CANCER

Cancers have been an occasional problem among wildlife. We provide some initial definitions. A neoplasm (= tumor) is a local, autonomous new growth and unregulated division of cells that does not serve a useful purpose for an organism.

Two distinctive features distinguish cancers from benign tumors. Cancers can invade healthy tissue, whereas benign tumors do not expand into new tissue. The term cancer is derived from “crab,” because of early histological observations that the cancer tissue invading healthy tissue superficially resembled the pincers of a crab. The other distinguishing feature of cancer is that it can metastasize—it can form a secondary growth of malignant neoplasm some distance from the primary site (Rensberger 1984).

When cancer cells become established, their rate of growth may not differ from those of nor­mal cells of the same tissue. However, in con­trast to the normal cells, cancer cells do not stop multiplying, as if the shut-down mechanism has become faulty. Cancer tends to be more common in tissues with a high rate of prolifera­tion such as skin, intestinal tract lining, and the uterine tract. In contrast, tissues with low pro­liferation such as nervous tissue tend to have low frequencies of cancer (Rensberger 1984).

Neither of the terms malignant or metastasis are limited to cancers. For example, the disease malignant catarrhal fever was a severe prob­lem in Africa for many years, and in Chapter 4 we addressed the notion of the metastasis of Echinococcus multilocularis hydatids.

Although affecting a wide variety of tissues and organs, cancers generally can be ascribed to one of three broad groups. Carcinomas are malignant neoplasms arising from epithelial cells—either on the outside or the inside the body. Sarcomas are cancers arising from connective tissue cells. Leukemias and lymphomas are cancers arising from blood­forming elements of bone marrow.

The term carcinogenic refers to something tending to cause cancer. Four common groups of causes have been proposed for cancers, includ­ing chemicals (e.g., cigarette smoke), radiation, viruses, and chromosomal rearrangements.

For wildlife, most causes of neoplasms are not well defined. Chromosomal rearrange­ments, radiation, viruses, and carcinogenic chemicals are some of the causes. Among viruses, papillomaviruses (Sundberg et al. 2001, Phalen 2007) and retroviruses (Drew 2007) are important causes. Other virus- induced neoplasms include Shope's rabbit fibroma virus among cottontail rabbits (Sylvilagus floridanus) (Kilham and Dalmat 1955, Dalmat 1958), mammary carcinoma virus of mice (Bittner 1936), rodent leukemia (Gross 1951), and bovine leukemia (Larson et al. 1970).

Most neoplasms are not well studied in wildlife, but in recent years there has been an upsurge in information (McAloose and Newton 2009). Currently, there is an infectious tumor affecting Tasmanian devils (Sarcophilus harrisii) that is of considerable importance; the tumor origin appears linked to key chromosomal rearrangements. True infectious tumors are very rare (Welsh 2011).

Devil Facial Tumor Disease (DFTD)

causative agent The causative agent is a cell from a malignant oral-facial tumor in which the chromosomes of the tumor cell have under­gone a complex rearrangement (Pearse and Swift 2006). It is a clonally transmissible tumor that appears to be a neural crest cell-lineage neoplasm (O'Neill 2010) of Schwann cell origin (Murchison et al. 2010). Based on genome sequencing, the cancer appears to have first arisen in a female Tasmanian devil, and there is evidence for a dis­tinct mutational process (Murchison et al.

In recent years, additional changes in chro­mosome configuration have been observed, producing several strains capable of transmis­sion (Murchison et al. 2012, Pearse et al. 2012). However, genomic differences between strains appear to be limited (Deakin et al. 2012).

host and distribution First described in 1996, this infectious tumor affects solely the Tasmanian devil on the island of Tasmania, Australia (Hawkins et al. 2006).

reservoir and transmission Transmis­sion of the tumor is closely linked with the aggressive behavior of Tasmanian devils and occurs by allograft, in which an infectious cell line is passed directly between the ani­mals through bites (Pearse and Swift 2006). Although aggressive behaviors and biting occur among all ages and both sexes, the mat­ing season may be the key period for disease transmission (Hamede et al. 2008).

clinical effects and diagnosis This is a malignant oral-facial tumor that obstructs the ability of the Tasmanian devils to properly feed (Pearse and Swift 2006). It is a very dis­figuring and debilitating neoplastic condition (Loh et al. 2006).

