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Cartilaginous Tumors: Fast Contrast-enhanced MR Imaging¹

¹ From the Departments of Radiology (M.J.A.G., J.L.B., H.J.v.d.W.), Pathology (P.C.W.H.), and Orthopedic Surgery (A.H.M.T.), Leiden University Medical Center, C2-S, Albinusdreef 2, P.O. Box 9600, 2300 RC Leiden, the Netherlands. From the 1996 RSNA scientific assembly. Received February 3, 1998; revision requested April 9, 1999; final revision received May 3; accepted June 28. Address reprint requests to M.J.A.G. (e-mail: j.l.bloem@radiology.azl.nl).

	Abstract

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
PURPOSE: To differentiate between benign and malignant cartilaginous tumors with fast contrast material–enhanced magnetic resonance (MR) imaging.

MATERIALS AND METHODS: In 37 patients, fast contrast-enhanced MR images were obtained in eight enchondromas, 11 osteochondromas, and 18 chondrosarcomas. Start of enhancement—early, within 10 seconds after arterial enhancement; delayed, between 10 seconds and 2 minutes; late, after 5 minutes on spin-echo images—and progression of enhancement were represented with three types of time–signal intensity curves. Findings were correlated with the surgical specimen in 27 cases, curettage material in three cases, and biopsy combined with long-term follow-up findings in seven cases.

RESULTS: Start of enhancement and the combination of start and progression of enhancement correlated significantly (P < .001) with benign and malignant tumors. Early enhancement was seen in chondrosarcoma, not seen in enchondroma, and seen in osteochondroma only when growth plates were unfused. The sensitivity was 89%, specificity 84%, positive predictive value 84%, and negative predictive value 89%. Differentiation of malignancy from benignity on the basis of early and exponential enhancement was possible with a sensitivity of 61%, specificity 95%, positive predictive value 92%, and negative predictive value 72%.

CONCLUSION: Preliminary results show that in the adult population fast contrast-enhanced MR imaging may assist in differentiation between benign and malignant cartilaginous tumors.

Index terms: Cartilage, MR, 40.121411, 40.121412, 40.12143 • Chondrosarcoma, 40.3211 • Enchondroma, 40.351 • Osteochondroma, 40.351 • Osteosarcoma, 40.322 • Sarcoma, 40.3211 • Soft tissues, MR, 40.12143

	Introduction

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
Cartilaginous tumors are typically well recognized on radiographs, but differentiation between benign and low-grade malignant cartilaginous tumors is a clinical problem and a radiologic-histologic challenge. Although high-grade chondrosarcomas exhibit distinct malignant radiographic features (1–3), the more frequently found low-grade chondrosarcomas are hard to discriminate from enchondroma (1,3–6).

The clinical relevance of differentiation of benign from low-grade cartilaginous tumors is that benign lesions do not require surgery, whereas the only curative treatment for chondrosarcoma is resection (7–13). Commonly, the diagnosis is based on a combination of clinical, radiologic, and histologic findings. Sampling errors, secondary to tumor heterogeneity, add to the problematic histologic differentiation of cartilaginous lesions (7,9,14–16). In cases of chondrosarcoma, the risk for (higher grade) local recurrence and development of metastases increases with intralesional procedures, thereby decreasing the life expectancy of patients (7,9,11,12).

Tissue characterization with magnetic resonance (MR) imaging has been used, both as an independent parameter and a guide to histologic sampling, in an attempt to decrease this diagnostic dilemma. In contrast material–enhanced MR imaging, septal and nodular enhancement is seen in patients with enchondroma and in patients with low-grade chondrosarcoma (17–19). Enchondroma consists of neoplastic cartilaginous cells embedded in areas of avascular cartilaginous matrix without overt induction of neovascularization. In contrast, chondrosarcoma induces a fibrovascular stroma between the avascular cartilaginous nodules (9). This histologic difference may potentially serve as a differentiating feature for perfusion-sensitive imaging techniques.

In the present study, a fast contrast-enhanced gradient-echo (GRE) MR subtraction technique was used to identify potential differences in enhancement features of benign and malignant cartilaginous tumors. The study focused on the start and progression of tumoral enhancement.

	MATERIALS AND METHODS

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
Patients
Thirty consecutive patients were prospectively included. In 27 patients (11 osteochondromas and 16 chondrosarcomas), findings on preoperative MR images and in resected specimens were correlated. In the other three patients (one enchondroma and two chondrosarcomas), findings on preoperative MR images and in curettage material were correlated.

In addition, we searched our files of patients with musculoskeletal tumors for definite enchondromas. The inclusion criteria were histologic diagnosis of enchondroma based on a biopsy specimen obtained 10–15 years ago, unchanged radiographic findings, absence of clinical symptoms during this 10–15-year follow-up, and willingness to participate. Patients with cartilaginous tumors of hands and feet were excluded. Seven patients were recruited. The medical ethical committee of our institution approved performance of gadolinium-enhanced MR imaging in these patients after informed consent was obtained.

