Value of diffusion-weighted magnetic resonance imaging (DWI) in differentiating orbital lymphoma from idiopathic orbital inflammatory pseudotumor
Egyptian Journal of Radiology and Nuclear Medicine volume 53, Article number: 235 (2022)
Diffusion-weighted MR imaging can provide physiological information complementing morphological findings from conventional MRI. It detects early tissue changes associated with changes in water content, such as changes in the permeability of cell membranes, cell swelling or cell lysis. Areas of diseased tissue are highlighted with increased signal intensity on diffusion-weighted MR imaging. A decrease in the ADC is expected with increased intracellular tissue caused by either cell swelling or increased cellular density. DWI can be performed without the need for the administration of exogenous contrast medium, so it may of use when contrast administration is contraindicated. It yields quantitative and qualitative information that reflects changes at the cellular level and indicates the integrity of cell membranes. The purpose of this study was mainly to assess the diagnostic value of DWI for the discrimination of orbital lymphoma from idiopathic orbital inflammatory pseudotumor.
Of our 53 cases presented with proptosis or visual disturbances, 32 cases (60.4%) had found to be present with idiopathic orbital inflammatory pseudotumor and 21 cases (39.6%) had orbital lymphoma. On conventional MR imaging, ill-defined tumor margin and orbital preseptal space involvement had a significant association with orbital lymphoma, whereas intense post-contrast enhancement of lesion and radiologic evidence of sinusitis were associated with orbital inflammatory pseudotumor. The mean ADC value of orbital lymphoma was significantly lower than those of benign inflammatory pseudotumor, yielding 100% sensitivity, 99% specificity, and 90.5% accuracy for differentiating both entities.
Diffusion-weighted MR imaging (DWI) is valuable in discriminating orbital inflammatory pseudotumor from malignant orbital lymphoma that help patients to initial management.
Idiopathic orbital inflammatory pseudotumor (IOIP) and orbital lymphoma constitute the most frequent orbital lymphoproliferative diseases [1, 2]. IOIP is an inflammatory “non-infectious” disorder of the orbit soft tissue, which usually displays indefinite morphological features . Most orbital lymphomas are primary, low-grade, B-cell, non-Hodgkin lymphomas, and the frequent subtype is mucosa-associated lymphoid tissue (MALT) .
Lymphoma is responsive to low-dose radiotherapy with concurrent chemotherapy for only high-grade or diffuse lesions, while inflammatory pseudotumor shows a good response to corticosteroid therapy [2, 3]. Therefore, the differentiation of lymphoma and IOIP is crucial for therapeutic management. However, diffuse types of IOIPs and dacryoadenitis are misinterpreted as orbital lymphoma because of alike both clinical and imaging features [5, 6]. Even as fine-needle aspiration cytology (FNAC) is the gold differentiating method, it is likely restricted in technically challenge in the far posterior orbit lesions .
Previous published studies displayed MRI appearance, such as signal changes on T2 WI, presence of flow void sign and degree of post-contrast enhancement in differentiating IOIP from lymphoma [8, 9]. However, overall diagnostic value of the morphological MRI features was still restricted and may be observer-dependent during the qualitative assessment .
Recently, some researchers have reported the use of diffusion-weighted imaging (DWI), with the apparent diffusion coefficient (ADC) measurements to be effective in distinguishing orbital inflammatory pseudotumor from orbital lymphoma . Orbital lymphoma exhibited lower mean ADC value than IOIP, yet mean ADC overlap still obtained with some controlled clinical findings. Moreover, the mean ADC value was manually got from drawing regions of interest (ROI), with possible measurement of sampling error and subjective bias [12, 13].
The focus of this study was to assess the combined value of conventional MR imaging and DWI/ADC map in discriminating orbital lymphoma from IOIP.
Search strategy and MR imaging
This retrospective study is based on cases with clinical suspicion of non-osseous orbital space occupying lesions. After obtaining the approval of local ethics committee, the included cases were subjected to MRI orbital study using a 1.5 Tesla MR scanner (Siemens, Magnetom Avanto, 32 channels). The head coil was used as a receiver coil. Written informed consent from patients was waived with keeping the confidentiality of medical reports.
