Karbe and Kerlin have questioned the classification of spongiosis hepatis as a preneoplastic lesion or even a benign neoplasm, designated as spongiotic pericytoma, and have proposed to use the term cystic degeneration for this lesion in rats and fish. However, the reclassification of spongiosis as cystic degeneration is unwarranted for several reasons. In the rat, spongiosis hepatis represents a specific pathomorphologic entity, originating from the perisinusoidal (Ito) cells; it may occur spontaneously in aged animals but its number and size increases significantly after exposure to various (hepato)carcinogens. Comparative morphological, immunohistochemical, and autoradiographic studies in rats exposed to N-nitrosomorpholine revealed that spongiosis hepatis is an integral part of larger proliferative Ito-cell aggregates showing an autonomous, progressive growth. The classification of spongiosis hepatis as a benign neoplasm is based on these findings that endorse and extend previous considerations on the preneoplastic or neoplastic nature of this lesion. Irrespective of the classification of spongiosis hepatis as a benign neoplastic or a preneoplastic lesion, there is compelling evidence for its reliability as a sensitive marker for (hepato)carcinogenic effects in rats and fish. The data collected by Karbe and Kerlin support rather than contradict the reliability of spongiosis hepatis as an effect marker for carcinogens.Keywords. Spongiosis hepatis; spongiotic pericytoma; perisinusoidal (Ito) cell neoplasm; perisinusoidal cell sarcoma; effect marker for (hepato) carcinogens.In their communication Karbe and Kerlin question the classification of spongiosis hepatis as a putative preneoplastic lesion (1, 2) or even a benign neoplasm (spongiotic pericytoma) in rat (3), and fish (4), and propose to use the term cystic degeneration for this lesion. The authors do not present any new data but base their proposal on a review of most, albeit not all, of the available literature. A reclassification of spongiosis hepatis as cystic degeneration, a term previously recommended in some diagnostic guidelines (eg, 5, 6), is unwarranted for several reasons.Karbe and Kerlin argue that the morphology of cystic degeneration/spongiosis hepatis "does not have standard neoplastic characteristics." For this reason the term spongiosis hepatis originally coined and introduced into the literature was deliberately descriptive (1). Nevertheless, a preneoplastic or neoplastic nature of spongiosis hepatis has been considered since its first description, which was exclusively based on morphologic criteria in both rats and fish (1, 2, 4, 7). Light and electron microscopic observations in these species revealed that spongiosis hepatis represents a specific pathomorphologic entity originating from the perisinusoidal (Ito) cells. This histogenetic relationship has been substantiated by the selective immunohistochemical demonstration of desmin (Figure 1) in both normal perisinusoidal liver cells and cells constituting spongiosis hepatis (3).T...