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Standardization of tumor assessment lays the foundation for validation of grading systems, permits reproducibility of oncologic studies among investigators, and increases confidence in the significance of study results. Currently, there is minimal methodological standardization for assessing tumors in veterinary medicine, with few attempts to validate published protocols and grading schemes. The current article attempts to address these shortcomings by providing standard guidelines for tumor assessment parameters and protocols for evaluating specific tumor types. More detailed information is available in the Supplemental Files, the intention of which is 2-fold: publication as part of this commentary, but more importantly, these will be available as “living documents” on a website (www.vetcancerprotocols.org), which will be updated as new information is presented in the peer-reviewed literature. Our hope is that veterinary pathologists will agree that this initiative is needed, and will contribute to and utilize this information for routine diagnostic work and oncologic studies. Journal editors and reviewers can utilize checklists to ensure publications include sufficient detail and standardized methods of tumor assessment. To maintain the relevance of the guidelines and protocols, it is critical that the information is periodically updated and revised as new studies are published and validated with the intent of providing a repository of this information. Our hope is that this initiative (a continuation of efforts published in this journal in 2011) will facilitate collaboration and reproducibility between pathologists and institutions, increase case numbers, and strengthen clinical research findings, thus ensuring continued progress in veterinary oncologic pathology and improving patient care. Accepted version

Supplemental Material, sj-pdf-9-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

Supplemental Material, sj-pdf-5-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

Supplemental Material, sj-pdf-4-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

Supplemental Material, sj-pdf-6-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

Supplemental Material, sj-pdf-7-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

Supplemental Material, sj-pdf-8-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

Supplemental Material, sj-pdf-10-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

Supplemental Material, sj-pdf-2-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

Supplemental Material, sj-pdf-3-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

In CBA/J mice, susceptibility to Mycobacterium tuberculosis (M.tb) is associated with low interferon-gamma (IFN-γ) responses to antigens (Antigen 85 (Ag85) and early secreted antigenic target-6 (ESAT-6)) that have been defined as immunodominant. Here, we asked whether the failure of CBA/J mice to recognize Ag85 is a consequence of M.tb infection or whether CBA/J mice have a general defect in generating specific T-cell responses to this protein antigen. We compared CBA/J mice during primary M.tb infection, Ag85 vaccination followed by M.tb challenge, or M.tb memory immune mice for their capacity to generate Ag85-specific IFN-γ responses and to control M.tb infection. CBA/J mice did not respond efficiently to Ag85 in the context of natural infection or re-infection. In contrast, CBA/J mice could generate Ag85-specific IFN-γ responses and protective immunity when this antigen was delivered as a soluble protein. Our data indicate that although M.tb infection of CBA/J mice does not drive an Ag85 response, these mice can fully and protectively respond to Ag85 if it is delivered as a vaccine. The data from this experimental model suggest that the Ag85-containing vaccines in clinical trials should protect M.tb susceptible humans.

Sepsis, iron loading, and aging cause independent increases in gut epithelial and splenic apoptosis. It is unknown how their combination will affect apoptosis and systemic cytokine levels.Hfe-/- mice (a murine homologue of hemochromatosis) abnormally accumulate iron in their tissues. Aged (24-26 months) or mature (16-18 months) Hfe-/- mice and wild type (WT) littermates were subjected to cecal ligation and puncture (CLP) or sham laparotomy. Intestine, spleen, and blood were harvested 24 h later and assessed for apoptosis and cytokine levels.Gut epithelial and splenic apoptosis were low in both aged septic and sham Hfe-/- mice, regardless of the amount of iron in their diet. Mature septic WT mice had increased apoptosis compared to age-matched sham WT mice. Mature septic Hfe-/- mice had similar levels of intestinal cell death to age-matched septic WT mice but higher levels of splenic apoptosis. Apoptosis was significantly lower in septic aged Hfe-/- mice than septic mature Hfe-/- animals. Interleukin-6 was elevated in septic aged Hfe-/- mice compared to sham mice.Although sepsis, chronic iron dysregulation, and aging each increase gut and splenic apoptosis, their combination yields cell death levels similar to sham animals despite the fact that aged Hfe-/- mice are able to mount an inflammatory response following CLP and mature Hfe-/- mice have elevated sepsis-induced apoptosis. Combining sepsis with two risk factors that ordinarily increase cell death and increase mortality in CLP yields an apoptotic response that could not have been predicted based upon each element in isolation.