Gene expression profiling of giant cell tumor of bone reveals downregulation of extracellular matrix components decorin and lumican associated with lung metastasis.

Giant cell tumor of bone (GCTB) displays worrisome clinical features such as local recurrence and occasionally metastatic disease which are unpredictable by morphology. Additional routinely usable biomarkers do not exist. Gene expression profiles of six clinically defined groups of GCTB and one group of aneurysmal bone cyst (ABC) were determined by microarray (n = 33). The most promising differentially expressed genes were validated by Q-PCR as potential biomarkers in a larger patient group (n = 41). Corresponding protein expression was confirmed by immunohistochemistry. Unsupervised hierarchical clustering reveals a metastatic GCTB cluster, a heterogeneous, non-metastatic GCTB cluster, and a primary ABC cluster. Balanced score testing indicates that lumican (LUM) and decorin (DCN) are the most promising biomarkers as they have lower level of expression in the metastatic group. Expression of dermatopontin (DPT) was significantly lower in recurrent tumors. Validation of the results was performed by paired and unpaired t test in primary GCTB and corresponding metastases, which proved that the differential expression of LUM and DCN is tumor specific rather than location specific. Our findings show that several genes related to extracellular matrix integrity (LUM, DCN, and DPT) are differentially expressed and may serve as biomarkers for metastatic and recurrent GCTB.

Dynamic contrast-enhanced MR imaging for differentiation between enchondroma and chondrosarcoma.

OBJECTIVES: To determine whether dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) can differentiate benign from malignant cartilage tumours compared to standard MRI. To investigate whether a cutoff value could be determined to differentiate enchondroma from low-grade chondrosarcoma (CS) more accurately. METHODS: One hundred six patients were included in this retrospective study: 75 with enchondromas (mean age = 41 years) and 31 with CS (mean age = 47 years). Within this population, a subgroup of patients was selected with the tumour arising in a long bone. At the time of diagnosis, the tumours were evaluated on MRI, including standard MRI, DCE-MRI, and region-of-interest (ROI) analysis to obtain information on tumour vascularisation and perfusion. RESULTS: The main cutoff value to differentiate enchondroma from CS contained a two-fold more relative enhancement compared with muscle, combined with a 4.5 (= 76°) slope value, with 100 % sensitivity and 63.3 % specificity. The prediction of CS diagnosis with DCE-MRI had 93.4 % accuracy. The accuracy of the standard MRI parameters was equal to the DCE-MRI parameters. CONCLUSIONS: Standard MRI and DCE-MRI both play an important and complementary role in differentiating enchondroma from low-grade CS. A combination of both imaging techniques leads to the highest diagnostic accuracy for differentiating cartilaginous tumours. KEY POINTS: • DCE-MRI plays an important role in differentiating benign from malignant cartilage tumours. • Retrospective study defined a threshold for 100 % detection of chondrosarcoma with DCE-MRI. • The threshold values were relative enhancement = 2 and slope = 4.5. • One hundred per cent chondrosarcoma detection corresponds with 36.7 % false-positive diagnosis of enchondroma. • Standard MRI is complementary to DCE-MRI in differentiating cartilaginous tumours.

Complications of bone tumors after multimodal therapy.

PURPOSE: To define and compare the complications of bone tumors after resection, extracorporeal irradiation and re-implantation, with or without radiotherapy. MATERIALS AND METHODS: Eighty patients (40 males and 40 females, ages 4-77 years) with 61 malignant and 19 benign bone tumors were evaluated for local and distant complications after treatment. Two groups of patients were studied: (1) 53 patients had resection without (43 patients) or with external beam radiotherapy (RadRx) (10 patients) and (2) 27 patients underwent extracorporeal irradiation and re-implantation without (22 patients) or with RadRx (5 patients). Patient follow-up varied from 1 month to 13.63 years with mean follow-up of 4.7 years. Imaging studies included bone and chest radiography, spin echo T1- and T2-weighted (or STIR) magnetic resonance imaging (MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), computed tomography (CT) for thoracic and abdominopelvic metastases and 3-phase technetium-99m-labeled-methylene-diphosphonate (Tc99m MDP) scintigraphy for bone metastases. RESULTS: DCE-MRI differentiated the rapidly enhancing recurrences, residual tumors and metastases from the slowly enhancing inflammation, and the non-enhancing seromas and fibrosis. Recurrences, metastases (mainly to lung and bone), and seromas were greater than twice as frequent in patients after resection than after ECCRI. Although 11.3% of post-resection patients had residual tumor, no ECRRI-treated patient had residual tumor. In contrast, after ECRRI, infection was almost three times as frequent and aseptic loosening twice as frequent as compared with the post-resection patients. Bones treated with RadRx and/or ECRRI showed increased prevalence of fractures and osteoporosis. In addition, muscle inflammation was more common in the externally irradiated patient as compared with the patient who did not receive this therapy. However, another soft tissue complication, heterotopic ossification, was rare in the patient after RadRx, but 25.6% of patients after resection and 40.9% after ECRRI showed heterotopic ossification. Unusual complications after resection or ECRRI involved adjacent nerves with partial denervation, amputation neuroma, or entrapment (secondary to recurrence or fibrosis) after resection or ECRRI with or without RadRx. One patient developed a posterior tibial artery pseudoaneurysm after ECRRI. CONCLUSIONS: Follow-up of patients with benign and malignant bone tumors demonstrated the efficacy of DCE-MRI for distinguishing rapidly enhancing viable tumor from the slowly enhancing or non-enhancing benign processes after different therapies. Although recurrences, residual tumors, metastases and seromas were more common after resection, fractures, osteoporosis, infection, and muscular atrophy predominated in the ECRRI-treated patient. RadRx further predisposed post-resection and post-ECRRI patients to develop fractures, osteoporosis and infection and was the major cause of persistent muscle inflammation at MRI. Because complications can evolve and resolve years after treatment, the patients with bone tumors, particularly sarcomas, must receive life-time multimodal imaging for maximal diagnosis and treatment.

