Spongiotic pericytoma: a benign neoplasm deriving from the perisinusoidal (Ito) cells in rat liver

Spongiosis hepatis has been known for some time to develop frequently in livers of rats and fish treated with hepatocarcinogens and was considered to derive from the perisinusoidal (Ito) cells (PSC). Using rat liver treated with N-nitrosomorpholine at different dose levels, we studied the cellular composition and origin as well as the proliferation kinetics of spongiosis hepatis by immunohistochemical demonstration of desmin, vimentin, and alpha-smooth-muscle actin, and by autoradiographic determination of [3H]-thymidine incorporation, respectively. The vast majority of the cells forming spongiosis hepatis were positive for desmin and vimentin but negative for alpha-smooth-muscle actin, confirming the cellular origin of spongiosis hepatis from PSC. In addition, immunohistochemical demonstration of desmin and vimentin revealed that spongiosis hepatis is an integral part of larger lesions consisting of focal PSC aggregates. These aggregates show a significantly increased incorporation of [3H]-thymidine compared with PSC in the extrafocal tissue and in the liver tissue of untreated control animals. In stop experiments, this increased labeling index was maintained many months after withdrawal of the carcinogen, in line with the earlier observation of a progressive behavior of spongiosis hepatis. We conclude that PSC may give rise to proliferative lesions appearing as PSC aggregates associated with more or less pronounced spongiosis hepatis. The persistence, the proliferative activity, and the slow expansive growth of these lesions suggest a benign neoplastic behavior. We therefore propose to classify these lesions as spongiotic pericytoma. Malignant tumors possibly originating from spongiotic pericytoma should consequently by classified as perisinusoidal (Ito) cell sarcomas.