Orbital Tumors Research Articles

Chimeric Antigen Receptor T Cell with an Inducible Caspase-9 Suicide Gene Eradicates Uveal Melanoma Liver Metastases via B7-H3 Targeting.

Uveal melanoma (UM) is the most common intraocular malignant tumor. Despite successful treatment of the primary tumor, about 50% of patients will recur with systemic diseases for which there are no effective treatment strategies. Here we investigated the preclinical efficacy of a chimeric antigen receptor (CAR) T-cell-based immunotherapy targeting B7-H3. B7-H3 expression on primary and metastatic human UM samples and cell lines was assessed by RNA sequencing, flow cytometry, and immunohistochemistry. Antitumor activity of CAR T cells targeting B7-H3 was tested in vitro with UM cell lines, patient-derived organotypic tumor spheroids from patients with metastatic UM, and in immunodeficient and humanized murine models. B7-H3 is expressed at high levels in >95% UM tumor cells in vitro and in vivo. We generated a B7-H3 CAR with an inducible caspase-9 (iCas9) suicide gene controlled by the chemical inducer of dimerization AP1903, which effectively kills UM cells in vitro and eradicates UM liver metastases in murine models. Delivery of iCas9.B7-H3 CAR T cells in experimental models of UM liver metastases demonstrates a durable antitumor response, even upon tumor rechallenge or in the presence of a significant metastatic disease burden. We demonstrate effective iCas9.B7-H3 CAR T-cell elimination in vitro and in vivo in response to AP1903. Our studies demonstrate more effective tumor suppression with iCas9.B7-H3 CAR T cells as compared to a B7-H3-targeted humanized monoclonal antibody. These studies support a phase I clinical trial with iCas9.B7-H3 CAR T cells to treat patients with metastatic UM.

B- Mode Ultrasonography of Ocular Abnormalities in Dogs

Background: Ultrasonography is a simple, safe and non-invasive method to examine the internal structures of eye in case of opacity of otherwise clear ocular medium like cornea, aqueous, lens, and vitreous. Methods: 123 dogs with ocular abnormalities from March 2021 to October 2022, presented to the Division of Veterinary Surgery and Radiology were included in this study. All of the animals underwent a thorough ophthalmic examination along with B-scan ultrasonography of both the eyes using a 7.5 MHz linear probe. Result: Ultrasonography revealed thin hyperechoic lines and a thin hyperechoic rim of the lens, indicating early cataract changes and cortical cataract, respectively. Sixty-two dogs were found to be affected by cataract; 20 dogs were affected by the disease Phthisis bulbi; 16 dogs had a complete retinal detachment showing a typical “morning glory” sign; 10 dogs had vitreous haemorrhage; 6 dogs had a damaged eye with lens dislocation; and 5 dogs had choroidal melanoma and intraocular tumours in 4 dogs out of 123 observed dogs. Further, out of 62 cataract cases, 16 dogs were affected by cortical cataracts, 41 had nuclear cataracts, and 5 dogs were affected by morgagnian cataracts. Therefore, B-scan ultrasonography of the eye was a quick, safe, and accurate way to examine the pathology, especially when opaque media inhibit direct examination or when exophthalmos is evident and the normal anatomy of the eye.

Advances in Imaging Techniques for Retinoblastoma with Subretinal Seeding

Retinoblastoma is a rare and highly malignant intraocular tumor primarily affecting young children. Subretinal seeding, specifically Type D, indicates an advanced stage of retinoblastoma with a high risk of metastasis and a poor prognosis. We present a case of a 4-year-old girl who presented with leukocoria, vision loss, and painless redness in her left eye. Examination of the posterior segment revealed a total retinal detachment and abnormal, tortuous retinal vessels in the left eye. No visible mass, vitreous seeding, or hemorrhage was observed. B-mode ultrasound confirmed a detached retina. Due to the poor visual prognosis and strong clinical suspicion of malignancy, enucleation was performed. Further histopathological analysis confirmed the diagnosis of diffuse infiltrative retinoblastoma.

Pathological and Molecular Diagnosis of Uveal Melanoma.