Post-treatment complications of soft tissue tumours.

PURPOSE: To identify local and distant complications of patients with soft tissue tumours and evaluate their relationships to types of therapy. METHODS AND MATERIALS: Fifty-one patients (29 males and 22 females, ages 14-80 years) with 34 malignant and 17 benign soft tissue tumours were evaluated for local and distant complications after resection or amputation only (26 patients) or after the addition of radiotherapy (25 patients: 17 patients had external beam therapy, 7 patients had external beam therapy and brachytherapy, and one patient had extracorporeal irradiation and reimplantation). Duration of follow-up averaged 3.75 years for malignant tumours and 2.79 years for benign tumours. Follow-up studies included radiography, T1- and T2-weighted magnetic resonance (MR) imaging, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), computed tomography for thoracic and abdominal metastases, and 3-phase technetium-99m-labeled-methylene-diphosphonate scintigraphy for bone metastases. RESULTS: Recurrent tumours were 2.2 times more frequent in patients who had undergone their initial resection at an outside hospital as compared with those first treated at the university hospital. Nine of 11 recurrences occurred after marginal surgery. Metastases from soft tissue sarcomas, most commonly to lung (nine patients) and to bone and muscle (five patients), showed no specific relationship to type of therapy. DCE-MRI differentiated rapidly enhancing soft tissue recurrences (11 patients) and residual tumours (6 patients) from slowly enhancing muscle inflammation, and non-enhancing fibrosis and seromas that usually did not enhance. Seromas developed in 76% of patients who had postoperative radiation therapy and in 7.7% of patients who had only surgery. Subcutaneous and cutaneous oedema and muscle inflammation was at least four times more frequent after adjunct radiotherapy than after resection alone. Irrespective of the type of treatment, inflammatory changes in muscle and subcutaneous and cutaneous tissue and the majority of seromas were evident at the first follow-up study. Although seromas after resection and external beam therapy resolved with time, seromas after additional brachytherapy persisted. Inflammatory changes in muscle and cutaneous and subcutaneous tissue after resection alone disappeared by the second follow-up study, whereas these changes after radiotherapy resolved months to years after treatment. Fourteen of 51 patients showed MR findings of chronic muscular atrophy, predominantly located in the lower extremity. Heterotopic ossification was seen in three patients after resection and amputation without radiotherapy. Except for one patient with aggressive fibromatosis, bone and nerve complications occurred in patients with soft tissue malignancy. Twelve patients had osteoporosis. Six patients sustained fractures in irradiated osteoporotic bone of the lower extremity, and one patient had a vertebral fracture in radiographically normal but irradiated bone. In addition, one patient was found to have a medullary infarct in an irradiated femur. In nerve entrapment, DCE-MRI demonstrated the rapidly enhancing recurrent tumour or non-enhancing fibrosis surrounding the slowly enhancing nerve. T1- and T2-weighted MR images displayed the acute and chronic sequelae of nerve entrapment and nerve transection with denervation as T2-hyperintense acute muscle atrophy or T1-hypertense chronic fatty muscular atrophy with decrease in muscle volume. CONCLUSION: This study suggests a possible relationship between types of treatment of soft tissue tumours and subsequent complications. Postoperative radiotherapy was associated with a significant number of patients with seromas, muscle, cutaneous and subcutaneous inflammation, and fractures. Incomplete or difficult surgery resulted in residual or recurrent tumours and heterotopic ossification. Muscle atrophy and nerve entrapment were related to both treatments (resection alone or radiotherapy after resection). Diligent follow-up of patients with soft tissue tumours with recognition of these complications and their differentiation from recurrent or residual tumour can help guide clinical care and may negate the need for surgery when benign disease is defined.

Parosteal osteosarcoma of the humerus.

The authors report the case of a 50-year-old man who presented with nontraumatic swelling of the left upper arm. The diagnosis of parosteal osteosarcoma of the humerus was made after diagnostic workup. A long diaphyseal segment of the humerus containing the tumor was resected with a healthy margin of soft tissues and was irradiated extracorporeally with a single dose of 30 Gray. The bony segment was then reimplanted after removal of the tumor using plate and screw fixation. Loosening of the proximal screws after one year required additional fixation and autologous cancellous bone grafting. The patient has a nearly three-year-follow-up and there are no signs of tumor recurrence or metastasis. The proximal osteotomy has healed nicely; the distal fixation osteotomy exhibits delayed healing. The pathogenesis of parosteal osteosarcoma is discussed.

Neurofibromatosis, gigantism, elephantiasis neuromatosa and recurrent massive subperiosteal hematoma: a new case report and review of 7 case reports from the literature.

The authors report the case of a 13-year-old patient with neurofibromatosis (NF-I), who suffered blunt trauma to the left tibia in 1993. The diagnosis of subperiosteal hematoma was made. Treatment consisted of temporary rest. There was a recurrence in 1996, and the subperiosteal hematoma was drained. In 1997, a shortening osteotomy of the left tibia was performed. However, massive gigantism with elephantiasis of the left leg remained, causing a serious functional and cosmetic problem. In 1999, the leg was amputated above the knee. The literature is reviewed and 7 case reports are compared. The pathogenesis of subperiosteal hematoma is discussed.

Recurrent massive subperiosteal hematoma in a patient with neurofibromatosis.

The authors report the case of a 13-year-old neurofibromatosis (NF-I) patient who suffered a blunt trauma in 1993. The diagnosis of subperiosteal hematoma was made. The pathogenesis of subperiosteal hematoma is discussed.