The tumors are large, solid, soft-tissue masses, typically with flattened, centrally ulcerated, and exudative surfaces; they are typi­cally multicentric, commonly appearing in the oral, facial, or neck regions (Loh et al. 2006).

Diagnosis of DFTD generally is based on his­topathology, cytogenetics, and clinical appear­ance of the disease in affected animals (Tovar et al. 2011). Based on immunohistochemistry, periaxin is a very sensitive marker to distinguish DFTD tumors from other types of neoplasms affecting Tasmanian devils (Tovar et al. 2011).

population effects This is an emerging disease that has become widespread and is considered a very serious threat to Tasmanian devils. There is a clear link between arrival of DFTD at a site and subsequent population decline (Hawkins et al. 2006, Lachish et al. 2007). The disease covers most of the host range and has led to an overall population decline exceeding 60% (McCallum 2008).

One impact of the rapid mortality is a shift from iteroparity toward single breeding among Tasmanian devils, since virtually all infected animals die soon after their first year of life (Lachish et al. 2009). Infected populations have had reported 16-fold increases in the proportion of individuals undergoing precocious sexual maturity (Jones et al. 2008). Offspring sex ratios of diseased mothers were more female biased than those of healthy mothers, evidence that the hosts may adjust offspring sex ratios in response to disease-induced changes in the mothers (Lachish et al. 2009).

Following the introduction of DFTD to Tasmanian devil populations and their sub­sequent decline, the remaining animals have changes in genetic structure as well as dispersal patterns (Lachish et al. 2011).

special problems The tumor is foreign to the host and is unusual in that it is both a tumor and a tissue graft, and is passed among susceptible hosts without eliciting an immune response (Siddle et al. 2007), despite the Tasmanian devils appearing to have relatively normal immune capacity (Kreiss et al. 2009).

Successful transmission is linked to the tumor sharing genes of the host major histo­compatibility complex (MHC), and with the fact that the tumor's limited genetic diversity does not allow it to be recognized by the devil as “nonself” (Woods et al. 2007). Spread of the disease is linked to this loss of host MHC and the aggressive behavior of the Tasmanian devil (Siddle et al. 2007, 2010). The low genetic diversity observed among Tasmanian devils likely preceded introduction of DFTD by at least 100 years (Miller et al. 2011).

Declines in Tasmanian devil populations are not being effectively offset by population compensatory responses (Lachish et al. 2007). Because of the severe population impacts, the Tasmanian devil is listed as a threatened spe­cies in Tasmania (Hawkins et al. 2006).

Very likely, without active human inter­vention, the Tasmanian devil faces extinction (Jones et al.

control Proposals for DFTD management include eradicating the disease where it occurs and establishment of “insurance populations” in captivity and in the wild (Jones et al. 2007). In one study, selective culling of infected Tasmanian devils only compensated for dis­ease mortality at the test site, and did not slow the rate of disease progression or reduce population-level impacts of DFTD. Failure of culling was linked to the frequency-dependent nature of DFTD, its long latent period, its high degree of infectivity, and the likely continual immigration of diseased individuals (Lachish et al. 2010) into the site. Population models further support the ineffectiveness of culling as a control strategy (Beeton and McCallum 2011).

Another strategy, finding an effective vac­cine, seems feasible over the long term, but not as a short-term strategy. It is argued that with a relatively stable genome, the tumor could be the target of a vaccine; but the immune system first needs to identify the tumor as nonself (Woods et al. 2007). There is evidence that natural killer (NK) cells might be incorporated into a process to develop a future vaccine (Brown et al. 2011).

Interestingly, there is evidence for unique MHC genotypes in northwestern Tasmania, an area where there also has been no rapid increase of disease prevalence or evidence of popula­tion decline, despite the presence of disease (Hamede et al. 2012). There may be important functional differences between the genotypes of DFTD tumors in this region, compared to those of more severely affected sites. Such find­ings hold some promise for future research.