A Rare Case of Cutaneous T-Cell Lymphoma With Central Nervous System Involvement: Navigating Diagnostic Uncertainty

Introduction/Background/Significance: Cutaneous T-cell lymphoma (CTCL) is a rare non-Hodgkin lymphoma with an incidence of approximately 8.5 cases per million individuals. Central nervous system (CNS) involvement is even more uncommon, occurring in only 2–3% of CTCL cases. Clinical recognition is challenging due to nonspecific neurologic manifestations and the low sensitivity of standard diagnostic modalities, including cerebrospinal fluid (CSF) cytology and neuroimaging. Early recognition of CNS dissemination is crucial to initiate timely therapy and optimize patient outcomes.

Materials and Methods/Case Presentation/Objective: A 64-year-old man with a history of CTCL, atrial fibrillation, hypothyroidism, and prior right-sided Bell's palsy (resolved) presented with progressive facial weakness and gait imbalance. Symptoms began shortly after chemotherapy initiation and worsened over three months, prompting hospital evaluation.

Vital signs were stable, but physical exam revealed right-sided facial droop, unilateral hearing loss, and bilateral lower extremity weakness. Initial differential diagnoses included ischemic stroke, chemotherapy neurotoxicity, Bell's palsy reactivation, meningitis, and CNS involvement of CTCL. Workup included brain MRI, CT angiography, and lumbar puncture with CSF flow cytometry, infectious panels, and paraneoplastic testing. Findings were limited to elevated opening pressure and CSF protein. Empiric treatment for aseptic meningitis was initiated, but neurological deficits continued to progress.

Interdisciplinary reassessment by neurology, radiology, oncology, and internal medicine integrated the evolving clinical picture with subtle diagnostic findings. CNS involvement of CTCL was diagnosed, and intrathecal chemotherapy was initiated.

Results/Description/Main Outcome Measures: This case demonstrates the diagnostic complexity of CNS dissemination in CTCL, particularly in the absence of classic risk factors such as advanced disease, bone marrow involvement, multiple extranodal sites, elevated LDH, or ALK-positivity. Standard diagnostic modalities frequently yield inconclusive results; CSF cytology sensitivity is approximately 2–3%, and imaging findings are often nonspecific. This underscores the need for maintaining a broad, dynamic differential diagnosis and incorporating clinical evolution and multidisciplinary insight to achieve timely recognition and intervention.

Conclusions: CNS involvement in CTCL represents a rare and diagnostically challenging complication. Recognition requires ongoing clinical vigilance, broad differential maintenance, and interdisciplinary collaboration, particularly when routine studies are nondiagnostic. Early identification of CNS dissemination enables timely therapeutic intervention and may improve outcomes.

References

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3. Peková S, et al. Central Nervous System Involvement in Peripheral T-Cell Lymphomas: A Multicenter Registry Study. Front Oncol. 2022;12:874462.