Gastrointestinal Stromal Tumor (GIST) Case Report

Ollie, a 7 year male neutered Golden retriever presented for a consultation regarding options of a abdominal mass. He had recent history of worsening orthopedic issues and would not rise one week ago. A workup by the primary care veterinarian revealed unremarkable bloodwork and chest radiographs. An abdominal ultrasound revealed two splenic nodules and a mass associated with the cecum. He was started on NSAID and his orthopedic issues resolved. He presented to the oncology and surgery service to discuss treatment options for the cecal tumor. Although his recent clinical signs were unrelated to the cecal tumor, it was recommended to pursue surgery to remove the tumor.

The patient was placed in dorsal recumbency and the ventral abdomen was clipped and prepped aseptically. A standard ventral midline abdominal incision was made. There was a 4 cm cecal mass, multiple 2-3 cm splenic masses, and 1 cm masses throughout the liver parenchyma. A typhlectomy was performed using a GIA 50 stapler and the staple line was oversewn with 4-0 PDS in a simple continuous pattern. A splenectomy was performed using a vessel sealing device. A liver biopsy was obtained from the left lateral liver lobe using a 6 mm punch biopsy and the Gelfoam was used to control hemostasis. The abdomen was flushed using sterile saline. The site of splenic removal and liver biopsy were reevaluated for bleeding and none was noted. The abdomen was closed routinely. The linea alba was closed using 0 PDS in a simple continuous pattern. The subcutaneous tissue was closed using 2-0 PDS in a simple continuous pattern. The intradermal tissue was closed using a subcuticular pattern using 3-0 Monocryl and the skin was closed using staples. The skin mass over the right elbow was removed with electrosurgery and two staples placed in the skin. The spleen/mass, cecal mass, skin tag mass, and liver biopsy were submitted for histopathology.

Histopathology was consistent with a low grade sarcoma of cecum, presumptive gastrointestinal stromal tumor (GIST) with a complete resection. Splenic nodular hyperplasia, with extramedullary hematopoiesis was documented in the spleen and hepatic glycogen accumulation in the hepatic sample evaluated.

Immunohistochemical (IHC) stains were performed and positive for CD-117 confirming the diagnosis of a gastrointestinal stromal tumor (GIST).

Image 1: Positive C-kit expression differentiates a gastrointestinal stromal tumor (GIST) from a leiomyosarcoma. Image courtesy of Matti Kiupel.

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Outcome: Based upon the diagnosis of a low grade gastrointestinal stromal tumor (GIST) with a complete excision and clean staging, no adjuvant therapy was recommend. Ollie is to return q 4-6 months for restaging for the next 2 years.

Background:

The incidence of intestinal tumors in dogs is low in comparison to people. Dogs can develop small intestinal tumors and large intestinal tumors and they tend to occur in older dogs (>6 years) Generally, clinical signs include anorexia, vomiting, weight loss, lethargy, diarrhea, and melena. Males and females tend to develop intestinal tumors at equal rates. The most common gastrointestinal tumors in dogs are lymphosarcoma, adenocarcinoma, leiomyosarcoma and gastrointestinal stromal tumor with adenocarcinoma being the most common primary intestinal tumor. Leiomyosarcomas are reported to be the most common sarcoma of the canine intestinal tract and comprise approximately 10% to 30% of all intestinal tumors in dogs. The advent of advanced immunohistochemistry (IHC) staining techniques has led to reclassification of gastrointestinal leiomyosarcomas (GILMSs). It has been recognized that tumors previously categorized as GILMSs are not composed entirely of smooth muscle but are principally derived from the interstitial cells of Cajal. These act as the pacemaker cells of the gastrointestinal tract and regulate intestinal motility and peristalsis. The ICC-derived tumors have been renamed GISTs. Gastrointestinal stromal tumors are IHC distinguishable from GILMSs or true smooth muscle tumors on the basis of expression of c-kit (CD- 117). Leiomyosarcomas do not express the c-kit protein. The c-kit protein is a transmembrane receptor with a tyrosine kinase component. GISTs often have activating c-kit mutations may be the driving force in gastrointestinal stromal tumor oncogenesis (similar to a proportion of mast cell tumors). The location of the mutation in GIST is similar in both humans and dogs.

Clinical signs in dogs are often nonspecific including anorexia, weight loss, and lethargy. Melena, hematemesis, and hematochezia are also commonly associated with GISTs. Some patients may present more emergent secondary to perforation of the gastrointestinal wall subsequent to tumor invasion (common when present in the cecum).

Staging includes routine bloodwork (CBC, serum chemistry, urinalysis), chest radiographs, and an abdominal ultrasound to ensure the disease is localized. A recent study noted ultrasonographic features including large tumor size, irregular margin and heterogeneous internal echogenicity with large hypoechoic areas, related closely with the presence of metastasis.

In regards to treatment, surgery is the mainstay of therapy and surgery alone is often associated with longterm survival. In one study a median survival time was 37.4 months for dogs with GISTs, vs. 7.8 months for dogs with GILMSs, and 2.9 months for dogs with undifferentiated sarcomas. The metastatic rate is generally considered low (most tumors are low grade). In humans, standard chemotherapy is associated with a low response rates and considered largely unsuccessful in the control of GISTs. The use of oral tyrosine kinase inhibitors are generally considered a standard of care in human in oncology and has resulted in prolonged survival times, compared with survival times associated with other treatments. In veterinary oncology anecdotal responses have been noted. Currently, only one product, toceranib phosphate (Palladia; Zoetis) is fully licensed by the FDA for use in dogs with MCT.

References:
Russell KN, Mehler SJ, Skorupski KA, et al. Clinical and immunohistochemical differentiation of gastrointestinal stromal tumors from leiomyosarcomas in dogs: 42 cases (1990-2003) J Am Vet Med Assoc. 2007;230:1329-33.
Gregory-Bryson E, Bartlett E, Kiupel M, et al. Canine and human gastrointestinal stromal tumors display similar mutations in c-KIT exon 11. BMC Cancer. 2010;10:559.
Kobayashi M, Kuroki S; Ito K, et al. Imatinib-associated tumour response in a dog with a non-resectable gastrointestinal stromal tumour harbouring a c-kit exon 11 deletion mutation. Vet J. 2013;198:271-4.

Submitted by:
Dr. Steven J Mehler DVM, DACVS and Dr. Craig A Clifford DVM, MS, DACVIM (Oncology)
Hope Veterinary Specialists

 

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