A 49-year old male patient presented with flank pain and hematuria. The CT scan showed a large pelvic tumor 18
cm in diameter (Figure ). A biopsy was performed and the pathologic examination revealed a spindle cell tumor with co-expression of CD117 and S100 protein, as well as a point mutation in c-kit exon 11, consistent with the diagnosis GIST. Due to the large tumor size, neoadjuvant therapy with imatinib 400
mg daily was initiated. After 6
months of treatment, the patient developed grade 3 hepatotoxicity with ALT and AST elevations from normal values to 882 U/l and 383 U/l, and an elevated bilirubin of 25 umol/l. Imatinib was paused for two weeks and parameters rapidly declined to normal limits. Treatment was then continued at 400
mg OD and sustained tumor shrinkage was seen in subsequent CT scans. After 16
months of neoadjuvant therapy tumor shrinkage ceased and tumor size was reduced from 18
cm to 14
cm (22% reduction). A complete tumor resection was performed at that time. Consistent with the clinical response, the pathological examination revealed a tumor regression of 20% (Figure ) with low expression of proliferation markers (MIB <1%). Due to the high risk of recurrence, adjuvant therapy with imatinib 400
mg OD was initiated. After 7
months of adjuvant treatment, grade 4 hepatotoxicity developed with an ALT 1837 U/l and AST 1022 U/l (Figure ) and an elevated bilirubin of 90 umol/l. Imatinib was paused for a total duration of 8
weeks, and subsequently the elevated transaminases declined to values within normal limits. Subsequent re-challenge of imatinib was associated with another episode of hepatotoxicity after 14
days of re-exposure. A corresponding MRI showed the development of cirrhotic changes of the liver (Figure ), which had been absent at the previous MRI 3
months before. Other possible causes of liver damage, including metastasis, alcoholic liver disease, hepatitis A, B, C, and E, autoimmune hepatitis and metabolic disorders were excluded. Imatinib was discontinued permanently and the transaminases returned to normal values within 6
months. Fifteen months after discontinuation of imatinib the patient is still without relapse, but cirrhotic changes of the liver remained sustained on MRI.
Figure 1 CT scan of the patient. GIST of the small bowel 18 x 10cm in size when it was first diagnosed prior nedoadjuvant treatment.
Photomicrograph of the GIST, (Hematoxylin– eosin; original magnification, x200. Tumor regression of 20% under neo-adjuvant treatment.
Development of transaminases under adjuvant imatinib treatment.
MRI of the liver. One month after discontinuing adjuvant treatment MRI shows clearly cirrhotic changes of the parenchyma.