Mesenchymal chondrosarcoma of the orbit: imaging features of CT and MRI

Abstract

Objective:

Mesenchymal chondrosarcoma (MCS) of the orbit is a rare and aggressive form of chondrosarcoma. The purpose of this study was to retrospectively identify the imaging features of mesenchymal chondrosarcoma of the orbit.

Methods:

This study included five patients with histologically confirmed MCS of the orbit who had undergone either CT, MRI, or both. Images were evaluated for the following: location, size, margin, CT density and presence or absence of calcification and/or ossification, MRI findings including dynamic contrast-enhancement and time-intensity curves.

Results:

CT was performed in four of the five patients, and all four (100%) demonstrated calcification and ossification of the mass. MRI was performed in all five patients. In two patients (40%), the mass demonstrated areas of hyperintensity on T₁ weighted images.

Conclusion:

The presence of a well-defined, orbital mass with calcification and ossification on CT and, marked heterogenous enhancement and a rapid-washout pattern on dynamic MRI indicate a high probability of MCS of the orbit. In addition, MCS of the orbit can demonstrate areas of hyperintensity on T₁ weighted images, representing bone marrow fat tissue of ossification.

Advances in knowledge:

MCS of the orbit is a highly malignant tumor, and early diagnosis by imaging is important. Radiologists should be aware of the imaging features of MCS of the orbit.

Introduction

Mesenchymal chondrosarcoma (MCS) is a rare, high-grade malignancy characterized by undifferentiated mesenchymal cells with islands of mature hyaline cartilage. Bony MCS was first described by Lichtenstein and Bernstein in 1959.¹ Subsequently, Dowling reported extraskeletal MCS in 1964.² Extraskeletal MCS of the orbit is very rare, and is primarily described by case reports in the literature.³ Approximately 41 cases of MCS of the orbit have been reported since this entity was first described by Cardenas et al. in 1971.^1,3–24 Since MCS of the orbit is a well-defined tumor, it is important to distinguish it from benign orbital lesions such as cavernous hemangioma. Therefore, radiologists should be aware of the CT and MRI features of MCS. MCS of the orbit has been reported to show isointensity on T₁ weighted image (T₁WI) in comparison with grey matter in previous literature.^{3, 7,16} However, in present study, MCS may exhibit areas of hyperintensity on T₁WI. The characteristics of orbital tumor containing bone marrow fat tissue can also be useful information for diagnosis of this unusual and rare neoplasm.

Here, we describe the clinical and imaging characteristics of orbital MCS in five patients.

Methods and materials

Patients

This study was approved by the institutional review board of Seirei Hamamatsu General Hospital. Informed consent was waived due to the retrospective nature of the study. A search of the radiology database was performed to identify patients with orbital MCS at our hospital between July 2002 and February 2016. The search yielded five patients with histopathology-proven MCS. The patients consisted of three females and two males (mean age, 22.6 years; range, 9–39 years at diagnosis). All five patients underwent MRI, four patients underwent CT imaging. All five patients underwent surgical resection of MCS. Clinical presentations, physical and ophthalmological examinations, and histological diagnoses were extracted from the medical records.

CT technique

Orbital CT was performed in four of the five MCS patients. Images were obtained in the axial plane using a Lightspeed 16-section CT system (GE Healthcare, Milwaukee, WI) or a Discovery CT750 HD 64-section CT system (GE Healthcare, Milwaukee, WI). The imaging parameters were as follows: 120 kV voltage; 150 mA current; 512 × 512 matrix; and section thickness of 0.62 mm. All CT images were reconstructed using both a soft-tissue algorithm and a bone algorithm. All images were viewed in a soft-tissue window setting (window width of 300 HU at a window level 15 HU) and in a bone window setting (window width of 4000 HU at a window level of 1000 HU). Coronal and sagittal reformatted images were also viewed. No patient underwent a contrast-enhanced CT study.

For detection of metastases, chest and abdominal CT was performed in all the patients.

