Diagnostic red flags: steroid-treated malignant CNS lymphoma mimicking autoimmune inflammatory demyelination

Abstract

The presence of inflammation and demyelination in a central nervous system (CNS) biopsypoints towards a limited, yet heterogeneous group of pathologies, of which multiple sclerosis(MS) represents one of the principal considerations. Inflammatory demyelination has alsobeen reported in patients with clinically suspected primary central nervous system lymphoma(PCNSL), especially when steroids had been administered prior to biopsy acquisition. Thehistopathological changes induced by corticosteroid treatment can range from mild reductionto complete disappearance of lymphoma cells. It has been proposed that in the absence ofneoplastic B cells, these biopsies are indistinguishable from MS, yet despite the clinicalrelevance, no histological studies have specifically compared the two entities. In this work,we analyzed CNS biopsies from eight patients with inflammatory demyelination in whomPCNSL was later histologically confirmed, and compared them with nine well defined earlyactive multiple sclerosis lesions. In the patients with steroid-treated PCNSL (ST-PCNSL) theinterval between first and second biopsy ranged from 3 to 32 weeks; all of the patients hadreceived corticosteroids before the first, but not the second biopsy. ST-PCNSL patients wereolder than MS patients (mean age: ST-PCNSL: 6264 years, MS: 3062 years), andhistological analysis revealed numerous apoptoses, patchy and incomplete rather thanconfluent and complete demyelination and a fuzzy lesion edge. The loss of Luxol fast bluehistochemistry was more profound than that of myelin proteins in immunohistochemistry,and T cell infiltration in ST-PCNSL exceeded that in MS by around fivefold (P50.005).Our data indicate that in the presence of extensive inflammation and incomplete,inhomogeneous demyelination, the neuropathologist should refrain from primarilyconsidering autoimmune inflammatory demyelination and, even in the absence of lymphomacells, instigate close clinical follow-up of the patient to detect recurrent lymphoma.