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.