MRI technique

All five patients underwent orbital MRI prior to surgery. In four patients, MRI examinations were performed using a 1.5 T MRI system (Signa Excite and Signa HDxt, GE Healthcare, Milwaukee, WI) with a standard 8-channel head coil. In one patient, the MRI examination was performed using a 3.0 T MRI system (Discovery 750, GE Healthcare, Milwaukee, WI) with a 32-channel head coil. Fast spin echo pulse sequences were used in all patients. All patients underwent unenhanced T₁WI and T₂WI and post-enhanced T₁WI in the axial, coronal, and sagittal planes. Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) water–fat images in the coronal plane were obtained in Patient 4. The imaging parameters were as follows: T₁WI: 500–600 ms repetition time (TR), 7.2–12 ms echo time (TE); T₂WI: 2500–3200 ms TR, 80–83 ms TE; number of excitation, 2; section thickness, 3 mm; slice spacing, 3.5 mm; flip angle, 90–111° matrix 256 × 160; FOV, 140 × 140 mm. IDEAL waterfat images: 2500 ms TR, 83.2 ms TE; number of excitation, 6; section thickness, 3 mm; slice spacing, 3.5 mm; internal gap, 0.5 mm; flip angle, 90° matrix 256 × 160; FOV, 140 × 140 mm.

Gadopentetate dimeglumine (Magnevist; Bayer Schering Pharma, Berlin, Germany) was administered intravenously at a rate of 2.5 ml s⁻¹ (total dose, 0.1 mmol kg^–1 of body weight) using a power injector (Sonic shot 50; Nemoto kyorindo, Tokyo), followed by a 20 ml normal saline flush. Detailed parameters for the dynamic contrast enhanced (DCE)-MRI were as follows: DCE-MRI was performed in the coronal plane using three-dimensional fast spoiled gradient echo before conventional contrast-enhanced T₁WI in three of the five patients. The following imaging parameters were used: 4.799 ms TR; 1.89 ms TE; 1 number of excitations; 256 × 160 matrix; Flip angle, 12° 14 × 14 cm FOV; 2.0 mm section thickness; 1.0 mm slice spacing; and no intersection gap. For multiphase DCE images, precontrast phase images were obtained first. Arterial phases of 3 consecutive series (Arterial Phase 1–3) were obtained with software [an automated bolus detection algorithm (SmartPrep, GE Healthcare)] to detect the arrival of contrast medium to the carotid artery, and delayed phase images were obtained 180 s after injection of the contrast medium. Each set included 76 images and took 83 s to acquire. The entire dynamic series took 3 min 45 s in total.

Image analysis

All images were evaluated visually. Board-certified radiologists reviewed all CT, and MR images.

The DCE-MRI source images were transferred to a standard work station (AW workstation, GE Healthcare, Milwaukee, WI) for further analysis. To avoid inclusion of calcified and cystic areas in the measurement of signal intensity, one author manually outlined regions of interest. The size of each region of interest was approximately 3–4 mm in diameter. When the contrast enhancement was heterogeneous, the signal intensities of multiple areas were measured and the area with maximal enhancement was selected. To minimize the effect of partial volume averaging, the lesion edges were avoided during region of interest determination.

In addition to arrival time, time intensity curves (TICs) were obtained for each lesion and categorized into three patterns proposed in a previously reported MRI-based study of orbital masses.²⁵ The TICs patterns were categorized as follows: Type 1 curves had a persistent pattern (i.e. SIlasttime = SIpeaktime or SIlasttime ≥ SIpeaktime), Type 2 curves had a plateau pattern (i.e. SIpeaktime−SIlasttime ≤10% of SIpeaktime), and Type 3 curves had a washout pattern (i.e. SIpeaktime–SIlasttime >10% of SIpeaktime).

Results

The most common clinical symptoms were progressive proptosis (five of five patients, 100%), visual field defect (four of five patients, 80%), anorthopia (three patients, 60%), and decreased visual acuity (one of five patient, 20%). At the time of diagnosis, the average duration of symptoms was 4.6 months (range, 1–10 months).

