Secretory Carcinoma of the Salivary Glands: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
May 5, 2026

Secretory carcinoma is a type of cancer that starts in the salivary glands — the glands that make saliva. It is one of the more recently described salivary gland cancers, and it has a few features that set it apart. First, it almost always carries the same specific change in its DNA — a fusion of two genes that drives tumor growth. Second, that genetic change can be matched with a targeted drug, which means a small but important number of patients with advanced secretory carcinoma can be treated with a drug aimed at the cancer’s underlying cause. Third, secretory carcinoma is closely related to a similar tumor that occurs in the breast and shares the same DNA change — a connection that is reflected in the tumor’s older name (described below).

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:

Secretory carcinoma — The current World Health Organization (WHO) name, in use since 2017 and confirmed in the 2022 update.
Mammary analogue secretory carcinoma (MASC) — The original name when the tumor was first described in 2010. The word “mammary” refers to breast tissue, and the name reflected the discovery that this salivary gland tumor shares the same DNA change as a similar tumor of the breast.
Acinic cell carcinoma — Before 2010, many secretory carcinomas were grouped with acinic cell carcinoma, another salivary gland cancer that looks similar under the microscope. If you have an older report (before about 2010 to 2015) that says “acinic cell carcinoma,” it is worth asking whether the tumor would be reclassified as secretory carcinoma today. This question is more than academic — secretory carcinoma can be treated with a class of drugs that does not work for true acinic cell carcinoma, as described later in this article.

What causes secretory carcinoma?

The cause of secretory carcinoma is not known in most cases. It is not linked to smoking, alcohol, infection, or any other lifestyle or environmental factor. We do know, however, that almost every secretory carcinoma has a specific change in its DNA. The most common change is a fusion between two genes called ETV6 and NTRK3. A fusion happens when two genes that are normally far apart on different chromosomes break and join together. The new combined gene then behaves abnormally. The ETV6-NTRK3 fusion creates an abnormal protein that tells the tumor cells to keep dividing, even when they should stop. A small number of secretory carcinomas have a fusion involving ETV6 and the RET gene, or, rarely, a fusion involving RET with another partner. 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 secretory carcinoma start?

Secretory carcinoma can start in any salivary gland, but is most often found in the parotid gland, which sits in front of and just below each ear. About 70% of secretory carcinomas arise in the parotid gland. The rest occur in the small minor salivary glands distributed throughout the lining of the mouth and throat — particularly in the inside of the cheek, the lip, and the palate (the roof of the mouth) — or in the submandibular gland (under the jaw). Tumors with the same DNA change can also occur in the breast (where they are called secretory carcinoma of the breast) and, rarely, in the skin and thyroid.

Secretory carcinoma can occur at any age but is most common between ages 30 and 60. It is slightly more common in men than in women.

What are the symptoms of secretory carcinoma?

Most secretory carcinomas grow slowly and produce few symptoms in the early stages:

Painless lump — A slow-growing, painless mass in the salivary gland is the most common finding by far. In the parotid gland, the lump is felt under the skin in front of or below the ear. In a minor salivary gland, it appears as a firm bulge inside the mouth.
Pain or tenderness — Uncommon at first. New pain may be a warning sign that the tumor has invaded a nerve or has undergone high-grade transformation.
Numbness or facial weakness — The facial nerve runs through the parotid gland. Tumors that press on or invade this nerve can cause weakness or paralysis of part of the face. This is uncommon in secretory carcinoma and, when present, suggests a more aggressive tumor.
Difficulty swallowing or speaking — Larger tumors of the minor salivary glands can interfere with normal mouth function.
Swelling in the neck — Sometimes caused by the spread of the tumor to nearby lymph nodes.

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. 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.

