A, Ultrasonographic scan showing the inferior peripheral retinal lesion and a small exudative retinal detachment at the base of the lesion. B, Fundus photograph showing the Inferior vasoproliferative tumor with vascular telangiectasia, tractional retinal detachment, and extensive proliferative vitreoretinopathy.
A, Excised tumor mass composed of spindle-shaped cells embedded in extracellular matrix that envelope telangiectatic blood vessels. Proliferating retinal pigment epithelial cells are seen at the base (hematoxylin-eosin, original magnification ×2.5). B, Aggregates of Ki-67–labeled cells (black arrowheads) in an area of hemosiderin-laden macrophages (red arrowheads) (3,3’-diaminobenzidine chromogen, original magnification ×16). C, Intense glial fibrillary acidic protein labeling of the tumor (3,3’-diaminobenzidine chromogen, original magnification ×2.5). D, Absence of retinaldehyde binding protein 1 (RLBP1) antibody staining of the lesion (3-amino-9-ethylcarbazole, original magnification ×20). Inset, Normal retina control showing positive RLBP1 staining (arrowhead) (3-amino-9-ethylcarbazole, original magnification ×20).
eTable. Following RNA extraction of tumor tissue and control retina; a large number of genes were over (4968) and underexpressed (4840) in the tumor.
Shehri M, Bouhenni R, Ghazi NG, Abu Safieh L, Edward DP. Retinal Reactive Astrocytic TumorGene Expression Profiling. JAMA Ophthalmol. 2014;132(6):773-775. doi:10.1001/jamaophthalmol.2014.299
Retinal vasoproliferative tumor is a benign tumor with glial cell and vascular components.1,2 The clinical picture was well characterized by Shields and colleagues.1,3 Histopathologically, the low-grade tumor is composed of glial fibrillary acidic protein–positive spindle cells and vascular channels.4 A recent study demonstrated that the main component of the lesion was reactive astrocytes and suggested renaming the lesion retinal reactive astrocytic tumor.4 The authors questioned whether Müller cells, the major retinal glia, were involved in the reactive lesions. In this study, we examined the pathologic features and gene expression profile of an excised vasoproliferative tumor and confirmed the expression of 2 important overexpressed and underexpressed genes.
A 28-year-old man presented with blurred vision in his right eye. Ocular and systemic histories were noncontributory. On examination, visual acuity was 20/40 OD and 20/20 OS. Anterior segment examination findings were unremarkable in both eyes. The inferior periphery of the right fundus exhibited a yellow elevated retinal lesion surrounded by a small cuff of subretinal fluid and subretinal exudates, confirmed by ultrasonography (Figure 1A). The patient initially refused treatment and returned 18 months later with visual acuity of hand motions OD. The clinical features of the lesion are demonstrated in Figure 1B. The patient underwent pars plana vitrectomy, membrane peeling, tumor resection, silicone oil tamponade, and scleral buckle. Postoperatively, visual acuity remained hand motions OD and the retina was attached under silicone oil.
Pathologic examination showed features that are demonstrated in Figure 2. Gene profiling of the tumor using normal retina as a control showed that most upregulated genes were expressed in astrocytes or reactive astrocytes or were related to inflammation and extracellular matrix function (eAppendix and eTable in Supplement). One angiogenic gene (phosphatidylinositol glycan anchor biosynthesis, class F [PIGF]) showed significant upregulation. Glial fibrillary acidic protein, which showed prominent tissue localization, was significantly upregulated but not among the top 50 upregulated genes when compared with normal retina. Gremlin and vimentin expressed by both astrocytes and Müller cells5 were significantly upregulated. The major pathways related to the upregulated genes included bone morphogenetic protein signaling, extracellular matrix, and inflammation. Some genes constitutively expressed in astrocytes and Müller cells were also significantly downregulated. The retinaldehyde binding protein 1 gene (RLBP1), which is specifically expressed in Müller cells,6 was significantly downregulated. The absence of RLBP1 expression in the tumor was confirmed by immunohistochemistry (eAppendix in Supplement and Figure 2D).
This study was approved by the institutional review board at King Khaled Eye Specialist Hospital. The patient provided oral informed consent.
The clinical findings and course of this patient were typical of what was previously described in patients with vasoproliferative tumor. Also, many of the histological features observed were typical of those previously described.4 This included intertwining aggregates, glial fibrillary acidic protein–positive spindle cells, prominent telangiectatic vasculature, an overall low Ki-67 index, and proliferating retinal pigment epithelium at the base. One interesting observation not previously described in such lesions was the presence of hemosiderin-laden macrophages in the region where aggregates of Ki-67–positive glial cells were noted. We suggest that glial cell proliferation as indicated by Ki-67 may be exacerbated in areas of extravasated blood from the abnormal vasculature (Figure 2B).
Gene profiling revealed that most significantly upregulated genes were expressed in both astrocytes and reactive astrocytes. Other genes were those related to inflammation and extracellular matrix; these pathways are upregulated in reactive astrocytes. Vascular- or angiogenesis-related genes were not prominent among the significantly upregulated genes. RLBP1, which is specifically expressed by Müller cells, was significantly downregulated in the lesion. Based on these findings, we conclude that this gliovascular lesion is predominantly astrocytic and reactive in nature. We therefore agree with Poole Perry and colleagues4 that retinal reactive astrocytic tumor might be an appropriate histologic nomenclature for this lesion, although clinically it has a prominently visible vascular component.
Corresponding Author: Deepak P. Edward, MD, King Khaled Eye Specialist Hospital, PO Box 7191, Al Arubah Road, Riyadh, 11462, Kingdom of Saudi Arabia (email@example.com).
Author Contributions: Dr Edward had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Shehri, Ghazi, Safieh, Edward.
Acquisition, analysis, or interpretation of data: Bouhenni, Ghazi, Safieh, Edward.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: Bouhenni, Ghazi, Edward.
Statistical analysis: Bouhenni.
Administrative, technical, or material support: Shehri, Ghazi, Safieh, Edward.
Study supervision: Shehri, Ghazi, Edward.
Conflict of Interest Disclosures: None reported.