Three MCS occurred in the right orbit and two in the left orbit. Four lesions were located in the retrobulbar intraconal space and one lesion extended from the intraconal to the extraconal space. The lesions appeared round, oval, or slightly lobular and had well-defined borders. The mean maximum diameter was 28.8 mm (range, 20–37 mm). The imaging characteristics are summarized in Table 1.

Table 1. .

Clinical and imaging findings in five patients with mesenchymal chondrosarcoma of the orbit

Patient no.	Age/ sex	Laterality/  location	Sizea (mm)	Therapy	Margin	Density on non-contrast CT scan/ calcification and/or ossification	Signal Intensity on MR Imagingb				Optic  nerve  involvement	HEY1- NCOA2gene  fusion
							T1WI/ hyperintense area	T2WI	Enhancement  Pattern /Degree	TIC  pattern
1	39 y/F	R/ From ICS to ECS	20	Evisceration, proton beam therapy, debulking surgery, radiation, streotactic radiotherapy	Well-defined	Isodense/yes	Isointense/no	Iso	Heterogenous/ marked	―	No	Positive
2	9 y/F	R/ ICS	29	Resection	Well-defined	­―	Isointense/no	Iso~hypointense	Heterogenous/ marked	Rapid-washout	No	Positive
3	18 y/F	L/ ICS	27	Resection	Well-defined	Isodense/yes	Isointense/yes	Iso~hypointense	Heterogenous/ marked	―	No	―
4	23 y/M	R/ ICS	31	Resection, chemotherapy  (VDC-IE)	Well-defined	Isodense/yes	Isointense/yes	Iso~hypointense	Heterogenous/ marked	Rapid-washout	No	Positive
5	24 y/M	L/ ICS	37	Evisceration, chemotherapy  (VDC-IE)	Well-defined	Isodense/yes	Isointense/no	Iso~hypointense	Heterogenous/ marked	Rapid-washout	No	Positive

ECS, extra conal space; ICS, intra conal space; T₁WI, T₁ weighted image; T₂WI, T₂ weighted image; VDC-IE, vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, etoposide.

^aSize was denoted as greatest diameter.

^bDensity and signal intensity of the tumor were compared with the cerebral grey matter.

Four out of five patients underwent CT imaging. On unenhanced CT, the lesions appeared inhomogeneously isodense to the grey matter, with various arc or amorphous calcifications (Figures 1 and 2) or foci of secondary ossifications (Figures 3 and 4). We observed no local bony remodeling or erosion of the orbital walls at the initial orbital CT scan.

Figure 1.

Patient number 1. Mesenchymal chondrosarcoma of the right orbit in a 39-year-old female. She underwent initial orbital exenteration and was histologically diagnosed with mesenchymal chondrosaroma. This is the image when the tumor recurred 3 years after the initial orbital exenteration. (a) Axial CT demonstrated a soft tissue mass with calcification in the right orbit. (b) Axial T₁WI showing an oval tumor with isointense-signal. (c) Coronal fat saturated T₂WI showing that the tumor is low to isointense relative to the grey matter. (d) Diffusion-weighted image showing that the tumor is hyperintense. (e) Enhanced axial T₁WI demonstrating a tumor with heterogeneous enhancement with intracranial infiltration. T₁WI, T₁ weighted image; T₂WI, T₂ weighted image.

Figure 2. .

Patient number 5. Mesenchymal chondrosarcoma of the left orbit in a 24-year-old male. (a) Axial CT image showing an oval isodense tumor with dense calcification. (b) Axial T₁WI showing an oval tumor with an isointense-signal. (c) Axial T₂ weighted image showing that the tumor is low to isointense relative to the grey matter. Coronal pre-contrast (d), and dynamic contrast-enhanced arterial phase (e) T₁WI demonstrating marked and heterogeneous enhancement of the tumor. T₁WI, T₁ weighted image.

Figure 3.

