DISCUSSION
It is conventionally believed that new liver masses in patients undergoing GIST surgery are usually considered to be metastatic lesions, and primary diseases are rare8. In this case, the small intestinal stromal tumor was larger than 5 cm and had mitoses >5 mitoses/50 HPFs, indicating a high risk of GIST metastasis, ranging from 71% to 90%9-11. Therefore, if a single lesion appears in the liver after resection of a small intestinal stromal tumor, it is more likely to be GIST liver metastasis. However, the treatment effect of imatinib failed to control the progression of the mass, leading to surgical resection, which confirmed the final pathology as hepatocellular carcinoma. Early-stage hepatocellular carcinoma often lacks obvious clinical manifestations and is challenging to differentiate from GIST liver metastasis. The patient has no history of carrying the hepatitis virus, and the laboratory indicators do not show abnormal elevation of serum alpha-fetoprotein or liver function damage. Both imaging features can show hypodensity, and heterogeneity may be observed on CT enhancement due to necrosis, hemorrhage, or cystic changes12, 13. If further diagnosis is required, invasive percutaneous liver puncture to obtain pathology is also necessary. GIST liver metastases and HCC require different treatment options. Early detection of single and easily resectable liver metastases, combined with complete tumor resection and imatinib-targeted therapy, can help improve the disease-free survival and overall survival rate of patients4, 9. Surgical treatment is the recommended approach for early-stage HCC, necessitating complete tumor resection and adequate liver function compensation14.
Imatinib is recommended as the first-line adjuvant treatment after GIST surgery. Prior to the liver cancer surgery, the patient had been regularly taking imatinib for an extended period. The size of the liver lesion had progressed to a limited extent, with no apparent signs of distant metastasis. The changes in the tumor microenvironment caused by imatinib treatment of GIST may have a regulatory effect on the progression of HCC. Research findings indicate that imatinib can inhibit the proliferation of liver progenitor cells and the formation of liver tumors in mice. Hepatocytes are therefore expected to become a new therapeutic target for TKI treatment of HCC15, 16. By establishing a hepatitis C virus-related xenograft liver cancer mouse model, imatinib was able to significantly reduce tumor growth and inhibit phospho-Akt and cyclin D1 expression in tumor-bearing mice17. Additionally, it was observed that the patient developed multiple GIST metastases quickly after discontinuing imatinib following surgical treatment of HCC. Continuous long-term application of imatinib is necessary to achieve GIST control, as TKIs cannot eliminate tumor cells18. A prospective multicenter study revealed that interrupting imatinib therapy is associated with disease progression in patients with advanced GIST19. Furthermore, it was found challenging to control the quality of response achieved after re-applying imatinib to the tumor state observed at the time of initial discontinuation20. Therefore, when GIST patients are complicated by HCC, a comprehensive assessment of the patient’s physical functional status, combined with surgical treatment, targeted therapy, and other treatment measures, as well as early application of postoperative adjuvant therapy, can help improve the patient’s prognosis and achieve a longer survival time.
This case report presents a rare occurrence of metachronous GIST coexisting with HCC, where the patient developed secondary GIST liver metastasis after treatment. Statistical analysis of follow-up data revealed an increased risk of developing secondary tumors in patients with GIST, and the most common secondary tumors include gastrointestinal cancers, genitourinary malignancies, and breast neoplasms21, 22. In a study involving 783 patients with GIST and other primary tumors, only 153 patients had a second tumor. Interestingly, only 2 of these patients had primary liver cancer prior to GIST, making the occurrence of primary liver cancer after GIST surgery even more rare23. This report aims to underscore the significance of long-term follow-up for GIST patients. When a patient detects a new lesion after GIST surgery, it is crucial to consider not only the tumor’s progression and metastasis but also its differentiation from other primary diseases. A comprehensive assessment is essential in determining the optimal timing of surgery and ensuring the best prognosis for the patient.