Histological and Immunohistochemical Studies on Spontaneous Rat Astrocytomas and Malignant Reticulosis

Abstract

Among spontaneous neoplasms of the rat central nervous system, the discrimination between astrocytoma and malignant reticulosis (MR) is sometimes difficult because of their similar cell morphology and infiltration patterns. In the present study, we carried out histological and immunohistochemical analyses on a total of sixty-four cases in Sprague-Dawley and F344 rats. These cases were diagnosed as benign/malignant astrocytoma containing no neoplastic oligodendroglial elements or MR according to the diagnostic criteria of the World Health Organization International Classification of Rodent Tumors (Mohr et al. 1994). Astrocytomas were divided into three types and MR into two types based on the number of lesions, cellularity and infiltration patterns, and so on. Although the neoplastic cells from all types showed various immunoreactivities for RM-4 (anti-rat macrophages and dendritic cells), ED-1, and/or vimentin, there were no distinctive differences among these types, and most cells that were positive for RM-4 were also positive for ED-1. None of the tumor types showed any reactivity for GFAP or S-100 protein. From the results of morphological and immunohistochemical examinations, it was indicated that there are no distinctive differences between spontaneous astrocytomas and MR in rats, and they are probably derived from the same cell lineage, that is, microglia, macrophage, or radial glia.

Incidence of Spontaneous Central Nervous System Tumors in CD-1 Mice and Sprague-Dawley, Han-Wistar, and Wistar Rats Used in Carcinogenicity Studies

“…It was observed in 1 Wistar rat and 1 CD-1 mouse across the 11-year period. The immunohistochemical profile of malignant reticulosis is similar to astrocytoma in many aspects, and both tumors are suspected to be derived from the same lineage (Nagatani et al 2009). …”

GFAP-Positive Neoplastic Astrocytes in Spontaneous Oligodendrogliomas and Mixed Gliomas of Rats

“…Morphological features of bizarre Rat spontaneous astrocytoma is said to be negative for GFAP, and, in fact, GFAP-positive spontaneous astrocytoma has not been reported in rats until today. On the other hand, this tumor has been reported to be positive for several immunohistochemical markers for macrophages or microglia (Nagatani et al 2009;Kolenda-roberts and Hardisty 2011). Therefore, the origin of this tumor has been controversial.…”

“…On the other hand, there are no reports describing the existence of GFAP-positive neoplastic astrocytes in rat spontaneous astrocytomas, although detailed immunohistochemical examinations have been done by many researchers (Krinke and Germer 1993;Krinke et al 2000;Nagatani et al 2009;Pruimboom-Brees et al 2004;Solleveld, Gorgacz, and Koestner 1991;Weber et al 2011).…”

Proliferative and Nonproliferative Lesions of the Rat and Mouse Central and Peripheral Nervous Systems

“…neoplastic astrocytes in the rat and mouse brain generally lack GFAP reactivity (Cardesa et al 1994;Krinke and Kaufmann 1996); in ENU-induced gliomas in rats, most astrocytomas were negative for GFAP and Leu-7 but positive for S-100 and (usually) vimentin (Zook, Simmens, and Jones 2000;Raju et al 1990); immunohistochemistry for macrophage/microglial markers like ED-1, Iba1, and RM-4 may help differentiate astrocyte-like neoplasms of histiocytic lineage from true astrocytomas (Nagatani et al 2009 typically includes multiple foci of necrosis and hemorrhage, cellular atypia and pleomorphism, and invasive growth as prominent features. glioma, mixed, low grade: a mixed tumor with neoplastic astrocytes and neoplastic oligodendroglia (the latter representing 20% or more of the mass; see definition in this glossary); astrocytosis (reactive gliosis): differentiation may be difficult, but these well-differentiated nonneoplastic cells express GFAP widely and intensely (see definition in this glossary).…”