Referat

GIANT CELL TUMOR

Arranged by: Elvina Indra Diva (G0007062)

Guided by: Dr. Tangkas Sibarani., Sp.OT, FICS.

THE CLINICAL DEPARTMENT OF SURGERY MEDICAL FACULTY OF SEBELAS MARET UNIVERSITY THE ORTHOPAEDIC HOSPITAL OF PROF. DR. SOEHARSO SURAKARTA 2011

LEGALITY SHEET Orthopaedic surgery paper with the title Giant Cell Tumor is arranged to fulfill the requirement of Clinical Department of Orthopaedic Surgery Sebelas Maret University/ Dr. Moewardi Hospital during stage RSOP by: Elvina Indra Diva (G0007062) Has been approved by the case presentation tutorial of the orthopaedic hospital of Prof. Dr. Soeharso Hospital, Surakarta on August, 2011.

Consultant,

Dr. Tangkas Sibarani., Sp.OT, FICS.

CHAPTER I PREFACE

Bone cancer occurs when bone cells grow uncontrollably. Unlike normal cells, cancer cells do not stop reproducing after they have doubled 50-60 times. These abnormal cells form clumps of tissue, called tumors, inside bones. The first symptom of bone cancer is typically pain in the affected bone(s). Sometimes, a bump either on the bone or in the tissues surrounding the bone may be felt. Primary bone cancer, or cancer that starts in the bone cells, is rare. Fewer than 2,500 Americans are diagnosed with this type of cancer each year. Children are more likely to develop primary bone cancer than adults. Most cases of bone cancer occur when cancer from another part of the body, such as breast, prostate, or lung, has spread to bone cells. This is sometimes called metastatic bone cancer or secondary bone cancer. There are several types of bone cancer, such as osteosarcoma, chondrosarcoma, Ewing's sarcoma and Giant cell Tumor. These cancers can be primary or secondary cancer. Surgery is often the main treatment for bone cancer. In addition to having bone tumors surgically removed, patients may also undergo chemotherapy, and/or radiation therapy. In some cases, patients may need to undergo a surgical amputation, but this is performed less often today. Specific treatment options depend on the type of bone cancer, as well as its location, size, and stage. In general, the prognosis for patients with bone cancer is based on many factors, including the type of cancer, at what stage the cancer was discovered, and where the tumor is located. For instance, if the tumor is small and limited to a localized area, the patient's prognosis is generally better than if the cancer has spread to other parts of the body.

CHAPTER II Discussion A. Background GCTs of bone have been described as the most challenging benign bone tumors. Although benign, GCTs show a tendency for significant bone destruction, local recurrence, and occasionally metastasis. The natural history of GCTs varies widely and can range from local bony destruction to local metastasis, metastasis to the lung, metastasis to lymph nodes (rare), or malignant transformation (rare). Gross specimen of a giant cell tumor that fills the entire distal radius. Despite cortical disruption, the periosteum remains intact (arrow). Once again, note the bloodfilled cystic areas and areas of orange discoloration. Approximately 3% of GCTs metastasize to the lung. The metastases appear as clusters of GCTs located within the lung. GCTs metastasis generally appear an average of 3-5 years after the initial diagnosis of the primary lesion. However, GCTs metastasis may not be detected for 10 years or longer. The natural history of these lung metastases is unpredictable. Pulmonary metastases that spontaneously regress, remain stable, continuously grow slowly, or rapidly progress have been reported. B. Definision A giant cell tumor is one that is made up of a large number of benign (noncancerous) cells that form an aggressive tumor - usually near the end of the bone near a joint. The location of a giant cell tumor is often in the knee, but can also involve the bones of the arms and the legs, or the flat bones such as the sternum (breastbone) or pelvis. Giant cell tumors most often occur when skeletal bone growth is complete. Most occur in the long bones of the legs and arms. They are most prevalent after age 20 and are rare after age 55. It is rare, but these tumors can occur in children. At any age, they are more commonly seen in females than males.

