Adenoid Cystic Carcinoma: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
May 4, 2026

Adenoid cystic carcinoma is a type of cancer that most often starts in the salivary glands — the glands that make saliva. It has two unusual features. First, it tends to grow slowly but can come back many years after surgery. Second, it rarely spreads to lymph nodes, but it often spreads along nerves and to distant sites such as the lungs. Most patients live many years with this diagnosis, but long-term cure can be hard to achieve. Adenoid cystic carcinoma can also start in other parts of the body, including the breast, lung, skin, tear glands, nose, sinuses, voice box, and windpipe. The way the tumor behaves depends on where it starts. For example, adenoid cystic carcinoma of the breast is much less aggressive than adenoid cystic carcinoma of the salivary glands, even though the two look the same under the microscope.

This article is about adenoid cystic carcinoma of the salivary glands. It will help you understand the findings in your pathology report — what each term means and why it matters for your care.

What causes adenoid cystic carcinoma?

The cause of adenoid cystic carcinoma is not known in most cases. Unlike many other head and neck cancers, it is not linked to smoking, alcohol, infection, sun exposure, or any other lifestyle or environmental factor. We do know, however, that almost every adenoid cystic carcinoma has a specific change in its DNA. The most common change is a fusion between two genes called MYB and NFIB. A fusion happens when two genes that are normally far apart on different chromosomes break and join together. This new combined gene then behaves abnormally. The MYB-NFIB fusion activates the MYB gene at very high levels in tumor cells, causing them to divide and form a tumor. A smaller number of adenoid cystic carcinomas exhibit a similar fusion involving a related gene, MYBL1. These tumors behave the same way. These genetic changes happen by chance during a person’s lifetime. They are not inherited and cannot be passed to children.

Where does adenoid cystic carcinoma start?

Within the salivary glands, adenoid cystic carcinoma can start in any of the major glands — the parotid gland (in front of and below each ear), the submandibular gland (under the jaw), or the sublingual gland (under the tongue). It can also start in the small minor salivary glands found throughout the lining of the mouth, throat, sinuses, and airway. Unlike most other salivary gland cancers, adenoid cystic carcinoma is more often found in the submandibular gland and the minor salivary glands than in the parotid gland. The most common minor salivary site is the palate (the roof of the mouth).

Adenoid cystic carcinoma can occur at any age but is most common between 40 and 70 years old. It is slightly more common in women than in men. It is rare overall, with fewer than 1 in 100,000 cancers being adenoid cystic carcinoma in most populations.

What are the symptoms of adenoid cystic carcinoma?

The symptoms depend on where the tumor is located, but a few patterns are typical of this type of cancer:

Slow-growing lump or swelling — A firm, often painless lump in the salivary gland is the most common finding. In the parotid or submandibular glands, the lump is usually felt in the neck or face. In the minor salivary glands of the palate, it appears as a firm bulge inside the mouth, sometimes with thinning or a sore on the surface.
Pain, numbness, or tingling — Adenoid cystic carcinoma has a strong tendency to grow along nerves. Unexplained nerve symptoms are one of the most unusual features of this cancer. New facial pain or numbness, weakness of the muscles of facial expression, or numbness of the tongue, lip, or palate can all be the first sign of the disease.
Slow facial weakness or paralysis — The facial nerve runs directly through the parotid gland. Tumors that involve this nerve can cause progressive weakness of one side of the face.
Nasal obstruction or bleeding — Tumors that start in the sinuses or nasal cavity can block the nose or cause repeated nosebleeds.
Hoarseness or breathing difficulty — Tumors of the voice box (larynx) or windpipe (trachea) can cause a hoarse voice, a long-lasting cough, or shortness of breath.
Cough or shortness of breath without an obvious cause — Sometimes the first sign of disease is a small spot found on a chest X-ray or CT scan. This spot represents spread of the cancer to the lungs from a salivary gland tumor that has not yet been noticed.

Because adenoid cystic carcinoma grows so slowly, many patients first see a doctor only after symptoms have been present for months or even years.

How is the diagnosis made?

The diagnosis is made after a tissue sample is examined under the microscope by a pathologist. Most patients first have an imaging test — usually an ultrasound, CT scan, or MRI — that shows a mass in the salivary gland. MRI is very useful for adenoid cystic carcinoma because it shows the tumor’s relationship to nearby nerves. A fine needle aspiration biopsy (FNAB) is often done first to take a small sample of cells through a thin needle. If the FNAB does not give a clear answer, a core needle biopsy may be done instead. In many cases, the entire tumor is removed in a single operation, and the diagnosis is made on this larger sample rather than on a separate biopsy.

