Neovascularization of bone marrow in patients with diffuse multiple myeloma: a correlative study of magnetic resonance imaging and histopathologic findings.

BACKGROUND: The goal of the current study was to assess the correlation between bone marrow histology and contrast enhancement in infiltrative diffuse myeloma. METHODS: Forty-four patients with homogeneous diffuse infiltration of bone marrow by multiple myeloma were examined using magnetic resonance imaging of the spine. The sequence protocol included T1-weighted spin-echo (pre- and post-gadolinium dimeglumine administration) and short-inversion time inversion recovery sequences. The percent increase in signal after intravenous gadolinium administration was calculated in bone marrow from patients with myeloma and from a control group of 86 patients who did not have bone marrow disease. Grade of infiltration with plasma cells, fat cell content, and hematopoietic marrow content were evaluated via histologic assessment of bone marrow, and microvessel density was evaluated via anti-CD34-positive immunostaining. RESULTS: Increased microvessel density was observed in association with increasing plasma cell content (Kruskall-Wallis test: P < 0.0001). Contrast enhancement increased in a stepwise manner according to grade of microvessel density (Mann-Whitney U test: P < 0.05 and P < 0.001 for increases from low to intermediate and intermediate to high grade) and was significantly higher in patients with myeloma compared with control patients (Mann-Whitney U test: P < 0.001). A significant correlation also was found between histologic extent of tumor infiltration and contrast enhancement (Mann-Whitney U test: P < 0.0001). The mean level of contrast enhancement was 18% in the control group, 26% in patients with low-grade infiltration, 49% in patients with intermediate-grade infiltration, and 90% in patients with high-grade infiltration. In addition, fat cell content was found to be inversely correlated with contrast enhancement (chi-square test: P < 0.01). CONCLUSIONS: As a consequence of increased microvessel density, decreased fat cell content, and increased cellularity, the presence of diffuse bone marrow infiltration in patients with multiple myeloma can be verified using gadolinium-enhanced magnetic resonance imaging.

A case of systemic mastocytosis associated with severe osteoporosis and pathologic fractures.

We describe the case of a 56-year-old man with rapidly progressive osteoporosis culminating in pathologic fractures of multiple lumbar vertebrae. With the exception of discrete brown-reddish cutaneous lesions, low back pain was the only prominent symptom. Laboratory evaluations excluded metabolic or endocrinological abnormalities. Serum tryptase was highly increased, as was urinary excretion of histamine. Iliac crest biopsy demonstrated mastocytosis, which was confirmed by skin biopsy and which was consistent with teleangiectasia macularis eruptiva perstans, a rare form of cutaneous mastocytosis. In cases of unusually marked osteoporosis, especially in men, mastocytosis should be considered in the differential diagnosis.

Diffusion-weighted imaging of bone marrow: current status.

Diffusion-weighted imaging allows for measurement of tissue microstructure and reflects the random motion of water protons. It provides a new method to study bone marrow and bone marrow alterations on the basis of altered water-proton mobility in various diseases. Different diffusion-weighted methods have proved to be capable of differentiating between benign edema and tumorous involvement of bone marrow. It is especially useful for the distinction of acute benign osteoporotic and malignant vertebral compression fractures. Diagnosis is based on the contrast to normal bone marrow. Hypo- or isointensity reflects acute benign collapse, whereas hyperintensity is indicative of the tumorous nature of a fracture. Apparent diffusion coefficients (ADC) are significantly lower in metastatic disease than in bone marrow edema. Furthermore, bone marrow cellularity can be estimated by ADC measurements. Diffusion-weighted imaging might be helpful for monitoring response to therapy in metastatic disease.

Acute osteoporotic and neoplastic vertebral compression fractures: fluid sign at MR imaging.

