Adrenal Cortical Carcinoma: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
May 29, 2026

Adrenal cortical carcinoma is a rare cancer that starts in the adrenal cortex, the outer part of the adrenal gland. There are two adrenal glands in the body, one on top of each kidney. The adrenal cortex normally produces hormones that help control blood pressure, salt and water balance, metabolism, sexual development, and the body’s response to stress. Adrenal cortical carcinoma develops when cells in the adrenal cortex grow uncontrollably and invade nearby tissue or spread to other parts of the body. About half of adrenal cortical carcinomas continue to produce hormones, which causes a separate set of symptoms beyond those of a growing mass.

Adrenal cortical carcinoma is uncommon, with roughly 1 to 2 new cases per million people each year. It is most often diagnosed in middle-aged adults, with a second, smaller peak in young children. The term adrenocortical carcinoma means the same thing and may also appear on pathology reports.

This article will help you understand the findings in your pathology report, what each term means, and why those findings matter for your care.

What causes adrenal cortical carcinoma?

For most adults with adrenal cortical carcinoma, doctors do not know the exact cause. These tumors are described as sporadic, meaning they appear without a known trigger and are not caused by anything the person did or was exposed to. Smoking has been associated with a slightly higher risk of adrenal cortical tumors in some studies, but the link is not strong.

A smaller but important group of adrenal cortical carcinomas occurs in people who carry an inherited genetic change. Genetic causes are especially common in children, where most cases are linked to an inherited syndrome. The most commonly identified hereditary causes include:

Li-Fraumeni syndrome — Caused by an inherited mutation in the TP53 gene, which normally helps cells repair DNA damage and prevent cancer. Li-Fraumeni syndrome substantially raises the lifetime risk of several cancers, including adrenal cortical carcinoma, breast cancer, soft tissue sarcoma, brain tumors, and leukemia. Almost all cases of adrenal cortical carcinoma in young children are associated with Li-Fraumeni syndrome.
Lynch syndrome — Caused by inherited changes in mismatch repair genes (MLH1, MSH2, MSH6, PMS2). Lynch syndrome is best known for colon and uterine cancer but also raises the risk of adrenal cortical carcinoma and several other cancers.
Beckwith-Wiedemann syndrome — A growth disorder caused by changes on chromosome 11. Children with this syndrome have an increased risk of adrenal cortical carcinoma along with Wilms tumor and hepatoblastoma.
Multiple endocrine neoplasia type 1 (MEN1) — Caused by inherited changes in the MEN1 gene. Adrenal cortical tumors are common in MEN1, although most are benign; carcinoma occurs in a minority of cases.
Carney complex and familial adenomatous polyposis (FAP) — Rarer hereditary causes.

Because of the strong inherited component, especially in younger patients, genetic counseling is often considered after a diagnosis of adrenal cortical carcinoma.

What are the symptoms of adrenal cortical carcinoma?

Symptoms come from two main sources: excess hormone production by the tumor, and the size or spread of the tumor itself.

About half of adrenal cortical carcinomas produce hormones. The most common pattern is excess cortisol, often together with excess sex hormones. Cortisol excess can cause symptoms of Cushing syndrome, including weight gain (especially around the abdomen), a rounded face, muscle weakness, easy bruising, mood changes, fatigue, high blood pressure, high blood sugar, thinning bones, and an increased risk of infections. Excess of sex hormones produces different symptoms depending on the hormone. In women, androgen (male hormone) excess may cause increased facial and body hair, acne, deepening of the voice, or changes in menstrual cycles, a pattern called virilization. In men, the symptoms of androgen excess are usually less noticeable. Rarely, an adrenal cortical carcinoma produces estrogen, which can cause breast enlargement in men. Tumors that produce aldosterone are very uncommon in adrenal cortical carcinoma and cause high blood pressure with low blood potassium.

The other source of symptoms is tumor growth itself. Patients may notice abdominal or flank pain, a feeling of fullness in the upper abdomen, nausea, or reduced appetite. In tumors that do not produce hormones, symptoms often appear only after the tumor has grown large or has spread to other organs.

Some adrenal cortical carcinomas are discovered by accident when imaging of the abdomen is performed for an unrelated reason. These are called incidental findings. About 1 in 10 adrenal cortical carcinomas are discovered this way.

How is the diagnosis made?

