Atypical orbital mass as the precursor for myelodysplastic syndrome recurrence: a case report

Abstract

Purpose

Myelodysplastic syndrome (MDS) has the potential to progress into acute myeloid leukemia (AML), even in patients in remission. Granulocytic sarcomas are extramedullary manifestations of AML that can rarely occur in the orbit and in the absence of systemic signs of disease. We describe the unusual presentation of an isolated orbital mass in an adult patient at high-risk for development of AML.

Observations

A 42-year-old male with a history of MDS in remission for nearly two years after chemotherapy and bone marrow transplant presented with unilateral eye pain and swelling, blurry vision, diplopia, and dizziness. Imaging revealed a unilateral intraconal extraocular mass, and laboratory workup at that time was negative for signs of systemic disease. Multiple biopsies showed no pathologic or immunohistochemical signs of malignancy. A bone marrow biopsy ultimately revealed MDS recurrence with AML.

Conclusions and Importance

This case highlights the unusual manifestation of AML as a unilateral extraocular mass and the importance of clinical correlation with negative pathological studies. It is crucial to accurately establish a diagnosis of AML to improve patient outcomes, especially in high-risk cases.

1. Introduction

Myelodysplastic syndromes (MDS) are a group of hematologic neoplasms with clonal disorders of hematopoietic stem cells resulting in ineffective hematopoiesis with the possibility to progress into acute myeloid leukemia (AML).¹ AML is the abnormal proliferation of immature myeloid-derived cells, termed blasts, in a patient's bone marrow and peripheral blood.² AML can rarely present as a collection of leukemic cells outside the bone marrow or blood, termed extramedullary involvement. Myeloid sarcomas are a possible extramedullary manifestation, where leukemic cells collect in soft tissue.^3,4 Rarely, myeloid sarcomas may form in the orbits. Existing literature documents myeloid sarcomas and other ocular involvement as complications of AML in both pediatric and adult populations.5, 6, 7 We highlight the case of a 42-year-old man with a history of MDS in remission who presented with unilateral proptosis and pain, who was ultimately diagnosed with AML.

2. Case presentation

A 42-year-old man with a history of myelodysplastic syndrome (MDS) in remission for the past 1 year and 11 months, status post chemotherapy and hematopoietic stem cell transplant (HPSCT), recurrent corneal erosion and dry eyes, Dubin-Johnson syndrome, prior hepatitis B viral (HBV) infection, and type 2 diabetes mellitus, presented to the emergency department (ED) with a two-week history of progressive left eye pain and swelling. He reported blurry vision, diplopia, and dizziness that worsened when looking to the right and resolved when closing one eye.

On examination, he had left eye proptosis with inferior scleral show (Fig. 1). Visual acuity was 20/25 in the right eye, and 20/20 in the left eye with normal intraocular pressures. There were no relative afferent pupillary defects. Left eye extraocular movements were limited in all directions and worse with rightward gaze.

Fig. 1.

Patient facial photograph showing left eye proptosis and arrow highlighting inferior scleral show.

Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a left intraconal extraocular mass that was displacing and infiltrating both the superior rectus and lateral rectus muscles (Fig. 2). The mass approximately measured 3.2 cm × 2.7 cm x 2 cm. The mass showed homogenous enhancement with extension laterally from and replacing the left lacrimal gland to the lateral rectus and surrounding the left optic nerve. The apparent diffusion coefficient (ADC) value favored a lymphoproliferative lesion over other differentials, including an idiopathic orbital inflammation. Laboratory testing at presentation was largely unremarkable, with a normal white blood cell (WBC) count of 4.50 × 10³/mL, normal hemoglobin (Hgb) of 14.5 g/dL, and normal platelet count of 253 × 10³/mL. CT of the chest, abdomen, and pelvis was also done and demonstrated a new left apical ground glass opacity and known prominent mediastinal lymph nodes, decreased in size from prior.

Fig. 2.

Patient MRI with arrows highlighting the left extra-ocular superolateral mass with homogenous enhancement that is displacing and infiltrating the superior rectus and the left lateral rectus muscles shown on (A) coronal T1-weighted, (B) sagittal T1-weighted images, and (C) axial fluid attenuated inversion recovery (FLAIR). Mass measures approximately 3.2 cm craniocaudal (CC) x 2.7 cm transverse (TR) x 2 cm anteroposterior (AP).

