CASE REPORT article

Front. Oncol., 24 April 2023

Sec. Surgical Oncology

Volume 13 - 2023 | https://doi.org/10.3389/fonc.2023.1116684

A large ectopic hepatocellular carcinoma with adrenal infiltration: a rare case report

  • Department of Urology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China

Abstract

Ectopic hepatocellular carcinoma (EHCC) originates from the ectopic liver, which refers to a liver organ or tissue unrelated to surrounding tissues. EHCC is a rare disease that lacks specific clinical signs, and preoperative diagnosis is often difficult. In a 61-year-old male patient with positive hepatitis B virus antibody, abdominal contrast-enhanced computed tomography scan showed a large heterogenously enhancing mass both on arterial and portal venous phase imaging arising from the right adrenal gland. Similar enhancement features were seen on magnetic resonance imaging. Serum potassium, aldosterone, cortisol, and plasma metanephrines were normal. The tumor markers of serum alpha-fetoprotein and alpha-fetoprotein-L3% were increased to 23.69 ng/mL and 82.1%, respectively. Exploratory laparotomy was performed and operative findings showed that the retroperitoneal tumor was disconnected from the right kidney and the liver, but invaded the right adrenal gland. Immunohistochemical examination showed that Arginase-1 was positive expression, and the retroperitoneal tumor was finally diagnosed as EHCC. We report a rare EHCC with adrenal infiltration that is difficult to diagnose preoperatively and mimics a retroperitoneal tumor or adrenal tumor, and we present a review of the literature on EHCC case reports.

Introduction

Ectopic hepatocellular carcinoma (EHCC) is defined as hepatocellular carcinoma arising from the hepatic parenchyma located in an extrahepatic organ or tissue (). It is reported that the incidence of ectopic liver during laparoscopy or autopsy ranges from 0.24% to 0.47% (). Ectopic liver can be located in various organs or tissues near the liver, such as gallbladder, adrenal gland, pancreas, peritoneum and thorax (). Due to the variable location, the clinical signs of EHCC are still not fully elucidated. Thus, EHCC is a very rare tumor disease with variable location and lack of specific clinical signs, which increases the difficulty of accurate preoperative diagnosis. Here, we report a case of EHCC with adrenal infiltration mimicking a retroperitoneal tumor or adrenal tumor and review the literature concerning EHCC.

Case presentation

The case was a 61-year-old male patient with positive hepatitis B virus antibody (HBV-DNA was 2.174 × 102), and he presented with abdominal distention and hyporexia for one week. Due to abdominal distension and hyporexia, the patient went to a nearby outpatient clinic, and abdominal ultrasound examination showed a large solid mass with mixed echogenicity. The patient had no history of hypertension, diabetes, cardiovascular and cerebrovascular diseases, and no history of surgery. His abdomen was soft and flat. There was mild tenderness in the right upper quadrant, but Murphy’s sign was negative. The liver was palpable 2 cm below the costal margin due to the push of the mass. The patient lost 5 kg in weight last month. (Eastern Cooperative Oncology Group: 0).

Abdominal contrast-enhanced computed tomography (CT) scan showed that the retroperitoneal tumor (11.8 × 11.0 × 8.3 cm) located in the right adrenal region, with obvious enhancement in arterial phase and continuous enhancement in venous phase (Figures 1A, B). Magnetic resonance imaging (MRI) displayed uneven enhancement in arterial phase and no abnormal signal focus in hepatobiliary phase (Figures 1C, D). On the laboratory tests, because the tumor was located in the adrenal region, serum potassium, aldosterone, cortisol, and plasma metanephrines were tested, and the results were normal. Serum alpha-fetoprotein (AFP) and AFP-L3% were 23.69 ng/mL and 82.1%, respectively.

Figure 1

The patient underwent an exploratory laparotomy to remove the tumor from an unknown primary organ in the adrenal region. On exploration, there was a large encapsulated oval solid tumor occupying the right retroperitoneal cavity, adjacent to the liver and right kidney, and infiltrating the adrenal tissue. The blood supply of the tumor is supplied by small branches of the right renal artery and abdominal aorta, and the adjacent liver, right kidney, and inferior vena cava are compressed and displaced by the tumor. The gross size of the resected specimen was about 16.0 × 14.0 × 10.0 cm and encapsulated in membrane, and the cut surface was reddish-yellow with intratumoral hemorrhage. Histopathological examination of tumor specimen showed that there were a large number of hepatoma cells arranged in beam, cord and nest shapes (Figure 2). Golden yellow adrenal tissue can be seen on the surface of the mass, and the pathological results suggest that cancer cells invade the adrenal gland. Pathological examination of the tumor specimen did not reveal any significant histological structure of the biliary tract. Therefore, it is speculated that ectopic hepatocytes may not have normal bile secretion functions, and this variation contributes to the degeneration or even canceration of hepatocytes. On immunohistochemical staining of the tumor specimen, Hepatocyte and Glypican-3 were negative and focal positive, respectively, but Arginase-1 (Arg-1) was positive. Moreover, GS-6 was positive, Ki67 was partly positive, Inhibin-a was negative, S-100 was negative, p53 was negative, and Melan-A was negative (Table 1). On postoperative laboratory tests, the levels of AFP and AFP-L3% had decreased to 5.98 ng/mL and 35.4%, respectively. Finally, we diagnosed the retroperitoneal tumor as EHCC. After the diagnosis of EHCC by histopathological examination, the patient received adjuvant treatment with the PD-1 blocker sintilimab and lenvatinib. Twelve months after operation, abdominal contrast-enhanced CT scan showed postoperative changes, and no tumor recurrence was found (Figure 3). Currently, twelve months have passed, the patient is still alive without recurrence.