While the exact cause of giant cell tumors remains unknown, in some cases, they have been linked to Paget's disease. Paget's disease of the bone is a chronic bone disorder in which bones become enlarged and deformed. C. Epidemiologi In the United States and Europe, GCTs represent approximately 5% of all primary bone tumors and 21% of all benign bone tumors. In China, GCTs account for 20% of all primary bone tumors. A female predominance exists, with a female-to-male ratio of 1.3-1.5:1. GCTs occur most commonly in the third decade of life; less than 5% of GCTs occur in patients who are skeletally immature. In the Mayo Clinic series, 84% of the GCTs occurred in patients older than 19 years. D. Presentation Most GCTs are located within the epiphyses of long bones but often extend into the metaphysis. In several published series, only 1.2% of GCTs involved the metaphysis or diaphysis without epiphyseal involvement. Approximately 50% of GCTs are located around the knee. The most common locations are the distal femur, the proximal tibia, and the proximal humerus and distal radius (see Image 1). Most commonly, GCTs are solitary lesions; less than 1% are multicentric. Multicentric involvement tends to be more clinically aggressive, and, unlike the solitary lesions, multicentric GCT has a propensity for the small bones of the hands and feet. Patients with multicentric lesions tend to be younger than those with lesions elsewhere.

Approximately 50% of giant cell tumors are located around the knee. The most common locations are the distal femur, the proximal tibia, and the proximal humerus and distal radius. Pain is the most common presenting symptom. Swelling and deformity are associated with larger lesions. Soft-tissue extension is common. The incidence of pathologic fracture at presentation is 11-37%. The presence of tumor is the indication for surgery. See Treatment, below, for detailed information. E. The Symptoms of a Giant Cell Tumor The following are the most common symptoms of a giant cell tumor. However, each individual may experience symptoms differently. Symptoms may include: 1. Pain at the adjacent joint 2. A visible mass 3. Swelling 4. Bone fracture 5. Limited movement in the adjacent joint 6. Fluid accumulation in the joint adjacent to the affected bone The symptoms of a giant cell tumor may resemble other medical conditions or problems. Always consult your physician for a diagnosis. F. Diagnosis In addition to a complete medical history and physical examination, diagnostic procedures for giant cell tumors may include the following: 1. Radiographically, these lesions are lucent and eccentrically located within the bone. GCTs can appear aggressive and are often characterized by extensive local bony destruction, cortical breakthrough, and soft-tissue expansion. When located in the epiphysis, GCTs generally extend to the articular surface. Although radiographs of GCTs demonstrate a narrow zone of transition, GCTs generally lack the dense peripheral sclerosis seen in nonossifying fibromas. Mineralization of the primary lesion is rare.

However, when GCTs occur in the soft tissue (metastasis or local recurrence), peripheral calcifications are common.

Giant cell tumor. Anteroposterior radiograph of the distal femur reveals an expansile lytic metaphyseal-epiphyseal lesion.

Giant cell tumor. Lateral radiograph of the same distal femur as in Image 2 in Multimedia reveals an expansile lytic metaphyseal-epiphyseal lesion.

Giant cell tumor. Anteroposterior radiograph of the distal radius reveals an aggressive lesion characterized by extensive local bony destruction, cortical breakthrough and significant soft-tissue expansion.

Giant cell tumor. Lateral radiograph of the same distal radius as in Image 4 in Multimedia reveals an aggressive lesion characterized by extensive local bony destruction, cortical breakthrough and significant soft-tissue expansion.

Campanacci et al proposed a grading system for GCTs that is based on the radiographic appearance of the tumors.The Campanacci grading system is similar to that proposed by Enneking for benign bone tumors.
1.

A grade 1 lesion (latent) has a well-defined margin and an intact cortex.

2.

A grade 2 lesion (active) has a relatively well-defined margin but no radiopaque rim, and the cortex is thinned and moderately expanded.

3.

A grade 3 lesion (aggressive) has indistinct borders and cortical destruction).

4.

No correlation exists between the grading systems and the incidence of local recurrence or metastases.

MRI often is performed to delineate the extent of the neoplasm.

5.

In the typical GCT, the signal intensity is homogeneous, and the lesion is well circumscribed.

6.

The lesions have low signal intensity on T1-weighted images and intermediate signal intensity on T2-weighted images (see Image 6).