PURPOSE: To evaluate the occurrence, location, and shape of the fluid sign in acute osteoporotic and neoplastic vertebral compression fractures at magnetic resonance (MR) imaging. MATERIALS AND METHODS: The study group comprised 87 consecutive patients with acute vertebral compression fractures due to osteoporotic (n = 52) or neoplastic (n = 35) infiltration. The MR imaging protocol included nonenhanced T1-weighted spin-echo and short inversion time inversion-recovery sequences and a 1.5-T system. Readers blinded to the outcome documented the occurrence, shape, and location of the fluid sign with consensus. The fluid sign was correlated with the cause, age, and severity of the fracture. The diagnosis was confirmed with surgery, follow-up MR imaging, clinical follow-up, or unequivocal imaging findings. Wilcoxon and chi(2) tests were used to assess significance. RESULTS: In fractured vertebral bodies, the fluid sign was adjacent to the fractured end plates and exhibited signal intensity isointense to that of cerebrospinal fluid. The fluid sign was linear (n = 16), triangular (n = 5), or focal (n = 2) and was significantly associated with osteoporotic fractures (21 [40%] of 52; P <.001). The fluid sign occurred in two (6%) of 35 neoplastic compression fractures. Histologic examination demonstrated osteonecrosis, edema, and fibrosis at the site of the fluid sign. There was a tendency toward older fractures exhibiting the fluid sign, but this relationship was not significant (P >.05). In osteoporotic fractures, the fluid sign was significantly associated with fracture severity (P <.05). CONCLUSION: The fluid sign is featured in acute vertebral compression fractures that show bone marrow edema. It can be an additional sign of osteoporosis and rarely occurs in metastatic fractures.

Magnetic resonance imaging as a supplement for the clinical staging system of Durie and Salmon?

BACKGROUND: This study evaluated the prognostic value of a three-grade staging system of spinal involvement using magnetic resonance imaging (MRI) in patients with multiple myeloma and determined its usefulness as an independent parameter in the staging system of Durie and Salmon. METHODS: Seventy-seven previously untreated patients with multiple myeloma underwent MRI of the thoracic and lumbar spine with unenhanced T1-weighted spin echo and short-tau inversion time inversion recovery sequences. The patients were evaluated according to their infiltration patterns and the extent of bone marrow involvement was staged using a three-grade scale: Stage I, no focal or diffuse infiltration; Stage II, 1-10 foci or mild diffuse infiltration; Stage III, more than 10 foci or strong diffuse infiltration. RESULTS: The infiltration patterns had no significant effect on survival. Of 77 patients, 25 would have been understaged using the standard staging system of Durie and Salmon without the findings of MRI and 8 patients would have been understaged if the staging was based only on MRI. The combination of the staging system of Durie and Salmon and MRI was highly significant with respect to survival (P < 0.0001, log rank analysis). MRI staging I-III was independent of the staging system of Durie and Salmon (Cox regression model). CONCLUSIONS: A three-grade staging of spinal MRI provides a significant prognostic tool for patients with multiple myeloma. The authors propose including it in the staging system of Durie and Salmon.

Response to neoadjuvant chemotherapy combined with regional hyperthermia predicts long-term survival for adult patients with retroperitoneal and visceral high-risk soft tissue sarcomas.

PURPOSE: To determine the efficacy of neoadjuvant chemotherapy combined with regional hyperthermia (RHT) for local tumor control and overall survival (OS) in adult patients with retroperitoneal or visceral (RP/V) high-risk soft tissue sarcomas (HR-STS). PATIENTS AND METHODS: From 1991 to 1997, 58 patients with HR-STS at RP/V sites were prospectively treated with four cycles of etoposide, ifosfamide, and doxorubicin combined with RHT followed by surgery, adjuvant chemotherapy, and radiation. RESULTS: Objective response rate assessable in 40 patients was 13% (five partial responses). Including minor responses (n = 8), the radiographic response rate was 33%. The pathologic response rate assessable in 26 patients after surgical resection was 42%. Median OS was 31 months. At a median observation time of 74 months, 5-year probability of local failure-free survival (LFFS), distant metastasis-free survival, event-free survival, and OS were 25%, 51%, 20%, and 32%, respectively. Averaged minimum temperatures (T(min)) and time-averaged temperatures achieved in 50% (T(50)) and 90% (T(90)) of all measured tumor sites differed significantly between responders and nonresponders (T(min), 39.3 degrees C v 38.0 degrees C; P =.002; T(50), 40.9 degrees C v 40.3 degrees C; P =.038; T(90), 40.1 degrees C v 39.3 degrees C; P =.017). At 5-year follow-up, probability of LFFS (59% v 0%; P <.001) and OS (60% v 10%; P <.001) was significantly in favor of patients responding to neoadjuvant thermochemotherapy. CONCLUSION: Response to neoadjuvant chemotherapy combined with RHT is predictive for an improved local tumor control resulting in a long-term survival benefit for patients with HR-STS at unfavorable RP/V sites; however, the impact of RHT has to be defined in a randomized phase III trial.

