Abstract
An 11-year-old Andalusian stallion developed marked signs of colic associated with an acute small intestine obstruction. Exploratory laparotomy revealed a distal jejunum full-thickness wall induration and multiple small adherent intraluminal masses. Fifteen centimeters of jejunum, including the induration, and several intraluminal masses were resected. Histologic examination revealed an adenocarcinoma and multiple polypoid adenomas. The horse was discharged, and no complications were reported 12 months postoperatively. Colic was considered secondary to partial jejunal lumen obstruction by the adenocarcinoma. Adenocarcinoma recurrence or transformation from remaining adenomas into an adenocarcinoma is still a major risk.
An 11-year-old Andalusian stallion was admitted to the Lyon Veterinary Teaching Hospital for colic. Twenty-four hours before admission, the stallion had an acute onset of apparent abdominal pain. Ringer lactate solution, a single dose of 1.1 mg/kg of flunixin meglumine, mineral oil, and 30 ml of butyl scopolamine were administered. This treatment improved the horse's comfort for 3 hours, after which the horse showed signs of colic. At that moment, heart rate was 60 beats per minute, and rectal palpation revealed several loops of distended small intestine.
On admission to the hospital, the horse's heart rate was 50 beats per minute, but the animal did not show any signs of discomfort. The horse had normal borborygmi. On rectal examination, 2 hard masses, approximately 3 cm in diameter, which could be palpated in a segment of small intestine. Blood sampling revealed a packed-cell volume (PCV) of 43% and a total protein concentration of 64 g/liter (reference range: 24–42% and 55–75 g/liter, respectively). Abdominocentesis yielded abundant clear fluid with a protein concentration of 30 g/liter (reference range: <25 g/liter) and normal color. Two liters of reddish-brown reflux were obtained on nasogastric intubation. Abdominal ultrasonography was unremarkable. The horse was placed in a stall for observation, and feed was withheld.
Abdominal discomfort returned and the decision made for celiotomy. A full-thickness wall induration of approximately 5 × 2 cm was palpated at 7 m from the ileocecal valve. The small intestine proximal to the indurated segment was distended by fluid and impacted food. The aboral part appeared normal. Small intestinal contents were gently forced through the stricture into the cecum. Multiple small adherent intraluminal masses were palpated throughout the entire length of the jejunum and ileum. Fifteen centimeters of jejunum, including the induration, were resected and an end-to-end anastomosis performed. Mesenteric lymph nodes were normal on palpation. The abdomen was closed routinely, and the horse was moved to the recovery room. During recovery, the animal was unable to breath because of upper airway obstruction. An emergency tracheotomy was necessary. The animal recovered and experienced some mild to moderate postoperative complications.
Immediately after surgery, the indurated segment was examined macroscopically. The main mass appeared to be intramural, fibrous, and ulcerated. The lesion had the appearance of a ring, involving almost the entire jejunal circumference and reducing the lumen diameter to 2 cm. Arising from the mucosa were numerous intraluminal, 2-mm- to 2-cm-diameter, multinodular, purple to tan, moderately firm to friable, occasionally hemorrhagic, polypoid masses (Fig. 1). Samples of the resected jejunum and portions of the ulcerated mass were immersed in 10% neutral buffered formalin, embedded in paraffin, sectioned at 5 μm thick, and stained with hematoxylin and eosin.
Histologically, the pedunculated masses showed an abrupt transition from the unaffected mucosa. Masses were composed of regularly shaped papillary projections supported by a core of thin bands of well-vascularized, dense collagenic stroma. Projections were lined by a single layer of cuboidal to columnar neoplastic epithelial cells with interspersed moderate numbers of goblet cells (Fig. 2). Mitotic figures were rare, and anisocytosis and anisokaryosis were minimal. A moderate number of lymphocytes and plasma cells were scattered within the stroma (Fig. 3).
