Chemotherapy-induced focal liver injury mimicking colorectal liver metastasis: a case description

Introduction

Chemotherapy plays a crucial role in the comprehensive treatment of intermediate- and advanced-stage colorectal cancer. Although frequently used as adjuvant chemotherapy for colorectal cancer, oxaliplatin-based chemotherapy often leads to liver injury (1). Sinusoidal obstruction syndrome (SOS), previously known as veno-occlusive disease, is a common complication, occurring in 51–79% of patients treated with oxaliplatin but only 21–30% of those receiving other forms of chemotherapy (2,3). The histological spectrum of SOS includes sinusoidal dilatation with hepatocellular necrosis, peliosis, and nodular regenerative hyperplasia (NRH). Severe localized liver damage can sometimes present as a focal lesion that mimics liver metastasis (4,5). In this report, we discuss a case of a newly identified liver lesion during chemotherapy following radical rectal cancer surgery. The lesion was initially misdiagnosed as a liver metastasis based on follow-up imaging, but after liver surgery was performed, the pathology confirmed it as focal liver injury induced by chemotherapy.

Case presentation

All procedures performed in this study were in accordance with the ethical standards of the Ethics Committee of the West China Hospital of Sichuan University (No. HX2024-436) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

The patient, a 34-year-old man, sought medical attention due to a change in bowel habit for 2 months and bloody stools for 2 weeks. He had no specific past medical history or family history of colorectal cancer. Physical examination indicated a good general health status of the patient. No palpable swelling was detected from anal fingertip inspection, but blood-stained finger cuffs were observed upon withdrawal. The colonoscopy revealed a substantial ulcerated neoplasm located in the rectum, approximately 9–14 cm from the anus, occupying three-fourths of the intestinal lumen. The biopsy result showed high-grade adeno-endothelial neoplasia with the formation of intramucosal carcinoma. Laboratory tests indicated elevated levels of carcinoembryonic antigen (CEA) at 13.2 ng/mL and carbohydrate antigen 72-4 (CA72-4) at 27.7 U/mL. Meanwhile, magnetic resonance imaging (MRI) revealed upper rectal cancer with involvement of the lateral lymph nodes, while contrast-enhanced computed tomography (CECT) showed no metastases to distant organs, including the liver (Figure 1). Consequently, the tumor was clinically staged as T4aN2M0. The patient underwent two cycles of oral capecitabine chemotherapy and received 28 concurrent radiotherapy sessions as neoadjuvant treatment. Two months after completion of the treatment, the patient underwent radical surgery for rectal cancer. During intraoperative exploration, no apparent metastatic nodes were identified in the liver. Postoperative pathology indicated T1N0M0 rectal mucinous adenocarcinoma. Following surgical intervention, the patient underwent 6 cycles of combined oxaliplatin and capecitabine chemotherapy.

Figure 1 A CECT scan for rectal cancer performed before neoadjuvant chemotherapy indicated the absence of distinct focal lesions on segment 6 of the liver during the portal phase. CECT, contrast-enhanced computed tomography.

After completion of the third cycle of postoperative chemotherapy, CECT in the portal phase identified a slightly hypodense lesion measuring 24 mm × 16 mm in size on segment 6 of the liver, adjacent to the inferior vena cava (IVC) (Figure 2). However, the lesion was less distinct in the unenhanced images and arterial phase. Despite the suspicion of a metastatic liver lesion due to its absence in previous examinations, the patient’s levels of CEA and CA72-4 were not elevated (1.14 ng/mL and <1.50 U/mL, respectively), and the treatment plan remained unchanged. After the completion of six postoperative chemotherapy cycles, neither contrast-enhanced MRI (CEMRI) nor contrast-enhanced ultrasound (CEUS) showed any significant changes in the lesion’s size. CEMRI revealed that the lesion was slightly hypointense on T1-weighted imaging (T1WI), isointense on T2-weighted imaging (T2WI), hypointense on diffusion-weighted imaging (DWI), and heterogeneously hypoenhanced in the arterial, portal, and delayed phases. Notably, during the hepatobiliary phase on MRI enhanced by liver-specific contrast (gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid, Gd-EOB-DTPA, Bayer Healthcare AG, Leverkusen, Germany), the lesion showed slight hypointensity compared to the surrounding liver parenchyma (Figure 3). On grayscale US, the lesion presented as a slightly hyperechoic mass with poorly defined margins. After the injection of contrast media (SonoVue, Bracco, Milan, Italy), the lesion demonstrated slight hyperenhancement during the arterial phase, mild washout in the early portal phase, and hypoenhancement in both the portal and delayed phases (Figure 4). Based on these findings, liver metastasis was suspected, and thus liver surgery was performed 3 months after chemotherapy. The postoperative pathology report indicated no tumor cells but did reveal a significant dilation of hepatic sinusoids accompanied by blood congestion, atrophy of hepatic plates, and disappearance of hepatocytes, with purpura-like changes also being observed. These pathological changes were irregularly distributed with peripheral hepatocellular proliferation, and the hepatic portal regions showed no evidence of fibrosis (Figure 5). Throughout the therapeutic process, the patient’s tumor markers remained within normal ranges. The patient recovered well after the liver surgery. At the time of writing, it has been 3 years since the patient’s initial rectal cancer surgery and 2 years since the partial hepatectomy, with no signs of recurrence being observed in regular 6-month follow-up appointments thus far.

