Unilateral Hypopyon as the First Sign of Relapse in Acute Lymphoblastic Leukemia

Background and Clinical Significance: Central nervous system involvement in Acute lymphoblastic leukemia (ALL) is well-documented; however, isolated extramedullary relapse with ocular manifestations is exceedingly rare in adults. Such cases typically present as neoplastic masquerade syndrome, where malignant cells mimic benign intraocular inflammation, often leading to diagnostic delays. In this report, we describe a case of malignant unilateral hypopyon presenting as the sole manifestation of relapse while the patient was in complete morphological bone marrow remission with negative cerebrospinal fluid (CSF) cytology. Case Presentation: A 28-year-old male with Philadelphia-negative B-ALL achieved morphological remission using the ALLTogether protocol. During consolidation therapy, he presented with blurred vision that was dependent on postural changes, specifically when bending forward. Ophthalmological examination revealed signs of uveitis and a unique, shifting hypopyon in the left eye. While bone marrow aspirate and CSF cytology remained negative for blasts, flow cytometry of the aqueous humor confirmed an isolated leukemic relapse. Therapeutic management involved escalated systemic chemotherapy, intrathecal injections, and eleven bilateral intravitreal methotrexate injections. Following the achievement of deep molecular remission, the patient underwent allogeneic stem cell transplantation and remains in remission after three years of follow-up. Conclusions: Ocular involvement can be a subtle yet critical sign of ALL relapse, even in the absence of detectable systemic disease. This case highlights the importance of maintaining a high index of clinical suspicion for ocular symptoms as potential indicators of isolated relapse, even when standard bone marrow and CSF surveillance suggest complete remission. Furthermore, this report supports the use of intravitreal methotrexate as an effective local adjunct to systemic therapy for achieving optimal disease control.