by Jason Wasserman MD PhD FRCPC
January 18, 2026
Adrenal cortical carcinoma is a rare but aggressive cancer that starts in the adrenal cortex, the outer part of the adrenal gland. The adrenal cortex normally produces hormones that help control blood pressure, salt and water balance, metabolism, and the body’s response to stress. Some adrenal cortical carcinomas produce excess hormones, while others mainly cause symptoms by forming a growing mass.
This article explains the pathology report for adrenal cortical carcinoma, including how it is diagnosed, what features pathologists look for, and how these findings relate to prognosis and treatment.
What are the symptoms of adrenal cortical carcinoma?
The symptoms of adrenal cortical carcinoma are often caused by excess hormone production, pressure from a growing tumour, or spread to other parts of the body.
About half of adrenal cortical carcinomas produce hormones. The most common pattern is excess cortisol, either alone or together with sex hormones. Cortisol excess can cause symptoms of Cushing syndrome, such as weight gain (especially around the abdomen), muscle weakness, easy bruising, mood changes, fatigue, high blood pressure, high blood sugar, osteoporosis, and increased susceptibility to infections. Sometimes, cortisol excess is mild and harder to detect without specialized testing.
In adults, virilization or feminization caused by an adrenal mass is an important warning sign for carcinoma. In women, androgen excess may cause increased facial hair, acne, voice deepening, or menstrual changes. In men, hormone excess may be less noticeable. Rarely, estrogen production causes breast enlargement in men. Aldosterone-producing adrenal cortical carcinoma is very uncommon.
Some patients have symptoms related to tumour growth, including abdominal or flank pain, a feeling of fullness, nausea, or reduced appetite. In Nonfunctioning tumours, symptoms may first appear only after the cancer has spread.
Who gets adrenal cortical carcinoma?
Adrenal cortical carcinoma most often affects adults and is diagnosed most commonly in middle age or later. It can also occur in children, where inherited genetic risk is more likely.
What causes adrenal cortical carcinoma?
Most cases occur sporadically, meaning they develop by chance and without a family history. Smoking has been associated with an increased risk of adrenal cortical tumours.
A small but significant subset of adrenal cortical carcinomas occurs in the setting of inherited cancer syndromes. The most well-known is Li–Fraumeni syndrome (caused by inherited TP53 mutations), which is especially important in children. Adrenal cortical carcinoma can also occur in people with Lynch syndrome, Beckwith–Wiedemann syndrome, Carney complex, familial adenomatous polyposis, multiple endocrine neoplasia type 1, and several other rare hereditary conditions. Because of this, genetic counselling and testing may be recommended in selected patients based on age, personal history, and family history.
How is the diagnosis made?
The diagnosis is made by combining clinical information (including hormone testing), imaging findings, and microscopic examination of tumour tissue. Pathologists determine whether a tumour is an adenoma (benign) or carcinoma (malignant) using specific microscopic features and scoring systems.
Imaging
Imaging studies such as CT and MRI help doctors estimate the likelihood that an adrenal mass is benign or malignant and assess whether the tumour has invaded nearby structures. Compared with adenomas, adrenal cortical carcinomas are more likely to be large and show a more heterogeneous appearance on imaging, sometimes with areas suggesting tumour necrosis or bleeding. Functional imaging, such as FDG PET, can provide additional information in some cases, but it is not perfect because some benign tumours can also show increased uptake.
Microscopic (pathologic) features
Under the microscope, adrenal cortical carcinoma is diagnosed based on evidence that the tumour comes from adrenal cortical cells and shows features of malignancy. Compared with adenomas, carcinomas more often show solid growth, broad trabeculae, and large nests of tumour cells. The tumour’s supporting framework (called the reticulin framework) is frequently disrupted or lost, which supports malignancy in the appropriate setting.
Pathologists also look carefully for invasion, which means tumour cells are breaking through normal boundaries or entering structures where they do not belong. Capsular invasion means tumour cells are growing into or through the capsule that surrounds the tumour or adrenal gland. This is important because it shows the tumour is behaving in a cancerous, infiltrative way. Lymphatic invasion means tumour cells are found inside lymphatic vessels. This matters because lymphatic vessels can provide a pathway for tumour cells to spread to lymph nodes.
Because no single microscopic feature is perfect on its own, pathologists typically use established multi-feature systems (such as the Weiss score or related algorithms) to support the diagnosis.
Vascular invasion
Vascular invasion means tumour cells are found inside blood vessels, most often veins. This is one of the most critical findings in adrenal cortical carcinoma because it is both a strong sign of malignancy and an important predictor of outcome.
Pathologists diagnose true vascular invasion when tumour cells are seen invading through a vessel wall and/or sitting inside a vessel space, often mixed with blood clot material (fibrin or thrombus). Vascular invasion increases the risk of spread and is associated with a higher chance of recurrence after surgery. In low-grade carcinomas, vascular invasion is one of the strongest predictors of reduced disease-free survival.
