Oncology · Adrenocortical Carcinoma

Staging and Your Pathology Report

At a Glance

For adrenocortical carcinoma, ENSAT stage, Ki-67 percentage, surgical margins, age, and hormone-related symptoms are combined in the S-GRAS score to estimate recurrence risk and help guide follow-up care.

Your pathology report and staging are the most important tools your care team uses to understand the nature of your Adrenocortical Carcinoma (ACC) and plan your follow-up care. Rather than looking at a single number, doctors use a combination of factors—your tumor’s size, how fast it is growing, and whether it was completely removed—to create a personal risk profile ^[1]^[2].

The ENSAT Staging System

The European Network for the Study of Adrenal Tumors (ENSAT) system is the standard way to describe how far the cancer has spread ^[3].

Stage I: The tumor is 5 cm (about 2 inches) or smaller and is still entirely inside the adrenal gland ^[3]^[4].
Stage II: The tumor is larger than 5 cm but is still confined within the adrenal gland ^[3]^[4].
Stage III: The tumor has begun to spread locally. This might mean it has grown into nearby fat, blood vessels (like the renal vein or vena cava), or nearby lymph nodes ^[5]^[4].
Stage IV: The cancer has spread to distant parts of the body, such as the lungs, liver, or bones ^[4]^[6].

Decoding the Pathology Report

When a pathologist looks at your tumor under a microscope, they are looking for specific clues about how aggressive the cancer is. It is highly recommended to have these results reviewed by an expert adrenal pathologist.

The Weiss Score

The Weiss score is the standard tool for diagnosing ACC in adults. The pathologist looks for nine specific features, such as the appearance of the cells’ nuclei and whether the tumor is invading blood vessels ^[7]. A score of 3 or more typically confirms that the tumor is a carcinoma (cancer) rather than a benign adenoma ^[8]^[9]. Note: The original Weiss system is primarily an adult tool; pediatric/adolescent tumors and specific variants, such as oncocytic tumors, may use different scoring algorithms.

The Ki-67 Index: The Growth Speedometer

The Ki-67 index is a measurement of how many cells in the tumor are actively dividing at any given moment ^[9]. You can think of it as a “speedometer” for the cancer. Because ACC can be patchy, pathologists often look for “hotspots”—the areas where the cells are growing the fastest—to get this number ^[10]^[11].

The percentage matters deeply for your treatment plan:

Low Growth (Ki-67 ≤10%): These tumors are generally less aggressive. If the tumor was small and completely removed, your doctor might suggest close monitoring instead of immediate medication ^[12]^[13].
Intermediate Growth (Ki-67 11–19%): These tumors fall into a middle risk category where treatment decisions are highly individualized ^[1]^[12].
High Growth (Ki-67 ≥20%): A score of 20% or higher indicates a fast-growing tumor. This is a major factor in deciding to start adjuvant (preventative) treatments like mitotane ^[1]^[14].

Surgical Margins: Was it all removed?

After surgery, the pathologist examines the edges (margins) of the tissue removed.

R0 (Negative Margins): No cancer cells were seen at the outer edge. This is the goal of surgery ^[15]^[16].
R1 (Microscopic Positive): The surgeon removed all visible cancer, but the pathologist found cancer cells at the edge under a microscope ^[17]^[16].
R2 (Macroscopic Positive): Some visible tumor could not be safely removed during surgery ^[1]^[15].
Rx: The margin status cannot be adequately assessed or documented ^[1].

Putting it Together: The S-GRAS Score

Modern medicine no longer looks at these factors in isolation. Many experts now use composite models like the S-GRAS score to act as a prognostic aid to predict the risk of the cancer returning ^[1]. It assigns points based on:

Factor	What it Measures	Points Assigned
Stage	Your ENSAT Stage (0 points for Stage I-II, up to 3 points for Stage IV)	0 to 3 points
Resection	Your surgical margin status (R0 = 0 points, R1 = 1 point, R2/Rx = 2 points)	0 to 2 points
Grade	Your Ki-67 Index percentage (≤9% = 0 points, 10-19% = 1 point, ≥20% = 2 points)	0 to 2 points
Age	Whether you are 50 or older	0 or 1 point
Symptoms	Whether you had hormone symptoms at diagnosis	0 or 1 point

A higher total score (on a scale of 0 to 9) correlates with a higher statistical risk of recurrence and helps your multidisciplinary team decide how aggressive your follow-up care should be ^[1]^[18]. Talk to your doctor about your specific S-GRAS score to better understand your path forward.