Thus, a total of 37 patients (21 male and 16 female patients; median age, 41 years; age range, 4–86 years) were included in this study.

Chondrosarcoma was diagnosed in 18 patients (median age, 48 years; age range, 17–86 years). Five chondrosarcomas were located in the femur; two each in the acetabulum, ilium, radius, and scapula; and one each in the humerus, spine, rib, metacarpal bone, and phalanx. There were 11 central and seven peripheral chondrosarcomas. Seven chondrosarcomas were histologically classified as grade I, nine as grade II, and two as grade III. Osteochondroma was diagnosed in 11 patients (median age, 22 years; age range, 4–49 years). Four osteochondromas were located in the tibia; two each in the ilium and femur; and one each in the humerus, scapula, and fibula. Enchondroma was diagnosed in eight patients (median age, 46 years; range, 25–66 years). Three enchondromas were located in the humerus, three in the femur, and two in the tibia.

MR Imaging
Twenty-eight tumors were examined with a 0.5-T superconducting MR system (T5-II; Philips Medical Systems, Shelton, Conn) and nine with a 1.5-T superconducting MR system (NT; Philips Medical Systems). Depending on tumor volume, a surface coil was used in 27 patients and a body coil in 10 patients. T1-weighted spin-echo (SE) MR images with short repetition and echo times (repetition time msec/echo time msec = 600/20) and T2-weighted fast SE images with long repetition and echo times (1,800–5,200/90–150, echo train length of eight) were obtained in at least two orthogonal planes.

The native T1-weighted SE and T2-weighted fast SE pulse sequences were used to plan the limited number of sections to be acquired at fast contrast-enhanced imaging. The planes that contained the largest tumor volume were preferably chosen to image as much lesional tissue as possible with this fast contrast-enhanced sequence. Contrast-enhanced imaging was performed with a T1-weighted magnetization-prepared GRE sequence after manual intravenous injection of a bolus of 0.1 mmol per kilogram of body weight gadopentetate dimeglumine (Magnevist; Berlex-Schering, Berlin, Germany). A 20-gauge intravenous catheter was placed in a right antecubital vein in each patient. All catheters were long, allowing the patient to remain within the imager while gadopentetate dimeglumine was injected. The injection rate was approximately 5 mL/sec immediately followed by a saline solution flush of 20 mL at the same injection rate. The hand injection was started 5 seconds after the start of data acquisition. The duration of this sequence was 2 minutes.

On the 0.5-T system, imaging was performed with the following parameters: 15/6.8; prepulse delay time, 741 msec; flip angle, 30°; section thickness, 10 mm; one signal acquired; matrix, 128 x 256; field of view, 250–400 mm. In this setting, the temporal resolution was 1.5 seconds for single-section dynamic studies and 3 seconds for studies comprising two parallel sections. On the 1.5-T system the following imaging parameters were used: 9.5–15/3.0–6.3; prepulse delay, 472–744 msec; flip angle, 30°; section thickness, 7–10 mm; one or two signals acquired; matrix, 128 x 256; field of view, 250–400 mm. The temporal resolution was 0.9 seconds for single-section studies and 2.7 seconds for studies comprising three parallel sections. These sets of parameters yielded the optimal sequences with regard to temporal and spatial resolution as obtained in our in vitro GRE studies obtained in a phantom with increasing concentrations of gadoteridol (Prohance; Squibb-Bracco, Princeton, NJ) (van der Woude HJ, unpublished data, 1994). All contrast-enhanced images were subtracted from the first nonenhanced GRE image.

The T1-weighted SE sequence was repeated 5 minutes after the injection of gadopentetate dimeglumine in at least two perpendicular planes. The morphology of enhancement was assessed on these equilibrium images.

Temporal Enhancement on Magnetization-prepared GRE Images
The following enhancement parameters were evaluated by three observers (M.J.A.G., J.L.B., H.J.v.d.W.) in concert.

Start of tumoral enhancement.—The interval between the start of arterial enhancement and the onset of lesional enhancement was visually assessed on the series of subtraction images. Tumoral enhancement depicted within 10 seconds after the start of arterial enhancement was defined as early enhancement. Tumoral enhancement that occurred after 10 seconds and before 2 minutes was defined as delayed enhancement. No images were obtained between the finish of the magnetization-prepared GRE sequence (until 2 minutes after the start of contrast agent injection) and the start of the SE sequence (5 minutes after the start of contrast agent injection).   Progression of enhancement.—Areas that enhanced earliest within the tumor were identified on subtraction images. Subsequently, regions of interest were plotted on these early enhancing areas and on normal reference tissue (muscle or bone marrow) and an artery visible within the same field of view. Three patterns of time–signal intensity curves were observed (Fig 1): (a) an exponential curve parallel to early arterial enhancement, followed by an early maximum plateau or followed by a slight increase in enhancement; (b) a curve representing gradual progression of enhancement in time, between arterial and reference tissue enhancement (lower absolute enhancement was obtained compared with that for the exponential curve); and (c) a curve showing no or slightly progressive enhancement equal to that of reference tissue (20–22).

