Case
A 19-year-old male presented with progressive vision loss in the right eye and pain on extraocular movement. He was diagnosed with pre-B cell acute lymphoblastic leukemia (ALL) with hyperdiploidy 5 years earlier, and he was treated successfully per Children’s Oncology Group (COG) protocol AALL1131. His cerebrospinal fluid (CSF) was not involved at the time of diagnosis. He suffered an isolated central nervous system (CNS) relapse two years later, and he was treated with a modified version of COG protocol AALL1331 due to prolonged myelotoxicity, acute renal failure, and nonalcoholic steatohepatitis incurred during treatment. During maintenance, he received 18 Gy of craniospinal radiation. One month after completion of these treatments, he started to develop his visual symptoms.
Examination showed visual acuity in the right eye of hand movement, which then progressed to no light perception. Visual acuity in the left eye was 20/20. The patient had right exotropia at presentation. Ophthalmoscopy demonstrated optic disc swelling and peripapillary hemorrhage in the right eye (Fig. 1A). The fundus of the left eye was normal. Two days after presentation, the right eye had the appearance of extensive central retinal vascular occlusion.
Magnetic resonance imaging showed a severely thickened right optic nerve (Supplemental Fig. S1), suspicious for leukemic infiltration of the optic nerve. There was no evidence for leukemic recurrence in the brain. A bone marrow (BM) aspiration with minimal residual disease testing and multiple lumbar punctures (LP) with CSF cytology were all negative for leukemia.
Given the patient’s history and suspicion of leukemic optic nerve infiltration, transvitreal fine needle aspiration biopsy (FNAB) of the optic nerve head was performed, showing very rare atypical cells suspicious for, but not diagnostic of, relapse (Fig. 2A; Wright-Giemsa stain, 1000x original magnification); thus, transconjunctival optic nerve biopsy was completed (Fig. 1B). Microscopic examination (Fig. 2B; hematoxylin and eosin, 40x original magnification) revealed extensive tumor necrosis and edema (majority of tissue shown) and a small intact segment of nerve with a mild perivascular infiltrate of viable leukemic B lymphoblasts (area as extreme right side of image) which were immunoreactive for the marker of immaturity, TdT (Fig. 2C; 200x original magnification, dark brown nuclear label), as well as the B-cell antigen, CD19 (Fig. 2D; 200x original magnification, dark brown cell membrane label) among other stains. These results were conclusive for recurrence of leukemia and the patient was then planned for proton beam radiation followed by more definitive leukemia therapy.