All studied cases were subjected to complete history taking, complete ophthalmological checkup and MR scanning of the orbit. MR protocol for orbital lesions included pre-contrast series, post-contrast series and diffusion-weighted MR imaging (DWI) with the involved sequences as following: axial T1-weigthed images (TR/TE, 620/9 ms), coronal T2-weighted images (TR/TE, 4000/108 ms), axial fat-saturated T2-weighted images (TR/TE, 4000/75 ms), as well as axial, coronal and sagittal contrast-enhanced fat-saturated T1-weighted images (TR/TE, 550/9 ms). The contrast material used was Gadolinium diethylene triamine pentacetic acid (Gad-DTPA) that injected manually or as single bolus via an injector with a standard 0.1 mmol/kg dose. There were no reactions to contrast material injection in our study.
Before contrast administration, the diffusion-weighted images were obtained in the axial plane by using a single-shot echo-planar and RESOLVE sequences with the sensitivity encoding technique. DW images were generated by using the three orthogonal axis images. The used parameters were TR/TE, 4000/100 ms; section thickness, 3 mm; flip angle (FA), 90°; field of view (FOV), 200 × 200 mm; matrix, 384 × 384 and b values 0, 500 and 1000 mm2/s. Diffusion-weighted images were processed to generate trace apparent diffusion coefficient (ADC) maps for the whole patients. ADC values were measured in n × 10–3 mm2/s. Complementary non-contrast CT scanning was done when needed using MDCT 128 scanner "Aquilion 128 Toshiba Medial system, Japan."
All MR images were reviewed independently by two radiologists, with 7 and 10 years of experience, who were blinded to the clinical data as well as the histopathological findings. Concurrence between the two readers was obtained by an auxiliary reading session.
The following data were assessed regarding the lesion: the laterality (unilateral/bilateral), the location (intraconal, extraconal or both), the margin (well-defined or ill-defined), the signal intensity on T1-WIs, T2-WIs and post-contrast enhancement degree (mild, moderate or intense) relative to extraocular muscles (hypo-, iso-, or hyperintense) and affection of orbit preseptal space. Also, criteria indicative of sinusitis should be considered: mucosal thickening (> 4 mm), fluid level or the presence of a retention cyst.
Then, quantitative assessment of DWI was performed using osirix workstation by two radiologists separately. For each case, volume of interest (VOI) was demarcated on all sections where the lesion can be seen. During image survey, T2-WI and contrast-enhanced images were used as reference to avoid intralesional necrotic areas and surrounding structures. To avoid false ADC values, the lesion periphery should be bypassed during examination. In cases with bilateral lesions, the larger lesion was assessed.
On all lesions, a circular region was placed over the entire lesion on “diffusion-weighted” images obtained with a b-value of 0 s/mm2. This region was then copied and pasted onto the ADC maps and the corresponding ADCs were measured. ADC measurements were repeated three times for each lesion, and the mean was calculated for further statistical analysis.
Final diagnosis was reached either by surgical findings with histopathological examination or therapeutic response or a consensus of clinical and imaging modalities.
The data collected were tabulated and analyzed by the Statistical Package for Social Science (SPSS) version 26.0. The data were demographically organized using percentage of total, mean, median, and range for cases’ ages, sex, and clinical presentations. Then, all the cases’ data were described in terms of their anatomical locations as well as their conventional MRI appearances and diffusion-weighted imaging. ADC values were organized and tabulated using mean, median, range and SD ratios. Our study results were analyzed using ROC “Receiver operating characteristic” curves as well as areas under the curves to detect sensitivity and specificity of DWI and ADC imaging for the discrimination of orbital lymphoma from idiopathic orbital inflammatory pseudotumor (IOIP). The results were also tested for their significance using student “t-test.”
Our study included 53 cases (27 females and 26 males) presented with proptosis or visual disturbances. Their ages ranged between 6 months and 82 years (mean age, 35.84 years and SD, 21.911).
Through a comprehensive search of our institutional medical report database over a consecutive period of 3 years (from February 2019 to January 2022), our cases were divided according to their final histopathological and clinical diagnosis into two groups: Group A which included 32 cases (60.4%) for benign lesions representing idiopathic orbital inflammatory pseudotumor and Group B which included 21 cases (39.6%) for malignant lesions representing orbital lymphoma.