View larger version (11K): [in this window] [in a new window]   Figure 1. Schematic of progression of enhancement as defined with time-signal intensity curves. Curve A shows arterial enhancement, with rapid progression of signal intensity that reaches a maximum value very shortly after arrival of the bolus of contrast material and declines immediately thereafter (washout). Curve 1 is exponential, parallel to the first phase of arterial enhancement, followed by a maximum plateau or a slight increase in enhancement. Curve 2 represents gradual progression of enhancement over time, between the level of early arterial enhancement and the prolonged reference tissue enhancement. No part of this curve parallels the early arterial enhancement. Lower absolute enhancement was obtained compared with that shown by the exponential curve. Curve 3 shows no or slightly progressive enhancement equal to that of the reference tissue. The signal intensity of this curve depends on the type of reference tissue used.

Standard of Reference
We used previously described criteria (7,9,14,23–27) for histopathologic diagnosis.

Architectural information was obtained by means of direct comparison of the MR sections to the corresponding macroslices of the 27 resected specimens (20,28). The MR images were used to plan and execute sawing of the specimens. Findings in the curettage specimens of one enchondroma and two grade I chondrosarcomas were correlated with the preoperative MR imaging findings.

Although no direct correlation with findings in a resected specimen or curetted material could be made in the seven patients with enchondromas, the long-term clinical and radiographic follow-up of 10–15 years of a biopsy-proved enchondroma was considered adequate proof of a benign clinical course.

Statistical Analysis
Sensitivity, specificity, positive predictive value, and negative predictive value were calculated to evaluate if the start and progression of tumoral enhancement as assessed on fast contrast-enhanced GRE MR images could help differentiate between benign and malignant cartilaginous tumors. For these percentages, the 95% CIs were calculated. The hypothesis was that early enhancement in an exponential manner would correlate with chondrosarcoma. In contrast, delayed enhancement in a gradual way or no enhancement would correlate with a benign tumor.

The statistical significance of differences in the start and progression of enhancement between benign and malignant tumors was calculated with the ² test. Differences in the morphologic enhancement patterns were assessed in the same way. P values less than or equal to .01 were considered to be significant. In view of the small number of patients and the multiple testing, a reduced level of significance of P less than .01 was considered appropriate.

	RESULTS

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
Differential Diagnosis Based on Enhancement Observed on Magnetization-prepared GRE Images
Start of temporal enhancement.—A statistically significant correlation was found between differences in the start of enhancement and benign or malignant tumor (P < .001) (Fig 2).

View larger version (136K): [in this window] [in a new window]   Figure 2a. Grade I chondrosarcoma in the left distal radius in a 33-year-old woman. (a) Coronal radiograph shows the lobulated morphology of the lesion. Also, endosteal scalloping (curved arrow) and expansion (straight arrow) are seen. (Reprinted, with permission, from reference 29.) (b) Subtraction image from the magnetization-prepared GRE series (15/6.3, 30° flip angle) in the coronal plane shows the early enhancement (arrows) seen in the lesion directly after enhancement in an artery (arrowheads) in the imaging plane. (c) Time-signal intensity curves are projected over one of the GRE images. Signal intensity in arbitrary units is displayed in the vertical axis of the graph, and the horizontal axis represents time in seconds. Curve 1 represents arterial enhancement. Curve 2 shows exponential enhancement depicted in the entire lesion. Curve 3 represents enhancement in bone marrow (reference tissue). (d) Photomicrograph of the corresponding histologic macroslice displays the lobular morphology (straight arrows) and scalloping (curved arrows) of the cortex. (Hematoxylin-eosin stain; original magnification, x10.) (e) Photomicrograph shows the fibrovascular septation (curved arrows) between the cartilaginous nodules (straight arrows). (Hematoxylin-eosin stain; original magnification, x400.)

View larger version (152K): [in this window] [in a new window]   Figure 2b. Grade I chondrosarcoma in the left distal radius in a 33-year-old woman. (a) Coronal radiograph shows the lobulated morphology of the lesion. Also, endosteal scalloping (curved arrow) and expansion (straight arrow) are seen. (Reprinted, with permission, from reference 29.) (b) Subtraction image from the magnetization-prepared GRE series (15/6.3, 30° flip angle) in the coronal plane shows the early enhancement (arrows) seen in the lesion directly after enhancement in an artery (arrowheads) in the imaging plane. (c) Time-signal intensity curves are projected over one of the GRE images. Signal intensity in arbitrary units is displayed in the vertical axis of the graph, and the horizontal axis represents time in seconds. Curve 1 represents arterial enhancement. Curve 2 shows exponential enhancement depicted in the entire lesion. Curve 3 represents enhancement in bone marrow (reference tissue). (d) Photomicrograph of the corresponding histologic macroslice displays the lobular morphology (straight arrows) and scalloping (curved arrows) of the cortex. (Hematoxylin-eosin stain; original magnification, x10.) (e) Photomicrograph shows the fibrovascular septation (curved arrows) between the cartilaginous nodules (straight arrows). (Hematoxylin-eosin stain; original magnification, x400.)

