What Are Giant Cells?
Giant cells are mononucleated or multinucleated cells that arise from monocyte precursors formed by different mechanisms. Giant cell nuclei appear to be irregularly shaped with clear chromatin and possess eosinophilic nucleolus. They are mostly multinucleated and are associated with many physiologic and pathologic conditions. It regulates inflammation, infection, and neoplasia through their differentiation into macrophages (a cell that eliminates foreign substances in the body by engulfing them). Multinucleated giant cells act as the mediators of tissue remodeling and repair.
What Are the Types of Giant Cells?
The different types of the giant cell include:
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Physiological Giant Cell: They are normal body cells that are responsible for certain physiological functions in the body. They are multinucleated. The different types include.
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Osteoclast (bone-resorbing cells).
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Megakaryocyte (responsible for platelet production).
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Syncytiotrophoblast (outer layer of the trophoblast that determines which substances cross the placenta).
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Pathologic Giant Cell: They develop due to various disorders and are not normally present in the body. They are either mono or multinucleated. They help in the diagnosis of different diseases associated with different types of pathological giant cells. It includes:
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Langhans giant cell.
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Foreign body giant cell.
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Touton giant cell.
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Tumor giant cell.
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Miscellaneous types: Reed-Sternberg cells, Warthin-Finkeldey giant cells.
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Multinucleated Giant Cells in COVID-19 Patients: The covid-19 outbreak and its impact led scientists to study more details about it. Various studies have been carried out to look into much deeper about its pathologic features. Cytopathological examination of bronchial secretion from the covid-19 patient revealed the presence of multinucleated giant cells. These multinucleated giant cells are referred to as “multinucleated syncytial cells.” It is also detected in the autopsy of covid-19 pneumonia patients.
What Is a Giant Cell Tumor (GCT)?
A giant cell tumor refers to a benign (non-cancerous), locally aggressive tumor that occurs rarely. It is characterized by the presence of multinucleated giant cells in it. Giant cell tumor of bone is often referred to as osteoclastoma as it resembles osteoclasts. It usually affects adults between the ages of 20 to 40 when the skeletal bone growth is complete. Female predilection is more.
The giant cell tumor of bone was first described in 1818 by Cooper. The malignant potential of giant cell tumors was suggested in 1846 by Virchow. Even though it is a benign condition, its highly aggressive nature results in the destruction of the bone involved. Giant cell tumors of bone rarely metastasize to the lungs. It mostly affects long bones in the body that include:
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Knee.
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Proximal tibia (shin bone).
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The distal part of the femur (hip bone).
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The distal part of the radius (forearm bones).
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Sacrum (bone at the base of the spine).
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Vertebral body (the thoracic spine is most commonly involved).
What Are the Causes of Giant Cell Tumors?
The exact cause is unknown. But in certain cases, giant cell tumors have been linked to Paget's disease of bone (a disease that disrupts the replacement of old bone tissue with new bone tissue). No environmental, genetic, or dietary factors contribute to its development.
What Are the Signs and Symptoms of a Giant Cell Tumor?
The symptoms vary from each other depending on the severity of the disease. It includes;
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Bone pain is the most common symptom. It tends to aggravate with increased physical activity and subsides on resting. In severe cases, destruction of surrounding bone with sudden onset of pain is seen; however, in some cases, patients experience no pain, but a visible swollen mass is seen.
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Swelling.
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Restricted movements of the affected bone.
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Fluid builds up in between joints.
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Weakening of bone results in an increased tendency to fracture.
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A localized pain in the lower back and sacrum is seen in the sacrum giant cell tumor.
How Is It Diagnosed?
In addition to clinical examination, various diagnostic methods are done to rule out giant cell tumors. It includes:
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Biopsy: A biopsy involves the removal of a small amount of tissue from the affected site and sent to pathologists for microscopic examination. It particularly pinpoints the histologic features of the lesion, which helps in ruling out giant cell tumors from other malignant tumors.
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X-rays: These give a detailed picture of the bone involved and the extent of its involvement. Giant cell tumors in X-rays appear as translucent lesions within the bone, usually seen near the joint line. A chest X-ray is advised by doctors to detect if any metastasis to the lungs is present.
