A cancer diagnosis is always a journey into the unknown. But when the diagnosis is a rare cancer like Adenoid Cystic Carcinoma (ACC), that journey can feel even more isolating and uncertain. Unlike common cancers that are frequently discussed in public health campaigns, ACC is a disease many people have never heard of. It is a relatively rare form of cancer that typically arises in glandular tissues, most often the salivary glands of the head and neck. ACC is known for its unique and often deceptive behavior. It tends to grow very slowly, but it has a notable propensity for spreading along nerves and recurring, sometimes many years after initial treatment. This guide offers a clear and comprehensive overview of Adenoid Cystic Carcinoma, explaining its nature, causes, and the specialized treatment approaches required to manage this complex disease.

Adenoid cystic carcinoma (ACC) is a rare and slow-growing canceroriginating in glandular cells. Glandular tissues are found throughout the body and are responsible for secreting substances, such as saliva, tears, sweat, and mucus. ACC can technically develop in any of these areas, but it is most found in the major and minor salivary glands located throughout the head and neck region. Other, less common sites include the tear gland (lacrimal gland), skin, breast, cervix, and respiratory tract.

What makes ACC distinct from many other cancers is its characteristic behavior and appearance under a microscope. Pathologists often describe its cellular structure as “cribriform,” resembling the pattern of Swiss cheese. However, its most defining clinical feature is its insidious nature, which is characterized by three key tendencies:

Slow but Relentless Growth: ACC is often described as an indolent or slow-growing tumor. A person might notice a small, painless lump that grows very gradually over months or even years. This slow progression can sometimes cause delays in diagnosis.

Perineural Invasion: This is the hallmark of Adenoid Cystic Carcinoma. Cancer cells have a unique and dangerous affinity for nerves. Think of the body’s nerves as an intricate network of electrical wiring that runs throughout our tissues. ACC has a remarkable ability to wrap around and travel along these nerve “wires” like a vine climbing a trellis. This “perineural invasion” allows the cancer to spread silently far beyond the visible, primary tumor. This is the main reason ACC treatment must be so aggressive.

Tendency for Late Recurrence and Distant Metastasis: Because of its slow growth and ability to travel along nerves, ACC has a high rate of recurring in the same local area, even after seemingly successful treatment. It also has a propensity to spread to distant parts of the body (metastasize) late in the course of disease, sometimes 10, 15, or even 20 years after the initial diagnosis. The most common site for distant metastasis is the lungs.

The exact cause of ACC remains unclear, but it is believed to be the result of genetic mutations that occur during a person’s lifetime, rather than inherited traits. These mutations lead to uncontrolled growth of glandular epithelial cells.

In a majority of cases, ACC is driven by a chromosomal translocation, which is a type of genetic mix-up. In this event, a piece of one chromosome breaks off and fuses with a piece of another chromosome. In ACC, this typically involves the genes MYB and NFIB. This fusion creates a new, abnormal gene, MYB-NFIB, which acts like a stuck accelerator pedal in the cell. The fusion protein produced by this gene continuously promotes cell growth and survival, leading to the development of the cancerous tumor.

It is crucial to understand that this is an acquired genetic change that happens within the cells of one individual. It is not an inherited mutation that is passed down through families.

Unlike many other cancers, especially those in the head and neck, there are no well-established lifestyle or environmental risk factors for developing Adenoid Cystic Carcinoma.

• It is not linked to smoking or alcohol use, which are major risk factors for other head and neck cancers like squamous cell carcinoma.
• It is not associated with any specific viral infections, such as HPV or EBV.

ACC is a cancer that appears to arise sporadically, without a clear cause of preventable risk factor. It affects men and women, though it is slightly more common in women. While it can occur at almost any age, it is most typically diagnosed in mid-adulthood, between the ages of 40 and 60. For nearly all patients, there is nothing they could have done to prevent the disease from developing.

Symptoms vary based on the location of the tumor, but ACC generally grows slowly and without pain, until it begins pressing on nearby nerves or structures.

When ACC develops in the salivary glands (the most common location), symptoms can include:

• A slow growing, often painless lump or swelling in the jaw, on the roof of the mouth (palate), under the tongue, or in the cheek.
• Numbness in the lower lip, chin, or tongue.
• Persistent, dull pain in the area of the lump.
• Difficulty swallowing or moving the tongue.
• Facial weakness or paralysis: This is a major red flag. If the tumor invades the facial nerve, it can cause one side of the face to droop.

