Current Status and Future Perspectives in Canine Oral Squamous Cell Carcinoma

Canine oral squamous cell carcinoma (OSCC) has been a focus of attention among researchers and clinicians in recent years. Although clinical studies point to an excellent outcome when successful surgical margins are achieved and there is no evidence of metastasis, ² a significant number of cases fails to reach this optimal endpoint. The failure of early detection of such tumors reflects its silent development and, ultimately, tumor size and intra-oral location limit treatment options. Early and accurate diagnosis is key to a successful outcome. Therefore, knowledge of the histopathologic and molecular features of canine OSCC may have great therapeutic implications now and in the future.

Studies of canine OSCC that focused on immunohistochemistry and molecular markers of cell cycle regulation, apoptosis, angiogenesis, adhesion, and degradation of extracellular matrix, among others, have improved medical knowledge and made it possible to compare mechanisms between species potentiating translational research. There are strong molecular similarities and comparable heterogeneity between canine OSCC and human head and neck SCC, ³ as well as similarities in histologic subtypes ⁹ and expression patterns of markers identified by immunohistochemistry techniques. ^5,6

Immunohistochemistry is used routinely in many veterinary diagnostic laboratories, contributing greatly to improving the diagnosis and consequently the prognosis in veterinary oncology. In cases when routine hematoxylin and eosin may be insufficient, the pathologist should indicate the most appropriate set of tumor markers to determine definitive diagnosis. On the other hand, oncologists might request additional information to guide their choice for the best treatment strategy for a given patient. Grade, along with proliferation markers, can provide important prognostic information in canine OSCC. Specifically, lower grades are associated with better postsurgical outcomes, ⁵ and proliferation markers can add information about biological behavior within canine OSCC types and locations. ^6,7 Squamous cell carcinoma of the skin shows less aggressive features when compared with OSCC in dogs. ⁷ Finally, different intra-oral locations have distinct histologic and immunohistochemical features that reflect their biologic behavior, such as higher grade and risk of metastasis in tonsilar versus nontonsilar locations and higher frequency of lymph node metastasis in OSCC cases with high proliferative index. ⁶

In this issue, Thaiwong et al ¹¹ provide new information about canine oral papillary squamous cell carcinoma (OPSCC), a histological subtype of canine OSCC with distinct biological behavior. Differentiation of OPSCC from other proliferative epithelial lesions might be a challenge, especially in cases of incompletely excised biopsy specimens. This article proposes an immunohistochemical panel to differentiate OPSCC from 2 differential diagnoses: conventional OSCC and acanthomatous ameloblastoma. Such information is very useful to the clinician facing a case that might have a completely different prognosis. Indeed, OPSCC in both dogs and humans is reported to have a more favorable outcome when compared with other histological OSCC subtypes, due to low if not absent metastatic rate and limited local invasion. ^1,8,10 In addition to the suggestion of a selected set of immunohistochemical markers for definitive diagnosis, this article also explores the possible involvement of papillomavirus in canine OPSCC. This virus has been implicated in about half of similar tumors in humans with recommended scanning in routine practice for papillary squamous cell carcinoma ⁴ and was also suggested to be involved in canine OPSCC due to their special morphologic features, age of affected individuals, and better survival. ⁸ Contributions in this field are warranted since such findings do not seem to parallel what is encountered in humans.

The article by Thaiwong et al ¹¹ is of interest not only to pathologists but also to oncologists, to provide the best standard of care to their patients. Furthermore, from the perspective of comparative oncology, the understanding of the molecular nature of OSCC can lead to a better clarification of its tremendous complexities. Only then can we aim to modify and subsequently improve the clinical outcomes in OSCC.