Under the microscope, the pathologist looks for a tumor composed of two distinct cell types. This is why adenoid cystic carcinoma is called a biphasic tumor (the prefix “bi” means two). The first type is the ductal cell, which lines small tube-like spaces. The second type is the myoepithelial cell, a specialized cell that surrounds the ductal cells and normally helps squeeze saliva out of the gland. The tumor cells are arranged in three classic patterns. Most adenoid cystic carcinomas show some combination of all three:

Tubular pattern — The cells form small round structures that look like tiny hollow tubes. This is the most well-formed pattern.
Cribriform pattern — The cells form large nests with many small round holes inside, which often contain pink or blue mucus-like material. This pattern gives the tumor a “Swiss cheese” appearance.
Solid pattern — The cells form sheets without recognizable tubes or holes. This pattern is linked with more aggressive behavior, as described in the histologic grade section below.

Once the diagnosis is suspected, the pathologist may order additional tests, such as immunohistochemistry, to confirm it. These tests look for specific proteins inside the tumor cells. The two cell types stain for different proteins — the ductal cells stain for proteins called cytokeratins and CD117 (also called KIT), while the myoepithelial cells stain for proteins called p63, p40, S100, smooth muscle actin, and calponin. Finding both cell types is a key feature of the diagnosis. A separate stain for the MYB protein is also commonly used. As described in the “What causes” section, almost all adenoid cystic carcinomas have a genetic change that activates the MYB gene at very high levels, and immunohistochemistry for MYB highlights this in tumor cells. A positive MYB result is helpful but not definitive, since some other tumors can also show MYB staining.

In some cases, molecular testing is also done. The underlying gene fusion can be detected directly using techniques such as fluorescence in situ hybridization (FISH) or next-generation sequencing. About 50–60% of adenoid cystic carcinomas have a MYB-NFIB fusion. A smaller group has a MYBL1-NFIB fusion. Finding one of these fusions confirms the diagnosis with very high accuracy. Molecular testing is used only in selected cases, mainly when immunohistochemistry alone is insufficient to establish the diagnosis. Once the diagnosis is confirmed, additional imaging is used to assess spread before treatment is planned.

Histologic grade

The histologic grade of adenoid cystic carcinoma is based on the percentage of the tumor that shows the solid pattern described above. The grading system is one of the most useful ways to predict how the tumor is likely to behave. Tumors with a more solid pattern are more aggressive and more likely to come back or spread.

Grade 1 — The tumor is made up almost entirely of tubular and cribriform patterns, with no solid pattern. These tumors generally have the best prognosis.
Grade 2 — The tumor shows mostly cribriform pattern with up to 30% solid pattern. Behavior is in between Grade 1 and Grade 3.
Grade 3 — More than 30% of the tumor shows the solid pattern. These tumors are more aggressive, more likely to spread, and have a worse prognosis.

This three-tier grading system is sometimes called the Perzin or Szanto grading system after the pathologists who first described it. Histologic grade is one of the most important findings on a pathology report for adenoid cystic carcinoma. It is looked at along with tumor size, lymph node status, perineural invasion, and surgical margin status when planning treatment and estimating prognosis.

High-grade transformation

High-grade transformation is a distinct and uncommon finding, distinct from grade 3 disease. In high-grade transformation, part of the tumor changes into a much more aggressive form of cancer that no longer looks like adenoid cystic carcinoma at all. The tumor cells become very abnormal-looking (pleomorphic), divide rapidly (with many mitotic figures), and often show areas of necrosis (cell death). High-grade transformation is linked with a much higher risk of spread to lymph nodes — which is otherwise unusual in adenoid cystic carcinoma — and a much worse prognosis. Treatment is usually stronger when this finding is reported, often including a neck dissection (removal of lymph nodes from the neck) and radiation therapy after surgery.

Tumor extension (extraparenchymal extension)

Extraparenchymal extension means the tumor has spread beyond the salivary gland into surrounding tissues, such as fat, muscle, or skin. This finding is reported only for tumors that start in one of the three major salivary glands — the parotid, submandibular, or sublingual gland. Tumors with extraparenchymal extension are given a higher pathologic stage (pT) and are at higher risk of coming back after surgery.

Lymphovascular invasion

Lymphovascular invasion means that tumor cells have entered small blood vessels or lymphatic vessels in or near the tumor. Lymphovascular invasion is uncommon in adenoid cystic carcinoma — much less common than perineural invasion, which is described next. When it is present, it raises the risk that the cancer will spread to distant sites such as the lungs. It may also influence the decision to recommend radiation therapy after surgery.

Perineural invasion

Perineural invasion means that tumor cells are growing around or along a nerve. It is one of the most unusual features of adenoid cystic carcinoma. Perineural invasion is found in most adenoid cystic carcinomas — far more often than in any other salivary gland cancer. It is one of the main reasons this tumor tends to come back near the original site after surgery. Tumor cells can travel along a nerve for many centimeters, far from the main mass. This makes complete surgical removal difficult and is the reason most patients are given radiation therapy after surgery, even when the margins look clear. Perineural invasion can also explain symptoms of pain, numbness, or facial weakness that develop before, during, or after treatment. The pathology report may describe whether the affected nerve is small or large, since invasion of larger named nerves is more important in treatment planning.