View larger version (144K): [in this window] [in a new window]   Figure 2c. Grade I chondrosarcoma in the left distal radius in a 33-year-old woman. (a) Coronal radiograph shows the lobulated morphology of the lesion. Also, endosteal scalloping (curved arrow) and expansion (straight arrow) are seen. (Reprinted, with permission, from reference 29.) (b) Subtraction image from the magnetization-prepared GRE series (15/6.3, 30° flip angle) in the coronal plane shows the early enhancement (arrows) seen in the lesion directly after enhancement in an artery (arrowheads) in the imaging plane. (c) Time-signal intensity curves are projected over one of the GRE images. Signal intensity in arbitrary units is displayed in the vertical axis of the graph, and the horizontal axis represents time in seconds. Curve 1 represents arterial enhancement. Curve 2 shows exponential enhancement depicted in the entire lesion. Curve 3 represents enhancement in bone marrow (reference tissue). (d) Photomicrograph of the corresponding histologic macroslice displays the lobular morphology (straight arrows) and scalloping (curved arrows) of the cortex. (Hematoxylin-eosin stain; original magnification, x10.) (e) Photomicrograph shows the fibrovascular septation (curved arrows) between the cartilaginous nodules (straight arrows). (Hematoxylin-eosin stain; original magnification, x400.)

View larger version (158K): [in this window] [in a new window]   Figure 2d. Grade I chondrosarcoma in the left distal radius in a 33-year-old woman. (a) Coronal radiograph shows the lobulated morphology of the lesion. Also, endosteal scalloping (curved arrow) and expansion (straight arrow) are seen. (Reprinted, with permission, from reference 29.) (b) Subtraction image from the magnetization-prepared GRE series (15/6.3, 30° flip angle) in the coronal plane shows the early enhancement (arrows) seen in the lesion directly after enhancement in an artery (arrowheads) in the imaging plane. (c) Time-signal intensity curves are projected over one of the GRE images. Signal intensity in arbitrary units is displayed in the vertical axis of the graph, and the horizontal axis represents time in seconds. Curve 1 represents arterial enhancement. Curve 2 shows exponential enhancement depicted in the entire lesion. Curve 3 represents enhancement in bone marrow (reference tissue). (d) Photomicrograph of the corresponding histologic macroslice displays the lobular morphology (straight arrows) and scalloping (curved arrows) of the cortex. (Hematoxylin-eosin stain; original magnification, x10.) (e) Photomicrograph shows the fibrovascular septation (curved arrows) between the cartilaginous nodules (straight arrows). (Hematoxylin-eosin stain; original magnification, x400.)

View larger version (172K): [in this window] [in a new window]   Figure 2e. Grade I chondrosarcoma in the left distal radius in a 33-year-old woman. (a) Coronal radiograph shows the lobulated morphology of the lesion. Also, endosteal scalloping (curved arrow) and expansion (straight arrow) are seen. (Reprinted, with permission, from reference 29.) (b) Subtraction image from the magnetization-prepared GRE series (15/6.3, 30° flip angle) in the coronal plane shows the early enhancement (arrows) seen in the lesion directly after enhancement in an artery (arrowheads) in the imaging plane. (c) Time-signal intensity curves are projected over one of the GRE images. Signal intensity in arbitrary units is displayed in the vertical axis of the graph, and the horizontal axis represents time in seconds. Curve 1 represents arterial enhancement. Curve 2 shows exponential enhancement depicted in the entire lesion. Curve 3 represents enhancement in bone marrow (reference tissue). (d) Photomicrograph of the corresponding histologic macroslice displays the lobular morphology (straight arrows) and scalloping (curved arrows) of the cortex. (Hematoxylin-eosin stain; original magnification, x10.) (e) Photomicrograph shows the fibrovascular septation (curved arrows) between the cartilaginous nodules (straight arrows). (Hematoxylin-eosin stain; original magnification, x400.)

View larger version (96K): [in this window] [in a new window]   Figure 3a. Painful left shoulder in a 46-year-old man. (a) Coronal radiograph shows popcorn and amorphous calcifications (straight arrows) and scalloping (curved arrow). (b, c) Coronal T1-weighted images (600/20) were obtained (b) before and (c) after intravenous injection of gadopentetate dimeglumine. The lesion exhibits a low signal intensity and is restricted to the intraosseous compartment. In c, marked enhancement in a septal (straight arrow) and nodular (curved arrow) pattern is seen. (d) In the time-signal intensity diagram superimposed on a magnetization-prepared GRE image (15/6.8, 30° flip angle), the vertical axis represents signal intensity in arbitrary units and the horizontal axis represents time in seconds. The diagram shows the gradual progression of enhancement, seen only focally in the tumor (curve 2, type 2 curve in Fig 1). Curve 1 represents arterial enhancement, and curve 3 (type 3 curve in Fig 1), enhancement in reference tissue. The lesion was curetted, and phenol was applied in the cavity. The curetted material showed benign cartilaginous nodules. No fibrovascular septations were found. Histologic diagnosis was enchondroma.

