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Purpose@#Appropriate preclinical mouse models are needed to evaluate the response to immunotherapeutic agents. Immunocompetent mouse models have rarely been reported for gastric cancer. Thus, we investigated immunophenotypes and responses to immune checkpoint inhibitor (ICI) in immunocompetent mouse models using various murine gastric cancer cell lines. @*Materials and Methods@#We constructed subcutaneous syngeneic tumors with murine gastric cancer cell lines, YTN3 and YTN16, in C57BL/6J mice. Mice were intraperitoneally treated with IgG isotype control or an anti–programmed death-ligand 1 (PD-L1) neutralizing antibody. We used immunohistochemistry to evaluate the tumor-infiltrating immune cells of formalin-fixed paraffin-embedded mouse tumor tissues. We compared the protein and RNA expression between YTN3 and YTN16 cell lines using a mouse cytokine array and RNA sequencing. @*Results@#The mouse tumors revealed distinct histological and molecular characteristics. YTN16 cells showed upregulation of genes and proteins related to immunosuppression, such as Ccl2 (CCL2) and Csf1 (M-CSF). Macrophages and exhausted T cells were more enriched in YTN16 tumors than in YTN3 tumors. Several YTN3 tumors were completely regressed by the PD-L1 inhibitor, whereas YTN16 tumors were unaffected. Although treatment with a PD-L1 inhibitor increased infiltration of T cells in both the tumors, the proportion of exhausted immune cells did not decrease in the non-responder group. @*Conclusion@#We confirmed the histological and molecular features of cancer cells with various responses to ICI. Our models can be used in preclinical research on ICI resistance mechanisms to enhance clinical efficacy.
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Objectives@#Adenosine triphosphate-binding cassette subfamily G member 2 (ABCG2) and CD133 are recognized stem cell markers of gastric cancer. Extensive research has examined the significance of these markers in different types of cancers and their impact on prognoses, linking them to unfavorable clinical outcomes in various tumors. However, the prognostic value of these markers for gastric cancer remains unclear. We investigated the expression of ABCG2 and CD133 and their relationship with clinical outcomes in gastric cancer. @*Methods@#ABCG2 and CD133 expression levels were analyzed, using immunohistochemistry and tissue microarrays, in tumor samples from 459 patients who underwent surgical resections due to gastric cancer. ABCG2 and CD133 expression levels were defined by intensity and dichotomized as medians. The associations among the expression levels of these markers, disease severity, and patient survival were also determined. @*Results@#In the 411 patients for whom we analyzed the expression levels of these markers, 74.9% and 80.5% were found to have high levels of ABCG2 and CD133, respectively. High expression levels of ABCG2 and CD133 were more commonly observed in well-differentiated (p<0.001 and p=0.004, respectively) and intestinal lesions (p<0.001 and p=0.002, respectively). High ABCG2 expression correlated with improved survival outcomes, whereas high CD133 expression was associated with poorer outcomes. Cox regression analysis confirmed that stage, high ABCG2 (overall survival [OS]: hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.41–0.91; p=0.015; recurrencefree survival [RFS]: HR, 0.55; 95% CI, 0.34–0.88; p=0.012), and CD133 expression (OS: HR, 1.59; 95% CI, 1.00–2.51; p=0.049; RFS: HR, 2.29; 95% CI, 1.21–4.34; p=0.011) were predictors of survival. A subgroup analysis indicated that ABCG2 expression was also associated with an improved RFS rate in patients who received systemic chemotherapy. @*Conclusions@#High ABCG2 expression and low CD133 expression in tumors correlated with improved survival outcomes in post-resection patients with gastric cancer, suggesting their potential utility as prognostic biomarkers.
