Multifocal giant cell tumour of bone in a skeletally immature patient--a case report

Giant cell tumor of bone is usually seen in adults affecting a single bone. Multiple giant cell tumour of bone occurring in skeletally immature patients is extremely rare. Multifocal giant cell tumor of bone in a ten year old boy involving upper end of humerus and tibia is being reported for its extreme paucity in literature.     

Histological and clinical characteristics of malignant giant cell tumor of bone

Malignant giant cell tumors of bone (MGCTB) are rare, and the diagnosis can be difficult due to the occurrence of a variety of malignant tumors containing giant cells. To better understand its clinicopathological features, we have reviewed our experience with 17 cases of MGCTB. Five cases were primary malignant giant cell tumor of bone (PMGCTB), and 12 cases were giant cell tumors of bone initially diagnosed as benign but malignant in a recurrent lesion (secondary MGCTB, SMGCTB). The patients included six women and 11 men (age ranged from 17 to 52 years; mean, 30.5 years). The tumor arose in the femur (six cases), the tibia (seven cases), the humerus (three cases), and the fibula (one case). Microscopically, PMGCTB showed both conventional giant cell tumor and malignant sarcoma features. SMGCTB were initially diagnosed as conventional giant cell tumor of bone, the recurrent lesion showing malignant features. Histologically, the malignant components included osteosarcoma (11 cases), undifferentiated high-grade pleomorphic sarcoma (two cases), and fibrosarcoma (four cases). SMGCTB cases showed strong expression of p53. Follow-up information revealed that four patients died of lung metastasis, two patients are alive with lung metastases, and 11 patients are alive without tumor. MGCTB should be considered as a high-grade sarcoma. It must be distinguished from GCTB and other malignant tumors containing giant cells. p53 might play a role in the malignant transformation of GCTB.     

Epidemiology of bone tumors in Mexico City: retrospective clinicopathologic study of 566 patients at a referral institution

A retrospective analysis of all bone tumors accessioned at a large referral center (Instituto Nacional de Rehabilitacion) in Mexico City between 2000 and 2005 is presented. A total of 6216 biopsies and surgical resection specimens were reviewed during this period, of which 566 corresponded to bone tumors. Benign bone tumors accounted for 71.6% of cases and malignant bone tumors for 28.4%. The tumors affected men in 53.7% of cases and women in 46.3% of cases, with an average age at presentation of 25 years. The femur was the most common location of the tumors (39.9%), followed by the tibia (17.7%) and humerus (11.8%). The commonest malignant bone tumors were osteosarcoma (46.6%) and chondrosarcoma (8.7%). Of malignant bone tumors, 18.6% corresponded to metastases of carcinomas from internal organs and 8.1% were multiple myeloma. The most common benign bone tumor was osteochondroma (43.7%) followed by giant cell tumor of bone (14.6%) and enchondroma (10.1%). The age distribution showed a peak in children and adolescents comprised predominantly of benign lesions and a second peak in young adults that corresponded to malignant bone tumors (principally osteosarcoma). Malignant bone tumors most often involved the femur, vertebra, and tibia. Our results parallel the findings previously reported in the world literature and show a similar distribution and epidemiology as in other developed and underdeveloped countries. Geographic location does not appear to represent a risk factor for any particular type of bone tumor and does not affect the age distribution, location, or histopathologic type of the lesions.     

Carcinosarcomatous malignancy, osteosarcoma and squamous cell carcinoma, in giant cell tumor of the right distal femur

We report a new type of secondary malignant giant cell tumor of bone, the malignancy of which was assigned to a carcinosarcoma, i.e., osteosarcoma and squamous cell carcinoma. It occurred 25 years after curettage and bone graft surgery under the diagnosis of giant cell tumor of the right distal femur. Although secondary malignant giant cell tumor is known as a sarcoma arising at the site of a previously diagnosed giant cell tumor, this case should be regarded as a new type of secondary malignant giant cell tumor of bone.     

Factors regulating the metastatic potential of benign giant cell tumour of bone--study of an unusual case with short review of literature

Benign giant cell tumour of bone with metastases to other bones and lungs is extremely rare. Benign metastasising giant cell tumour is distinctly separate from multicentric giant cell tumour, primary and secondary malignant giant cell tumour. Factors regulating the local recurrence and metastatic potential of this benign tumour depend on its aggressiveness which can be better assessed by clinical and radiological parameters rather than the histopathological appearance. A benign giant cell tumour of ischium with metastasis to vertebra and lung over an eleven year period is discussed. Extreme paucity of literature prompted to publish the article. A short review of factors determining the recurrence and metastatic spread of benign giant cell tumour of bone is highlighted.     