Figure 2 CECT performed after three cycles of postoperative chemotherapy following radical rectal cancer surgery revealed a slightly hypointense lesion (yellow arrowhead) on segment 6 of the liver during the portal phase. CECT, contrast-enhanced computed tomography.

Figure 3 CEMRI following six cycles of postoperative chemotherapy revealed a lesion (yellow arrowheads). (A) The lesion was slightly hypointense on T1WI, (B) isointense on T2WI, and (C) hypointense without evident diffusion restriction on DWI. (D,E) The lesion appeared heterogeneously hypoenhanced in both the arterial phase and portal phase and (F) demonstrated mild hypointensity during the hepatobiliary phase. CEMRI, contrast-enhanced magnetic resonance imaging; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging; DWI, diffusion-weighted imaging.

Figure 4 CEUS performed after six cycles of postoperative chemotherapy indicated a lesion (yellow arrows and red arrowheads). (A) The lesion appeared as a slightly hyperechoic mass on the grayscale image. (B) In the arterial phase, the lesion exhibited slight hyperenhancement. (C) In the early portal phase, the lesion displayed mild washout. (D,E) The lesion subsequently demonstrated hypoenhancement in both the portal and delayed phases. CEUS, contrast-enhanced ultrasound.

Figure 5 The hematoxylin and eosin-stained pathological sections of the liver lesion. (A) Significant dilatation of the hepatic sinusoids in the central area (40× magnification). (B) The dilatation of sinusoids in the margin was less severe compared to that in the central area (40× magnification). (C) Presence of cystically dilated, blood-filled sinusoids (100× magnification). (D) Significant hepatic plate atrophy (100× magnification).

Discussion

Chemotherapy-induced liver injuries often have a detrimental impact on subsequent treatment and prognosis in patients with colorectal cancer, highlighting the importance of monitoring such injuries in oncology treatment (6). SOS is the most prevalent hepatic complication following chemotherapy. The associated pathological changes form a spectrum that encompasses hepatic sinusoidal dilatation, peliosis, perisinusoidal fibrosis, and NRH (3). The pathological mechanism of these conditions involves the initiation of endothelial cell disruption by chemotherapy agents, leading to the loss of sinusoidal wall integrity. This disruption results in extravasation of red blood cells into the space of Disse through opened gaps. Additionally, collagens are deposited at the space of Disse, which is exposed to the sinusoids, leading to pathologic conditions known as peliosis and perisinusoidal fibrosis. The combination of damaged necrotic sinusoidal endothelial cells, extravasated red blood cells, and perisinusoidal fibrosis leads to obstruction and increased pressure in the sinusoids. Subsequently, sinusoidal dilatation, disruption of hepatic plates, and hyperplasia of hepatocytes occur due to alterations in hepatic blood flow. The proliferation of hepatocytes, surrounded by atrophic hepatocytes, forms NRH on pathology (3-5). One study demonstrated that oxaliplatin has a higher likelihood of inducing SOS as compared to other chemotherapeutic drugs (7). Patients with SOS typically present with no symptoms, although they are at an increased risk of intraoperative bleeding due to the liver’s softening and brittleness resulting from diffuse sinusoidal injury (5,6). As oxaliplatin is commonly administered as an adjuvant chemotherapeutic agent in the treatment of colorectal cancer, it is crucial that vigilant monitoring be maintained for those liver injuries associated with its use.