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Background@#The metastatic brain tumor is the most common brain tumor. The aim of this study was to demonstrate the clinicopathological and molecular pathologic features of brain metastases (BM). @*Methods@#A total of 269 patients were diagnosed with BM through surgical resection at Seoul St. Mary’s Hospital from January 2010 to March 2020. We reviewed the clinicopathological features and molecular status of primary and metastatic brain tissues using immunohistochemistry and molecular pathology results. @*Results@#Among 269 patients, 139 males and 130 females were included. The median age of primary tumor was 58 years (range, 13 to 87 years) and 86 patients (32.0%) had BM at initial presentation. Median BM free interval was 28.0 months (range, 1 to 286 months). The most frequent primary site was lung 46.5% (125/269), and followed by breast 15.6% (42/269), colorectum 10.0% (27/269). Epidermal growth factor receptor (EGFR) mutation was found in 50.8% (32/63) and 58.0% (40/69) of lung primary and BM, respectively. In both breast primary and breast cancer with BM, luminal B was the most frequent subtype at 37.9% (11/29) and 42.9% (18/42), respectively, followed by human epidermal growth factor receptor 2 with 31.0% (9/29) and 33.3% (14/42). Triple-negative was 20.7% (6/29) and 16.7% (7/42), and luminal A was 10.3% (3/29) and 7.1% (3/42) of breast primary and BM, respectively. In colorectal primary and colorectal cancer with BM, KRAS mutation was found in 76.9% (10/13) and 66.7% (2/3), respectively. @*Conclusions@#We report the clinicopathological and molecular pathologic features of BM that can provide useful information for understanding the pathogenesis of metastasis and for clinical trials based on the tumor’s molecular pathology.
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The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
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The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements.The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
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Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.
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Sorafenib, an oral multi-target tyrosine kinase inhibitor (MTKI) for treatment of radioiodine-refractory differentiated thyroid cancer can induce acute or chronic pancreatitis as an adverse event. However, there have been no reports of pancreatic cancer associated with MTKI, especially among long-term MTKI user. A 60-year-old male patient visited our outpatient cancer clinic due to aggravated abdominal and back pain. He had been taking sorafenib for over five years for advanced thyroid cancer with multiple lung metastases, without any adverse events except mild hand-foot syndrome and slightly increased liver enzymes at the initial phase. Laboratory findings showed increasing serum amylase and lipase levels. An abdominal CT scan showed a 5.2 cm heterogeneous hypointense mass-like lesion on the pancreas distal body area. Under suspicion of pancreatic cancer, extensive surgery of distal pancreatectomy, unilateral nephrectomy, and unilateral adrenalectomy confirmed moderately differentiated adenocarcinoma with a background of chronic pancreatitis accompanying fibrosis and fat necrosis. Pancreatic cancer should be considered as well as pancreatitis in long-term MTKI users who show abrupt increases in serum pancreatic enzymes, although a causal relationship between long-term MTKI use and pancreatic cancer has not been elucidated.
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Purpose@#Isoform 2 of tight junction protein claudin-18 (CLDN18.2) is a potential target for gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC). @*Materials and Methods@#We evaluated CLDN18.2, RhoGAP, and E-cadherin expression using two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line platinum-based chemotherapy between March 2015 and February 2017. @*Results@#CLDN18.2 and E-cadherin expression was significantly lower in patients with peritoneal metastasis (PM) than those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), whereas it was significantly higher in patients who never developed PM from diagnosis to death than in those who did (P=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin expression levels were significantly higher in patients with bone metastasis than in those without bone metastasis (P=0.010 and 0.001, respectively).Moreover, we identified a positive correlation between the expression of CLDN18.2 and E-cadherin (P<0.001), RhoGAP and CLDN18.2 (P=0.004), and RhoGAP and E-cadherin (P=0.001). Conversely, CLDN18.2, RhoGAP, and E-cadherin expression was not associated with chemotherapy response and survival. @*Conclusions@#CLDN18.2 expression was reduced in patients with PM but significantly intactin those with bone metastasis. Furthermore, CLDN18.2 expression was positively correlated with other adherens junction molecules, which is clinically associated with mDGC and PM pathogenesis.
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Purpose@#Expanded indications for endoscopic submucosal dissection (ESD) in early gastric cancer (EGC) remain controversial due to the potential risk of undertreatment after adequate lymph node dissection (LND). Regional LND (RLND) is a novel technique used for limited lymphadenectomy to avoid gastrectomy. This study established the safety and effectiveness of RNLD as an additional treatment option after ESD for expanded indications. @*Materials and Methods@#A total of 69 patients who met the expanded indications for ESD were prospectively enrolled from 2014 to 2017. The tumors were localized using intraoperative esophagogastroduodenoscopy (EGD) before RLND. All patients underwent RLND first, followed by conventional radical gastrectomy with LND. The locations of the preoperative and intraoperative EGD were compared. Pathologic findings of the primary lesion and the RLND status were analyzed. @*Results@#The concordance rates of tumor location between the preoperative and intraoperative EGD were 79.7%, 76.8%, and 63.8% according to the longitudinal, circumferential, and regional locations, respectively. Of the 4 patients (5.7%) with metastatic LNs, 3 were pathologically classified as beyond the expanded indication for ESD and 1 had a single LN metastasis in the regional lymph node. @*Conclusions@#RLND is a safe additional option for the treatment of EGC in patients meeting expanded indications after ESD.
