Oncocytic Adrenal Cortical Carcinoma: Understanding Your Pathology Report

Section Editor: Jason Wasserman MD PhD FRCPC
May 29, 2026

Oncocytic 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. Oncocytic adrenal cortical carcinoma is a recognized subtype of adrenal cortical carcinoma. The term adrenocortical carcinoma means the same thing as adrenal cortical carcinoma and may also appear on pathology reports.

The word oncocytic describes the appearance of the tumor cells under the microscope. Oncocytic cells are filled with numerous energy-producing structures called mitochondria, which make the cytoplasm of each cell appear bright pink and granular. For a tumor to be classified as oncocytic, more than 90 percent of the tumor cells must show these features. The current World Health Organization (WHO) classification, published in 2022, recognizes oncocytic adrenal cortical carcinoma as a distinct subtype that is evaluated using a specific scoring system (the Lin-Weiss-Bisceglia system, described in detail below).

Compared with the more common conventional adrenal cortical carcinoma, oncocytic carcinomas tend to be less likely to produce hormones and, as a group, behave somewhat less aggressively. They can still spread to other parts of the body, however, and the same general approach to treatment, follow-up, and surveillance applies.

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 oncocytic adrenal cortical carcinoma?

For most adults, doctors do not know the exact cause of oncocytic adrenal cortical carcinoma. 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, including oncocytic ones, occurs in people who carry an inherited genetic change. 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.
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.
Lynch syndrome, Carney complex, and familial adenomatous polyposis (FAP) — Rarer hereditary causes that can include adrenal cortical carcinoma as part of a broader cancer pattern.

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

What are the symptoms of oncocytic adrenal cortical carcinoma?

Many oncocytic adrenal cortical carcinomas do not produce hormones. These tumors are often discovered because they grow large enough to cause symptoms by pressing on nearby organs, or because they are seen by chance on an imaging test performed for another reason (an incidental finding). Symptoms from a growing mass can include:

Abdominal or flank pain or discomfort.
A feeling of fullness in the upper abdomen.
Nausea, reduced appetite, or feeling full after eating only a small amount.
A lump that can be felt in the upper abdomen.
Unexplained weight loss.
Back pain when the tumor presses on structures behind the abdomen.

When the tumor does produce hormones, the most common pattern is excess cortisol, sometimes together with sex hormones. Cortisol excess can cause symptoms of Cushing syndrome, including weight gain (especially around the abdomen and face), muscle weakness, easy bruising, mood changes, fatigue, high blood pressure, high blood sugar, thinning bones, and an increased risk of infections. Sex hormone excess can cause virilization in women (increased facial and body hair, deepening of the voice, irregular menstrual cycles) or, more rarely, feminization in men (breast enlargement). Aldosterone production is very uncommon in oncocytic adrenal cortical carcinoma.

How is the diagnosis made?

The workup usually begins when an adrenal mass is found on an imaging test, or when a patient develops symptoms of hormone excess. 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, are used to evaluate the size and appearance of the tumor and to look for spread.

Needle biopsy is generally avoided when adrenal cortical carcinoma is suspected, because 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 confirms that the tumor cells have the oncocytic appearance and then evaluates several features to decide whether the tumor is an oncocytoma (benign), an oncocytic neoplasm of uncertain malignant potential (borderline), or an oncocytic carcinoma (malignant). The features assessed include the number of dividing cells (mitotic count), whether any dividing cells look abnormal in shape (atypical mitoses), tumor cell death (necrosis), tumor size and weight, and whether tumor cells have invaded blood vessels, lymphatic channels, or surrounding tissue. The Lin-Weiss-Bisceglia system, described in the next section, combines these features into a structured framework specifically designed for oncocytic tumors. Oncocytic adrenal cortical tumors require extensive tissue sampling because the diagnostic features can be focal, and a single missed feature can change the diagnosis.

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.

The Lin-Weiss-Bisceglia system

The Lin-Weiss-Bisceglia (LWB) system is the scoring system recommended by the WHO 2022 classification for evaluating oncocytic adrenal cortical tumors. Unlike the standard Weiss score used for conventional tumors, the LWB system was developed specifically for oncocytic tumors because they behave differently and because some features that would be worrisome in a conventional tumor (such as large nuclei or pink cytoplasm) are part of the normal appearance of oncocytic cells.

The LWB system divides features into three major criteria and four minor criteria.

Major criteria

High mitotic count — More than 5 mitotic figures per 50 high-power fields (a defined area of tumor examined under the microscope).
Atypical mitotic figures — Dividing cells with an abnormal shape or pattern.
Venous invasion — Tumor cells inside a vein.

Minor criteria

Large tumor — More than 10 centimeters across or weighing more than 200 grams.
Necrosis — Areas of tumor cell death.
Capsular invasion — Tumor cells growing into or through the fibrous capsule that surrounds the tumor.
Sinusoidal invasion — Tumor cells inside small blood-filled spaces within the tumor.

