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대한내과학회지: 제 88 권 제 2 호 2015
http://dx.doi.org/10.3904/kjm.2015.88.2.202
간세포암종에서 발생한 공동 형태의 폐 전이
서울대학교 의과대학 서울대학교병원 호흡기내과
조용숙·배 원·김주혜·이하연·곽낙원·고성준·이창훈
Cavitary Form of Lung Metastasis from Advanced Hepatocellular Carcinoma
Yong Suk Jo, Won Bae, Joo Hae Kim, Ha Youn Lee, Nak Won Kwak, Sung Jun Ko, and Chang-Hoon Lee
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine,
Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
The most common site of extrahepatic metastasis in cases of advanced hepatocellular carcinoma is the lung. A 60-year-old
Korean male had been previously diagnosed with hepatocellular carcinoma and was treated several times with transcatheter arterial
chemoembolization prior to a regime of sorafenib after multiple bone metastases were detected. Despite 2 months of systemic treatment, the disease progressed, and newly developed cavitary nodules and ground glass opacities were observed on a chest computed
tomography scan. Initially the patient was diagnosed with septic pneumonia and was subsequently treated with antibiotics over 2
weeks, with no observable improvement. A percutaneous transthoracic needle aspiration biopsy was performed to ascertain the
noninfectious origin of the lung lesions. As a result, a rare form of pulmonary metastasis from hepatocellular carcinoma was
discovered. Unfortunately, there were no available treatment options for the patient and so end-of-life care was recommended.
(Korean J Med 2015;88:202-206)
Keywords: Hepatocellular carcinoma; Infection; Metastasis
INTRODUCTION
nodules, generally in the peripheral parenchyma, combined with
diffuse interstitial thickening [2].
In advanced hepatocellular carcinoma, metastasis is most of-
Because multiple cavitary pulmonary nodules can have di-
ten seen intrahepatically, while the lung is the most common
verse etiologies such as septic pneumonia, fungal infections,
site of extrahepatic metastasis [1]. The typical radiologic find-
Mycobacterium tuberculosis infection, vasculitis, and lung meta-
ings of pulmonary metastases are multiple, round,variously sized
stasis, identifying their origin can be difficult.
Received: 2014. 6. 17
Revised: 2014. 7. 22
Accepted: 2014. 8. 28
Correspondence to Chang-Hoon Lee, M.D.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital,
Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea
Tel: +82-2-2072-4743, Fax: +82-2-762-9662, E-mail: [email protected]
*Conflict of Interest: The authors disclose no potential conflicts of interest.
Copyright ⓒ 2015 The Korean Association of Internal Medicine
This is an Open Access article distributed under the terms of the Creative Commons Attribution
- 202 - Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits
unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
－ Yong Suk Jo, et al. Atypical lung metastasis －
Figure 1. Transaxial chest computed tomography scan demonstrating multiple cavitary lesions and ground glass opacities in
both lung fields.
This case highlights the importance of considering pulmonary
metastasis of a hepatocellular carcinoma, even when disease
Figure 2. Transaxial chest computed tomography scan demonstrating percutaneous transthoracic needle aspiration biopsy of
the left upper lung cavitary lesion.
vealed no abnormal pulmonary parenchymal lesions, which
would suggest emphysema.
The patient underwent a complete work-up, including com-
symptoms present with unusual or novel features.
puted tomography of the chest. The CT revealed multiple cavitary lesions, patchy consolidation, and ground glass opacities in
CASE REPORT
both lungs (Fig. 1). At this time, serum levels of acute phase
A 60-year-old Korean male was diagnosed 7 years previously
proteins were high (C-reactive protein [CRP], 21.45 mg/dL), fe-
with chronic hepatitis B with related liver cirrhosis and hep-
ver was sustained, and radiological findings supported an in-
atocellular carcinoma, which was diagnosed 3 years ago. He had
fectious condition. Metastasis was not immediately suspected,
undergone transcatheter arterial chemoembolization five times
despite a marked increased in tumor marker expression (alpha-
because of intrahepatic recurrences and metastases. When bone
fetoprotein [AFP], 379.8 ng/mL), as cavitary nodular lung meta-
metastases were detected after a work-up to investigate back
stases are rarely encountered in hepatocellular carcinoma. Septic
and chest pain, he underwent palliative radiation therapy to his
pneumonia appeared to be a more likely diagnosis based on the
sternum and his cervical and thoracic spine to alleviate bone
fever, high CRP levels, and multiple peripheral nodules with
pain. Subsequently, sorafenib, a tyrosine kinase inhibitor, was
cavitation. Despite our efforts to uncover a septic cause, none
prescribed. After 2 months on sorafenib, he was admitted to our
could be determined. However, during CT scan and echocardio-
hospital with a fever, progressive dyspnea upon exertion, and
gram of the abdomen we observed progression of the hepato-
general weakness. A chest radiograph identified multiple periph-
cellular carcinoma with portal vein tumor thrombus. After sev-
eral nodules with cavitation in both lungs. The patient had never
eral days of antibiotic treatment, the patient’s fever did not sub-
smoked and his baseline lung function was normal. A chest
side and radiographic findings showed no improvement. No
computed tomography (CT) scan performed 3 years prior re-
causative microbiological factors were identified despite a multi-
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－ 대한내과학회지: 제 88 권 제 2 호 통권 제 654 호 2015 －
A
B
C
D
Figure 3. Histopathological findings of the lung. (A) Hematoxylin and eosin staining; original magnification 200×. (B) Immunonegativity for thyroid transcription factor-1 (immunohistochemistry [IHC], 400×). (C) Immunopositivity for cytokeratin 7 (IHC, 400×). (D)
Immunopositivity for alpha-fetoprotein (IHC, 400×).
