Case 2 -

Giant cell tumor with osteogenesis Patrizia Bacchini, MD

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Case History: A 40 year old man with right sacro-iliac pain, two years duration. On April 2005, on x-rays a right iliac wing lytic lesion was detected. Use mouse to enlarge A biopsy was performed. Case 2 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer The HE slide is from the incisional biopsy. Diagnosis: Giant cell tumor with osteogenesis Discussion Giant cell tumor of bone is distinctly unusual, comprising just about 4-5% of all primary bone tumors and approximately a quarter of benign primary bone tumors. Giant cell tumors occur predominantly in young adults : 15-20 to 40-50 years old. It is rare in the skeletally immature subjects ( about 2% of the cases in the Rizzoli Institute files). Just less than 10%were over the age of fifty, and the oldest patient was 74 y.o. in the Mayo clinic files. Giant cell tumor has a slight predilection for females (in contrast to most tumors of bone). Giant cell tumors are unusual in patients with open epiphyseal plates. Most giant cell tumors are found at the ends of long bones. Approximately half of the lesions occur around the knee joint involving the distal femur and the proximal tibia. The distal radius is the third most common locations, and the sacrum is the fourth most common. Giant cell tumor is distinctly unusual in the spine above the level of the sacrum. When a giant cell tumor involves the vertebrae, it tends to involve the body predominantly. On the other hand, aneurismal bone cysts, which may be in the differential diagnosis, tend to involve the posterior elements. Giant cell tumor rarely involve the small bones of the hands and feet. When they do, they do involve the end of the bone with an epiphyseal plate. It is unusual to see giant cell tumors in rare locations such as the skull, the scapula or the ribs. When these sites are involved, the possibility of another condition simulating a giant cell tumor such as hyperparathyroidism should be considered Giant cell tumor rarely occurs in flat bones. The pelvis is the most frequent site (4%). Nearly half of the cases involving the flat bones occur in the ilium and pubis ( the most frequent sites: iliac crest and acetabulum). According with Dave Dahlin teaching, there are no examples of giant cell tumor involving the jawbones in the Mayo Clinic files. Some giant cell reparative granulomas may have areas were the histological features are identical to those of a giant cell tumor. One of the characteristic features of a giant cell tumor is that the lesion always extends to the end of a bone invading into subarticular bone. There are very few cases in the adult centered in the metaphysis. The rare giant cell tumor occurring prior to the closure of the growth plate are in the metaphysis. There are none in the diaphysis. When a giant cell tumor-like lesion involves the metaphysis or the diaphysis, consideration should be given to a variant such as a giant cell rich osteosarcoma or an aneurysmal bone cyst. Symptoms are non-specific as is true with most bone lesions. The classical teaching about the roentgenographic appearance of giant cell tumor is that it is always purely lytic eccentric destructive lesion. It is assumed that giant cell tumors are incapable of producing bone. However, this is not true. When the tumor extends into soft tissues, frequently a shell of new bone is formed around it. The gross appearance of a giant cell tumor may be diagnostic. It has a very characteristic dark brown color. Several secondary changes may occur in a giant cell tumor. It is not unusual to see cystic change focally. This reflects a component of secondary aneurysmal bone cyst. The cystic component may dominate and fleshy, tumor-like tissue may be seen only as mural nodules. It is not unusual to see focal, yellow discoloration suggesting the presence of foam cells. This, again, may be a dominant feature, and there may be only small foci of the typical dark brown tumor. The histopathologic appearance of a giant cell tumor is dominated by the proliferation of giant cells. The giant cells usually are quite large and uniformly distributed. The giant cells may contain sixty to one hundred nuclei scattered evenly throughout the cytoplasm. The proliferating cell in a giant cell tumor is considered to be the mononuclear cell in the background. These cells typically have round to oval nuclei. One of the chracteristic features is that the nuclear morphology of the mononuclear cell is identical to that of the nuclei in the giant cells. Mitotic figures are not uncommon in a giant cell tumor. These are found only in the mononuclear cells and not in the giant cell nuclei. Mitotic figures have no prognostic significance. Atypical mitotic figures, however, are not present in a typical giant cell tumor. The above description is that of a typical giant cell tumor. Just as the gross specimen may have quite a bit of variation, so does the microscopic appearance. Focal areas of cystic change are not unusual. There may be large areas with the appearance of aneurysmal bone cyst. Foam cell change in the mononuclear cells is another common feature. Rarely, a giant cell tumor will have a predominance of foam cells. Such areas also show a predominance of spindle cells rather than the typical oval-shaped mononuclear cells. The spindle cells may be arranged in a