A Rare Case of Giant-Cell Tumor of Hand in a Young Male
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Giant-cell tumor (GCT) of the bone affecting the hand is a rare lesion that is usually diagnosed at an advanced stage and has a high rate of recurrence. In the current literature, GCT is described as a predominantly osteoclastogenic stromal cell tumor of mesenchymal origin. It is composed of three cell types: the neoplastic GCT stromal cells; mononuclear monocyte cells; and multinucleated giant cells. Clinical imaging is basic for the diagnosis of a GCT. This tumor within the hand tends to be less eccentric and most often central. GCT of metacarpals is noted to be a rare location, with the incidence being as low as 2%. GCT on hand as compared to other sites is locally more aggressive, grows faster, and has a higher recurrence rate. A 22-year-old male patient presented with swelling over the left hand for 7 months, spontaneous in onset, gradually progressive in size, and painfully restricting the joint movement, with no history of fall or trauma. On examination, diffuse swelling of size 5 × 5 × 3 cm was tender on palpation, restricting the movement at the 4th metacarpophalangeal joint. A plain radiograph followed by an MRI scan revealed a Campanacci's Grade III GCT of the 4th metacarpal. An open biopsy showed an expanded and lytic mass with areas of hemorrhage and necrosis. There were few mitotic figures and the tumor was diagnosed to be a GCT. On surgical resection, friable tumor tissue was noted over the region of the entire 4th metacarpal except for the base. The patient was managed by surgical intralesional excision of the mass, followed by Kirschner-wire fixation and reconstruction with synthetic bone graft. The excised tissue was sent for histopathological examination. The patient was followed up at regular intervals, with initial splinting, followed by wire removal at 6-week post-op, and with adequate physiotherapy, as tolerated by the patient. On a 3-month follow-up, the range of motion had returned to a functional level, with good uptake of graft, and no other complications. GCT of the hand is a rare presentation of the disease and requires meticulous workup, including a thorough clinical exam, hematological, radiological, and pathological workup. The various treatment modalities described in the literature for GCTs are curettage alone, curettage and bone graft, en-bloc resection, amputation, and resection with reconstruction, but curettage alone or curettage with bone graft is not effective even for GCTs of long bones and hand, too. Such a procedure creates a skeletal void and hence furthers the need for a challenging reconstructive procedure requiring reconstruction using autograft, allograft, or silastic (synthetic) implant.Keywords:
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Giant Cell Tumors
Abstract Context.—Previous studies have demonstrated p63 overexpression in giant cell tumors of bone and advocate its use as a potential diagnostic marker. Although routine histology is often all that is required to diagnose giant cell tumor of bone, immunohistochemistry could prove useful to distinguish it from other benign and malignant giant cell–containing lesions of bone and soft tissue on needle biopsies and unusual clinical settings. Objective.—To assess p63 expression in giant cell–containing lesions of bone and soft tissue. Design.—p63 immunohistochemistry was performed in 23 giant cell tumors of bone, 8 primary aneurysmal bone cysts, 12 chondroblastomas, 4 giant cell reparative granulomas, 4 osteosarcomas, 15 tenosynovial giant cell tumors, 6 nonossifying fibromas, and 4 pigmented villonodular synovitides. Results.—p63 overexpression was identified in 20 of 23 giant cell tumors of bone (86.9%), 5 of 8 primary aneurysmal bone cysts (62.5%), 10 of 12 chondroblastomas (83.3%), 4 of 4 giant cell reparative granulomas (100%), 2 of 4 osteosarcomas (50%), 1 of 15 tenosynovial giant cell tumors (6.6%), 1 of 6 nonossifying fibromas (16.6%), and 1 of 4 pigmented villonodular synovitides (25%). The sensitivity, specificity, positive predictive value, and negative predictive value of p63 immunohistochemistry for the diagnosis of giant cell tumor of bone were 86.95%, 53.36%, 45.45%, and 91.17%, respectively. Conclusions.—This study shows that although p63 is expressed by most giant cell tumors of bone, its lack of specificity limits its use as an immunohistochemical marker in the differential diagnosis of giant cell–containing lesions of bone and soft tissue.
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Aneurysmal Bone Cyst
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In three cases of a giant cell tumor-like lesion of bone, the histological characteristics of the lesions were a fibrogenic stroma, capillaries, thick-walled blood vessels, multinucleated giant cells, osteoid tissue and bone trabeculae. It is believed that tumors of that kind are another giant cell variant that should be separated from the true giant cell tumor if for no other reason than the favorable response to conservative surgical therapy.
