Polymorphous Adenocarcinoma: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
May 6, 2026

Polymorphous adenocarcinoma is a slow-growing type of cancer that starts in the salivary glands. Unlike most other salivary gland cancers, it almost always starts in one of the small minor salivary glands found in the lining of the mouth and throat — most often in the palate (the roof of the mouth). The word “polymorphous” means “many shapes.” It refers to the many different patterns the tumor cells form under the microscope. Most polymorphous adenocarcinomas are low grade, behave in a slow-growing way, and are cured by surgery alone.

This article will help you understand the findings in your pathology report — what each term means and why it matters for your care.

A note on the name

The name of this tumor has changed over the years, and you may encounter different terms in older reports:

Polymorphous adenocarcinoma — The current World Health Organization (WHO) name, in use since 2017.
Polymorphous low-grade adenocarcinoma (PLGA) — The older name for this tumor. The word “low-grade” was removed from the name in 2017 because the WHO recognized that some of these tumors can behave more aggressively than others, and the new grading system (low, intermediate, high) is now used to describe behavior.
Cribriform adenocarcinoma (of the salivary glands) — A closely related tumor that the 2022 WHO classification now recognizes as a separate diagnosis. It looks similar to polymorphous adenocarcinoma under the microscope but tends to start in the base of the tongue rather than the palate, and has its own set of DNA changes (described in the “How is the diagnosis made?” section). Some pathologists still consider polymorphous adenocarcinoma and cribriform adenocarcinoma variants of the same disease, while others treat them as separate entities. If your pathology report uses one of these names rather than the other, the difference matters mostly for terminology and follow-up.

What causes polymorphous adenocarcinoma?

The cause of polymorphous adenocarcinoma is not known. It is not linked to smoking, alcohol, or any other lifestyle factor. We do know, however, that most polymorphous adenocarcinomas have a specific DNA change. The most common change is a mutation in the PRKD1 gene. The mutation locks the PRKD1 protein in the “on” position, sending a constant signal that tells tumor cells to grow and divide. About 70% of classic polymorphous adenocarcinomas have this specific mutation. The closely related cribriform adenocarcinoma (described in the “Note on the name” section above) more often has a different kind of change — a fusion involving the PRKD1, PRKD2, or PRKD3 genes, in which two genes that are normally far apart break and join together. Either way, the result is a constant grow-and-divide signal in the tumor cells. These genetic changes happen by chance during a person’s lifetime. They are not inherited and cannot be passed to children.

Where does polymorphous adenocarcinoma start?

Polymorphous adenocarcinoma almost always starts in the small minor salivary glands that line the mouth and throat. The most common site is the palate (the roof of the mouth), where about 60% of cases arise. Other common locations include the inside of the cheek, the lip, the floor of the mouth, and the base of the tongue. Cribriform adenocarcinoma is more often found in the base of the tongue. Polymorphous adenocarcinoma very rarely starts in one of the major salivary glands (the parotid, submandibular, or sublingual gland).

Polymorphous adenocarcinoma is most common in people aged 50 to 70. It is slightly more common in women than in men.

What are the symptoms of polymorphous adenocarcinoma?

Most polymorphous adenocarcinomas grow slowly over months or years and produce only mild symptoms in the early stages:

Painless lump or swelling in the mouth — A firm, slow-growing bulge inside the mouth — most often on the palate — is the most common finding.
A sore or ulcer that does not heal — The thin lining over the tumor can break down, causing a sore that doctors and dentists may notice on routine examination.
Discomfort or mild pain — Pain is uncommon at first. New pain can be a warning sign that the tumor has invaded a nerve.
Difficulty swallowing or speaking — Larger tumors can interfere with normal mouth function.
Numbness — Tumors that invade nerves can cause numbness of the palate, lip, or tongue.

Because the tumor 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. The first step is usually a clinical examination by a dentist, oral surgeon, or head and neck surgeon, who notices an abnormal lump or sore inside the mouth. Imaging tests, such as a CT scan or MRI, may be done to see the size of the tumor and whether it has invaded nearby bone. The diagnosis is then confirmed with a biopsy, in which a small sample of the tumor is removed for examination. In many cases, the entire tumor is removed in a single operation, and the diagnosis is made on this larger sample.