(1) Background: Uveal melanoma (UM) is a common malignant intraocular tumor that presents with significant genetic differences to cutaneous melanoma and has a high genetic burden in terms of prognosis. (2) Methods: A systematic literature search of several repositories on uveal melanoma diagnosis, prognosis, molecular analysis, and treatment was conducted. (3) Results: Recent genetic understanding of oncogene-initiation mutations in GNAQ, GNA11, PLCB4, and CYSLTR2 and secondary progression drivers of BAP1 inactivation and SF3B1 and EIF1AX mutations offers an appealing explanation to the high prognostic impact of adding genetic profiling to clinical UM classification. Genetic information could help better explain peculiarities in uveal melanoma, such as the low long-term survival despite effective primary tumor treatment, the overwhelming propensity to metastasize to the liver, and possibly therapeutic behaviors. (4) Conclusions: Understanding of uveal melanoma has improved step-by-step from histopathology to clinical classification to more recent genetic understanding of oncogenic initiation and progression.

Construction of oxidative phosphorylation-related prognostic risk score model in uveal melanoma

BackgroundUveal melanoma (UVM) is a malignant intraocular tumor in adults. Targeting genes related to oxidative phosphorylation (OXPHOS) may play a role in anti-tumor therapy. However, the clinical significance of oxidative phosphorylation in UVM is unclear.MethodThe 134 OXPHOS-related genes were obtained from the KEGG pathway, the TCGA UVM dataset contained 80 samples, served as the training set, while GSE22138 and GSE39717 was used as the validation set. LASSO regression was carried out to identify OXPHOS-related prognostic genes. The coefficients obtained from Cox multivariate regression analysis were used to calculate a risk score, which facilitated the construction of a prognostic model. Kaplan-Meier survival analysis, logrank test and ROC curve using the time “timeROC” package were conducted. The immune cell frequency in low- and high-risk group was analyzed through Cibersort tool. The specific genomic alterations were analyzed by “maftools” R package. The differential expressed genes between low- or high-risk group were analyzed and performed Gene Ontology (GO) and GSEA. Finally, we verified the function of CYC1 in UVM by gene silencing in vitro.ResultsA total of 9 OXPHOS-related prognostic genes were identified, including NDUFB1, NDUFB8, ATP12A, NDUFA3, CYC1, COX6B1, ATP6V1G2, ATP4B and NDUFB4. The UVM prognostic risk model was constructed based on the 9 OXPHOS-related prognostic genes. The prognosis of patients in the high-risk group was poorer than low-risk group. Besides, the ROC curve demonstrated that the area under the curve of the model for predicting the 1 to 5-year survival rate of UVM patients were all more than 0.88. External validation in GSE22138 and GSE39717 dataset revealed that these 9 genes could also be utilized to evaluate and predict the overall survival of patients with UVM. The risk score levels related to immune cell frequency and specific genomic alterations. The DEGs between the low- and high- risk group were enriched in tumor OXPHOS and immune related pathway. In vitro experiments, CYC1 silencing significantly inhibited UVM cell proliferation and invasion, induced cell apoptosis.ConclusionIn sum, a prognostic risk score model based on oxidative phosphorylation-related genes in UVM was developed to enhance understanding of the disease. This prognostic risk score model may help to find potential therapeutic targets for UVM patients. CYC1 acts as an oncogene role in UVM.

Automated segmentation for early detection of uveal melanoma

ObjectiveUveal melanoma is the most common intraocular malignancy in adults. Current screening and triaging methods for melanocytic choroidal tumours face inherent limitations, particularly in regions with limited access to specialized ocular oncologists. This study explores the potential of machine learning to automate tumour segmentation. We develop and evaluate a machine-learning model for lesion segmentation using ultra-wide-field fundus photography. MethodA retrospective chart review was conducted of patients diagnosed with uveal melanoma, choroidal nevi, or congenital hypertrophy of the retinal pigmented epithelium at a tertiary academic medical centre. Included patients had a single ultra-wide-field fundus photograph (Optos PLC, Dunfermline, Fife, Scotland) of adequate quality to visualize the lesion of interest, as confirmed by a single ocular oncologist. These images were used to develop and test a machine-learning algorithm for lesion segmentation. ResultsA total of 396 images were used to develop a machine-learning algorithm for lesion segmentation. Ninety additional images were used in the testing data set along with images of 30 healthy control individuals. Of the images with successfully detected lesions, the machine-learning segmentation yielded Dice coefficients of 0.86, 0.81, and 0.85 for uveal melanoma, choroidal nevi, and congenital hypertrophy of the retinal pigmented epithelium, respectively. Sensitivities for any lesion detection per image were 1.00, 0.90, and 0.87, respectively. For images without lesions, specificity was 0.93. ConclusionOur study demonstrates a novel machine-learning algorithm's performance, suggesting its potential clinical utility as a widely accessible method of screening choroidal tumours. Additional evaluation methods are necessary to further enhance the model's lesion classification and diagnostic accuracy.