View larger version (178K): [in this window] [in a new window]   Figure 3b. Painful left shoulder in a 46-year-old man. (a) Coronal radiograph shows popcorn and amorphous calcifications (straight arrows) and scalloping (curved arrow). (b, c) Coronal T1-weighted images (600/20) were obtained (b) before and (c) after intravenous injection of gadopentetate dimeglumine. The lesion exhibits a low signal intensity and is restricted to the intraosseous compartment. In c, marked enhancement in a septal (straight arrow) and nodular (curved arrow) pattern is seen. (d) In the time-signal intensity diagram superimposed on a magnetization-prepared GRE image (15/6.8, 30° flip angle), the vertical axis represents signal intensity in arbitrary units and the horizontal axis represents time in seconds. The diagram shows the gradual progression of enhancement, seen only focally in the tumor (curve 2, type 2 curve in Fig 1). Curve 1 represents arterial enhancement, and curve 3 (type 3 curve in Fig 1), enhancement in reference tissue. The lesion was curetted, and phenol was applied in the cavity. The curetted material showed benign cartilaginous nodules. No fibrovascular septations were found. Histologic diagnosis was enchondroma.

View larger version (123K): [in this window] [in a new window]   Figure 3c. Painful left shoulder in a 46-year-old man. (a) Coronal radiograph shows popcorn and amorphous calcifications (straight arrows) and scalloping (curved arrow). (b, c) Coronal T1-weighted images (600/20) were obtained (b) before and (c) after intravenous injection of gadopentetate dimeglumine. The lesion exhibits a low signal intensity and is restricted to the intraosseous compartment. In c, marked enhancement in a septal (straight arrow) and nodular (curved arrow) pattern is seen. (d) In the time-signal intensity diagram superimposed on a magnetization-prepared GRE image (15/6.8, 30° flip angle), the vertical axis represents signal intensity in arbitrary units and the horizontal axis represents time in seconds. The diagram shows the gradual progression of enhancement, seen only focally in the tumor (curve 2, type 2 curve in Fig 1). Curve 1 represents arterial enhancement, and curve 3 (type 3 curve in Fig 1), enhancement in reference tissue. The lesion was curetted, and phenol was applied in the cavity. The curetted material showed benign cartilaginous nodules. No fibrovascular septations were found. Histologic diagnosis was enchondroma.

View larger version (145K): [in this window] [in a new window]   Figure 3d. Painful left shoulder in a 46-year-old man. (a) Coronal radiograph shows popcorn and amorphous calcifications (straight arrows) and scalloping (curved arrow). (b, c) Coronal T1-weighted images (600/20) were obtained (b) before and (c) after intravenous injection of gadopentetate dimeglumine. The lesion exhibits a low signal intensity and is restricted to the intraosseous compartment. In c, marked enhancement in a septal (straight arrow) and nodular (curved arrow) pattern is seen. (d) In the time-signal intensity diagram superimposed on a magnetization-prepared GRE image (15/6.8, 30° flip angle), the vertical axis represents signal intensity in arbitrary units and the horizontal axis represents time in seconds. The diagram shows the gradual progression of enhancement, seen only focally in the tumor (curve 2, type 2 curve in Fig 1). Curve 1 represents arterial enhancement, and curve 3 (type 3 curve in Fig 1), enhancement in reference tissue. The lesion was curetted, and phenol was applied in the cavity. The curetted material showed benign cartilaginous nodules. No fibrovascular septations were found. Histologic diagnosis was enchondroma.

View larger version (145K): [in this window] [in a new window]   Figure 4a. Painful lump in the right calf in a 49-year-old man. (a) Sagittal radiograph displays the characteristics of an osteochondroma (straight arrows) of the tibia. Osteolysis (curved arrow) is seen in the cranial portion. (b) Transverse T1-weighted nonenhanced image (600/20) shows the lesion, with high signal intensity of the fatty marrow and intermediate signal intensity centrally (straight arrow) and peripherally (curved arrow). (c) Transverse T1-weighted image (600/20) obtained after intravenous injection of gadopentetate dimeglumine shows some nodular enhancement (arrows). (d) Time-signal intensity diagram is superimposed on a subtraction magnetization-prepared GRE image (15/6.8, 30° flip angle) acquired at a different transverse level from that in c. The vertical axis represents signal intensity in arbitrary units, and the horizontal axis represents time in seconds. The region of interest is plotted in the region with the earliest enhancing lesional tissue (12 seconds after arterial enhancement). Gradual progression of enhancement is seen (curve 2, type 2 curve in Fig 1). Curve 1 represents arterial enhancement, and curve 3 (type 3 curve in Fig 1) represents enhancement of reference tissue. The corresponding resected specimen (not shown) revealed the characteristics of an osteochondroma, with some cellular cartilage nodules but without malignant transformation.

