Answer: Malignant lymphoma

Histology: Most primary central nervous system lymphomas are high grade and, in this case, the neoplastic cells are large with round or reniform nuclei and prominent nucleoli. At low magnification, the infiltrates are typical patchy, poorly demarcated and prominently angiocentric. The last feature is a key histologic feature of lymphoma. Another characteristic feature of most cases of primary central nervous system lymphoma is the presence of varying numbers of small, and cytologically benign lymphocytes accompanied by histiocytes and reactive astrocytes. Around blood vessels, the small lymphocytes may be intimately admixed with the large neoplastic cells, but in other areas the small lymphocytes may be the only hematopoetic element. The majority of peripheral central nervous system lymphomas exhibit a B cell immunophenotype, as did the cells in this particularly case.

Discussion: The differential diagnosis of primary central nervous system lymphoma is centered on two issues. If the lesion is clearly neoplastic, other tumors such as high grade glioma or metastatic carcinoma need to be excluded. If the lesion is clearly hematopoetic in nature, but not clearly malignant, the distinction between inflammatory and neoplastic process must be resolved. The cytologic atypia of most primary central nervous system lymphomas makes their distinction from chronic inflammatory lesions relatively straight forward. There are exceptions however, because in rare instances, the lymphoma may be well-differentiated, and in other instances, the B cells of a higher grade lesion may be obscured by an inflammatory T-cell infiltrate. This latter problem impacts the use of sterotactic needle biopsy for the diagnosis of cerebral lymphoma. The small specimens obtained by this method may not be representative, and may include only a mixed and reactive-appearing infiltrate, rather than the dense perivascular population of atypical cells. Cytologic preparations, and use of frozen section can insure that overtly neoplastic tissue has been obtained and will usually resolve this problem.

Differentiation from high-grade glioma is based on the lack of the vascular proliferation seen in high-grade glioma. Peripheral palisading of tumor cells is also typically absent. The cells of primary central nervous system lymphoma may infiltrate the brain parenchyma, but they will have large and vesicular nuclei, a feature not common to cells of the central nervous system. Differentiation from metastatic carcinoma may be difficult, but clinical information and immunocytochemical techniques should resolve the issue. On frozen section, the absence of cohesive groups of cells, and the diffuse permeative growth pattern of brain invasion by lymphoma would help to separate that lesion from metastatic carcinoma.