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Purpose@#Isoform 2 of tight junction protein claudin-18 (CLDN18.2) is a potential target for gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC). @*Materials and Methods@#We evaluated CLDN18.2, RhoGAP, and E-cadherin expression using two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line platinum-based chemotherapy between March 2015 and February 2017. @*Results@#CLDN18.2 and E-cadherin expression was significantly lower in patients with peritoneal metastasis (PM) than those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), whereas it was significantly higher in patients who never developed PM from diagnosis to death than in those who did (P=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin expression levels were significantly higher in patients with bone metastasis than in those without bone metastasis (P=0.010 and 0.001, respectively).Moreover, we identified a positive correlation between the expression of CLDN18.2 and E-cadherin (P<0.001), RhoGAP and CLDN18.2 (P=0.004), and RhoGAP and E-cadherin (P=0.001). Conversely, CLDN18.2, RhoGAP, and E-cadherin expression was not associated with chemotherapy response and survival. @*Conclusions@#CLDN18.2 expression was reduced in patients with PM but significantly intactin those with bone metastasis. Furthermore, CLDN18.2 expression was positively correlated with other adherens junction molecules, which is clinically associated with mDGC and PM pathogenesis.
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Purpose@#Expanded indications for endoscopic submucosal dissection (ESD) in early gastric cancer (EGC) remain controversial due to the potential risk of undertreatment after adequate lymph node dissection (LND). Regional LND (RLND) is a novel technique used for limited lymphadenectomy to avoid gastrectomy. This study established the safety and effectiveness of RNLD as an additional treatment option after ESD for expanded indications. @*Materials and Methods@#A total of 69 patients who met the expanded indications for ESD were prospectively enrolled from 2014 to 2017. The tumors were localized using intraoperative esophagogastroduodenoscopy (EGD) before RLND. All patients underwent RLND first, followed by conventional radical gastrectomy with LND. The locations of the preoperative and intraoperative EGD were compared. Pathologic findings of the primary lesion and the RLND status were analyzed. @*Results@#The concordance rates of tumor location between the preoperative and intraoperative EGD were 79.7%, 76.8%, and 63.8% according to the longitudinal, circumferential, and regional locations, respectively. Of the 4 patients (5.7%) with metastatic LNs, 3 were pathologically classified as beyond the expanded indication for ESD and 1 had a single LN metastasis in the regional lymph node. @*Conclusions@#RLND is a safe additional option for the treatment of EGC in patients meeting expanded indications after ESD.
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Although microscopic analysis of tissue slides has been the basis for disease diagnosis for decades, intra- and inter-observer variabilities remain issues to be resolved. The recent introduction of digital scanners has allowed for using deep learning in the analysis of tissue images because many whole slide images (WSIs) are accessible to researchers. In the present study, we investigated the possibility of a deep learning-based, fully automated, computer-aided diagnosis system with WSIs from a stomach adenocarcinoma dataset. Three different convolutional neural network architectures were tested to determine the better architecture for tissue classifier. Each network was trained to classify small tissue patches into normal or tumor. Based on the patch-level classification, tumor probability heatmaps can be overlaid on tissue images. We observed three different tissue patterns, including clear normal, clear tumor and ambiguous cases. We suggest that longer inspection time can be assigned to ambiguous cases compared to clear normal cases, increasing the accuracy and efficiency of histopathologic diagnosis by pre-evaluating the status of the WSIs. When the classifier was tested with completely different WSI dataset, the performance was not optimal because of the different tissue preparation quality. By including a small amount of data from the new dataset for training, the performance for the new dataset was much enhanced. These results indicated that WSI dataset should include tissues prepared from many different preparation conditions to construct a generalized tissue classifier. Thus, multi-national/multi-center dataset should be built for the application of deep learning in the real world medical practice.
