Assessment of Tumor Angiogenesis by Expression of CD 105 in Ameloblastoma, Odontogenic Keratocyst and Central Giant Cell Lesion.

BACKGROUND: Angiogenesis is critical for tumor growth and reflects the aggressive behavior of invasive odontogenic lesions [like Ameloblastoma (AM), Odontogenic Keratocyst (OKC) and Central giant cell lesion (CGCL)]. Mean vascular density (MVD) shows the angiogenic potential and CD105 is an ideal endothelial biomarker due to its specificity to new blood vessels for MVD detection. The aim of the study was to compare the MVD (angiogenic potential) among AM, OKC and CGCL in comparison to Pyogenic Granuloma (PG) using CD105 biomarker. METHODS: Sixty-four primary cases of odontogenic invasive tumors (AM, OKC and CGCL) and PG, diagnosed clinically and histologically were included in the study, with 16 samples in each group. Tissue samples of peripheral AM, Peripheral GCL of jaws, malignant AM, and specimen with insufficient tissue were excluded. Tissue sections were embedded, processed and stained using Hematoxylin and Eosin (H and E). Immunohistochemistry was performed using antibodies against CD105, with positive brown cytoplasmic staining in the endothelial cells of neo-vasculature. Distinct countable, positively stained endothelial cell or clusters were evaluated under light microscope for identification of MVD. ANOVA and t-test were applied for statistical analysis of data. RESULTS: Highest MVD was displayed in CGCL (32.99±0.77) and the minimum was observed in OKC (7.21± 0.75) respectively. CGCL showed significantly higher MVD to AM, OKC and PG lesions (p <0.05). AM (8.07± 0.36) and Odontogenic Keratocyst (7.21± 0.75) showed comparable MVD, which was lower than PG (14.7± 0.96) and CGCL vascular density (p < 0.01) respectively. CONCLUSION: CGCL was most aggressive, with highest MVD among the investigated odontogenic lesions (OKC, AM and PG). The proliferative aggressive behavior of Odontogenic Keratocyst is comparable to AM due to comparable mean vascular density.
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[Giant cell tumor of the C2 colonized by an aneurismal bone cyst. Report of case]. / Tumeur à cellules géantes de C2 colonisée par un kyste anévrismal. À propos d'un cas.

Giant cell tumor is colonized by aneurismal bone cyst in only 15% of cases and cervical localisation accounts for less than 1% of giant cell tumors. We are reporting a rare case of a C2 hypervascularized giant cell tumor colonized by an aneurismal bone cyst treated with an effective preoperative Onyx embolization followed by a full tumor resection. The patient experienced a moderate cervical spine injury 2 months prior admission followed by a progressive stiff neck and cervicalgia. CT and MRI identified a lytic lesion of the body and lateral masses of the C2 with encasement of both vertebral arteries. The angiography showed a hypervascularization of the lesion from the vertebral and external carotid arteries as well as a thrombosis of the V3 segment of the right vertebral artery at the C1 level. A posterior occipito-C3/C4 fixation and a tumor biopsy were performed. Histopathological examination concluded to a giant cell tumor colonized by an aneurismal bone cyst. Three weeks later, the patient developed a right upper extremity deficit. The MRI showed an increased C1-C2 stenosis and an increase of the hypervascularization. Three sessions of embolization by the onyx were performed. During surgery a near total tumor devascularisation was observed and a complete resection of the tumor was achieved through an anterolateral approach. Reconstruction consisted of a cementoplasty of the C2 body and odontoïd process with an anterior C3-prosthesis plate. The postoperative course was uneventful.

Immunohistochemical evaluation of giant cell tumors of the jaws using CD34 density analysis.

