Unilateral Proptosis As An Initial Sign Of Acute Myeloid Leukemia In A Child: A Case Report

Background

Orbital myeloid sarcoma (chloroma) as an initial symptom of acute myeloid leukemia (AML), is a rare medical condition. Allen Burns published the first reported case of myeloid sarcoma in 1811, in which he described it as a green tumor involving the orbit.¹ These tumors show a characteristic green color, hence the name chloroma (in Greek “chloros” means green).² The diagnosis of orbital myeloid sarcoma can be challenging, especially when there is an absence of systemic leukemic manifestations. We report this case as AML rarely presents solely as unilateral proptosis in a young child.

Case Report

A previously healthy one-year old Saudi boy presented to emergency ophthalmic room accompanied by his family with history of rapidly progressive proptosis of the left globe over the course of two weeks. There was no associated night sweat, fever, or weight loss and the patient had no previous illnesses. Systemic review showed that the patient was born at full term, of SVD, developmentally and vaccination is up to age. The patient had no known allergies, and no surgical history. The patient had stable vital signs, was active and alert. Ophthalmic examination revealed upper and lower lid edema, proptosis with mild downward and outward displacement of the eye without any signs of inflammation or chemosis of the left eye. Vision was central, steady, and maintained. EOM was mildly restricted with normal intraocular pressure. He had normal anterior segment and round, regular, reactive pupil and normal lens and fundus. Right eye examination was within normal limit. A complete physical examination was unremarkable, no signs of acute infection, and no palpable lymph nodes. The investigations ordered for the patient were full blood count (CBC), peripheral blood film, bone marrow aspiration, and CT and MRI imaging of orbits to determine the exact location and size of tumor.

Complete blood count and peripheral blood smears showed elevated, unexpected, and abnormal high level of white blood cell count of 84.01 × 10⁹/L with few atypical and blast cells which pointed toward acute leukemia. Chemistry was normal.

Computed tomography (CT) of the head and orbit disclosed about 2.5 × 1 × 0.6 cm ill-defined focal lesion seen at the left orbital extra-conal region at the superomedial aspect causing inferolateral displacement of the left eye globe with mass effect also on the superior bony orbital roof. The mass showed mild homogenous enhancement after IV contrast (Figures 1–3). Orbital magnetic resonance imaging (MRI) showed left orbital mass of superomedial aspect of left orbit causing inferolateral displacement of left globe and medial orbital wall erosion with periosteal reaction, and opacification of left ethmoid and both maxillary sinuses (Figures 4–6). Based on the clinical, lab, and imaging study results, the differential diagnosis included: leukemia, lymphoma, rhabdomyosarcoma, eosinophilic granuloma, and idiopathic orbital inflammation (inflammatory pseudotumor). The patient was referred to a tertiary center where the patient was cared for by pediatric oncology team for diagnosis and treatment. The patient underwent thorough investigations in which bone marrow biopsy demonstrated leukemic cells and a diagnosis of acute myeloid leukemia (AML) with orbital granulocytic sarcoma was made.

Figure 1 Non-enhanced coronal view CT of head and orbit, showing ill-defined soft tissue mass measuring about 2.7 cm, height 0.2 cm* transverse 1.3 cm located in the superomedial aspect of left orbit, extra-conal involving underlying bone erosion and periosteal reaction with opacification of left ethmoid and both maxillary sinuses.

Figure 2 Non-enhanced sagittal view CT of head and orbit, showing ill-defined soft tissue mass of superomedial aspect of left orbit causing inferolateral displacement of left eye globe.

Figure 3 Non-enhanced axial view CT of head and orbit, showing ill-defined soft tissue mass at the medial aspect of left orbit causing lateral displacement of left globe.

Figure 4 T2 weighted image, coronal view of head and orbit, showing extra-conal isointense soft tissue mass of superomedial aspect of left orbit causing inferolateral displacement of left globe and medial orbital wall erosion with periosteal reaction, and opacification of left ethmoid and both maxillary sinuses. Surrounding fat planes are preserved.

Figure 5 T2 weighted image, sagittal view of head and orbit, showing slightly homogenously enhanced lesion seen at superomedial aspect of left globe.

Figure 6 T2 weighted image, axial view of head and orbit, showing homogenous isointense lesion, seen at superomedial aspect of left globe causing mild lateral proptosis of left eye globe.

