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) biopsy points towards a limited, yet heterogeneous group of pathologies, of which multiple sclerosis (MS) represents one of the principal considerations. Inflammatory demyelination has also been reported in patients with clinically suspected primary central nervous system lymphoma (PCNSL), especially when steroids had been administered prior to biopsy acquisition. The histopathological changes induced by corticosteroid treatment can range from mild reduction to complete disappearance of lymphoma cells. It has been proposed that in the absence of neoplastic B cells, these biopsies are indistinguishable from MS, yet despite the clinical relevance, no histological studies have specifically compared the two entities. In this work, we analyzed CNS biopsies from eight patients with inflammatory demyelination in whom PCNSL was later histologically confirmed, and compared them with nine well defined early active multiple sclerosis lesions. In the patients with steroid-treated PCNSL (ST-PCNSL) the interval between first and second biopsy ranged from 3 to 32 weeks; all of the patients had received corticosteroids before the first, but not the second biopsy. ST-PCNSL patients were older than MS patients (mean age: ST-PCNSL: 62 ± 4 years, MS: 30 ± 2 years), and histological analysis revealed numerous apoptoses, patchy and incomplete rather than confluent and complete demyelination and a fuzzy lesion edge. The loss of Luxol fast blue histochemistry was more profound than that of myelin proteins in immunohistochemistry, and T cell infiltration in ST-PCNSL exceeded that in MS by around fivefold (P = 0.005). Our data indicate that in the presence of extensive inflammation and incomplete, inhomogeneous demyelination, the neuropathologist should refrain from primarily considering autoimmune inflammatory demyelination and, even in the absence of lymphoma cells, instigate close clinical follow-up of the patient to detect recurrent lymphoma.

A Case of Multiple Sclerosis—Like Relapsing Remitting Encephalomyelitis Following Allogeneic Hematopoietic Stem Cell Transplantation and a Review of the Published Literature

“…The initial brain biopsy showed a macrophage rich lesion with loss of myelin, but relative preservation of axons, which would be consistent with a demyelinating pathology. It is a rare histological feature of hematological neoplasm and may be erroneously diagnosed as inflammatory demyelination if corticosteroid therapy is used prior to the brain biopsy (20). Acute plaques of demyelination usually have T cells, which tend to be localized perivascularly and are less prevalent than macrophages (21).…”

“…Acute plaques of demyelination usually have T cells, which tend to be localized perivascularly and are less prevalent than macrophages (21). In tumefactive MS, T cells are detected at lower levels than in biopsies that subsequently turn out to be lymphoma (20). However in a small biopsy sample, it is possible that these changes may not be well represented, which is a ubiquitous problem independent of disease studied (21).…”

Two cases of primary ocular adnexal lymphomas diagnosed after pre-biopsy corticosteroid treatment using polymerase chain reaction-based gene rearrangement analysis

“…Corticosteroids may also be administered after a non-diagnostic biopsy to control progressive symptoms of lymphoid disorders, as seen in the cases presented herein. Corticosteroid treatment induces lymphocytolysis and alters the cytohistological structure 10, 11, 12, 13. Furthermore, corticosteroid treatment diminishes immunophenotype characteristics of each lymphoproliferative disorder 10, 11, 12, 13.…”

“…Several clinical conditions may induce non-diagnostic biopsies. Pre-biopsy corticosteroid administration can cause inaccurate diagnosis of lymphomas10, 11, 12, 13; however, there is a lack of published literature reporting on the diagnostic strategy for steroid-treated primary OALs. Herein, the authors discuss the diagnostic usefulness and limitations of standardized BIOMED-2 multiplex polymerase chain reaction (PCR)-based gene rearrangement assays 14 , 15 in detecting clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements in steroid-treated hyalinized hypocellular OAL tissues.…”

Is ultrasound combined with computed tomography useful for distinguishing between primary thyroid lymphoma and Hashimoto’s thyroiditis?

“…Hashimoto's thyroiditis (HT) is known to be characterised by serological test and ultrasound examination, increased antithyroglobulin and anti-thyroperoxidase antibody, and typical micronodular or microcystic change (1-6 mm) with surrounding echogenic septations in ultrasonic images combined with other clinical information has been considered as suggestive of benign disease [10][11][12]. By contrast, a few cases of evaluation of PTL by ultrasound and computed tomography (CT) have been reported, with confused and atypical features in the images [13]. The differences in the findings on ultrasound and CT between PTL and HT were not distinctly addressed.…”