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.

Imaging evaluation of the response of high-grade osteosarcoma and Ewing sarcoma to chemotherapy with emphasis on dynamic contrast-enhanced magnetic resonance imaging.

Response of high-grade osteosarcoma and Ewing sarcoma to preoperative chemotherapy can significantly affect the surgical approach to patients with these tumors and their disease-free survival. This article presents the findings and limitations of different imaging modalities (radiography, angiography, sonography, scintigraphy, and magnetic resonance [MR] imaging and spectroscopy) for evaluating this chemotherapeutic response. Particular emphasis is given to the currently most effective modality--dynamic contrast-enhanced MR imaging.

Dynamic contrast-enhanced MRI with subtraction of aggressive soft tissue tumors after resection.

OBJECTIVE: To report the application of dynamic contrast-enhanced subtraction MRI for detecting recurrences in aggressive or malignant soft tissue tumors. DESIGN: The imaging studies consisted of static (T1- and T2-weighted spin-echo) acquisitions, followed by dynamic conventional spin-echo short TR/TE images (at 45 s, 1 min 30 s and 5 min) after a bolus of intravenous contrast medium. Contrast images were subtracted from the precontrast scan on the console. PATIENTS: Ninety-eight patients were studied who had had aggressive or malignant soft tissue tumors treated by surgery, and were followed up to assess recurrences. RESULTS: Subtraction MRI characterized recurrences better than routine sequences in 10 patients (1 lesion was seen only with this technique, 6 were better delineated, and 3 inflammatory pseudotumors were identified), and less well in 4 cases. CONCLUSION: As the number of levels studied on dynamic images is limited, and all but one recurrence were detected on T2-weighted images, it remains logical to start the examination with T2-weighted spin-echo images, and to use the dynamic study only if contrast injection is required.

Primary tumors of the musculoskeletal system.

The excellent soft-tissue contrast and multiplanar imaging capabilities of MR imaging have led to its emergence as the most significant advance in the imaging of musculoskeletal tumors. MR imaging is the modality of choice for local staging, evaluating response to preoperative chemotherapy, and long-term follow-up in bone tumors. MR imaging is the most effective modality for both primary staging of soft-tissue malignancy and detecting recurrences. This article reviews the role of conventional spin echo techniques versus newer techniques, and then discusses the indications in the diagnosis, staging, evaluation of preoperative chemotherapy, and detection of recurrences in bone and soft-tissue tumors.

Can clinical data help to screen patients with lymphoma for MR imaging of bone marrow?

BACKGROUND: Previous studies have suggested combining magnetic resonance (MR) imaging and biopsy in patients with lymphoma but association between MR results and clinical symptoms have never been investigated. The purpose of this retrospective study was to better delineate patients profiles requiring bone marrow (BM) imaging in lymphoma. MATERIAL AND METHODS: 50 MR studies and blind biopsies (BB) were reviewed in 40 patients with lymphoma. MR results were compared to clinical, laboratory-based and BM follow-up data to determine potential associations between MR results and these parameters. RESULTS: 46% of MR studies were abnormal with a normal BB; 2% were normal with an abnormal BB. Abnormal MR results were significantly associated with subsequent bone marrow involvement (p < 0.01). Abnormal MR studies were significantly associated with constitutional symptoms, bone pains (p < 0.05) and an elevated alkaline phosphatase level (p < 0.01). MR imaging excluded malignancy in three patients and caused therapy to be modified in three. CONCLUSION: Abnormal clinical and laboratory-based data should be used to screen patients with normal BB for MR imaging, especially in patients with Hodgkin's disease and high grade non-Hodgkin's lymphoma.

Periosteal Ewing sarcoma.

PURPOSE: To evaluate the imaging and histopathologic findings and clinical course of patients with periosteal Ewing sarcoma (PES). MATERIALS AND METHODS: Conventional radiographs, computed tomographic (CT) scans, and magnetic resonance (MR) images in 10 adolescents and one adult were evaluated for the extent and character of PES. RESULTS: Ten of 11 masses were in the proximal extremities and one in the fibula; nine were diaphyseal and two, metadiaphyseal. Radiographs and CT scans showed a subperiosteal mass that did not invade the medullary cavity, was contiguous with and elevated the periosteum, and produced a Codman triangle and periosteal reaction. No PES exhibited osseous or cartilaginous matrix calcifications. MR imaging and histopathologic examination helped confirm the sparing of cancellous bone and the subperiosteal location. CONCLUSION: PES differs from the more common medullary and soft-tissue Ewing sarcomas in location, marked male predominance, and lack of presenting metastases. Except for the absence of matrix calcifications, PES resembles other periosteal sarcomas in imaging characteristics and a less aggressive clinical course.

