Depressed cell-mediated immunity in patients with primary intracranial tumors. Characterization of a humoral immunosuppressive factor.

Tumor immunity in patients with primary intracranial tumors was assessed in relation to the general status of host immunocompetence. Lymphocyte sensitization to tumor-specific membrane antigens was demonstrated by the proliferative response of lymphocytes in the presence of autochthonous tumor cells. Paradoxically, one-half of the patients could not be sensitized to a primary antigen, dinitrochlorobenzene; existing delayed hypersensitivity was also depressed, as measured by skin tests and lymphocyte transformation in response to common antigens. A heat-stable factor in patients' sera blocked cell-mediated tumor immunity. In addition, these "enhancing" sera consistently suppressed the blastogenic response of autologous and homologous lymphocytes to phytohemagglutinin and to membrane antigens on allogeneic cells in the one-way mixed lymphocyte culture. When patients' leukocytes were washed and autologous plasma replaced with normal plasma, reactivity in the mixed lymphocyte culture increased to normal values. In vitro immunosuppressive activity in patients' plasma or sera correlated with depressed delayed hypersensitivity. After removal of the tumor, suppressor activity disappeared. IgG fractions of patient sera contained strong immunosuppressive activity. These data suggest that the suppressor factor may be an isoantibody elicited by the tumor that also binds to receptors on the lymphocyte membrane. In addition to specifically blocking cell-mediated tumor immunity, enhancing sera may broadly depress host immunocompetence.

Phagocytic astrocytes and neurons in old encephalomalacia.

Cytoplasmic accumulation of hemosiderin was observed within astrocytes and neurons as well as in other phagocytes associated with old encephalomalacia. The first patient was 3 years old when she died with malnutrition and superimposed infection. A cortical infarct had been caused by an old thrombus in a small artery. The second case was a 9-year-old girl who had old encephalomalacia in the pineal region after extirpation of a pineoloma. The third patient was a 22-year-old man who had a cortical infarct from an embolus associated with chronic rheumatic endocarditis. Granules of hemosiderin had accumulated within the perikaryon of many astrocytes and other phagocytes in all cases, and in a few neurons in the second instance. Review of the literature reveals that cytoplasmic accumulation of particulate matter has been described infrequently with regard to neuroepithelial derivatives. Our findings indicate that astrocytes and neurons as well as derivations of mesenchyme may act as phagocytes of old blood.

Melanotic neuroectodermal tumors of the brain and skull.

A case of melanotic neuroectodermal tumor in the cerebellum of a 21-year-old man is presented. Melanin was found mainly in small neoplastic cells rather than in large epithelioid cells. The tumor also contained neurons, as well as neoplastic tissue of ependyma, choroid plexus; and astrocytes. We propose that this neuroectodermal tumor resulted from a combination of cells originating in the neural crest and in the neural tube. The small cells have been described as medulloblasts, but they may be poorly differentiated ependymal cells, or, sympathicoblasts. The presence of pigment in these cells is compatible with an origin in the neural crest. The so-called melanotic progonoma, occurring most often in the maxilla of infants, is reviewed in relation to the melanotic neuroectodermal tumor of the brain. The tumor in facial bone occurs in adults as well as infants, in locations other than the maxilla, and has malignant forms. Melanotic neuroectodermal tumors, whether in brain or bone, are therefore similar in behavior as well as histologic appearance. The finding of similar tumors in these different locations is readily explained embryologically.

Pigmented ganglioneuroblastoma: relation of melanin and lipofuscin to schwannomas and other tumors of neural crest origin.

An unusual case of ganglioneuroblastoma containing melanin is presented. Electron microscopy revealed various stages of development of melanosomes in neoplastic cells of Schwann, the first direct demonstration in human material that these cells are malanogenic. The frequent occurrence of neuromelanin in autonomic ganglia and in ganglioneuromas is interpreted as the presence of altered lipofuscin. Review of ultrastructural and other observations indicates a relation between various pigmented tumors, the cell of Schwann, and other cells arising from the neural crest.