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MRI (Magnetic Resonance Imaging): MRI gives a more detailed assessment of the bone that is affected.
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CT (Computed Tomography) Scan: CT scan offers a more detailed view of a tumor than X-rays. It gives different cross-sectional images of the lesion. CT scan in the lungs rules out any metastasis in the lungs associated with the tumor.
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Bone Scan: A bone scan uses a radioactive dye that is either injected into the patient's body or given as a pill. The radioactive dye once entered into the body, is absorbed by the cancerous or abnormal cells. Once absorbed, it discriminates against the affected area by picturizing a “hot spot” in the scan.
Radiological Features of Giant Cell Tumor:
The characteristic radiographic features of giant cell tumor include;
- Well-defined osteolytic or radiolucent lesion with a non-sclerotic margin, although less than 5 percent of the lesions may show some sclerosis.
- Periosteal reaction may be seen.
- Pathological fracture might be present.
- CT scan depicts giant cell tumor as solitary radiolucent bone lesions.
- Haemorrhagic areas, soft tissue extension, and surrounding bone marrow edema can be seen in MRI images.
What Are the Classifications of Giant Cell Tumors?
Giant cell tumor is classified into three distinct grades by Enneking and later by Campanacci based on radiographic appearance.
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Grade 1 Tumor: It describes the latent stage of the tumor. In this, the tumor shows a well-marginated border with a thin cortex.
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Grade 2 Tumor: The tumor shows well-defined margins with no radiopaque rim, and the cortex becomes thinner.
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Grade 3 Tumor: Describes that the tumor is in an aggressive condition. The tumor shows indistinct borders with cortical expansion.
What Are the Treatment Options for Giant Cell Tumors?
The main aim of treatment is to remove the tumor and avoid bone damage and its recurrence. Doctors may suggest treatments based on the severity of the condition. The treatment options include:
Non-surgical Treatment:
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Medications: Medications like Bisphosphonates inhibit osteoclastic activity and thus decrease bone resorption. They are broadly used in cases where surgical treatment does not apply to patients.
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Role of Denosumab in Giant Cell Tumor: Denosumab is a monoclonal antibody that specifically binds to RANKL ( receptor activator of nuclear factor-kB ligand) and acts as an antagonist to it. RANKL plays a key role in the pathogenesis of giant cell tumors. Denosumab by acting against it and inhibits osteoclast-mediated bone resorption. It reduces tumor size to a large extent; however, it did not show any effect in reducing tumor recurrence.
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Embolization: Embolization refers to a process by which specific arteries that supply blood to the tumor are blocked, resulting in the death of tumor cells. In cases of sacral giant cell tumor, transarterial embolization helps in treating it to a large extent.
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Radiation Therapy: Radiation therapies are sometimes used in giant cell tumors as an alternative approach to surgical treatment. It shrinks the tumor cells and reduces their growth. One of the major drawbacks of radiation therapy is that it is sometimes associated with the malignant transformation of giant cell tumors.
Surgical Treatment:
Surgical treatment is the most effective treatment option for giant cell tumors. Surgical removal and reconstruction are highly valuable in treating tumors with excessive bone or tissue damage and recurrence. Reconstruction of bone after surgery is done using bone grafts or artificial joints (prosthesis), or a combination of both. Amputation is done in severe cases.
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Curettage: Curettage is the most common surgical procedure in treating giant cell tumors. Curettage is followed by adjuvant therapy (treating with medicines after surgery) to avoid recurrence of the tumor.
Does Giant Cell Tumor Show Any Recurrence After Treatment?
Yes, it does recur. Post-operative recurrence is observed within 24 months after surgery. The rate of recurrence depends on the severity of the tumor and the type of surgical procedure carried out. Incomplete removal of the tumor results in a high recurrence rate.
Conclusion:
A giant cell tumor is a benign, locally aggressive tumor that mostly affects adults. However, it is a benign condition, and the aggressive nature of the tumor results in severe bone deformity. It can be well treated by various treatment options. However, a regular follow-up with your doctor after treatment avoids its recurrence.