Title : Beyond the masquerade: Navigating diagnostic labyrinths and socioeconomic barriers to achieve remission in paediatric primary CNS lymphoma - A case series shaping a resource-aware neuro-oncology paradigm from a regional cancer centre in south India
Abstract:
Background: Pediatric CNS lymphoma is exceptionally rare (<1% of childhood brain tumors), contrasting with adult PCNSL (3-4%). Its nonspecific presentation causes diagnostic delays, compounded in resource-limited settings by financial barriers to chemotherapy. We present two cases that successfully achieved remission despite diagnostic and socioeconomic challenges, providing valuable insights for global neuro-oncology practice in managing this rare malignancy.
Case 1: The Encephalitis Masquerader
6-year-10-month girl from consanguineous marriage presented with fever and recurrent focal seizures progressing to status epilepticus requiring intubation and PICU care. Initially managed as suspected encephalitis , but comprehensive autoimmune panel and acute encephalitis syndrome panel workup turned out to be negative. CT àmultifocal cerebral edema. Family left against medical advice due to financial constraints. Following an asymptomatic period, a subsequent MRI à heterogeneously enhancing frontal lesions. Right frontal craniotomy and lobectomy done.
Case 2: The Silent Aggressor
13-year-old male presented with 2-months of early morning headache and projectile vomiting. Neurological examination àbilateral papilledema without focal deficits. Neuroimaging à large homogeneously enhancing right anterior temporal mass with significant vasogenic edema, mass effect, and 11mm midline shiftàunderwent right temporal craniotomy and decompressive lobectomy.
Diagnosis:
Case 1 : Histopathology revealed dense lymphoid infiltrate with angio-destruction and steroid-induced morphological alterations. Immunohistochemistry àB-cell lineage (CD20+) with kappa light chain restriction and Bcl2 expression. Proliferative index suppressed (Ki-67 10%), consistent with steroid effect. Staging confirmed disseminated CNS disease, establishing Stage IV PCNSL(Group C).
Case 2 : Histopathology àsheets of atypical lymphoid cells with angiocentric pattern and brisk mitotic activity. Immunohistochemistry à CD20 positivity with high proliferative index (Ki-67 90-95%). Staging àmultifocal CNS involvement with FDG-avid lymph nodes, establishing Stage IV PCNSL (Group C).
Treatment course: Both patients were initiated on the MATRix protocol (high-dose Methotrexate, Cytarabine, and Rituximab).
Impact of Financial Constraints: Rituximab was delayed due to cost—omitted for first two cycles in Case 1 and first cycle in Case 2. This modification created natural experiment in protocol efficacy.
Supportive Care Requirements: Both patients required substantial haematological support with packed red cell and platelet transfusions and G-CSF (mean :9-12 days /cycle).No PICU admissions required.
Conclusion: Both cases achieved complete remission despite diagnostic challenges and delayed rituximab.
Key Lessons:
- Diagnostic Vigilance: Maintain high suspicion for PCNSL masquerading as encephalitis in children with atypical or relapsing CNS symptoms.
- Protocol Adaptability: The MATRix regimen retains significant efficacy even with delayed rituximab, crucial finding for resource-limited settings.
- Supportive Care: Robust hematological and infectious complication management is essential.
- Early Survivorship Focus: Proactive monitoring and management of neurocognitive and behavioural sequelae .
Future Research Priorities:
- Develop cost-effective diagnostic biomarkers for PCNSL vs. CNS infections
- Optimize rituximab scheduling in MATRix for cost-effectiveness
- Establish multicenter collaborations for rare pediatric neuro-oncology cases
- Study long-term neurocognitive outcomes