Giant cell tumour of soft tissue--a case report

Giant cell tumor is seen in late adolescence or in the third or fourth decade of life. It arises from epiphysis of long bones, the commonest site being the distal end of the femur and the proximal end of tibia. This paper presents a case report of giant cell tumor of soft tissue.     

The mechanism of metastasis in the so-called “benign giant cell tumor of bone”

A case of so-called “benign giant cell tumor of bone” with an incidental histologic finding of intratumor vascular invasion is reported. The mechanism and biology of metastasis are briefly discussed. For the purposes of this presentation, the mechanism of metastasis is divided into two types—active and passive. An active type of metastasis indicates malignancy, whereas a passive type denotes a benign process. The malignant features of the conventional or typical giant cell tumor of bone are demonstrated. It is proposed that this neoplasm be labeled malignant despite its seemingly benign histologic appearance. Relative to the degree of malignancy, a lesion of this nature may be classified as either a low or a high grade type of malignant giant cell tumor.     

Malignant fibrous histiocytoma of bone: a study of 35 cases.

Thirty-five cases of primary malignant fibrous histiocytoma of bone are reported. Twenty of these cases were collected from a retrospective analysis of other malignant bone tumors. The age range was from 11 to 69 years; the average age was 34 years. The tumor occurred most commonly in the distal femur and proximal tibia. The distinguishing histologic feature was a storiform arrangement of spindle cells. The differential diagnosis included fibrosarcoma, osteogenic sarcoma, malignant giant cell tumor, malignant lymphoma, and metastatic carcinoma. Follow-up of at least three years was available in 21 cases. Of these, nine patients were alive and free of metastases three and one-half to 12 years after treatment. Two were alive with solitary metastases at three years, and 10 patients died between three months and three years after treatment. In four cases the lesions were multicentric at the time of diagnosis and in four cases were associated with bone infarction. This tumor must be recognized as an important complication of bone infarction and should be suspected when a patient with a known history of bone infarction develops a change in symptoms. Because the prognosis of this tumor is significantly better than that in those tumors with which it had been previously grouped, and in view of its association with bone infarction, it deserves to be maintained as a distinct clinicopathologic entity. Amputation is the treatment of choice.     

Pulmonary metastasis of giant cell tumor of the bone diagnosed by fine-needle aspiration biopsy

Giant cell tumor is a benign but locally aggressive tumor that primarily affects the epiphyses of long bones of young adults. Pulmonary metastases in giant cell tumor are rare (about 1-9%). Here, we report a case of metastatic pulmonary giant cell tumor in a patient who had a previous history of giant cell tumor of the distal femur with multiple recurrences. The diagnosis of pulmonary metastasis was achieved by cytologic evaluation with concurrent immunohistochemical studies in material obtained by fine-needle aspiration biopsy. The aspirate smears contained clustered and dispersed mononuclear and osteoclast-like giant cells that had bland nuclei with inconspicuous nucleoli. All multinucleated cells showed immunoreactivity to KP-1 antibody, a histiocytic marker (not lineage specific) and only a subset of mononuclear cells (30%) stained with this marker. Twenty percent of the mononuclear cells also displayed increased Ki-67 and p53 protein expression. The pulmonary metastasis was similar morphologically and immunophenotypically to the recurrent giant cell tumor of the bone.     

Secondary malignant giant cell tumour of bone--a study of five cases with short review of literature

Secondary malignant giant cell tumour of bone occurs as a result of previous attempts at local control of a benign giant cell tumour of bone (GCT). Out of the total 445 conventional benign GCT of bone, therapeutic irradiation was given in 39 cases as the lesions were located in the vertebrae and pelvic bones where debulking surgery was not possible and the tumours were pressing on the spinal cord. The patients were followed up for 21 years. Out of 39 cases, 5 patients developed sarcomas of which 3 were fibrosarcomas, 1 was malignant fibrous histiocytoma while 1 was an osteosarcoma. All the patients developing post-radiation sarcomas died within a few months due to lung metastasis. In conclusion, all the patients with benign GCT of bone treated with radiation must be followed life long as they are prone to develop sarcomas.     

Multifocal benign chondroblastomas: Report of a case

Benign chondroblastoma is an unusual solitary bone tumor occurring usually in the second decade in a long bone. The tumor is often sited on epiphyseal cartilages. Very few examples of malignant variants have been documented, although local recurrence of benign tumors is not unusual.We wish to report a patient who developed two chondroblastomas in two distinct anatomical sites (tibia and calcaneus) over the space of seven years, with no clinical or histological features of malignant disease.     