The patient underwent a left frontal orbitotomy with lesional excision and biopsy. Initial pathology showed fibrotic tissue and a rare focus of reactive inflammatory cells, but no identifiable malignancy. A second left orbitotomy with excision and biopsy was thus performed. An unusual white-appearing orbital lesion conformed to the left eye was biopsied and showed fibrous tissue and fat with a minute focus of chronic perivascular inflammation. Immunohistochemical testing revealed mixed lymphocytes and no immunophenotypic evidence of malignancy, and included CD3, CD20, CD34, CD45-LCA, MUM-1, EBER, Kappa and Lambda, and PAX-5. Flow cytometry was negative for clonal or aberrant lymphoid cell populations. The patient was followed closely by ophthalmology and oncology for concern of MDS recurrence. Three months after presentation, a complete blood count (CBC) revealed neutropenia (WBC count of 2.35 x 103/mL) with 50 % lymphocytes and 37 % neutrophils. A positron emission tomography (PET) scan was done and showed hypermetabolic soft tissue mass in the superior rectus muscle, hypermetabolic cervical lymph nodes, and left axillar lymphadenopathy, suspicious for malignancy or metastasis. Fine needle aspiration (FNA) of the lymph nodes showed mixed lymphocytes, but no evidence of malignancy.

With continued suspicion of disease recurrence, a bone marrow biopsy was done and showed 20–30 % blasts on CD34 analysis. A repeat CBC showed anemia (Hgb of 13.0 × 10³/mL), thrombocytopenia (platelet count of 80 × 10³/mL), and neutropenia (WBC count of 3.07 × 10³/mL) with 41 % neutrophils and 48 % lymphocytes. A diagnosis of MDS recurrence with AML was made at this time. The patient was started on induction chemotherapy with a combination of venetoclax and cladribine, idarubicin, and cytarabine (CLIA) and has completed multiple infusion cycles with good response thus far. He has undergone 15 months of clinical and radiologic surveillance since initially presenting, with ophthalmology visits every 6 months and oncology visits twice weekly.

3. Discussion

Myelodysplastic syndromes (MDS) are a group of hematologic neoplasms characterized by cytopenia, ineffective hematopoiesis, and bone marrow dysplasia. MDS can progress into acute myeloid leukemia (AML) in up to 30 % of patients, with increasing numbers of immature myeloid-derived cells, called blasts, in a patient's peripheral blood or bone marrow and decreased survival rates.^1,7 AML can initially manifest in the absence of other symptoms at extramedullary sites, such as skin, soft tissue, organs, and bones, as collections of leukemic cells. Granulocytic sarcomas, also called chloroma, are extramedullary tumors made of leukemic cells that can occur at various sites, and rarely in the orbit, causing proptosis.² These extramedullary manifestations can occur months before AML is diagnosed. Bone marrow biopsy, complete blood counts, and immunohistochemistry are all pivotal in the diagnosis of AML, but a negative result should not exclude a diagnosis, and clinical correlation is always recommended.⁸

This case emphasizes the importance of clinical suspicion for AML in a high-risk patient presenting with an orbital mass and negative pathology results that did not delineate a diagnosis of malignancy. Unilateral and bilateral granulocytic sarcomas have been well-documented in both pediatric and adult patients as an initial manifestation of AML.^3,9, 10, 11, 12, 13 Our case is unique in that two sets of orbital lesion pathology results showed benign fibrous tissue with small foci of inflammation, rather than the more commonly expected granulocytic sarcoma. Making the diagnosis of AML can be difficult when there is no systemic evidence, making clinical suspicion even more important.

Documented ocular complications of MDS and AML include corneal ulcers, hyphema, retinal hemorrhage, vitreous hemorrhage, optic neuritis, and cotton wool spots. Existing literature shows that these complications occur at a similar frequency between MDS and AML.¹⁴ Orbital tumors are a relatively rare complication but are still worrisome as a possible precursor for AML, even in the absence of systemic signs.¹⁵ This patient's history of recurrent corneal erosion and dry eyes may be a possible complication of his MDS, given the variety of associated ocular complication.

It is critical to recognize the presentation of MDS and AML to initiate prompt treatment and reduce morbidity and mortality, especially in high-risk patients. Even after achieving complete remission with HPSCT, there is over a 30 % chance of MDS recurrence.¹⁶ This patient was in remission for one year and eleven months status post-HPSCT, but he was still at high risk for disease recurrence. Treatment and overall prognosis of extramedullary orbit-related AML depend on prompt recognition of the underlying disease and correct treatment. This patient was started on appropriate therapy for AML or high-risk MDS with a venetoclax and a cladribine, cytarabine, and idarubicin (CLIA) chemotherapy regimen.¹⁷

In conclusion, this case highlights an unusual presentation of MDS recurrence with AML presenting as an orbital mass with negative pathological studies. Two separate biopsies showed only benign fibrous tissue and no signs of malignancy, unlike other documented cases of granulocytic sarcomas as the initial manifestation of AML. This highlights the importance of clinical and morphologic correlation of biopsy results, especially in high-risk patients, to promptly and correctly diagnose AML.

CRediT authorship contribution statement

Nicholas Demas: Writing – review & editing, Writing – original draft. Janice Hernandez: Writing – review & editing, Supervision, Investigation. Peter Timoney: Writing – review & editing, Supervision, Investigation.

Patient consent

Consent to publish this case report has been obtained from the patient in writing.

Authorship

All authors attest that they meet the current ICMJE criteria for Authorship.

Funding

No funding or grant support.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.