CT scans of the lesion reveal an absence of bone and intralesional mineralization. 2. Radionuclide bone scans - a nuclear imaging method to evaluate any degenerative and/or arthritic changes in the joints; to detect bone diseases and tumors; to determine the cause of bone pain or inflammation. This test is to rule out any infection or fractures. 3. Biopsy - a procedure in which tissue samples are removed (with a needle or during surgery) from the body for examination under a microscope; to determine if cancer or other abnormal cells are present. G. Histopatology On gross inspection, these lesions are characteristically chocolate brown, soft, spongy, and friable. Yellowish-to-orange discoloration due to hemosiderin may be present. Cystic cavities within the tumor are common. Often, these cavities are blood filled. Examination of resected specimen reveals a variable degree of cortical expansion and disruption. Despite the cortical disruption, the periosteum remains intact.

Giant cell tumor. Anteroposterior radiograph of the distal tibia demonstrates extension of the lesion to the articular surface.

Giant cell tumor. Lateral radiograph of the same distal tibia as in Image 7 in Multimedia demonstrates extension of the lesion to the articular surface. Histologically, the lesions tend to be cellular. Although the multinucleated giant cell is the characteristic cell type, these lesions have a background network of stromal mononuclear cells. The mononuclear cells are plump and round, oval, or spindle shaped. They may have prominent mitotic activity, but cellular atypia is rare. The degree of mitotic activity has no prognostic significance. Multinucleated giant cells, as the name suggests, have numerous centrally located nuclei as opposed to the peripherally located nuclei of Langerhans -type giant cells seen in atypical infections. The nuclei tend to be compact and oval and contain prominent nucleoli. These are similar in appearance to those of the surrounding stromal cells, and the giant cell often appears to be a syncytium of these stromal cells.

Giant cell tumor. Sagittal MRI of the same distal tibia as in Images 7-8 in Multimedia demonstrates extension of the lesion to the articular surface.

Anteroposterior radiograph of a wrist arthrodesis performed for a giant cell tumor. Soft tissue recurrence is present. Note the peripheral mineralization about the soft-tissue recurrence (arrow). Giant cells generally are distributed throughout the lesion. The concentration of multinucleated giant cells varies considerably from tumor to tumor. Some tumors have many multinucleated giant cells, whereas others have a few giant cells nestled in swirls of spindle-shaped stromal cells. The concentration of multinucleated giant cells is not related to the incidence of local recurrence or metastases. In some lesions, giant cells invade the small perforating vessels. This intravascular invasion can be found in approximately 5% of cases. This invasion, although appearing aggressive, is not correlated with the prognosis.

Sagittal T1-weighted MRI shows a giant cell tumor with low signal intensity.

Giant cell tumor. CT scan of the distal femur reveals an absence of matrix within the lesion. At histologic analysis, the differential diagnosis includes brown tumors of hyperparathyroidism; aneurysmal bone cysts; and, rarely, chondroblastoma, osteoblastoma, or osteosarcoma. In an attempt to relate the histologic features with the clinical course, several histologic grading systems have been developed. The earliest was devised by Jaffe et al in 1940. In grade I at the benign end of the spectrum, giant cells are numerous, mononuclear cells are rare, and mitotic activity is absent. In grade II, mononuclear stromal cells are numerous, and moderate atypia and mitotic activity is seen. In grade III, giant cells are few and small, atypia and pleomorphism are common, and mitotic activity is frequent. However, this grading system has no prognostic significance. In an attempt to improve the prognostic relevance of the histologic grading system, several authors

have modified the staging system of Jaffe et al. Generally, these staging systems include sarcomatous lesions as grade III lesions. Unfortunately, these modified systems, like that of Jaffe et al, are of little value in predicting patient outcomes.

H. Treatment Specific treatment for giant cell tumors will be determined by your physician based on: 1. your age, overall health, and medical history 2. extent of the disease 3. your tolerance for specific medications, procedures, or therapies 4. expectations for the course of the disease 5. your opinion or preference The goal for treatment of a giant cell tumor is to remove the tumor and prevent damage to the affected bone. Treatment may include: 1. Medical Therapy Pulmonary metastases have been cited as the cause of death in 16-25% of reported cases. The need for early detection and treatment of these metastases has been emphasized. Pulmonary metastases have been treated with wide resection, chemotherapy, radiation therapy, and interferon alpha. When possible, wide surgical resection is the treatment of choice. When the pulmonary metastases cannot be completely surgically excised, adjuvant treatment, such as chemotherapy or radiation therapy, has been advocated. In addition, in situations when the metastases are unresectable, both chemotherapy and radiation have been used as solitary agents. At University of Texas MD Anderson Cancer Center, interferon has been used with promising results. Spontaneous malignant transformation of GCT is not uncommon. Malignant transformation has been defined as a sarcoma associated with a benign typical GCT at presentation or as a sarcoma arising at the site of a preexisting GCT. Malignant