Subarachnoid spinal hemorrhage in a case of systemic lupus erythematosus.

A 50-year-old woman with an 18-year history of systemic lupus erythematosus (SLE) died after an exacerbation of the illness, characterized by deteriorating mentation and right hemiplegia. Necropsy revealed massive spinal subarachnoid hemorrhage resulting from aneurysmal dilation and rupture of the posterior spinal artery, which was involved by vasculitis. The left parietal lobe and internal capsule contained recent infarcts. To our knowledge, this is the first reported case of SLE with spinal subarachnoid hemorrhage revealed by necropsy.

Combined congenital vascular anomalies and neuroepithelial (colloid) cysts.

We present two unique cases of intracranial congenital lesions of different origins. A 29-year-old woman had an angioma of the choroid plexus of the third ventricle and paraventricular region; a small neuroepithelia cyst was also included in the lesion. This case is the first known description of a choroidal angioma in the third ventricle. The other patient, a 39-year-old woman, had a ruptured saccular aneurysm at the junction of the anterior communicating and left anterior cerebral arteries, a cerebellar hemangioma, and a small neuroepithelial cyst with numerous papillary infoldings in the pineal region. The presence of choroid plexus in this cyst is further evidence of a developmental malformation. Review of the literature disclosed that vascular malformations and neuroepithelial cysts are occasionally associated with other congenital anomalies. The findings support the congenitally derived nature of these lesions.

Melanosis of the choroid plexua.

A unique case of melanosis of the choroid plexus in a 74-year-old man who died of hypertensive cardiovascular disease is described. The cerebral lesion did not cause symptoms. The proposed pathogenesis is the conversion of choroidal epithelial lipofuscin into melanin. Our findings also may explain the origin of a previously reported primary malignant melanoma of the choroid plexus and of black cortical adenomas of the adrenal gland.

Multiple neuroepithelial (colloid) cysts: association with other congenital anomalies.

A 4-year-old boy had three neuroepithelial cysts, one in the third ventricle and two in the supratentorial subarachnoid space, and also had stenosis of the cerebral aqueduct, obstructive internal hydrocephalus, frontoethmoidal meningoencephalocele, and right microphthalmia. The occurence of these combined lesions supports the congenitially derived nature of the cysts. The cysts originated from neuroepithelium including ectopic ependyma-lined structures. The exception may be those cysts arising in or near the floor of the third ventricle; these cysts could be derived from the cleft of Rathke's pouch, an endodermal derivative. Folding of the neuroepithelium in contact with mesenchyma or neuroglial tissue is proposed as the mode of formation of most "colloid" cysts. Review of the literature as well as our experience indicates that neuroepithelial cysts are widely distributed throughout the central nervous system.

Pathogenesis of pigment and spheroid formation in Hallervorden-Spatz syndrome and related disorders.

In a case of Hallervorden-Spatz syndrome, neuromelanin was found in neurons and, extracellularly, in the globus pallidus and pars reticulata of the substantia nigra. Some cells of pars compacta contained Lewey bodies. We propose that neuromelanin is formed by a metal-catalyzed pseudoperoxidation of lipofuscin, involving increased amounts of iron and copper in the affected regions. A similar mechanism of spheroid formation, often associated with neuromelanin, may result from pathologic accumulations of lipid peroxides during fatty acid oxidation of myelin. We suggest that neuromelanin is a late stage in the metabolism on intraneuronal and extraneuronal lipopigments. Discrepancies among the histochemical features of the pigment in different cases may be explained by differences in amounts of lipofuscin, neuromelanin, and their precursors. We propose relation of peroxidation to the pathogenesis of some related degenerative diseases.

Location of human pyramidal tract in the internal capsule: anatomic evidence.

A patient with a small infarct located posteriorly in the internal capsule had 9 years of weakness of the contralateral face, arm, and leg. At necropsy, it was found that degeneration of the corticospinal tract was almost complete in the midbrain and medullary pyramid. This case supports the increasing evidence that the human pyramidal tract is located in the third quarter of the posterior limb of the internal capsule.