Extrahepatically growing hepatocellular carcinoma diagnosed after presentation with peritoneal dissemination: a case report

Abstract

A man in his 40s presented with mildly elevated alpha-fetoprotein (AFP) levels during routine screening. Initial evaluation, including abdominal ultrasonography, revealed no intrahepatic mass, and the patient was placed under surveillance. Approximately 20 months later, AFP and PIVKA-II levels increased to > 200 000 ng/mL and 1524 mAU/mL, respectively. Contrast-enhanced computed tomography (CT) demonstrated diffusely enhancing peritoneal nodules with ascites; however, no definite intrahepatic tumor was detected. Diagnostic laparoscopy revealed multiple soft, reddish-brown nodules involving the peritoneum, omentum, and mesentery. Histopathological examination with immunohistochemistry confirmed disseminated hepatocellular carcinoma (HCC). Retrospective image review identified a small hypervascular nodule with washout extending from the left lateral liver segment toward the left triangular ligament, consistent with a pedunculated extrahepatic HCC. Despite treatment, the patient died 14 months after diagnostic laparoscopy. This case demonstrates that extrahepatically growing HCC may initially present with peritoneal dissemination, even in the absence of an apparent intrahepatic mass.

Introduction

Extrahepatically growing hepatocellular carcinoma (HCC) is a rare macroscopic subtype of primary liver cancer. Pedunculated HCC has been reported to account for only 0.24–3.00% of all HCC cases in Japan [1], and it has been described mainly in case reports and small case series. It is broadly categorized into (i) extrahepatically growing HCC (pedunculated and protruding types) and (ii) ectopic HCC [2]. Peritoneal dissemination from primary HCC is uncommon compared with intrahepatic metastasis via the portal venous system [3]. However, an extrahepatic growth pattern has been associated with peritoneal spread [4, 5]. Initial presentation with diffuse peritoneal dissemination, without an obvious intrahepatic mass, is particularly unusual.

Case report

A man in his 40s with no notable medical or family history was referred to our department for evaluation of markedly elevated tumor markers. He reported occasional alcohol use and no history of smoking. Twenty months before referral, routine screening revealed mildly elevated alpha-fetoprotein (AFP) (34 ng/mL). Further evaluation at another hospital, including abdominal ultrasonography, revealed no hepatic mass, and the patient was placed under surveillance. At the previous hospital, the patient was followed every 3 months, during which a gradual increase in AFP levels was observed. At presentation, he tested negative for hepatitis B surface antigen and hepatitis C antibodies. Liver function was preserved (Child-Pugh class A, 5 points). Laboratory findings were as follows: carcinoembryonic antigen 2.5 ng/mL, carbohydrate antigen 19–9 17.6 U/mL, cancer antigen 125 137 U/mL, protein induced by vitamin K absence or antagonist-II (PIVKA-II) 1524 mAU/mL, and AFP > 200 000 ng/mL.

Contrast-enhanced computed tomography (CT) demonstrated diffusely enhancing nodules along the peritoneum with ascites, as well as additional nodules in the retroperitoneal and pelvic spaces (Figure 1). No definite intrahepatic mass was detected. Peritoneal dissemination from carcinoma of unknown primary origin was suspected, and diagnostic laparoscopy was performed. Laparoscopy revealed numerous soft, reddish-brown nodules distributed throughout the peritoneum, omentum, and mesentery. No visible tumor was identified on the liver surface. Dense adhesions between the omentum and the left upper abdomen limited detailed inspection of the region extending from the left lateral segment to the left triangular ligament. Bloody ascites were present in the Douglas pouch (Figure 2). An omental nodule was submitted for intraoperative frozen section analysis, which suggested HCC.

Figure 1.

Contrast-enhanced computed tomography (CT) at presentation demonstrating numerous enhancing peritoneal nodules (arrows) with ascites. No definite intrahepatic mass was identified at that time.

Figure 2.

Laparoscopic findings. (a) Multiple soft disseminated nodules (arrows) diffusely distributed throughout the abdominal cavity. (b) Dense adhesions in the left upper abdomen limited detailed inspection of the region extending from the left lateral segment to the left triangular ligament. (c) Pelvic disseminated nodules (arrows) with bloody ascites in the Douglas pouch.

Permanent histopathological examination showed solid proliferation of atypical cells with eosinophilic cytoplasm and prominent nucleoli, partially arranged in a trabecular pattern. Immunohistochemistry was positive for HepPar-1, glypican-3, arginase-1, and AFP, confirming peritoneal dissemination of HCC (Figure 3). Postoperatively, retrospective review of the preoperative CT identified a small nodule with arterial hyperenhancement and washout in the equilibrium phase extending from the left lateral liver segment toward the left triangular ligament. The lesion showed minimal continuity with the liver parenchyma, consistent with a pedunculated extrahepatically growing HCC as the primary tumor (Figure 4).

