Rhinosporidiosis is a chronic granulomatous disease of the nose caused by Rhinosporidium seeberi. Though R seeberi was discovered by Guillermo Seeberi in Argentina in 1900 and its life cycle described by Ashworth in 1923, 1 the taxonomy of the organism remained uncertain. The lack of a known natural host or reservoir and the inability to grow the organism in culture media compounded the problem. Though initially thought to be a protozoan, the organism was later considered a fungus, and currently, R seeberi is classified as

Objectives: Diffuse infiltrative “non-mass-like” parenchymal lesions on MRI brain are a known presentation of an aggressive condition called lymphomatosis cerebri (LC) but are often misdiagnosed due to its non-specific clinical and imaging findings. We aim to identify clues to differentiate lymphomatosis from its less aggressive mimics based on imaging features. Material and Methods: MRI brain studies showing diffuse infiltrative “non-mass-like” parenchymal lesions between January 2013 and March 2020 were retrospectively identified and read for lesion location, signal characteristics, and enhancement pattern by two radiologists. Additional findings on MRI spine and whole-body fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) were recorded wherever available. The clinical diagnosis, patient demographics, symptoms, laboratory and histopathology results, treatment details, and follow-up details were also noted. Results: Of the 67 patients, 28 (41.7%) were diagnosed with lymphomatosis. The remaining 39 (13.4%) patients were classified as non-lymphomas (infective, vasculitis, and inflammatory conditions). Diffusion restriction on MRI (20/67, P = 0.007) and increased regional activity on FDG PET-CT (12/31, P = 0.017) were the two imaging parameters found to significantly favor lymphomatosis over other conditions, whereas the presence of microhemorrhages on susceptibility-weighted imaging was significantly associated with vasculitis (P = 0.002). Rapid clinical or imaging deterioration on a short trial of steroids (P = 0.00) was the only relevant clinical factor to raise an early alarm of lymphomatosis. Positive serological markers and non-central nervous system systemic diseases were associated with non-lymphomatous diseases. Conclusion: LC and its less aggressive mimics can be differentiated on diffusion-weighted imaging-MRI and PET-CT when read in conjunction with rapid progression of clinical features, serological workup, and systemic evaluation.