Giant cell tumor of bone is a tumor that develops inside a bone, usually near a joint. It is named for the very large cells with many nuclei that are found throughout the tumor.
Most giant cell tumors of bone are not cancer, and they rarely spread to other parts of the body. They can, however, destroy the surrounding bone and come back after surgery. For this reason, pathologists place them in a middle category between noncancerous and cancerous tumors, described as locally aggressive.
Giant cell tumor of bone usually affects adults between 20 and 50 years old, after the bones have stopped growing. It is slightly more common in women.
This article explains how giant cell tumor of bone is diagnosed and what your pathology report findings mean.
Giant cell tumor of bone usually develops at the end of a long bone, close to the joint. About half develop around the knee, at the lower end of the thigh bone or the upper end of the shin bone. Other common locations include the wrist end of the forearm bone, the upper arm bone near the shoulder, and the sacrum at the bottom of the spine.
This tumor differs from giant cell tumor of the tendon sheath, which shares part of the name but develops in the soft tissue around joints and tendons.
The most common symptom is pain near a joint, often with swelling. The pain usually builds over weeks or months, and it may make it harder to move the nearby joint.
Because the tumor thins the surrounding bone, the bone can break with little or no force. This is called a pathologic fracture and causes a sudden increase in pain.
More than 9 out of 10 giant cell tumors of bone have a change in a gene called H3F3A. This gene makes a protein called histone H3.3, which helps control how the cell uses its genetic instructions. The change is usually written as G34W.
The change is found only in the small, single-nucleus cells of the tumor, which are the true tumor cells. These cells release signals that attract the large giant cells, which then break down the surrounding bone. This is why the tumor contains so many giant cells and why it destroys bone.
The H3F3A change develops in the tumor during a person’s lifetime. It is not inherited and cannot be passed on to children. Doctors do not know why it happens.
X-rays, CT, and MRI usually show a tumor that has worn away the end of a bone, often reaching close to the joint surface. The diagnosis is confirmed with a biopsy, in which a small sample of the tumor is removed and examined by a pathologist.
Under the microscope, the tumor is made of two kinds of cells:
Immunohistochemistry uses antibodies to show which proteins cells make. For giant cell tumor of bone, a stain that detects the H3.3 G34W protein is the most useful test. It is positive in the nuclei of the mononuclear cells in about 9 out of 10 tumors.
This stain matters because many other bone conditions also contain giant cells. These include aneurysmal bone cyst, chondroblastoma, and the bone changes caused by an overactive parathyroid gland. Some cancers, including a giant-cell-rich type of osteosarcoma, can look similar as well. A positive H3.3 G34W stain strongly supports giant cell tumor of bone.
In almost all cases, no. Giant cell tumor of bone does not spread in the way a cancer does, and most people are cured with surgery. It is described as locally aggressive because it can destroy the bone around it and tends to come back if any tumor is left behind.
Rarely, a giant cell tumor spreads to the lungs. Unlike spread from a cancer, these lung growths usually grow very slowly, and many people with them live for many years.
Very rarely, it develops a cancerous form. This is called malignant giant cell tumor of bone. It most often appears in a tumor that has come back after earlier treatment, particularly radiation therapy. Your report will clearly state whether any cancerous features were found.
Your report may describe whether the tumor has broken through the outer shell of the bone into the surrounding soft tissue, or reached the joint. A tumor that has extended beyond the bone is harder to remove completely and is more likely to come back.
A margin is the edge of tissue cut by the surgeon. Margins are reported only when the surgeon removes the tumor in one piece, called a resection.
Many giant cell tumors are instead scraped out of the bone in a procedure called curettage. In that case, the tissue arrives in many pieces, and margins cannot be assessed. The surgeon then judges whether tumor remains based on the tissue and on imaging after surgery.
Some people receive a medication called denosumab before surgery. Denosumab blocks the signal tumor cells use to call in giant cells, which stops bone destruction and often shrinks the tumor.
Denosumab changes how the tumor looks under the microscope. The giant cells largely disappear, and new bone forms within the tumor. If you received denosumab, your report may describe these changes. The H3.3 G34W stain still identifies the tumor cells, which remain present even when the giant cells are gone.
The outlook for giant cell tumor of bone is very good. Most people are cured, and the tumor rarely threatens life.
A tumor that comes back can usually be treated again with further surgery. These figures describe groups of people and cannot predict what will happen to one person.
Giant cell tumor of bone is best treated by a team at a center experienced in bone tumors. The choice of treatment depends on the size and location of the tumor and how much of the joint can be saved.