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Abstract
Epidemiologic studies of feline vaccine-associated sarcoma (FVAS) require accurate sarcoma case definitions free from unverified assumptions for valid causal inference. This study developed methodologic approaches to improve reliable differentiation of vaccine versus nonvaccine-associated sarcomas on histologic characteristics using time windows of vaccine histories and body geographic information. Four case and five control definitions were used to classify 124 sarcomas. Results showed presence in the subcutis versus dermis, increased nuclear pleomorphism, more granulation tissue, and higher presence of inflammation in FVAS than presumptive non-FVAS. Correctly classifying sarcomas using stringent classification criteria as employed in this study will help reduce misclassification of FVAS in future epidemiologic studies of comparative risk.
Highlights
Twenty years have elapsed since the initial recognition of feline vaccine-associated sarcoma (FVAS), this iatrogenic malignancy remains a pervasive problem to cat owners and veterinarians [1]
Earlier work using statistical models to compare histologic characteristics of presumptive feline vaccine-associated sarcomas and presumptive nonFVAS implicitly assumed that a sarcoma was vaccine induced if the sarcoma arose at a site conventionally used for vaccination in the cat [9, 10]
A sarcoma can only be defined as vaccine associated if it develops at or near a vaccination site following a biologically plausible induction interval
Summary
Twenty years have elapsed since the initial recognition of feline vaccine-associated sarcoma (FVAS), this iatrogenic malignancy remains a pervasive problem to cat owners and veterinarians [1]. Considerable research has been conducted to better define the determinants of these tumors either in individual cats [2, 3] or populations [4,5,6,7], and despite changes in vaccine formulation and administration strategies over the last 15 years, cases of FVAS continue to be reported This iatrogenic condition has not been reproduced in experimental studies due to its rarity [8], epidemiologic research has convincingly demonstrated a causal relationship, with respect to rabies and feline leukemia virus vaccines, and the veterinary medical and vaccine manufacturing communities have taken steps to try to ameliorate incidence. How close should a tumor be to a vaccination site to be associated? What is a biologically plausible induction interval following vaccination? Such nonidentifiability makes the extent of misclassification in earlier publications impossible to know, ISRN Pathology but careful consideration of these issues can potentially minimize misclassification of FVAS diagnoses and vaccine exposures
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