Special focus on diagnostic veterinary oncologic pathology

Over a decade ago, a special issue of Veterinary Pathology was dedicated to neoplasia in companion animals (2011, Volume 48, Issue 1). A lot has happened since that time, and this current issue of Veterinary Pathology provides a series of original and review articles that seek further answers to some of the enduring questions of veterinary oncologic pathology. For the diagnostic veterinary pathologist, oncologic pathology remains the cornerstone of any surgical pathology service. With advancements in immunohistochemistry, in situ hybridization, and molecular analysis, we are better able to refine our diagnoses and provide valuable data that can be used in prognostic studies. Over the last decade, interest in using spontaneously arising neoplasia in companion animals as models for similar human cancers has been renewed and revitalized. These include common but devastating neoplasms such as osteosarcoma, melanoma, and glioma. While there remains much to be elucidated about the pathogenesis and prognosis of companion animal cancer, the articles presented herein provide a window into some of the advancements and refinements that have occurred over the last decade and offer new avenues of exploration.

The field of veterinary pathology has been slow to adapt universal guidelines for tumor evaluation including, but not limited to, margin assessment, trimming consistency, and tissue plane barriers. These are critical features of any standard tumor assessment and herein are presented detailed and elaborate guidelines for diagnostic pathologists to follow so that there is uniform and consistent analysis of tumors. ¹⁷ In addition to providing more accurate information to referring veterinarians and therefore promoting the role of veterinary pathologists in supporting the care of oncologic animal patients, this article sets the stage for collaborative multi-institutional studies that all utilize and embrace similar tumor assessment. Also, of utmost importance in generating adequate prognostic data is an understanding of the current histologic grading schemes including when to use them and what are their limitations. Readers will find a broad review of grading systems used in diagnostic veterinary pathology as well as an in-depth analysis of our current state of knowledge regarding canine mast cell tumors, which, while remaining one of the most common canine skin malignancies, remains the subject of prognostic confusion due to different grading schemes. ^2,4

Pathologists sometimes suffer from the silo effect where we are prone to forget about the wealth of clinical, statistical, and molecular data that can be utilized to better understand cancer pathogenesis and eventual outcome. This includes the importance of correlating imaging with the pathology and is nicely highlighted by a cosmopolitan look at assessing bone tumors. ⁸ Of equal interest is a research article focused on using computed tomography in feline injection site sarcomas to better determine marginal disease, excision, and guide histologic analysis. ¹³ And, of course, to evaluate the data gathered, we must have a solid understanding of statistical analysis and what is appropriate for each study. ⁶

Equally important is the emerging role of molecular diagnostics in tumor pathobiology. Melanoma remains one of the deadliest tumors in human and veterinary medicine and there are broad similarities between canine melanoma and its human counterpart. An extensive review discussing the pros and cons of our canine companions as a model for human oral melanoma provides a much-needed update to the current literature. ⁷ Of similar importance to genomic analysis is the appropriate application and interpretation of immunohistochemistry. This is and will continue to remain one of the core facets of diagnostic pathology; however, it is a methodology that is prone to error, misinterpretation, and overreliance. Critical to interpreting immunohistochemistry and using it as a tool for supporting the diagnosis and prognostication of companion animal neoplasia is a solid understanding of how to correctly validate an antibody, and we hope that an exhaustive review of standardization and validation of immunohistochemistry provides some much-needed clarity to diagnosticians and reassurance to clinicians. ¹⁹

Of course, any special issue dedicated to diagnostic oncologic pathology is expected to introduce novel findings that are clinically applicable. This includes articles focusing on diffuse small-cell B cell lymphoma in the dog and a study determining the applicability of the World Health Organization’s human classification scheme of lacrimal tumors to the same tumors in the dog. ^9,10 So as to not leave our lagomorph friends behind, the special issue also includes 2 studies detailing types of neoplasia and their prevalence in pet rabbits, with both articles offering additional insight into common and uncommon tumors of this species. ^3,5

Immunohistochemistry remains a mainstay for the diagnostic pathology, and several articles of the special issue describe the expression of novel immunohistochemical markers in canine tumors such as periostin in canine osteosarcoma and nestin in canine mammary carcinoma. ^1,20 Correlation of these markers with follow-up data offers insights on the prognostic significance and potential clinical relevance of these markers. Immunohistochemistry was also used to study the immune cell microenvironment in an article on the role of mutated BRAF^V595E in influencing the recruitment of regulatory T lymphocytes in canine urothelial carcinoma. ¹⁴ A wide-reaching investigation of the stem cell marker, SOX2, and its distribution in a diverse set of canine malignancies informs on the role that SOX2 may have in canine cancer pathogenesis. ¹⁸

Last, but certainly not least, are several articles focused on neoplastic entities of the central nervous system (CNS). Canine gliomas have recently been the focus of advanced histologic, immunohistochemical, and molecular studies culminating in a novel canine glioma grading scheme. ¹¹ This grading scheme was mostly developed using necropsy specimens, and herein an article applies the grading scheme to canine glioma biopsies and further defines the critical prognostic features of low- versus high-grade canine gliomas. ¹⁶ The immune cell microenvironment was again highlighted by a study analyzing the presence of different lymphocyte populations in canine astrocytoma, oligodendroglioma, and undefined glioma. ¹² The focus on the CNS wraps up with a review of proliferative vascular disorders. This review codifies our knowledge on this challenging group of lesions and offers simplistic ways to separate the entities utilizing histochemical and immunohistochemical stains. ¹⁵

Publication of the works herein would not have been possible without the dedicated editorial and administrative staff at Veterinary Pathology. We hope that the reader enjoys this collection of articles and is able to use them in their diagnostic practice. Furthermore, we eagerly await the next update to diagnostic oncologic pathology to appear in Veterinary Pathology in the years to come!