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THE PRESENCE of multinucleated giant cells in a variety of bone lesions has led to inclusion of certain neoplastic, inflammatory, developmental, and metabolic disorders of bone under the diagnosis of giant-cell tumor or giant-cell tumor variant. In 1940, Jaffe, Lichtenstein, and Portis (1) offered a specific definition of giant-cell tumor which has gained wide, though not universal, acceptance. They considered it a distinctive neoplasm apparently arising in the nonosteoblastic connective tissue, composed of a vascularized network of spindle-shaped or ovoid stromal cells interspersed with multinuclear giant cells (which they regarded as syncytial stromal cells). In subsequent publications Jaffe and Lichtenstein (2–6) identified as distinct clinical and pathologic entities many of the lesions formerly classed as giant-cell tumor variants. Accurate identification of lesions in this category is of considerable practical importance. Most of the socalled giant-cell tumor variants are fundamentally benign lesions offering an excellent prognosis, while the true giantcell tumor is a distinctly more formidable neoplasm. Lichtenstein (7) has stated that approximately half of the proved giant-cell tumors will respond favorably to proper management, approximately a third will prove more aggressive and will recur after treatment, and the remainder ultimately will be frankly malignant. Changing concepts of the pathology of bone tumors have prompted Dahlin and associates to undertake a comprehensive review of the bone lesions encountered at the Mayo Clinic. Tissues obtained at surgical operation have been subjected to detailed gross and microscopic study, and the lesions have been reclassified in accordance with current concepts. Approximately 5 per cent of the lesions in which material was available for their review were giant-cell tumors. One practical result of a critical review in the light of changing concepts can be shown by the experience of the Mayo Clinic. In 1932, Kirklin and Moore (8) reported on the roentgenographic appearance of 86 pathologically confirmed giantcell tumors seen over a twenty-year period. On review, however, only 42 lesions encountered during that period met the revised criteria for the pathologic diagnosis of giant-cell tumor. Some of the lesions originally diagnosed as giant-cell tumor have now been reclassified pathologically as aneurysmal bone cyst, benign chondroblastoma, fibroma, benign giant-cell reparative granuloma, unicameral bone cyst, osteogenic sarcoma, fibrosarcoma, and fibrous dysplasia. The Cases Studied Williams, Dahlin, and Ghormley (9) have recently reported on the clinical and pathologic features of the giant-cell tumors observed at the Mayo Clinic. Their report was based on 101 cases seen from 1905 through December 1953. Since that report 1 of the lesions included in the series has been reclassified as an aneurysmal bone cyst and 4 new cases have been added.
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Giant cell tumor of bone was originally described in the early 1800s. It is thought by most to be a benign tumor of bone, although “metastasis” to the lung is not uncommon. It is a tumor that consists of osteoclast like giant cells containing numerous nuclei as well as a mononuclear stromal component. Occasionally, giant cell tumor of bone can undergo malignant transformation. This review will examine the clinical and imaging characteristics of this giant cell tumor of bone. The pathology and genetics will also be discussed. Treatment, both surgical and nonsurgical will be examined. In addition, unusual presentations of giant cell tumors will also be considered.Keywords: Giant cell tumor of bone, review, radiology, pathology, therapy, denosumab
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Giant cell tumors of the bone are local invasive diseases that are mainly composed of neoplastic monocytes and nonneoplastic multinucleated giant cells, mostly in the long bones of patients with mature bones. A specific H3F3A mutation is the key to its diagnosis. The present paper reports a case of giant cell tumor of the bone (GCTB) characterized by diffuse cholesterol crystals with few multinucleated giant cells. Imaging examination combined with immunohistochemical H3.3 G34W positivity was used to diagnose the patient with GCTB. Understanding the unique histological morphology of this patient will help doctors correctly diagnose giant cell tumors of bone and avoid misdiagnosis.
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Specimens from 29 cases of giant cell tumors of bone and 42 cases of other bone tumors were pathohistologically examined, with emphasis on the relationship between the multinucleated giant cells and the fibrous stroma in them. The results were summarized as follows: The giant cell tumor of bone is an osteogenic tumor characterized by the appearance of multinucleated giant cells constituting a cellular osteoid tissue, with the grade of malignity indicated by the behavior of the mono-nucleated tumor cells. With the advance of malignity, the organoid giant cells fall into hypoplasia or dysplasia, oligonucleated giant cells and those of malignant-type coming forth, and the tumor gradually takes on the histological picture of a polymorphous-cell sarcoma. Giant cell tumor tissues may be found sometimes in benign osteoma, osteofibroma and malignant osteoplastic osteosarcoma, too.
