Variability of differentiation patterns in xenotransplanted spindle cell sarcomas: a histomorphological, immunohistochemical, and ultrastructural study.

Abstract

Three leiomyosarcomas, 3 nerve sheath sarcomas, 1 rhabdomyosarcoma, and 1 sarcoma not otherwise classifiable with 17 of their xenografts, grown on nude mice, were analyzed to assess the degree of concordance between histomorphology, immunohistochemistry, and ultrastructure in spindle cell sarcoma xenograft differentiation. Histomorphology was inconclusive or misleading in 4/8 sarcoma strains and immunohistochemistry in 4/8 originals and in 10/17 xenografts, although specific patterns had been identified ultrastructurally. Electron microscopy was superior to immunohistochemistry and histomorphology in spindle cell sarcoma differential diagnosis. A further purpose of this study was to clarify whether spindle cell sarcoma xenografts retain the morphological characteristics of their primaries. Histomorphological features of the primaries were preserved over all passages, whereas the immunohistochemical marker profiles as well as the ultrastructural phenotypes changed in 14/17 xenografts and in 8/17 xenografts, respectively. Moreover, unusual bidirectional or tridirectional patterns of differentiation were identified ultrastructurally with leiomyomatous as well as Schwann cells occurring side by side and with MFH-like areas in 5/17 xenotransplants. These findings suggest genetic instability of tumor cells and may be important in the consideration of mesenchymal differentiation pathways.