transformations have resulted in osteosarcoma, fibrosarcoma, or malignant histiocytoma. Periods of 4-40 years for malignant transformation have been reported. 2. Surgical Therapy In the past, GCTs were treated with amputation or with wide resection and reconstruction. However, with the knowledge that GCT is a locally aggressive yet benign disease, the surgical treatment of GCTs is intralesional for most locations. Various treatment options have been advocated, including the following:
a. Curettage b. Curettage and c. Curettage and

bone grafting insertion of polymethylmethacrylate (PMMA)

d. Primary resection e. Radiation f.

therapy

Embolization of the feeding vessels

3. Resection Although intralesional procedures remain the treatment of choice for most GCTs, wide en bloc resection offers the lowest recurrence rate and can be performed in expandable bone. In the proximal fibula, wide resection without reconstruction is often performed. Similarly, GCTs of the distal radius often are resected and reconstructed with autograft or allograft.

Intraoperative photograph of giant cell tumor in the distal femur. However, in the long bones, resection necessitates prosthetic or allograft reconstruction and is generally reserved for grade III lesions.

4.Intralesional procedures Intralesional curettage and bone grafting is a limb-sparing option that is associated with good functional and oncologic outcomes. However, simple curettage with or without bone graft has recurrence rates of 27-55%. The high risk of recurrence led several surgeons to replace bone graft packing of the lesion with PMMA packing.

Gross specimen of the same giant cell tumor in the distal femur as in Image 14 in Multimedia displays the typical chocolate brown and spongy appearance. The heat given off by the hardening PMMA is thought to lead to thermal necrosis of the remaining tumor cells in the curetted cavity. The PMMA technique, compared with bone grafting, offers the advantages of lack of donor-site morbidity, an unlimited supply, immediate structural stability, low cost, and ease of use. In addition, the barium contained in the methylmethacrylate results in a radiopaque substance that sharply contrasts with the surrounding bone. Local recurrences are more readily apparent than in cases in which bone graft is used.

Bisected gross specimen of the giant cell tumor in Image 15 reveals blood-filled cystic areas and inner yellow and orange discoloration.

The disadvantages of using cement include difficulty in removing it when revision is needed and the possibility that subchondral cement may predispose the joint to early degenerative osteoarthritis. The latter is a theory that remains to be proven. In fact, using a canine model, Frassica et al showed that subchondral PMMA did not cause joint degeneration. However, in a later study, Frassica and colleagues showed that subchondral bone grafts are superior to cement for restoration of the normal subchondral anatomy. However, investigators have shown no differences in recurrence when comparing bone graft with PMMA. Several authors have added the technique of high-speed burring of the cavity after simple intralesional curettage. A large cortical window is necessary to expose the entire tumor and tumor cavity, allowing thorough curettage and burring of the cavity.

Gross specimen of a giant cell tumor that fills the entire distal radius. Despite cortical disruption, the periosteum remains intact (arrow). Once again, note the bloodfilled cystic areas and areas of orange discoloration. This has been found to reduce the recurrence rates to 12-25%. The high-speed burr not only adds a thermal component to eradication of the tumor but also allows more thorough removal of the tumor. High-speed burring of the cavity then may be followed by a chemical or physical adjuvant and packing of the lesion with PMMA or a bone graft.