How the criteria are interpreted

The combination of features in a tumor determines which diagnosis it receives:

Adrenal cortical oncocytoma (benign) — No major and no minor criteria are present.
Oncocytic adrenal cortical neoplasm of uncertain malignant potential (borderline) — One or more minor criteria are present, but no major criteria. These tumors usually behave in a benign way but cannot be confidently called benign, so long-term follow-up is recommended.
Oncocytic adrenal cortical carcinoma (malignant) — At least one major criterion is present, regardless of how many minor criteria are also present. This is the diagnosis described in this article.

Your pathology report will usually list which features were present and which were not. This information helps the pathology team explain the diagnosis and helps your treatment team plan the next steps.

Tumor grade

The WHO 2022 classification divides adrenal cortical carcinomas into two grades based on the mitotic count, measured per 10 square millimeters of tumor:

Low-grade — 20 or fewer mitoses per 10 square millimeters.
High-grade — 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. The mitotic count used for grading (per 10 square millimeters) is measured slightly differently from the LWB major criterion (more than 5 per 50 high-power fields), but both reflect how actively the tumor cells are dividing.

Other scoring systems that may appear on your report

Pathologists sometimes apply additional scoring systems to oncocytic adrenal cortical tumors. These are not replacements for the Lin-Weiss-Bisceglia system, but they can provide additional information that supports the diagnosis or helps estimate the risk of recurrence.

Helsinki score

The Helsinki score combines three features into a single number:

The mitotic count (multiplied by 3 if greater than 5 per 10 square millimeters).
The presence of necrosis (5 points if present, 0 if absent).
The Ki-67 percentage from the most active area of the tumor (added directly).

In a tumor already diagnosed as a carcinoma by the LWB system, the Helsinki score provides additional information about the risk of spread rather than confirming whether the tumor is malignant. A Helsinki score above 8.5 supports the diagnosis of carcinoma when other features are equivocal, and a score above 17 has been linked to a higher risk of metastasis.

Reticulin algorithm

The reticulin algorithm uses a special stain that highlights the supporting fiber network around tumor cell groups. In benign adenomas and oncocytomas, this network is intact; in carcinomas, it is broken up or lost. The diagnosis of carcinoma is supported 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 to oncocytic tumors as an additional check.

Vascular invasion

Vascular invasion means that tumor cells are seen inside a blood vessel, most often a vein. 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. In oncocytic adrenal cortical carcinoma, the most important form of vascular invasion is venous invasion, which is one of the major criteria in the Lin-Weiss-Bisceglia system and on its own is enough to confirm the diagnosis of carcinoma.

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.

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 oncocytic adrenal cortical carcinoma, complete removal of the tumor in one piece, with the surrounding fat and the tumor’s 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 oncocytic 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 uncommon at the time of diagnosis but 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 oncocytic 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.” 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 tests before surgery, not by the pathology report. Most oncocytic adrenal cortical carcinomas are non-functional, but a minority do produce cortisol, sex hormones, or (rarely) aldosterone. 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. Patients with cortisol excess need temporary hormone replacement after surgery while the suppressed normal adrenal gland recovers.

Genetic and molecular testing

Molecular testing is not required for every oncocytic adrenal cortical carcinoma but may be helpful in selected cases. Common findings in adrenal cortical carcinomas 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 changes in the IGF2 region on chromosome 11. 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. Oncocytic adrenal cortical carcinoma is staged using the same system as conventional adrenal cortical carcinoma: the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 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 oncocytic adrenal cortical carcinoma depends most strongly on the stage at the time of diagnosis and on whether the tumor can be completely removed. Compared with conventional adrenal cortical carcinoma, oncocytic tumors as a group tend to behave somewhat less aggressively, with lower rates of recurrence and metastasis in published case series. However, individual outcomes vary widely, and oncocytic carcinomas can still spread to other parts of the body, especially when major criteria such as a high mitotic count or venous invasion are present.

Pathologic features that have been 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.
Venous invasion — A major LWB criterion that strongly predicts recurrence and distant spread.
High mitotic count or atypical mitoses — Other major LWB criteria associated with more aggressive behavior.
Lymph node involvement at diagnosis — Linked to worse overall survival.
Distant metastasis at diagnosis — The strongest single predictor of poor outcome.
Large tumor size (over 10 centimeters) or weight (over 200 grams) — Linked to higher recurrence rates.
High Ki-67 proliferation index — A higher percentage is linked to a higher risk of recurrence.
High Helsinki score (especially above 17) — Associated with a higher risk of metastasis.

Because oncocytic 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, LWB criteria) 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 and weight of my tumor, and was it confined to the adrenal gland?
Which Lin-Weiss-Bisceglia major and minor criteria were present in my tumor?
Was the tumor completely removed, and were the margins clear?
Was the capsule of the tumor intact during surgery?
Is my tumor low-grade or high-grade, and what was the mitotic count?
Was a Helsinki score or reticulin algorithm result reported, and what does it mean in my case?
What was the Ki-67 proliferation index, and how does it affect my follow-up plan?
Was vascular (venous) 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?