Pattern of primary tumors and tumor-like lesions of bone in children: retrospective survey of biopsy results

Background: Although primary bone tumors are relatively uncommon, they constitute the most important tumors in patients less than 20 years. We aimed to determine the frequencies of primary bone tumors and tumor-like lesions of bone and the anatomical sites of their occurrence. Methods: A retrospective review of histopathology reports of all bone specimens received in a private pathology laboratory in Istanbul between 2009 and 2015. Results: A total of 57 patients (aged 5 to 18 years) with a mean of 13.12 years were studied. Thirty five patients (61.4%) were males and 22 (38.6%) were females. Fifty five (94.4%) of the tumors were benign. Osteochondroma was the commonest tumor accounting for 31 cases (54.3%) followed by osteoid osteoma, 9 cases (15.7%). Chondrosarcoma observed in two patients and Ewing sarcoma in one patient as malignant tumors. Of the 57 bone tumors 13 (22.8%) occurred in the upper extremities, while 44 (77.2%) were in the lower extremities. Proximal humerus was the most commonly involved site in upper extremity tumors, with osteochondromas representing the most frequent type of tumor (4 patients; 7%). In the lower extremities again osteochondromas were the most common type of tumor (8 cases, 14%), with the femur being the most common site of involvement (18 patients, 31.5%). Of the patients with tumor-like lesions; four patients had fibrous dysplasia, 4 patients had non-ossified fibromas, 4 patients had simple bone cysts and 3 had aneurismal bone cyst. Conclusion: This study showed that primary bone tumors were mainly benign, settled predominantly in the lower extremities mostly in the femur with a male preponderance. Osteochondroma was the most common benign bone tumor. We didn’t observed osteosarcoma, which is the most frequent malignant bone tumor.     

A diagnosis of giant cell-rich tumour of bone is supported by p63 immunohistochemistry,when more than 50 % of cells is stained

Some primary malignant or benign tumours of bone contain numerous multinucleated cells. These “giant cell-rich tumours of bone” have overlapping features and clinical and radiological data are needed to reach an accurate pathological diagnosis. We studied the potential contribution of p63 immunohistochemistry to the reliability of the histological diagnosis. We performed a multicentric retrospective study of 291 giant cell-rich tumours of bone which included 119 giant cell tumours of bone (GCTB), 76 aneurysmal bone cysts (ABC), 49 chondroblastomas (CB), 15 nonossifying fibromas (NOF), 10 giant cell reparative granulomas (RG) of jaws, 1 giant cell lesion of small bones, 2 hyperparathyroidism-related brown tumours (BT), 17 bone sarcomas with numerous osteoclasts and 2 malignant giant cell tumours of bone. p63 is expressed in ABC, CB, NOF, RG, BT and GCTB, but its expression in more than 50 % of mononuclear cells is strongly suggestive of a diagnosis of GCTB. In contrast, malignant GCTB were mostly negative. Our results show that p63 is expressed in a broad range of benign giant cell-rich tumours of bone, consistent with data in the recent literature, while infrequent in malignant tumours. With a cut-off 50 %, the presence of p63 positive cells is useful in supporting a diagnosis of giant cell-rich tumour of bone. However, a final diagnosis cannot be made without due consideration of all clinical/radiological and pathological data.     

Ultrastructural findings supporting the angioblastic nature of the so-called adamantinoma of the tibia

Electron microscopy of a case of adamantinoma of the tibia shows features which support a mesenchymal angioblastic origin rather than epithelial. Comparison is made between tissue from this tumour and a squamous cell carcinoma of the femur arising in chronic osteomyelitis. In adamantinoma no desmosomes are found between tumour cells and their cytoplasmic ultrastructure shows features of mesenchymal cell type including evidence of pinocytic activity and bundles of filaments resembling hyperplastic endothelial cells. The stroma shows features similar to fibrous dysplasia of bone with fibroblasts, histiocytes and fibrolipoblastic lipid-laden mesenchymal cells. It is condluded that adamantinoma of the tibia should be considered to be an angioblastic tumour of bone.     

Malignant phyllodes tumor of the breast with osteoclast-like giant cells: a case report

Breast tumors, particularly of stromal origin, containing multinucleated osteoclast-like giant cells (OLGC) are rarely reported in the literature. We report here the first case of a malignant phyllodes tumor associated with OLGC occurring in a 43 year-old African woman who presented with a painful palpable mass of the outer upper quadrant of the right breast. After surgical excision, histological examination showed a malignant phyllodes tumor in which the stromal component displayed evident sarcomatous changes and was densely populated with benign multinucleated OLGC. These cells expressed the CD68 histiocytic marker. No evidence of osseous or cartilaginous differentiation was seen throughout the lesion. This lesion ressembles giant cell tumor of bone. However, the nature of the OLGC is not well precised yet.     

