MACROSCOPIC APPEARANCES

PCNSL in the post-mortem brain is often multifocal. The lesions appear quite well demarcated despite microscopic infiltration of surrounding tissue (Figs 41.1, 41.2). The affected brain tissue is softened, cream or brown in color, and may be focally hemorrhagic. Infiltrated meninges appear thick, and subependymal intraventricular spread may manifest as areas of irregularity and softening.

MICROSCOPIC APPEARANCES

Many PCNSLs are characterized by sheets of lymphoma cells separated by areas of necrosis. The cells tend to invade the walls of small cerebral blood vessels and accumulate in perivascular spaces (Fig. 41.3). This produces a characteristic lacy pattern of reduplicated perivascular reticulin (Fig. 41.4), which is evident even in necrotic tissue. Small-cell PCNSLs tend to be more infiltrative and less necrotic than large-cell PCNSLs. At its infiltrative edge, PCNSL diffusely invades CNS tissue, mimicking a glioma (Fig. 41.5). Like some neuroepithelial neoplasms, PCNSL also spreads through the subarachnoid space and invades the pial surface of the brain. Meningeal and intraventricular spread can be extensive (Fig. 41.6, see also Fig. 41.2b).

Diffuse large B cell lymphomas (DLBCLs) account for more than 95% of PCNSLs. All morphological variants of DLBCL, including centroblastic, immunoblastic, and anaplastic, occur in the CNS. They contain cells somewhat resembling centrocytes, centroblasts or immunoblasts, but their histology is not identical to that of nodal diffuse large B cell lymphomas. Neoplastic cells are admixed with smaller cells, including reactive T cells (Fig. 41.7), and there are many mitotic figures and apoptotic bodies.

Fewer than 5% of PCNSLs are low grade B cell lymphomas with lymphocytic or lymphoplasmacytoid cytology. Cells in these neoplasms are more monomorphic than those in their high grade counterparts (Fig. 41.8). The low grade marginal zone B cell (or MALT) lymphoma characteristically presents as a meningeal mass (Fig. 41.9).

T cell PCNSLs are very rare, and comprise monomorphic and pleomorphic neoplasms. They often have a subcortical location and vasculitic features (Figs 41.10, 41.11).

The infiltrated brain parenchyma shows reactive changes such as astrocytosis and an increase in activated microglia. These changes may be florid and can lead to a misdiagnosis of an inflammatory rather than a neoplastic disorder.

The neoplastic cells of the rare CNS angiotropic lymphoma (previously termed malignant angioendotheliomatosis), which is usually a large B cell lymphoma, fill the lumina of small cerebral vessels and invade the surrounding parenchyma in only a few places (Fig. 41.12). These neoplasms tend to cause vascular occlusion and hemorrhagic infarcts. Most are systemic lymphomas that preferentially affect the CNS and the skin.

Immunohistochemistry with a panel of antibodies allows characterization of PCNSLs (Fig. 41.13). PCNSL may be distinguished from gliomas and metastatic small-cell carcinomas by immunolabeling of neoplastic cells with an antibody to CD45 (leukocyte common antigen). B cell lymphomas can be differentiated from T cell lymphomas by antibodies to the following antigens:

Immunohistochemistry with antibodies to κ and λ light chains may show light chain restriction in some lymphomas. However, interpretation of these preparations can be difficult, and light chain restriction may be better demonstrated by in situ hybridization. Epstein–Barr virus may be demonstrated in some PCNSLs by immunohistochemistry or in situ hybridization (Fig. 41.14).

Populations of neoplastic lymphoid cells may be revealed using the polymerase chain reaction to detect clonal immunoglobulin or T cell receptor gene rearrangements. All B cell PCNSLs examined so far have been clonal.