Typing of amyloidosis in renal biopsies: diagnostic pitfalls.

CONTEXT: Amyloidosis represents a group of diseases with extracellular deposition of congophilic fibrils of similar morphology but differing chemical composition. The types commonly involving the kidney are AL (light chain amyloid) and AA (serum amyloid A). Familial amyloidosis can also affect the kidney, but we have not encountered such a case during the study period. Distinguishing between the AL and AA forms of amyloid is clinically important because of the different treatments and outcomes. The classification of amyloidosis is made by immunostaining with antibodies to kappa and lambda immunoglobulin light chains and for serum amyloid A protein. OBJECTIVE: To draw attention to the nonspecific immunofluorescence staining patterns in renal biopsies with amyloidosis, causing potential diagnostic pitfalls. DESIGN: Renal biopsies from 15 patients, including 13 cases of AL and 2 cases of AA amyloidosis, were studied. Immunofluorescence staining with routine antibody panel and immunoperoxidase staining for amyloid A were performed. RESULTS: Of the 13 cases of AL amyloidosis, 2 cases showed little difference in staining intensity between kappa and lambda light chains (2+ and 3+, respectively) and 4 cases showed only moderate intensity (2+) of the predominant light chain. The 2 cases diagnosed as AA amyloidosis also exhibited staining for light chains. One case had strong (3+) signal for kappa and moderate (2+) for lambda light chain, while the other showed weaker staining. CONCLUSIONS: Immunofluorescence staining for immunoglobin light chains on renal biopsy, as the first step to differentiate between AL and AA amyloidosis, may sometimes be inconclusive or even misleading. Applying amyloid A immunostain on a routine basis and detailed clinical history are essential to avoid misclassification.

The role of anti-endothelial cell antibody-mediated microvascular injury in the evolution of pulmonary fibrosis in the setting of collagen vascular disease.

We encountered 16 patients with connective tissue disease in whom pulmonary fibrosis developed. Routine light microscopic, ultrastructural, and direct immunofluorescent analyses were conducted, and circulating antibodies, including those of endothelial cell derivation, were assessed using indirect immuno-fluorescence and Western blot assays. Underlying diseases were dermatomyositis, scleroderma, mixed connective tissue disease, sclerodermatomyositis, Sjögren syndrome, rheumatoid arthritis, and anti-Ro-associated systemic lupus erythematosus. Antibodies to one or more Ro, RNP, Jo 1, OJ, and/or nucleolar antigens were seen in all cases and antiphospholipid antibodies in half. All biopsies revealed microvascular injury in concert with intraparenchymal fibrosis; in some cases, there were corroborative ultrastructural findings of microvascular injury. Patterns of fibroplasia represented nonspecific interstitial pneumonitis and usual interstitial pneumonitis. We noted IgG, IgA, and/or complement in the septal microvasculature. In 6 cases with available serum samples, indirect immunofluorescent endothelial cell antibody studies were positive and Western Blot studies showed reactivity of serum samples to numerous endothelial cell lysate-derived proteins. Pulmonary fibrosis, a recognized complication of systemic connective tissue disease, develops in connective tissue disease syndromes with pathogenetically established immune-based microvascular injury at other sites. A similar mechanism of antibody-mediated endothelial cell injury may be the basis of the tissue injury and fibrosing reparative response.

Proteomic patterns analysis: a new era of screening cancers.

Cancer is the second leading cause of death among Americans. It is estimated that 1.28 million new Americans are diagnosed with cancer annually (1). The estimated overall annual cost of cancer being $171 Billion (1). Decreasing the costs of the screening and diagnostic tests will automatically decrease the total cost of cancer by limiting not only the direct medical costs but also by containing the indirect costs of morbidity and mortality. New screening and diagnostic tests are obviously needed. Screening methods are emerging in the evaluation of proteomic patterns. In proteomic pattern analysis, we can screen for not only one cancer but a chip may be able to screen for multiple cancers. New screening and diagnostic methods (2) investigated by NCI and FDA (3) (4) are correlating gene and protein expression patterns for early detection of cancer. Many papers have been published in the last 12 months (3) (4) (5) utilizing this new technique of molecular analysis in screening and diagnosing cancers with high sensitivity and specificity.