Malignant fibrous histiocytoma of bone. Clinical pathology and histological diagnosis

Malignant fibrous histiocytoma of bone is a histologically well-defined tumor. Our aim is to describe five own cases and to analyze the published cases in order to demonstrate, the controversial aspects of clinical pathology. The essential histological criteria are the storiform tissue pattern and the presence of fibroblastic and histiocytic cells and giant cells. Inclusive of our cases, the total number reported stands at 196. There are features of malignant fibrous histiocytoma of bone about which there is almost general agreement: 1. The tumor occurs at all ages with an average onset from the age of 10 to the age of 50. 2. The tumor occurs in both the long and flat bones, but the main sites are the distal femur and the proximal tibia. 3. The tumor lacks any initial distinctive features in its clinical phase, but with respect to its biological behaviour, malignant fibrous histiocytoma of bone can be distinguished from osteosarcoma.     

Primary malignant giant cell tumor of bone: "dedifferentiated" giant cell tumor

Well documented examples of primary malignant giant cell tumor of bone (giant cell tumor and concurrent sarcoma arising de novo) are exceedingly rare in the literature. We report a case arising in the left ischium of a 44-yr-old man. He had no previous history of radiation therapy or multiple resections. Histologically, the tumor was a typical giant cell tumor of bone juxtaposed to a malignant fibrous histiocytoma (MFH). The juxtaposition of a high grade sarcoma (MFH) and a locally aggressive nonmalignant neoplasm such as giant cell tumor is analogous to several other tumors of bone and soft tissue in which a low grade malignant or locally aggressive tumor can be associated with MFH or fibrosarcoma de novo, namely chondrosarcoma, chordoma, liposarcoma, and well differentiated intraosseous and parosteal osteosarcoma. The presence of a high grade malignant component in each of the aforementioned neoplasms generally portends a more ominous prognosis, although this is not invariably true. Recognition of the phenomenon of "dedifferentiation" (or tumor progression) in some bone tumors and sarcomas is important to ensure appropriate treatment. Distinction from secondary malignant giant cell tumors which are usually radiation induced is also important, since the latter have a much worse prognosis than those with dedifferentiation occurring de novo.     

Osteocalcin expression in primary bone tumors--in situ hybridization and immunohistochemical study.

Osteocalcin is one of the most abundant noncollagenous proteins found in adult bone. It is a highly conserved gamma-carboxyglutamic acid-containing protein that is believed to be produced exclusively by osteoblasts. In this study, intracellular and extracellular localization of osteocalcin in osteosarcoma was examined with anti-osteocalcin antibody and in situ hybridization using a synthetic oligonucleotide. Immunohistochemically, osteoblastic osteosarcomas were all positive for osteocalcin. The chondroblastic osteosarcomas were positive on the neoplastic chondrocytes. The five fibroblastic osteosarcomas out of seven were positive for osteocalcin immunostaining over the neoplastic spindle cells. Five cases of osteoblastic osteosarcomas out of seven were positive for osteocalcin in situ hybridization. Two cases of chondroblastic osteosarcomas and three cases of fibroblastic osteosarcomas were positive for in situ demonstration of osteocalcin. The malignant tumor giant cells were positive for osteocalcin immunostaining 83%. They were also positive for in situ hybridization. The benign giant cells in five giant cell tumors and five aneurysmal bone cysts were negative for osteocalcin immunostaining. The benign giant cells in three chondroblastoma and three Paget''s disease were positive for osteocalcin. In this study, the osteocalcin in situ hybridization and immunostaining has very important meaning for making differential diagnoses of, especially giant cell rich bone forming tumors.     

Malignant giant cell tumor of bone

Summary The fine structure of the different cell types constituting a primary malignant giant cell tumor of bone has been studied and the localization of acid phosphatase in relation to the subcellular organelles been demonstrated. Three distinct cell types with characteristic ultrastructural features were observed: giant cells, fibroblast-like cells, and cells with abundant lipid inclusions and mitochondria. Certain differences were noted between these three cell types and their counterparts in benign giant cell tumors of bone (described in a separate report). The enzyme histochemical and morphological data suggested that the giant cells in the malignant tumor might possess a more active and expansive lysosomal apparatus than corresponding cells in the benign variant.This investigation has been aided by a grant from the Swedish Cancer Society (grant 77:64, project No. 617-B77-06XA)