A ganglioneuroma is an uncommon, noncancerous tumor that develops from sympathetic nervous system cells. This part of the body’s nerve network controls automatic functions such as heart rate, blood pressure, and digestion.
Ganglioneuroma is the most mature member of a family called the neuroblastic tumors. Less mature members include neuroblastoma, a cancer, and ganglioneuroblastoma, which contains a mixture of mature and immature cells. Over time, a less mature tumor can mature into a ganglioneuroma. This article explains what appears on a ganglioneuroma pathology report, why the pathologist looks so closely for immature areas, and when this diagnosis raises questions about an inherited condition.
Ganglioneuromas form wherever sympathetic nerve tissue is present. The commonest sites are the adrenal gland, which sits above each kidney, the chest behind the lungs, and the abdomen or pelvis alongside the spine. They can also occur in the wall of the digestive tract, a distinct situation covered in its own section below.
Because they grow slowly, ganglioneuromas can become large and press on nearby structures. They rarely grow into surrounding tissue, and they do not spread to other parts of the body.
Ganglioneuroma is most often diagnosed in older children and adolescents, and it also occurs in adults. In adults,s an adrenal ganglioneuroma is usually found incidentally on a scan performed for an unrelated reason.
The cause of a ganglioneuroma is not known, and it is not linked to diet, activity, injury, or anything in the environment.
These tumors are understood to arise when immature nerve cells called neuroblasts gradually mature. They become normal-looking nerve cells, called ganglion cells, alongside Schwann cells, the nervous system’s supporting cells. Some ganglioneuromas appear to have started as a neuroblastoma that matured on its own, either spontaneously or after treatment. This explains why the ganglioneuroma is the most mature and most favorable member of the neuroblastic tumor family.
Most ganglioneuromas cause no symptoms at all and are found incidentally on imaging done for another reason. When symptoms occur, they are usually caused by the size or position of the tumor rather than by anything the tumor produces.
Imaging often raises suspicion of a ganglioneuroma. CT or MRI usually shows a solid, well-defined mass that takes up contrast slowly, and calcium deposits are sometimes visible. Imaging alone cannot separate a ganglioneuroma from the less mature members of the family. A pathologist confirms the diagnosis only after examining the tissue under a microscope.
The tissue may come from a biopsy or from the whole tumor after surgery. Where the tumor is in the adrenal gland, urine or blood tests for adrenaline-like hormones are often done first. These tests check whether the tumor is producing hormones and help distinguish it from a pheochromocytoma, which arises in the same place.
Under the microscope, a ganglioneuroma has two cell types, and both must be present for diagnosis.
Pathologists recognize two subtypes, both of which are noncancerous. In a maturing ganglioneuroma, the ganglion cells are a mixture of developing and fully mature forms. The developing cells vary in size and shape and can contain more than one nucleus. In a mature ganglioneuroma, all of the ganglion cells are fully developed and are often surrounded by small supporting cells called satellite cells, giving the tumor a very orderly appearance.
In both subtypes, the ganglion cells lack neuropil, the tangle of bare nerve fibers seen in less mature neuroblastic tumors. Instead, Schwann cells wrap their nerve processes. The absence of neuropil is one feature that separates a ganglioneuroma from a ganglioneuroblastoma.
Immunohistochemistry uses antibodies to detect specific proteins in the tumor cells. It is not always needed for a ganglioneuroma, because the appearance under the microscope is often distinctive. It is used when the diagnosis is uncertain or when the sample is small.
The Schwann cell component is typically positive for S100. The ganglion cells are typically positive for synaptophysin and other nerve cell markers. These results also help separate a ganglioneuroma from tumors that can look similar. Those include schwannoma and neurofibroma, which contain Schwann cells but no ganglion cells, and, in the digestive tract, gastrointestinal stromal tumor.
Neuroblastic tumors form a spectrum from fully immature to mature fully, and where a tumor sits on that spectrum determines how it is treated.
Because these tumors sit on one spectrum, a pathologist examining a ganglioneuroma looks systematically for any immature area. Finding one changes the diagnosis.
A ganglioneuroma can contain a small focus of less mature tumor somewhere within it, and a needle biopsy samples only a narrow core of tissue. A report based on a biopsy may therefore include a comment noting that the diagnosis reflects the tissue available, and recommending either complete removal or careful follow-up.
This does not mean the pathologist is uncertain about what they examined. It states what a small sample can and cannot exclude. When the whole tumor is removed and examined, the pathologist can sample it thoroughly, and the comment usually disappears from the final report.
Ganglioneuromas that arise in the wall of the stomach, bowel, or rectum behave differently from those in the adrenal gland or chest. They also raise a question the others usually do not.
The conditions most often involved are neurofibromatosis type 1, multiple endocrine neoplasia type 2B, and PTEN hamartoma tumor syndrome, which includes Cowden syndrome. Each has other features a doctor can look for, and each has implications for relatives. If your report describes widespread or multiple ganglioneuromas in the digestive tract, it is reasonable to ask whether referral for genetic assessment is appropriate. You can read more in our article What is a hereditary cancer syndrome?
A ganglioneuroma in the adrenal gland, chest, or alongside the spine is usually an isolated finding and does not by itself point to an inherited condition.
The outlook after a ganglioneuroma diagnosis is excellent. These tumors are benign, meaning they do not spread to other parts of the body, and complete removal is usually curative.
Even when the whole tumor cannot be removed, most people do well and have no long-term problems from it. Surgeons sometimes deliberately leave a small amount behind rather than risk damaging a nerve or a blood vessel the tumor has grown around. That decision does not usually affect the outcome.
Recurrence is uncommon. The main reason for follow-up imaging is not the ganglioneuroma itself. It is the small possibility that an immature area was present in a part of the tumor that was not examined.
What follows a ganglioneuroma diagnosis depends on the size of the tumor, where it is, and whether it is causing symptoms.
Surgery to remove the tumor is the usual treatment, and it is generally the only treatment needed. No chemotherapy or radiation is required. If the tumor is small, causes no symptoms, and is confidently diagnosed, some centers will observe it with periodic imaging instead of operating. This applies particularly to adults with an adrenal tumor found by chance.
The margin may be described on the report after surgery, meaning whether tumor was present at the cut edge of the tissue. For a benign tumor, this carries far less weight than it would for a cancer, and a positive margin does not usually lead to further surgery.
Follow-up imaging is typically arranged for a period after surgery, and in children it may also include the urine hormone tests used for the neuroblastic tumors generally. Your team will explain what applies in your case.