Malignant lymphoma of bone.

Malignant lymphoma of bone is rare. In many cases, its diagnosis is delayed because of unspecific clinical signs and equivocal radiographs. Therapy in general is multimodal, including surgery and radio- and chemotherapy. Our objective was to demonstrate the clinical and radiological aspects of the lesion to optimize diagnostic approaches and to evaluate treatment and prognostic factors. Thirty-six patients with malignant lymphoma of bone who were surgically treated over a 15-year-period were retrospectively reviewed. Seventeen of them showed a singular bone non-Hodgkin's lymphoma (NHL) which was classified as primary lymphoma of the bone (PLB). In 13 cases, dissemination of the disease with multiple bone or visceral involvement was apparent (dNHL). Six patients suffered from bone involvement due to Hodgkin's disease (HD). Surgical treatment was indicated for diagnostic reasons or complications due to the disease. Radiation and chemotherapy were part of the oncological treatment. The patients' mean age was 57 years. The main symptom in malignant bone lymphoma in 33 patients was pain, with an average duration of 8 months. In the secondary cases, bone involvement appeared on average 57 months after the initial diagnosis. An osteolytic pattern was seen in 58% of the lesions. Soft-tissue involvement was seen in 71% of cases (PLB 80%, dNHL 73%, HD 40%) and was the primary diagnostic sign associated with this disease. The 5-year survival rate was 61% (PLB 88%, dNHL 38%, HD 50%). Multiple vs solitary bone involvement was the most significant factor in the prognosis. Extraskeletal involvement significantly decreased survival. No correlation was found between gender, age, location, or histological subtypes and survival. Bone involvement in NHL appears late in the extraskeletal disease. The clinical appearance is nonspecific, and the delay between the onset of symptoms and diagnosis is often long. One of the major radiologic signs is the existence of a soft-tissue tumor surrounding the bone with little or no bone involvement on plain films. Treatment generally is conservative, based on the stage of the disease. Local radiation with or without systemic chemotherapy should be used. The long-term survival is favorable, but dependent on the stage of the disease and the amount of bone involvement.

Diffusion-weighted imaging of the spinal column.

Diffusion-weighted imaging of the musculoskeletal system including the spine is a new MR imaging method. Several studies have shown significantly different diffusivities for various pathologic conditions such as edema and tumor. The specificity of diagnosis may be increased and therapeutic effects may be monitored. Diffusion-weighted sequences especially have been shown to be an additional tool for differentiating vertebral fractures caused by osteoporotic collapse with bone marrow edema and metastatic collapse. Inclusion criteria should include: (1) unknown reason for the vertebral collapse, (2) lack of sclerosis, and (3) no prior therapy. Patients with trauma or treated metastases may exhibit different signal intensities. In general, those patients do not pose problems in differential diagnosis. New sequence developments and higher magnetic field gradients should be able to increase spatial resolution and decrease problems from motion artifacts. Studies with larger patient groups and sequences that quantify the results with ADCs are the necessary next steps.

Surgical treatment of bone metastases in patients with breast cancer.

In this retrospective study, the effect of surgical therapy on a series of 70 patients with breast cancer who were surgically treated for metastasis of the bone was evaluated. At presentation, 19 patients had one osseous lesion, 19 patients had multiple bone lesions, and 32 patients had additional visceral involvement. The surgical procedures included 60 palliative procedures, six radical resections, and four biopsies. In 14 surviving patients, the mean observation period was 35.6 +/- 40.1 months. Of the six patients with radically resected solitary bone lesions, five patients had systemic progression of the disease develop. Of the 19 patients with presumably solitary bone lesions, five currently are free of tumor. Of the 19 patients with multiple bone lesions and initially no visceral tumor spread, only two are alive. Of the 32 patients with additional visceral metastases at surgery, four are alive with the disease. For the entire group, the survival rate was 59% after 1 year, 36% after 2 years, 13% after 5 years, and 7% after 10 years. The only two independent factors that were associated with survival were the extent of the disease and the duration of symptoms from bone metastasis. These findings suggest that in orthopaedic surgery in patients with bone metastases secondary to breast cancer, wide resection is not likely to be necessary. Patients with solitary bone lesions have a 39% chance of living 5 years.