Acinic cell carcinoma: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
May 4, 2026

Acinic cell carcinoma is a type of cancer that starts in the salivary glands — the glands that produce saliva. Most acinic cell carcinomas grow slowly, are limited to the gland in which they arise, and are cured by surgery alone. However, a small but important subset of acinic cell carcinomas show a feature called high-grade transformation, in which part of the tumor changes into a more aggressive form of cancer. The presence or absence of high-grade transformation is one of the most important findings in your pathology report because it strongly influences both the treatment plan and the long-term outlook.

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

What causes acinic cell carcinoma?

The exact cause of acinic cell carcinoma is not known. Most tumors arise out of nowhere, with no identifiable risk factor and no link to smoking, alcohol, infection, or any environmental exposure. What scientists have learned is that almost every acinic cell carcinoma carries the same specific genetic change inside its tumor cells. A piece of DNA called an enhancer — a region that controls how strongly nearby genes are switched on — is moved from its normal location on chromosome 4 (within a cluster of salivary gland genes called the SCPP cluster) to a new location on chromosome 9, right next to a gene called NR4A3. This rearrangement causes NR4A3 to be expressed at very high levels in tumor cells, driving them to divide and form a tumor. The genetic change happens by chance during a person’s lifetime; it is not inherited and cannot be passed to children. The same change is now used as a diagnostic marker, as described in the biomarker section below.

Where does acinic cell carcinoma start?

Acinic cell carcinoma can develop in any salivary gland, but is most often found in the parotid gland, which sits in front of and just below each ear. About 80% of acinic cell carcinomas arise in the parotid gland. The remainder occur in the submandibular gland (under the jaw), the sublingual gland (under the tongue), or in the small minor salivary glands distributed throughout the lining of the mouth and throat. In a small number of patients (1–3%), tumors arise in both parotid glands at the same time.

Acinic cell carcinoma can occur at any age but is most common between 40 and 60. There is a slight female predominance. It is the most common salivary gland cancer in children and young adults, although it is still uncommon in this age group overall.

Major salivary glands

What are the symptoms of acinic cell carcinoma?

Most acinic cell carcinomas grow slowly over months or years and produce only mild symptoms in the early stages:

Painless lump — A slow-growing, painless mass in the salivary gland is by far the most common finding. In the parotid gland, the lump is usually felt under the skin in front of or below the ear. In the submandibular gland, it is felt under the jaw. Tumors in minor salivary glands appear as a lump inside the mouth.
Pain or tenderness — Uncommon at presentation. New pain can 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 compress or invade this nerve can cause weakness or paralysis of part of the face. This is uncommon in acinic cell carcinoma and, when present, raises concern for a more aggressive tumor.
Difficulty swallowing or speaking — Larger tumors of the minor salivary glands or sublingual gland can interfere with normal mouth function.
Swelling in the neck — Occasionally caused by the spread of the tumor to nearby lymph nodes. Spread to lymph nodes is uncommon in acinic cell carcinoma without high-grade transformation.

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 study — typically an ultrasound, CT scan, or MRI — that shows a mass within the salivary gland. A fine needle aspiration biopsy (FNAB) is often performed first, in which a thin needle is used to collect a small sample of cells. If the FNAB is not conclusive, a core needle biopsy may be performed instead. In many cases, the entire tumor is removed in a single operation, and the diagnosis is made on the resection specimen rather than on a separate biopsy.

Under the microscope, the pathologist looks for cells that resemble the acinar cells of a normal salivary gland — the cells that normally produce saliva. The tumor cells are typically large, rounded, and filled with small purple-staining granules called zymogen granules, which represent saliva-producing enzymes packaged inside the cell. Special stains such as periodic acid-Schiff (PAS) with diastase digestion (PAS-D) highlight these granules. The cells may be arranged in solid sheets, in small groups, or surrounding small fluid-filled spaces called microcysts or follicles. A characteristic feature of acinic cell carcinoma is a heavy accumulation of immune cells, especially lymphocytes, around or within the tumor — this is called tumor-associated lymphoid proliferation and is a helpful clue to the diagnosis. Once the diagnosis is confirmed by microscopy and immunohistochemistry, additional imaging is performed to assess spread before surgery is planned.

High-grade transformation

High-grade transformation is the most important histologic feature in any pathology report for acinic cell carcinoma. It means that part of the tumor has changed from the slow-growing classic appearance into a much more aggressive form of cancer. In areas of high-grade transformation, the tumor cells lose their resemblance to normal acinar cells. They become atypical, with marked variation in size and shape (pleomorphism), and the pathologist sees a dramatic increase in mitotic figures (dividing tumor cells) and areas of necrosis (cell death).

This finding matters because high-grade transformation profoundly changes the behavior of the tumor. Acinic cell carcinomas with high-grade transformation are much more likely to spread to lymph nodes in the neck and to distant sites such as the lungs. Treatment typically becomes more aggressive — often including a neck dissection (removal of regional lymph nodes) and adjuvant radiation therapy — and the long-term prognosis is considerably worse than for classic acinic cell carcinoma. Reported 5-year survival drops from over 90% for classic acinic cell carcinoma to roughly 30–40% when high-grade transformation is present.

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. The presence of extraparenchymal extension means the tumor is more advanced and is given a higher pathologic stage (pT). It is also associated with a higher risk of recurrence 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. Lymphovascular invasion is uncommon in classic acinic cell carcinoma and is much more often seen when high-grade transformation is present. When found, it is associated with a higher risk that the cancer will return after treatment, 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 directly through the parotid gland and is the most commonly involved nerve in parotid acinic cell carcinoma. Perineural invasion can cause new pain, numbness, or facial weakness. When seen on a pathology report, it raises the risk that the tumor will recur near the original site, and your doctor may recommend radiation therapy after surgery to reduce 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 determine 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 of local recurrence and may lead to a recommendation for adjuvant radiation therapy.
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 additional surgery or adjuvant radiation therapy.

