Co-ocurrence of polyradiculopathy and systemic sclerosis delaying the diagnosis of primary neurolymphomatosis

Abstract

Case Presentation: A 57-year-old male presented a slowly progressive proximal flaccid paraparesis associated with dermatomal sensory loss and severe neuropathic pain. Shortly after, he also developed systemic symptoms compatible with systemic sclerosis, which was confirmed after skin biopsy. Initial neurologic investigation was unremarkable. After initiation of methotrexate, he substantially improved his neurological picture; however, dosage was titrated down due to pneumonitis and the patient evolved with marked clinical worsening. Reinvestigation revealed neurolymphomatosis as the cause of the polyradiculopathy; magnetic resonance imaging showed bone lesions in the skull and vertebrae, and positron emission tomography with fluorodeoxyglucose showed hypermetabolic lymph nodes, visceral lesions, and uptake along spinal roots and the spinal cord. Biopsy confirmed diffuse large B cell lymphoma with meningeal involvement. Discussion: Neurolymphomatosis is a rare variant of non-Hodgkin lymphoma and most commonly presents as rapidly progressive asymmetric polyneuropathy. The diagnostic investigation of this patient illustrates the challenge of identifying this condition as the cause of chronic polyradiculopathy. The initial clinical presentation suggested radicular involvement, but early magnetic resonance imaging and electroneuromyography were normal. Diagnostic delay is more than doubled in primary neurolymphomatosis when compared to secondary cases, and misdiagnosis is reported in half of them. Slow progression and root involvement, as seen in our patient, are factors consistently linked to diagnostic delay. In this case, the diagnosis of systemic sclerosis - which has been linked to non-Hogkin lymphoma - also contributed to delaying the diagnosis. Cerebrospinal fluid analysis showing lymphomononuclear pleocytosis and elevated protein reinforced the hypothesis of an inflammatory process. Diffuse inflammatory polyradiculopathy is unusual in systemic sclerosis and electrophysiological findings in this case did not support this diagnosis; however, initial improvement with immunoglobulin and methotrexate further corroborated this interpretation. Clinical relapse associated with worsening cerebrospinal fluid abnormalities prompted diagnostic reassessment. This time, magnetic resonance imaging and positron emission tomography were essential in raising the diagnosis and identifying extra-neurological sites suitable for biopsy. They are considered at least as sensitive as the gold-standard nerve biopsy. Final Comments: This case highlights an unusual presentation of neurolymphomatosis as chronic painful polyradiculopathy preceding the diagnosis of lymphoma and occurring in a patient with systemic sclerosis, a rare association that significantly contributed to diagnostic delay. It reinforces the complexity of overlapping neurological and rheumatological manifestations, which may be causally related but may also coexist due to a third condition.