Common questions in this guide

How does ENSAT staging describe my adrenocortical carcinoma?

ENSAT staging describes how far adrenocortical carcinoma has spread. Stage I is a tumor 5 cm or smaller confined to the adrenal gland, stage II is larger but still confined, stage III involves nearby tissue, blood vessels, or lymph nodes, and stage IV has spread to distant organs. The stage is one part of the information used to estimate recurrence risk and plan follow-up.

What does the Ki-67 percentage mean on an ACC pathology report?

The Ki-67 percentage estimates how many tumor cells are actively dividing, so it acts as a measure of growth speed. ACC can be uneven, so the pathologist may report a hotspot, the area with the most active growth. A result of 20% or higher is considered high in this framework and may prompt discussion of additional treatment, such as mitotane.

What does a Weiss score of 3 or higher mean?

In adults, a Weiss score of 3 or more typically supports a diagnosis of adrenocortical carcinoma rather than a benign adrenal adenoma. The score is based on nine microscopic features, including cell appearance and blood-vessel invasion. Children, adolescents, and some oncocytic tumors may need different scoring methods.

How do R0, R1, R2, and Rx margins differ?

R0 means no cancer cells were seen at the examined edge of the removed tissue. R1 means cancer cells were found at the edge only under a microscope, while R2 means visible tumor remained after surgery. Rx means the margin status could not be adequately assessed or documented.

What is the S-GRAS score used for in ACC?

S-GRAS combines ENSAT stage, surgical margin status, Ki-67 percentage, age, and hormone-related symptoms at diagnosis into a score from 0 to 9. A higher score is associated with a higher statistical risk of recurrence, but it does not predict one person’s outcome with certainty. Your multidisciplinary team can use it to help plan the intensity of follow-up and discuss additional treatment.

Does a high Ki-67 automatically mean I need mitotane?

No. A Ki-67 of 20% or higher is an important factor when doctors consider adjuvant mitotane after surgery, but treatment decisions also depend on stage, margin status, and your overall situation. Ask your oncology team whether mitotane or a monitored approach is appropriate for you.

Should an expert review my ACC pathology report?

Because ACC is uncommon and its microscopic features can be complex, review by a pathologist experienced with adrenal tumors may help confirm the diagnosis and clarify the Weiss score, Ki-67, and margin status. Ask whether your report has been reviewed by a specialist before making treatment or follow-up decisions.

Get notified when new evidence is published on adrenal carcinoma.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.

Key takeaways

ENSAT stage describes how far adrenocortical carcinoma has spread: stages I and II remain within the adrenal gland, stage III is locally advanced, and stage IV is distant.
In adults, a Weiss score of 3 or more typically supports an adrenocortical carcinoma diagnosis rather than a benign adenoma; pediatric and oncocytic tumors may require other scoring systems.
The Ki-67 index measures actively dividing tumor cells, and a result of 20% or higher is considered high and may influence adjuvant mitotane discussions.
R0 means no cancer was seen at the examined margin, R1 means microscopic cancer reaches the edge, R2 means visible tumor remains, and Rx cannot be adequately assessed.
The S-GRAS score combines stage, margin status, Ki-67, age, and hormone symptoms to estimate recurrence risk, with higher scores indicating higher statistical risk.

References (18)