Margin assessment is particularly challenging in parotid surgery because the surgeon must work around the facial nerve, which limits how widely the tumor can be cut around. 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 acinic cell carcinoma are those in the neck, particularly in the area called level II, immediately below the angle of the jaw. 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 likely to be performed when high-grade transformation is present, when the tumor is large, or when imaging or examination has suggested 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. Your 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 acinic cell carcinoma but is much more frequent when high-grade transformation is present. The pattern of lymph node involvement is used to determine the pathologic nodal stage (pN) and helps guide decisions about radiation therapy after surgery.

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 make a diagnosis, predict how the tumor will behave, or decide whether a particular treatment is likely to work. In some cancer types (such as breast cancer or lung cancer), biomarker testing is performed routinely on every case because the results directly determine which drugs will be used. Acinic cell carcinoma is different. Most acinic cell carcinomas can be diagnosed by their microscopic appearance alone, and there are currently no biomarker results that change the standard treatment, which is surgery with or without radiation therapy. For these reasons, biomarker testing is not performed on every acinic cell carcinoma; it is reserved for situations where the diagnosis is uncertain under the microscope or where another tumor type is being considered. The three tests below are the ones most commonly used.

NR4A3 immunohistochemistry

As described in the “What causes” section, almost all acinic cell carcinomas carry a specific genetic change that causes the NR4A3 gene to be turned on at very high levels. Immunohistochemistry for the NR4A3 protein is now the most useful single test for confirming the diagnosis. Most acinic cell carcinomas show strong, uniform staining of the tumor cell nuclei, while other salivary gland tumors are typically negative. The result is reported as “NR4A3 positive” or “NR4A3 negative.”

DOG1 and SOX10

DOG1 and SOX10 are two other proteins that are highlighted by immunohistochemistry. Acinic cell carcinoma is typically positive for both, with DOG1 showing a characteristic pattern of staining around the edge of the cell and within the small fluid-filled spaces of the tumor. These tests are often used in combination with NR4A3 to confirm the diagnosis and help distinguish acinic cell carcinoma from other salivary gland tumors with overlapping features.

Molecular testing

When immunohistochemistry alone is insufficient to establish the diagnosis, the underlying genetic rearrangement involving NR4A3 can be detected directly using techniques such as fluorescence in situ hybridization (FISH) or next-generation sequencing. These tests are used selectively, particularly in unusual cases or when a different salivary gland tumor — most often secretory carcinoma — is in the differential diagnosis. Secretory carcinoma was once grouped with acinic cell carcinoma but is now recognized as a separate diagnosis with its own genetic change involving the ETV6 gene. Many tumors that were called acinic cell carcinoma before about 2010 would today be reclassified as secretory carcinoma. If you have an older report, this is worth discussing with your doctor.

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 for the size and extent of the primary tumor, N for involvement of regional lymph nodes, and M for spread to distant parts of the body. Staging applies only to acinic cell carcinomas of the major salivary glands; tumors of the minor salivary glands are staged using the system for the area of origin (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 acinic cell carcinoma is excellent. The tumor as a group is one of the more favorable salivary gland cancers, and complete surgical removal cures most patients. The overall 5-year survival rate for classic acinic cell carcinoma is greater than 90%, and the 10-year survival rate is approximately 80%. Recurrence after complete surgery is uncommon but can occur many 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 adverse feature. 5-year survival drops to approximately 30–40% when present.
Tumor size larger than 4 cm — Larger tumors are more likely to have spread and to recur.
Extraparenchymal extension — Tumors that have grown beyond the salivary gland are at higher risk of recurrence.
Positive surgical margins — Incompletely removed tumors are more likely to come back.
Lymph node involvement — Spread to lymph nodes raises the risk of distant recurrence and worsens overall prognosis.
Perineural and lymphovascular invasion — Both are associated with a higher risk of local recurrence.

What happens after the diagnosis?

Treatment for acinic cell carcinoma is led by a head and neck surgeon, often working 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 mainstay of treatment is surgery to remove the entire tumor.

Parotidectomy — Removal of part or all of the parotid gland. Most acinic cell carcinomas are treated with a superficial parotidectomy or, for deeper tumors, a total parotidectomy. The facial nerve is preserved whenever possible. Submandibular and sublingual tumors are removed along with the entire affected gland.
Neck dissection — Removal of lymph nodes from one or both sides of the neck. Performed 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 acinic cell carcinomas.
Radiation therapy — Recommended after surgery 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 delivered as a series of daily treatments over several weeks.
Systemic therapy — Standard chemotherapy is generally not effective in acinic cell carcinoma and is reserved for selected patients with metastatic or unresectable disease. Targeted therapy options are being studied; for the rare tumors that turn out to be secretory carcinoma rather than true acinic cell carcinoma, NTRK-inhibitor drugs (such as larotrectinib and entrectinib) are highly active.
Long-term surveillance — Regular clinical examination of the head and neck, with imaging as needed, is performed for many years after treatment. Late recurrence — even more than 10 years after the original surgery — has been reported, particularly in tumors with adverse features.

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 NR4A3 immunohistochemistry, or was molecular testing performed?
If my report is from before 2010, could the tumor actually be a secretory carcinoma rather than an acinic cell carcinoma?
Will I need radiation therapy or systemic 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 dryness of the mouth from the surgery?
Are there any clinical trials I should consider?