VACCINE

Veterinary Pathology • March 2001
Feline vaccine-associated fibrosarcoma:
an ultrastructural study of 20 tumors 1996-1999
Author information
Madewell BR1, Griffey SM, McEntee MC, Leppert VJ, Munn RJ.
Department of Surgical and Radiological Sciences, School of Veterinary Medicine
University of California, Davis 95616 USA
brmadewell@ucdavis.edu
Abstract
Twenty feline vaccine-associated sarcomas were examined by transmission electron microscopy. Tumors contained
pleomorphic spindle cells, histiocytoid cells, and giant cells. Most tumors contained myofibroblasts, which
had morphologic features similar to those of fibroblasts. These cells were further distinguished by subplasmalemmal
dense plaques and thin cytoplasmic actin myofilaments organized as elongated bundles concentrated at
irregular intervals forming characteristic dense bodies. Intracellular crystalline particulate material was found in
5 of the 20 tumors. Energy dispersive X-ray spectroscopy was used to identify the crystalline material within one
tumor as aluminum-based. One tumor from a feline leukemia virus-infected cat contained budding and immature
retroviral particles.
In one of the first reports of feline vaccine-associated sarcomas, dense crystalline material was recognized by
electron microscopy within macrophages surrounding tumor cells.9 Subsequent electron-probe microanalytical
studies demonstrated aluminum in the cytoplasm of the macrophages within these sarcomas, suggesting the role
of aluminum-containing adjuvant as irritant in the pathogenesis of vaccine-associated sarcomas.9 The role of
vaccine adjuvant in the etiopathogenesis of these tumors remains unclear. The most prevalent adjuvants used in
licensed veterinary vaccines are aluminum salts and oil emulsions; all of these formulations are considered to act
as depots for injected vaccines.1 Aluminum hydroxide adjuvants are used in many human and veterinary vaccines,
presumably because of their safety and low cost. Aluminum has been detected at the site of subcutaneous
injections for up to 1 year in animals.3 That the tissues collected in this study represented tumors that developed
months to years after vaccination when the precise site of vaccination was unknown and that most tumors were
several centimeters in diameter or greater at the time of excision suggest that a large amount of aluminum, indeed,
was contained within these adjuvanted vaccines to allow its detection in randomly selected ultrathin (60–90 nm
thick) tissue sections examined in the electron microscope.
“The results of this study
support previous morphologic observations
of feline vaccine-associated sarcomas. The role
of the myofibroblast in vaccine-associated sarcomas is
unclear but perhaps reflects a continuum of the
inflammatory response that characterizes, in part,
these unique neoplasms. The role of adjuvant,
similarly, in these tumors is unknown.”
The results of this study support previous morphologic observations of feline vaccine-associated sarcomas. The
role of the myofibroblast in vaccine-associated sarcomas is unclear but perhaps reflects a continuum of the inflammatory
response that characterizes, in part, these unique neoplasms. The role of adjuvant, similarly, in these
tumors is unknown.
Full Report: http://vet.sagepub.com/content/38/2/196.long