Surgical margins

A margin is the edge of the tissue that the surgeon cuts when removing the tumor. The pathologist examines these edges under the microscope to see whether any tumor cells reach the cut surface.

Negative margin — No tumor cells are seen at the cut edge. This suggests the tumor was completely removed and lowers the chance of it growing back. However, adenoid cystic carcinoma can come back even after a negative margin because of microscopic spread along nerves that goes beyond what the surgeon could remove.
Close margin — Tumor cells are very close to the cut edge but do not reach it. The pathologist may report the exact distance in millimeters. A close margin raises the risk of the tumor coming back near the original site and often leads to a recommendation for radiation therapy after surgery.
Positive margin — Tumor cells are seen at the cut edge of the tissue. This means tumor cells were almost certainly left behind. A positive margin usually leads to a recommendation for either more surgery or radiation therapy after surgery.

Getting wide negative margins is especially difficult in adenoid cystic carcinoma. The tumor can spread for long distances along nerves before any visible mass is present. The surgeon also has to work around important structures such as the facial nerve, the brain, or the eye. For these reasons, close or positive margins are common even after careful surgery, and radiation therapy after surgery is often recommended no matter what the margin status.

Lymph nodes

Lymph nodes are small immune organs scattered throughout the body. Spread to lymph nodes is uncommon in classic adenoid cystic carcinoma — this is one of the features that sets it apart from most other head and neck cancers. Lymph node involvement is more likely when high-grade transformation is present, when the primary tumor is very large, or when the tumor has invaded a wide area of surrounding soft tissue. During surgery, lymph nodes near the tumor may be removed and sent to the laboratory in a procedure called a neck dissection. This is most often done when the tumor shows worrying features rather than as a routine part of treatment.

Negative lymph node — No tumor cells are found in the node.
Positive lymph node — Tumor cells are found inside the node. The report will describe how many nodes contain tumor, the size of the largest deposit, and whether the tumor has grown beyond the outer wall of the node — a feature called extranodal extension.

Biomarker and molecular testing

A biomarker is something that can be measured in a tumor sample — most often a protein on the surface of the tumor cells or a change in the tumor’s DNA — that helps doctors predict how the tumor will behave or decide whether a treatment is likely to work. Adenoid cystic carcinoma is usually diagnosed based on its appearance under the microscope, and additional immunohistochemistry and molecular testing are used to confirm the diagnosis, as described in the “How is the diagnosis made?” section above. The biomarker test most relevant to treatment in adenoid cystic carcinoma — particularly for patients with advanced disease — is a NOTCH1 gene mutation test.

NOTCH1 mutation testing

About 10–15% of adenoid cystic carcinomas harbor a mutation in the NOTCH1 gene. These tumors tend to be more aggressive than other adenoid cystic carcinomas and are more likely to come back or spread. Testing for NOTCH1 mutations is not yet routine, but it is becoming more common in advanced disease. NOTCH1-mutated tumors may respond to a class of targeted drugs called notch inhibitors (also called gamma-secretase inhibitors). Several of these drugs are currently being studied in clinical trials for advanced adenoid cystic carcinoma.

Pathologic stage (pTNM)

Pathologic staging describes the size of the tumor and how far it has spread, based on the findings at surgery. It uses the TNM system: T stands for the size and extent of the primary tumor, N stands for involvement of nearby lymph nodes, and M stands for spread to distant parts of the body. Staging applies only to adenoid cystic carcinomas of the major salivary glands. Tumors of the minor salivary glands are staged using the system for the area where they started (such as the oral cavity, oropharynx, sinuses, or larynx).

Tumor stage (pT)

T1 — The tumor is 2 cm or smaller and confined to the salivary gland.
T2 — The tumor is larger than 2 cm but not larger than 4 cm and is still confined to the salivary gland.
T3 — The tumor is larger than 4 cm, or has spread beyond the salivary gland into surrounding soft tissue (extraparenchymal extension).
T4a — The tumor has invaded skin, the jawbone, the ear canal, or the facial nerve.
T4b — The tumor has invaded the base of the skull, nearby bones, or major blood vessels.

Nodal stage (pN)

N0 — No tumor cells in any examined lymph nodes.
N1 — A single lymph node on the same side of the neck contains tumor, and is 3 cm or smaller, with no extranodal extension.
N2a — A single lymph node on the same side of the neck is between 3 and 6 cm, or any lymph node shows extranodal extension.
N2b — Multiple lymph nodes on the same side of the neck contain tumor, none larger than 6 cm, with no extranodal extension.
N2c — Lymph nodes on both sides of the neck or on the opposite side from the tumor contain tumor, none larger than 6 cm, with no extranodal extension.
N3a — A lymph node larger than 6 cm contains tumor.
N3b — Any positive lymph node shows extranodal extension (apart from the single small node category covered under N2a).

