Perineural invasion (PNI) is a process where cancer cells grow into, around, and along the body’s nerves. This is a microscopic finding, identified by a pathologist looking at tissue under a microscope, and is not something a patient feels or that is immediately obvious. For many people, the first time they encounter this term is after a biopsy or surgery when reviewing the findings with their doctor.
This process is a recognized feature in many types of cancer that represents a specific way a tumor can travel. The presence of PNI provides insight into the tumor’s behavior and helps guide conversations about a patient’s care plan and prognosis.
The Biological Mechanism of Invasion
The body’s network of nerves can be thought of as an intricate highway system. For cancer cells, the path along these nerves represents a route of least resistance for migration. This is not a random occurrence, as a complex biological crosstalk unfolds between the tumor and nerve cells. Tumors can release chemical attractants, such as neurotrophic factors and chemokines, that actively draw them toward nerves, creating a microenvironment favorable for movement.
The structure of a nerve provides a channel for this invasion. Nerves are wrapped in layers of tissue, and the space within these sheaths, called the perineural space, offers a pathway for malignant cells to travel. Once cancer cells are in this space, they can move along the nerve, extending beyond the primary tumor’s visible boundaries. This is not a passive process, as the cancer cells and nerve cells engage in a dynamic interaction.
This invasive behavior is a multistep process involving changes in the environment around the nerve and enhancements in the cancer cells’ ability to move. The cancer cells hijack the nerve structure, using it as a scaffold to advance into surrounding tissues. This mechanism of spread can occur independently of the cancer entering the bloodstream or lymphatic system.
Diagnosis and Associated Cancers
The diagnosis of perineural invasion is made through histological examination of a tissue sample obtained from a biopsy or the surgical removal of a tumor. A pathologist looks for cancer cells within any of the three layers of the nerve sheath or surrounding at least 33% of a nerve’s circumference to confirm the diagnosis.
PNI is not visible on standard imaging tests like CT scans or MRIs unless the invasion is extensive. Because the process begins at a cellular level far too small for most imaging to detect, its initial identification relies on the pathological review of tissue.
Perineural invasion is a known characteristic of several types of cancer, particularly those in areas with a rich nerve supply. It is most frequently associated with:
- Cancers of the head and neck
- Prostate cancer
- Pancreatic cancer
- Colorectal cancer
- Certain skin cancers
- Biliary tract tumors
Prognostic Significance
The identification of perineural invasion in a pathology report is an adverse prognostic factor. Its presence is statistically associated with a more aggressive cancer and a higher likelihood of the cancer returning after initial treatment. This information helps doctors assess the risk of recurrence and disease progression.
A primary concern with PNI is the increased risk of local recurrence, which is the cancer coming back in the same area where it first started. Because cancer cells can travel along nerves beyond the main tumor mass, these microscopic extensions may not be completely removed during surgery and can create the potential for the cancer to regrow.
The presence of PNI has been linked to lower overall survival rates in several types of cancer. For example, studies in cervical cancer and gallbladder cancer have shown that patients with PNI have a poorer prognosis compared to those without it. In prostate cancer, PNI is associated with an increased risk of biochemical recurrence, where blood markers for the cancer rise after treatment.
How Perineural Invasion Affects Treatment
A finding of perineural invasion influences treatment recommendations, often prompting a more aggressive therapeutic approach. The primary goal is to address the microscopic spread of cancer cells along nerve pathways to reduce the chance of the cancer returning. Treatment plans are frequently adjusted to be more comprehensive than they might have been otherwise.
In the context of surgery, PNI necessitates wider surgical margins. A surgeon may need to remove a larger area of tissue around the visible tumor to clear out the cancerous cells that have migrated along the nerves. The aim is to achieve “negative” margins, meaning no cancer cells are found at the edge of the removed tissue.
Following surgery, adjuvant radiation therapy is frequently recommended. Radiation is used to target the nerve pathways that the cancer may have used to spread. By treating the area where the tumor was located and the associated nerve routes, doctors aim to eliminate any residual microscopic cancer cells that surgery might have missed.
The presence of PNI can also affect decisions about using systemic therapies, such as chemotherapy. While surgery and radiation are local treatments, the aggressive nature indicated by PNI might suggest a higher risk of the cancer spreading to distant parts of the body. In such cases, systemic treatments that travel throughout the body may be considered to address this possibility.