Subject(s)
Adenocarcinoma , Classification , Dataset , Diagnosis , Learning , Observer Variation , StomachABSTRACT
Vulvar squamous cell carcinoma (SCC) consists of two different etiologic categories: human papilloma virus (HPV)-associated (HPV (+)) and HPV-non-associated (HPV (−)). There have been no genome-wide studies on the genetic alterations of vulvar SCCs or on the differences between HPV (+) and HPV (−) vulvar SCCs. In this study, we performed whole-exome sequencing and copy number profiling of 6 HPV (+) and 9 HPV (−) vulvar SCCs and found known mutations (TP53, CDKN2A and HRAS) and copy number alterations (CNAs) (7p and 8q gains and 2q loss) in HPV (−) SCCs. In HPV (+), we found novel mutations in PIK3CA, BRCA2 and FBXW7 that had not been reported in vulvar SCCs. HPV (−) SCCs exhibited more mutational loads (numbers of nonsilent mutations and driver mutations) than HPV (+) SCCs, but the CNA loads and mutation signatures between HPV (+) and HPV (−) SCCs did not differ. Of note, 40% and 40% of the 15 vulvar SCCs harbored PIK3CA and FAT1 alterations, respectively. In addition, we found that the SCCs harbored kataegis (a localized hypermutation) in 2 HPV (+) SCCs and copy-neutral losses of heterozygosity in 4 (one HPV (+) and 3 HPV (−)) SCCs. Our data indicate that HPV (+) and HPV (−) vulvar SCCs may have different mutation and CNA profiles but that there are genomic features common to SCCs. Our data provide useful information for both HPV (+) and HPV (−) vulvar SCCs and may aid in the development of clinical treatment strategies.
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BACKGROUND: Mutations in the KRAS gene have been identified in approximately 50% of colorectal cancers (CRCs). KRAS mutations are well established biomarkers in anti–epidermal growth factor receptor therapy. Therefore, assessment of KRAS mutations is needed in CRC patients to ensure appropriate treatment. METHODS: We compared the analytical performance of the cobas test to Sanger sequencing in 264 CRC cases. In addition, discordant specimens were evaluated by 454 pyrosequencing. RESULTS: KRAS mutations for codons 12/13 were detected in 43.2% of cases (114/264) by Sanger sequencing. Of 257 evaluable specimens for comparison, KRAS mutations were detected in 112 cases (43.6%) by Sanger sequencing and 118 cases (45.9%) by the cobas test. Concordance between the cobas test and Sanger sequencing for each lot was 93.8% positive percent agreement (PPA) and 91.0% negative percent agreement (NPA) for codons 12/13. Results from the cobas test and Sanger sequencing were discordant for 20 cases (7.8%). Twenty discrepant cases were subsequently subjected to 454 pyrosequencing. After comprehensive analysis of the results from combined Sanger sequencing–454 pyrosequencing and the cobas test, PPA was 97.5% and NPA was 100%. CONCLUSIONS: The cobas test is an accurate and sensitive test for detecting KRAS-activating mutations and has analytical power equivalent to Sanger sequencing. Prescreening using the cobas test with subsequent application of Sanger sequencing is the best strategy for routine detection of KRAS mutations in CRC.
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Humans , Biomarkers , Codon , Colorectal NeoplasmsABSTRACT
Gas gangrene, a subset of necrotizing myositis, is a bacterial infection that produces gas in tissues in gangrene. It is usually caused by Clostridium species, most commonly Clostridium perfringens. Streptococcus anginosus is a rare cause of gas gangrene, with very few cases reported. We report a rare case of traumatic gas gangrene caused by S. anginosus in a 57-year-old female with diabetes after being stabbed with scissors.
Subject(s)
Female , Humans , Middle Aged , Bacterial Infections , Clostridium , Clostridium perfringens , Diabetes Mellitus , Gangrene , Gas Gangrene , Myositis , Streptococcus anginosus , StreptococcusABSTRACT
Hemobilia is a rare gastrointestinal bleeding, usually caused by injury to the bile duct. Hemobilia after endoscopic retrograde cholangiopancreatography (ERCP) is generally self-limiting and patients will spontaneously recover, but some severe and fatal hemorrhages have been reported. ERCP-related bowel or bile duct perforation should be managed promptly, according to the type of injury and the status of the patient. We recently experienced a case of late-onset severe hemobilia in which the patient recovered after endoscopic biliary stent insertion. The problem was attributable to ERCP-related bile duct perforation during stone removal, approximately 5 weeks prior to the hemorrhagic episode. The removal of the stent was performed 10 days before the onset of hemobilia. The bleeding was successfully treated by two sessions of transarterial coil embolization.
