Case-based review: primary central nervous system lymphoma

Abstract

Primary CNS lymphoma (PCNSL) is a rare diffuse large B-cell lymphoma originating within the central nervous system. The overall incidence of PCNSL is rising, particularly in the elderly population. Immunosuppression is a strong risk factor, but most patients with this tumor are apparently immunocompetent. Diagnosis of PCNSL can be challenging. Non-invasive or minimally invasive tests such as ophthalmological evaluation and spinal fluid analysis may be useful, but the majority of patients require tumor biopsy for definitive diagnosis. Our knowledge concerning optimum treatment of PCNSL is fragmentary due to paucity of adequately sized trials. Most patients are now initially treated with high-dose-methotrexate-based chemotherapy alone, as the addition of whole-brain radiotherapy at standard doses has not been shown to increase survival and does increase the risk of neurological toxicity. Ongoing trials are addressing issues such as the roles of reduced-dose radiotherapy, the addition of the CD20 antibody rituximab to chemotherapy, high-dose chemotherapy followed by autologous stem cell transplantation, and maintenance therapy in the primary management of PCNSL.

Keywords: high-dose methotrexate; neurotoxicity; primary CNS lymphoma; whole-brain radiotherapy.

Fig. 1

Initial CT and MR imaging. (A) Noncontrast head CT depicts a deep left-frontal mass lesion isointense to gray matter with surrounding vasogenic edema and subfalcine herniation. (B) T2-weighted fluid-attenuated inversion recovery (FLAIR) MR imaging depicts the extent of edema to better advantage. (C) Postgadolinium T1-weighted MR imaging shows intense, homogeneous enhancement of the deep left-frontal tumor. (D) Diffusion-weighted imaging (DWI) shows increased signal in this region. (E) Apparent diffusion coefficient (ADC) image demonstrates foci of reduced signal (one indicated by black arrow) within the region of increased DWI signal indicating true restricted diffusion.

Fig. 2

Initial biopsy after corticosteroid therapy and subsequent diagnostic biopsy at tumor recurrence. Nondiagnostic biopsy after corticosteroid therapy (A-D). White matter shows a marked lymphocytic infiltrate (A, x200) composed of small lymphocytes with dark blue nuclei, parenchymal and perivascular. Small dark apoptotic nuclei (one indicated by the short black arrow) and macrophages (one indicated by the long black arrow) are present in areas of the biopsy (B, x400). The small lymphocytes are nearly exclusively CD3-positive, consistent with reactive T-lymphocytes (C, x200). There are no CD20-positive cells in the infiltrate (D, x200). Diagnostic biopsy at recurrence (E-H). Primary CNS lymphoma cells diffusely infiltrate the parenchyma (E, x200) with monomorphous, large blastic cells largely replacing the tissue (F, x400). While a moderate number of small infiltrating CD3-positive reactive T-lymphocytes is present (G, x200), similar to the first biopsy (C), most cells express the B-cell marker CD20 (H, x200). The morphologic findings in conjunction with the immunophenotype confirm the diagnosis of diffuse large B-cell lymphoma.

Fig. 3

Serial MR imaging after corticosteroid therapy. Serial gadolinium-enhanced T1-weighted MR images (A) prior to corticosteroid therapy, (B) 3 days after the initiation of corticosteroids, (C) 5 days after the initiation of corticosteroids; note interval biopsy defect within the left frontal region of enhancement, (D) 3 months after biopsy, and (E) 8 months after biopsy.

Fig. 4

MR imaging at recurrence and after high-dose methotrexate (HDMTX)-based chemotherapy. (A) T2-weighted fluid-attenuated inversion recovery (FLAIR) and (B) T1-weighted post-gadolinium images at time of radiographic progression. (C) T2-weighted FLAIR and (D) T1-weighted post-gadolinium images following the completion of HDMTX-based chemotherapy demonstrate a complete response.