Immunohistochemistry
Immunohistochemistry uses special stains to detect proteins inside tumour cells. It helps confirm that a tumour arises from the adrenal cortex and excludes other tumours that can involve the adrenal gland, such as pheochromocytoma or metastatic cancer.
The most reliable marker confirming adrenal cortical origin is SF1. Other supportive markers include melan-A, inhibin, calretinin, and synaptophysin, although these are less specific and must be interpreted in context. Pheochromocytomas, in contrast, are typically positive for chromogranin A and INSM1.
Molecular testing
Molecular testing is not routinely needed to diagnose adrenal cortical carcinoma. It may be considered in selected cases for risk stratification or when an inherited cancer syndrome is suspected. Genetic testing is particularly important in children, young adults, and patients with a suggestive personal or family history.
Tumour grade
Adrenal cortical carcinomas are commonly divided into low-grade and high-grade based on the rate of tumour cell division. Faster-growing tumours tend to behave more aggressively.
One way to measure growth rate is mitotic count, the number of tumour cells observed dividing (mitotic figures) when the tissue is examined under the microscope. Pathologists count mitotic figures in a defined area (often reported as a number per 10 mm²).
In many practices, tumours are classified as:
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Low grade when there are 20 or fewer mitoses per 10 mm².
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High grade when there are more than 20 mitoses per 10 mm².
Another way to measure growth is the Ki-67 proliferation index, determined by immunohistochemistry. Ki-67 highlights tumour cells that are actively cycling. The result is reported as a percentage, usually measured in the most active area of the tumour (“hot spot”). For example, the report may state: “Ki-67 proliferation index: 8%” or “Ki-67: approximately 25% in hot spots.” Higher Ki-67 values are associated with worse prognosis and may influence decisions about additional therapy after surgery.
What is the Helsinki score?
The Helsinki score is a scoring system used by some pathology teams to help assess adrenal cortical tumours. It combines three features into a single score: tumour mitotic activity, tumour necrosis, and the Ki-67 proliferation index.
The Helsinki score is calculated as follows: (3 × mitotic count) + (5 × necrosis) + (Ki-67 percentage).
Necrosis means tumour cell death. It is scored as present or absent (if present, it contributes points), and Ki-67 is added as the measured percentage from the tumour hot spot.
The result is reported as a single number (for example, “Helsinki score: 12”). A score greater than 8.5 supports the diagnosis of adrenal cortical carcinoma in the appropriate setting. Higher values are associated with more aggressive behaviour, and some centres use higher cutoffs (e.g.,>17) to identify particularly high-risk tumours.
Margins
A margin is the edge of tissue that the surgeon cuts through to remove the tumour. The pathologist carefully examines margins to determine whether the tumour was completely removed.
For adrenal cortical carcinoma, margins are especially important because:
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A negative margin means no tumour cells are seen at the cut edge of the tissue. This suggests the tumour was entirely removed and is associated with a lower risk of local recurrence.
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A positive margin means tumour cells are present at the cut edge. This indicates that some tumour may have been left behind and is associated with a higher risk of the cancer coming back in the same area.
If margins are close but not involved, the report may include the distance (usually measured in millimetres) between the tumour and the nearest margin. Your doctors use margin status, together with tumour stage and other risk factors, to decide whether additional treatment or closer follow-up is needed.
How is adrenal cortical carcinoma staged?
Adrenal cortical carcinoma is staged using either the AJCC/UICC TNM system or the ENSAT staging system. Staging takes into account tumour size, local invasion into surrounding tissues or major veins, lymph node involvement, and distant metastases. Stage at diagnosis is one of the most important predictors of prognosis.
What is the prognosis for a person with adrenal cortical carcinoma?
Prognosis depends on tumour stage, completeness of resection, hormone production, vascular invasion, tumour grade, Ki-67 index, and margin status. Completely removed localized tumours without vascular invasion may be curable. Advanced tumours, especially those with distant spread, have a much poorer outlook.
Because this cancer is rare and complex, treatment and follow-up are best coordinated through a specialized centre with experience managing adrenal tumours.
What happens after the diagnosis?
After diagnosis, patients typically undergo complete staging with imaging and hormone testing. Surgery is the most important treatment when the tumour can be entirely removed. Additional therapy may be recommended based on risk factors, including stage, vascular invasion, margins, tumour grade, Ki-67, and scoring systems such as the Helsinki score. Long-term follow-up is essential to monitor for recurrence.
Questions to ask your doctor
- Was the tumour completely removed, and were the margins clear?
- Was vascular invasion identified?
- Is my tumour low-grade or high-grade, and what were the mitotic count and Ki-67 results?
- Was a Helsinki score reported, and what does it mean in my case?
- What stage is my cancer, and has it spread beyond the adrenal gland?
- Should I be evaluated for an inherited cancer syndrome?
- How often will I need follow-up imaging and hormone testing?
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