Shunichiro Ueda

Orbital Lymphoproliferative Disorders (OLPDs): Value of MR Imaging for Differentiating Orbital Lymphoma from Benign OPLDs

After retrospectively analyzing MR images of 47 patients with proven orbital lymphoproliferative disease, the authors propose that ill-defined lesion margins suggest lymphoma whereas the presence of accompanying sinusitis and intralesional flow voids suggest benign lymphoproliferative disease. Lower ADC and contrast enhancement also suggest lymphoma. BACKGROUND AND PURPOSE: Accurate discrimination of orbital lymphoma from benign orbital lymphoproliferative disorders is crucial for treatment planning. We evaluated MR imaging including DWI and contrast-enhanced MR imaging for differentiating orbital lymphoma from benign orbital lymphoproliferative disorders. MATERIALS AND METHODS: Forty-seven histopathologically proved orbital lymphoproliferative disorders (29 orbital lymphomas and 18 benign orbital lymphoproliferative disorders) were evaluated. Two board-certified radiologists reviewed visual features on T1-weighted, fat-suppressed T2-weighted, diffusion-weighted, and contrast-enhanced MR images. For quantitative evaluation, ADC and contrast-enhancement ratio of all lesions were measured and optimal cutoff thresholds and areas under curves for differentiating orbital lymphoma from benign orbital lymphoproliferative disorders were determined using receiver operative characteristic analysis; corresponding sensitivities and specificities were calculated. RESULTS: Multivariate logistic regression analysis showed that ill-defined tumor margin (P = .003) had a significant association with orbital lymphoma whereas the “flow void sign” (P = .005) and radiologic evidence of sinusitis (P = .0002) were associated with benign orbital lymphoproliferative disorders. The mean ADC and contrast-enhancement ratio of orbital lymphomas were significantly lower than those of benign orbital lymphoproliferative disorders (P < .01). An ADC of less than 0.612 × 10−3 mm2/s and a contrast-enhancement ratio of less than 1.88 yielded areas under curves of 0.980 and 0.770, sensitivity of 94.1% and 95.5%, and specificities of 93.3% and 80.0% for predicting orbital lymphoma, respectively. CONCLUSIONS: Some characteristic MR imaging features and quantitative DWI and contrast-enhanced MR imaging are useful in further improving the accuracy of MR imaging for differentiation of orbital lymphoma from benign orbital lymphoproliferative disorders.

Immune Mediators in Vitreous Fluids from Patients with Vitreoretinal B-Cell Lymphoma

PURPOSE Various immune mediators are hypothesized to have important roles in the pathogenesis of vitreoretinal B-cell lymphoma, although the exact mechanisms remain unclear. We determined the immune mediator profile in the vitreous of eyes with vitreoretinal B-cell lymphoma. METHODS We studied 28 eyes (23 patients) with vitreoretinal B-cell lymphoma, and 27 eyes (27 patients) undergoing vitrectomy for macular hole and epiretinal membrane served as controls. Undiluted vitreous samples were collected, and cytometric bead array and ELISA were used to determine the vitreous concentrations of 38 immune mediators, including 14 interleukins (IL); interferon (IFN)-γ; oncostatin M (OSM); IFN-γ-inducible protein (IP)-10; monocyte chemoattractant protein (MCP)-1; macrophage inflammatory protein (MIP)-1α; MIP-1β, regulated on activation, normal T-cell expressed and secreted (RANTES); monokine induced by IFN-γ (Mig); stromal cell-derived factor (SDF)-1α; B-cell-attracting chemokine (BCA)-1; basic fibroblast growth factor (bFGF); Fas ligand; granzyme A; and granzyme B. RESULTS Vitreous levels of BCA-1, bFGF, Fas ligand, granzyme A, granzyme B, IFN-γ, IL-6, IL-8, IL-10, IP-10, MCP-1, Mig, MIP-1α, MIP-1β, OSM, RANTES, and SDF-1α were significantly higher in vitreoretinal B-cell lymphoma patients than in controls. A moderate-to-strong positive correlation was observed between granzyme A and BCA-1, IFN-γ, or MIP-1β; between IFN-γ and Mig or SDF-1α; between IL-6 and IL-8, IL-10, IP-10, or MCP-1; between IL-8 and MCP-1, Mig, or MIP-1β; between IL-10 and MCP-1 or MIP-1α; between Mig and IP-10 or Mig; and between MIP-1α and MIP-1β. CONCLUSIONS Our study suggested that elevated vitreous levels of various immune mediators inducing growth, migration, and apoptosis of B-cell lymphoma are involved possibly in the pathophysiology of vitreoretinal B-cell lymphoma.

