From the Archives of the AFIP: Primary Central Nervous System Lymphoma

Radiologic-Pathologic Correlation

Abstract Introduction Prevalence Historical Perspective

Pathogenesis Clinical Presentation Pathologic And Histologic Features Radiologic Features

Prognosis and Treatment Summary Source Information References

Pathologic And Histologic Features

There are four gross pathologic manifestations of primary CNS lymphoma. Intraaxial nodules occur most commonly and are more frequently seen in the cerebral hemispheres than in the posterior fossa. Diffuse meningeal or periventricular involvement is seen in 24% of cases; uveal or vitreous lesions and focal intradural spinal masses are much less frequent (1,7).

At gross pathologic examination, CNS lymphoma manifests as a grayish-tan to pink, homogeneous, circumscribed nodular mass with firm to friable consistency and a granular surface. The lesion is frequently surrounded by edema, commonly spreads to the leptomeninges and subpial region, and is multifocal in almost half of the cases (6,41,50). Focal necrosis and hemorrhage are common (6,29,41,51).

At histologic analysis, CNS lymphoma exhibits sheets of monotonous, closely packed blue cells; has a high degree of cellularity; and infiltrates far beyond the borders of the grossly observed mass. Necrosis and hemorrhage are much more frequently seen in the lesions of immunocompromised patients (6,50). The neoplastic cells tend to cluster along vascular channels, a phenomenon that supports the theory that CNS lymphoma spreads diffusely through the brain by way of the perivascular (Virchow-Robin) spaces (5). Thus, the lesion infiltrates blood vessel walls, simulating the histopathologic appearance of vasculitis (Figure 1, Figure 2) (7).

Today, immunohistochemical analysis is essential in the pathologic diagnosis of primary CNS lymphoma. The most commonly used antibodies are directed against common leukocyte antigens, pan-B antigens, and pan-T antigens. Tumors typically contain a population of atypical pleomorphic B cells mixed with reactive T cells, most likely recruited as a host response to the tumor. Accordingly, even though primary CNS lymphomas are considered monoclonal, the lesions virtually always contain two cell populations, one neoplastic and one reactive (Figure 1, Figure 2).

Primary CNS lymphoma is almost always a B-cell lymphoma. Attempts to correlate the radiologic features of CNS lymphoma with the specific histologic subtype have been less than successful (16,50). Jack et al (16) found that CNS lymphomas of the mixed cell type tended to be multifocal compared with other types and that small noncleaved lymphomas (as classified according to the Working Formulation) tended to occur in the central gray matter or corpus callosum. There is also a tendency for smaller CNS lymphomas to be of a higher histologic grade (16).

Just as with the early history of the nomenclature for primary CNS lymphoma, the histopathologic classification of CNS lymphoma has been difficult and fraught with controversy. Many different schemes, such as the Rappaport system for non-Hodgkin lymphomas, have been proposed, partially used, and then partially abandoned for various reasons. An attempted compromise system, known as the Working Formulation of Non-Hodgkin Lymphomas, was created in the early 1980s to better stratify the many types and subvariants identified by pathologists. Although this classification received wide acceptance in the United States, European investigators remained loyal to the Kiel classification. Therefore, in 1992, the Revised European-American Lymphoma (REAL) classification was established, in part from a desire to create a single, internationally recognized classification system (52). In general, lymphomas are divided into low-grade, high-grade, and possibly intermediate-grade non-Hodgkin lymphomas.

As with other extranodal non-Hodgkin lymphomas, primary CNS lymphoma is usually high grade, and all cases of primary CNS lymphoma fit in the diffuse histologic category (Rappaport system) (1,7). Primary CNS lymphomas in patients with AIDS and in those without are indistinguishable on pathologic or immunopathologic grounds (1). Until 1983, primary CNS lymphomas were overwhelmingly high-grade tumors (88% of cases), and only 12% of cases were intermediate-grade lesions. However, since that time, no intermediate-grade CNS lymphomas have been reported. This observation—along with the fact that large cell, noncleaved lymphoma increased in prevalence from 10% of all CNS lymphomas before 1981 to 33% of all CNS lymphomas since that time—has led investigators to conclude that CNS lymphoma has undergone a fundamental biologic change in behavior. Today, almost half of CNS lymphomas are of the high-grade, large cell, immunoblastic subtype (1).

Abstract Introduction Prevalence Historical Perspective

Pathogenesis Clinical Presentation Pathologic And Histologic Features Radiologic Features

Prognosis and Treatment Summary Source Information References