PURPOSE: To compare CD34 expression in both aggressive and nonaggressive giant cell lesions of the jaws and identify any associations between tumor vascular density and biologic behavior. MATERIALS AND METHODS: This was a retrospective study of subjects treated for giant cell lesions of the jaws at Massachusetts General Hospital from 1992 to 2006. The primary predictor variable was tumor classification (aggressive or nonaggressive); tumors were considered aggressive if they were greater than 5 cm in size, recurred after treatment, or exhibited 3 of the following: presence of root resorption, tooth displacement, or cortical bone thinning or perforation. Secondary predictor variables, recorded for each patient, were demographic, anatomic, and clinical measures. The outcome variable was the average CD34 staining density of histologic specimens quantified in 2 different areas. Descriptive and bivariate statistics were computed to identify predictors associated with vascular density. RESULTS: The study sample was composed of 32 subjects with a mean age of 24.4 +/- 19.77 years (range: 2-83); 23 subjects (71.8%) were female. Of the tumors included, 11 (34.4%) were located in the maxilla, 21 (65.6%) in the mandible. Twenty-six tumors (81.2%) were classified as aggressive; the remainder (18.8%) were nonaggressive. There were no statistically significant differences between subjects with aggressive versus nonaggressive tumors with regard to age, gender, or location. Subjects with aggressive tumors had a significantly higher CD34 staining density (P = .02). None of the secondary predictors was associated with vascular density. CONCLUSION: Vascular density of giant cell tumors of the jaws is significantly increased in aggressive tumors.

Serial arterial embolization for large sacral giant-cell tumors: mid- to long-term results.

STUDY DESIGN: Level III retrospective case series with historical controls. OBJECTIVE: To evaluate the mid- to long-term outcomes of serial arterial embolization as a primary treatment modality for large sacral giant-cell tumors (SGCT). SUMMARY OF BACKGROUND DATA: Giant-cell tumors are potentially aggressive benign tumors that can cause significant morbidity and may occasionally prove lethal. Large GCTs in the sacrum present a significant challenge, and treatment methods, including surgical resection and radiation, are associated with morbid complications and high recurrence rates. This report presents the mid- to long-term follow-up results of our cases of SGCT treated with serial arterial embolization. METHODS: Nine consecutive patients with biopsy-proven SGCTs received initial primary treatment with serial arterial embolization between 1984 and 2006. All patients underwent angiography and selective arterial embolization at the time of diagnosis, followed by repeat embolization every 6 weeks until no new vessels were noted, and then at 6 and 18 months following stabilization of the lesion. Patients were closely monitored with MRI and/or CT every 6 months for 5 years and annually thereafter. Functional outcomes were measured using the 1993 Musculoskeletal Tumor Society Rating Scale (MSTS93). RESULTS: The mean duration of follow-up in this series was 8.96 years (median, 7.8 years; range, 3.8-21.2 years). No progression was noted in 7 of the 9 cases. Two cases experienced tumor progression of less than 1 cm early in the treatment course and continued to remain asymptomatic. Adjuvant radiation therapy provided local control in 1 of these cases, while radiation and chemotherapy failed in the other case with ultimate mortality. All patients demonstrated substantial pain relief. Cross-sectional MSTS93 scores were obtained in the 8 surviving patients at their most recent follow-up visit with a mean score of 29/30. CONCLUSIONS: Serial arterial embolization is a useful primary treatment modality for large SGCTs given the favorable long-term results and potential morbidity of alternative treatments.

Osteoclast-like giant cell tumors of the pancreas and liver.

Osteoclast-like giant cell tumors (OGCT) are rare abdominal tumors, which mainly occur in the pancreas. The neoplasms are composed of two distinct cell populations and frequently show an inhomogenous appearance with cystic structures. However, due to the rarity of these tumors, only very limited clinical data are available. Imaging features and sonographic appearance have hardly been characterized. Here we report on two cases of osteoclast-like giant cell tumors, one located within the pancreas, the other within the liver, in which OGCTs are extremely rare. Both patients were investigated by contrast sonography, which demonstrated a complex, partly cystic and strongly vascularized tumor within the head of the pancreas in the first patient and a large, hypervascularized neoplasm with calcifications within the liver in the second patient. The liver OGCT responded well to a combination of carboplatin, etoposide and paclitaxel. With a combination of surgical resection, radiofrequency ablation and chemotherapy, the patient's survival is currently more than 15 mo, making him the longest survivor with an OGCT of the liver to date.