Under the microscope, the pathologist looks for a tumor made up of cells that all look very similar to one another but that grow in many different patterns within the same tumor — this is the feature that gives polymorphous adenocarcinoma its name. The patterns include small round structures called tubules, narrow strands called trabeculae, finger-like projections called papillae, sieve-like patterns called cribriform, and solid sheets. One of the most helpful clues to the diagnosis is a characteristic pattern in which tumor cells form rings around nerves and small blood vessels — pathologists call this a “targetoid” or “eye of the storm” pattern because it resembles the calm center of a hurricane. The cells themselves are uniform and bland, with little of the marked variation in size and shape that is seen in more aggressive cancers. Mitotic figures (cells in the act of dividing) are usually few. The cribriform variant shows a similar overall picture, but the cribriform and papillary patterns dominate, and small round structures called glomeruloid bodies (named for their resemblance to the kidney’s glomerulus) are commonly seen.

To confirm the diagnosis, the pathologist often uses immunohistochemistry, a stain that highlights specific proteins in the tumor cells. Polymorphous adenocarcinoma is typically positive for proteins called cytokeratin 7 (CK7), S100, SOX10, and p63. It is typically negative for a closely related protein called p40. The combination of p63-positive and p40-negative is especially helpful because it rules out other tumors that can look similar — particularly squamous cell carcinoma. The most important tumor that polymorphous adenocarcinoma must be told apart from is adenoid cystic carcinoma, which can also show a cribriform pattern and a tendency to grow along nerves, but behaves much more aggressively. The two can be distinguished by their staining patterns and, when needed, by molecular testing.

In some cases, molecular testing is also done. The most useful test looks for the specific change in the PRKD1 gene that is found in most classic polymorphous adenocarcinomas, or for one of the related PRKD1, PRKD2, or PRKD3 fusions found in cribriform adenocarcinoma. The tests used to find these changes include next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH). Molecular testing is most useful when microscopic features are atypical or when the differential diagnosis with adenoid cystic carcinoma cannot be resolved by immunohistochemistry alone. Once the diagnosis is confirmed, additional imaging is used to assess spread before treatment is planned.

Histologic grade

The 2022 WHO classification uses a three-tier grading system for polymorphous adenocarcinoma based on the appearance of the tumor cells under the microscope:

Low grade — The tumor cells are uniform with little variation in size and shape, mitotic figures are rare, and there is no necrosis (areas of cell death). Most polymorphous adenocarcinomas are low grade. These tumors grow slowly and are unlikely to spread.
Intermediate grade — The tumor cells show some variation in size and shape, more mitotic figures are seen, and small areas of necrosis may be present. Many cribriform adenocarcinomas fall into this category.
High grade — The tumor cells are markedly abnormal, mitotic figures are frequent, and necrosis is often seen. High-grade polymorphous adenocarcinoma is uncommon and behaves more like other aggressive salivary gland cancers.

Tumor extension

Tumor extension describes how far the tumor has grown beyond the salivary gland tissue where it started. Because polymorphous adenocarcinoma almost always arises in a minor salivary gland in the mouth, the most important kinds of extension to watch for are growth into the underlying bone (such as the bone of the palate or jaw) and growth into nearby muscles or soft tissues. Bone invasion is given a higher pathologic stage and may require a more extensive operation to fully remove the tumor.

Lymphovascular invasion

Lymphovascular invasion means that tumor cells have entered small blood vessels or lymphatic vessels in or near the tumor. These vessels can carry the cells to lymph nodes or to distant parts of the body. Lymphovascular invasion is uncommon in low-grade polymorphous adenocarcinoma but is more common in cribriform and higher-grade tumors. When found, it raises the risk that the cancer will come back, and it may influence the decision to recommend radiation therapy after surgery.

Perineural invasion

Perineural invasion means that tumor cells are growing around or along a nerve. Polymorphous adenocarcinoma has a strong tendency to grow along nerves, which is one of the reasons it can come back near the original site after surgery, even when the margins look clear. Perineural invasion can cause new pain, numbness, or weakness in the area around the tumor. When seen on a pathology report, it raises the risk that the tumor will come back near the original site, and your doctor may recommend radiation therapy after surgery to lower that risk. Perineural invasion is so common in polymorphous adenocarcinoma that it is sometimes called one of its defining features.

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 the chance of it growing back is much lower.
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 can raise the risk that the tumor will come back near the original site.
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 can be challenging in polymorphous adenocarcinoma because the tumor’s tendency to grow along nerves can extend microscopic spread beyond what the surgeon can see. For this reason, careful examination of the margins by the pathologist is especially important.

Lymph nodes

Lymph nodes are small immune organs scattered throughout the body. The lymph nodes most likely to be involved by polymorphous adenocarcinoma are those in the neck. Spread to lymph nodes is uncommon in classic polymorphous adenocarcinoma — about 10% of patients overall — but is somewhat more common in cribriform adenocarcinoma, where rates of around 25% have been reported. 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 there is clinical or imaging evidence of lymph node involvement, when the tumor is intermediate or high grade, or when it is the cribriform variant.

