Intestinal Neoplasia in Horses

Intestinal neoplasia is a rare condition in horses associated with abnormal cellular replication (i.e. tumors), which is then classified as either benign, malignant or malignant-metastatic in nature. Lymphoma and adenocarcinoma are the two neoplasia types diagnosed most commonly, however many cell types in the intestinal tract can become neoplastic, including smooth muscle cells, nerve cells and epithelial cells.

Some intestinal neoplasias only grow locally, while others can disseminate throughout the intestine, or metastasize aggressively throughout the body.  All segments of the alimentary system can be affected, however the small intestine is most commonly involved.

The clinical signs of intestinal neoplasia  tend to be nonspecific and can include weight loss, colic, inappetence and fever.  Many diseases present with similar clinical signs, such as inflammatory bowel disease, intestinal ulceration, helminthosis, kidney and liver disease, and other types of neoplasia that arise from outside of the intestinal tract.

The long-term prognosis for horses with intestinal neoplasia is generally very poor.  Surgical removal of focally growing tumours might be curative. The field of equine oncology is developing and treatment options such as chemotherapy are becoming more available, however at this stage, limited information is available on the success rates of treatments for intestinal neoplasia in horses.

It’s important to note that that not many large scale research studies currently exist on intestinal neoplasia, only small studies, and sometimes the information reported is different. The findings referenced in this article represent statements most researchers were making in the existing literature.

Pathophysiology & Presentation of Intestinal Neoplasia in Horses

The most common forms of intestinal neoplasia include lymphoma, adenocarcinoma and squamous cell carcinoma. Less common forms are neoplastic smooth muscle (leiomyomas and leiomyosarcomas), neurofibromas, and metastatic neoplasia that initially form outside the intestinal tract. Common clinical signs of intestinal neoplasia include weight loss, colic, anorexia and fever (Taylor, 2006).

Table 1. A summary of most likely intestinal neoplasia types to be found in different anatomical locations.

ANATOMICAL LOCATIONNEOPLASIA TYPEFOCAL/DISSEMINATEDTREATMENT/PROGNOSIS
EsophagousSCC, leiomyosarcomaFocalGrave prognosis
StomachSCC
Gastric adenocarcinoma
Focal, can metastasize
Focal
Poor prognosis
Small IntestineLymphosarcoma


Adenocarcinoma, leiomyosarcoma, neurofibroma
Lipoma - strangulating
Disseminated


Focal


Focal
Chemotherapy might be possible, poor prognosis.
Surgical removal might be possible

Surgical resolution might be possible
Large IntestineLymphosarcoma
Adenocarcinoma
Disseminated
Focal, metastasize
Poor Prognosis
Surgical removal might be possible

Squamous Cell Carcinomas

Squamous cell carcinomas (SCC) have been reported to occur in the esophagus and stomach. Up to 80% of stomach tumors are reported to be SCCs. SCCs can metastasize into the abdominal cavity and the surrounding viscera. There is no breed, or sex predilection for SCCs, but they tend to occur in older horses. SCCs of the stomach and esophagus can present in a variety of ways including choke, gastric reflux, colic and weight loss.

Lymphosarcoma/Lymphoma

Lymphosarcoma/Lymphoma of the intestinal tract may occur as either the alimentary form or the multicentric form. Veterinary pathologists prefer the term Lymphoma to Lymphosarcoma, as there is no benign form of this disease in horses.

Alimentary Lymphoma

Alimentary lymphoma is the most common form of intestinal neoplasia and tends to affect middle aged horses, with a mean age of 16 years (Taylor et al., 2006). The Standardbred breed may be more at risk (Durham et al., 2013). Alimentary lymphoma arises most commonly from the small intestine and tends to spread diffusely, metastasizing to the intestinal and visceral lymph nodes and may spread to the liver, spleen and kidney. Peripheral lymphadenopathy usually does not occur. Alimentary lymphoma causes weight loss, mild recurrent colic, and/or recurrent episodes of fever. Diarrhea is uncommon, but the fecal consistency may be altered.