Subject(s)
Humans , Bile Ducts , Cholangiopancreatography, Endoscopic Retrograde , Embolization, Therapeutic , Hemobilia , Hemorrhage , Plastics , StentsABSTRACT
Endoscopic retrograde cholangiopancreatography (ERCP)-related complications should be promptly and properly managed in accordance with the type and severity of the complication and the comorbidity of the patient. Neurologic complications occur very rarely, but despite of the prompt management, the patient status can severely deteriorate and sometimes result in fatality. A female patient visited SAM Medical Center for abdominal pain and yellow skin. She has taken a current medication for essential hypertension since 10 years ago. Initial laboratory findings showed obstructive jaundice and abdominal computed tomography (CT) showed two common bile duct stones with moderate dilation of bile duct. Her vital sign with oxygen saturation was stable until the first attack of seizure 12 hours later after removal of stones through the ERCP. Emergent brain CT and magnetic resonance imaging revealed multiple cerebral infarctions of both hemispheres with right predominance of middle cerebral artery territory and no evidence of air emboli. She died four days later despite of intensive care including high oxygen therapy and intravenous broad spectrum antibiotics with antiplatelet drug. We report a rare, delayed occurrence of a fatal multiple cerebral infarctions 12 hours after ERCP.
Subject(s)
Female , Humans , Abdominal Pain , Anti-Bacterial Agents , Bile Ducts , Brain , Cerebral Infarction , Cholangiopancreatography, Endoscopic Retrograde , Common Bile Duct , Comorbidity , Hypertension , Critical Care , Jaundice, Obstructive , Magnetic Resonance Imaging , Middle Cerebral Artery , Oxygen , Seizures , Skin , Vital SignsABSTRACT
Gastric cancer frequently disseminates to the liver, lung, and bone via hematogeneous, lymphatic, or peritoneal routes. However, gastric adenocarcinoma that metastasize to the colon and that shows typical linea platisca pattern on colonofiberscopy has rarely been reported. Recently, the authors experience a case of advanced gastric cancer with colonic metastases in a 55-year-old female patient. Multiple colonic lymphoid hyperplasias were detected on colonofiberscopy and biopsy revealed metastatic gastric cancer to the colonic wall. She was treated with mFOLFOX (5-FU, oxaliplatin, leucovorin) and has achieved stable disease status without disease progression. Herein, we report a rare case of signet ring-cell gastric cancer which metastasized to the colon in the form of multiple colonic lymphoid hyperplasias.
Subject(s)
Female , Humans , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonic Neoplasms/diagnosis , Colonoscopy , Fluorouracil/administration & dosage , Gastroscopy , Hyperplasia/diagnosis , Leucovorin/administration & dosage , Organoplatinum Compounds/administration & dosage , Positron-Emission Tomography , Stomach Neoplasms/diagnosis , Tomography, X-Ray ComputedABSTRACT
Brunner's gland adenoma is a rare benign small bowel neoplasm and it represents 10% of small bowel benign tumor. Most of adenoma manifest as polypoidal, multiple and size does not exceed 1 cm and mostly asymptomatic, but the lesion larger than 1cm is solitary and can cause bleeding, obstruction, intussusception and there are some reports of showing malignant transformation. Until the present, there are two cases of over cm huge Brunner's gland adenoma in Korea and each of their chief complaint was abdominal discomfort and melena, but there is no case report of over 8cm Brunner's gland adenoma accompanied with acute bleeding as seen in this case. We diagnosed an 8cm sized, huge duodenal Brunner's gland adenoma which accompanied with acute bleeding and treated it by endoscopic resection using an IT-knife, successfully.
Subject(s)
Adenoma , Endoscopy , Hemorrhage , Intussusception , Korea , MelenaABSTRACT
The occurrence of hepatocellular carcinoma (HCC) is closely associated with viral hepatitis or alcoholic hepatitis. Although active surveillance is ongoing in Korea, advanced or metastatic HCC is found at initial presentation in many patients. Metastatic HCC presents with a hypervascular intrahepatic tumor and extrahepatic lesions such as lung or lymph node metastases. Cases of HCC presenting as carcinoma of unknown primary have been rarely reported. The authors experienced a case of metastatic HCC in a patient who presented with a metastatic bone lesion but no primary intrahepatic tumor. This case suggests that HCC should be considered as a differential diagnosis when evaluating the primary origin of metastatic carcinoma.