What is the prognosis?

The prognosis for adenoid cystic carcinoma is unusual among cancers because of its slow but ongoing behavior. Short-term outcomes are reasonably good, but the picture changes a lot over the long term:

5-year survival — Approximately 70–90% of patients are alive 5 years after diagnosis.
10-year survival — Drops to approximately 50–70%, depending on stage and grade.
15- to 20-year survival — Often less than 50%. This reflects the long-term tendency of this tumor to come back many years after the original treatment.

The most important features in the pathology report that affect prognosis are:

Histologic grade — Grade 3 (more than 30% solid pattern) and the presence of high-grade transformation are the strongest warning signs.
Tumor size and extension — Larger tumors, and tumors that have spread beyond the salivary gland, are more likely to come back.
Surgical margins — Positive margins raise the risk that the cancer will come back near the original site, even with radiation therapy after surgery.
Perineural invasion of large named nerves — Major nerve involvement is a strong warning sign that the cancer may come back near the original site.
Distant metastases — Spread to the lungs, bone, or liver lowers long-term survival, although patients can sometimes live many years with stable lung metastases.

One distinctive feature of adenoid cystic carcinoma is that distant spread, especially to the lungs, can be slow-growing and may not need immediate treatment. Some patients live for many years with small, stable lung metastases, especially when the original tumor was low grade. This pattern is unusual among cancers. It is one of the reasons adenoid cystic carcinoma is sometimes managed by simply watching closely rather than treating right away when small distant deposits are found.

What happens after the diagnosis?

Treatment for adenoid cystic carcinoma is led by a head and neck surgeon. The surgeon often works closely with a radiation oncologist, a medical oncologist, and (for tumors involving the facial nerve, eye, or skull base) a reconstructive surgeon and a neurosurgeon.

Surgery — The main treatment is complete surgical removal of the tumor with as wide a border of healthy tissue as the location allows. For parotid tumors, this is usually a parotidectomy. For submandibular tumors, the entire submandibular gland is removed. For tumors of the palate or other minor salivary sites, the tumor is removed along with a rim of healthy tissue, sometimes with reconstruction. The facial nerve is preserved whenever possible.
Radiation therapy after surgery — Almost all patients with adenoid cystic carcinoma receive radiation therapy after surgery, no matter what the margin status. This is because the tumor’s tendency to spread along nerves makes the risk of coming back near the original site high. Newer techniques, such as proton beam radiation and neutron beam radiation, are sometimes used for tumors near critical structures such as the eye or brain.
Chemotherapy — Standard chemotherapy is generally not very effective in adenoid cystic carcinoma. It is reserved for some patients with advanced disease.
Targeted therapy and clinical trials — Several drugs that target specific genetic changes in adenoid cystic carcinoma — including notch inhibitors for NOTCH1-mutated tumors and other drugs that target the MYB pathway — are being studied in clinical trials. Patients with advanced or recurrent disease should ask whether a clinical trial is available.
Long-term surveillance — Because adenoid cystic carcinoma can come back many years after the original treatment, follow-up examinations and imaging continue for at least 10 to 15 years, and often longer. CT or MRI of the head and neck is used to watch for the cancer coming back near the original site, and CT of the chest is used to watch for spread to the lungs.
Watch-and-wait for slow-growing distant disease — When small, stable lung metastases are found, treatment is sometimes delayed, and the spots are simply watched on imaging done at regular intervals. This approach takes advantage of the slow-growing nature of the disease and avoids the side effects of treatment when treatment is unlikely to extend life.

Questions to ask your doctor

Where exactly did the tumor start, and how large was it?
What is the histologic grade of my tumor (Grade 1, 2, or 3)?
Was high-grade transformation seen anywhere in the tumor?
What is the pathologic stage (pT, pN, and overall TNM stage) of my cancer?
Was the tumor completely removed? What were the surgical margins?
Was perineural invasion identified, and did it involve a small or large named nerve?
Were any lymph nodes involved by tumor?
Was molecular testing performed, and if so, what was found?
Was my tumor tested for a NOTCH1 mutation? If not, would testing be appropriate now or in the future?
Will I need radiation therapy after surgery, and what type?
What is my estimated risk of the cancer coming back at 5, 10, and 15 years?
What is the schedule for follow-up imaging, and how long will it continue?
Are there clinical trials I should consider, particularly for new targeted therapies?
If lung metastases develop, what are my options, and would watch-and-wait be appropriate?
Will I have any lasting facial weakness, numbness, or dryness of the mouth from the surgery and radiation?