Epithelioid germinal centers in overwhelming childhood infections. The aftermath of nonspecific destruction of follicular B cells by natural killer cells.

The destruction of proliferating lymphoid cells within germinal centers with subsequent replacement by histiocytoid cells has been described in infants and children dying of viral and bacterial infections. The etiology and significance of "epithelioid germinal centers" (EGCs) are unknown. The cells implicated in forming EGCs have included histiocytes and dendritic reticulum cells. We have studied four children at autopsy who died at ages ranging from 10 months to 7 years. Three contracted fatal infections, one with fulminant meningococcemia, one with bacterial sepsis, and one with viral hepatitis. The fourth child contracted viral pneumonitis and died of acetaminophen toxicity. Epithelioid germinal centers were found in numerous lymphoid organs (spleen, lymph nodes, and Peyer's patches) in all four cases. Avidin-biotin complex immunohistochemical analysis performed on formalin-fixed splenic tissue from the first three cases and snap-frozen splenic tissue from the second case revealed an absence of B cells in the follicular centers. The mantle zones surrounding follicles were thin but intact. The histiocytoid cells expanding the germinal centers were positive for S100 and R4/23 (dendritic reticulum cells) and negative for numerous histiocyte markers (alpha 1-antitrypsin, alpha 1-antichymotrypsin, and lysozyme). Increased numbers of killer cells (Leu-7) were present within the affected germinal centers in the three cases in which material was available for immunohistochemical studies. Overwhelming infections in these patients seem to result in anomalous natural killer cell activation resulting in localized nonselective destruction of follicular centers similar to anomalous natural killer cell activity reported to occur in fatal infectious mononucleosis. This may lead to an acquired immunodeficiency that precludes long-term survival in affected patients.

Castleman's disease of the leptomeninges. Report of three cases.

Castleman's disease is a rare, benign lymphoproliferative disorder that usually arises in lymph nodes, most commonly in the mediastinum. The authors report the clinical and pathological features of three patients with localized Castleman's disease of the leptomeninges. There were two women, aged 63 and 82 years, and one 25-year-old man. Two patients had progressive focal motor seizures of 3 and 24 months' duration, and the third patient presented acutely with generalized seizures. The clinical diagnosis was meningioma in each case, based on computerized tomography scans, cerebral arteriography, and the operative findings. All three lesions arose in the leptomeninges, compressed the underlying cerebral cortex, and infiltrated the overlying dura to a variable extent. Surgical excision of the tumor resulted in marked clinical improvement in all three patients. Histologically, two cases were classified as the hyaline-vascular type and one as the plasma cell type. Immunohistochemical stains of the latter case revealed a monoclonal population of mature plasma cells. Only a few scattered polyclonal plasma cells were seen in the other two cases. The authors conclude that Castleman's disease involving the leptomeninges is a rare disorder that may mimic meningioma clinically and radiographically.

Radiation-induced neoplasms of the brain.

The histopathology of two patients with radiation-induced neoplasms of the brain following therapeutic irradiation for intracranial malignancies is described. The second neoplasms were an atypical meningioma and a polymorphous cell sarcoma, respectively. They occurred 12 and 23 years after irradiation (4000 rad), within the original field of irradiation. In both cases, the radiation-induced tumors were histologically distinct from the initial medulloblastomas. Both patients were retreated with local irradiation using permanent implantation of radioactive iodine-125 seeds.