Massive retinal infiltrates as the presenting sign of chronic myeloid leukemia: Clinical and imaging features of leukemic retinopathy

Purpose: To describe the clinical and optical coherence tomography (OCT) features of two cases with bilateral diffuse retinal infiltrates as the only presenting feature of chronic myeloid leukemia (CML) on initial diagnosis and upon relapse. Methods: We reported two patients with CML, one at initial diagnosis and one in remission who presented with bilateral subacute visual impairment. Fundal examination revealed bilateral symmetrical leukostatic appearance with increased vascular tortuosity, diffuse retinal infiltrates with size up to 6 disk diameters, retinal hemorrhages, and Roth’s spots. OCT showed multiple intra-retinal hyper-reflective foci corresponding to intra-retinal hemorrhages, and outer retinal hyper-reflective foci in area corresponding to retinal infiltrate. The different retinal layers were relatively preserved and distinguishable. Results: White cell count (WCC) were elevated in both patients ranging from 544 to 810 × 109/L. Bone marrow biopsy confirmed the diagnosis of CML in the patient without prior diagnosis and relapse of CML in another patient. Cytogenetic test detected Abelson murine leukemia (ABL) – breakpoint cluster region (BCR) fusion transcript in both cases. Both patients were started on oral imatinib, subsequently WCC returned to within normal values in both cases. Vision and OCT abnormalities improved and reduction in retinal hemorrhages and infiltrates were observed in follow up. Conclusion: This report highlights the important role of ophthalmologists and detailed fundus examination in making a prompt diagnosis of leukemia in patients with visual complaints. Appropriate systemic investigation and hematologist referrals for prompt treatment of CML may improve survival rate and preserve vision.

Chronic myeloid leukaemia-associated retinopathy

A 38-year-old man presented with mild blurring of vision in both eyes for the past 1 week. On examination, the retinal vessels were dilated and tortuous, along with multiple dot blot haemorrhages all over the fundus with yellowish white focal retinal infiltrates at the macula temporal to the fovea. The salmon pink discolouration of the blood column made us look at the peripheral blood smear, which was suggestive of chronic myeloid leukaemia, leading to a diagnosis of leukaemic retinopathy in both the eyes.

Myeloid Sarcoma of the Orbit and Ocular Adnexae

Abstract 1463 Background: Myeloid sarcoma of the orbit and ocular adnexae (OMS) is a rare extramedullary manifestation of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs). Currently there are no standard treatment guidelines for OMS. Methods: On a retrospective review of the medical records, we identified 10 patients (pts) with OMS evaluated at our institution. We explored the pathologic, conventional cytogenetic and molecular cytogenetic features of these pts and analyzed their clinical features, treatments, and outcomes. Results: Among 10 acute leukemia pts with OMS, 6 (60%) were male; the median age of OMS onset was 49 yrs (range, 19 to 79). Morphological review of bone marrow (BM) aspirate smears and core biopsy specimens revealed treatment-related AML (t-AML) (n=4), AML with t(8;21) (q22;q22) (n=2), AML without maturation (n=1), AML with mutated NPM1 (n=1), CML-blast phase (n=1), and myeloperoxidase (MPO)-positive acute leukemia of ambiguous lineage (n=1). Monocytic or myelomonocytic differentiation was noted in 5 pts (50%). Conventional and/or FISH analyses performed on bone marrow in 10 pts demonstrated: +8 (n=3), t(8;21)(q22;q22) (n=2), −7 (n=2), del(7q) (n=2), t(1;3)(q21;q21) (n=1), t(2;11)(q14;q24) (n=1), t(10;11)(p13;q21) (n=1), diploid (n=2), and BCR/ABL1 rearrangement (n=1). Molecular genetic analysis, available in 8 cases, demonstrated NPM1 mutation (n=1) and NRAS mutation (n=1). Ocular symptoms were the first sign of leukemia in 4 pts, 2 with concurrent BM disease. Of the 2 presenting with isolated OMS without BM disease, one developed BM disease 321 days after OMS, while the other remained without BM disease. Six pts developed OMS after the initial leukemia diagnosis: during disease progression before treatment initiation (n=1), during AML treatment of resistant disease (n=1), at relapse with concurrent BM relapse (n=2), or as the site of isolated relapse without concurrent BM involvement (n=2). Clinical manifestations of OMS included: conjunctivitis, iris infiltration, lacrimal gland lesion, episcleritis, orbital mass, periorbital erythema or swelling, ocular secretions, ocular pain, visual problems, and/or retinal infiltrates. The diagnosis of OMS was confirmed by histologic and immunophenotypic analyses of biopsy specimens in the 8 pts from whom tissue could be obtained safely. Of the 2 pts who were not candidates for biopsy, 1 had a conjunctival lesion that involved the lacrimal gland and biopsy-confirmed skin and mediastinal disease. The second pt had intermittent bilateral blurred vision, with fundoscopically-visualized leukemic retinal infiltrates, intraretinal hemorrhages, and cotton wool spots. In both pts the ocular symptoms and lesions resolved with chemotherapy. Treatment modalities included chemotherapy alone (n=3, including 2 who received intrathecal chemotherapy), chemotherapy and surgery (n=5), chemotherapy with focal radiation (XRT) (n=1), and XRT with surgery (n=1). Three pts underwent allogeneic stem cell transplantation (SCT) after OMS diagnosis. In addition to OMS, 7 pts developed extramedullary disease in at least one other site, either concurrently with OMS or at other times during the disease course, including: CSF (n=1), breast (n=1), skin (n=3), lymph node (n=1), lung/mediastinum (n=2), and bone (n=1). Two pts are in CR, 3 and 4 years after OMS diagnosis. Six died either of progressive leukemia or treatment complications. The median time from OMS diagnosis to death was 278 days (range, 39–779 days). Of the 6 pts who died, the OMS either improved or resolved with local or systemic treatment. Two pts have been lost to follow-up, 1 in CR 2 years after OMS diagnosis, and 1 with breast and BM relapse 10 months after OMS diagnosis. Conclusion: OMS may be the initial sign of AML, with or without concurrent BM disease. OMS may also present as an isolated manifestation of relapse, without BM relapse. Extramedullary disease often develops in other sites during the disease course in AML pts with OMS. While OMS symptoms are non-specific, leukemic ocular involvement should be considered and a complete ocular exam is warranted. While t(8,21) is known to occur with extramedullary myeloid sarcoma and OMS, we also identified trisomy 8 in 30% of pts in our series. Disclosures: No relevant conflicts of interest to declare.