disciplinary approach culturing sputum, blood, and urine as well
atin 7, and AFP (Fig. 3C and 3D, respectively) and negative for
as bronchoscopic alveolar lavage fluid. Considering the possi-
thyroid transcription factor-1 (Fig. 3B). Subsequently, the multi-
bility of combined radiation pneumonitis, a short-term systemic
ple cavitary lung lesions were identified as metastasis from the
steroid was administered intravenously, and the patient’s fever
primary hepatocellular carcinoma. At this time antibiotic treat-
subsequently subsided. However, his condition still showed no
ment was terminated. Unfortunately, there were no further treat-
clinical or radiographic improvements. His continued lack of re-
ment options for the patient and end-of-life care was recommended.
sponse to treatment for pneumonia suggested a noninfectious con-
Administration of sorafenib was also discontinued. Although the
dition. Therefore, a percutaneous transthoracic needle aspiration
patient had been taking it regularly, the drug had no effect on
biopsy of the lung was performed to ascertain the etiology of
the progression of the disease. After discontinuation of the sys-
the cavitary lesions (Fig. 2). Histological examination of the spe-
temic steroid, the patient’s fever returned; however, there were
cimen revealed a poorly differentiated carcinoma (Fig. 3A). Im-
no other signs or symptoms suggestive of an infection. The pa-
munohistochemistry identified tumor cells positive for cytoker-
tient was sent to a convalescent hospital for supportive care, and
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－ 조용숙 외 6인. 공동성 결절로 발생한 간세포암 폐 전이 －
piration pneumonia. Noninfectious causes of cavitary lesions in-
did not return to the outpatient clinic.
clude primary tumors and metastasis, various granulomatous diseases, such as sarcoidosis and Wegener’s granulomatosis, arte-
DISCUSSION
riovenous malformation, pneumoconiosis, and rheumatoid arthriHepatocellular carcinoma is the sixth most common form of
tis [6]. Cavitary lesions are detected in only 4% of metastatic
cancer worldwide, with predominance in Asia over other regions.
nodules, of which approximately 70% are metastatic squamous
While it can be successfully treated if diagnosed at an early
cell carcinoma [7]. To our knowledge, this is the first report of
stage, it remains the third-leading cause of cancer-related deaths
cavitary pulmonary metastasis from hepatocellular carcinoma.
globally [3]. Although intrahepatic recurrence and metastasis of
We believe that central necrosis may have occurred in the rap-
hepatocellular carcinoma occur frequently, they can be managed
idly growing metastatic nodules or that intratumoral necrosis
successfully through various multidisciplinary modalities includ-
may have been the cause of cavitary lung metastasis in our
ing surgical resection, transcatheter arterial chemoembolization
patient. These atypical findings may aid clinicians in cases in
and percutaneous ablation or alcohol injection [4]. Therefore, in-
which a pulmonary metastasis is difficult to distinguish from an
trahepatic recurrence and metastasis can be reasonably managed,
infectious condition or where the appropriate treatment plan is
prolonging patient survival. Due to the development of new di-
unclear. Furthermore, while early lung metastasis is relatively
agnostic techniques extrahepatic metastasis is now more fre-
asymptomatic, severe respiratory difficulties could develop as
quently diagnosed than previously, making it an important in-
disease progresses [8]. Additional confounding factors, specifi-
dicator of prognosis. The most commonly observed site of ex-
cally in our case, included elevated CRP levels, which can be
trahepatic hepatocellular carcinoma metastasis is to the lung.
related to tumor burden; and fever, which can be triggered by
Hepatocellular carcinoma with extrahepatic metastasis is re-
pyrogenic cytokines produced by the liver in cases of hep-
garded as a terminal condition as there are currently no standard
atocellular carcinoma [9,10].
In conclusion, pulmonary metastasis from an advanced hep-
treatment courses available [1].
In most cases of pulmonary metastasis from hepatocellular
atocellular carcinoma should be considered even if typical pul-
carcinoma, the classic radiologic findings include multiple, round
monary features are observed. Careful analysis of tumor markers
nodules of various size, usually in the peripheral parenchyma,
is recommended in these cases.
combined with diffuse interstitial thickening [2]. Previously, Assed
et al. reported a case of a 26-year-old female, with no history
중심 단어: 간세포암; 감염; 전이
of disease, who presented with multiple nodules, of various size,
in both lungs by CT and multiple hyperechoic nodules in the
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