View larger version (151K): [in this window] [in a new window]   Figure 4b. Painful lump in the right calf in a 49-year-old man. (a) Sagittal radiograph displays the characteristics of an osteochondroma (straight arrows) of the tibia. Osteolysis (curved arrow) is seen in the cranial portion. (b) Transverse T1-weighted nonenhanced image (600/20) shows the lesion, with high signal intensity of the fatty marrow and intermediate signal intensity centrally (straight arrow) and peripherally (curved arrow). (c) Transverse T1-weighted image (600/20) obtained after intravenous injection of gadopentetate dimeglumine shows some nodular enhancement (arrows). (d) Time-signal intensity diagram is superimposed on a subtraction magnetization-prepared GRE image (15/6.8, 30° flip angle) acquired at a different transverse level from that in c. The vertical axis represents signal intensity in arbitrary units, and the horizontal axis represents time in seconds. The region of interest is plotted in the region with the earliest enhancing lesional tissue (12 seconds after arterial enhancement). Gradual progression of enhancement is seen (curve 2, type 2 curve in Fig 1). Curve 1 represents arterial enhancement, and curve 3 (type 3 curve in Fig 1) represents enhancement of reference tissue. The corresponding resected specimen (not shown) revealed the characteristics of an osteochondroma, with some cellular cartilage nodules but without malignant transformation.

View larger version (153K): [in this window] [in a new window]   Figure 4c. Painful lump in the right calf in a 49-year-old man. (a) Sagittal radiograph displays the characteristics of an osteochondroma (straight arrows) of the tibia. Osteolysis (curved arrow) is seen in the cranial portion. (b) Transverse T1-weighted nonenhanced image (600/20) shows the lesion, with high signal intensity of the fatty marrow and intermediate signal intensity centrally (straight arrow) and peripherally (curved arrow). (c) Transverse T1-weighted image (600/20) obtained after intravenous injection of gadopentetate dimeglumine shows some nodular enhancement (arrows). (d) Time-signal intensity diagram is superimposed on a subtraction magnetization-prepared GRE image (15/6.8, 30° flip angle) acquired at a different transverse level from that in c. The vertical axis represents signal intensity in arbitrary units, and the horizontal axis represents time in seconds. The region of interest is plotted in the region with the earliest enhancing lesional tissue (12 seconds after arterial enhancement). Gradual progression of enhancement is seen (curve 2, type 2 curve in Fig 1). Curve 1 represents arterial enhancement, and curve 3 (type 3 curve in Fig 1) represents enhancement of reference tissue. The corresponding resected specimen (not shown) revealed the characteristics of an osteochondroma, with some cellular cartilage nodules but without malignant transformation.

View larger version (96K): [in this window] [in a new window]   Figure 4d. Painful lump in the right calf in a 49-year-old man. (a) Sagittal radiograph displays the characteristics of an osteochondroma (straight arrows) of the tibia. Osteolysis (curved arrow) is seen in the cranial portion. (b) Transverse T1-weighted nonenhanced image (600/20) shows the lesion, with high signal intensity of the fatty marrow and intermediate signal intensity centrally (straight arrow) and peripherally (curved arrow). (c) Transverse T1-weighted image (600/20) obtained after intravenous injection of gadopentetate dimeglumine shows some nodular enhancement (arrows). (d) Time-signal intensity diagram is superimposed on a subtraction magnetization-prepared GRE image (15/6.8, 30° flip angle) acquired at a different transverse level from that in c. The vertical axis represents signal intensity in arbitrary units, and the horizontal axis represents time in seconds. The region of interest is plotted in the region with the earliest enhancing lesional tissue (12 seconds after arterial enhancement). Gradual progression of enhancement is seen (curve 2, type 2 curve in Fig 1). Curve 1 represents arterial enhancement, and curve 3 (type 3 curve in Fig 1) represents enhancement of reference tissue. The corresponding resected specimen (not shown) revealed the characteristics of an osteochondroma, with some cellular cartilage nodules but without malignant transformation.

Progression of enhancement.—No statistically significant correlation was found between differences in progression of enhancement and benign or malignant tumor (P = .014). An exponential enhancement curve was seen in 11 chondrosarcomas and in one osteochondroma (Table 1, Fig 2). This one exponentially enhancing osteochondroma was located on the scapula in a 4-year-old boy. Sensitivity for detection of malignancy was 61%, specificity 95%, positive predictive value 92%, and negative predictive value 72%. A gradual enhancement curve was seen in three of eight (38%) enchondromas (Fig 3), in five of 11 (45%) osteochondromas, and in seven of 18 (39%) chondrosarcomas (Table 1).

Start and progression of enhancement combined.—A statistically significant correlation was found between differences in the combination of the start and progression of enhancement and benign or malignant tumor (P < .001). Early and exponential enhancement was seen in 11 of 18 chondrosarcomas and in one osteochondroma (Fig 2). In 18 of 19 benign tumors, no early exponential enhancement was seen. Thus, sensitivity for detection of malignancy was 61%, specificity 95%, positive predictive value 92%, and negative predictive value 72% (Table 2).

