Glomerular lesions in lymphomas and leukemias.

Renal lesions in lymphoid malignancies are rare, with most lesions observed in association with Hodgkin's disease. In two large series of patients with Hodgkin's disease, only 0.4 percent had minimal-change lesion whereas 0.1 percent had amyloidosis. The non-Hodgkin's lymphomas and leukemias comprise large and heterogeneous groups with equally diverse renal lesions. As in Hodgkin's disease, the most frequent lesion is minimal-change nephrotic syndrome. Also recognized are rare reports of renal disease associated with the atypical lymphoid proliferations of angioimmunoblastic lymphadenopathy, giant lymph node hyperplasia syndrome, and acquired immune deficiency syndrome. Broad generalizations regarding the pathogenesis of renal disease in these syndromes are difficult, partly due to the paucity and sporadic reporting of such cases. Mechanisms proposed to explain the renal pathologic findings include autologous nontumor antigens, tumor antigens, fetal antigen expression, immune complex deposition, viral antigens, and disordered T cell function.

Pathologic findings associated with interleukin-2-based immunotherapy for cancer: a postmortem study of 19 patients.

The use of interleukin-2 (IL-2), either alone or in combination with lymphokine-activated killer cells, tumor infiltrating lymphocytes, or other immunotherapeutic agents has added a new list of alternatives to conventional antineoplastic regimens. Little information is available about the pathologic changes occurring in patients treated with these agents. In this study, we reviewed the necropsy materials from 19 patients, 12 men and 7 women, with a variety of malignancies including melanoma, renal cell carcinoma, gastrointestinal and pulmonary adenocarcinoma, and metastatic gastrinoma, who died after receiving IL-2-based immunotherapy. Death occurred at intervals ranging from less than 1 hour to 143 days following the last dose of therapy. All patients dying at or less than 43 days following cessation of therapy had lymphoid infiltrates of varying intensity in residual tumor. At necropsy, the major cause of death unrelated to the presence of metastatic tumor was bacterial sepsis. In addition, we found evidence of significant cardiac and pulmonary toxicity: two patients with acute myocardial infarction, one with and one without significant coronary artery disease, two cases of unexplained lymphocytic myocarditis, and one case of fatal pulmonary capillary plugging following an infusion of lymphokine-activated killer cells. Thus, not unlike other forms of therapy for cancer, IL-2-based immunotherapy does not appear to be without significant toxicity.

Mechanisms and factors regulating the growth of glomerular cells.

The hallmark of end-stage renal disease is progressive sclerosis. The composition of the sclerotic material and its cellular source are under study and only partly elucidated. Sclerosis, in part, is composed of extracellular matrix components normal to the area, the sole exception thus far recognised is crescentic glomerulonephritis associated with Bowman's basement membrane disruption in which the sclerotic tissue contains interstitial connective tissue. The source of the extracellular matrix is the local glomerular cells. The complete composition of the extracellular matrix synthesised by individual glomerular cells is under current study, but it appears that all glomerular cells are capable of synthesising many of the various basement membrane components. The respective role of each cell type in sclerosing diseases and the initiating and propagating factors await further investigation.

Renal lesions in plasma cell dyscrasias: ultrastructural observations.

The renal biopsies from 47 patients with plasma cell dyscrasias were studied by light and electronmicroscopy, and by immunohistochemical methods. This report is primarily concerned with the ultrastructural features of 24 cases of Bence Jones cast nephropathy and of ten cases of light chain deposit disease. In Bence Jones cast nephropathy, crystals derived from light chain proteins were detected in the majority of cases within the casts or in tubular cells and appeared to be related to the "hard" and "fractured" appearance of the casts as well as to the presence of foreign body type giant cells, the latter probably being of monocyte-macrophage origin. In light chain deposit disease, linear deposits of light chain proteins (eight kappa and two lambda) were present in a subendothelial position along the glomerular basement membrane and along the outer aspect of the tubular basement membranes in all cases, quite often in the mesangial matrix, but much less commonly in the interstitium and in the wall of small arteries. The light and electronmicroscopic features of both Bence Jones cast nephropathy and light chain deposit disease can be considered diagnostic for plasma cell dyscrasia. The possible pathogenetic mechanisms of these two different forms of renal involvement are discussed briefly.