Hepatocellular carcinoma Diagnostic study of choice
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dildar Hussain, MBBS [2]
Overview
Hepatocellular carcinoma is best diagnosed on a core biopsy of the liver. Core biopsy is done in a single visit at the hospital.
Diagnostic Study of Choice
Liver biopsy
- The diagnosis of hepatocellular carcinoma is confirmed by percutaneous biopsy and histopathologic analysis.
- Percutaneous biopsy should only be performed when diagnostic imaging results are uncertain.
- Percutaneous core liver biopsy is the gold standard test for the diagnosis of hepatocellular carcinoma.
- In addition to the percutaneous approach, there are various other approaches to obtain a sample of the hepatic tissue, such as:[1][2][3]
- Transjugular approach
- Laparoscopic radiographically guided fine-needle approach
- Endoscopic ultrasound (EUS)-guided fine-needle biopsy (EUS-FNA)
- Percutaneous biopsy of focal lesions may be performed in combination with either ultrasound or CT imaging.[4]
- Percutaneous liver biopsy remains the cornerstone of diagnosis. It is a quick and simple to perform liver biopsy in a patient with normal platelet count and INR.[5]
- Surgical resection
- Two out of the following three positive stains upon liver biopsy confirm HCC:[6][7]
Hep Par 1 Antibody Stain
- Tissue microarray technology is uses to test Hep Par 1 antibody stain which is showing promising results in differential diagnosis of HCC.[8]
- A biopsy is not necessary if the clinical, laboratory, and radiologic data suggest hepatocellular carcinoma.
- Liver biopsy may be suggestive of etiology as the following:
- Alcoholic liver disease : Liver biopsy may show hepatocyte necrosis, presence of mallory bodies, neutrophilic infiltration and perivenular inflammation.
- Primary biliary cirrhosis : Gold standard diagnostic modality is the detection of antimitochondrial antibodies along with liver biopsy as confirmation of florid bile duct lesions.
- There is a small but significant risk associated with liver biopsy, and the underlying cirrhosis in the patients with HCC itself predisposes to complications due to liver biopsy.[9]
- There is a 3% risk of tumor spread in the percutaneous needle path, risks of liver biopsy include:[10]
- Hemorrhage
- Biliary peritonitis
- Hematoma
- Perforation of other viscera
- Mortality rates of between 0.01% and 0.1%
- Patients with moderate coagulopathy:
- Plugged liver biopsy : Injection of gelatin sponges or metal coils down the tract after biopsy
- Laparoscopic liver biopsy performed on a sedated patient with moderate coagulopathy
- Advantage:
- Allows direct visualization of the liver
- Advantage:
Transjugular liver biopsy:
- Used in patients with severe clotting disorders
- Advantage:
- Risk of intraperitoneal bleed is less
- Disadvantages:
- Advantage:
The comparison table for diagnostic studies of choice for hepatocellular carcinoma:[11]
| Diagnostic Test | Sensitivity | Specificity |
|---|---|---|
| Percutaneous Ultrasound guided liver biopsy | 90% | 91% |
| Percutaneous CT guided liver biopsy | 92% | 98% |
Sequence of Diagnostic Studies
The core needle biopsy should be performed when:[12]
- A positive hepatic leision is detected in the patient on imaging studies.
- The patient has underlying risk factors i.e HBV infection, HCV infection or liver cirrhosis.
Diagnostic Criteria
- Hepatocellular carcinoma may be diagnosed at any time if the following criteria is met:
Staging of hepatocellular carcinoma
According to the TNM staging system, there are four stages of hepatocellular carcinoma based on the tumor size, lymph node involvement, and distant metastasis.Although the TNM staging system is widely used for the staging of hepatocellular carcinoma, the Cancer of the Liver Italian Program (CLIP) system is used widely because it is adopted from the original Okuda classification system that involves cirrhosis into account.[14]
Primary tumor
| TX | Primary tumour cannot be assessed |
| T0 | No evidence of primary tumour |
| T1 | A single tumour with no invasion into the blood vessels of the liver |
| T2 | A single tumour with invasion into the blood vessels or multiple tumours, none more than 5 cm in size |
| T3a | Multiple tumours, with any tumour larger than 5 cm |
| T3b | The tumour has grown into either the portal or hepatic vein |
| T4 | The tumour has grown into nearby organs (other than the gallbladder) or the tumour has grown into the layer of tissue that covers the organs in the abdomen (visceral peritoneum) |
Regional lymph node
| NX | Regional lymph nodes cannot be assessed |
| N0 | No regional lymph node metastasis |
| N1 | Regional lymph node metastasis |
Distance metastasis
| M0 | No distant metastasis |
| M1 | Distant metastasis |
Clip and Okuda Staging Systems for Hepatocellular Carcinoma
Cancer of the Liver Italian Program (CLIP) system is used widely because it is adopted from the original Okuda classification system that involves cirrhosis into account.[15]
CLIP Classification
| Points | |||
|---|---|---|---|
| Variable | 0 | 1 | 2 |
| i.Tumor number (%) | Single | Multiple | – |
| Hepatic replacement by tumor | <50 | <50 | >50 |
| ii. Child-Pugh score | A | B | C |
| iii. α Fetoprotein level (ng/mL) | <400 | ≥400 | – |
| iv.Portal vein thrombosis (CT) | No | Yes | – |
| CLIP stages (score = sum of points): CLIP 0, 0 points; CLIP 1, 1 point; CLIP 2, 2 points; CLIP 3, more than 3
points. | |||
OKUDA Classification
| OKUDA Classification | |||||||
| Tumor Extent* | Bilirubin (mg/dL) | Albumin (g/L) | Ascites | ||||
| ≥50% | <50 | ≥ 3 | <3 | ≤3 | >3 | + | – |
| (+) | (−) | (+) | (−) | (+) | (−) | (+) | (−) |
| Okuda stages: stage 1, all (−); stage 2, 1 or 2 (+); stage 3, 3 or 4 (+). | |||||||
References
- ↑ Cholongitas E, Quaglia A, Samonakis D, Senzolo M, Triantos C, Patch D, Leandro G, Dhillon AP, Burroughs AK (2006). "Transjugular liver biopsy: how good is it for accurate histological interpretation?". Gut. 55 (12): 1789–94. doi:10.1136/gut.2005.090415. PMC 1856467. PMID 16636018.