The workup usually begins when a patient develops symptoms of excess hormone production or when an adrenal mass is identified on imaging. Blood and urine tests measure cortisol, sex hormones, aldosterone, and catecholamine metabolites (the hormones produced by the adrenal gland’s inner part, the medulla). These tests determine whether the tumor is producing hormones and help rule out pheochromocytoma, a different type of adrenal tumor that arises from the medulla. Imaging tests, most often CT and MRI of the abdomen, help estimate the likelihood that an adrenal mass is benign or malignant by measuring the size, appearance, and behavior of the tumor. Adrenal cortical carcinomas are often large at the time of diagnosis, frequently more than 5 centimeters across, and tend to show areas of bleeding or tissue death on imaging. Functional imaging, such as an FDG PET scan, may be added in selected cases.

Needle biopsy of an adrenal mass is generally avoided when adrenal cortical carcinoma is suspected. A needle biopsy can spread tumor cells along the needle track and rarely changes management. The diagnosis is made after the tumor has been surgically removed, usually together with the adrenal gland, and examined under the microscope by a pathologist.

Under the microscope, the pathologist’s main task is to decide whether the tumor is an adrenal cortical adenoma (benign) or an adrenal cortical carcinoma (malignant). The two can look very similar, so the diagnosis depends on a combination of features rather than any single finding. The pathologist evaluates the tumor’s architecture, the appearance of the cells, the number of dividing cells (mitotic count), areas of tumor cell death (necrosis), and whether the tumor invades blood vessels, lymphatic channels, or surrounding tissue. Pathologists also assess the tumor’s supporting framework, called the reticulin network, which is often disrupted in carcinoma but preserved in benign adenomas. To integrate these features, several scoring systems are used, including the Weiss score, the modified Weiss score, the Helsinki score, and the reticulin algorithm. These systems and the features that go into them are explained in the sections below.

Immunohistochemistry uses antibodies to detect specific proteins in tissue. It is used to confirm that the tumor arises from the adrenal cortex and to exclude other tumors that can involve the adrenal gland, such as pheochromocytoma, metastatic cancer from another organ, or renal cell carcinoma extending into the adrenal. The most reliable marker confirming adrenal cortical origin is SF1. Other supportive markers include melan-A, inhibin, calretinin, and synaptophysin. Pheochromocytomas, in contrast, typically express chromogranin A and INSM1 but lack the cortical markers.

Histologic subtypes

The current World Health Organization (WHO) classification, published in 2022, recognizes three histologic subtypes of adrenal cortical carcinoma in addition to the conventional type. The subtype is determined by how the tumor cells look under the microscope.

Conventional adrenal cortical carcinoma — The most common subtype. The tumor cells resemble normal adrenal cortical cells and may have either clear (pale) or eosinophilic (pink) cytoplasm.
Oncocytic adrenal cortical carcinoma — The tumor cells are filled with large numbers of energy-producing structures called mitochondria, which makes the cytoplasm appear bright pink under the microscope. Oncocytic tumors are evaluated using a separate scoring system called the Lin-Weiss-Bisceglia system. As a group, oncocytic carcinomas tend to behave somewhat less aggressively than conventional carcinomas.
Myxoid adrenal cortical carcinoma — The tumor cells are surrounded by a sticky, gel-like material called myxoid stroma. Recognizing this pattern is important because it can be mistaken for other tumor types.
Sarcomatoid adrenal cortical carcinoma — A rare and fast-growing subtype in which some of the tumor cells take on a spindle (elongated) shape resembling a sarcoma. Sarcomatoid carcinomas tend to behave more aggressively than conventional ones.

The subtype is reported alongside the diagnosis and may influence which scoring system the pathologist uses and how the tumor is expected to behave.

Tumor grade and multiparametric scoring systems

The WHO 2022 classification divides adrenal cortical carcinomas into two grades based on the number of dividing cells (mitotic count) seen under the microscope. A mitotic figure is a tumor cell caught in the act of dividing. The pathologist counts the number of mitotic figures in a standard area of tumor (10 square millimeters):

Low-grade adrenal cortical carcinoma — 20 or fewer mitoses per 10 square millimeters.
High-grade adrenal cortical carcinoma — More than 20 mitoses per 10 square millimeters.

High-grade carcinomas tend to grow more quickly, recur sooner, and spread more often than low-grade carcinomas.

To make the diagnosis itself (whether a tumor is a carcinoma or an adenoma) and to estimate how aggressive a carcinoma is likely to be, pathologists use multiparametric scoring systems that combine several features into a single score. Several systems are in current use:

Weiss score and modified Weiss score

The Weiss score is the most widely used system for conventional adrenal cortical carcinoma. It looks at nine features and assigns one point for each one that is present:

High mitotic count (more than 5 mitoses per 50 high-power fields).
Atypical mitoses (dividing cells with an abnormal shape).
Cells that look very different from each other (high nuclear grade).
Areas of tumor cell death (necrosis).
Solid growth in more than one-third of the tumor.
Clear cells in less than one-quarter of the tumor.
Sinusoidal invasion (tumor cells inside small blood-filled spaces).
Venous invasion (tumor cells inside a vein).
Capsular invasion (tumor cells growing through the tumor’s fibrous outer layer).

