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Peripapillary retinal leukemic infiltration associated with papilledema in a T-ALL patient without cranial or optic nerve involvement

Abstract

Purpose

To present a rare case of bilateral peripapillary retinal leukemic infiltration associated with papilledema without retrobulbar optic nerve involvement in a patient with acute lymphoblastic leukemia (ALL).

Methods

This was a retrospective case report.

Results

A 24-year-old man with T-cell ALL and 2-month history of papilledema presented to our department with reduction of visual acuity in the left eye. Visual acuity was 20/60 in the right eye and hand movements in the left eye. Fundus examination revealed grade 3 papilledema, bilateral peripapillary leukemic infiltration, and intraretinal hemorrhages. Cranial magnetic resonance imaging did not show any sign of cranial mass or optic nerve involvement. Pulse steroid therapy and oral acetazolamide was started. At day 18, visual acuity improved to 20/40 in the right eye and 20/60 in the left eye, while papilledema improved to grade 1 and hemorrhages regressed.

Conclusions

To our knowledge, there is no other report of peripapillary leukemic infiltration in the absence of retrobulbar optic nerve involvement. We suspect that papilledema might have facilitated peripapillary retinal infiltration due to altered vascular permeability. The reverse could also be possible: leukemic infiltration leading to increase in vascular permeability may also contribute to papilledema.

Tumori 2016; 102(Suppl. 2): e128 - e130

Article Type: CASE REPORT

DOI:10.5301/tj.5000490

Authors

Osman Çekiç, Esra Biberoglu, Fehim Esen

Article History

Disclosures

Financial support: No financial support was received for this submission.
Conflict of interest: None of the authors has conflict of interest with this submission.
Meeting presentation: Presented at the 7th Mediterretina Club International Meeting, İstanbul, Turkey, 2014.

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Introduction

Ocular involvement in patients with acute leukemias is not rare. Ocular involvement was found to be present in 17% of childhood acute leukemia cases, while only 3.6% of the children were symptomatic (1). In that series, the most commonly observed ocular finding was intraretinal hemorrhages (11%) and papilledema was only observed in a single case among 82 children with leukemias (1.2%) (1). In acute leukemia cases, papilledema has been reported to be mostly associated with cranial involvement (2, 3), optic nerve involvement (4, 5), optic perineuritis (6), or medications causing pseudotumor cerebri (7). Here, we report a rare case of bilateral peripapillary retinal leukemic infiltration associated with preexisting papilledema, in the absence of the above-mentioned predisposing factors, in a patient with acute lymphoblastic leukemia (ALL).

Case report

A 24-year-old man was referred to our clinic for routine ophthalmologic examination before initiation of the fourth course of hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) chemotherapy. The patient did not have visual complaints before and had been diagnosed 3 months previously with T-cell ALL. The initial bone marrow biopsy revealed blastic cell infiltration with small nuclei, thick chromatin, and vacuolated cytoplasm, which constituted 70% of the cells in the bone marrow. Molecular cytogenetic screening was performed for t(15;17)(q22;q21.1), inv(16)(p13q22), t(8;21)(q22;q22), t(9;22)(q34;q11.2) with fluorescein in situ hybridization; the results were negative. The blastic cells expressed CD3, TdT, and CD34 and did not express CD20 or PAX5. On complete blood count, the hemoglobin was 11.0 g/dL, white blood cell count (WBC) was 290,000/mm3, and platelets were 13,000/mm3 at the time of diagnosis. His WBC count was 6,300/mm3 during his first ophthalmologic examination under hyper-CVAD regimen. Best-corrected Snellen visual acuity was 20/20 bilaterally. Color vision score with Ishihara charts was 11/20 in the right and 9/20 in the left eye. Intraocular pressure was 15 mm Hg in the right eye and 15 mm Hg in the left eye. Bilateral anterior segment examination was nonspecific. Light reflexes were bilaterally normal and no relative afferent papillary defect was observed. Bilateral fundus examination revealed grade 4 papilledema and some flame-shaped hemorrhages along the superotemporal arcades (Fig. 1, A and B). Cranial and orbital magnetic resonance imaging was within normal limits (Fig. 2, A and B), while opening pressure of spinal tap was high (380 mm H20). Oral acetazolamide 3 × 250 mg was started to reduce intracranial pressure by the Department of Neurology. Cytopathologic examination of the lumbar puncture fluid did not reveal any malignant cells. There was no history of drug use associated with pseudotumor cerebri. We decided to follow-up the patient closely. One month later, bilateral visual acuity remained the same, papilledema regressed to grade 1, and the hemorrhages disappeared under his hyper-CVAD regimen. The patient had herpes labialis infection that started 15 days before this visit and was on antiviral treatment (intravenous acyclovir for 9 days followed by oral valacyclovir after discharge). Bone morrow biopsy performed 2 days after this examination was found to be consistent with relapse of T-cell ALL.

