Neurological immune-related adverse events (irAEs) are rare toxicities that occur following immune checkpoint inhibitor therapy. We propose that patients with thymic malignancies and graft-versus-host disease (GVHD) are predisposed to irAEs.

We present two patients, one patient with thymoma and one patient with GVHD, who developed asymptomatic abnormal brain MRIs following treatment with programmed cell death protein 1 inhibitors. 

The first patient, with thymic cancer and thymoma, developed pontine enhancing MRI lesions resembling Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement responsive to Steroids (CLIPPERS) following treatment with pembrolizumab. Serum tests for inflammatory disease were normal (ANA <40, C3 114, C4 28.1, anti-dsDNA, RF <10, anti ENA RNP, and anti ENA Smith). Cerebrospinal fluid (CSF) contained 1 red blood cell (RBC), 3 white blood cells (WBC) (lymphocytes 97%, monocytes 3%), glucose 59 mg/dL, protein 37 mg/dL, and 4 unique oligoclonal bands. Negative CSF studies included C-reactive protein, interleukin (IL)-6, VDRL, gram stain and culture, meningitis/encephalitis panel, fungal culture, acid-fast stain, paraneoplastic panel, and cytology.

The second patient, with prior GVHD, developed pachymeningeal enhancement following a single dose of nivolumab. CSF studies showed 455 RBC, 27 WBC  (81% lymphocytes, 18% monocytes, 1% neutrophils), glucose 72 mg/dL, protein 70 mg/dL. Negative CSF studies included gram stain and bacterial and fungal cultures, meningitis/encephalitis panel, and cytology. Serum paraneoplastic panel was also negative. Bone marrow biopsy did not show evidence of AML relapse. Skin biopsy pathologic findings were consistent with sclerodermatous GVHD with lichenoid dermatosis.

Despite asymptomatic status, patients with history of thymic cancer or GVHD presenting with abnormal brain MRIs require further evaluation for mimickers of irAEs. Diagnosis of irAEs impacts the treatment strategy for these patients.