Sinusoidal obstruction syndrome (SOS) and nodular liver regenerates (NRH): Tracking FOLFOX liver injury with CEUS

Purpose: In a challenging case of 5 new focal liver lesions in a patient 6 years after colon carcinoma characterization by follow-up CEUS was supplemented by detailed histopathological workup.

Material and methods: 46-year old patient, colon carcinoma 6 years ago (pT3pN1cM0G3). Postoperatively due to high-risk situation (N1) and young age yearly ultrasound examinations including CEUS were performed. 6 years after an adjuvant oxaliplatin-based chemotherapy (FOLFOX4) 5 new hypervascularized focal liver lesions of 3 – 8 mm were detected by B-mode US and CEUS, 2 of them intraoperatively. One lesion showed a wash-out phenomenon in the late phase. MRI and CT did not show any lesions.

GE Logiq E9, C1 – 5 und L-9 probe (intraoperative), CEUS pulse inversion technique; 1 or 2 ml depending on the probe). MRI: 1.5T. Ultrasound-controlled operative resection of all lesions. Detailed histopathological workup with HE-, EvG-, Reticulin- and CD31-staining.

Results: Perfusion by performing CEUS showed transabdominally and intraoperatively hypervascularization of the nodules. Surprisingly histology by frozen section did not show a distinct lesion. After formalin-fixation EvG- and Reticulin-staining revealed hyperregenerative nodules with dilated sinusoids. Vasculature-specific immunohistochemistry (CD31) demonstrated extensive neovascularization of the nodules. Injury of portal vein branches was present, a described adverse effect of oxaliplatin.

Conclusion: Oxaliplatin-based chemotherapy may cause vascular liver injury: acute SOS and late-term NRH. Studies show such adverse effects might occur in up to 60% of patients. The resulting microcirculation/disturbance may induce neovascularization in areas of increased regeneration (30%). In the presented case, suspicious liver-nodules demonstrate hypervascularization in arterial phase of CEUS and different perfusion behaviour in late phase. Thus an unambiguous assignment cannot be made. Histologically the increased perfusion in CEUS can be tracked down to extensive neovascularisation. Due to intensive US-follow-up in this patient we can determine NRH-development to 5 years after drug exposure, thus makes it an important differential diagnoses to metastates.