The tumor forms a pinkish gray, soft, ill-defined, infiltrative mass in the brain, difficult at times to distinguish from an astrocytoma. Perivascular and meningeal spread results in shedding of cells into the CSF, accounting perhaps for the multifocal appearance of the tumor in many cases. The neoplasm is highly cellular and grows around and into blood vessels (“angiocentric” pattern) but elicits no tendency to necrosis. The nuclei are oval or bean-shaped with scant cytoplasm, and mitotic figures are numerous. B-cell markers applied to fixed tissue define the lymphoblastic cell population as monoclonal and identify the tumor cell type. The stainability of reticulum and microglial cells also serves to distinguish this tumor microscopically. There is no tumor tissue outside the brain.
Several of our cases of meningeal and cranial nerve lymphoma with similar histologic characteristics to primary CNS lymphoma were complications of chronic lymphatic leukemia, a type of so-called Richter transformation.
Primary lymphoma involving the cerebral hemispheres initially pursues a clinical course somewhat similar to that of the gliomas but with a vastly different response to treatment. Behavioral and personality changes, confusion, dizziness, and focal cerebral signs predominate over headache and other signs of increased intracranial pressure as presenting manifestations. Seizures may occur but are less common, in our experience, than they are as the introductory feature of gliomas. Most cases occur in adult life, but some have been observed in children, in whom the tumor may simulate the cerebellar symptomatology of medulloblastoma.
The finding on CT and MRI of one or several dense (hypercellular), homogeneous, enhancing, infiltrating, nonnecrotic, nonhemorrhagic, periventricular masses is characteristic (Fig. 30-9). However, rim enhancement also occurs, and any part of the brain may be involved. There is often restriction of diffusion on MRI because of the tumor’s dense cellularity. The radiologic appearance in the immunosuppressed patient is less predictable and may be difficult to distinguish from that of toxoplasmosis, progressive multifocal leukoencephalopathy (PML), or another process with which lymphoma may coexist.
In some cases, a multitude of deep cerebral white matter lesions, some radially oriented and thereby simulating multiple sclerosis, are seen. Tumor enhancement with contrast agents tends to be more prominent and homogeneous than with the acute lesions of multiple sclerosis. A similar multinodular appearance occurs with intravascular lymphoma discussed in a later section. Characteristic of primary CNS lymphoma is the disappearance on imaging of the lesions or complete but transient resolution of contrast enhancement in response to corticosteroids.
Lymphocytic and mononuclear pleocytosis of CSF is more frequent than with gliomas and metastatic tumors, occurring in up to half of cases. The immunohistochemical demonstration in CSF of monoclonal lymphocytes or an elevated beta-2 microglobulin points to leptomeningeal spread of the tumor (Li et al), but frequently the diagnosis is not possible from CSF cytologic examination. Gene rearrangements within the monoclonal cell populations, especially of the immunoglobulin heavy chain gene (IGH) are used a diagnostic test that is more sensitive than cytology of the spinal fluid. These findings occur in approximately one-quarter of patients with proved CNS lymphoma; as noted, it reflects the monoclonality of the lymphocytes.