MR imaging in the follow-up of malignant and aggressive soft-tissue tumors: results of 511 examinations.

PURPOSE: To present magnetic resonance (MR) imaging findings from 511 follow-up examinations of aggressive soft-tissue tumors. MATERIALS AND METHODS: One hundred eighty-two patients with aggressive soft-tissue tumours underwent postoperative T1- and T2-weighted imaging; 41 also underwent 51 gadolinium-enhanced T1-weighted examinations, and five underwent dynamic gadolinium-enhanced subtraction imaging. RESULTS: Twenty-four of 25 patients (101 of 102 examinations) without high signal intensity (HSI) at T2-weighted imaging had no recurrence. Among 79 patients (321 examinations) who demonstrated HSI without a mass, only two tumors recurred within 1 year. An HSI mass was found in 88 studies of 78 patients and represented recurrence (n = 60), hygroma (n = 24), or a radiation-induced pseudomass (n = 4). Hygromas did not enhance, while recurrences enhanced at 1-3 minutes and postirradiation change enhanced at 4-7 minutes. CONCLUSION: T2-weighted imaging can be used to identify possible recurrence of aggressive soft-tissue tumors, while gadolinium-enhanced imaging can be used to differentiate recurrences from hygromas and inflammatory change.

Aggressive fibrous dysplasia of the maxillary sinus.

Fibrous dysplasia is usually a slowly progressive, benign disease that develops over several years and presents with deformity or mild symptomatology. Five of 34 patients (ages 4-21 years), who were subsequently diagnosed histologically as having fibrous dysplasia of the maxillary sinus, rapidly developed soft tissue masses of the malar region over a period of less than 4 months with accompanying pain (2 patients) and nasal obstruction and exophthalmos (2 patients). Each was clinically suspected of having a sarcoma; two had been thought to have an "osteofibrosarcoma" on initial biopsy at outside hospitals. After resection, all lesions developed regrowth. At histopathologic examination, both initial and recurrent masses proved to be typical fibrous dysplasia with spicules of woven bone in cellular, sometimes vascular, fibrous tissue. No malignant degeneration was found. On conventional radiography, aggressive fibrous dysplasia produced opacification and expansion of the maxillary sinus and apparent disruption of its wall with an associated soft tissue mass. Computed tomography (CT) demonstrated voluminous heterogeneous masses with "ground glass appearance", calcifications, areas of enhancement, low attenuation, cystic areas, and a thinned, sometimes interrupted, maxillary wall. Despite the aggressive clinical course for both initial and recurrent lesions, the CT findings of a "ground glass" mass with calcifications surrounded by a maxillary sinus wall, even if incomplete, can suggest the diagnosis of aggressive fibrous dysplasia.

Bone metastases as the presenting manifestation of rhabdomyosarcoma in childhood.

Rarely, rhabdomyosarcoma can present with bone pain and bone lesions on radiographs without evidence of a primary tumor. Of 428 children with biopsy-proven rhabdomyosarcoma, four presented with radiographic evidence of bone metastases, but no primary tumor was found on subsequent evaluation. On radiographs, these metastases, located most commonly in the metaphyses of the extremities and in the spine, displayed a destructive or diffusely permeative pattern without sclerotic margins and mimicked the more common neuroblastoma. One patient also had diaphyseal cortical lytic metastases of the tibia. Radiographs defined metastases of the extremities better than the correlative bone scans. In the spine, on T2-weighted magnetic resonance (MR) images, metastases displayed high signal intensity which contrasted with the low-signal-intensity marrow in these pediatric patients. On histopathologic examination, metastatic rhabdomyosarcoma was composed of small cells of variable size, shape, and growth pattern similar to other round cell tumors. A positive desmin immunohistochemical test helped to establish the diagnosis. The radiologist, pathologist, and clinician should be aware of this unusual presentation of rhabdomyosarcoma so that suitable immunohistochemical tests are performed and appropriate chemotherapy given.

Assessment of breast cancer recurrence with contrast-enhanced subtraction MR imaging: preliminary results in 26 patients.

