Gastrointestinal Stromal Tumor (GIST)


Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract and develops preferentially in the stomach. Previously, the comorbidity of tumors with different tissue origins was thought to be rare; however, advancements in technology and diagnostic measurements have revealed such cases. The comorbidity that occurs most frequently in patients with GIST is gastrointestinal cancer. Adenocarcinoma, a tumor of epithelial origin and the most common primary gastric cancer, is the tumor that most often coexists with GIST. Patients with both GIST and gastric cancer tend to be older than individuals with GIST alone. After gastrointestinal cancers, other frequent GIST comorbidities include lymphoma, prostate cancer, breast cancer, kidney cancer, lung cancer, female genital cancer, soft tissue and bone sarcomas, malignant melanoma, and seminoma.1 Researchers have hypothesized that 2 different tumor types may develop in the same patient when a single carcinogen induces carcinogenesis or a gene mutation in 2 different tissues.2 Helicobacter pylori infection is associated with the development of gastric cancer, but it is unknown whether H pylori causes GIST. Further investigations are required to ascertain if H pylori infections contribute to both gastric cancer of epithelial origin and GIST.1 

Comorbid tumors of different tissue types may be diagnosed preoperatively, intra-operatively, or postoperatively. Preoperatively, GIST diagnosis may prove difficult. A GIST may be missed because of the limitations of gastric biopsy. GIST locations are deeper than those of epithelial tumors; they may be submucosal, intramural, or subserosal. In addition, a GIST may not be large enough to visualize on radiographic imaging. To improve the diagnosis of comorbid tumors of different types, the preoperative examination must include enhanced computed tomography (CT), gastroscopy, endoscopic ultrasonography (EUS), and careful intra-operative palpation of the rest of the stomach to detect smaller GISTs. Surgeons should consider the possibility that these small lesions are not metastases, but rather tumors of different tissue origin. Postoperative pathologic examination distinguishes between the 2 cancerous tissue types.1

A concomitant malignancy is found in 1.2% to 2.5% of patients with sarcomas. A case series conducted in Florida reported a nonrandom association between sarcomas and sarcoidosis. Of the 8 patients in whom sarcomas were identified, 5 had a GIST. Sarcoidosis was diagnosed before sarcoma in 3 patients, after sarcoma in 4 patients, and concurrently with sarcoma in 1 patient.3

A Surveillance, Epidemiology, and End Results (SEER) Program study examined data from 4224 patients with GIST between 2010 and 2015. Of these, 388 (9.19%) had liver metastasis, 32 (0.76%) had lung metastasis, and 20 (0.47%) had bone metastasis. Investigators determined the median overall survival of the patients with liver, lung, and bone metastases to be 49, 20, and 18 months, respectively. The prognosis of patients who had GIST with liver, lung, or bone metastasis was poorer than that of patients who had GIST without metastasis to these sites. Researchers concluded that liver metastasis might not be associated with lung or bone metastasis and that the liver may play a more dominant role in the prognosis of patients who have GIST with metastasis than the 2 other sites. Careful attention to the condition of the liver during the diagnosis and treatment of patients with GIST is necessary to improve survival.4 

A population-based retrospective study conducted in Hong Kong examined the prevalence of comorbidities in 3358 patients with sarcomas, among which GIST was included. Investigators identified comorbidities and calculated the Charlson Comorbidity Score (CCS), defined by 19 medical conditions according to risk for mortality at the time sarcoma was diagnosed. The 5 most common comorbidities in patients with sarcomas were diabetes mellitus (9.8%), cerebrovascular disease (4.8%), ischemic heart disease (3.8%), chronic lung disease (2.9%), and congestive heart failure (2.6%). These comorbidities may reflect the advanced age of individuals in whom sarcomas like GIST are diagnosed. The mean age of patients at presentation was 54.2 years; the majority of patients were between 40 and 65 years of age.5 

Surgical resection is the standard treatment for GISTs and the only treatment that offers the possibility of a cure. One challenge facing surgeons is that surgical resection may be contraindicated because of the presence of the comorbidities that accompany aging. An alternative to open surgical resection when it is contraindicated is endoscopic ultrasound (EUS)-guided alcohol ablation for GIST treatment. Alcohol injection may also be used to treat metastatic lesions in the liver, adrenal glands, or pelvic lymph nodes.6 

Certain syndromes are associated with GIST. Carney triad manifests with gastric GIST, pulmonary chondroma, and paraganglioma.7 Carney-Stratakis syndrome is characterized by gastric GIST and paraganglioma.7 Neurofibromatosis type 1 manifests with wild-type, multicentric GISTs that contain spindle-shaped tumor cells and are located primarily in the small intestine.7 Neurofibromatosis is a genetic disorder that predisposes individuals to the development of nerve cell tumors.8

References

  1. Li L, Wan S, Zhang Y, Tao K, Wang G, Zhao E. Comorbidity of gastrointestinal stromal tumor and adenocarcinoma in stomach: a report of three cases and review of literature. Int J Clin Exp Med. 2016; 9:19491-19501. ISSN:1940-5901/IJCEM0031009
  2. Liu SW, Chen GH, Hsieh PP. Collision tumor of the stomach: a case report of mixed gastrointestinal stromal tumor and adenocarcinoma. J Clin Gastroenterol. 2002;35(4):332-334. doi:10.1097/00004836-200210000-00010
  3. Espejo AP, Ramdial JL, Wilky BA, Kerr DA, Trent JC. A nonrandom association of sarcoidosis in patients with gastrointestinal stromal tumor and other sarcomas. Rare Tumors. 2018;10:2036361318787626. doi:10.1177/2036361318787626
  4. Yang DY, Wang X, Yuan WJ, Chen ZH. Metastatic pattern and prognosis of gastrointestinal stromal tumor (GIST): a SEER-based analysis. Clin Transl Oncol. 2019;21(12):1654-1662. doi:10.1007/s12094-019-02094-y
  5. Loong HH, Wong CK, Ho C-W, et al. O2-5-4 – Prevalence and prognostic impact of comorbidities in sarcomas: a population-based study of 3746 patients in Hong Kong. Ann Oncol. 2019;30(Suppl 6):vi88. doi:10.1093/annonc/mdz339.024
  6. Parab TM, DeRogatis MJ, Boaz AM, et al. Gastrointestinal stromal tumors: a comprehensive review. J Gastrointest Oncol. 2019;10(1):144-154. doi:10.21037/jgo.2018.08.20
  7. Choti MA. Gastrointestinal stromal tumors (GISTs): etiology. Medscape. Updated March 17, 2021. Accessed June 29, 2021.
  8. Neurofibromatosis. MedlinePlus. Updated June 3, 2021. Accessed June 29, 2021.

Article reviewed by Kyle Habet, MD, on July 1, 2021.

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