Genome-Wide Analysis of Ocular Adnexal Lymphoproliferative Disorders Using High-Resolution Single Nucleotide Polymorphism Array

PURPOSE We identified the genomic signature of ocular adnexal lymphoproliferative disorders (LPDs), especially ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma, IgG4-related ophthalmic disease (IgG4-ROD), reactive lymphoid hyperplasia (RLH), and diffuse large B-cell lymphoma (DLBCL). METHODS We included 52 subjects with ocular adnexal LPDs (13 orbital MALT lymphomas, 16 conjunctival MALT lymphomas, 13 IgG4-RODs, 4 RLHs, and 6 DLBCLs) who had been treated at the Tokyo Medical University Hospital from 2008 to 2012. Genomic DNA was extracted from the tumor tissues and subjected to high-resolution single nucleotide polymorphism array (SNP-A) karyotyping using GeneChip Human Mapping 250K SNP arrays. The array data were investigated using Copy Number Analysis for GeneChips (CNAG) software. RESULTS In ocular adnexal MALT lymphomas, the most frequent copy number (CN) gain region was trisomy 3 detected in 31% (9/29), followed by trisomy 18 in 17% (5/29), and 6p and 21q in 14% (4/29). The most frequent CN loss regions were 6q and 9p, detected in 7% (2/29). Uniparental disomy was detected on 6q in 14% (4/29), followed by 3q in 10% (3/29). Copy number variations (CNVs) were not detected in IgG4-RODs and RLHs. Conversely, CNVs were more frequent in DLBCLs than in ocular adnexal MALT lymphomas. Copy number variations were detected in 77% (10/13) of orbital MALT lymphomas and in 67% (11/16) of conjunctival MALT lymphomas. CONCLUSIONS High-resolution single nucleotide polymorphism array is a useful method for discriminating ocular adnexal lymphomas from benign LPDs. The differences in the chromosomal abnormality patterns may reflect the activity of ocular adnexal LPDs.

Immunoglobulin G4-Related Ophthalmic Disease Involving the Sclera Misdiagnosed as Intraocular Tumor: Report of One Case

Aims: Immunoglobulin G4 (IgG4)-related disease is known to have diverse clinical manifestations. We report a case of IgG4-related ophthalmic disease misdiagnosed as intraocular tumor. Methods: Case report. Results: A 41-year-old man was referred to our department with a diagnosis of intraocular tumor, presumably choroidal melanoma. Although MR imaging was compatible with choroidal melanoma, he had been observed periodically without treatment because fundus findings were not typical of melanoma and visual function was preserved. He was again referred to us 15 years later due to increased tumor size and visual field disturbance. Transscleral biopsy of the intraocular tumor was attempted to make a histopathological diagnosis. During the biopsy procedure, thick placoid tissue adhering to the sclera was found at a location consistent with the site of the elevated intraocular lesion. Histopathological examination of this extraocular material revealed proliferation of dense fibrous tissue with follicular proliferation of lymphocytes and plasmacytes. The plasmacytes were diffusely positive for IgG and IgG4. Serum IgG4 level was slightly elevated and no extraocular lesion was detected. Despite administration of systemic corticosteroids after biopsy, the intraocular mass was not reduced. Visual acuity of 20/20 has been maintained as of the last follow-up. Conclusion: IgG4-related disease should be included in the differential diagnosis of intraocular elevated lesion.

A case of orbital sebaceous gland carcinoma developing in an anophthalmic socket 65 years after enucleation

Although conjunctival squamous cell carcinoma is known to develop as a result of chronic irritation from wearing an ocular prosthesis, orbital sebaceous gland carcinoma arising in an anophthalmic pocket is extremely rare. We report a 68-year-old female who developed a sebaceous gland carcinoma 65 years after her right eye was enucleated (at the age of three years) due to congenital glaucoma. The patient had noticed increasing discharge and swelling of her right eyelid. Incisional biopsies of an underlying orbital mass revealed poorly differentiated sebaceous gland carcinoma. The sebaceous gland carcinoma in this case could have been caused by chronic irritation as a result of long-standing use of a poorly fitted ocular prosthesis. The current case of a malignant tumor occurring 65 years after enucleation emphasizes the importance of long-term clinical surveillance to monitor for tumor formation. Careful examination of the anophthalmic socket should be part of the physical examination.