Multicentric Lymphoma

Multicentric lymphoma affects older horses, with a mean age of 20 years (Taylor et al., 2006). Multicentric lymphoma presents as a more severe form of disease as it affects more organ systems, with clinical signs such as peripheral lymphadenopathy, emaciation and ventral edema a feature of the disease.

Lymphomas can be further classified by immunophenotyping, which can help equine oncologists develop treatment regimes, and assist in prediction of the response to treatment and the prognosis.

The immunophenotypes reported to occur most commonly with alimentary lymphoma include: T-cell-rich Large B cell lymphoma, Peripheral T cell lymphoma and Enteric-associated T cell lymphoma. The first 2 immunophenotypes are also common forms seen with multicentric lymphoma (Durham et al., 2013).

Adenocarcinomas

Adenocarcinomas are malignant tumors that arise from the glandular cells that line the intestinal tract. This tumor type can affect the stomach, small intestine, large intestine and cecum – the latter two sites are most commonly affected. These tumors tend to grow locally, but also can metastasize aggressively, and by the time they are diagnosed, tumor proliferation is often extensive (Völker et al., 2017). Metastatic disease to the bone marrow has been reported. Adenocarcinomas are diagnosed in middle aged to older horses, and present with nonspecific clinical signs such as recurrent colic and weight loss. The Arabian breed may be predisposed to this type of neoplasia (Taylor et al., 2006).

Leiomyosarcomas and Leiomyomas

Leiomyosarcomas and Leiomyomas are rare smooth muscle tumors (malignant and benign respectively) that can occur throughout the intestinal tract, from the oesophagus to the small colon. They are focally growing tumors that are usually only diagnosed once they cause obstruction of the intestinal lumen, resulting in symptoms of colic or choke. Leiomyosarcoma can metastasize (Taylor et al., 2006).

Neurofibromas

Neurofibromas are a nerve-sheath tumour that occur rarely, and are a focally growing tumor that usually only cause symptoms once they are obstructing the intestinal lumen.

Other

Metastatic disease of origin outside the intestinal tract can also affect the alimentary system – some possibilities include bile duct carcinomas and mesothelioma.

Lipomas

Lipomas are a benign form of fatty tumor that occur in older horses. Lipomas grow from adipocytes in the intestinal mesentery, and as they grow in size, the increasing weight of the tumor pulls at the mesentery, creating a pedunculated attachment. This free-swinging tumor can then become entangled in the motile small intestine or the less motile small colon and rectum. In its most severe form, the pedunculated lipoma can strangulate intestinal loops (particularly in the small intestine), resulting in sudden onset severe colic symptoms that require emergency treatment.  Older, overweight Quarterhorse broodmares have been reported to be more prone to this disease, as are older geldings and ponies (Smith, 2015; Reed, 2010).

Paraneoplastic Syndromes

Paraneoplastic syndromes occur rarely as a consequence of intestinal neoplasia, and are caused either by the release of hormones or cytokines from the neoplastic cells, or by activation of the host immune system. Reported paraneoplastic syndromes have included:

  • Pruritis and alopecia
  • Hypertrophic osteopathy
  • Pemphigus
  • Hypoglycemia
  • Hypercalcemia
  • Erythrocytosis
  • Neuropathies
  • Immune-mediated haemolytic anemia

Diagnosing Intestinal Neoplasia in Horses

The clinical signs for intestinal neoplasia will depend on the location of the lesion, and the size and metastasizing nature of the disease.  The diagnostic work-up will therefore need to be adapted for the individual case.

Neoplasia of the esophagus or stomach can present with symptoms of gastric reflux or choke, and there may be difficulty passing a nasogastric tube. Endoscopy or barium contrast radiography may be most useful to visualize the lesion. Biopsy of the lesion in these locations can be challenging.

Neoplasia of the small and large intestine requires a full work-up to first rule out more common causes of weight loss, colic and fever.

