Acinic cell carcinoma

by Jason Wasserman MD PhD FRCPC
November 28, 2024

Acinic cell carcinoma is a type of cancer that primarily affects the salivary glands. There are three major pairs of salivary glands: the parotid glands, the submandibular glands, and the sublingual glands, along with hundreds of minor salivary glands located throughout the mouth and throat. Acinic cell carcinoma can develop in any of these glands but is most commonly found in the parotid gland. This type of cancer is characterized by its slow growth, although it can still metastasize (spread) to lymph nodes or other parts of the body.

What causes acinic cell carcinoma?

At present, doctors do not know what causes acinic cell carcinoma. However, most tumours contain a genetic change that places a part of the SCPP gene cluster close to the NR4A3/NOR-1 gene. What causes this genetic change to occur is still unknown.

What are the symptoms of acinic cell carcinoma?

Most acinic cell carcinomas are slow-growing and painless. Depending on its location, it may be seen as a lump under the skin or on the inside surface of the oral cavity. Tumours that show high-grade transformation (see below) tend to grow more quickly and may cause pain as they grow into surrounding nerves.

How is this diagnosis made?

The diagnosis of acinic cell carcinoma can be made after a small tumour sample is removed in either a core or fine needle aspiration biopsy (FNAB). It can also be made after the entire tumour is removed in an excision or resection. The tissue removed is then sent to a pathologist for examination under the microscope.

Microscopic features of this tumour

When examined under the microscope, the tumour cells in most acinic cell carcinomas look very similar to the acinar cells normally found in the salivary glands. Like normal acinar cells, the tumour cells contain small round structures called zymogen granules, which can be seen on the routine H&E stained slide and when special stains such as PAS and PAS-D are performed. The tumour cells are often arranged in groups called sheets or in round structures called cysts or follicles. In many cases, the tumour cells are surrounded by immune cells called lymphocytes. Pathologists describe this as “tumour-associated lymphoid proliferation” (TALP).

High grade transformation

High grade transformation in acinic cell carcinoma means that the tumour has started to change, resulting in more aggressive behaviour. When examined under the microscope, tumours with high grade transformations have lost some of the features typically seen in an acinic cell carcinoma. In particular, the tumour cells will no longer look like normal acinar cells. These cells may be described as being atypical or pleomorphic. In addition, tumours with high grade transformation often have more mitotic figures (tumour cells dividing to create new tumour cells) and a type of cell death called necrosis may also be seen. High grade transformation is important because these tumours are more likely to metastasize (spread) to lymph nodes and the lungs.

Extraparenchymal extension

In the context of a salivary gland tumour such as acinic cell carcinoma, extraparenchymal extension (EPE) is the spread of the tumour beyond the salivary gland into the surrounding tissues. This condition is often associated with a more aggressive form of cancer, indicating that the tumour can invade beyond its original site. The presence of extraparenchymal extension is associated with more aggressive tumours and a worse prognosis.

Extraparenchyma, extension impacts the pathologic stage but only for tumours arising from one of the major salivary glands (parotid, submandibular, and sublingual). Tumours with extraparenchymal extension are generally classified at a higher stage, reflecting their advanced nature and the associated challenges in treatment and management.

Lymphovascular invasion​

Lymphovascular invasion occurs when cancer cells invade a blood vessel or lymphatic vessel. Blood vessels are thin tubes that carry blood throughout the body, unlike lymphatic vessels, which carry a fluid called lymph instead of blood. These lymphatic vessels connect to small immune organs known as lymph nodes scattered throughout the body. Lymphovascular invasion is important because it spreads cancer cells to other body parts, including lymph nodes or the liver, via the blood or lymphatic vessels.

Perineural invasion​

Pathologists use the term “perineural invasion” to describe a situation where cancer cells attach to or invade a nerve. “Intraneural invasion” is a related term that specifically refers to cancer cells found inside a nerve. Nerves, resembling long wires, consist of groups of cells known as neurons. These nerves, present throughout the body, transmit information such as temperature, pressure, and pain between the body and the brain. The presence of perineural invasion is important because it allows cancer cells to travel along the nerve into nearby organs and tissues, raising the risk of the tumour recurring after surgery.

Margins

In pathology, a margin is the edge of tissue removed during tumour surgery. The margin status in a pathology report is important as it indicates whether the entire tumour was removed or if some was left behind. This information helps determine the need for further treatment.

Pathologists typically assess margins following a surgical procedure, like an excision or resection, that removes the entire tumour. Margins aren’t usually evaluated after a biopsy, which removes only part of the tumour. The number of margins reported and their size—how much normal tissue is between the tumour and the cut edge—vary based on the tissue type and tumour location.

Pathologists examine margins to check if tumour cells are present at the tissue’s cut edge. A positive margin, where tumour cells are found, suggests that some cancer may remain in the body. In contrast, a negative margin, with no tumour cells at the edge, suggests the tumour was fully removed. Some reports also measure the distance between the nearest tumour cells and the margin, even if all margins are negative.

Lymph nodes​

Small immune organs, known as lymph nodes, are located throughout the body. Cancer cells can travel from a tumour to these lymph nodes via tiny lymphatic vessels. For this reason, doctors often remove and microscopically examine lymph nodes to look for cancer cells. This process, where cancer cells move from the original tumour to another body part, like a lymph node, is termed metastasis.