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The article by Kaban et al1 appearing in this month's issue ofPediatrics is of interest because it describes, to the best of my knowledge, the first completely successful medical treatment of a primary giant cell tumor of the bone with the angiogenesis inhibitor interferon α-2a. Previously, a 37-year-old woman with a benign giant cell tumor of the leg that spread to the lungs demonstrated a significant decrease in pulmonary metastases and stabilization of disease following treatment with interferon α-2a.2 Giant cell tumors of the bone have 3 major cell types: 1) proliferating mononuclear cells thought to be the neoplastic element of the tumor, 2) nonproliferating mononuclear cells, and 3) multinucleated giant cell that are fused mononuclear cells.3 The incidence of giant cell tumors among primary bone neoplasms is 4% to 5%, with most occurring around the knee and <1% in the skull. Because 95% are benign, the incidence of these tumors among benign bone tumors rises to 18%.4,5 More than 50 cases of pulmonary metastases associated with benign giant cell tumors have been described.6 Aneurysmal bone cysts are associated with almost 15% of giant cell tumors, as was the case in this present study. With rare exceptions, giant cell tumors occur in skeletally mature individuals, with about 75% occurring in patients between 15 and 40 years of age. It has been estimated that only 1.7% of giant cell tumors occur in skeletally immature individuals.4The treatment for giant cell tumors is problematic. Approximately 40% to 70% of these lesions recur after marginal resection (curettage), although this rate can be decreased to about 25% if the lesion has a low histologic stage. Less than 10% of these tumors recur after wide resection; a procedure often limited because of the location of the lesion and/or the desire to preserve limb function.4 Conventional anticancer chemotherapy has occasionally been reported to be effective,5 while radiation therapy is associated with a recurrence rate of about 50%. The problem with radiotherapy is that it not only carries the usual risk of radiation-induced sarcoma but also the risk of radiation-induced giant cell tumor-specific sarcomas. This later risk has been estimated to be from 7% to 33%, although modern radiation techniques are said to decrease this risk.4Because of the rather limited success of current therapeutic modalities, the apparent success of interferon α-2a therapy is a welcome discovery. Many more typical patients, (ie older with extremity lesions), will have to be successfully treated before one can say with any surety that this inhibitor of angiogenesis is effective.7 After attending a lecture at which Dr Folkman discussed the case described in this month's issue, we gave interferon α-2a to a 17-year-old female with a nonosseous, pelvic, giant cell tumor that could not be removed surgically and was completely resistant to radiotherapy and embolization. A significant reduction in tumor size was observed and the patient regained some of the function that was compromised as a result of compression and local infiltration.In addition to those tumors discussed by Kaban et al that are responsive to interferon, interferon has also been shown to be effective in immunoblastic lymphadenopathy8 and, along with interleukin 2, renal cell carcinoma.9 Administration of interferon has been associated with fever, fatigue, anorexia, myelosuppression, and central nervous system and gastrointestinal toxicity.10 Cardiovascular complications have been observed and they include rhythm abnormalities, myocarditis, cardiomyopathy, myocardial infarction, and hypotension. Some of these cardiac problems may be attributable, in part, to the inhibitory effects of interferon on neovascularization which, in turn, may lead to an increase in the thickness of the endothelial processes of myocardial capillary walls.11The web site for the National Cancer Institute lists more than 20 phase I-III trials, each evaluating a different angiogenesis inhibitor, that are currently open for patients with various types of cancer. If only some of these studies are successful, we will have added to our armamentarium antitumor agents that, either alone or in combination with current antineoplastic agents, are less toxic and more tumor-specific than our present therapeutic regimens. Furthermore, because these agents have a unique mechanism of action, they may prove effective when other, more conventional, therapy fails. The study of angiogenesis inhibitors is of intense interest and promise.
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Introduction:Giant cell lesions of bone include true giant cell tumors & numerous benign osteoclasts and pseudo-anaplastic-appearing giant cells containing variants.Many times it is difficult to differentiate between true giant cell tumor and other tumor like conditions.Aims:To study histopathology of various giant cell rich tumor and tumor like conditions of bone.Methods and Material: Retrospective analysis of 50 cases of giant-cell rich lesions of bone diagnosed and treated at Smt. N.H.L. Municipal Medical College Ahmedabad, Gujarat during 1st January 2002 to 1st January 2003 included in the study. Patients’ clinical, radiological details, histopathological examination were studied using structured proforma. The cases were classified in different categories according to age groups, types of tumour, benign versus malignant category.Results: The most common giant cell containing benign tumor is giant cell tumor (19 cases) followed by Aneurysmal bone cyst (5), Most of the giant cell containing tumors of bone are found in younger age group and are located in epiphysis The common giant cell containing malignant tumor is osteogenic sarcoma (7 cases) followed by Talangiectatic O.S (01). The majority of cases found in age between 15 - 28 years and most common sites are epiphysis of long bones.Conclusion:The most common giant cell rich benign bone tumor is giant cell tumor and most common giant cell rich malignant bone tumor is osteosarcoma commonly occurs in younger age groups in the epiphysis region long bonesDOI:10.21276/APALM.1524
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Epiphysis
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Giant cell tumor of the bone (GCTOB) is a relatively uncommon tumor of the bone. It is characterized by the presence of multinucleated giant cells. Giant-cell tumor of the bone accounts for 4-5% of primary bone tumors and ∼20% of benign bone tumors. Giant cell tumors of the hand are rare, accounting for only 2-4% of all giant cell tumors. Giant cell tumor (GCT) of the bones of the hand has some special features as compared to GCT at other sites. Because of the aggressive nature of this lesion, adequate assessment of the treatment method is required. The aim is to eradicate the disease but preserve as much hand function as possible. Methods of treatment include curettage with or without bone grafts, local resection possibly combined with reconstruction using homologous or autologous bone, amputation, and resection of one or more rays.
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Primary bone
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Giant Cell Tumors
Multinucleate
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