzilli R, Partelli S, Cannizzaro R, et al.

    Advances in medical sciences 2016; (61(1)):147-53.

    PMID: 26774266

This page explains pancreatic neuroendocrine tumor pathology terminology for educational purposes only. Your pathologist and oncologist are the best sources for interpreting your specific report.

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