Clinical Geriatrics

INTRODUCTION
Radiation-induced^1,2 second primary malignant tumors include meningiomas, sarcomas, and gliomas. Patients who received prophylactic intracranial irradiation and intrathecal methotrexate for acute lymphocytic leukemia or lymphoma may occasionally also develop brain tumors. Such tumors consist mainly of glioma. Rarely, meningioma, meningeal melanocytoma, fibrosarcoma, and primitive neuroectodermal tumor have also been described.^1,3 We report herein an interesting case of primary central nervous system (CNS) lymphoma developing 8 years after irradiation for cavernous sinus angioblastic meningioma.

CASE PRESENTATION
A 64-year-old Caucasian male presented to his primary care physician with decreased appetite, slowness, unsteady gait, and increased sleepiness for 2 weeks. Head computed tomographic scan and magnetic resonance imaging scan revealed a mass involving the splenium, body of the corpus callosum, occipital horn of the right lateral ventricle, hypothalamus, and basal ganglia (Figure 1). Subsequent brain biopsy showed large B-cell malignant lymphoma.

The patient developed cerebral edema and left hemiplegia during his hospital stay, and died approximately 1 month after the admission because of complications attributed to the brain tumor, acute confluent necrotizing bronchopneumonia, and acute myocardial infarction secondary to severe coronary arteriosclerosis. There was no evidence of extracranial lymphoma at postmortem evaluation.

The clinical history indicated a left craniotomy 8 years earlier for cavernous sinus hemangiomatous tumor, compatible with angioblastic meningioma, that was followed by 35 treatments of irradiation with a total dose of 3500 rads.

Pathologic findings
A round, fairly well demarcated, gray/white, 3.7 x 2.8 x 2.0–centimeter mass involved the right frontal, parietal, and temporal lobes, with infiltration of the right lateral ventricle. The latter was also narrowed by the tumor, and the right cerebrum was edematous (Figure 2). No residual angioblastic meningioma was found at autopsy.

The tumor cells were large, malignant lymphoid cells. They showed prominent nuclear membrane irregularities and nuclear lobulation, with scant cytoplasm (Figure 3). Occasional abnormal mitoses were present. Perivascular neoplastic cell cuffing was prominent.

Immunohistochemistry study revealed tumor cell positivity for leukocyte common antigen, B-lymphocyte markers (CD20, CD45RA) (Figure 4), and negative reaction for T-lymphocyte markers (CD3, CD5, CD43, OPD4 and CD8), glial fibrillary acid protein, keratins, and synaptophysin. The diagnosis was confirmed on the biopsy and autopsy tumor materials as primary malignant lymphoma, large B-cell type.

Complete postmortem studies, including gross and microscopic evaluation of the spleen, lymph nodes of various location, mediastinum, bone marrow, and liver, failed to reveal lymphomatous infiltrates.

DISCUSSION
Radiation-induced second primary malignant tumors in the brain have been well documented. These are in a descending order of occurrences: meningiomas, gliomas, and sarcomas.^1-9 These tumors appear after a latent period ranging from 1 to 47 years. Among patients receiving prophylactic cranial irradiation and intrathecal methotrexate for acute lymphocytic leukemia or lymphoma, such tumors consist mainly of gliomas. Rarely, meningioma and an instance of meningeal melanocytoma, fibrosarcoma, and primitive neuro-ectodermal tumor have been recorded.¹

Cahan et al⁴ have established four criteria for post-radiation osteogenic sarcomas: (1) microscopic or roentgenographic evidence of the nonmalignant nature of the initial bone condition; (2) the presence of the subsequent sarcoma in the area of irradiation; (3) a long, asymptomatic latent period; and (4) histological verification of the sarcoma.