Granular cell lesions in the distal female reproductive tract of aged Sprague-Dawley rats

During the review of a rat carcinogenicity study, a spectrum of granular ce ll lesions was recognized in the distal female reproductive tract. To verif y the diagnoses, cell populations of nine granular cell alterations of the cervix or vagina were characterized immunohistochemically and four were eva luated ultrastructurally. Immunoreactivity was demonstrated in 8/9 cases wi th S100 protein, 6/9 cases with neuron-specific enolase, and 7/9 cases with Leu-7. Granular cells were negative for smooth muscle-specific actin and c alretinin. The immunohistochemical profile of these lesions was similar to that previously reported in other species, including humans. Ultrastructura lly, as expected many lysosomal bodies were present in the cytoplasm of gra nular cells in all specimens evaluated. Based on the detailed evaluation of a series of lesions, we adopted the following diagnostic criteria and nome nclature for the granular cell changes of the female reproductive tract of rats. Granular cell aggregates were non-space-occupying lesions composed of clusters of typical granular cells. Benign granular cell tumors were space occupying lesions that typically contained prominent interstitial collagen and were either discrete masses or were difficult to discern from the surr ounding tissues. Some benign tumors also contained foci of spindle cells wi th decreased granularity. Malignant tumors exhibited pleomorphism and an in creased nucleus:cytoplasm ratio morphologically but had the same biologic b ehavior as the benign tumors. We applied these diagnostic criteria during t he review of controls from 9 carcinogenicity studies. Up to 23% of control females in those carcinogenicity studies had granular cell lesions that cou ld be classified into one of the three categories. Granular cell lesions ap pear to be common in the cervix/vagina of the Sprague-Dawley rat, and tumor s may develop from granular cell aggregates.