Blood work:

  • Anemia is common, especially with lymphoma and adenocarcinoma, and may be attributed either to chronic inflammation, immune-mediated hemolytic anemia, or blood loss into the intestinal lumen.
  • The leukogram is often inflammatory (lymphocytosis and/or neutrophilia), but in rare instances, may be leukemic due to infiltration of neoplastic cells into the bone marrow.
  • Hypoalbuminemia is a common finding, due to malabsorption or leakage from intestinal damage.
  • Hypocalcaemia is usually seen concurrent to the hypoalbuminemia.  Hypercalcaemia, as a paraneoplastic syndrome, is rare.
  • Hyperfibrinogenaemia is reported as a frequent feature of adenocarcinoma, and may be seen with other neoplastic types.
  • Liver enzymes might be elevated with metastatic disease, or secondary to intestinal stasis.  Azotemia might be found in dehydrated horses, or if metastatic disease affects the kidney.

Rectal palpation can help identify abdominal masses, or distended loops of bowel.

Peritoneal fluid is usually diagnosed as a transudate or modified transudate, unless intestinal damage is severe, then hemorrhage or peritonitis might be present. The peritoneal fluid can occasionally yield neoplastic cells. Lymphoma, SCC and adenocarcinoma have been diagnosed from peritoneal fluid, with lymphoma being most commonly identified.   Researchers have found that between 21-50% of cases of alimentary lymphoma are positive for neoplastic cells in the peritoneal fluid.

Abdominal and transrectal ultrasound can be used to identify:

  • Intestinal wall that is thickened or has abnormal echogenicity,
  • Intestinal masses,
  • Abdominal lymphadenopathy,
  • Peritoneal effusion
  • Splenic and hepatic masses (Janvier et al., 2016).

Transrectal ultrasound is particularly useful for examining the lumboaortic lymph nodes.

An Oral Glucose Absorption Test may be positive in cases where the neoplasia is affecting a large portion of intestine, causing malabsorptive disease.

A fecal occult blood test might be positive.  Taylor et al. (2016) found that adenocarcinoma was most likely to yield a positive fecal occult blood test, and that these horses also were anemic, suggesting significant bleeding into the intestinal lumen.

Rectal biopsy frequently appears inflammatory in cases of intestinal neoplasia.  Rectal biopsy is also occasionally diagnostic, particularly in cases of alimentary lymphoma (Taylor et al., 2006)

Exploratory laparotomy and biopsy of the affected intestine is often required for a definitive diagnosis. Laparoscopic biopsy may be available in specialist centers.

Immunophenotyping of the biopsy sample can be useful to classify lymphoma types.

Treatment of Intestinal Neoplasia in Horses

Focally growing, non-metastasizing tumors that affect a small area of intestine may be resolved with surgical resection. Strangulating lipomas can also be fixed surgically. In both cases, resection of bowel and anastomosis is highly likely to be needed.

Lymphoma has the potential to be treatable with chemotherapy. It is worth contacting a specialist equine hospital to find out what chemotherapy regimes are possible, as this is an evolving field of research. Alimentary lymphoma may also respond in the short term to corticosteroid treatment.

Prevention

There is no known instigating cause for intestinal tumors yet – no specific bacterial or viral agent has been identified, against which a vaccination or such could be produced.

 

References

Durham, A.C. et al. (2013) Two Hundred Three Cases of Equine Lymphoma Classified According to the World Health Organisation (WHO) Classification Criteria. Vet Pathol, 1:86-93.

Janvier, V. et al. (2016) Ultrasonographic findings in 13 horses with lymphoma. Vet Radiol Ultrasound, 57:65-74.

Reed, S.M. et al. (2010) Equine Internal Medicine, 3rd Ed. Saunders Elsevier, St Louis, pp. 894-5.

Smith, B. (2015) Diseases of the Alimentary System, in Large Animal Internal Medicine, chapter 32. Mosby, Missouri.

Taylor, S. et al. (2006) Intestinal neoplasia in horses. J Vet Intern Med, 20:1429-1436.

Völker, I. et al. (2017) Intestinal adenocarcinoma in ponies: Clinical and pathological findings. Equine Vet Educ, doi:10.1111/eve.12738.