Colonic gastrointestinal stromal tumor (GIST) presenting with colocolonic intussusception: A rare case report

Abstract

An 8-year-old spayed female British bulldog was presented with vomiting, hyporexia, and large-bowel diarrhea. Abdominal ultrasound revealed a focal colonic mass with an intussusception located immediately oral to the mass. The intussusception encompassed the ascending and transverse colon and was non-reducible. Colonic resection and anastomosis were completed to include the intussusception and colonic mass. Histopathological examination of the mass demonstrated a spindle cell neoplasm arising within the muscular wall of the intussuscepted segment that obliterated normal architecture. Mild-to-moderate cytoplasmic immunoreactivity of the tumor cell population for CD117 and smooth muscle actin was consistent with a diagnosis of a gastrointestinal stromal tumor. The dog described herein remains alive and free of progressive disease at the time of writing.

Key clinical message:

The entire gastrointestinal tract should be evaluated in any animal with gastrointestinal symptoms. A gastrointestinal stromal tumor remains a plausible differential diagnosis, regardless of the intestinal segment affected, and tumorassociated intussusception is a rare but urgent clinical finding.

Intestinal intussusception is a relatively common gastrointestinal disorder in dogs and cats. It is described as the invagination of 1 portion of the gastrointestinal tract (the intussusceptum) into the lumen of an adjoining segment (the intussuscipiens) (1). Young animals (< 12 mo) have a much higher incidence of intussusception. The condition may be associated with infectious or parasitic agents, foreign bodies, prior abdominal surgery, or intestinal neoplasia in older animals, or it may be idiopathic (2,3). To the authors’ knowledge, there is no previous publication documenting an intussusception associated with a gastrointestinal stromal tumor (GIST) in dogs. Gastrointestinal stromal tumors are mesenchymal tumors of the gastrointestinal tract, specifically arising from the interstitial cells of Cajal. They are thought to arise due to a mutation in the KIT proto-oncogene (c-KIT) that leads to a continuously activated state of this receptor tyrosine kinase and resultant neoplastic transformation (4).

Mutations in the proto-oncogene c-KIT in exons 11, 9, 13, and 17 of the c-KIT gene have been observed in human GISTs. The mutation with the highest frequency is located in exon 11 (5). In canine GISTs, mutations occur frequently in exon 11, as in humans (6). However, in humans, ~5 to 10% of GISTs are KIT-negative or only weakly positive (7–9). Markers such as PDGFRA, protein kinase Θ (PKΘ), and DOG1 (discovered on gastrointestinal stromal tumors protein 1) have been explored in human tumors in hopes of identifying GISTs in this subgroup (8,9). Similar to the human counterpart, DOG1 is also a specific and sensitive immunohistochemical marker in dogs (10).

In veterinary medicine, GISTs are common in the cecum (59 to 66%) and small intestine (34%) (11,12). In humans, however, GISTs are most common in the stomach (60 to 70%), with a smaller proportion arising in the small intestine (20 to 30%) (5,13). Pathological lead points, such as polyps, submucosal lipomas, and malignant neoplasms including GISTs, are identified in ~65% of adult humans who present with intussusception (13). Here, we present a case of an 8-year-old spayed female British bulldog with colocolonic intussusception identified concurrently with a colonic GIST.

Case description

An 8-year-old spayed female British bulldog was presented on referral for further consultation regarding a possible abdominal mass. The dog had a 1-month history of progressive large bowel diarrhea, weight loss, hematochezia, hyporexia, and vomiting. Prior to referral, the dog’s oral medications included prednisone (0.25 mg/kg q12h) and tylosin (10 mg/kg q12h). On physical examination, the dog had a decreased body condition score, was cardiovascularly stable, and had no palpable abdominal mass.

Abdominal ultrasound imaging was subsequently obtained using an 8 MHz microconvex transducer (Cannon Aplio i800; Canon Medical Systems Canada, Markham, Ontario). A focal, hypoechoic, heterogenous, descending colonic mass with an associated intussusception was identified (Figures 1, 2, 3). Mild multifocal colonic mural thickening, mild multifocal distal ileal mural thickening, and mild jejunal lymphadenopathy were also identified.

Figure 1.

Cross-sectional ultrasonographic image of the colonic mass in an 8-year-old British bulldog. The mass measured 2.64 × 3.73 cm and is characterized by a hyperechoic core surrounded by a hypoechoic periphery.

Figure 2.

Multiple hypoechoic and hyperechoic parallel lines are visible in a longitudinal ultrasonographic image of the colonic intussusception in an 8-year-old British bulldog.

Figure 3.

Cross-sectional ultrasonographic image of the colocolonic intussusception in an 8-year-old British bulldog. The lesion consists of a concentric arrangement of hypoechoic rings (colonic wall). The central, hyperechoic region represents the intussusceptum, which is superimposed by a hyperechoic outer ring representing the intussuscipiens.