storiform pattern. Such an appearance may lead to a diagnosis of a fibrous histiocytoma. Areas of necrosis may be found in a giant cell tumor. Most benign tumors do not show necrosis in the absence of a pathological fracture. Giant cell tumors are an exception. The areas of necrosis have the appearance of infarct with persistence of ghost outlines of cells and no inflammatory reaction to the necrosis. Large areas of necrosis may be found in a giant cell tumor, and occasionally, an entire giant cell tumor may undergo infarction. Giant cell tumors have always been considered to be incapable of producing an osteoid matrix. However, they commonly do so when extending into soft tissues. The so-called benign pulmonary metastases also frequently show bone formation. Hence, it is clear that the cells of a giant cell tumor are capable of producing bony matrix. Such areas may be found within a giant cell tumor also. If this matrix is calcified, it may be visible on plain roentgenograms or computerized tomograms. Bertoni et al found matrix production in 9% of giant cell tumors of bone. The mineralization may or may not be identified radiographically. The clinical behaviour was similar to giant cell tumor without matrix. Vascular permeation may be found at the edges of giant cell tumors. Whether this has any prognostic significance is not clear. Giant cell tumors can be extremely invasive into soft tissues. The tumor tipically invades as nodules of tumor and not as single cells. This quality obviously, has prognostic significance as far as local recurrences are concerned. Some giant cell tumors will metastasise to lung. The incidence is between 3% and 5% of all giant cell tumors .The cytological features are those of a benign giant cell tumor. The metastasis may be a solitary nodule or may be multiple. Most patients are cured by resection of metastases. Some showed spontaneous regressions of metatsasis. Only a small percentage of patients with metastasizing giant cell tumor will get progressive disease and die. Malignant giant cell tumor is also a confusing subject. Many sarcomas of bone can have giant cells, and occasionally, the giant cells may be the dominant feature. Osteosarcomas and malignant fibrous histiocytomas both can have areas simulating a giant cell tumor. Hence, the term malignant giant cell tumor should be reserved only for tumors in which a benign giant cell tumor component can be histologically verified. The benign giant cell component and the sarcomatous component may be synchronous or metachronous. Some sarcomas arise in patients with giant cell tumor treated with radiation therapy (Post radiation sarcoma). Whatever the clinical circumstances, the malignancy is usually a high grade sarcoma and the prognosis is that of a high grade sarcoma. The differential diagnosis of a giant cell tumor involves many lesions of bone. It is very important to make sure that the patient is an adult and that the lesion is in the right location before a diagnosis of a giant cell tumor is entertained. Anurysmal bone cysts are frequently mistaken for giant cell tumors. However, aneurysmal bone cysts occur in patients who are in the first two decades of life and hardly ever involve the end of the bone. It is typically a lesion of the metaphysis of a long bone. Aneurysmal bone cysts are composed of spindle cells whereas giant cell tumors are composed of round to oval cells. Reactive new bone formation is frequently found in an aneurysmal bone cyst whereas it is infrequent in a giant cell tumor. Metaphyseal fibrous defects are also frequently mistaken for a giant cell tumor. However, metaphyseal fibrous defects occur in the metaphysis of young children. The lesion is composed of spindle cells in a storiform pattern. These, however, may have areas where the histological appearance simulates that of a giant cell tumor. Hence, the age of the patient and the location in the bone are of paramount importance. The most difficult differential diagnostic problem may be that of a giant cell rich osteosarcoma. The cytological features can be extremely subtle in giant cell rich osteosarcoma. A lesion which has the appearance of a neoplasm (that is, it does not have the reactive appearance of an aneurismal bone cyst) situated in an unusual location such as the metaphysis or diaphysis should be suspected to be be osteosarcoma.( As indicated previously, rarely a giant cell tumor will occur in the metaphysis or diaphysis). In most instances of giant cell rich osteosarcoma, the mononuclear cells will show pronounced cytological atypia supporting a diagnosis of malignancy. When the cytological features are subtle the differential diagnosis can be very difficult and only follow-up may give the answer. References Unni KK, Inwards CY, Bridge JA, Kindblom LG, Wold LE: Tumors of the Bones and Joints – AFIP Atlas of Tumor Pahology- Series 4, Armed Forces Institute of Pathology, Washington D.C.,2005, pag.281- 298 Bertoni F, Inwards CY, Beabout JW . Giant cell tumor of bone with matrix production. Modern Pathology ,13:8A,(abstract n^ 24),2000 Campanacci M. :Bone and Soft Tissue Tumors. 2nd Edition :Springer-Verlag-Piccin Nuova Libraria,1999, pag.99-142 Unni KK : Dahlin's Bone Tumors.General Aspects and Data on 11087 cases.Fifth Edition,Lippincott-Raven,1996, pag.263-289 Huvos AG : Bone Tumors. Diagnosis, treatment, and prognosis.Second Edition. W.B.Saunders Company,1991, pag.429 – 467