Orbital Metastasis as the First Manifestation of Hepatocellular Carcinoma, and Its Effective Treatment with Combined Dual Immunotherapy: A Case Report and Review of the Literature.

BACKGROUND Orbital metastasis originating from hepatocellular carcinoma (HCC), particularly as an initial manifestation in patients without a known history of HCC, is rare. Few reports exist on the treatment of patients having HCC with orbital metastasis using targeted therapy or immunotherapy. CASE REPORT We report a case of advanced-stage HCC in a 65-year-old man who first presented with progressive, painless blurred vision and proptosis of the right eye for 2 weeks. The patient had no history of chronic liver disease or cancer. Computed tomography revealed an enhancing hyperdense extraconal mass in the right orbit; a biopsy revealed metastatic HCC. Abdominal CT, which was performed to investigate the primary cancer, revealed a 1.2×1.6-cm arterial-enhancing nodule with venous washout in hepatic segment 5, associated with liver cirrhosis. The patient's serum alpha-fetoprotein level was 70.27 ng/dL. Chest computed tomography revealed lung metastasis. Thus, first-line systemic therapy combining durvalumab and tremelimumab was initiated alongside palliative radiotherapy targeting the right orbit, which began 1 week after the first dose of dual immunotherapy. The patient had significant clinical improvement, reduced proptosis, and serum alpha-fetoprotein levels. CONCLUSIONS Although orbital metastasis is a rare manifestation of HCC, physicians should recognize and consider aggressive investigations for early diagnosis, especially in patients with existing risk factors for HCC. Dual immunotherapy with durvalumab and tremelimumab in combination with radiotherapy can be considered a potential treatment option for managing advanced HCC with orbital metastasis.

[Interdisciplinary Management of Orbital Diseases]. / Interdisziplinäre Therapie der Erkrankungen der Orbita.

Diagnosis and therapy of orbital diseases is an interdisciplinary challenge, in which i.e. otorhinolaryngologists, ophthalmologists, radiologists, radiation therapists, maxillo-facial surgeons, endocrinologists, and pediatricians are involved. This review article describes frequent diseases which both, otolaryngologists and ophthalmologists are concerned with in interdisciplinary settings. In particular the inflammatory diseases of the orbit including orbital complications, autoimmunological diseases of the orbit including Grave´s orbitopathy, and primary and secondary tumors of the orbit are discussed. Beside describing the clinical characteristics and diagnostic steps the article focusses on the interdisciplinary therapy. The review is completed by the presentation of most important surgical approaches to the orbit, their indications and possible complications. The authors tried to highlight the relevant facts despite the shortness of the text.

Metastasis of small cell lung cancer to bilateral extraocular muscles: a case report.

BACKGROUND: Orbital metastasis is a possible complication of small cell lung cancer and a pattern of bilateral invasion of the extraocular muscles has rarely been reported in literature. CASE PRESENTATION: A 46-year-old white male with a past medical history of smoking and stage IV small cell lung carcinoma presented with loss of vision and pain in the left eye. Examination revealed bilateral proptosis and left afferent pupillary defect, and visual acuity was hand motion on the left eye and 4/10 on the right eye. An orbital computed tomography scan showed a compression of the left optic nerve between the extraocular muscles at the apex, and a lateral canthotomy was performed for a new-onset compressive optic neuropathy, with residual visual improvement. There was also significant enlargement of the extraocular muscles in the right orbit. The patient was maintained in palliative treatment with both chemotherapy and local medical and surgical (amniotic membrane cover for exposure keratopathy) ophthalmological treatments until he eventually died 5 months after. CONCLUSION: Bilateral metastasis to the extraocular muscles is a very rare manifestation of small cell lung cancer and the palliative treatment in these cases is challenging.

Orbital Solitary Fibrous Tumor in a Commercial Airline Pilot.