Under the microscope, the pathologist looks for a tumor made up of large cells with pink (eosinophilic) cytoplasm. The cells have round nuclei (the part of the cell that holds DNA), and most cells have a small dot called a nucleolus in the center of the nucleus. The tumor cells are arranged in several typical patterns, often within the same tumor — they may form small round structures called tubules, large open spaces called cysts, finger-like projections called papillae, or solid sheets. The hollow spaces of the tubules and cysts often contain a pink or blue fluid produced by tumor cells, which is why they are called “secretory” (the cells secrete a fluid). Mitotic figures (cells in the act of dividing) are present but usually few.

Once the diagnosis is suspected, the pathologist confirms it using immunohistochemistry, a staining technique that highlights specific proteins in tumor cells. Almost all secretory carcinomas show strong staining for two proteins called S100 and mammaglobin. The combination is one of the most reliable signs of the diagnosis. Other commonly observed proteins include SOX10 and cytokeratin 7. Secretory carcinoma is typically negative for proteins called p63 and DOG1, which are usually positive in other salivary gland tumors that can look similar under the microscope. The pattern of positive and negative stains, taken together, helps the pathologist tell secretory carcinoma apart from these other tumors. In some cases, additional molecular testing is performed to identify the underlying gene fusion, as described in the biomarker and molecular testing section below.

High-grade transformation

High-grade transformation means that part of the tumor has changed into a much more aggressive form of cancer. In areas of high-grade transformation, the tumor cells lose the typical features of secretory carcinoma. They become very abnormal looking (atypical and pleomorphic), divide rapidly (with many mitotic figures), and often show areas of necrosis (cell death). High-grade transformation is uncommon in secretory carcinoma, but when it is present, the tumor is much more likely to spread to lymph nodes and to distant sites such as the lungs. 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 arise 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. These vessels can carry the cells to lymph nodes or to distant parts of the body. When found, lymphovascular invasion 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. The facial nerve, which controls the muscles of facial expression, runs through the parotid gland and is the most commonly involved nerve when secretory carcinoma arises there. Perineural invasion can cause new pain, numbness, or facial weakness. When seen in 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.

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, and may lead 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.

Margin assessment is especially difficult in parotid surgery because the surgeon must work around the facial nerve. For this reason, close margins are common even when the surgery has been carefully performed.

Lymph nodes

Lymph nodes are small immune organs scattered throughout the body. The lymph nodes most likely to be involved by secretory carcinoma are those in the neck. During surgery, lymph nodes near the tumor may be removed and sent to the laboratory in a procedure called a neck dissection. This is more often performed when high-grade transformation is present, when the tumor is large, or when imaging or examination suggests that lymph nodes may be involved.

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.

Spread to lymph nodes is uncommon in classic secretory carcinoma but is much more frequent when high-grade transformation is present.

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. In some cancer types, biomarker testing is routinely performed because the results determine which drugs will be used. Secretory carcinoma is one of the few salivary gland cancers where this is true: the same gene fusion that defines the disease is also the target of an approved class of drugs. Biomarker testing is most important for patients whose tumor has recurred, spread, or cannot be removed by surgery, but it also confirms the diagnosis when other findings leave the diagnosis uncertain.

ETV6-NTRK3 and ETV6-RET fusion testing

Molecular testing looks for the specific gene fusion that drives secretory carcinoma. The most common fusion involves the ETV6 and NTRK3 genes — about 95% of secretory carcinomas have this fusion. A smaller number have a fusion involving ETV6 and RET, or, rarely, RET with another partner gene. The tests used to find these fusions include fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS). Detecting one of these fusions confirms the diagnosis with very high accuracy. For patients with advanced disease (described in the next section), the same test result also identifies them as candidates for targeted drug therapy.

