PMC8486559_01
(a) External color photograph demonstrating a cutaneous ash leaf spot on the patient's forearm. (b) MRI of the brain showing FLAIR hyperintensities involving the right posterior parietal lobe demonstrating a cortical tuber (circled).
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A 20-year-old Caucasian woman received the diagnosis of TSC at an early age following seizure attacks with findings of multiple central nervous system subependymal nodules, cortical tubers, cutaneous ash leaf spots (Figure 1), and facial angiofibromas.
Fundus exam at 12 years of age of the right eye showing significant elevation of the optic disc from peripapillary solid infiltration of the retina.
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By then, the right optic disc was severely elevated with peripapillary solid infiltration of the retina and an overlying lace-like network of "filigree" vessels (Figure 2) well-illustrated on fluorescein angiography (Figure 3).
Fluorescein angiogram of the right eye at 12 years of age. (a) Early phase shows filling of the arteries and laminar flow in the veins. (b) Arteriovenous phase reveals filling of a fine network of "filigree" vessels around the optic nerve head. (c) and (d) The late phases show diffuse hyperfluorescence and nodular staining of the tumor.
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By then, the right optic disc was severely elevated with peripapillary solid infiltration of the retina and an overlying lace-like network of "filigree" vessels (Figure 2) well-illustrated on fluorescein angiography (Figure 3).
Fundus exam at 15 years of age of the right eye continues to show significant elevation of the optic disc with peripapillary exudation and peripapillary hemorrhages from the filigree vessels.
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At this time, fundus exam showed significant elevation of the optic disc with peripapillary exudation and hemorrhages from the filigree vessels (Figures 4 and 5) with serous macular elevation on spectral domain optical coherence tomography (SD-OCT) (Figure 6).
At age 15, fluorescein angiogram of the right eye shows extensive peripapillary leakage in the late phase (c) and (d) from the filigree vascular network of the tumor with fluid extending into the macula.
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At this time, fundus exam showed significant elevation of the optic disc with peripapillary exudation and hemorrhages from the filigree vessels (Figures 4 and 5) with serous macular elevation on spectral domain optical coherence tomography (SD-OCT) (Figure 6).
Preinjection (a) and (b) and postinjection (c) and (d) optical coherence tomography (OCT) photos of the right eye over the macula (a) and (c) and nerve (b) and (d). The preinjection OCT photo over the nerve (b) shows the optic disc tumor with peripapillary subretinal fluid extending to the macula (a). Significant improvement in subretinal fluid is seen after intravitreal injection of anti-VEGF (c) and (d). Despite improvement on the OCT, the vision remained stable at 20/200.
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At this time, fundus exam showed significant elevation of the optic disc with peripapillary exudation and hemorrhages from the filigree vessels (Figures 4 and 5) with serous macular elevation on spectral domain optical coherence tomography (SD-OCT) (Figure 6).
(a) Full montage of the enucleation specimen. (Left) The right eye showed complete serosanguinous retinal detachment, ectropion uveae, and anterior and posterior synechiae. The optic nerve head (*) is expanded and hypercellular with focal calcifications. In this image, the retrolaminar optic nerve appears normal (**) (hematoxylin and eosin stain). (Right) These areas are positive for glial fibrillary acidic protein (GFAP). (b) Astrocytic proliferation in the optic nerve head reminiscent of pilocytic astroctyoma. (Left panel) Areas of necrosis and prominent neovascularization are seen (10x). (Middle panel) Scattered calcifications throughout the lesional tissue (20x). Few eosinophilic granular bodies (arrows) are seen (40x). (Right panel) Immunohistochemistry for glial fibrillary acidic protein (GFAP) highlights the astrocytic proliferation (40x) (Left and middle panels: hematoxylin and eosin stain). (c) Astrocytic proliferation in the retrolaminar optic nerve reminiscent of subependymal giant cell astrocytoma. (Left panel) Large eosinophilic polygonal cells involving the optic nerve. There are focal calcifications (10x). (Middle panel) These large cells were located in between nerve fibers forming cords or distributed as single cells throughout the retrolaminar optic nerve. At higher magnification, the peripheral vacuolization and plump, granular, and eosinophilic cytoplasm of these cells is apparent. The nuclei and nucleoli are readily visible with some cells displaying irregular nuclear contours. (Right panel) Immunohistochemistry for glial fibrillary acidic protein (GFAP) is positive in these large epithelioid cells supporting a glial/astrocytic origin (20x) ((a)-(c): hematoxylin and eosin stain).
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On microscopic examination, histologic sections showed an astrocytic proliferation at the optic nerve (Figure 7(a)) that differed as to location within the nerve. At the optic nerve head and adjacent retina, the astrocytic proliferation showed a fibrillary background with a variable number of microcysts (Figure 7(b), left panel). Focal calcifications were present (Figure 7(b), middle panel). At higher magnification, occasional eosinophilic granular bodies were seen (Figure 7(b), middle panel inset). In addition, foci of subretinal necrosis with acute inflammation and extensive preretinal neovascularization were observed (Figure 7(b), left and middle panels). In contrast, the retrolaminar optic nerve showed a proliferation of large polygonal cells with abundant eosinophilic cytoplasm with variable vacuolization, oval to round nucleus, and prominent nucleolus that diffusely infiltrated through the nerve fibers (Figure 7(c), left and middle panels). Focal calcifications were also identified (Figure 7(c), left panel). By immunohistochemistry, the astrocytic proliferation at both the optic nerve head (Figure 7(b), right panel) and retrolaminar area (Figure 7(c), right panel) was diffusely and strongly positive for glial fibrillary acidic protein (GFAP).