Making the Diagnosis

Spindle cell tumors of the skin of horses are very common. Numerous studies have shown that, worldwide, equine sarcoids are the most common tumor of horses. ^8,10,11 The term itself was first published in 1936 and was used to try to distinguish this tumor from the other spindle cell tumors of horses. ⁴ The behavior of these tumors was described at that time as having “a high propensity for recurrence.” Since then, their association with one of a number of bovine papillomaviruses (BPVs) has been discovered, if not entirely understood. ^1,7,9 In theory, the diagnosis of these tumors should be of little difficulty. Similar to how US Supreme Court Justice Potter Stewart described pornography “I know it when I see it.” But as diagnosticians dealing with surgical biopsies from horses, we know that this is not always the case.

Typically, sarcoids are characterized based on their clinical features, and 5 types are usually described. These include occult, nodular, verrucose, fibroblastic, and mixed, ⁵ the last of which exhibits features of 2 or more of the previous types. Rarely, malevolent sarcoids have been described; ⁵ these are said to exhibit metastatic behavior, which is not typical of other types of sarcoids, begging the question as to whether these are actual sarcoids. The typical histological features of a sarcoid include a proliferation of bundles of interlacing cells and whorls of spindle-shaped fibroblasts within the dermis, overlain with epidermal hyperplasia and hyperkeratosis with long thin rete peg-like extensions into the tumor mass. ⁶ Frequently, in some portion of the tumor, a picket fence–like arrangement of neoplastic cells along the dermal-epidermal border can be found. This is the “typical” sarcoid appearance, and the spindle-shaped fibroblasts are indeed consistently present. However, the other features are not consistently seen, and it is not possible to determine the clinical type based on the histologic features. ⁶ To further complicate matters, many times biopsies have confounding factors such as extensive ulceration or secondary inflammation that mask these classic features. In addition, other spindle cell tumors of horses do exist, and separating these morphologically similar but otherwise clinically different tumors from sarcoids can be a diagnostic challenge. These spindle cell tumors include equine sarcoids, of course, but also peripheral nerve sheath tumors, fibrosarcomas, fibromas, other sarcomas, and, somewhat uniquely in the horse, exuberant granulation tissue.

Numerous groups have worked to define the diagnostic features of spindle cell tumors of horses to improve the consistency and quality of diagnosis. In other companion animal species, particularly dogs and to a somewhat lesser degree cats, diagnostic features of tumors are well identified, and further research is continuing to better define individual subtypes, prognostic markers, and therapeutic options. In horses, there is a comparatively poor understanding of many of these features. The association of BPV with sarcoids should, in theory, make diagnosis easier, but numerous studies have shown that the mere presence of BPV DNA does not provide much value in the diagnosis of sarcoids as numerous nonsarcoid lesions and even apparently normal skin can contain BPV DNA.

The lack of clear diagnostic criteria has hampered further research into sarcoid behavior and treatment. Sarcoids are notorious for their variable behavior, such that some clinicians are reluctant to biopsy suspected sarcoids for fear that this may induce a change to a more clinically aggressive type. Alternatively, some sarcoids, for reasons that are not currently understood, may undergo spontaneous regression. Clearly, important features of these tumors need further clarification. The difficulty in diagnosing which tumors are truly sarcoids significantly impedes this type of research.

Determination of new diagnostic or prognostic markers is an important milestone in our understanding of tumor biology and is eagerly awaited by pathologists, oncologists, and clinicians. The publication of these markers is not an end point, however, but should begin the testing of such markers by other groups and other populations of affected animals. Groups such as Bogaert et al ² have strived to make diagnosis clearer, defining particular features and markers such as the combined presence of BPV DNA and S100. In this issue of Veterinary Pathology, Epperson and Castleman ³ use these features on a group of equine tumors to determine if, in their hands, these diagnostic criteria can distinguish sarcoids from peripheral nerve sheath tumors, fibrosarcomas, fibromas, myxosarcomas, and other spindle cell tumors. Unfortunately for the diagnostic world, it appears that these proposed markers were unsuccessful in differentiating sarcoids from other types of spindle cell tumors. It is unfortunate that this type of study is not published more frequently. It can be difficult to obtain funding for follow-up studies working to validate the findings of an unrelated research group. In addition, it can be difficult to publish material that support or dispute diagnostic methods as they are sometimes seen as not being as novel or influential as the publication of new markers or methods.

Until markers and diagnostic features are accepted that allow for the accurate and repeatable classification of these tumors, it is impossible to move forward with reliable prognostic tests. If we cannot be certain of the specific diagnosis, then evaluation of treatment options or methodologies becomes complex. However, studies on diagnostic markers for use on equine tumors are difficult. Horses are large animals and expensive to keep, and so research studies involving large numbers of horses are very rare, and therefore studies are mostly retrospective in nature. Veterinary studies often involve far fewer subjects than similar studies performed in human medicine, and this is only exacerbated in published equine studies. Researchers should be commended on both the examination of new diagnostic methods and evaluation of methods already published. Until fundamental questions regarding the accurate diagnosis of these tumors are answered, there will remain many mysteries around equine sarcoids. Resolving some of these may provide great benefits to horse owners and clinicians worldwide.