Supplementary Material for: Peripheral T-cell lymphoma mimicking CLIPPERS: a case report with confirmatory brain biopsy and longitudinally extensive transverse myelitis

Background: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a steroid-responsive relapsing-remitting disorder of the central nervous system. However, CLIPPERS-like presentations have been increasingly recognized as potential early manifestations of underlying lymphoma, most commonly B-cell types. T-cell lymphomas in this context remain exceedingly rare.

Case presentation: We report the first case of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), mimicking CLIPPERS with confirmatory brain biopsy evidence. A 33-year-old man initially presented with pontocerebellar dysfunction and punctate gadolinium-enhancing hindbrain lesions, fulfilling diagnostic criteria for probable CLIPPERS. He achieved transient remission with corticosteroids but later developed relapsing neurological and pulmonary symptoms, radiological progression with supratentorial and spinal involvement including longitudinally extensive transverse myelitis (LETM), and steroid resistance. Despite non-diagnostic lung biopsy and the absence of malignant cells on cerebrospinal fluid (CSF) cytology, CSF circulating tumor DNA (ctDNA) analysis revealed pathogenic mutations in FAS and TET2. Stereotactic biopsy of a right frontal lesion ultimately confirmed PTCL-NOS. The patient’s disease progressed despite chemotherapy, leading to death six months after diagnosis.

Conclusions: This case highlights that central nervous system (CNS) infiltration by PTCL-NOS can closely mimic CLIPPERS both clinically and radiologically. LETM may represent an additional warning feature in such presentations. Vigilance for clinical and radiologic red flags, the adjunctive use of CSF ctDNA analysis, and early reconsideration of diagnosis with timely biopsy should be emphasized to improve outcomes in patients with CLIPPERS-like syndromes.