- ↑ Hollerbach S, Reiser M, Topalidis T, König M, Schmiegel W (2003). "Diagnosis of hepatocellular carcinoma (HCC) in a high-risk patient by using transgastric EUS-guided fine-needle biopsy (EUS-FNA)". Z Gastroenterol. 41 (10): 995–8. doi:10.1055/s-2003-42920. PMID 14562197.
- ↑ Wang L, Geng J, Li J, Li T, Matsumori A, Chang Y, Lu F, Zhuang H (2011). "The biomarker N-terminal pro-brain natriuretic peptide and liver diseases". Clin Invest Med. 34 (1): E30–7. PMID 21291633.
- ↑ Schirmacher P, Fleig WE, Tannapfel A, Langner C, Dries V, Terracciano L, Denk H, Dienes HP (2004). "[Bioptic diagnosis of chronic hepatitis. Results of an evidence-based consensus conference of the German Society of Pathology, of the German Society for Digestive and Metabolic Diseases and of Compensated Hepatitis (HepNet)]". Pathologe (in German). 25 (5): 337–48. doi:10.1007/s00292-004-0692-7. PMID 15278290.
- ↑ Tannapfel A, Dienes HP, Lohse AW (2012). "The indications for liver biopsy". Dtsch Arztebl Int. 109 (27–28): 477–83. doi:10.3238/arztebl.2012.0477. PMC 3402072. PMID 22833761.
- ↑ 6.0 6.1 "Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia". Hepatology. 49 (2): 658–64. 2009. doi:10.1002/hep.22709. PMID 19177576.
- ↑ Karabork A, Kaygusuz G, Ekinci C (2010). "The best immunohistochemical panel for differentiating hepatocellular carcinoma from metastatic adenocarcinoma". Pathol. Res. Pract. 206 (8): 572–7. doi:10.1016/j.prp.2010.03.004. PMID 20400233.
- ↑ Fan, Zhen; van de Rijn, Matt; Montgomery, Kelli; Rouse, Robert V. (2003). "Hep Par 1 Antibody Stain for the Differential Diagnosis of Hepatocellular Carcinoma: 676 Tumors Tested Using Tissue Microarrays and Conventional Tissue Sections". Modern Pathology. 16 (2): 137–144. doi:10.1097/01.MP.0000052103.13730.20. ISSN 0893-3952.
- ↑ Grant, A (1999). "Guidelines on the use of liver biopsy in clinical practice". Gut. 45 (Suppl 4): 1–11. PMID 10485854.
The main cause of mortality after percutaneous liver biopsy is intraperitoneal haemorrhage as shown in a retrospective Italian study of 68,000 percutaneous liver biopsies in which all six patients who died did so from intraperitoneal haemorrhage. Three of these patients had had a laparotomy, and all had either cirrhosis or malignant disease, both of which are risk factors for bleeding.
- ↑ Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A (2012). "Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report". Lancet Oncol. 13 (1): e11–22. doi:10.1016/S1470-2045(11)70175-9. PMC 3417764. PMID 22047762.
- ↑ El-Serag HB, Marrero JA, Rudolph L, Reddy KR (2008). "Diagnosis and treatment of hepatocellular carcinoma". Gastroenterology. 134 (6): 1752–63. doi:10.1053/j.gastro.2008.02.090. PMID 18471552.
- ↑ Song DS, Bae SH (2012). "Changes of guidelines diagnosing hepatocellular carcinoma during the last ten-year period". Clin Mol Hepatol. 18 (3): 258–67. doi:10.3350/cmh.2012.18.3.258. PMC 3467428. PMID 23091805.
- ↑ Di Tommaso L, Roncalli M (2017). "Tissue Biomarkers in Hepatocellular Tumors: Which, When, and How". Front Med (Lausanne). 4: 10. doi:10.3389/fmed.2017.00010. PMC 5322593. PMID 28280721.
- ↑ Canadian Cancer Society.http://www.cancer.ca/en/cancer-information/cancer-type/liver/staging/?region=ab
- ↑ Kasper, Dennis. Harrison's principles of internal medicine. New York: McGraw Hill Education. ISBN 978-0-07-1802161.