Enucleated eyes after failed intra-arterial infusion of chemotherapy for unilateral retinoblastoma: histopathologic evaluation of vitreous seeding

Abstract

Selective intra-arterial chemotherapy (IAC) has been adopted by many ocular oncology centers to treat advanced intraocular retinoblastoma. In this report, we describe two patients with unilateral intraocular retinoblastoma and persistent vitreous seeding, who were treated with IAC after failed systemic chemotherapy. Despite multiple sessions and increasing dosage of drug delivery, vitreous seeding in these cases failed to respond to IAC, and ultimately both eyes were enucleated for tumor control. Based on the histopathologic findings in these two cases, IAC appears to have limitations in treating persistent vitreous seeding in eyes which have failed systemic chemotherapy. Possible causes for failure of IAC to treat persistent vitreous seeding include poor vitreous penetration, inactive state of tumor seeds within the avascular vitreous cavity, and chemotherapeutic drug resistance.

Keywords: chemotherapy; enucleation; eye; failure; intra-arterial; retinoblastoma.

Figure 1

(A) One-month-old child with unilateral retinoblastoma and a left macular tumor. (B) Excellent regression of the tumor after three sessions of systemic chemotherapy, causing complete calcification of the macular lesion. (C) Tumor recurrence along temporal edge of the tumor, with associated vitreous seeding. (D) Excellent regression of the retinal tumor recurrence but no response by vitreous seeding after systemic chemotherapy.

Figure 2

(A) Diffuse periocular edema following intra-arterial infusion of melphalan, which resolved without sequelae. (B) Fundus photograph showing progression of vitreous seeding despite two sessions of intra-arterial chemotherapy.

Figure 3

(A) Gross photograph of enucleated eye showing a calcific scar of the regressed macular retinoblastoma and extensive vitreous seeding. (B) Section through the macula with the optic nerve to the right of the photograph. Macular scar in area without calcification; the scar consists of glial cell proliferation and retinal pigment epithelium hyperplasia. In addition, a portion of the retina has shifted into the choroid through a break in Bruch’s membrane (hematoxylin-eosin, original magnification 100×). (C) Temporal, equatorial retina with numerous tumor seeds (basophilic cells, see arrow) in the overlying vitreous (hematoxylin-eosin, original magnification 100×). (D) Vitreous seeds with markedly positive nuclear reaction to Ki67 (original magnification 200×).

Figure 4

(A) Fundus photograph of the right eye showing partially regressed superotemporal tumor and vitreous seeds overlying the macula. (B) Same view of right fundus showing no regression of the vitreous seeds despite three sessions of intra-arterial chemotherapy.

Figure 5

(A) Gross photograph of enucleated eye showing main superotemporal tumor and vitreous seeds overlying the macula (arrow). (B) The main tumor consisting of well-differentiated cells with abundant cytoplasm (hematoxylin-eosin, original magnification 400×). (C) A vitreous seed containing differentiated cells, with negative staining with Ki67 (hematoxylin-eosin, original magnification 400×).