Focal nodular hyperplasia (FNH) is a benign condition that affects normal liver with low prevalence. Recently, the extensive use of oxaliplatin to treat patients with colorectal cancer has been reported to be associated with the development of different liver injuries, as well as focal liver lesions. The present work describes two patients with multiple bilateral focal liver lesions misdiagnosed as colorectal liver metastases, and treated with liver resection. The first patient had up to 15 small bilateral focal liver lesions, with magnetic resonance imaging consistent with colorectal liver metastases (CLM), and fluorodeoxyglucose (FDG)-positron emission tomography (PET) negative. The second patient had up to 5 small focal liver lesions, with computed tomography consistent with CLM, and FDG-PET negative. They had parenchyma sparing liver surgery, with uneventful postoperative course. At the histology the diagnosis was multiple FNHs. The risks of oxaliplatin-based chemotherapy regimens in development of liver injuries, such as FNH, should not be further denied. The value of the modern multidisciplinary management of patients with colorectal cancer relies also on the precise estimation of the risk/benefit for each patient.

Focal nodular hyperplasia (FNH) is a benign condition that affects normal liver with prevalence up to 2.6% in autopsy studies[1,2]. Most of the patients are asymptomatic, while few of them may develop portal hypertension[3,4]. The physiopathology of FNH remains unknown, but non-specific chronic distortion of the intrahepatic blood flow has been considered a potential cause[5]. Recently, the extensive use of oxaliplatin to treat patients with colorectal cancer has been reported to be associated with the development of different liver injuries[5,6]. The present work describes two patients with multiple bilateral focal liver lesions misdiagnosed as colorectal liver metastases (CLM), and treated with liver resection.

The presented cases showed two patients affected by colorectal cancer with multiple FNHs potentially inducedby oxaliplatin-based chemotherapy. Both of them had no history of chronic liver disease, and the chronological correlation between the chemotherapy, its duration, and the appearance of the liver lesions suggests a cause-effect association.

There is a burgeoning use of preoperative chemotherapy in patients with CLM, and a corresponding burgeoning literature reporting non-tumoral liver lesions induced by different chemotherapy regimens[6]. Some direct correlations between chemotherapy agents, specific liver toxicity and postoperative morbidity have been also reported[7,8]. In particular, the development of FNH during oxaliplatin-based systemic chemotherapy has been reported up to 15% of the patients treated with preoperative chemotherapy[9]. Based on a recent review on such topic the damages associated with oxaliplatin-based chemotherapy are complex and heterogeneous. Both erythrocyte extravasation and hepatocytic plate disruption have been reported being signs of sinusoidal wall rupture[5,10]. However, the pathogenesis of FNH remains unclear. Changes in intrahepatic blood flow are supposed to be the primary cause. Such changes may be due to portal vein injuries at the level of the sinusoids, and the resulting portal hypertension plays an important role. The natural history of FNH remains unknown, too. Few spontaneous regressions after the suspension of the chemotherapy have been reported as well as some protective effects of bevacizumab on the development of this toxicity[5,11,12].

From the clinical standpoint their proper diagnosis is a delicate matter, since they occur in oncological patients with generally well-documented, and extensive negative imaging. In our two patients to these consideration the multinodular pattern has further biased the diagnostic conclusion. Indeed, only Hubert et al[11] previously reported two cases of multiple FNHs occurred in similar circumstances while other authors described patients with single lesions[5,6,9]. Our experience is conveying a further peculiarity, which could be useful for further discussion and experiences in this sense. Indeed, to our knowledge no previous studies on the use of FDG-PET in such specific clinical setting have been reported. Even if no conclusions can be drawn based on two cases, and considering also the tendency of lower accuracy of FDG-PET after chemotherapy[13], a potential value of such imaging modality should be further investigated, and taken into account during the workup in such circumstances.

In conclusion, an increasing proportion of patients with CLM nowadays receive oxaliplatin-based chemotherapy, including postoperative treatment after stage III colon cancer, induction therapy in patients with extensive metastases, and perioperative treatment in patients with resectable metastases. The risks of such chemotherapy regimens in development of FNHs, as well as of other forms of liver injuries, should not be further denied. The value of the modern multidisciplinary management of patients with colorectal cancer relies also on the precise estimation of the risk/benefit for each patient.