When ACC arises in other locations, the symptoms will be different:

• Lacrimal Gland (Tear Gland): Bulging of the eye, changes in vision, or pain.
• Larynx or Trachea (Voice Box or Windpipe): Hoarseness, changes in the voice, or difficulty breathing.
• Skin: A slow growing lump or nodule on the scalp or other areas.

Diagnosis involves a combination of imaging, biopsy, and microscopic examination of the tumor. Because ACC grows slowly and deeply, it’s important to assess not just the surface but also how far it has invaded.

1. Physical Examination and History: A doctor—often an ear, nose, and throat (ENT) specialist—will perform a thorough head and neck exam and take a detailed medical history.
2. Imaging: Imaging studies are crucial for determining the size and extent of the tumor and, importantly, for looking for signs of nerve involvement. Magnetic Resonance Imaging (MRI) is often the preferred method because it provides excellent detail of soft tissues and nerve pathways. A CT scan may also be used.
3. Biopsy: This involves taking a small sample of the tumor tissue, which is then examined under a microscope by a pathologist. The pathologist will identify the characteristic cellular patterns of ACC. A fine-needle aspiration (FNA) may be done first, but often a larger incisional or excisional biopsy is needed for a conclusive diagnosis.

Clinically, biopsy remains the gold standard, under the microscope, ACC has a very distinct “cribriform” pattern, which helps confirm the diagnosis.

Staging: Once ACC is diagnosed, it must be staged. Staging is the process of determining the size of the tumor (T), whether it has spread to nearby lymph nodes (N), and whether it has metastasized to distant parts of the body (M).

Treatment focuses on complete tumor removal, followed by radiation therapy to reduce the risk of recurrence. Chemotherapy is rarely effective but may be used in advanced cases.

1. Surgery: Surgery is the primary and most important treatment for localized Adenoid Cystic Carcinoma.

• The goal is to perform a wide local excision, removing the entire visible tumor along with a margin of surrounding healthy tissue.
• Because of ACC’s tendency for perineural invasion, the surgery is often very extensive. The surgeon must attempt to trace any involved nerves as far back as possible to remove all cancerous cells. This can sometimes require sacrificing nerves, which can lead to permanent numbness or muscle weakness (e.g., facial paralysis).

2. Radiation Therapy: Radiation therapy is almost always recommended after surgery (this is called adjuvant radiation).

• Its purpose is to destroy any microscopic cancer cells that may have been left behind after the operation, especially along nerve pathways or at the surgical margins.
• Giving radiation after surgery has been shown to significantly reduce the risk of the cancer coming back in the same location (local recurrence).
• Advanced radiation techniques like Intensity Modulated Radiation Therapy (IMRT) or proton beam therapy are often used to deliver a high dose of radiation to the target area while minimizing damage to surrounding healthy structures like the eyes and brain.

3. Systemic Therapy (Chemotherapy and Targeted Drugs): The role of systemic therapy in ACC is more limited and is an area of active research.

• Traditional Chemotherapy: ACC is a slow-growing cancer, and traditional chemotherapy drugs, which work by killing rapidly dividing cells, have unfortunately shown very limited effectiveness against it. Chemotherapy is generally not part of the standard initial treatment and is typically reserved for patients whose cancer has spread widely (metastasized) and is causing symptoms, with the goal of slowing its progression.
• Targeted Therapy and Clinical Trials: Because of the limited success of chemotherapy, there is intense research into new drugs that can target the specific molecular drivers of ACC, such as the MYB-NFIB fusion gene. For patients with advanced or recurrent disease, participating in a clinical trial is often the best option and provides access to the very latest treatment innovations.

Adenoid Cystic Carcinoma is a rare cancer with a unique and challenging biology. Its slow-growing but tenacious nature, particularly its ability to spread along nerves, sets it apart from many other cancers. The standard of care, aggressive surgery followed by radiation therapy, is aimed at achieving long term local control. While the risk of late recurrence and distant metastasis remains a lifelong concern, it is important to understand that many patients live for a very long time with this disease. The key to successful management is treatment by an experienced, multidisciplinary team and a commitment to lifelong, vigilant follow-up with regular imaging.

• National Cancer Institute (NCI). (2023). Salivary Gland Cancer Treatment (PDQ®)–Health Professional Version. Retrieved from https://www.cancer.gov/types/head-and-neck/hp/salivary-gland-treatment-pdq
• National Organization for Rare Disorders (NORD). (2023). Adenoid Cystic Carcinoma. Retrieved from https://rarediseases.org/rare-diseases/adenoid-cystic-carcinoma/
• National Cancer Institute. (2023). Rare tumors: Adenoid cystic carcinoma. https://www.cancer.gov