Case Presentation: We describe a 55-year-old lady who presented with a three-day-history of right-sided ptosis, and ophthalmology. She also reported diplopia, subjective fevers, anorexia, and an unintentional weight loss of five pounds over the preceding ten days. She denied headaches, nausea, and vomiting. Her medical problems include HIV, on highly aggressive antiretroviral therapy, history of pulmonary embolism for which she is on apixaban, and hypertension. Bedside ophthalmologic examination showed normal visual acuities, visual fields, and pupils; the right eye was notable for ptosis, with deficits in supraduction, infraduction, adduction, and abduction. There were no deficits in the left eye. The trigeminal, and facial nerves were intact. The fundus was normal in both eyes. Admission labs revealed a hemoglobin of 6 g/dl, platelets of 75000 cells/mm3, blood urea nitrogen of 87 mg/dl, creatinine of 4.7 mg/dl, lactate dehydrogenase (LDH) of 1156 U/l, 17% CD4, CD4 count of 17%, and uric acid of 19 mg/dl. Contrasted magnetic resonance imaging of the brain revealed diffuse pachymeningeal enhancement, asymmetric enhancement of the right hemipons, a pituitary macroadenoma with mass effect on the optic chiasma, enhancement of the ventral brainstem, suspected enhancement of the right abducens nerve, and questionable enhancement of bilateral oculomotor nerves; there was no abnormality of either optic nerve or the extraocular muscles. Computerized tomography of the chest, abdomen, and pelvis revealed diffuse lymphadenopathy, and interval infiltrative high-density soft tissue within bilateral renal sinus and pelvicalyceal systems, and the right ureter. Neuro-ophthalmology, infectious disease, and oncology were consulted. Peripheral blood flow cytometry showed CD 10-positive lambda light chain-restricted B cells of 0.39%. Hemolytic work-up was negative, as were studies for Cryptococcus, Histoplasma, cytomegalovirus, SARS-CoV-2, and parvovirus. Epstein-Barr virus viral load was 1500 copies/ml. A bone marrow biopsy revealed diffuse large B-cell lymphoma (DLBCL). Patient was initiated on therapy with the EPOCH-R (etoposide, prednisone, doxorubicin, vincristine, cyclophosphamide, and rituximab) regimen. Her ptosis completely resolved within ten days of initiating therapy. As of this writing, the patient is still receiving chemotherapy, and her ptosis remains resolved.

Discussion: : Orbital metastases from solid organ malignancies, and orbital infiltrates from lymphomas involving the oculomotor nerve have previously been described in literature. We describe a rare presentation of an AIDS-defining illness – diffuse large B-cell lymphoma of the central nervous system (CNS) – which presented primarily with ptosis secondary to infiltration of the cranial nerves. In our case, the bicytopenia, elevated LDH, and HIV-positive status raised suspicion for malignancy as a possible etiology.

Conclusions: A CNS lymphoma should be considered in the differential diagnosis of a HIV-positive patient with focal neurological deficits, and hematologic abnormalities.