Cancer cells usually first migrate to lymph nodes near the tumour, although distant lymph nodes may also be affected. Consequently, surgeons typically remove lymph nodes closest to the tumour first. They might remove lymph nodes farther from the tumour if they are enlarged and there’s a strong suspicion they contain cancer cells.

Pathologists will examine any lymph nodes that have been removed under a microscope, and the findings will be detailed in your report. A “positive” result indicates the presence of cancer cells in the lymph node, while a “negative” result means no cancer cells were found. If the report finds cancer cells in a lymph node, it might also specify the size of the largest cluster of these cells, often referred to as a “focus” or “deposit.” Extranodal extension occurs when tumour cells penetrate the lymph node’s outer capsule and spread into the adjacent tissue.

Examining lymph nodes is important for two reasons. First, it helps determine the pathologic nodal stage (pN). Second, discovering cancer cells in a lymph node suggests an increased risk of later finding cancer cells in other body parts. This information guides your doctor in deciding whether you need additional treatments, such as chemotherapy, radiation therapy, or immunotherapy.

Pathologic stage

Pathologic staging is a system doctors use to describe the size and spread of a tumour. This helps determine how advanced the cancer is and guides treatment decisions. The pathologic stage is usually determined after the tumour is removed and examined by a pathologist, who analyzes the tissue under a microscope. For acinic cell carcinoma, staging is based on the “TNM” system, where “T” stands for the size and extent of the primary tumour, “N” refers to lymph node involvement, and “M” indicates whether the cancer has spread to other parts of the body.

Tumour stage (pT)

The tumour stage describes the size of the tumour in the salivary gland and whether it has spread into nearby tissues.

• T0 means there is no evidence of a primary tumour in the salivary gland.
• Tis refers to carcinoma “in situ,” meaning the cancer cells are limited to where they started and have not invaded deeper tissues.
• T1 means the tumour is 2 cm or smaller and has not spread beyond the salivary gland.
• T2 refers to a tumour larger than 2 cm but not larger than 4 cm, still confined to the salivary gland.
• T3 means the tumour is larger than 4 cm or has spread to nearby soft tissues.
• T4 describes more advanced tumours. T4a means the tumour has spread to the skin, jawbone, ear canal, or facial nerve. T4b indicates very advanced cancer that has spread to the base of the skull, nearby bones, or major blood vessels.

Nodal stage (pN)

The nodal stage indicates whether the cancer has spread to the lymph nodes, which are small glands that help the body fight infection. Lymph node involvement can increase the risk of cancer spreading further.

• N0 means there is no spread to nearby lymph nodes.
• N1 indicates the cancer has spread to a single lymph node on the same side of the neck, measuring 3 cm or smaller.
• N2 describes more extensive lymph node involvement:
  • N2a: A single lymph node on the same side of the neck is affected, measuring up to 6 cm, or smaller nodes that show signs of cancer outside the node.
  • N2b: Multiple lymph nodes on the same side of the neck are affected, none larger than 6 cm.
  • N2c: Cancer has spread to lymph nodes on both sides of the neck or on the opposite side, none larger than 6 cm.
• N3 indicates more advanced lymph node involvement. N3a means a node larger than 6 cm is affected. N3b involves multiple nodes or any nodes where cancer has spread outside the lymph node into nearby tissues.

Prognosis for patients with acinic cell carcinoma

The prognosis for a patient diagnosed with acinic cell carcinoma is generally favourable, and most patients are cured through surgery alone. The following list describes factors that influence prognosis.

Stage of the cancer at diagnosis

• Early-stage cancers that are small in size and confined to the salivary gland have a better prognosis.
• Advanced-stage cancers that have metastasized (spread) to nearby tissues, lymph nodes, or distant parts of the body tend to have a worse prognosis.

Tumor size and location

• Smaller tumours typically have a better outcome, as they are often easier to remove completely with surgery.
• Tumors in locations that are difficult to surgically remove may have a poorer prognosis.

High grade transformation

• High grade transformation means that the tumour has changed into a more aggressive form of cancer. Tumours with high grade transformation are more likely to spread to lymph nodes and are associated with worse prognosis.

Lymph node involvement

• The presence of cancer cells in the lymph nodes is associated with a higher risk of recurrence and a poorer prognosis.

Resection margins

• Complete surgical removal of the tumour with negative margins (no cancer cells found at the edge of the removed tissue) is associated with a lower risk of recurrence and a better prognosis.
• Positive margins (cancer cells found at the edge of the removed tissue) may require additional treatments, such as radiation, and are associated with a higher risk of the cancer returning.

Age and overall health

• Younger patients and those in good overall health may have a better prognosis due to a better ability to tolerate surgery and other treatments.
• Older patients or those with significant comorbidities may have a more challenging recovery and treatment course.

Recurrence

• Patients whose cancer recurs after initial treatment tend to have a poorer prognosis.

Treatment response

• A favourable response to initial treatment, especially complete surgical removal, is associated with a better prognosis.

About this article

Doctors wrote this article to help you read and understand your pathology report. Contact us if you have questions about this article or your pathology report. For a complete introduction to your pathology report, read this article.