Growth inhibition of dermatofibrosarcoma protuberans tumors by the platelet-derived growth factor receptor antagonist STI571 through induction of apoptosis.

Dermatofibrosarcoma protuberans (DFSP) and giant cell fibroblastoma (GCF) are recurrent, infiltrative skin tumors that presently are treated with surgery. DFSP and GCF tumors are genetically characterized by chromosomal rearrangements fusing the collagen type Ialpha1 (COLIA1) gene to the platelet-derived growth factor B-chain (PDGFB) gene. It has been shown that the resulting COL1A1/PDGF-B fusion protein is processed to mature PDGF-BB. Autocrine PDGF receptor stimulation has therefore been predicted to contribute to DFSP and GCF tumor development and growth. Here we demonstrate presence of activated PDGF receptors in primary cultures derived from six different DFSP and GCF tumors. Three of the primary cultures were further characterized; their in vitro growth displayed an increased sensitivity to treatment with the PDGF receptor tyrosine kinase inhibitor STI571, as compared with normal fibroblasts. Transplantable tumors, displaying a DFSP-like histology, were established from one of the DFSP primary cultures. Treatment of tumor-bearing severe combined immunodeficient mice with STI571 reduced tumor growth. The growth-inhibitory effects in vitro and in vivo occurred predominantly through induction of tumor cell apoptosis. Our study demonstrates growth-inhibitory effects of PDGF receptor antagonists on human DFSP- and GCF-derived tumor cells and demonstrates that autocrine PDGF receptor stimulation provides antiapoptotic signals contributing to the growth of these cells. These findings suggest targeting of PDGF receptors as a novel treatment strategy for DFSP and GCF.

Preoperative evaluation of giant cell tumors of the radius with magnetic resonance angiography.

We report three clinical cases of giant cell tumor of the distal radius in which reconstructions were performed with vascularized fibular grafts. Magnetic resonance angiography, a newer and noninvasive technique, was used in addition to preoperative magnetic resonance imaging. All patients had routine digital subtraction arteriography, with which magnetic resonance angiography compared favorably, demonstrating the carpal arch anatomy and other major vessels at the tumor site. In two patients the trifurcation vessels of both legs were also studied with magnetic resonance angiography before fibular harvest. In one case, the fibula graft was successfully harvested on the basis of the magnetic resonance angiographic findings. In the other case, digital subtraction arteriography had been done to evaluate suspected peripheral vascular disease. In that case magnetic resonance angiography correlated well with the digital subtraction arteriographic study, showing bilateral anterior tibial artery occlusions and patent posterior tibial and peroneal arteries. Magnetic resonance angiography has the potential to replace conventional angiography in preoperative evaluation of upper-extremity tumors.

Combined MRI and MRA for limb salvage planning.

Magnetic resonance angiography (MRA) was performed in two patients with primary bone neoplasms being staged for differing types of limb-salvage procedures. A gated two-dimensional (2D) phase contrast MRA sequence that is capable of variable velocity encoding throughout the cardiac cycle was used to acquire the MRA images. The resulting cardiac phase images were added with a matched filter algorithm to create a single high signal-to-noise ratio image. An SE MR image in the same plane and field of view was then added to the MRA image. This displayed the relationship of vascular and stationary tissues within a composite picture: a "2D combined angiographic-stationary tissue" image. The anatomy represented gave information equivalent to conventional angiography. While this technique is not an ideal 3D rendering, it is easier to use. Along with other SE sequences acquired as needed for staging, it provides a complete preoperative evaluation of a tumor bed or donor site for a vascularized graft harvest.

