The crested black macaque (Macaca nigra) is an Old World primate that lives in the rainforest of Sulawesi Island, Indonesia. Nowadays, it is considered one of the most endangered species [14].
There are several reports regarding intestinal neoplasms in primates. A study on prevalence of spontaneous neoplasm in two colonies of Captive Rhesus Macaques found that the gastrointestinal system was the most commonly affected. It also established adenocarcinoma as the most prevalent identified tumor [1]. Other study described carcinomas in 2 rhesus macaques (M. mulatta) and 4 common marmosets [15]. Regarding to leiomyoma in non-human primates, some research have described their findings at gastrointestinal level in dwarf galagos (Galagoides demidovii) and cotton-tap tamarins (Saguinus oedipus) [13]. A research conducted in two populations of Captive Rhesus Macaques (Macaca mulatta), one leyomioma in stomach was differenced from 127 gastrointestinal diagnosed tumors [1]. Regarding females of chimpanzees, the most common tumor was the leiomyoma of the uterus, cervix and vagina [16]. Referred to Rhesus Macaques (Macaca mulatta), from 61 tumors diagnosed in uterus, 30 of them corresponded to leiomyoma [1]. A review compiling 247 neoplasms founded in 217 prosimians, three leiomyoma were described in uterus (two in Coquerel’s giant mouse lemur and one in Mongoose lemur [17]). Finally, a case of splenic angioleiomyoma was discovered in an Owl monkey (Aotus nancymae) as a rare benign neoplasm [18]. The epidemiologic studies on small bowel tumors are limited, in part, due to their low incidence [10], or by the low susceptibility of this anatomical region to neoplasm [15]. According to Lu et al., 2012 [19], in human medicine, tumor in small bowel is rare, representing only 5% of gastrointestinal tumor cases. Likewise, small bowel rarely develops malignant tumors [20]. Fewer than 2% of all GI malignancies are originated in the small bowel [21]. In relation to benign tumor in small bowel, leiomyoma is the most common type [10], representing 20 to 30% of tract tumors [22]. Some analysis showed that leiomyomas account for almost one fourth of all benign tumors in small bowel [12]. Therefore, the low reporting of benign tumor in small intestine of non-human primates is due to similar behavior of neoplasm in human.
The most common clinical symptoms associated with small bowel tumor are related to obstruction and bleeding. Obstruction usually manifests as recurrent crampy abdominal pain. The pain is usually periumbilical or epigastric, occurring after meals. Some people may experience associated bloating, nausea, or vomiting [10]. However, in many cases, the diagnosis is difficult due to the absence of symptoms [22]. In a retrospective analysis conducted on 10 common marmosets (Callithrix jacchus) suffering from small intestinal adenocarcinoma, nine of them had common symptoms related to weight loss and an intractable diarrhea, with variable presence of blood [15]. Human patients from other reports showed symptoms of anorexia, and recurrent episodes of diarrhea with loose stools and vomiting.
Related to present study, patient´s symptoms such as anorexia, and recurrent episodes of diarrhea, with loose stools, and vomiting, match tract tumor cases reported in previous studies and revisited bibliography. Moreover, abdominal bloating symptom coincides with an accumulation of gas produced by a tumor intestinal obstruction, among other causes, as previously found in human [23–25]. In other words, a relationship between those symptoms and bowel tumor can be established.