Patient number 3. Mesenchymal chondrosarcoma of the left orbit in an 18-year-old female. (a) Axial CT image showing an oval isodense tumor with ossification. (b) Axial T₁WI demonstrating areas of hyperintensity within the tumor (arrow). (c) Axial T₂WI showing hyperintensity in the tumor (arrow). (d) Axial fat-suppressed T₂WI demonstrating that the tumor is low to isointense relative to the grey matter. Note that the fat signal that showed hyperintense on T₂WI is saturated by fat-suppressed T₂WI (arrow). (e) Post-contrast axial T₁WI showing heterogeneous tumor enhancement. T₁WI, T₁ weighted image; T₂WI, T₂ weighted image.

Figure 4.

Patient number 4. Mesenchymal chondrosarcoma of the right orbit in a 23-year-old male. (a) Axial CT image showing an oval isodense tumor with ossification. The fat attenuation is inside the ossification (arrow). (b) Coronal T₁WI demonstrating areas of hyperintensity within the tumor (arrow). (c) Coronal IDEAL fat image demonstrating fat tissue within the tumor (arrow). Coronal pre-contrast (d), dynamic contrast-enhanced arterial Phase 1 (e), arterial Phase 2 (f), arterial Phase 3 (g), and delay (h) enhanced T₁WI showing heterogeneous tumor enhancement. T₁WI, T₁ weighted image; T₂WI, T₂ weighted image.

Chest and abdominal CT revealed no metastasis.

All patients underwent MRI (Figures 1–5). All five MCS appeared isointense to the grey matter on T₁WI. The lesions were heterogeneously isointense to hypointense relative to the grey matter on T₂WI. These low signal intensity foci on T₂WI appeared to correspond to calcifications on the CT images. Two lesions contained areas of hyperintensity on T₁WI. In Patient 3, hyperintense regions on T₁WI were recognized as hyperintense regions on fast spin echo T₂WI, which decreased the signal intensity on fat-suppressed T₂WI. In Patient 4, areas of hyperintensity on T₁WI showed signals that were equal to fat tissue for IDEAL fat images. These were thought to be bone marrow fat tissue within the ossification.

Figure 5. .

Patient number 2. Mesenchymal chondrosarcoma of the right orbit in a 9-year-old girl. (a) Axial T₁WI showing that an oval tumor in her right orbit is isointense compared to the grey matter. (b, c) Coronal and sagittal T₂WI demonstrating that the tumor is low to isointense relative to the grey matter. Coronal pre-contrast (d), coronal dynamic contrast-enhanced arterial Phase 1 (e), and axial delay enhanced T₁WI (f) showing heterogeneous enhancement. T₁WI, T₁ weighted image; T₂WI, T₂ weighted image.

The lesions clearly demonstrated heterogeneous enhancement on conventional contrast-enhanced T₁WI. The TICs) of three patients (patients 2, 4, and 5) showed a rapid enhancement and rapid washout pattern (curve Type 3) (Figure 6).

Figure 6.

The time intensity curves reveal rapid enhancement and early washout of contrast medium within the tumor. MCS, mesenchymal chondrosarcoma.

Microscopically, all tumors had a bimorphic pattern and were composed of undifferentiated, small mesenchymal cells and well-differentiated cartilaginous foci. The mesenchymal cells appeared small, round to spindle-shaped, with hyperchromatic nuclei and scanty cytoplasm, and occurred in sheets. In Patient 2, mesenchymal cells surrounded vascular spaces in a hemangioperycytoma-like manner. Multiple calcifications and ossification within the cartilaginous central zone were present in all patients. In patients 3 and 4, bone marrow fat tissue within the ossification in the tumor were observed. In patients 1, 2, and 5, obvious bone marrow fat tissues were not present. The presence or absence of calcification, ossification, and fat tissue with in each case are summarized in Table 2.

Table 2. .

Histopathological findings

Patient no.	Calcification	Ossification	Fat tissue
1	+	+	−
2	+	+	−
3	+	+	+
4	+	+	+
5	+	+	−

In Patient 5, the tumor infiltrated the sclera of the eye ball. In patients 1–4, there was no lesion that had infiltrated the optic nerve, the surrounding extraocular muscles, and orbital structures pathologically.

On immunohistochemical analysis, the chondroid areas stained positive for S-100 protein and vimentin and stained negative for epithelial membrane antigen. In contrast, the small cells stained positive for vimentin and negative for S-100 and epithelial membrane antigen. These findings are consistent with a diagnosis of MCS.