A total Weiss score of 3 or more supports a diagnosis of adrenal cortical carcinoma. A score of 0 or 1 supports a benign adenoma. Scores of 2 are uncertain and prompt the pathologist to seek additional evidence.

The modified Weiss score is a simpler version that uses only five of the nine features and is more reproducible between pathologists. A modified Weiss score of 3 or more also supports a diagnosis of carcinoma.

Helsinki score

The Helsinki score combines three features into a single number:

The mitotic count (multiplied by 3).
The presence of necrosis (5 points if present, 0 if absent).
The Ki-67 percentage (added directly).

A Helsinki score greater than 8.5 supports a diagnosis of adrenal cortical carcinoma. Higher scores are linked to a higher risk of recurrence and spread. Some centers use a score above 17 to identify tumors at particularly high risk.

Reticulin algorithm

The reticulin algorithm uses a special stain that highlights the supporting fiber network around tumor cell groups. In benign adenomas, this network is intact; in carcinomas, it is broken up or lost. The diagnosis of carcinoma is made when the reticulin network is disrupted, and at least one of the following is present: increased mitotic activity, tumor cell death, or vascular invasion. The reticulin algorithm is simple, reproducible, and applicable across all histologic subtypes, including oncocytic and pediatric tumors.

Wieneke system

The Wieneke system is used specifically for adrenal cortical tumors in children. The features that predict malignant behavior in children differ from those in adults, and applying adult criteria to pediatric tumors can overcall them as carcinoma. The Wieneke system uses tumor weight, tumor size, and several microscopic features tailored to pediatric tumors.

Vascular invasion

Vascular invasion means that tumor cells are seen inside a blood vessel, most often a vein. In adrenal cortical carcinoma, vascular invasion is one of the most important findings in the pathology report. The WHO 2022 classification emphasizes vascular invasion as a key feature for both confirming malignancy and predicting outcome.

The pathologist diagnoses true vascular invasion when tumor cells are seen invading through a vessel wall or present within a vessel along with blood clot material. The presence of vascular invasion increases the risk that the cancer will recur after surgery or spread to other parts of the body, especially the liver and lungs. In low-grade carcinomas, vascular invasion is one of the strongest predictors of recurrence and shorter time without disease.

Lymphatic invasion

Lymphatic invasion means that tumor cells are seen inside a lymphatic channel. Lymphatic channels are small thin-walled vessels that carry a clear fluid called lymph from tissues toward the lymph nodes. The WHO 2022 classification asks pathologists to report lymphatic invasion separately from vascular invasion, because the two findings have different patterns of spread. Lymphatic invasion increases the risk that tumor cells will reach the regional lymph nodes.

Surgical margins

A margin is the cut edge of the tissue removed at surgery. The pathologist examines the margins to determine whether the tumor was completely removed. For adrenal cortical carcinoma, complete removal of the tumor in one piece, with the surrounding fat and capsule intact, gives the best chance of long-term cure.

Negative margin — No tumor cells are seen at the cut edge. This is the most favorable result and is the strongest single predictor of long-term survival.
Positive margin — Tumor cells reach the cut edge. A positive margin indicates that some tumor may have been left behind and is linked to a higher risk of local recurrence. Additional surgery or adjuvant therapy may be considered.
Close margin — Tumor cells come within a few millimeters of the cut edge without reaching it. The pathology report often gives the distance in millimeters. A close margin is generally more favorable than a positive margin but may still influence the surveillance plan.
Capsular rupture during surgery — If the surface of the tumor was disrupted at the time of operation, tumor cells may have spilled into the surgical bed. This is associated with a higher risk of recurrence even when the formal margin is negative.

Lymph nodes

Lymph nodes are small bean-shaped structures throughout the body that filter fluid and house immune cells. The lymph nodes that drain the adrenal gland are located behind the abdominal organs, around the major blood vessels (the aorta and the inferior vena cava) and near the kidneys. The pathology report will state how many lymph nodes were examined and how many contained tumor cells. Routine removal of all nearby lymph nodes is not standard for every patient with adrenal cortical carcinoma, but the surgeon may remove suspicious lymph nodes or perform a wider dissection when the tumor is large or when imaging suggests involvement. Lymph node involvement is reported in roughly 1 in 10 patients at the time of diagnosis and is associated with a higher pathologic stage and a worse prognosis.