BACKGROUND: In the literature, central serous retinopathy (CSR) accompanying solitary fibrous tumors (SFT) in a pilot has not been reported. In airline pilots, mass effect-related symptoms such as diplopia, ptosis, etc., seen with orbital tumors may endanger flight safety.CASE REPORT: A 62-yr-old male commercial airline pilot presented with blurred vision in the right eye. He had been receiving treatment for 2 mo because of CSR. His visual acuity was 10/20 in the right eye and 20/20 in the left. During examination, ptosis and exophthalmos were noticed in the right eye. Ocular movements were free in all cardinal directions and there was downward displacement in the right eye. There was no diplopia. Magnetic resonance imaging revealed a 1.5- to 2-cm well-defined contrast-enhancing mass in the lateral extraconal orbit. His medical flight certificate was suspended for 3 mo due to decreased visual acuity and superior visual defect. Superior orbitotomy was performed without any complication. Ptosis and CSR had regressed 1 wk after surgery. All systemic and ophthalmological examinations met aviation medical certificate requirements. He returned to flight on the condition of being checked every 3 mo. At the 1-yr follow-up, there was no sign of recurrences of SFT or CSR.DISCUSSION: SFTs are slow-growing neoplasms that can manifest symptoms related to mass effect. In the current literature, there are no reported cases of the coexistence of orbital SFT and CSR or pilots able to resume flight duties only 1 wk after a successful orbitotomy and tumor resection surgery.Altinbas M, Ozpinar A, Akbaba M, Nacaroglu SA, Sargolzaeimoghaddam M, Sargolzaeimoghaddam M. Orbital solitary fibrous tumor in a commercial airline pilot. Aerosp Med Hum Perform. 2024; 95(6):333-336.

[Metastasis in the periocular region]. / Metastase in der periokulären 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.

Rare Orbital Involvement Originating from Extranodal Marginal Zone Lymphoma.

Ocular adnexa region (OAR) primary lymphomas are uncommon, accounting for 1-2% of non-Hodgkin lymphomas and 8% of extranodal lymphomas. Extranodal marginal zone lymphoma (EMZL) originates from several epithelial tissues, including the stomach, salivary gland, lung, small intestine, thyroid gland, and ocular adnexa region. Here, we report a 66-year-old female patient who was diagnosed with EMZL of OAR. In consideration of the possible side effect of radiotherapy, such as conjunctivitis, visual acuity impairment, and even retinal complications, she received six cycles of triweekly targeted chemotherapy with rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) without radiotherapy. Then, she remained in complete remission up to the present day.

Isolated cavernous venous malformation of the eyelid.

Cavernous hemangioma, currently known as "cavernous venous malformation," is a common, benign, non-infiltrative, slowly progressive vascular malformation of the orbit presenting in adults. We report the case of a 9-year-old girl who presented with a painless palpable mass over the right upper eyelid of 7 years' duration. A computed tomography scan of the orbits revealed a heterogeneously enhancing, well-circumscribed mass in the right upper eyelid with no orbital extension. A transcutaneous excisional biopsy with histopathology disclosed cavernous venous malformation. The majority of cavernous venous malformations are intraconal and present in the fourth to fifth decade of life.

A Case of Blastic Plasmacytoid Dendritic Cell Neoplasm with Orbital Tumor as the Initial Symptom.

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy arising from precursor dendritic cells. It is a rare and challenging clinical presentation. For decades, there has been no treatment course for managing BPDCN and its overall prognosis is poor. METHODS AND RESULTS: We report a 27-year-old man who was admitted to the hospital due to an orbital tumor as the first symptom. Progressive enlargement of the orbital tumor was accompanied by multiple purple circular nodules on the body trunk. Pathological confirmation of BPDCN after resection of the orbital mass. Bone marrow smear and flow cytometry on examination indicate AML-M5. Performance of chemotherapy and peripheral blood autologous stem cell transplantation. CONCLUSIONS: The clinical manifestations of blastic plasmacytoid dendritic cell neoplasms are diverse. The diagnosis of BPDCN can be difficult due to overlapping morphologic, immunophenotypic, and clinical features of other hematologic AML. Relapsed and refractory BPDCN remains an elusive therapeutic challenge. The future of new targeted therapeutic drugs is expected.

Declining incidence and improving survival of ocular and orbital lymphomas in the US between 1995 and 2018.