Recently, a genetic mutation has been detected in MCS, a gene fusion between hairy/enhancer-of-split related with YRPW motif 1 and the nuclear receptor coactivator 2 (HEY1-NCOA2).²² Based on the recent report,²² we identified the HEY1-NCOA2 fusion gene with fluorescence in situ hybridization in four of the five patients. One patient could not be examined due to decalcification of the specimen.

Patients 1 and 5 underwent evisceration, while patients 2, 3, and 4 underwent surgical resection. In accordance with the Ewing sarcoma/primitive neuroectodermal tumor regimen, patients 4 and 5 received adjuvant chemotherapy with VDC/IE alternating therapy (vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide). Patient 1 had a tumor recurrence 3 years after the initial surgery. The recurrent tumor was treated with proton beam therapy 50 GyE, debulking surgery, radiation therapy 41.4 Gy, and stereotactic radiotherapy 41.4 Gy.

Patient 1 died 12 years after the initial diagnosis due to intracranial infiltration of the recurrent orbital tumor (details are unknown because Patient 1 was transferred to another hospital for palliative care).

After the operation, patients 2, 3, 4 and 5 did not show recurrence for 56 months, 44 months, 36 months and 37 months, respectively, and they are alive at the time of writing this report.

Discussion

MCS is a rare, highly aggressive type of chondrosarcoma that has a tendency for local recurrence and distant metastasis. Extraskeletal MCS is less common, accounting for approximately 30% of all MCSs.^{17, 19,23} Involvement of the orbit is rare.^{17, 20} The orbit is the third most common MCS location, following the meninges and the lower extremities.^{8, 9} MCS tends to develop in young patients in their second or third decades of life, with a female predominance.^{14, 19,21} The age at presentation ranges from 9 to 39 years, although there are some reports in congenital¹¹ or middle-aged patients,^{18, 19} with most cases occur between 10 and 30 years of age.^{11, 14} MCS of the orbit mainly affects female patients,¹¹ and our study, which included three females and two males, supports this finding.

Clinically, MCS causes compression of the eyeball resulting in progressive proptosis and visual abnormalities,^19–21 including gradually decreasing visual acuity and anorthopia. In the present study, all patients had progressive proptosis.

MCS of the orbit is usually located in the intraconal space and characteristically appears as a well-defined mass.^{3,7,8,11–16,24} In the present study, MCS appeared as well-defined masses on CT imaging. MCS attenuation has been shown to be isodense relative to the cerebral grey matter.⁵ Similar to previous reports,^{3, 14} we observed calcification and ossification of the orbital mass in all patients for whom CT imaging was available (4/4;100%). Because the lesion is usually well-defined, it is easily confused with benign tumors of the orbit. Therefore, the presence of calcification or ossification inside the tumor is of crucial importance to the diagnosis of MCS.

Shinaver first reported the MRI features of orbital MCS.⁷ The non-calcified MCS components usually demonstrate low-to-intermediate signal intensity compared to grey matter on T₁WI, and are typically isointense on T₂WI.^{7–9,11,12,16} We observed that the MCS of the orbit in our cases were isointense on T₁WI with heterogeneous low to isointensity on T₂WI. The calcified components of the MCS display low signal intensity on both T₁WI and T₂WI. In patients 3 and 4, the MCS demonstrated areas of hyperintensity on the T₁WI. This finding has not been previously reported and, based on histopathological analysis, represents bone marrow fat tissue within the ossification. In terms of pathologically, there are reports in past literature that the cartilage constitution of MCS becomes a secondary foci of ossification depending on the degree of maturity.^5–7,12,23 In this study, ossification was confirmed microscopically in MCS by identifying osteocytes and the presence of bone marrow fat tissue was confirmed when osteocytes and fat tissue coexisted in an area. In the case of patients 3 and 4, a calcified area including the fat tissue, which was demonstrated on images was recognized as ossification. However, it might be difficult for CT or MRI to distinguish ossification from calcification without detectable fat tissue within the calcified area. Therefore, in this study, this phenomenon is described as ossification, and it is distinguished from calcification.