5. Adjuvant therapies Adjuvant therapies, such as phenol, liquid nitrogen, or H2 O2 and argon beam coagulation, all have advantages and disadvantages. However, they all offer a method for eradication of microscopic disease. Many authors suggest that phenol is an effective means of decreasing the recurrence rate of giant cell tumors. After curettage is performed and all perforations in the bone are sealed, phenol is poured into the cavity. This results in a cellular death at a depth of approximately 1-2 mm. The use of 5% phenol has been advocated. Recurrence rates with curettage and phenol and packing with PMMA or bone grafts are 5-17%. Phenol is systemically toxic. Preventing exposure to the surrounding tissues while at the same time allowing exposure to the entire curetted cavity is difficult. It can cause a serious chemical burn, and it is also readily absorbed through the skin and mucosa. The material has a hazardous effect on the nervous system, heart, kidneys, and liver. It damages the DNA, coagulates protein, and causes cellular necrosis. Several authors have raised the concern of the rapid absorption of the phenol through cancellous bones. Many authors advocate cryosurgery as an adjuvant. Liquid nitrogen is a chemical reagent used in cryosurgery. In the direct-pour technique, after the curettage is performed and after all perforations in the bone are sealed, liquid nitrogen is poured through a stainless steel funnel into the cavity.

Photomicrograph of a giant cell tumor reveals the typical appearance. Multinucleated giant cells are dispersed throughout on a background of mononuclear cells. The liquid nitrogen is left in the cavity until it all evaporates. The surrounding tissues are irrigated with warm sodium chloride solution in an attempt to prevent or minimize thermal injury to the surrounding tissues. The process is repeated 2-3 times, resulting in cellular death at a depth of approximately 1-2 cm. The cavitary defect is then reconstructed with PMMA or bone grafts. Recurrence rates with cryosurgery have been reported to be 2-12%. The disadvantages of cryosurgery include the need for wide exposure, the need to protect the soft tissues, skin necrosis, osteonecrosis, and fracture. Fracture is the most commonly reported and gravest complication. Malawer et al noted that internal fixation with Steinmann pins and reconstruction of the cavitary defect with PMMA significantly reduced the incidence of fracture and suggested that all patients who undergo cryosurgery receive internal stabilization as well.

Photomicrograph of a giant cell tumor reveals the typical appearance. Multinucleated giant cells are dispersed throughout on a background of mononuclear cells. Some authors, as an alternative to cryosurgery and phenol therapy, have advocated argon-beam coagulation. It lacks the application hazards identified with both phenol and liquid nitrogen. Thermal coagulation applied through a concentrated argon gas is used to paint the tumor cavity.

Photomicrograph of a giant cell tumor reveals prominent mitotic activity and rare cellular atypia. The penetration is approximately 2-3 mm. Recurrence rates for this procedure when paired with PMMA have been reported at 7%. No acute complications were noted. Long-term follow-up is warranted to assess the effect of argon beam coagulation on joint and/or subchondral physiology and on the incidence of pathologic fracture.

CHAPTER III Conslusion

Giant cell tumor accounts for 5 to 9 percent of all primary bony tumors. It possibly is the most common bone tumor in the young adults aged 25 to 40. Giant cell tumor is are found more commonly in women than men, and occur most often during the third decade. Most patients present with slowly progressive pain, with or without a mass. Symptoms arise when the lesion begins to destroy the cortex and irritate the periosteum or when the weakening of the bone caused by the tumor causes pain due to imminent pathologic fracture. Some giant cell tumors present with a pathologic fracture. Radiologic findings demonstrate the lesion is most often eccentrically placed to the long axis of the bone. The center is most radiolucent with increasing density towards the periphery. Treatment of giant cell tumors is by medical therapy, surgery, resection, Intralesional procedures, adjuvant therapies. .

REFERENCES:

Balke M, Schremper L, Gebert C, et al. (March 2008). "Giant cell tumor of bone: treatment and outcome of 214 cases". J. Cancer Res. Clin. Oncol. Dickson, B. C., Li, S.-Q., Wunder, J. S., Ferguson, P. C., Eslami, B., Werier, J. A., et al. (2008). Giant-cell tumor of bone express p63. Modern Pathology Thomas, D. M., & Skubitz, T. (2009). Giant-cell tumour of bone. Current Opinion in Oncology Valerae O Lewis, MD; Chief Editor: Harris Gellman, MD.2011. Giant Cell Tumor.www.emedicine.medscape.com Lesley-Ann Goh, MBBS, FRCR; Chief Editor: Felix S Chew, MD, MBA, EdM.2011.Giant Cell Tumor Imaging. www.emedicine.medscape.com