Local relapse was suspected in 26 women treated conservatively for breast cancer. All women underwent routine magnetic resonance (MR) imaging and a dynamic MR subtraction study after injection of gadolinium-tetraazacyclododecanetetra-acetic acid. Twelve women had no local relapse. Surgical biopsy enabled confirmation of recurrence in 14 patients. Routine MR imaging did not allow differentiation of recurrence from glandular or scar tissue. Except for one case of fat necrosis, patients without local relapse showed no contrast enhancement 1 minute 34 seconds after injection. At dynamic MR imaging, all recurrences showed contrast enhancement 1 minute 34 seconds after injection. Nodular enhancement (n = 11) was found in invasive carcinoma, whereas linear enhancement was seen in intraductal carcinoma (n = 3). Subtraction of precontrast from postcontrast images always allowed better visualization of contrast enhancement. Contrast-enhanced subtraction dynamic MR imaging may prove to be accurate in diagnosis of local relapses of breast cancer.

Extraskeletal mesenchymal chondrosarcoma.

Among seven patients with extraskeletal mesenchymal chondrosarcoma (EMC), three children (aged 3-6 years) developed EMC in a central location and four adults (aged 38-54 years) developed EMC in both central and peripheral sites. Conventional radiography and tomography and computed tomography (CT) depicted EMC as a soft-tissue mass with ring, arc, stippled, and highly opaque calcifications in four patients. Contrast-enhanced CT showed lobulation and peripheral tumoral enhancement, sometimes with central low-attenuation areas. On magnetic resonance (MR) images, EMC was a lobulated mass with high signal intensity on T2-weighted images and enhancement with low-signal-intensity focal areas on contrast-enhanced T1-weighted images. All adults developed recurrences and/or metastases and died. Of the three children, two were living and free of disease at the end of the study and the third child died of chemotherapeutic-induced leukemia. Although imaging features of EMC are nonspecific, its chondroid-type calcifications and foci of low signal intensity within enhancing lobules may reflect its dual histopathologic morphologic characteristics of differentiated cartilage islands interspersed within vascular undifferentiated mesenchyme.

Epidermoid cysts of testes and role of sonography.

Four patients with histologically proved epidermoid cysts of the testicle were managed with radical orchiectomy. High-resolution testicular sonography demonstrated similar findings in all cases, but these findings were not specific and did not preclude other malignant or teratomatous lesions. The lack of both unique clinical features and specific sonographic findings would suggest that extreme caution must be used if wedge resection or enucleation is contemplated for a patient with presumed epidermoid cyst.

Osteosarcoma after chemotherapy: evaluation with contrast material-enhanced subtraction MR imaging.

A new magnetic resonance (MR) technique, gadolinium-enhanced subtraction MR imaging, was developed to evaluate the response of patients with osteosarcoma to chemotherapy. Ten patients, who had received chemotherapy for osteosarcoma of the lower extremity, underwent MR imaging 3 days before surgery. After routine MR imaging was performed, subtraction MR was performed in the plane in which the tumor was best visualized. With gadopentetate dimeglumine (0.1 mmol per kilogram) on a standard MR console, subtraction images were created by subtracting precontrast images from gadolinium-enhanced T1-weighted images. The time of maximal tumoral vascular uptake was 1 1/2 minutes after injection, and, therefore, the subtracted image obtained at this time was used for evaluation of viable tumor. Independently, radiologists and histopathologists examined their respective studies for viable tumor to differentiate responders from nonresponders. Four of 10 osteosarcomas were classified as good responders because they appeared as nonenhancing masses, with or without enhancing thin lines, or small nodules (< or = 3 mm wide). At histopathologic examination, all were good responders with less than 3% viable tumor. Six of 10 osteosarcomas were classified as nonresponders because they appeared as enhancing high-signal-intensity masses measuring more than 3 mm in width. Five tumors had between 18% and 43% viable tumor cells.

Synovial sarcomas of the head and neck: CT and MR findings.

The authors present three cases of histologically proved synovial sarcoma. CT is useful in assessing erosive or destructive changes in bone, and in demonstrating calcifications. MR characteristics are nonspecific; calcifications within these tumors can be missed on MR. MR can help to assess tumor extension, vascular invasion, and hemorrhage within the tumor.

Imaging in the follow-up of soft tissue tumors.

Local recurrences of aggressive soft tissue tumors are frequent and very difficult to detect clinically after surgery and radiation therapy. Ultrasound is limited because the skin is thick. On contrast-enhanced CT, both scars and recurrences increase their signal. MRI is the best technique, and the only one we presently use in the detection of recurrent tumors. We are reporting 511 follow-up examinations in 182 patients after tumor removal. All patients had histologic confirmation or at least 6 months follow-up. There were 164 malignant tumors and 18 cases of aggressive fibromatosis.