Inflammatory Demyelinating Lesions: True Sentinel Lesion or Immune-Mediated Response to Lymphoma?

Background: Inflammatory demyelinating changes in the absence of malignant cells can sometimes be found on initial biopsies preceding the diagnosis of primary central nervous system lymphoma (PCNSL), resulting in the term "sentinel" lesion. Sentinel lesions have been reported sporadically in literature, resulting in many cases of misdiagnosis and delayed treatment. We aim to address the problem of misdiagnosis in PCNSL presenting as inflammatory demyelinating changes or sentinel lesions on initial biopsies, and to discuss our view of the mechanism underlying this phenomenon.

Case Description: Herein we report 3 cases of PCNSL that were diagnosed via brain biopsy. We retrospectively reviewed 2 cases of initially misdiagnosed PCNSL presenting with sentinel lesions at our institution. Careful revision of preoperative magnetic resonance imaging (MRI) revealed heterogeneously enhancing tumors with strong peripheral enhancement and hypoenhancing cores. Analysis of our 2 cases revealed that initial biopsy samples in both patients were taken from the hypoenhancing regions on MRI. In the third case, we targeted the peripherally enhancing region for sampling and arrived at the proper diagnosis of PCNSL on initial biopsy.

Conclusions: Based on our cases and those reported in literature, we speculate that the inflammatory demyelinating changes observed on initial biopsies are immune-mediated responses that coexist with PCNSL in different tumor regions, and that they are the direct result of inadvertent sampling from hypoenhancing regions of the tumor, rather than sentinel lesions, as their name implies. We strongly recommend that biopsy target the most enhanced region on MRI when there is high clinical and radiologic suspicion for PCNSL.