Metastasis in the periocular region

Orbital and periocular metastatic tumors used to be considered very rare; however, with the constant updating of drugs and detection methods for cancer treatment, new chemotherapies and radiation treatments are being used. The life expectancy of cancer patients has become longer and periocular metastases are becoming easier to detect. Our knowledge of this rare disease of metastases also needs to be updated. This article reviews the incidence, symptomatic presentation, clinical features, diagnostic approaches and current treatment of metastatic tumors of the orbit and ocular adnexa in these patients.

Advances in Diagnostic Imaging Studies of Orbital Tumors

Advances in Diagnostic Imaging Studies of Orbital Tumors

Image-guided navigation in posterior orbital tumour surgery: a comparative cohort study

ABSTRACT Purpose The posterior orbit is a confined space, harbouring neurovascular structures, frequently distorted by tumours. Image-guided navigation (IGN) has the potential to allow accurate localisation of these lesions and structures, reducing collateral damage whilst achieving surgical objectives. Methods We assessed the feasibility, effectiveness and safety of using an electromagnetic IGN for posterior orbital tumour surgery via a comparative cohort study. Outcomes from cases performed with IGN were compared with a retrospective cohort of similar cases performed without IGN, presenting a descriptive and statistical comparative analysis. Results Both groups were similar in mean age, gender and tumour characteristics. IGN set-up and registration were consistently achieved without significant workflow disruption. In the IGN group, fewer lateral orbitotomies (6.7% IGN, 46% non-IGN), and more transcutaneous lid and transconjunctival incisions (93% IGN, 53% non-IGN) were performed (p = .009). The surgical objective was achieved in 100% of IGN cases, with no need for revision surgery (vs 23% revision surgery in non-IGN, p = .005). There was no statistically significant difference in surgical complications. Conclusion The use of IGN was feasible and integrated into the orbital surgery workflow to achieve surgical objectives more consistently and allowed the use of minimal access approaches. Future multicentre comparative studies are needed to explore the potential of this technology further.

A Systematic Review and Meta-Analysis on the Diagnostic and Prognostic Values of 18F-FDG PET in Uveal Melanoma and Its Hepatic Metastasis.

In this systematic review and meta-analysis (PRISMA-compliant), we tried to investigate diagnostic and prognostic values of 18F-FDG PET in uveal melanoma. A systematic search was conducted on the main medical literature databases to include studies that evaluated 18F-FDG PET as the imaging modality to evaluate patients with uveal melanoma. Overall, 27 studies were included. Twelve had data about the detection rate of 18F-FDG PET in primary intra-ocular tumours. The pooled sensitivity was 45% (95%CI: 41-50%). Furthermore, studies showed that the larger the primary tumour, the higher its uptake. Among the included studies, 13 assessed 18F-FDG PET in detecting metastasis. The pooled sensitivity and specificity were 96% (95%CI: 81-99%) and 100% (95%CI: 94-100%), respectively. Regarding liver metastasis, they were 95% (95%CI: 79-99%) and 100% (95%CI: 91-100%), respectively. Noteworthy, the level of 18F-FDG uptake was a strong predictor of patient survival. Lastly, 18F-FDG PET could characterise lesions from the histopathology perspective, distinguishing high-risk from low-risk diseases. Overall, although not reliable in detecting primary intra-ocular tumours, 18F-FDG PET is highly accurate for diagnosing metastatic uveal melanomas. It can also be a highly valuable modality in terms of patient prognostication. Thus, 18F-FDG PET can be recommended in patients diagnosed with uveal melanoma to enhance decision-making and patient management.

Gastric Inhibitory Polypeptide Receptor (GIPR) Overexpression Reduces the Tumorigenic Potential of Retinoblastoma Cells.