Regarding the clinical evidence, the most common encountered symptom was proptosis in 46 out of 53 cases (86.8%), followed by orbital pain in 41 cases (77.4%). Also, 36 cases (67.9%) were presented by blurring of vision, 30 cases (56.6%) were presented by diplopia and 17 cases (32.1%) were by visual field defects. Fever, redness and hotness encountered in 15 cases (28.3%). Palpebral edema, as well as epiphora (excessive tearing), was encountered in 15 cases (28.3%), for each symptom. Three cases (5.7%) complained of unilateral sudden loss of vision, whereas unilateral gradual decrease in visual acuity was counted in 11 cases (20.8%). Ten cases (18.9%) had limited painful eye movement. Canthal swelling counting about five cases (9.4%), while the lasted encountered symptom was ptosis seen in three cases (5.7%) (Table 1).
Radiologically, variable MR features were found important for differentiating orbital lymphoma from IOIP. Of all the 53 cases, the characteristics of ill-defined margin (12/53, 22.6%), hyperintensity on T2 WI (9/53, 17%), and mild degree of contrast enhancement (18/53, 34%) were more frequently seen in orbital lymphoma than in IOIP. Radiologic sinusitis findings were seen significantly more often in IOIP (26/53, 49%) than in orbital lymphoma (4/53, 7.5%). Other imaging finding was included in our study, the involvement of orbit preseptal space that was detected more in lymphoma (15/53, 28.3%) than in IOIP (4/53, 7.5%).
Concerning the anatomical distribution of the lesion within the orbit, we found 23/53 cases (43.4%) with the lesion seen extraconal in location; 15 of them were IOIP and 8 were lymphoma. While 21/53 cases (39.6%) were intraconal extraocular; 17 of them were IOIP and 4 were lymphoma. The remaining nine cases (17%) were intraocular and all of them were found to be lymphoma.
On diffusion-weighted images, 19 out of 53 cases (35.8%) showed evident diffusion restriction appearing hypointense on ADC maps with all cases were lymphoma. While 34/53 cases (64.2%) were non-restricted with facilitated diffusion including all the 32 cases of the orbital inflammatory pseudotumors, only two cases were found to be lymphoma. The detailed qualitative MR imaging features of both entities are listed in Table 2.
Regarding ADC values of both study groups, the ADC values of all the 53 cases ranged from 0.13 × 10–3 mm2/s to 2.5 × 10–3 mm2/s with a mean (± SD) of 0.91 (± 0.44) × 10–3 mm2/s. When, analyzing each group; the 32 cases with inflammatory pseudotumor had ADC values ranging from 0.53 to 2.5 × 10–3 mm2/s with a mean (± SD) of 1.15 (± 0.37) × 10–3 mm2/s, while the ADC values of the 21 cases with lymphoma ranged from 0.13 to 1.53 × 10–3 mm2/s with a mean (± SD) of 0.56 (± 0.29) × 10–3 mm2/s (Fig. 1).
By performing the ROC analysis, with a threshold ADC value of 0.876 × 10–3 mm2/s, ADC showed 100% sensitivity, 99% specificity, and 90.5% accuracy for differentiating orbital lymphoma from IOIP. Unpaired independent 2-sample Student “t-test” for means of the ADC values was done to detect significance of the results of the ROC curve for both study groups expressing that the p value < 0.0001 for all the test results (Highly significant).
Differentiation of orbital inflammatory pseudotumor and orbital lymphoma has a treatment planning benefit. The clinical differentiation between these two entities is limited. Therefore, there is a need for an effective and non-invasive method to differentiate them. MRI plays an important role in evaluating the orbital lesions and provides supplementing information beyond clinical examination .
Orbital lymphoma is generally present with a progressive course of low-grade proptosis and minimal pain, whereas IOIP generally presents more acutely, with symptoms of proptosis, ocular motility disturbance, pain, erythema, and chemosis. Nonetheless, these features can be common to both entities with a variable onset and both commonly present as a mass on CT and MR imaging, further complicating the distinction between these diseases .
Prior studies [15, 16] indicated that some specific MR imaging features such as lesion shape, the involvement of orbit preseptal space and imaging findings suggestive of sinusitis might be potentially useful for differentiating inflammatory pseudotumor from lymphoma. However, the qualitative assessment of MRI features is a subjective process with limited interreader reproducibility, hence indicating a need for more objective methods to improve the diagnostic accuracy and confidence.