Giant-cell tumor of bone, stage II, displaying translocation t(12;19)(q13;q13).

A new case of giant-cell tumour (GCT) of bone with benign histological features, clinical stage II, has been reviewed with immunohistochemistry and electron microscopy. After short-term tissue culture the karyotype, using G-banding techniques, presented a consistent translocation t(12;19)(q13;q13). Nude mice xenografts of the tumour were unsuccessful after 6 months of follow-up. Presence of such chromosomal rearrangement may be related to locally aggressive, histologically benign giant-cell tumors of bone.

Scintigraphic evaluation of giant cell tumor of bone.

Technetium-99m methylene diphosphonate bone scans were performed in 21 patients with giant cell tumors of bone. All tumors showed increased radiophosphate uptake, often more intense at the tumor periphery than in its center. However, radionuclide bone scanning often overestimated intraosseous tumor extent as a result of increased tracer uptake beyond true osseous tumor limits. In addition, it failed to detect soft-tissue tumor extension in nine patients. Therefore, scintigraphy is less useful than either computed or conventional tomography in planning surgical margins of giant cell tumors. Gallium-67 citrate scans obtained in seven patients showed slight uptake in four tumors and no uptake in three. Radiogallium imaging is thus of limited use in evaluation of suspected giant cell tumors of bone.

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.

Role of arteriography in the evaluation of musculoskeletal tumors.

The clinical application of arteriography, which was performed in 141 patients with musculoskeletal tumors, is described. The characteristic arteriographic signs indicating various tumors are also described. Although it is not possible to determine the histological type of a tumor by angiography, it is still one of the most useful techniques in establishing the existence of various neoplasms, particularly the malignant ones. It defines their extent, assesses the pattern of neovasculature, assists in the selection of sites for a productive biopsy and helps in the planning of a surgical resection. Arteriography also demonstrates the effect of irradiation therapy on a given malignant tumor. It is suggested that arteriography improves both the accuracy of diagnosis and effectiveness of treatment of these neoplasms.

Facilitation of removal of a hypervascularized cervical vertebral body tumour by intraoperative temporary occlusion of the tumour-feeding vertebral artery, using intraarterial catheterization.

The surgical treatment of a highly vascularized tumour that destroyed the fourth cervical vertebral body in a young patient, without neurological deficits, is reported. After posterior stabilization an anterior approach was used in order to replace the affected vertebral body with an acrylic prosthesis. The tumour-feeding vessels originated largely from the right vertebral artery. In order to maintain optimal visibility, intraoperative haemorrhage was kept at a minimum by temporarily occluding the tumour-feeding vertebral artery with an intraarterial catheter.

Late recurrence of giant-cell tumor of bone: pharmacoangiographic evaluation.

Late recurrence (more than five years) of benign giant-cell tumor of bone is uncommon. Two patients were evaluated by angiography, including injection of vasoactive drugs, because of osteolytic lesions developing six and seven years after primary operation for benign giant-cell tumor. Angiography established a probable recurrence in both cases. Angiography also permitted accurate evaluation of tumor extension, facilitating pre-operative planning. Giant-cell tumors are predominantly hypervascular lesions. Angiographic evaluation is therefore recommended when a recurrent lesion is suspected.

Giant-cell tumor of the sacrum. Clinical and radiologic features in 13 patients.

Thirteen patients were found to have giant-cell tumors during a study of 91 primary tumors of the sacrum. This tumor was second only to the chordoma in incidence. Giant-cell tumor is by far the commonest benign lesion of the sarcrum, yet it has a bad prognosis. Recurrences occurred in seven patients and five died of disease or a complication. All were histologically benign when first seen, but one developed a malignant giant-cell tumor and died within two years, and one developed a radiation-induced sarcoma 10 years following treatment. Computed tomography in two recent patients proved to be the most valuable single examination. Arteriography is helpful in showing the degree of vascularity of the tumor and the exact position of the large vessels, particularly important when surgical resection is planned.