Figure 2

Table 1

VariablesResults
CK7Positive
CK19Positive
CD10Positive
CD34Positive
Glypican-3Focal positive
GS-6Positive
HepatocyteNegative
Arg-1Positive
SynNegative
CgANegative
p53Negative
Ki67Positive (80%)
S-100Negative
Melan-ANegative
Inhibin-aNegative
SF-1Negative

Details of immunohistochemical staining of the resected tumor specimen.

Figure 3

Discussion

EHCC is a rare carcinomas defined as an HCC arising from ectopic liver organ or tissue. The incidence rate of ectopic liver is about 0.24% to 0.47%. When we searched for “ectopic hepatocellular carcinoma” as a “Text Word” in PubMed, only 28 full-text case reports written in English were obtained (Table 2) (, ). Ectopic liver tissue can occur in the adrenal gland, pancreas, peritoneum, gallbladder, bile duct, thoracic cavity, abdominal cavity, diaphragm, spleen, and chest wall, of which the diaphragm is the most common site (, , , , , , ).

Table 2

CaseStudyAge (year)SexSize (cm)NumberLocationVirus
infection
AFP (ng/mL)MetastasisTreatmentFollow-up
(months)
Outcome
1Our case/202261M11.8×11.0 ×8.3SingleRight adrenalHBV23.69NoLaparotomy + Lenvatinib6No Recurrence
2Liu et al. ()59M1.8×1.4SingleTail of pancreasNegative3.1NoLaparotomy84No Recurrence
3Wei et al. ()71M9.1×8.2×8.6SingleRight adrenalNegativeNormalNoLaparotomy10Recurrence
4Adachi et al. ()81F6.0SingleHead of pancreasHCV30.1NoLaparotomy8No Recurrence
5Ko et al. ()73M5.5MultiplePeritoneumNegative1.164YesLaparoscopy + Sorafenib12Recurrence and died
6Rorris et al. ()53M3.2SingleRight adrenalHCVNormalYesLaparotomyN/ANo Recurrence
7Li et al. ()44F5.0 × 4.0MultipleNear the pancreasNegative553.90NoLaparotomy17No Recurrence
8Jin et al. ()56M30.0 × 20.0 × 15.0MultipleAbdominalNegative8.03YesLaparotomy22Recurrence and died
9George et al. ()69MN/ASingleCholedochal cystNegative2.90NoRefuse
resection
N/AN/A
10Cheng et al. ()54MN/ASingleBile duct and gallbladderHBV3724.75NoLaparotomy3No Recurrence
11Cui et al. ()63M4.6 × 2.2MultipleThoracic and abdominal cavitiesHBV24,793YesPalliative surgery + Sorafenib13Progression free survival
12Lee et al. ()65M3.8×3.2×1.2SingleLeft subphrenic regionNegativeNormalNoSurgical resection17No Recurrence
13Aarås et al. ()64F3.5×2.5×1.0SingleDiaphragmNegative200NoLaparoscopy48Recurrence
14Segura-Sánchez et al. ()49F12.0SingleGallbladderNegative13,785NoLaparotomy36No Recurrence
15Miyake et al. ()42M1.0MultipleAbdominal cavityNegative241YesLaparoscopy + chemotherapyN/AN/A
16Nishikawa et al. ()64MN/AMultipleLeft diaphragmNegative84,865YesN/AN/AN/A
17Nenekidis et al. ()68M7.0Multiplechest wall and skullNegativeElevatedYesSurgical resection24No Recurrence
18Singh et al. ()60M8.0×8.0×8.0SingleLeft suprarenal regionHBV35NoLaparotomy6Recurrence and died
19Matsuyama et al. ()69M6.0×4.0MultipleSpleenN/AN/ANoChemotherapy25Recurrence and died
20Kanzaki et al. ()59F2.0SingleLeft diaphragmNegative2,508NoLaparoscopy18No Recurrence
21Schmelzle et al. ()75MN/ASingleExtrahepatic bile ductN/A7.8NoLaparotomyN/AN/A
22Seo et al. ()59M4.5SingleLeft subphrenic spaceNegativeNormalNoLaparoscopyN/AN/A
23Kubota et al. ()56M6.3×6.2SingleTail of pancreasNegativeN/ANoLaparotomy36No Recurrence
24Huang et al. ()62F16.0×14.0×5.0SingleDiaphragmNegative45,000NoLaparotomy + chemotherapy8No Recurrence
25Shigemori et al. ()72M14.0×10.0SingleLower abdomenNegative99,100 NoLaparotomy + TACE12No Recurrence
26Tsushimi et al. ()72F2.7×2.1SingleBile ductNegativeN/ANoLaparotomy12No Recurrence
27Kim et al. ()43F10.0×7.0SingleBetween spleen and diaphragmHBVN/ANoLaparotomy + TACE23Recurrence
28Asselah et al. ()66M17.0×10.0×8.0SingleLeft chest wallHCVNormalNoSurgical resection36No Recurrence
29Takayasu et al. ()57M5.0×4.0SingleLeft diaphragmNegative2,207NoLaparotomy96No Recurrence