Retinoblastoma (RB) is the most common malignant intraocular tumor in early childhood. Gene expression profiling revealed that the gastric inhibitory polypeptide receptor (GIPR) is upregulated following trefoil factor family peptide 1 (TFF1) overexpression in RB cells. In the study presented, we found this G protein-coupled transmembrane receptor to be co-expressed with TFF1, a new diagnostic and prognostic RB biomarker for advanced subtype 2 RBs. Functional analyses in two RB cell lines revealed a significant reduction in cell viability and growth and a concomitant increase in apoptosis following stable, lentiviral GIPR overexpression, matching the effects seen after TFF1 overexpression. In chicken chorioallantoic membrane (CAM) assays, GIPR-overexpressing RB cells developed significantly smaller CAM tumors. The effect of GIPR overexpression in RB cells was reversed by the GIPR inhibitor MK0893. The administration of recombinant TFF1 did not augment GIPR overexpression effects, suggesting that GIPR does not serve as a TFF1 receptor. Investigations of potential GIPR up- and downstream mediators suggest the involvement of miR-542-5p and p53 in GIPR signaling. Our results indicate a tumor suppressor role of GIPR in RB, suggesting its pathway as a new potential target for future retinoblastoma therapy.

Modulating DNA damage response in uveal melanoma through embryonic stem cell microenvironment

BackgroundUveal melanoma (UVM) is the most common primary intraocular tumor in adults, with a median survival of 4–5 months following metastasis. DNA damage response (DDR) upregulation in UVM, which could be linked to its frequent activation of the PI3K/AKT pathway, contributes to its treatment resistance. We have reported that embryonic stem cell microenvironments (ESCMe) can revert cancer cells to less aggressive states through downregulation of the PI3K signaling, showing promise in modulating the DDR of UVM.MethodsSince nonhomologous end joining (NHEJ) is the main DNA repair mechanism in UVM, this study utilized gene expression analysis and survival prognosis analysis to investigate the role of NHEJ-related genes in UVM based on public databases. Xenograft mouse models were established to assess the therapeutic potential of ESC transplantation and exposure to ESC-conditioned medium (ESC-CM) on key DNA repair pathways in UVM. Quantitative PCR and immunohistochemistry were used to analyze NHEJ pathway-related gene expression in UVM and surrounding normal tissues. Apoptosis in UVM tissues was evaluated using the TUNEL assay.ResultsPRKDC, KU70, XRCC5, LIG4 and PARP1 showed significant correlations with UM progression. High expression of PRKDC and XRCC5 predicted poorer overall survival, while low PARP1 and XRCC6 expression predicted better disease-free survival in UVM patients. ESCMe treatment significantly inhibited the NHEJ pathway transcriptionally and translationally and promoted apoptosis in tumor tissues in mice bearing UVM. Furthermore, ESC transplantation enhanced DDR activities in surrounding normal cells, potentially mitigating the side effects of cancer therapy. Notably, direct cell-to-cell contact with ESCs was more effective than their secreted factors in regulating the NHEJ pathway.ConclusionsOur results suggest that NHEJ-related genes might serve as prognostic markers and therapeutic targets in UVM. These findings support the therapeutic potential of ESC-based therapy in enhancing UVM sensitivity to radiochemotherapy and improving treatment outcomes while minimizing damage to healthy cells.

Amelanotic Choroidal Melanoma with Extraocular Extension in a 51 Year-Old Female: A Rare Case

Introduction: Melanoma is a dangerous malignancy primarily involving the choroid, ciliary body, or iris. The most frequent primary intraocular malignant tumor is choroidal melanoma. The tumor most often affects Caucasians of Northern Europe ranging between the ages of 50 and 80. Most choroidal melanomas are pigmented, however, non-pigmented or mixed pigmented and non-pigmented forms can also happen. Compared with other amelanotic choroidal lesions, amelanotic choroidal melanoma showed markedly greater basal diameter, thickness, frequent connection with subretinal fluid, and ultrasonic hollowness. Extrascleral extension is currently detected in 10% to 28% of choroidal melanoma patients, and the mortality rate is much greater than in those without the extension. Case Presentation: We reported a rare case of extraocular extension in a 51-year-old female patient with amelanotic melanoma. The primary complaint was a painful and bleeding mass on her left eye that had developed two months prior to admission. On the conjunctiva of the left eye, there was a solid, palpable mass measuring 4 x 3.5 x 1 cm. It was red, well-defined, and had a hard, solid consistency. It was fixed at the base, had minimal bleeding, and pressed on her eyeball from the inferolateral direction. The cornea appears clear, and there is no light perception in visual acuity. The orbital focus computed tomography scan revealed an Enhancing solid mass containing a fat component. The mass was in the left intraocular, extending from intraconal to extraconal. Conclusions: Amelanotic melanoma with extraocular extension is a rare condition that can be difficult to detect due to its unclear clinical symptoms and wide range of possible causes. Patients and their families must be educated to receive the appropriate first therapy and prevent the illness from worsening. Melanoma management depends on several factors: tumor size, location, related characteristics, opposite eye status, systemic status, and patient preference. Orbital exenteration is one of the management options for choroidal melanoma with significant extraocular extension. By the time ocular treatment begins, the patient's survival may already be predetermined, and this realization could impact how uveal melanoma is treated in the years to come.

