Demyelination as a harbinger of lymphoma: a case report and review of primary central nervous system lymphoma preceded by multifocal sentinel demyelination

Abstract

BackgroundPrimary central nervous system lymphoma (PCNSL) may rarely be preceded by “sentinel demyelination,” a pathologic entity characterized by histologically confirmed demyelinating inflammatory brain lesions that mimic multiple sclerosis (MS) or acute disseminated encephalomyelitis (ADEM). Interpreting the overlapping radiologic and clinical characteristics associated with each of these conditions—contrast-enhancing demyelination of white matter and relapsing and remitting steroid-responsive symptoms respectively—can be a significant diagnostic challenge.Case presentationWe describe a 57-year-old woman with an unusual clinical course who presented with multi-focal enhancing white matter lesions demonstrated to be inflammatory demyelination by brain biopsy. Despite a good initial response to steroids and rituximab for treatment of presumed tumefactive multiple sclerosis, the patient’s condition rapidly deteriorated, and a repeat brain biopsy six months later was consistent with a diagnosis of diffuse large B-cell lymphoma.ConclusionsEarly clinical suspicion for PCNSL and awareness that biopsied lesions may initially show sentinel demyelination suggestive of alternate diagnoses may be essential for early initiation of appropriate therapies and mitigation of disease progression. Clinical, pathophysiological, and diagnostic aspects of sentinel demyelination and PCNSL are discussed.

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

“…Consistent with previous publications (2,6,7,9,12,(16)(17)(18), we show that a histologically confirmed diffuse large B cell lymphoma can initially manifest as a demyelinating lesion with prominent inflammation and no evidence of lymphoma cells, a finding often referred to as 'sentinel lesion'. Most of the literature describes patients who, similar to our cohort, underwent corticosteroid therapy prior to biopsy acquisition, thus reinforcing the view that the sequential manifestation of demyelination and diffuse large B cell lymphoma could be related to the corticosteroid treatment (2,(7)(8)(9)14).…”

“…Most often a clinical and pharmacological review of the cases reveals that steroids had been administered prior to biopsy acquisition. It has been suggested that the tissue features found in these biopsies may be indistinguishable from classical autoimmune inflammatory demyelinating diseases such as MS, although no studies specifically addressing this question have been reported (4,(14)(15)(16). Moreover, the utility of molecular diagnostic approaches may be limited when no histological evidence of lymphoma cells is available, thus underscoring the importance of identifying histological hallmarks for the differential diagnosis of these two entities (4,9).…”

Brain invasion by chronic lymphocytic leukemia

“…12 In multiple sclerosis, the enhancing lesion of the open ring sign represents the area of active inflammation, while the non-enhancing area represents the inflammatory process in its most chronic phase. 13,14 In fact, myelinoclasis was confirmed pathologically in the present case. Although the cause of the myelinoclasis was unclear, the findings of occluded small arterioles by massive leukemia cell invasion to the Virchow-Robin space suggest ischemia as the cause of the myelinoclasis.…”

“…The discontinuous ring enhancement observed in the present case is similar to the open ring sign, and its specificity for demyelination is 93.8% . In multiple sclerosis, the enhancing lesion of the open ring sign represents the area of active inflammation, while the non‐enhancing area represents the inflammatory process in its most chronic phase . In fact, myelinoclasis was confirmed pathologically in the present case.…”

Multifocal central nervous system lymphoma misdiagnosed as acute disseminated encephalomyelitis

“…Кроме того, в дальнейшем у пациентки развилась зависимость от ГКС -уменьшение дозировки препаратов или прекращение терапии крайне быстро (в течение нескольких суток) приводило к выраженному ухудшению состояния. Этот признак характерен для лимфом ЦНС, однако не наблюдается при ОРЭМ и других демиелинизирующих заболеваниях, что делает его важным для проведения дифференциальной диагностики этих заболеваний [19].…”