The infiltration and invasion of nerve trunks, nerve roots, and cranial nerves by lymphomatous
malignant cells is defined as “neurolymphomatosis”. It is mainly caused by lymphoma cells directly
infiltrating the peripheral nerves, with a low incidence. Neurolymphomatosis is a rare condition of neoplastic
endoneurial invasion, which is primary or secondary to non-Hodgkin’s lymphoma and leukemia. We describe
a case of primary peripheral neurolymphomatosis of multifocal involvement in a 77-year-old male patient.
He presented with left lower limb pain and was diagnosed with CD20+ diffuse large B cell lymphoma
(DLBCL). Magnetic resonance imaging (MRI), fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission
tomography (PET) computed tomography (CT), and nerve biopsy contributed to the diagnosis. Genomic
profiling, programmed death ligand-1 (PD-L1) expression and tumor mutational burden (TMB) were also
assessed. CDKN2A/CDKN2B deletions have been identified. PD-L1 expression assessed by 28-8 antibody
was 1% positivity, and TMB of the sample was 11.6 muts/Mb. The patient responded well to rituximab
combined with chemotherapy, however, he died after 3 cycles of chemotherapy due to severe lung infection
and subsequent complication of respiratory failure. Here we report the clinical, radiological, pathological and
molecular findings of the patient affected by multifocal neurolymphomatosis without systemic involvement
of other organs.