The patient underwent systemic antileukemic chemotherapy, where the standard regimen for AML was given in the pediatric oncology unit. The regimen was two cycles of highly intensive chemotherapy. The first cycle of chemotherapy consisted of allopurinol, high doses of vitamin A, together with intrathecal methotrexate and dexamethasone, daunorubicin hydrochloride, and intrathecal vidarabine for central nervous system prophylaxis. No side effects or complications of chemotherapy were noted during the follow up period. Two weeks after chemotherapy, remarkable improvement and decrease of proptosis were observed, and the patient was scheduled for further follow up and a second cycle of chemotherapy in the coming weeks.

The parent of the patient provided written informed consent for the case details to be published, and no institutional approval was required to publish the case details.

Discussion

Granulocytic sarcoma occurs in a different locations in the body including the orbit,^3,4 even before the diagnosis of leukemia.^3,5 It presents during childhood with mean age approximately 7 years old, and can be observed in as early as infancy.^3,4 This is consistent with the case we present. Orbital myeloid sarcoma was reported in only 1 of 250 cases in a previous study,⁵ and orbital infiltration in leukemia was the third most common extramedullary manifestation of acute leukemia.⁶ The direct infiltration of the orbits in leukemia can present with proptosis, chemosis, lid edema, intra‑retinal macular or sub‑hyaloid hemorrhages, cotton wool spots, blurring of vision, diplopia, palsies of the extra‑ocular muscle, or papilledema due to the increased intracranial pressure.⁵ Most cases of orbital involvement in AML present with unilateral proptosis,^7–11 and few case reports have reported bilateral orbital involvement as an initial manifestation of AML.^12,13

Granulocytic sarcoma originates in bone marrow and cells spread through the Haversian canals to gather in the sub-periosteum and form a soft tissue mass. These tumors can affect the orbit,¹⁴ and proptosis occurs as a result of the leukemic infiltrates in the orbital tissues, retrobulbar hemorrhage, orbital muscle infiltration or venous blockage.³

In a study done by the USA Armed Forces Institute of Pathology, Washington D.C. presented at the Tenth Pan American Congress of Ophthalmology in 1975, in the majority of cases (88%), orbital or eyelid involvement was the initial clinical manifestation,³ while orbital involvement was reported as 14% in chronic leukemia versus 7.3% in acute cases in the Wilmer institute study.¹⁵ Myeloid sarcoma was recorded as the second commonest orbital tumor after Burkitt’s lymphoma that causes proptosis.¹⁶ In Arab studies, proptosis was the first manifestation of orbital processes among pediatric population and the first cause of these processes was reported to be secondary to tumors such as chloroma.^17,18

The diagnosis of orbital granulocytic sarcoma can be challenging, especially when there is absence of systemic leukemic manifestations, and it is commonly confused with malignant lymphoma, rhabdomyosarcoma, African Burkitt’s lymphoma, idiopathic inflammatory pseudotumor, and neuroblastoma.³ In our case, the development of orbital granulocytic sarcoma occurred before any evidence of systemic leukemia.

Granulocytic sarcoma has a predilection for the orbit and surrounding bone in children, with a male (3:2) and non-Caucasian predominance.^19,20 Most cases, in patients without a previous diagnosis, progress to AML within a few months. However, some patients do not develop leukemic hematologic evidence of the disease for as long as 30 months following the presence of an orbital tumor.²¹ In our case, the orbital mass preceded any hematologic manifestations at the time of presentation. In such cases a high index of suspicion and proper diagnosis of orbital cases by ophthalmologists is helpful in prompt and early detection and referring these patients to the available pediatric oncology units for proper management.

Studies have found that low dose of radiation was recommended for patients with residual orbital disease after chemotherapy. It was found to improve the local disease and quality of life.^22,23 One of these studies assessed the effectiveness of various radiotherapy doses for extramedullary leukemic manifestation (chloroma), and low-dose radiotherapy (≤26 Gy) was found to have good local control compared to high-dose regimes.²⁴ Another promising line of treatment with proven survival benefit for poor risk cases of AML is the allogeneic hematopoietic stem cell transplantation (alloSCT). AlloSCT improves survival in patients with unfavorable-risk AML in remission by reducing the risk of relapse, and provides long-term survival in certain patients with advanced AML.²⁵

Conclusion

Acute myeloid leukemia in the form of granulocytic sarcoma (chloroma) should be considered in the differential diagnosis of unilateral proptosis even in the absence of systemic leukemic manifestations.