This epidemiological study examined ocular and orbital lymphomas in the United States from 1995 to 2018, using data from the North American Association of Central Cancer Registries database of 87,543 patients with ocular and adnexal malignancies. We identified 17,878 patients (20.4%) with ocular and orbital lymphomas, with an age-standardized incidence rate (ASIR) of 2.6 persons per million (ppm). The incidence was the highest in the orbit (ASIR = 1.24), followed by the conjunctiva (ASIR = 0.57). Non-Hodgkin B-cell lymphoma was the most prevalent subtype (85.4%), particularly marginal-zone lymphoma (45.7%). Racial disparities were noted, with Asia-Pacific Islanders showing the highest incidence (orbit, 1.3 ppm). The incidence increased significantly from 1995 to 2003 (Average Percent Change, APC = 2.1%) but declined thereafter until 2018 (APC = - 0.7%). 5-year relative survival (RS) rates varied, with the highest rate for conjunctival lymphoma (100%) and the lowest for intraocular lymphoma (70.6%). Survival rates have generally improved, with an annual increase in the 5-year RS of 0.45%. This study highlights the changing epidemiological landscape, pointing to initial increases and subsequent decreases in incidence until 2003, with survival improvements likely due to advancements in treatment. These findings underscore the need for further research to investigate the root causes of these shifts and the declining incidence of ocular lymphoma.

Biological identity of orbital cavernous venous malformations.

Vascular anomalies comprise a wide spectrum of clinical manifestations related to disturbances in the blood or lymph vessels. They correspond to mainly tumors (especially hemangiomas), characterized by high mitotic activity and proliferation of the vascular endothelium, and malformations, endowed with normal mitotic activity and no hypercellularity or changes in the rate of cell turnover. However, the classifications of these lesions go beyond this dichotomy and consist various systems adapted for and by different clinical subgroups. Thus, the classifications have not reached a consensus and have historically caused confusion regarding the nomenclatures and definitions. Cavernous venous malformations of the orbit, previously called cavernous hemangiomas, are the most common benign vascular orbital lesions in adults. Herein, we have compiled and discussed the various evidences, including clinical, radiological, morphological, and molecular evidence that indicate the non-neoplastic nature of these lesions.

Preliminary study on the optical diagnosis of orbital rhabdomyosarcoma by Raman spectroscopy.

To investigate the Raman spectral features of orbital rhabdomyosarcoma (ORMS) tissue and normal orbital tissue in vitro, and to explore the feasibility of Raman spectroscopy for the optical diagnosis of ORMS. 23 specimens of ORMS and 27 specimens of normal orbital tissue were obtained from resection surgery and measured in vitro using Raman spectroscopy coupled to a fiber optic probe. The important spectral differences between the tissue categories were exploited for tissue classification with the multivariate statistical techniques of principal component analysis (PCA) and linear discriminant analysis (LDA). Compared to normal tissue, the Raman peak intensities located at 1450 and 1655 cm-1 were significantly lower for ORMS (p < 0.05), while the peak intensities located at 721, 758, 1002, 1088, 1156, 1206, 1340, 1526 cm-1 were significantly higher (p < 0.05). Raman spectra differences between normal tissue and ORMS could be attributed to the changes in the relative amounts of biochemical components, such as nucleic acids, tryptophan, phenylalanine, carotenoid and lipids. The Raman spectroscopy technique together with PCA-LDA modeling provides a diagnostic accuracy of 90.0%, sensitivity of 91.3%, and specificity of 88.9% for ORMS identification. Significant differences in Raman peak intensities exist between normal orbital tissue and ORMS. This work demonstrated for the first time that the Raman spectroscopy associated with PCA-LDA diagnostic algorithms has promising potential for accurate, rapid and noninvasive optical diagnosis of ORMS at the molecular level.

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.

Clinical outcomes and complications of eyelid versus eyebrow approaches to supraorbital craniotomy: systematic review and indirect meta-analysis.