Figure 3.

Histopathology of a peritoneal nodule. Atypical cells with eosinophilic cytoplasm proliferating in solid and partially trabecular patterns. Immunohistochemistry was positive for HepPar-1, glypican-3, arginase-1, and alpha-fetoprotein (AFP), consistent with disseminated hepatocellular carcinoma (HCC).

Figure 4.

Retrospective review of multiphasic CT. (a, b) a nodule extending from the left lateral segment toward the left triangular ligament, showing arterial hyperenhancement and washout in the equilibrium phase (arrows). (c) Minimal continuity between the nodule and the liver parenchyma is indicated by an arrow, suggesting pedunculated extrahepatically growing HCC.

The final diagnosis was extrahepatic HCC with peritoneal dissemination (stage IVB). Systemic therapy was initiated. Sorafenib resulted in progressive disease after 3 months, regorafenib after 1 month, and ramucirumab after 6 cycles. The patient subsequently received best supportive care at home and died 14 months after diagnostic laparoscopy.

Discussion

Peritoneal dissemination from primary HCC is uncommon, with intrahepatic spread through the portal venous system being more frequent [3]. Reported risk factors for peritoneal dissemination include advanced stage, poor differentiation, and tumor rupture. Extrahepatic growth has also been proposed as a predisposing factor for peritoneal spread [4, 5]. Previous reports of extrahepatically growing or pedunculated HCC with peritoneal dissemination have often involved large tumors, rupture, or postoperative recurrence. In contrast, the present case is notable because diffuse peritoneal dissemination was the initial manifestation, whereas the primary pedunculated lesion was small and recognized only retrospectively. Extrahepatically growing HCC is classified as (i) pedunculated or protruding types and (ii) ectopic HCC arising from ectopic liver tissue [2, 6]. In this case, retrospective imaging demonstrated minimal continuity between the tumor and the liver parenchyma, supporting a pedunculated type. This morphology has been associated with accessory liver lobes and developmental anomalies that maintain parenchymal and vascular continuity with the main liver, potentially providing a substrate for tumorigenesis.

Extrahepatic HCC may enlarge rapidly because it is less constrained by surrounding hepatic parenchyma. Peritoneal dissemination has been reported as a recurrence pattern in this subtype after resection [5]. Tumor rupture is frequently observed in cases with peritoneal dissemination. In pedunculated tumors, detachment of the stalk may release tumor cells into the peritoneal cavity, leading to dissemination. In our patient, dense adhesions were observed in the left upper abdomen, corresponding to the region where the primary lesion was later identified on CT. Although this remains speculative, these findings may reflect prior capsular disruption, rupture, or partial detachment of the pedunculated tumor, providing a plausible mechanism for diffuse peritoneal dissemination.

This case also illustrates a diagnostic challenge. When the intrahepatic component is small or inconspicuous, the primary lesion may be overlooked, particularly in the presence of diffuse peritoneal disease. In retrospect, the combination of markedly elevated AFP and PIVKA-II levels with peritoneal dissemination should have prompted careful evaluation for extrahepatically growing HCC, including detailed assessment of the subphrenic region and ligamentous attachments, such as the triangular ligament, on multiphasic imaging [4, 5]. Earlier recognition might have allowed diagnosis before dissemination. Although the AFP level at the initial presentation 20 months earlier was only mildly elevated, cross-sectional imaging such as dynamic CT or MRI could have been considered despite the unremarkable ultrasonography. At the previous hospital, the patient was followed every 3 months, during which a gradual increase in AFP levels was observed; however, escalation to cross-sectional imaging was delayed. In retrospect, earlier multiphasic CT or MRI might have identified the small pedunculated lesion before diffuse peritoneal dissemination developed. This case therefore underscores that even modest AFP elevation should not be dismissed when it is unexplained, and that persistent or increasing AFP levels warrant further evaluation beyond ultrasonography. Earlier detection may be clinically important because pedunculated tumors can be amenable to limited hepatic resection in selected cases; however, prognosis remains poor once dissemination has occurred, as demonstrated in this case.

In conclusion, pedunculated extrahepatically growing HCC may remain radiologically occult and initially present with peritoneal dissemination in the absence of an obvious intrahepatic mass. Markedly elevated AFP and PIVKA-II levels should prompt meticulous re-evaluation of the liver surface, ligamentous attachments, and perihepatic spaces on multiphasic imaging. Diagnostic laparoscopy is useful for obtaining a definitive diagnosis in atypical cases presenting with peritoneal dissemination of unknown origin.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Funding

No funding was received for this work.

Ethical approval

Ethical approval was waived for this single case report in accordance with institutional policy.

Consent

Written informed consent was obtained from the patient for the publication of this case report and the accompanying images.

Guarantor

Kosuke Isomura is the guarantor of this work.