Targeted drug therapy

The fusion that defines secretory carcinoma is more than a diagnostic clue — it is also a treatment target. ETV6-NTRK3 and other NTRK fusions can be blocked by a class of drugs called NTRK inhibitors. Two NTRK inhibitors, larotrectinib and entrectinib, are approved for any cancer that has an NTRK fusion, which includes secretory carcinoma. Patients with advanced, recurrent, or unresectable secretory carcinoma can have substantial and long-lasting responses to these drugs. Tumors with the rarer RET fusion can be treated with a different class of drugs called RET inhibitors (selpercatinib and pralsetinib), which are approved for cancers with RET rearrangements. Most patients with secretory carcinoma do not need targeted drug therapy, because surgery alone is curative — but for patients whose tumor has come back or has spread, this is one of the most important conversations to have with the medical team.

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 secretory 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 or oropharynx).

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 outlook for most patients with secretory carcinoma is excellent. The tumor is generally slow-growing, and complete surgical removal cures most patients. The 5-year survival rate for classic secretory carcinoma is greater than 90%. Recurrence after complete surgery is uncommon but can occur years later, which is why long-term follow-up is recommended.

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

High-grade transformation — The single most important warning sign. Survival drops substantially when this is present.
Tumor size larger than 4 cm — Larger tumors are more likely to have spread and to come back.
Extraparenchymal extension — Tumors that have grown beyond the salivary gland are at higher risk of coming back.
Positive surgical margins — Incompletely removed tumors are more likely to come back.
Lymph node involvement — Spread to lymph nodes raises the risk of distant spread and worsens overall prognosis.
Perineural and lymphovascular invasion — Both are linked with a higher risk of the tumor coming back near the original site.

What happens after the diagnosis?

Treatment for secretory carcinoma is led by a head and neck surgeon. The surgeon often works with a radiation oncologist, a medical oncologist (when high-grade or advanced disease is present), and a speech-language pathologist for any rehabilitation needs. The main treatment is surgery to remove the entire tumor.

Parotidectomy — Removal of part or all of the parotid gland. Most secretory carcinomas of the parotid gland are treated with a superficial parotidectomy or, for deeper tumors, a total parotidectomy. The facial nerve is preserved whenever possible. Submandibular and minor salivary gland tumors are removed along with the entire affected gland or a rim of healthy tissue.
Neck dissection — Removal of lymph nodes from one or both sides of the neck. Done when there is clinical or imaging evidence of lymph node involvement, when high-grade transformation is present, or when the tumor is very large. Neck dissection is often not needed for small, classic secretory carcinomas.
Radiation therapy after surgery — Recommended when high-grade transformation is present, when surgical margins are positive or close, when perineural or lymphovascular invasion is identified, when lymph nodes are involved, or for advanced-stage tumors. Radiation is given as a series of daily treatments over several weeks.
Targeted drug therapy — NTRK inhibitors such as larotrectinib or entrectinib are an option for patients with secretory carcinoma that has come back, has spread, or cannot be removed by surgery. Patients whose tumor has the rarer RET fusion may instead be treated with a RET inhibitor (selpercatinib or pralsetinib). These drugs are taken as pills.
Standard chemotherapy — Generally not very effective in secretory carcinoma and is mostly replaced by targeted drug therapy when systemic treatment is needed.
Long-term surveillance — Regular clinical examination of the head and neck, with imaging as needed, continues for many years after treatment.

Questions to ask your doctor

Where exactly did the tumor start, and how large was it?
What is the pathologic stage (pT, pN, and overall TNM stage) of my cancer?
Was high-grade transformation seen anywhere in the tumor?
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?
Were perineural or lymphovascular invasion identified?
Were any lymph nodes involved by tumor, and was extranodal extension present?
Was the diagnosis confirmed with S100 and mammaglobin staining, or with molecular testing?
Was the specific gene fusion identified — was it ETV6-NTRK3, ETV6-RET, or another fusion?
If my tumor has come back or has spread, am I a candidate for an NTRK inhibitor or RET inhibitor?
Will I need radiation therapy after surgery?
What is my estimated risk of the cancer coming back?
What is the schedule for follow-up examinations and imaging, and how long will it continue?
Will I have any lasting facial weakness, numbness, or dry mouth from the surgery?
Are there any clinical trials I should consider?