(A, B) Fundus images at the first presentation, before the development of peripapillary leukemic infiltration. Bilateral papilledema and flame-shaped retinal hemorrhages are observed. (C, D) Fundus images obtained 2 months after the initial presentation, when the patient experienced visual loss for the first time. Massive bilateral peripapillary infiltrates and retinal hemorrhages are prominent; margins of the optic disc cannot be appreciated. (E, F) Fundus images at the third month, 18 days after the initiation of pulse steroid and oral acetazolamide treatment. The margins of the optic disk became visible; papilledema and retinal hemorrhages regressed.

(A, B) Coronal and transverse cranial magnetic resonance images of the patient did not reveal any sign of optic nerve involvement or intracranial mass lesions, obtained at 2 months after his initial presentation, when the patient become symptomatic. (C, D) Optical coherence tomography images of the peripapillary retinal leukemic infiltrates radiating from the optic disk at the same visit.

At the second month of follow-up, the patient presented with reduced vision: visual acuity was 20/60 in the right eye and hand movements in the left eye. Massive bilateral peripapillary retinal leukemic infiltration was observed with indirect ophthalmoscopy (Fig. 1, C and D) and the margins of the optic disc could not be appreciated. Optical coherence tomography confirmed the intraretinal localization of the infiltrates radiating from the optic disc (Fig. 2, C and D). Oral acetazolamide 3 × 250 mg was continued to reduce intracranial pressure by the Department of Neurology. A repeated lumbar puncture was requested, but the quality of the lumbar puncture fluid was not good enough for reliable cytopathologic examination. A FLAG-IDA (fludarabine, cytarabine, idarubicin, and filgrastim) regimen was started after relapse was determined by bone marrow biopsy. The WBC count of the patient was 16,500/mm3 at this visit under this regimen. Repeat magnetic resonance imaging did not reveal any intracranial mass or optic nerve infiltration. We suggested intravenous 1 g methylprednisolone for 3 days followed by a maintenance dose of 72 mg oral methylprednisolone that was tapered gradually. Response to pulse steroid therapy was quick. The vision improved to 20/40 in the right eye and 20/200 in the left eye within 5 days. Papilledema regressed to grade 2 and retinal hemorrhages started to disappear. Left relative afferent pupillary defect was noted. At day 18, visual acuity was 20/40 in the right and 20/60 in the left eye. Papilledema improved to grade 1, and the majority of the retinal hemorrhages were regressed (Fig. 1, E and F). Further ophthalmologic follow-up of the patient was not available, as the general health condition of the patient deteriorated; the patient had to be admitted to the intensive care unit and did not recover.

Discussion

Papilledema is a rare finding associated with ALL. In the literature, there are few cases reporting direct infiltration of the optic nerve by the leukemic cells (4, 5) or optic perineuritis (6), describing either cases with associated pseudotumor cerebri (2) or papilledema due to a mass lesion in the brain (3). In our case, peripapillary leukemic infiltration was not associated with the involvement of the rest of the optic nerve or any cerebral mass lesion. In the previous reports of papillary infiltration together with optic nerve or cranial involvement, early initiation of systemic chemotherapy, intrathecal methotrexate, or cranial radiotherapy was suggested along with high-dose intravenous methylprednisolone and intrathecal hydrocortisone treatment to reduce optic nerve swelling (5). Our case did not have such a clinical picture and was already treated systemically. We decided to start pulse steroid treatment in order to reduce vascular permeability and subsequent tissue edema endangering the viability of retinal nerve fibers. This ocular condition responded well to systemic steroid treatment.

We observed peripapillary infiltration of the leukemic cells, under the clinical picture of preexisting papilledema. It seems that papilledema facilitated retinal infiltration by altering vascular permeability. The reverse could also be possible: leukemic infiltration-related increase in vascular permeability might have resulted in papilledema. Because papilledema preceded peripapillary retinal infiltration, and no central nervous system or retrobulbar involvement was detected by cranial magnetic resonance imaging, the first hypothesis seems more consistent with the presented case.

Disclosures

Financial support: No financial support was received for this submission.
Conflict of interest: None of the authors has conflict of interest with this submission.
Meeting presentation: Presented at the 7th Mediterretina Club International Meeting, İstanbul, Turkey, 2014.
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Authors

Affiliations

  • Department of Ophthalmology, Marmara University Medical School, Istanbul - Turkey

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