The pathologist also looks for extranodal extension, which means that tumor cells have broken through the outer capsule of a lymph node into surrounding tissue. When present, extranodal extension is an adverse finding.

Biomarker and molecular testing

Biomarker testing supports the diagnosis of adrenal cortical carcinoma, helps estimate the risk of recurrence, and identifies patients who may benefit from referral to genetic counseling.

Ki-67 proliferation index

Ki-67 is a protein that appears only in cells that are actively dividing. The pathologist counts the percentage of tumor cells with Ki-67 staining; this number is called the Ki-67 proliferation index. It is usually measured in the most active area of the tumor, called the hot spot. Results are reported as a percentage, for example “Ki-67: 8 percent” or “Ki-67 approximately 25 percent in hot spots.” Most adrenal cortical carcinomas show a Ki-67 index above 5 percent, often much higher than the index seen in benign adenomas. A higher Ki-67 index is associated with a higher risk of recurrence after surgery and may influence decisions about additional therapy. WHO 2022 does not endorse a single fixed Ki-67 cutoff for grading, since the index varies continuously rather than fitting cleanly into categories, but the value is reported and used as one of several pieces of information when planning follow-up.

Hormone production

Whether the tumor produces hormones is determined by blood and urine testing before surgery, not by the pathology report. However, the pathology report may comment on the appearance of the surrounding normal adrenal cortex. A thinned (atrophic) cortex around the tumor supports excess cortisol production from the tumor. Hormone production has clinical relevance because cortisol-producing carcinomas have, in some studies, been associated with a higher risk of recurrence and worse outcomes than non-functioning tumors. Patients with cortisol excess also need temporary hormone replacement after surgery while the suppressed normal adrenal gland recovers.

Genetic and molecular testing

Molecular testing is not required for every adrenal cortical carcinoma but is increasingly important for risk assessment and for identifying inherited causes. Common findings include changes in the TP53 gene (which encodes the p53 protein and is also affected in Li-Fraumeni syndrome), changes in the CTNNB1 gene (which encodes the beta-catenin protein and is associated with a worse prognosis), and changes in the IGF2 region on chromosome 11. Testing for these changes may be performed on tumor tissue, a blood sample, or both. A blood test that identifies an inherited (germline) genetic change can confirm Li-Fraumeni syndrome or another hereditary cancer syndrome, with important implications for the patient and for relatives who may also carry the change.

Genetic counseling and testing are most often considered when the patient is a child, when the patient is young at diagnosis, when there is a family history of cancers in the Li-Fraumeni spectrum (breast, sarcoma, brain, leukemia), or when other features of an inherited syndrome are present.

For more information on biomarker testing in cancer, please visit our Biomarkers section.

Pathologic stage (pTNM)

The pathologic stage describes how far the cancer has spread. Adrenal cortical carcinoma is staged using the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, currently in its 8th edition, which adopted the staging system originally proposed by the European Network for the Study of Adrenal Tumours (ENSAT). The system has three parts: tumor (pT), nodal (pN), and metastasis (pM). The M category (whether the cancer has spread to distant organs) is determined by imaging rather than by pathology.

Tumor stage (pT)

pT1 — The tumor is 5 centimeters or less in greatest dimension, with no spread outside the adrenal gland.
pT2 — The tumor is larger than 5 centimeters, still with no spread outside the adrenal gland.
pT3 — The tumor extends into the surrounding fat or soft tissue but does not invade adjacent organs.
pT4 — The tumor directly invades adjacent organs (such as the kidney, pancreas, spleen, liver, or diaphragm) OR a tumor thrombus is present in the renal vein or the inferior vena cava (the large vein draining the abdomen).

Nodal stage (pN)

pN0 — No tumor cells in any regional lymph nodes examined.
pN1 — Tumor cells are present in one or more regional lymph nodes.

Stage grouping

Stage I — pT1, pN0, M0. Tumor 5 cm or less, confined to the adrenal gland, no nodal or distant spread.
Stage II — pT2, pN0, M0. Tumor larger than 5 cm, confined to the adrenal gland, no nodal or distant spread.
Stage III — Tumor of any size with either local extension beyond the adrenal gland (pT3 or pT4) OR regional lymph node involvement (pN1), without distant spread.
Stage IV — Distant spread (M1), regardless of the pT or pN category.

What is the prognosis?

