Carcinogenicity: P14: Immunohistochemical study of astrocytoma and malignant reticulosis in rats

In rat spontaneous neoplasms of the central nervous system, the discrimination between astrocytoma and malignant reticulosis is sometimes difficult because of their similar cell morphologies and growth and infiltration patterns. The derivation of malignant reticulosis is proposed to be lymphocytes, microglias or histiocytes, although their precise origin has not been established yet. In the present retrospective study we examined immunohistochemical analyses from a total of 43 cases in Sprague-Dawley (SD) rats and 21 cases in F344 rats which were diagnosed as benign astrocytoma, malignant astrocytoma or malignant reticulosis according to the diagnostic criteria of WHO International Classification of Rodent Tumours (IARC No. 122). The tumours were classified into five categories as follows: (1) early stage of astrocytoma: 7 cases (SD: 3 cases, F344: 4 cases); they are composed of one lesion of moderate cellularity in the parenchyma. (2) common type of astrocytoma: 41 cases (SD: 29 cases, F344: 12 cases), which includes not only a single lesion with dense cellularity but also multiple extending lesions in the parenchyma, with infiltration into peripheral meninges or perivascular space. (3) glioblastoma type of astrocytoma: 12 cases (SD: 10 cases, F344: 2 cases); necrosis with peripheral palisading is observed. (4) intermediate type of astrocytoma and malignant reticulosis: 2 cases (SD: 1 case, F344: 1 case); neoplastic cells are infiltrated more diffusely in meninges and perivascular space with obvious parenchymal infiltration. (5) malignant reticulosis: 2 cases (both in F344); neoplastic cells are infiltrated diffusely in meninges and perivascular space without obvious parenchymal infiltration. The neoplastic cells from all categories showed various immunoreactivities for vimentin, RM-4 (anti-rat macrophages and interdigitating cells) and ED-1. However, no distinct difference among these categories was observed. The positive cells for RM-4 mainly corresponded to those of ED-1. The reactivity for vimentin was more intense than that of RM-4 and ED-1. A few neoplastic cells from the common and glioblastoma types demonstrated positive reaction for nestin. No reactivity for GFAP or S-100 was observed in any case of any category. Perivascular or intercellular reticulin fibers which were stained with Watanabe's silver impregnation method were observed in some or many cases in each category except for the early stage of astrocytoma. The results of the malignant reticulosis generally coincided with those of astrocytomas. In conclusion, no difference in the cell origin between astrocytoma and malignant reticulosis could be found.