From the Ophthalmic Research Center of Shahid Beheshti University (M-AJ, MRK, AF, NN, FM); and the Department of Pediatrics and Pediatric Hematology (AR), Tehran University of Medical Science, Tehran, Iran.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Mohammad-Ali Javadi, MD, Ophthalmic Research Center, No. 5, Amir Ebrahimi St., Boostan 9 St., Pasdaran Ave., Tehran 16666, Iran.
Acute lymphoblastic leukemia accounts for 80% of cases of childhood leukemia1 with unusual external eye involvement as a manifestation of extramedullary relapse.2 Conjunctival involvement is an uncommon feature in patients with lymphocytic leukemia.3 Clinically, the lesion presents as salmon patch conjunctival involvement with corkscrew vessels.3,4 Histopathologic examination shows diffuse or patchy infiltration of leukemic cells at all levels of the substantia propria, especially along blood vessels.5
To the authors’ knowledge, there are limited reports of leukemic infiltration of the conjunctiva in acute lymphoblastic leukemia.4,6 This report describes the clinicopathological features of extramedullary relapse of acute lymphoblastic leukemia as a conjunctival mass in a 9-year-old girl.
A 9-year-old girl with a history of acute lymphoblastic leukemia of small uniform blast cell type (type L1) presented with redness in the right eye. She had stopped receiving chemotherapy 4 years ago and her disease was in remission. Slit-lamp biomicroscopy showed a subconjunctival infiltrative mass at the temporal bulbar conjunctiva, with superficial corkscrew vessels (Fig. 1A). Findings on other ocular examinations were unremarkable. Ipsilateral preauricular lymphadenopathy was also present, but the findings on blood cell profile were within normal limits. The patient was referred to her oncologist, who recommended only observation of the lesion, with no suspicion of extramedullary relapse. After 2 weeks, the patient had lacrimation of the right eye. Slit-lamp biomicroscopic examination at that time showed corneal dellen on the temporal side and enlargement of the subconjunctival mass, together with hemorrhagic patches (Fig. 1B). Topical lubricants were prescribed, and excisional biopsy of the lesion was considered for both cosmetic and diagnostic purposes. Blood cell findings at the time of surgery were again within normal limits.
Figure 1. (A) Right Temporal Bulbar Subconjunctival Mass. (B) Corneal Dellen and Enlarged Mass.
Histopathologic examination of the specimen showed a diffuse proliferation of small blue cells with scattered mitoses (Fig. 2). The cells were immunoreactive for CD10, LCA, and TdT (terminal deoxynucleotidyl transferase) immunostaining (Fig. 2C), but not for CD20, CD3, cyclin D1, and CD5 (Fig. 2D). The histopathologic features were strongly suggestive of subconjunctival leukemic infiltration caused by relapsed acute lymphoblastic leukemia of pre–B-cell type (type L1). After the patient was referred to her oncologist, bone marrow aspiration showed relapse of acute lymphoblastic leukemia. The patient was treated favorably with systemic doxorubicin (Adriamycin; Pharmacia S.p.A., Milan, Italy) cytosine arabinoside, L-asparaginase, and prednisolone, followed by intrathecal methotrexate. At the last follow-up, the subconjunctival mass had completely disappeared (Fig. 3).
Figure 2. (A and B) Sheets of Small Lymphoid Cells with a Few Mitoses in the Conjunctival Substantia Propria at Low and High Magnification (hematoxylin–Eosin, Magnification [A] ×400 and [B] ×1,000). (C) Strong Immunoreactivity of the Tumor Cells for CD10 Immunostaining (original Magnification ×400). (D) No Immunoreactivity of the Cells for CD3 Immunostaining (original Magnification ×400).
Figure 3. No Residual Tumor Is Seen at the Last Follow-Up.
Acute lymphoblastic leukemia of pre–B-cell type is a malignant transformation of lymphoid precursors and the most common cancer in childhood.7 It occurs in children younger than 6 years and accounts for 80% to 85% of cases of acute lymphoblastic leukemia.8 Kincaid and Green2 reported ocular involvement in 80% of patients with leukemia; this involvement was more common in the lymphoblastic type. Leukemic ophthalmic involvement is classified into two categories: primary, or direct leukemic infiltration, and secondary, or indirect involvement. In the first type, the disease may involve the retina, anterior segment, uvea, orbit, and optic nerve. Secondary changes are caused by anemia, thrombocytopenia, hyperviscosity, and immunosuppression, which can induce retinal or vitreous hemorrhage, infection, and vascular occlusion.3
The eye is an unusual extramedullary site of relapse.2 Campagnoli et al.6 reported a conjunctival mass as an isolated extramedullary relapse of acute lymphoblastic leukemia in a 10-year-old boy. In another report by Cook and Bartley,4 conjunctival involvement occurred as a relapse of T-cell acute lymphoblastic leukemia after bone marrow transplantation. The current patient was a 9-year-old girl with a diagnosis of acute lymphoblastic leukemia (type L1) who was no longer receiving chemotherapy and had been in remission for 4 years. The patient presented with a conjunctival mass as an extramedullary relapse in the presence of normal findings on blood cell profile. After histopathologic evaluation of the lesion, bone marrow aspiration showed medullary relapse of the disease, necessitating prompt systemic and intrathecal chemotherapy. The finding of medullary involvement in the current patient suggests that bone marrow aspiration should be performed, despite normal findings on blood cell profile, in the presence of a conjunctival mass with suspicion of extramedullary relapse of acute lymphoblastic leukemia.
The conjunctiva may be an uncommon site of leukemic infiltration in acute lymphoblastic leukemia and may indicate extramedullary relapse, even in the presence of normal findings on blood cell profile.
- Champlin R, Gale RP. Acute lymphoblastic leukemia: recent advances in biology and therapy. Blood. 1989;73:2051–2066.
- Kincaid MC, Green WR. Ocular and orbital involvement in leukemia. Surv Ophthalmol. 1983;27:211–232. doi:10.1016/0039-6257(83)90123-6 [CrossRef]
- Sharma T, Grewal J, Gupta S, Murray PI. Ophthalmic manifestations of acute leukemias: the ophthalmologist’s role. Eye. 2004;18:663–672. doi:10.1038/sj.eye.6701308 [CrossRef]
- Cook BE Jr, Bartley GB. Acute lymphoblastic leukemia manifesting in an adult as a conjunctival mass. Am J Ophthalmol. 1997;124:104–105.
- Allen RA, Straatsma BR. Ocular involvement in leukemia and allied disorders. Arch Ophthalmol. 1961;66:490–508.
- Campagnoli M, Parodi E, Linari A, D’Alonzo G, Onnis E, Farinasso L. Conjunctival mass: an unusual presentation of acute lymphoblastic leukemia relapse in childhood. J Pediatr. 2003;142:211. doi:10.1067/mpd.2003.2 [CrossRef]
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- Brunning R, Borowitz M, Matutes E. Precursor B-cell and T-cell neoplasms. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health Organization of Tumours: Pathology and Genetics of Tumours of Haematopoetic and Lymphoid Tissues. Lyon: IARC Press, 2001:109–117.