Selective immunohistochemical staining in the paraneoplastic retinopathy syndrome.
BACKGROUND: The mechanism leading to visual loss in paraneoplastic retinopathy is not known. An autoimmune process has been imputed based on immunologic investigations of several patients and by analogy to certain other paraneoplastic syndromes. METHODS: Two patients with documented small cell carcinoma of the lung who had clinical evidence of paraneoplastic retinopathy are described. Histopathologic examination of the retina from one patient and immunohistochemical staining of human retina with serum from control subjects and both patients were performed. RESULTS: Electroretinograms demonstrated dysfunction of photoreceptors in both patients, with predominant loss of rod function in one patient. Post mortem examination showed patchy loss of photoreceptors of the extramacular retina and relative sparing of cones, findings consistent with the clinical and electrophysiologic test results. Serum from both patients stained the retina in an identical manner, with restriction of the stain to the outer retina. Stain was present over the outer plexiform layer, the outer nuclear layer, and the inner and outer segments of most photoreceptors. A sharp demarcation was present between those areas that did and did not stain. All rod inner and outer segments appeared to stain, and many cone inner segments were not stained. Immunologic tests obtained elsewhere did not show serum antibody to the 23 kD protein. CONCLUSION: These findings support the concept of an autoimmune pathogenesis by showing selectivity of the immune response and correlation between the apparent target of the immune response and the clinical and pathologic findings. The mechanism by which cell loss occurs in the retina is not answered by this study. The absence of antibody to the 23 kD protein does not exclude the diagnosis of paraneoplastic retinopathy.