Clinical approach for solid intraocular metastases

Intraocular metastases arising from solid tumors are found in approximately 2% of patients with metastatic tumor diseases and are therefore more frequent than originally assumed. They often affect the uvea and are associated with apoor prognosis. Due to the difficult diagnosis and an inconsistent treatment regimen, ophthalmologists have aspecial responsibility here. This article gives a summary of the various types of intraocular metastases with respect to clinical features, diagnostics, treatment and prognosis as well as recommendations for follow-up care. A selective literature search was carried out on the topic of intraocular metastases using PubMed and Google Scholar. Intraocular metastases most frequently affect the uvea, specifically the choroid. In most cases the underlying disease is breast or lung cancer, but other rarer primary tumors have also been reported in the literature. Metastatic lesions can show very different morphological manifestations but can be distinguished based on the corresponding structure of manifestation in the eye and with the aid of targeted staging, thus providing valid information on the type of primary tumor. The treatment is partly experimental and usually depends on the primary tumor and leading symptoms of the patient. A differentiation between acurative or palliative treatment situation must always be made. Intraocular metastases are the most frequent intraocular tumor and are usually associated with apoor prognosis. Accurate diagnostics for finding the treatment as well as interdisciplinary collaboration and the presentation of the patient on the tumor board are essential.

Adjunctive transseptal corridor: Technique for endoscopic resection of orbital tumor.

The transnasal endoscopic approach is increasingly used for resection of tumors that are located inferiorly and medially within the orbit. However, this usually requires multiple-handed manipulations, which demand a second corridor for an assistant. Here, we introduce a simple transseptal corridor from the contra-nare, to facilitate assistant instrument maneuverability. This simple, minimally invasive skill greatly improves operation efficiency and deserves greater attention in endoscopic orbital surgery.

Ocular metastases profile in a tertiary hospital in São Paulo, Brazil

ObjectiveOcular metastases are the most common intraocular tumours in adults. Data regarding the occurrence of these tumours in the Brazilian population is scarce. We aimed to investigate the profile of ocular metastases of patients referred to tertiary hospital service in São Paulo, Brazil.DesignRetrospective study.ParticipantsPatients referred to the Ocular Oncology service of the Federal University of São Paulo with initial diagnostic hypothesis of ocular metastasis.MethodsData was retrospectively collected from medical records from June 2017 to June 2023. Age, sex, primary tumour site, previous knowledge of the systemic diagnosis, laterality, initial visual acuity (VA), local or systemic treatment and mean follow-up period were obtained.ResultsA total of 37 cases were referred to the ocular oncology division due to a suspected ocular metastasis, 15 (40.5%) were confirmed. Mean age at diagnosis was 53.47 ± 16.01 years old, the majority (86.7%) of patients already knew the systemic diagnosis. Breast cancer (66.7%) was the most common primary site, followed by Lung cancer (26.7%). Both eyes were affected in 66.67% of the cases, all patients had metastases at the choroid (100.0%), and the mean initial VA was 1.37 ± 1.04 logMAR. Chemotherapy was the main systemic treatment modality (73.3%), and most patients had no ocular treatment (53.3%). The mortality rate along the follow-up period was 30.0%.ConclusionsConsidering the number of new patients absorbed by the Ocular Oncology service over the study period, the frequency of ocular metastases was relatively low. The patients’ characteristics was comparable to data published in the international literature.

Malignant Medulloepithelioma of the Ciliary Body Revealed by Neovascular Glaucoma in a 13-Year-Old Child

Medulloepithelioma of the ciliary body is a rare congenital intraocular tumor occurring more frequently in children. It develops from the unpigmented epithelium of the ciliary body. Positive diagnosis relies essentially on anatomopathological examination. In our article, we report a case of malignant medulloepithelioma of the ciliary body in a 13-year-old child revealed by severe panuveitis complicated by neovascular glaucoma and non-axial exophthalmos.

Management of Intraocular Retinoblastoma: ICMR Consensus Guidelines.