Angiolymphoid hyperplasia with eosinophilia occurring in bilateral eyelids

BackgroundAngiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign lesion, primarily occurring in the head and neck. ALHE arising from the ocular adnexa is rare, and the bilateral presentation is especially rare in the eyelids.Case presentationA 64-year-old Japanese man presented with tearing. Multiple nodules, approximately 5 mm in size, were observed in bilateral upper and lower eyelids. Surgical excisions of the both eyelids masses were performed. Histopathological examination of the excised masses demonstrated proliferated blood vessels lined by plump endothelial cells together with a lymphoid and eosinopilic infiltrate, compatible with a diagnosis of ALHE. Flow cytometry studies showed that the mass consisted of mostly CD3-positive cells. During two-year follow-up, no recurrence of the mass was observed and the patient had no subjective symptom of tearingConclusionALHE may occur in the bilateral eyelids. The cause of ALHE remains uncertain, but our results of flow cytemetry suggest that T cells are related to the pathogenesis of this disease.

PERSISTENT OVERPRODUCTION OF INTRAOCULAR VASCULAR ENDOTHELIAL GROWTH FACTOR AS A CAUSE OF LATE VITREOUS HEMORRHAGE AFTER VITRECTOMY FOR PROLIFERATIVE DIABETIC RETINOPATHY.

Purpose: The purpose of this study was to investigate whether vitreous levels of vascular endothelial growth factor (VEGF) predict late vitreous hemorrhage (VH) after vitrectomy for proliferative diabetic retinopathy, and how VEGF level changes in patients with postoperative late VH. Methods: Eighty-five eyes of 68 patients with proliferative diabetic retinopathy who underwent vitrectomy were analyzed retrospectively. Vitreous samples were collected from eyes undergoing primary vitrectomy and from eyes with late VH undergoing second vitrectomy. Vitreous VEGF levels were measured using enzyme-linked immunosorbent assay. The relationship between VEGF level and late VH (>4 weeks) occurring during follow-up as well as clinical findings, and changes in VEGF level in eyes with late VH undergoing second vitrectomy were analyzed. Results: Late VH occurred in 20 (24%) of 85 eyes, and 9 eyes required second vitrectomy. Vitreous levels of VEGF were significantly higher (median: 1,945 pg/mL; P < 0.0001) in eyes with late VH than in those without. Preexisting iris neovascularization (P < 0.0001), hypertension (P = 0.002), and proteinuria (P = 0.040) were also significant risk factors of late VH. Multivariate logistic regression analysis showed that a higher vitreous VEGF level was independently associated with a risk of postoperative late VH in patients with proliferative diabetic retinopathy (odds ratio: 20.8, 95% confidence interval: 2.72–159.47; P = 0.003). Vitreous VEGF level at second vitrectomy in patients with late VH was significantly lower compared with that at primary vitrectomy, but remained elevated (median: 1,610 pg/mL; P = 0.023). Conclusion: In patients with proliferative diabetic retinopathy, high intraocular VEGF level at primary vitrectomy was identified as an independent risk factor of postoperative late VH. Persistent overproduction of intraocular VEGF may be associated with postoperative late VH.

Aqueous immune mediators in malignant uveal melanomas in comparison to benign pigmented intraocular tumors.

BackgroundTo examine the usefulness of measuring immune mediators in aqueous humor samples for differentiating malignant uveal melanoma from benign pigmented intraocular tumors.MethodsThirteen eyes of 13 patients with uveal melanoma were studied, and 13 eyes of 13 patients with benign pigmented intraocular tumors served as controls. Undiluted samples of aqueous humor were collected, and a cytometric bead array was used to determine the aqueous humor concentrations of 35 immune mediators comprising 14 interleukins (IL), interferon-γ, interferon-γ-inducible protein-10, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, MIP-1β, regulated on activation normal T cell expressed and secreted, monokine induced by interferon-γ, basic fibroblast growth factor, Fas ligand, granzyme A, granzyme B, eotaxin, interferon-inducible T-cell alpha chemoattractant, fractalkine, granulocyte macrophage colony-stimulating factor, granulocyte colony-stimulating factor, vascular endothelial growth factor, angiogenin, tumor necrosis factor-α, lymphotoxin-α, and CD40L.ResultsAqueous humor levels of angiogenin, IL-8, and MCP-1 were significantly higher in eyes with malignant melanoma than in those with benign tumors (p < 0.05).ConclusionsAngiogenin, IL-8, and MCP-1 levels in aqueous humor may be potential markers for distinguishing malignant uveal melanoma from benign pigmented intraocular tumors, and may be a useful adjunct to histomorphology, diagnostic imaging, and other biomarkers for the diagnosis and appropriate clinical management of malignant uveal melanoma.