CNS B cell infiltration in tumefactive anti-myelin oligodendrocyte glycoprotein antibody-associated disease

Abstract

Background: Few studies have examined B cells among patients with anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), including brain pathology.

Objective: To describe cases of tumefactive MOGAD with B-cell dominant central nervous system (CNS) infiltration.

Methods: In this study, we reviewed three cases with clinical and brain histopathological features with tumefactive MOGAD.

Results: Forty-nine cases of tumefactive brain lesions (TBL) between January 2003 and December 2023 were included; of these, seven had MOGAD. Three underwent a brain biopsy. B-cell dominant CNS infiltration was observed in two cases. In two cases with B-cell dominant CNS infiltration, symptoms included fever, headache, nausea, somnolence, and focal neurological deficits. Cerebrospinal fluid examination revealed both mild pleocytosis and negative oligoclonal IgG bands. Magnetic resonance imaging of the brain revealed large abnormal lesions extending from the basal ganglia to the parietotemporal lobe in both cases. These cases showed a good response to steroids; however, one case relapsed. Brain pathology showed demyelination and perivascular lymphocytic infiltration. One showed small vessel vasculitis. Deposition of the activated complement component was absent or rarely observed. Loss of MOG was observed in two cases.

Conclusion: MOGAD could exhibit B-cell dominant CNS infiltration and small vessel vasculitis. MOGAD should be considered in differential diagnosis of TBL.

Keywords: Anti-myelin oligodendrocyte glycoprotein antibody-associated disease; B cell; brain histopathology; brain tumor; myelin oligodendrocyte glycoprotein; tumefactive brain lesion.

Figure 1.

Brain imaging ((a)–(c)) and histopathological findings ((d)–(p)) of case 1. (a) FLAIR imaging reveals tumefactive high-intensity lesions from the right thalamus to the parietotemporal lobe. A midline shift is observed. (b) T1-weighted imaging after gadolinium enhancement shows patchy enhancement. (c) Methionine-PET reveals a high methionine uptake (maximum standardized uptake value, 4.3; target-to-normal tissue ratio, 3.4) in the lesion (arrowhead). (d) HE staining shows prominent perivascular lymphocytic infiltration. (e) KB staining shows perivascular demyelination. (f) The staining for MOG shows a loss of MOG immunoreactivity in the perivascular lesion. (g) GFAP staining shows reactive gliosis. (h) Olig2 staining shows immunoreactivity in the nuclei of oligodendrocytes. The immunohistochemistry for CD3 (i) and CD20 (j) reveal T- and B-cell infiltrates around the vessels. Infiltrating lymphocytes are B-cell dominant. (k) Iba-1 positive microglia are observed. No significant monoclonality of λ light chain (l) or κ light chain (m) is observed. (n) The result of in situ hybridization for Epstein–Barr virus-encoded early small RNA (EBER) is negative. HE staining (o) and EVG staining (p) shows the disruption of several blood vessel walls. (q) FLAIR imaging reveals high-intensity lesions extending from the left basal ganglia to the insula 4.5 years after onset. (r) T1-weighted imaging after gadolinium enhancement shows heterogeneous enhancement. Scale bars in (d), (e), (f), (g), (h), (l), (m), (n), (o), and (p) = 50 μm. Scale bars in (i), (j), and (k) = 100 μm. EVG: Elastica van Gieson; FLAIR: fluid-attenuated inversion recovery; GFAP: glial fibrillary acidic protein; HE: hematoxylin-eosin; Iba-1: ionized calcium-binding adapter molecule 1; KB: Klüver-Barrera; MOG: myelin oligodendrocyte glycoprotein; NFP: neurofilament protein; Olig2: oligodendrocyte transcription factor 2; PET: positron emission tomography.

Figure 2.

Brain imaging ((a)–(c)) and histopathological findings ((d)–(l)) of case 2. (a) FLAIR imaging reveals a tumefactive high-intensity lesion from the left basal ganglia (caudate nucleus and putamen) to the parietotemporal lobe. (b) T1-weighted imaging after gadolinium enhancement shows marginal enhancement. (c) Methionine PET reveals a high methionine uptake (maximum standardized uptake value, 2.5; target-to-normal tissue ratio, 2.2) in the lesion (arrowhead). (d) HE staining shows perivascular lymphocytic infiltration. (e) KB staining shows perivascular demyelination. (f) Staining for MOG shows a loss of MOG immunoreactivity in the perivascular lesion. (g) GFAP staining shows reactive gliosis. ((h)–(j)) Immunohistochemistry for CD3 (h), CD4 (i), and CD20 (j) reveal both T- and B-cell infiltrates around the vessels. Infiltrating lymphocytes are B-cell dominant. (k) CD68-positive macrophages are also observed in the perivascular lesion. (l) Deposition of the activated complement component (C9neo) is rarely observed. (m) FLAIR imaging reveals a high-intensity lesion in the pons 9 months after brain biopsy. (n) T1-weighted imaging after gadolinium enhancement shows marginal enhancement. Scale bars in (d), (f), (g), (h), (i), (j), (k), and (l) = 50 μm. Scale bar in (e) = 100 μm. FLAIR: fluid-attenuated inversion recovery; GFAP: glial fibrillary acidic protein; HE: hematoxylin-eosin; FLAIR: fluid-attenuated inversion recovery; KB: Klüver-Barrera; MOG: myelin oligodendrocyte glycoprotein; PET: positron emission tomography.

Figure 3.

Brain imaging ((a), (b), (m), and (n)) and histopathological findings ((c)–(l)) of case 3. (a) FLAIR imaging reveals a tumefactive high-intensity lesion from the left basal ganglia to the parietotemporal lobe. (b) T1-weighted imaging after gadolinium enhancement shows open-ring enhancement. (c) and (d) HE staining reveal perivascular lymphocytic infiltration (c) and marked foamy macrophages (d). (e) KB staining shows prominent demyelination. (f) The staining for MOG shows a loss of MOG immunoreactivity in the perivascular lesion. (g) GFAP staining shows reactive gliosis. (h) and (i) Immunohistochemistry for CD3 (h) and CD20 (i) reveal both T- and B-cell infiltrates around the vessels. Infiltrating lymphocytes are T-cell dominant (compatible CD4 + and CD8+ T cells). (j) CD68-positive macrophages are observed in the perivascular lesion. (k) Deposition of the activated complement component (C9neo) is rarely observed in the perivascular lesion. (l) FLAIR imaging reveals a high-intensity lesion in the right occipital lobe 6 months after brain biopsy. (m) T1-weighted imaging after gadolinium enhancement shows a ring-like enhancement. Scale bars in (c), (d), and (g) = 50 μm. Scale bars in (f), (h), (i), (j), and (k) = 100 μm. Scale bars in (e) = 200 μm. FLAIR: fluid-attenuated inversion recovery; GFAP: glial fibrillary acidic protein; HE: hematoxylin-eosin; FLAIR: fluid-attenuated inversion recovery; KB: Klüver-Barrera; MOG: myelin oligodendrocyte glycoprotein; PET: positron emission tomography.