Morphologic Pattern of Enhancement Correlated with Histologic Findings
No statistically significant correlation was found between differences in morphologic enhancement patterns and benign or malignant tumor (P = .023). Eventually, all 18 chondrosarcomas displayed a late septal and nodular enhancement pattern on the SE images. In addition, components with homogeneous enhancement were seen in the two grade III chondrosarcomas. In the 16 resected and two curetted chondrosarcomas, fibrovascular tumoral stroma in between cartilaginous nodules was found to correlate with the enchancing septa on the morphologic equilibrium images. The enhanced septa depicted on the SE MR images were thicker than the fibrovascular septations. The nodular enhancement, which was always seen in combination with enhancing septa, corresponded to cartilaginous nodules of varying cellularity. The homogeneous enhancing parts found in two chondrosarcomas corresponded to vascular tumor tissue with high cellularity without prominent chondroid matrix formation. These areas had progressed histologically toward grade III chondrosarcoma, which was the definite diagnosis. No lobular morphology could be recognized in these homogeneously enhancing components.

On the SE images, six of 11 osteochondromas showed only a peripheral enhancement, and the other five showed a septal and nodular pattern (Fig 4). The peripherally enhancing outer rim, seen in six patients, represented reactive tissue that covered the nonenhancing hyaline cartilage. In two of these patients, the walls of bursae also enhanced (delayed). The early enhancement observed in three young patients with osteochondroma represented the reactive tissue mentioned previously.

In five osteochondromas with septal and nodular enhancement, cartilaginous islands with secondary calcification and transition into woven bone were found. No fibrovascular stroma was seen surrounding this cartilage. The reactive tissue that covered the cartilaginous cap also enhanced in this pattern.

Seven of the eight enchondromas showed a septal and nodular enhancement pattern on the SE images. One enchondroma did not show any enhancement. The one enchondroma that was curetted showed a delayed gradual enhancement and a septal and nodular morphologic pattern (Fig 3). Multinodular cartilage was found in the curettage material. No fibrovascular tumoral stroma was seen within the lesion. The nodules were separated by preexisting bone marrow. The biopsy specimens from seven enchondromas displayed histologic findings identical to those seen in the one curetted enchondroma.

	DISCUSSION

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
In our patient population, the combination of early and exponential enhancement correlated significantly with malignant cartilaginous tumor (P < .001). This combination was found to be a predictor of chondrosarcoma with few false-positive findings (specificity 95%, positive predictive value 92%). All false-positive findings were seen in young patients with unfused growth plates. When only adult patients were included, a specificity and positive predictive value of 100% were reached. Because of the substantial number of false-negative findings, this combination of parameters cannot be used to exclude malignancy (sensitivity 61%, negative predictive value 72%). In our patients, only the absence of early or delayed enhancement excluded malignancy (sensitivity and negative predictive value of 100%). Unfortunately, only 45% of osteochondromas and 63% of enchondromas did not enhance on the fast GRE MR images.

When only early enhancement (10 seconds) was used as the differentiating parameter, malignancy was unlikely, with a sensitivity and negative predictive value of almost 90%, whereas the number of false-positive diagnoses of malignancy (specificity and positive predictive value 84%) is still limited. Early enhancement as the only parameter correlated significantly with malignant cartilaginous tumor (P < .001). Enhancement characteristics are influenced by age of the patient, as well as temporal resolution at MR imaging and defined cutoff values. These findings can be explained on the basis of histopathologic correlation.

All chondrosarcomas showed early or delayed enhancement. The enhancing septa on the equilibrium SE images correlated histologically with tumoral neovascularization. Although more than half of the enchondromas did not show early or delayed (within 2 minutes) enhancement, seven of eight enchondromas eventually showed a septal and nodular morphologic enhancement pattern in the equilibrium phase. A similar observation was made in the osteochondromas. Almost half of these lesions did not show early or delayed enhancement, and all 11 osteochondromas displayed peripheral or septal and nodular enhancement in the equilibrium phase. The early enhancement observed in chondrosarcomas is probably the result of tumoral neovascularization which, according to the Folkman hypothesis (30), turns these tumors from a predominantly diffusion-dependent into a predominantly perfusion-dependent metabolism. Diffusion predominantly determines late enhancement patterns in benign and malignant cartilaginous tumors.

Variations in timing of imaging as reported in various studies, might explain the differences in enhancement patterns observed in benign and malignant cartilaginous tumors (17–19,31–33). When equilibrium contrast-enhanced SE MR images were obtained a few minutes after intravenous administration of gadopentetate dimeglumine, a similar septal and nodular enhancement pattern was often seen in enchondroma, osteochondroma, and well-differentiated chondrosarcoma. In earlier studies of contrast-enhanced MR imaging with time–signal intensity curves (34), differences in slope of enhancement could not be used to differentiate between enchondromas and central low-grade chondrosarcomas, probably because of insufficient temporal resolution. In a more recent large study comprising 100 patients with a large variety of bone and soft-tissue lesions including seven enchondromas, four osteochondromas, and two chondrosarcomas, differences in slopes of enhancement could be detected between benign and malignant cartilaginous tumors (22). Correlation with histopathologic findings was lacking in 42% of the benign lesions, however, and fast contrast-enhanced MR images were acquired of only one section in each patient.