Hepatic imaging studies are consistent in reporting diffuse changes associated with SOS (3,4,8). Nonetheless, focal liver injuries may occasionally resemble liver metastases, presenting a challenge for radiologists in their differentiation and potentially influencing subsequent treatment strategies, thus resulting in overtreatment (4,9).

The patient in this report did not exhibit any liver metastases on CECT prior to postoperative chemotherapy for rectal cancer. However, after three cycles of chemotherapy consisting of oxaliplatin and capecitabine were completed, a new lesion with poorly defined margins was identified on routine CT. This lesion was located adjacent to the IVC on segment 6 of the liver. Notably, the patient did not demonstrate significant hepatic changes following neoadjuvant chemotherapy with capecitabine alone, suggesting that oxaliplatin might have played a central role in the development of this lesion. After completing 6 cycles of chemotherapy, the patient underwent CEMRI and CEUS of the liver, none of which showed any significant change in this lesion. Considering that chemotherapy can occasionally lead to atypical imaging presentations of liver metastases, we could not definitively rule out metastasis. Three months after completing postoperative chemotherapy, the patient underwent surgical resection of the lesion. Following the postoperative examination, pathology revealed significant sinusoidal dilatation, congestion, hepatic plate atrophy, and irregularly distributed peliosis. Notably, these pathological changes are similar to those that appear in the early and middle stages of SOS.

After retrospectively comparing the imaging manifestations of the lesion with those of typical liver metastases of colorectal cancer, we were able to perceive several distinctions. The magnetic resonance (MR) images of the lesion indicated isointensity on T2WI, hypointensity on DWI, and slight hypointensity in the hepatobiliary phase. This suggested the presence of functioning hepatocytes in the lesion capable of uptaking the liver-specific contrast agent used in this case—Gd-EOB-DTPA (10). Therefore, the lesion in this patient did not exhibit MRI manifestations typical of metastasis, which include mild hyperintensity on T2WI, hyperintensity on DWI, and clear mass defects in the hepatobiliary phase due to the absence of functioning hepatocytes absorbing the contrast (10). On US, the lesion appeared slightly hyperechoic with blurred margins and slightly hyperenhanced in the arterial phase of the contrast-enhanced study. In comparison, liver metastases often appear as hypoechoic nodules or masses with hyperenhancement in the arterial phase (11). Nevertheless, such lesions are often suspected as being liver metastases because they are newly emerging focal changes in patients with a history of colorectal cancer. Moreover, chemotherapy can lead to atypical imaging manifestations of liver metastases, but as practitioners’ knowledge of chemotherapy-induced focal liver injury is inadequate, this is rarely considered in clinical practice. Few cases of focal liver lesions associated with oxaliplatin that mimicked metastases and were eventually confirmed to be liver injury by postoperative pathology have been reported (9,12,13). In contrast to the reports mentioned, the patient in our case underwent three imaging examinations. It has been suggested that, unlike colorectal cancer liver metastases, focal liver injuries do not exhibit significant uptake of fluorodeoxyglucose (FDG) on positron emission tomography (PET), which could aid in identification (5). Histopathological biopsy remains the gold standard for diagnosing these lesions, yet it carries a risk of bleeding (3), and caution is required for such patients after chemotherapy.

Conclusions

Liver injuries caused by chemotherapy can present as focal lesions resembling hepatic metastases. If such lesions are detected in imaging studies, a meticulous identification should be executed with respect to the patient’s therapeutic regimen. Additional imaging tests may be required to exclude the possibility of metastases. In certain cases, a liver biopsy may be necessary for an accurate diagnosis but should be implemented with caution. This case report emphasizes the importance of raising the awareness of this rare condition and may contribute to the prevention of unnecessary surgical interventions.

Acknowledgments

None.

Footnote

Funding: The study was supported by the Sichuan Natural Science Foundation Project (grant No. 2024NSFSC0043).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-338/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the Ethics Committee of the West China Hospital of Sichuan University (No. HX2024-436) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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