Complete staging was recommended, including a complete blood (cell) count, biochemical profile, and 3-view thoracic radiographs. There was no evidence of metastases and no overt clinical abnormalities other than a marginal neutrophilia [13.9 × 10⁹/L, reference interval (RI): 2.9 to 12.7 × 10⁹/L), a marginal thrombocytosis (487 × 10⁹/L, RI: 143 to 448 × 10⁹/L), a marginal hypoalbuminemia (24 g/L, RI: 27 to 39 g/L), a moderate increase in alkaline phosphatase (843 U/L, RI: 5 to 160 U/L), a mild decrease in urea (2.3 mmol/L, RI: 3.2 to 11 mmol/L), and a moderate increase in creatinine kinase (463 U/L, RI: 10 to 200 U/L). Surgical resection of the colonic mass and concurrent intussusception was recommended to alleviate clinical symptoms and obtain a histopathological diagnosis.

An exploratory laparotomy was completed and confirmed an intramural mass located in the descending colon with concurrent intussusception encompassing the ascending and transverse colon. The colonic mass and intussuscepted segment were resected, and an anastomosis performed. A liver biopsy and a colonic lymph node biopsy were also obtained. The dog recovered postoperatively and was discharged without incident within 48 h. The dog was prescribed gabapentin (100 mg, PO, q8h), and prednisone (5 mg, PO, q24h) was continued for a further 3 d to facilitate gradual withdrawal.

Histopathological examination of the mass demonstrated a spindle cell neoplasm arising within the muscular wall of the intussuscepted segment that obliterated normal tissue architecture. There was 3-fold anisokaryosis and the mitotic count was 21 mitotic figures in 10 high-power (2.37 mm²) fields, with several atypical mitoses noted. Smooth muscle actin immunostaining revealed patchy, sparse-to-moderate cytoplasmic immunoreactivity (Figure 4). Neoplastic cells (including mitotic figures) exhibited mild-to-moderate immunoreactivity for CD117 (Figure 5). Immunoreactivity was variable and present in ~20% of neoplastic cells. There was no evidence of metastasis in the excised colonic lymph node or liver biopsy.

Figure 4.

Neoplastic spindle cells displaying mild-to-moderate immunoreactivity to smooth muscle actin immunostaining. Scale bar: 25 μm.

Figure 5.

Scattered neoplastic cells, including a mitotic figure, exhibiting sparse granular cytoplasmic immunoreactivity to CD117 (c-KIT) immunostaining. Scale bar: 25 μm.

Postoperatively, the dog was reported to have soft, albeit markedly improved, stool. At 10 mo of follow-up (repeated staging tests), the dog is doing well and remains disease-free.

Discussion

Gastrointestinal stromal tumors are rare gastrointestinal tumors that arise from the interstitial cells of Cajal (14). Common clinical signs in dogs with GISTs are typically a result of the location in which they manifest and may include lethargy, anorexia, and diarrhea (15). Intussusceptions share similar gastrointestinal clinical symptoms but are most common in younger dogs (16). To our knowledge, an intussusception directly and intimately associated with a concurrent GIST has yet to be described in the veterinary literature. Ultrasonography was used in this case to localize the colonic mass and associated intussusception. It is a highly reliable tool for the diagnosis of intussusception in veterinary medicine (17), which appears as a multilayered, target-like lesion with associated proximal fluid accumulation and decreased intestinal motility (18). In humans, computed tomography is generally the preferred imaging modality, but it can be cost-prohibitive and less widely available in veterinary medicine. Computed tomography may also be a more sensitive modality for identification of underlying pathologies concurrent with or causing intussusception (19). In this case, we suspect the GIST was the lead point that propelled the colonic wall in an aboral direction, resulting in an intussusception immediately oral to the GIST. The ultrasonographic appearance of the colonic GIST was consistent with previous reports and could not be distinguished from other gastrointestinal neoplasms such as a leiomyoma or leiomyosarcoma (20). Furthermore, histopathological differentiation of GISTs from other gastrointestinal sarcomas is challenging due to their identical appearances under light microscopy.

Before the advent of immunohistochemistry, many GISTs were classified as leiomyosarcomas (21). However, CD117 (KIT) is a specific and sensitive marker in the diagnosis of GISTs (21,22). The DOG1 marker is considered a more sensitive and specific biomarker for GISTs and is recommended in negative c-KIT on cytological specimens with histopathological suspicion for GIST (23). As our specimen was c-KIT-positive, DOG1 staining was not done. In a recent study, stronger intensity of c-KIT staining in a GIST had a positive association with overall survival time, in comparison to a weaker c-KIT staining (24). This study also demonstrated that a mitotic count of < 9 results in fewer metastases and an overall increase in survival time. The median overall survival time for dogs with surgically resected GISTs ranges from 11.6 to 36 mo (11,15,24). In this case, our patient had a high mitotic index and mild-to-moderate c-KIT immunoreactivity. It is unknown if colonic GISTs or GISTs with associated intussusceptions have poorer prognoses than primary tumors located elsewhere in the gastrointestinal tract, and further studies are required to evaluate colonic location and/or concurrent intussusception as valuable prognostic factors other than in the immediate perioperative setting. Based on the authors’ experience with this case, a colonic GIST is a plausible differential diagnosis in a dog with gastrointestinal clinical signs and may present concurrently with an intussusception. Ultrasonography was an accurate, reliable tool used to identify tumor location and intussusception. Surgical resection and anastomosis of the affected segment of colon has resulted in a disease-free patient at 10 mo of follow-up.