Concerning the conventional MR imaging in our literature, most inflammatory pseudotumor patients were having T1 hypointense and T2 isointense signals, whereas lymphomas showed mildly hyperintense signal on T2 compared to extraocular muscles but can show variability.
We found orbit preseptal space affection was commonly observed in orbital lymphomas than IOIPs. Nasser et al.  reported that nearly half of orbit lymphoma lesions were located in conjunctiva, and Gerbino et al.  detected that eyelid was involved in 35% of orbital lymphomas. We also found that imaging findings indicative of sinusitis were more commonly seen in IOIP than orbital lymphoma. Haradome et al.  and Xu et al.  have shown an extension of inflammatory changes to the paranasal mucosa in orbital inflammatory disorders.
In our study, intense post-contrast enhancement was observed more frequently in cases with orbital inflammatory pseudotumor. Haradome et al.  reported that the degree of inflammatory pseudotumor enhancement was significantly higher than that of lymphoma, suggesting its hypervascular nature.
Previous descriptive analyses, comparing IOIP and lymphoma on conventional MR imaging, did not show differences specific enough for differentiating these diseases. Because the clinical findings and morphological MRI findings in both entities often have considerable overlap, it can be difficult to make a definitive diagnosis without a pathologic specimen. Therefore, it would be clinically useful to have a non-invasive method to help distinguish these processes, yielding the value of diffusion-weighted MR imaging in differentiating both lesions .
In agreement with previous studies, [20,21,22,23] we found that the mean ADC of orbital lymphoma (0.56 × 10–3 mm2/s) was significantly lower than that of IOIP (1.15 × 10–3 mm2/s). It is suspected that the uniformly and atypical lymphocyte infiltrations in orbital lymphoma lead to higher cellularity and less extracellular space with subsequent low ADC value . However, two cases with lymphoma show high ADC value as some previous studies [25 and 26] mentioned that the small necrotic foci in the malignant tumor, which are not identifiable at MRI, are considered the major reason for that finding. Regarding the benign IOIP, interstitial edematous changes in this lesion give rise to high ADC value promoting a significant ADC value difference .
Our studies orbital lesions were identified at an optimal threshold ADC value of 0.876 × 10–3 mm2/s, that showed about 100% sensitivity, as well as 99% specificity for differentiating orbital inflammatory pseudotumor (Figs. 2, 3, 4, 5, 6) from orbital lymphoma (Figs. 7, 8, 9, 10, 11), indicating the significant role of ADC values in discriminating both entities. The previous results were comparable to that of Xu et al. . The aforementioned study conducted a similar randomized trial on DWI/ADC imaging role in differentiating orbital lymphoma from IOIP with nearly similar results having 90.9% sensitivity and specificity 100% using ADC cutoff value of 0.886 × 10–3 mm2/s in their study.
In conclusion, diffusion-weighted MR imaging (DWI) is valuable in discriminating orbital inflammatory pseudotumor from malignant orbital lymphoma that may help triage patients to either early intervention or initial conservative treatments. So, we recommend introduction of DWI as routine sequence in all MRI examinations of the orbit to minimize the need for invasive diagnostic method.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Apparent diffusion coefficient
Fine-needle aspiration cystology
Idiopathic orbital inflammatory pseudotumor
Gadolinium diethylene triamine pentacetic acid
Mucosa-associated lymphoid tissue
Multidetector computed tomography
Magnetic resonance imaging
Readout segmentation of long variable echo trains
Receiver operating characteristic curve
Region of interest
Statistical Package for Social Science
Volume of interest
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This study had no funding from any resource.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation Institutional Review Board (IRB) of National Liver Institute Menoufia University and with the Helsinki Declaration of 1964 and later versions. Committee’s reference number is unavailable (NOT applicable). No consent was obtained from the patients since it was a retrospective study.
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Abdelgawad, M.S., Mohamed, W.M.A. & Aly, R.A. Value of diffusion-weighted magnetic resonance imaging (DWI) in differentiating orbital lymphoma from idiopathic orbital inflammatory pseudotumor. Egypt J Radiol Nucl Med 53, 235 (2022). https://doi.org/10.1186/s43055-022-00918-6
- Diffusion-weighted imaging (DWI)
- Inflammatory pseudotumor
- Magnetic resonance imaging (MRI)