MCS often show prominent, heterogeneous enhancement on contrast-enhanced MRI.^{7, 19} DCE-MRI allows in vivo imaging of the microcirculation, providing critical information about the vasculature. For example, a TIC based on DCE-MRI data may provide valuable information to differentiate benign from malignant lesions.^{3, 25} The TICs of three patients (patients 2, 4, and 5) in the present study showed a rapid enhancement and rapid-washout pattern (curve Type 3). MCS tends to be a highly malignant tumor and is therefore, typically hypervascular with increased perfusion. The results of this study are consistent with prior reports.³

There are several reports on the ¹⁸F-fludeoxyglucose (FDG) PET/CT findings in extraskeletal MCS. As with the MCS of the heart, spleen, and spine,^26–28 the MCS of the orbit also shows high FDG uptake.²⁹ MCS is a high grade variant of chondrosarcoma, and the results showing high FDG uptake in the orbital lesion are consistent.

The presence of calcification within the MCS tumor, as detected by CT imaging, is the key to an imaging diagnosis. As such, CT should be the first imaging technique used to determine the presence of calcifications. MRI is useful to determine the position of the orbital MCS and to identify areas of infiltration and the relationship of the tumor to adjacent structures.

The differential diagnosis of MCS of the orbit includes cavernous malformation, hemangiopericytoma, meningioma, orbital amyloidosis, and metastasis.^{7, 9,11} In adults, cavernous malformation is the most common vasculogenic tumor of the orbit. These lesions appear as well-circumscribed, homogenous, ovoid masses and are more often located in the intraconal space of the orbit, rather than the extraconal space. Calcification is extremely rare in cavernous malformations.³⁰ The lesions demonstrate hyperintense signals on T₂WI and delayed enhancement on DCE-MRI.²⁵ Hemangiopericytomas arise in the extraconal space of the orbit more often than in the intraconal space. These lesions generally have no calcifications. On CT and MRI, they appear as well-circumscribed masses with aggressive features that include infiltrative borders and osseous erosion, and marked arterial phase enhancement with rapid washout.³⁰ Orbital ectopic meningioma is less common and tends to appear as homogeneously isointense, with marked homogeneous enhancement after the administration of contrast medium. Orbital amyloidosis is rare and typically appears as an isodense mass associated with thickening and irregularity of the adjacent bone, with diffusely scattered coarse, streaky, and amorphous calcification within the lesion on CT images. These lesions tend to have a lower signal intensity on T₂WI.^{7, 8} Orbital metastases from other cancers constitute 1–13% of orbital tumors. Orbital metastases tend to demonstrate infiltrative growth. Clinical symptoms generally manifest rapidly, with progression occurring over weeks to months.³¹

Complete resection of the tumor is currently the only treatment for MCS. Adjuvant VDC/IE alternation chemotherapy may be undertaken according to the Ewing sarcoma/primitive neuroectodermal tumor regimen, but a standard treatment protocol has not been established. Patient 1 was treated with proton beam therapy, radiotherapy, and stereotactic radiotherapy, but local control of the recurrent tumor could not be achieved. In orbital MCS, symptoms tend to appear at an early stage, and long-term survival can be expected if the tumor is completely resected. Thus, early diagnosis on the basis of imaging plays an important role in the MCS treatment strategy.

Our study has several strengths. First, we identified the HEY1-NCOA2 gene fusion in four of five patients. Second, despite this being a single-institution study, the number of MCS patients was relatively high compared to previously published case reports.

Our study also had several limitations. First, the study was retrospective with a small sample size, which is typical for most reports of this rare malignancy. Second, the images were not obtained in exactly the same manner or under the same conditions.

Conclusions

In conclusion, the presence of a well-defined, orbital mass with calcification and ossification on CT and, marked heterogenous enhancement and a rapid-washout pattern on dynamic MRI indicate a high probability of MCS of the orbit. In addition, MCS of the orbit can demonstrate areas of hyperintensity on T1WI, representing bone marrow fat of ossification.