Microscopically, the architecture of the jejunal mucosa, submucosa, muscularis, and serosa were focally markedly altered by a large, infiltrative, nonencapsulated, sparsely cellular mass, which showed abrupt transition from the unaffected mucosa. The mass was composed of variably sized and shaped islands and tubules of neoplastic epithelial cells, supported by abundant well-vascularized desmoplastic stroma. The neoplastic cells were cuboidal to polygonal, mitotic figures were rare, and anisocytosis and anisokaryosis were moderate. Cellular atypia, such as karyomegaly, cytomegaly, and multiple nucleoli, were noted in a moderate number of cells. Some tubules were distended by proteinic material with occasionally admixed necrotic neoplastic cells. The surface of the mass was extensively ulcerated and covered by a thick layer of viable and degenerate neutrophils, fibrin, and morphologically variable bacterial colonies. The subtending stroma superficially contained numerous neutrophils and few lymphocytes and plasma cells in deeper regions. The morphologic diagnoses were multiple polypoid adenomas and jejunal adenocarcinoma, respectively (Fig. 4).
Equine small intestinal adenomatous polyps (adenomas) and adenocarcinomas are rare with few cases reported. 3,5,6 Early diagnosis of intestinal neoplasia is difficult because clinical signs are rare until growth of the tumor is advanced. 4 Weight loss, inappetence, intermittent colic, diarrhea, fever, exercise intolerance, or hypoalbuminemia are clinical signs reported in equine intestinal neoplasia. 6,8 It is often a diagnostic challenge to differentiate the latter from inflammatory bowel disease, nonintestinal intraabdominal neoplasia, and internal abscessation. 6
The malignant transformation of an adenoma into an adenocarcinoma could be speculated in this horse. The transformation in humans involves sequential mutations in the K-ras oncogene and in several specific tumor-suppressor genes. 1 At the level of the small intestine and colon, this transformation is related to the number and size of polyps. 1,2 In benign canine colorectal epithelial tumors, a greater overall positive immunohistochemical staining for p53 protein is reported in tumors with malignant transformation. Mutation of the p53 gene may be an early occurrence in the progression in dogs. 7 In human tumor progression, mutation of the p53 gene is a late event. 5
In many cases of intestinal adenocarcinoma, metastasis and invasion of regional lymphatics is common. 6,4 In this case, there was no gross evidence of metastasis at the time of surgery. Fecal occult blood test in adjunction with other diagnostics tools was found to be an indicator for the detection of intestinal adenocarcinomas. 6 Ultrasound can also be a sensitive diagnostic tool when a complete exam is performed. In this case, complete ultrasound examination was unremarkable.
A recent study 6 reported 34 cases of intestinal neoplasia: 11 (32%) were adenocarcinomas, 9 (82%) of which involved the small intestine with 1 case demonstrating complete obstruction of the jejunal lumen. Three of the 9 horses affected with adenocarcinomas were discharged from the hospital. Two of the 3 animals were subsequently euthanized at 3 and 5 years posttreatment because of the recurrence of signs similar to those observed at the time of original presentation. 6
The presence of adenomas in conjunction with an adenocarcinoma in this horse supports the hypothesis of malignant transformation from adenoma to adenocarcinoma. Recurrent colic was considered secondary to partial jejunal lumen obstruction by the adenocarcinoma, as described in other cases. 3,6 Long-term prognosis of horses with small intestine adenocarcinoma seems poor. 6 Twelve months after surgery, the stallion in this case was performing correctly, and no signs of colic or metastasis were reported by the referring veterinarian. However, adenocarcinoma recurrence or transformation from remaining adenomas into an adenocarcinoma is still a major risk.
Luminal aspect of the resected segment. Ulcerated adenocarcinoma (black arrow) and multiple polypoid adenomas (white arrow) are shown. Note the hemorrhagic character of some of the polypoids (white head arrow).
Photomicrograph of a polypoid adenoma. Note the pedunculated mass showing abrupt transition from the unaffected mucosa and lined by proliferating benign neoplastic epithelial cells. Hematoxylin and eosin stain. 2× magnification.
Photomicrograph of the jejunal adenocarcinoma showing extensive infiltration into the submucosa and muscularis (arrow). Hematoxylin and eosin stain. 4× magnification.
Photomicrograph of islands and tubules of neoplastic epithelial cells, supported by abundant well-vascularized desmoplastic stroma, showing anisocytosis and anisokaryosis. Hematoxylin and eosin stain. 40× magnification.