Literature review of ectopic hepatocellular carcinoma (EHCC).

HBV, hepatitis B virus; HCV, hepatitis C virus; N/A, none of available; TACE, transcatheter arterial chemoembolization.

Of the 29 patients including this case, 26 patients underwent surgery treatment (, , , , , ) and two patients did not undergo surgery due to serious complications (, ). Traditional laparotomy and laparoscopy can be performed as the surgical methods, and seven patients received adjuvant therapy after surgery (, , , , , ). For unresectable hepatocellular carcinoma, lenvatinib or sorafenib can be used as targeted drugs for adjuvant therapy in EHCC (). After surgical resection alone or combined with adjuvant therapy, EHCC patients have a relatively good oncological prognosis, with 7/23 (30.4%) patients experiencing tumor recurrence. Therefore, if the patient does not have surgical contraindications, surgery should be recommended first. During follow-up, the clinical features of the tumors in the dead patients were multiple or relatively large in size. Thus, for patients with multiple or large tumors, a more rigorous follow-up plan should be developed to detect tumor recurrence early.

In previous case reports, three out of 28 tumors were located in the adrenal gland, but only one of them was located in the left adrenal gland region, while this case was located in the right adrenal gland region (, , ). Because the tumor is located in the adrenal region, it is difficult to diagnose EHCC before surgery, and it is easy to be misdiagnosed as an adrenal tumor. The tumor in this case invaded the adrenal tissue, which increased the difficulty of preoperative diagnosis. For EHCC located in the adrenal region, preoperative adrenal-related hormone testing is needed to determine whether the tumor has endocrine function. Except for one patient who did not undergo endocrine evaluation due to hemodynamic compromise and type I respiratory failure requiring emergency surgery, the other three patients underwent adrenal endocrine function evaluation. According to the test results, serum potassium, aldosterone, cortisol, and plasma metanephrines were normal, and the adrenal gland had no abnormal endocrine function (, , ).

Conclusion

Preoperative diagnosis of EHCC is usually very difficult. The tumor located in the adrenal region further increase the difficulty of diagnosis, and it is easy to be misdiagnosed as an adrenal tumor. Adrenal-related hormone testing can be performed to evaluate tumor endocrine function if radiographic studies reveal a tumor in the adrenal region. Early surgical treatment of EHCC will provide good long-term outcomes.

Patient perspective

His family is pleased that the patient is alive, and that the patient’s liver and kidney are protected during the operation. Both the patient and his families feel that if this exploratory laparotomy could ensure complete tumor resection and minimize damage to surrounding organs, they would like to choose such a surgical treatment strategy.

Statements

Data availability statement

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

Ethics statement

The studies involving human participants were reviewed and approved by the Ethics Committee of Hunan Provincial People’s Hospital. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the participant/patient(s) for the publication of this case report.

Author contributions

Manuscript writing: YY and YL; Clinical case diagnosis and treatment: YY, QL, and YL; Data collection and literature resarch: YY, ZL, and CW; Manuscript review and revision: YY and QL. All authors contributed to the article and approved the submitted version.

Funding

This study was supported by by the Natural Science Foundation of Hunan Province (No.2021JJ40513), Hunan Provincial Inclusive Policy and Innovative Environment Construction Plan (2020SK50902), Excellent Youth Project of Hunan Provincial Department of Education (22B0099), and Doctoral Foundation of Hunan Provincial People’s Hospital (No.BSJJ202116).

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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Summary

Keywords

ectopic hepatocellular carcinoma, retroperitoneal tumor, adrenal infiltration, endocrine function, case report

Citation

Yang Y, Lu Q, Li Z, Wang C and Li Y (2023) A large ectopic hepatocellular carcinoma with adrenal infiltration: a rare case report. Front. Oncol. 13:1116684. doi: 10.3389/fonc.2023.1116684

Received

05 December 2022

Accepted

05 April 2023

Published

24 April 2023

Volume

13 - 2023

Edited by

Ulrich Ronellenfitsch, Medical Faculty of the Martin-Luther-University Halle-Wittenberg, Germany

Reviewed by

Praveen Peddu, Kings Health Partners, United Kingdom; Alastair Young, St James’s University Hospital, United Kingdom

Updates

Copyright

*Correspondence: Yuanwei Li,

This article was submitted to Surgical Oncology, a section of the journal Frontiers in Oncology

Disclaimer

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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