Lower gastrointestinal tract tumor is uncommon in domestic animal, especially in horse and production animals. However, this tumor has been found frequently in surgical biopsy applied to dogs and cats. Malignant neoplasm is more common than benign tumor. With the exception of lymphosarcoma, carcinomas are the most [26]. In human, a variety of infectious, genetic and environmental factors may contribute to gastrointestinal tumorigenesis. It is well known that Helicobacter sp. bacteria is involved in the development of gastric and colonic carcinoma in human and immunodeficient mouse. Isolation of this species of bacteria in cotton-toptamarins (Saguinus oedipus), suffering from chronic colitis, showed no connection with a potential tumor formation [15]. On the other hand, different members of the family Herpesviridae can affect primates, having different biological characteristics, and producing latent infections in secretion glands, lymphoid organs, kidneys and other tissues. In addition to, they can produce irreversible cytolitic effects and severe systemic inflammatory reactions [27]. Epstein-Barr virus, a human herpes virus has been commonly associated with lymphoproliferative diseases including lymphosarcoma and gastric adenocarcinomas. The Epstein-Barr related virus such as Callitrichine Herpesvirus 3 (CHV-3) has been isolated from common marmosets with lymphosarcoma, but an association with other malignancies in these marmosets has not been determined [15]. Non-human primate is very popular in zoological collections and also an important focus for the social sciences and biomedical research. Direct and indirect contact associated with this animal have repeatedly demonstrated the movement of major infectious diseases related to an interspecies manner. The prevention to infectious disease exposure is important and fundamental for the conservation of primates [28].
In human, there is a genetic predisposition to gastrointestinal cancer due to a defect in repair genes, or DNA mismatch repair genes (MMR), causing hereditary nonpolyposis colorectal cancer (HNPCC). Affected individuals are predisposed to develop neoplasms, and more frequently develop adenocarcinomas of the colon [29]. As a support for environmental carcinogens, epidemiological studies have been performed, which suggest relationships between the development of cancer and exposure to picolinic acid herbicides and phenoxides and high population densities. On the other hand, the ingestion of diets high in fat constitutes a major risk factor for colorectal cancer [29]. Based on genetic similarities between human and non-human primates, it is important to gather and study several cases of gastrointestinal neoplasms in order to establish a new spontaneous animal model for future comparative surveys.
Immunohistochemical study revealed neoplastic cells negative for cytokeratin, and positive for vimentin and α-smooth muscle actin, which his consistent with an IHC profile of a smooth muscle neoplasm. Despite this, there are other immunohistohemical markers that could be useful in this case such as S-100, CD34 and CD117 (c-KIT). The c-KIT is expressed in gastrointestinal stromal tumor (GIST) [30, 31] together with CD34 as double-positive reactivity [32] and therefore must be taken into account in the differential diagnosis. S-100 antibody is a marker of neurogenic differentiation, lacking of leiomyomas [30]. Unfortunately, we are unable to test immunoreactivity to c-KIT, CD34 and S-100 due to loss of the remaining paraffin embedded tissue during transport between Colombia and Brazil. Thus, in future assays, the use of these markers would be very important in order to classify more accurately primary intestinal tumors.
The hematological examination revealed leukocytes, exhibiting prominent neutrophilia and eosinophilia. Neutrophilia is a common indicator for an inflammatory response to an infectious or non-infectious origin. Likewise, eosinophilia is characteristic of allergic inflammation or parasites [33]. Both, neutrophilia and eosinophilia, are usually considered as indicators of a parasitic infection [34]. Despite of, no parasite was identified in the necropsy and microscopic evaluation.
The serum chemistry parameters reached increased levels of ALT, AST and ALP, which collectively indicate liver injury. This was confirmed by histopathological analysis of the liver that revealed lymphoplasmacytic infiltrate in addition to several intracytoplasmic vacuolation (steatosis). By itself, creatinine is formed in the muscle during the metabolism of creatine. Then, it is subsequently diffuse into the blood, which is transported to the kidney, where is filtered by the glomerulus and, finally, is excreted in the urine [35]. Creatinine once formed in the muscle cannot longer be re-converted into creatine, its predecessor. Thus, this metabolite is used as an indicator of muscle metabolism and renal function. The increased level of this substance in the patient blood suggested alteration in muscle or kidney. Finally, once the kidney was analyzed by means of histological procedures, the alteration suffered by the organ was confirmed. In other words, the increase of creatinine was caused by a kidney failure of the animal.
