Lysozyme-Containing Renal Tubular Hyaline Droplets in F344 Rats Bearing a Rat Fibrosarcoma-Derived Transplantable Tumor

Abstract

Renal tubular hyaline droplets developed in male and female F344 rats bearing a rat fibrosarcoma-derived transplantable tumor (SS). The droplets accumulated exclusively in the proximal renal tubular epithelia as eosinophilic granules of various sizes in hematoxylin and eosin-stained sections. The granules stained bright red with azan-Mallory stain. Immunohistochemically, the droplets were positive for lysozyme to various degrees but were negative for alpha 2u-globulin, albumin, and alpha 1-antitrypsin. These findings indicated the involvement of lysozyme, a low-molecular-weight protein, in the droplet formation. The morphological and immunohistochemical findings of the hyaline droplets bore a close resemblance to those reported in rats as a secondary lesion to spontaneous histiocytic sarcomas. Others have speculated that renal tubular hyaline droplets in histiocytic sarcoma-bearing rats are formed in lysosomes through cellular overload of lysozyme secreted excessively by the tumor cells. However, neoplastic cells of SS tumors were negative to lysozyme. The pathogenesis of renal hyaline droplets appearing in SS tumor-bearing rats remains to be investigated.

Eosinophilic Crystals as a Distinctive Morphologic Feature of a Hyaline Droplet Nephropathy in a Mouse Model of Acute Myelogenous Leukaemia

“…The impaired lysosomal degradation of cortical tubular epithelium, probably related to the excessive amount of filtrated protein, may lead to storage of these proteins in cytoplasmic hyaline droplets or, in more severe cases, in intracellular and luminal crystals resulting in the histopathological picture that we observed. These findings parallel those described for hyaline droplet nephropathy in association with histiocytic sarcoma in mice and rats (Hard and Snowden 1991;Luz and Murray, 1991; Yamate et al, 1997), and with transplantable fibrosarcoma and meningioma in rats (Yamate et al, 1998; Yamate et al, 1994). Hyaline droplet nephropathy, when associated with the above‐mentioned tumours is caused by accumulation and storage of lysozyme.…”

Sex and Strain Differences in the Brush Border and PAS-Positive Granules and Giant Bodies of the Mouse Renal S3 Segment Cells.

“…Similar bodies to the PAS-positive giant bodies have been reported in the uriniferous tubules of abnormal animals, e.g. mice with inherited lysosomal storage diseases [9], in rats bearing a histiocytic sarcoma [4], rats bearing a fibrosarcoma [13], the NON (Non-Obese Non-Diabetic) mice, considered a model of type II diabetes [10] and the MCC strain of mastomys with pink eyes, diluted hair color and green-brown kidneys [2]. However, the present PAS-positive giant bodies were localized in the S3 segment cells of normal mouse kidneys, and such a finding has not been previously reported.…”

A Fast Histochemical Staining Method to Identify Hyaline Droplets in the Rat Kidney

“…The comparable distribution of CAB-and immunostained droplets indicate that α 2u -globulin is a protein that can be detected by the Chromotrope 2R dye. As has also been described by others (6,12), the hyaline droplets in the kidney of the female rats with histiotic sarcoma or fibrosarcoma and rats with CPN (10) did not contain α 2u -globulin. However, they were strongly bright-red colored after CAB-staining.…”

“…In contrast to this type of drug-induced nephropathy, accumulations of hyaline droplets in association with histiocytic-and fibrosarcoma do not contain α 2u -globulin and are found in both male and female animals. In these animals a different protein, lysozyme, seems to be responsible for the hyaline droplet formation (6,12). Intracytoplasmic hyalin droplets also can appear in cases of chronic progressive nephropathy (CPN).…”