1
S-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT study.
Elhassan YS, Altieri B, Berhane S, et al.
European journal of endocrinology 2021; (186(1)):25-36.
PMID: 34709200
2
Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection.
Beuschlein F, Weigel J, Saeger W, et al.
The Journal of clinical endocrinology and metabolism 2015; (100(3)):841-9 doi:10.1210/jc.2014-3182.
PMID: 25559399
3
[Are there still indications for open adrenalectomy?]
Holzer K, Bartsch DK
Chirurgie (Heidelberg, Germany) 2022; (93(9)):856-860 doi:10.1007/s00104-022-01678-9.
PMID: 35788865
4
[ADRENOCORTICAL CARCINOMA].
Kranjčević K
Acta medica Croatica : casopis Hravatske akademije medicinskih znanosti 2016; (70(4-5)):315-8.
PMID: 29087170
5
Prognostic factors in stage III-IV adrenocortical carcinomas (ACC): an European Network for the Study of Adrenal Tumor (ENSAT) study.
Libé R, Borget I, Ronchi CL, et al.
Annals of oncology : official journal of the European Society for Medical Oncology 2015; (26(10)):2119-25 doi:10.1093/annonc/mdv329.
PMID: 26392430
6
Advanced adrenocortical carcinoma successfully treated with gemcitabine plus capecitabine as second-line chemotherapy.
Yamamoto A, Nakai Y, Oka T, et al.
IJU case reports 2020; (3(6)):270-273 doi:10.1002/iju5.12214.
PMID: 33163922
7
How to Differentiate Benign from Malignant Adrenocortical Tumors?
Viëtor CL, Creemers SG, van Kemenade FJ, et al.
Cancers 2021; (13(17)) doi:10.3390/cancers13174383.
PMID: 34503194
8
[Guidelines of the French National ENDOCAN-COMETE, Association of Endocrine Surgery, Society of Urology for the management of adrenocortical carcinoma].
Libé R, Haissaguerre M, Renaudin K, et al.
Bulletin du cancer 2023; (110(6)):707-730 doi:10.1016/j.bulcan.2023.03.015.
PMID: 37061367
9
Data set for reporting of carcinoma of the adrenal cortex: explanations and recommendations of the guidelines from the International Collaboration on Cancer Reporting.
Giordano TJ, Berney D, de Krijger RR, et al.
Human pathology 2021; (110()):50-61 doi:10.1016/j.humpath.2020.10.001.
PMID: 33058949
10
Comparison of the methods for measuring the Ki-67 labeling index in adrenocortical carcinoma: manual versus digital image analysis.
Yamazaki Y, Nakamura Y, Shibahara Y, et al.
Human pathology 2016; (53()):41-50.
PMID: 26980031
11
Diagnosis and grading of adrenal cortical carcinoma.
Vocino Trucco G, Duregon E, Papotti M, Volante M
Virchows Archiv : an international journal of pathology 2026; (488(1)):193-210 doi:10.1007/s00428-025-04278-0.
PMID: 41057662
12
Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study.
Terzolo M, Fassnacht M, Perotti P, et al.
The lancet. Diabetes & endocrinology 2023; (11(10)):720-730 doi:10.1016/S2213-8587(23)00193-6.
PMID: 37619579
13
European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors
Fassnacht M, Dekkers OM, Else T, et al.
European journal of endocrinology 2018; (179(4)):G1-G46 doi:10.1530/EJE-18-0608.
PMID: 30299884
14
Adjuvant mitotane therapy is beneficial in non-metastatic adrenocortical carcinoma at high risk of recurrence.
Calabrese A, Basile V, Puglisi S, et al.
European journal of endocrinology 2019; (180(6)):387-396.
PMID: 30991359
15
Adrenocortical Carcinoma: Impact of Surgical Margin Status on Long-Term Outcomes.
Margonis GA, Kim Y, Prescott JD, et al.
Annals of surgical oncology 2016; (23(1)):134-41 doi:10.1245/s10434-015-4803-x.
PMID: 26286195
16
Survival impact of treatment utilization and margin status after resection of adrenocortical carcinoma.
Memeh K, Abou Azar S, Afolaranmi O, Vaghaiwalla TM
American journal of surgery 2025; (239()):115999 doi:10.1016/j.amjsurg.2024.115999.
PMID: 39427460
17
Impact of Micro- and Macroscopically Positive Surgical Margins on Survival after Resection of Adrenocortical Carcinoma.
Anderson KL, Adam MA, Thomas SM, et al.
Annals of surgical oncology 2018; (25(5)):1425-1431 doi:10.1245/s10434-018-6398-5.
PMID: 29500765
18
External validation of the S-GRAS score for predicting recurrence in patients with adrenocortical carcinoma: implications for adjuvant mitotane therapy.
Jimenez-Fonseca P, Álvarez-Escola C, Ballester Navarro I, et al.
European journal of endocrinology 2025; (193(2)):320-328 doi:10.1093/ejendo/lvaf171.
PMID: 40810251

This page is for informational purposes only and does not constitute medical advice. An adrenal pathologist and oncology team should interpret your ACC report and discuss your staging, recurrence risk, and treatment plan.

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