Insulin-like growth factor II mRNA binding protein 3 is highly expressed in primary diffuse large B-cell lymphoma of the CNS

Abstract

Primary diffuse large B-cell lymphoma of the central nervous system (CNS-DLBCL) can be difficult to diagnose because of the limited amount of biopsy tissue. Here, we analyzed the utility of insulin-like growth factor II mRNA binding protein 3 (IMP3) immunohistochemistry (IHC) as an adjunctive diagnostic tool for CNS-DLBCL. IHC was performed on 57 biopsy samples (55 brain biopsy samples and two vitreous cell blocks) from 54 patients with CNS-DLBCL, including three biopsy samples initially diagnosed as negative or indeterminate for CNS-DLBCL. Additionally, IMP3 IHC was performed on 68 DLBCLs other than CNS-DLBCL and 12 inflammatory brain diseases. Cytoplasmic IMP3 expression was noted in ≥50% of tumor cells in 100% (57/57) of CNS-DLBCLs and 88.2% (60/68) of non-CNS-DLBCLs. In contrast, no IMP3-positive CD20-positive B cells were observed in the inflammatory brain disease (P < 0.0001). In conclusion, IMP3 is highly expressed in CNS-DLBCL. However, it is also expressed in other types of DLBCLs, making it less specific. Most CNS-DLBCL cases can be diagnosed without performing IHC for IMP3 expression, but it may be a useful adjunctive tool to differentiate from reactive lesions when tumor cells are few or deformed.

Keywords: immunohistochemistry; insulin-like growth factor II mRNA binding protein 3; primary diffuse large B-cell lymphoma of the central nervous system.

Fig. 1

Primary diffuse large B-cell lymphoma of the CNS. Lymphoma cell infiltration around blood vessels and within brain parenchyma. Lymphoma cells are large, with vesicular nuclei and prominent nucleoli (inset) (A). Lymphoma cells are positive for CD20 (B) and IMP3 (C). Diffuse large B-cell lymphoma of the vitreoretinal in cell block specimens. A few degenerated lymphoma cells are observed in the vitreous fluid (D) and are positive for CD20 (E) and IMP3 (F).

Fig. 2

First biopsy from a patient with primary diffuse large B-cell lymphoma of the CNS (CNS-DLBCL) for which a definite diagnosis of lymphoma could not be made. Perivascular cuffing lymphocytes. (A) with CD20 expression (B). Crush artifacts limit cytomorphological evaluation. Retrospective analysis revealed strong IMP3 expression by lymphocytes, suggesting CNS-DLBCL (C). Primary CNS vasculitis. Perivascular cuffing of small lymphocytes is observed (D). Lymphocytes are positive for CD20 (E), but negative for IMP3 (F).