The hypothesis of perfusion- and diffusion-dependent enhancement can also explain why the enhancing septa seen in chondrosarcomas are thicker than the fibrovascular septa found at histologic examination. Diffusion of contrast material takes place in an early phase as a result of tumoral neovascularization and with a higher permeability than occurs in the benign lesions, which allows both the fibrovascular septa and surrounding tissue to enhance. In osteochondromas with bursa formation, reactive neovascularity is seen histologically in the wall of the bursa. This is an acceptable substrate for the delayed gradual enhancement seen in two of our patients with osteochondroma.

Early enhancement of osteochondroma in young patients is an important finding. In patients with unfused growth plates, the presence of numerous physiologic physeal vessels can explain the early enhancement seen in these patients (35).

Fortunately, the incidence of (secondary) chondrosarcoma in young patients is extremely rare (8,13,26). On the other hand, two of our fairly young patients (aged 17 and 33 years) had central grade I chondrosarcoma that displayed early enhancement, whereas the radiographs and biopsy specimens did not raise the suspicion of chondrosarcoma. Early enhancement in patients in the first and second decade is not a reliable sign of malignancy in cases of osteochondroma but might be in cases of central cartilaginous tumor.

Differentiation of benign from low-grade malignant cartilaginous tumors is one of the most difficult tasks in bone tumor pathology (9,11,12,23,27). Tumor heterogeneity is a recognized cause of sampling error. Optimal tissue sampling of cartilaginous tumors is required to obviate mutilating surgery or worsening of prognosis (11,12,36–39). On the other hand, biopsy procedures are sources of local tumor spread and may be the initiator of active tumor behavior of a previously inert lesion (13,37–40). There are some indications that MR has the potential to assist in the acquisition of representative tissue samples. It has been shown that tissue characterization in cartilaginous tumors is increased with gadolinium-enhanced MR imaging (17,33,41). Fast contrast-enhanced MR imaging may also be of value. It may be possible to guide the biopsy needle to early- and exponentially enhancing areas with fast contrast-enhanced MR imaging (22).

There are several disadvantages of this study. The number of patients in this study is fairly small. This is caused by the low incidence of cartilaginous tumors in general and by the inclusion criteria, especially the long follow-up of enchondromas. Because seven of eight enchondromas enhanced on the equilibrium images, it is unlikely that this skews the results. Also, a significance level less than .01 instead of less than .05 was chosen to allow reliable conclusions. Another disadvantage is the subjective method of choosing enhancing areas; therefore, the dynamic curves are operator dependent. Improved software that can process multisection parametric images and allow assessment of large tumor volumes will increase the reproducibility of dynamic curves. Also, the manual injection of gadopentetate dimeglumine can be seen as an operator-dependent variable. This is, however, not likely to be important because we use the arterial curve as reference. Finally, the matching of findings on MR images to those in histologic macroslices is a qualitative time-consuming procedure that does not allow a perfect match to be made with histopathologic findings.

In conclusion, fast contrast-enhanced MR imaging has the potential to help differentiation between enchondroma, osteochondroma, and chondrosarcoma. In the adult patient, both early and exponential enhancement are predictors of malignancy. The specificity for diagnosis of chondrosarcoma is increased when a combination of early and exponential enhancement is found. In this study, absence of early or delayed enhancement excluded malignancy. If these findings can be confirmed in larger studies, the current indication for biopsy in the adult population may change. These preliminary results warrant further prospective analysis in a larger patient population.

	Acknowledgments

 
We thank Jo Hermans, PhD, and Berend C. Stoel, PhD, for statistical advice and the drawing of Figure 1.

	Footnotes

 
Abbreviations: GRE = gradient echo SE = spin echo

Author contributions: Guarantors of integrity of entire study, M.J.A.G., J.L.B.; study concepts, M.J.A.G., J.L.B., H.J.v.d.W.; study design, M.J.A.G., P.C.W.H., J.L.B., H.J.v.d.W.; definition of intellectual content, M.J.A.G., P.C.W.H., J.L.B.; literature research, M.J.A.G.; clinical studies, M.J.A.G., H.J.v.d.W., A.H.M.T.; data acquisition, M.J.A.G., H.J.v.d.W.; data analysis, M.J.A.G., J.L.B., H.J.v.d.W.; statistical analysis, M.J.A.G., J.L.B.; manuscript preparation, M.J.A.G., J.L.B., H.J.v.d.W.; manuscript editing, M.J.A.G., J.L.B.; manuscript review, all authors.

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