OBJECTIVE: Eyebrow supraorbital craniotomy is a versatile keyhole technique for treating intracranial pathologies. The eyelid supraorbital approach, an alternative approach to an eyebrow supraorbital craniotomy, has not been widely adopted among most neurosurgeons. The purpose of this systematic review and meta-analysis was to perform a pooled analysis of the complications of eyebrow or eyelid approaches for the treatment of aneurysms, meningiomas, and orbital tumors. METHODS: A systematic review of the literature in the PubMed, Embase, and Cochrane Review databases was conducted for identifying relevant literature using keywords such as "supraorbital," "eyelid," "eyebrow," "tumor," and "aneurysm." Eyebrow supraorbital craniotomies with or without orbitotomies and eyelid supraorbital craniotomies with orbitotomies for the treatment of orbital tumors, intracranial meningiomas, and aneurysms were selected. The primary outcomes were overall complications, cosmetic complications, and residual aneurysms and tumors. Secondary outcomes included five complication domains: orbital, wound-related, scalp or facial, neurological, and other complications. RESULTS: One hundred three articles were included in the synthesis. The pooled numbers of patients in the eyebrow and eyelid groups were 4689 and 358, respectively. No differences were found in overall complications or cosmetic complications between the eyebrow and eyelid groups. The proportion of residuals in the eyelid group (11.21%, effect size [ES] 0.26, 95% CI 0.12-0.41) was significantly higher (p < 0.05) than that in the eyebrow group (6.17%, ES 0.10, 95% CI 0.08-0.13). A subgroup analysis demonstrated significantly higher incidences of orbital, wound-related, and scalp or facial complications in the eyelid group (p < 0.05), but higher other complications in the eyebrow group. Performing an orbitotomy substantially increased the complication risk. CONCLUSIONS: This is the first meta-analysis that quantitatively compared complications of eyebrow versus eyelid approaches to supraorbital craniotomy. This study found similar overall complication rates but higher rates of selected complication domains in the eyelid group. The literature is limited by a high degree of variability in the reported outcomes.

Ultrasound-Based Predictive Model to Assess the Risk of Orbital Malignancies.

OBJECTIVE: Ultrasound (US) is widely used for evaluating various orbital conditions. However, accurately diagnosing malignant orbital masses using US remains challenging. We aimed to develop an ultrasonic feature-based model to predict the presence of malignant tumors in the orbit. METHODS: A total of 510 patients with orbital masses were enrolled between January 2017 and April 2023. They were divided into a development cohort and a validation cohort. In the development cohort (n = 408), the ultrasonic and clinical features with differential values were identified. Based on these features, a predictive model and nomogram were constructed. The diagnostic performance of the model was compared with that of MRI or observers, and further validated in the validation cohort (n = 102). RESULTS: The involvement of more than two quadrants, irregular shape, extremely low echo of the solid part, presence of echogenic foci, cast-like appearance, and two demographic characteristics (age and sex) were identified as independent features related to malignant tumors of the orbit. The predictive model constructed based on these features exhibited better performance in identifying malignant tumors compared to MRI (AUC = 0.78 [95% CI: 0.73, 0.82] vs. 0.69 [95% CI: 0.64, 0.74], p = 0.03) and observers (AUC = 0.93 [95% CI: 0.90, 0.95] vs. Observer 1, AUC = 0.80 [95% CI: 0.76, 0.84], p < 0.01; vs. Observer 2, AUC = 0.71 [95% CI: 0.66, 0.76], p < 0.01). In the validation cohort, the predictive model achieved an AUC of 0.88 (95% CI: 0.81, 0.94). CONCLUSION: The ultrasonic-clinical feature-based predictive model can accurately identify malignant orbital tumors, offering a convenient approach in clinical practice.

Transorbital and endonasal resection of a rare orbital ectopic atypical meningioma.

A female patient in her early 20s presented with increasing proptosis of her left eye over 2 months. She had no other signs of diplopia, pain or visual loss on initial presentation. Subsequent imaging of her orbits revealed a medial rectus tumour. A transorbital open biopsy of this tumour was non-diagnostic/inconclusive, hence a combined transorbital and endonasal resection of this tumour was performed. Histopathology of the resected tumour revealed an unusual inflammatory-rich spindle cell neoplasm, which was determined to be a primary orbital ectopic atypical meningioma. These tumours are exceedingly rare, with only case reports/series reported in the literature. Complete surgical resection with margins is the proposed treatment. The role of radiotherapy is still controversial. More studies are required to improve our knowledge of this condition.