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.

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.

Because polymorphous adenocarcinoma almost always arises in a minor salivary gland in the mouth or throat, staging is based on the system for the area where the tumor started — most often the oral cavity (for tumors of the palate, cheek, lip, or floor of mouth) or the oropharynx (for tumors of the base of the tongue). The major salivary gland staging system is used only in rare cases where polymorphous adenocarcinoma arises in the parotid, submandibular, or sublingual gland. The general principles are the same across these systems: smaller tumors confined to the original site are early-stage; larger tumors, tumors that invade nearby bone, and tumors that have spread to lymph nodes or distant sites are higher-stage. Your pathology report will give the specific T, N, and M categories for your tumor based on the appropriate site-specific system.

What is the prognosis?

The outlook for polymorphous adenocarcinoma is generally excellent. Most tumors grow slowly, are confined to where they started, and are cured by surgery alone:

Classic polymorphous adenocarcinoma — 10-year overall survival is greater than 95%. About 15–30% of tumors come back near the original site, often years later. Spread to distant sites, such as the lungs, is very rare.
Cribriform adenocarcinoma — Behaves somewhat more aggressively. Rates of lymph node involvement are higher (around 25%), but overall survival is still very good.
Higher-grade or larger tumors — A small number of polymorphous adenocarcinomas behave more aggressively, more like other salivary gland cancers. These tumors have a less favorable outlook and are usually treated more intensively.

Several features in the pathology report can identify patients at higher risk of a worse outcome:

Higher histologic grade — Intermediate- and high-grade tumors are more likely to come back or spread.
Positive surgical margins — Incompletely removed tumors are more likely to come back near the original site.
Bone invasion — Tumors that have grown into the underlying jaw or palate bone are at higher risk of coming back.
Lymph node involvement — Spread to lymph nodes raises the risk of distant spread.
Cribriform pattern — The cribriform variant is somewhat more aggressive than classic polymorphous adenocarcinoma.

One distinctive feature of polymorphous adenocarcinoma is that recurrence — when it occurs — often happens many years after the original surgery. Long-term follow-up is therefore recommended for all patients.

What happens after the diagnosis?

Treatment for polymorphous adenocarcinoma is led by a head and neck surgeon, often working with an oral and maxillofacial surgeon, a radiation oncologist, and a dentist or prosthodontist for any later dental rehabilitation. The main treatment is surgery to remove the entire tumor with a rim of healthy tissue.

Surgery — The mainstay of treatment. For tumors of the palate, the surgeon removes the tumor along with a rim of healthy tissue, sometimes including a portion of the underlying bone. Larger tumors of the palate may require a partial maxillectomy (removal of part of the upper jaw), which is then reconstructed with a dental appliance called an obturator or with a tissue flap.
Neck dissection — Removal of lymph nodes from one or both sides of the neck. Often not needed for small, low-grade classic polymorphous adenocarcinomas. More likely to be done for the cribriform variant, for higher-grade tumors, for larger tumors, or when there is clinical or imaging evidence of lymph node involvement.
Radiation therapy after surgery — Recommended when surgical margins are positive or close, when there is extensive perineural invasion, when lymph nodes are involved, or for higher-grade tumors. Many low-grade tumors removed with negative margins do not need radiation. Radiation is given as a series of daily treatments over several weeks.
Chemotherapy — Rarely needed for polymorphous adenocarcinoma. Reserved for the small number of patients with advanced or recurrent disease that cannot be controlled with surgery and radiation.
Long-term surveillance — Because polymorphous adenocarcinoma can come back many years after the original treatment, follow-up examinations and imaging continue for at least 10 to 15 years. Regular dental and oral examinations are important for monitoring the primary site, and imaging of the head and neck is used to assess both local recurrence and lymph node involvement.

Questions to ask your doctor

Where exactly did the tumor start, and how large was it?
Is my tumor classic polymorphous adenocarcinoma or the cribriform variant?
What grade is my tumor — low, intermediate, or high?
What is the pathologic stage of my cancer?
Was the tumor completely removed? What were the surgical margins?
If a margin was positive or close, will I need more surgery or radiation therapy?
Did the tumor invade any underlying bone?
Was perineural invasion identified, and how extensive was it?
Were any lymph nodes involved by tumor?
Was molecular testing performed, and was a PRKD1, PRKD2, or PRKD3 change identified?
Will I need radiation therapy after surgery?
What is my estimated risk of the cancer coming back, and at what time point?
What is the schedule for follow-up examinations and imaging, and how long will it continue?
Will I need any reconstruction of my palate or jaw, and what does that involve?
Will I have any lasting numbness, changes in my speech, or changes in my ability to eat?