Retinoblastoma (RB) is the most common childhood intraocular malignancy. Delayed presentation due to a lack of awareness and advanced intraocular tumors are a common scenario in low-middle income countries (LMICs). Remarkable treatment advances have been made in the past few decades allowing globe salvage in advanced intraocular RB (IORB) including systemic chemotherapy with focal consolidation and targeted treatments like intraarterial chemotherapy and intravitreal chemotherapy. However, a lack of availability and affordability limits the use of such advances in LMICs. External beam radiotherapy, despite risk of second cancers in RB with germline mutations, still remains useful for recalcitrant RB not responding to any other treatment. When choosing conservative treatment for advanced IORB, the cost and long duration of treatment, morbidity from multiple evaluation under anesthesias (EUAs), side effects of treatment and risk of treatment failure need to be taken into account and discussed with the parents. In this article, the authors discuss the ICMR consensus guidelines on the management of IORB.

Global incidence and prevalence of malignant orbital tumors

PurposeAims to provide an overview of the contemporary epidemiology of malignant orbital tumors by analyzing population-based incidence patterns across various regions worldwide. MethodsIn this article, we retrieved orbital malignancy data from the MEDLINE database and analyzed the incidence and prevalence of orbital malignancies worldwide. We performed the literature search by searching on the Mesh terms for malignant orbital tumors ("orbital", "tumor", "lymphoma", "malignant", "cancer", "incidence", and "epidemiology"). All included studies were published between 1993 and 2023 and were written in English. ResultsOcular or ophthalmic lymphoma most frequently occurred in the orbit, with a prevalence ranging from 47% to 54%. The incidence of malignant orbital tumors was increasing in the USA (2.0 per million (1981–1993), Netherlands (0.86 (1981–1985) to 2.49 (2001–2005) per million) and South Korea (0.3–0.8 per million (1999–2016)), respectively. Ophthalmic lymphoma which includes orbit lymphoma was increasing in Canada (0.17–1.47 per million (1992–2010)), Denmark (0.86 per million (1981–1985) to 2.49 per million (2001–2005)), respectively. ConclusionsThe predominant primary malignant orbital tumor in adults was lymphoma. Ocular or ophthalmic lymphoma most frequently occured in the orbit. The limited data available suggested an increasing trend in the incidence of malignant orbital tumors in each country included, which were mainly attributed to the increase in lymphoma. Generally, incidence rates were found to increase with advancing age, with no difference between males and females.

Toward Precision Diagnosis: Machine Learning in Identifying Malignant Orbital Tumors With Multiparametric 3 T MRI.

Orbital tumors present a diagnostic challenge due to their varied locations and histopathological differences. Although recent advancements in imaging have improved diagnosis, classification remains a challenge. The integration of artificial intelligence in radiology and ophthalmology has demonstrated promising outcomes. This study aimed to evaluate the performance of machine learning models in accurately distinguishing malignant orbital tumors from benign ones using multiparametric 3 T magnetic resonance imaging (MRI) data. In this single-center prospective study, patients with orbital masses underwent presurgery 3 T MRI scans between December 2015 and May 2021. The MRI protocol comprised multiparametric imaging including dynamic contrast-enhanced (DCE), diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), as well as morphological imaging acquisitions. A repeated nested cross-validation strategy using random forest classifiers was used for model training and evaluation, considering 8 combinations of explanatory features. Shapley additive explanations (SHAP) values were used to assess feature contributions, and the model performance was evaluated using multiple metrics. One hundred thirteen patients were analyzed (57/113 [50.4%] were women; average age was 51.5 ± 17.5 years, range: 19-88 years). Among the 8 combinations of explanatory features assessed, the performance on predicting malignancy when using the most comprehensive model, which is the most exhaustive one incorporating all 46 explanatory features-including morphology, DWI, DCE, and IVIM, achieved an area under the curve of 0.9 [0.73-0.99]. When using the streamlined "10-feature signature" model, performance reached an area under the curve of 0.88 [0.71-0.99]. Random forest feature importance graphs measured by the mean of SHAP values pinpointed the 10 most impactful features, which comprised 3 quantitative IVIM features, 4 quantitative DCE features, 1 quantitative DWI feature, 1 qualitative DWI feature, and age. Our findings demonstrate that a machine learning approach, integrating multiparametric MRI data such as DCE, DWI, IVIM, and morphological imaging, offers high-performing models for differentiating malignant from benign orbital tumors. The streamlined 10-feature signature, with a performance close to the comprehensive model, may be more suitable for clinical application.