The prognosis of adrenal cortical carcinoma depends most strongly on the stage at the time of diagnosis and on whether the tumor can be completely removed. Survival is highly variable, and individual outcomes can differ significantly from average statistics. Reported five-year overall survival rates from large patient registries are approximately:

Stage I — 60 to 80 percent.
Stage II — 50 to 60 percent.
Stage III — 35 to 50 percent.
Stage IV — Less than 15 percent, although patients with limited metastatic disease and good response to treatment can live considerably longer.

Pathologic features that have been independently linked to a higher risk of recurrence or worse overall outcome include:

Positive surgical margin or capsular rupture during surgery — Tumor cells may have been left behind.
Vascular invasion — Particularly important in low-grade carcinomas, where it strongly predicts recurrence.
Lymphatic invasion or lymph node involvement — Linked to worse overall survival.
Distant metastasis at diagnosis — The strongest single predictor of poor outcome.
Larger tumor size (over 5 centimeters) and higher tumor weight — Linked to higher recurrence rates.
High-grade tumor (more than 20 mitoses per 10 square millimeters) — Associated with faster recurrence and worse survival.
High Ki-67 proliferation index — A higher percentage is linked to a higher risk of recurrence.
Cortisol-producing tumors — Have been associated with worse outcomes than non-functioning tumors in some studies.
Sarcomatoid histologic subtype — Behaves more aggressively than the conventional or oncocytic subtypes.

Because adrenal cortical carcinoma is rare and complex, follow-up is best coordinated through a specialized center with experience in adrenal tumors.

What happens after this diagnosis?

The pathology findings guide the next steps in care rather than dictating a single treatment. After complete staging with imaging and hormone testing, the treatment team typically considers:

Surgical re-evaluation — If the margin is positive or the capsule was disrupted at the first operation, further surgery may be considered when feasible.
Adjuvant mitotane — Mitotane is a drug that suppresses the adrenal cortex and is the only medication specifically approved as adjuvant therapy for adrenal cortical carcinoma. It is typically considered after surgery in patients with high-risk features such as a high Ki-67 index, vascular invasion, positive margins, or advanced stage. The decision to use mitotane is made by the medical oncology team and is anchored to specific pathology findings.
Adjuvant radiation therapy — May be considered in selected cases when the margin is positive in a location where re-operation is not feasible, or for symptomatic local recurrence.
Systemic chemotherapy — Reserved for advanced or metastatic disease. The most established combination is mitotane plus etoposide, doxorubicin, and cisplatin (EDP). The medical oncology team decides whether and when chemotherapy is appropriate, based on the pathology findings and the extent of disease.
Hormone replacement — Patients whose tumor produced large amounts of cortisol often need temporary steroid replacement after surgery, since the normal adrenal cortex on both sides has been suppressed and takes time to recover.
Long-term surveillance — Imaging of the abdomen and chest along with hormone tests are repeated at regular intervals, usually every few months for the first several years, then less often. The pathology features (stage, grade, margin status, Ki-67) help the treatment team decide how closely to follow up.
Genetic counseling — Considered for all patients, and particularly important for children, young adults, and anyone with a family history suggestive of Li-Fraumeni syndrome or another inherited cancer syndrome.
Multidisciplinary care — Endocrine surgery, endocrinology, medical oncology, radiation oncology, and (where relevant) genetics work together to plan treatment and follow-up. Palliative care is sometimes involved alongside other treatments, particularly for advanced disease, to help manage symptoms such as pain and the effects of hormone excess.

Questions to ask your doctor

What was the size of my tumor, and was it confined to the adrenal gland?
Was the tumor completely removed, and were the margins clear?
Was the capsule of the tumor intact during surgery?
Which histologic subtype is my tumor (conventional, oncocytic, myxoid, or sarcomatoid)?
Is my tumor low-grade or high-grade, and what was the mitotic count?
What were the Weiss, modified Weiss, or Helsinki scores in my case, and what do they mean?
What was the Ki-67 proliferation index, and how does it affect my follow-up plan?
Was vascular invasion or lymphatic invasion present?
How many lymph nodes were examined, and were any involved by tumor?
What is my pathologic stage (pT, pN, and pM)?
Did my tumor produce hormones, and will I need temporary hormone replacement after surgery?
Should I be referred for genetic counseling and testing for Li-Fraumeni syndrome or another inherited cause?
Is adjuvant mitotane being considered based on my pathology findings?
How often will I need follow-up imaging and hormone testing, and for how long?
Would referral to a center experienced in adrenal cortical carcinoma help guide my care?