6. Conclusions

Figure 1. Diagnostic algorithm of hepatocellular carcinoma. 1—Recommended by the American Association for the Study of the Liver diseases (AASLD). 2—Recommended by the European Association for the Study of the Liver (EASL). Abbreviations: RFs, risk factors; vs, versus; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; US, ultrasonography; CT, computed tomography; MRI, magnetic resonance imaging; HGDN, high-grade dysplastic nodule; FNH, focal nodular hyperplasia; IHC, immunohistochemistry; SIR, systemic inflammatory response; mi,

micro; RNA; ribonucleic acid.

36 Hepatocellular Carcinoma - Advances in Diagnosis and Treatment

HCC is a frequent and aggressive malignant tumour, estimated to range sixth by incidence and second by mortality in the global cancer statistics. The high ratio of mortality to incidence (0.95) and the close geographic correlation between incidence and mortality reflects the dismal prognosis. However, longer survival can be reached in early diagnosed and properly treated cases.

expression of at least two markers in a panel consisting from glypican-3, heat shock protein 70 and glutamine synthetase; (2) diffuse expression of CD34 due to higher oxygen tension in HCC and (3) loss of perifocal CK7- and CK19-positive ductular reaction as a sign of invasive growth. Regarding molecular classification of HCC, reasonable success has been reached by French research group and trans-ancestry study team. However, no unified classification has been

Diagnostic Algorithm of Hepatocellular Carcinoma: Classics and Innovations in Radiology and Pathology

established yet. Molecular profile can have both diagnostic and prognostic value.

BS was financially supported by post-doctoral research project 1.1.1.2./VIAA/1/16/242.

, Arturs Kalva1

, Arnis Abolins<sup>1</sup> and Janis Gardovskis<sup>2</sup>

[1] Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO Classification of Tumours of the

[2] Ryerson AB, Eheman CR, Altekruse SF, Ward JW, Jemal A, Sherman RL, Henley SJ, Holtzman D, Lake A, Noone AM, Anderson RN, Ma J, Ly KN, Cronin KA, Penberthy L, Kohler BA. Annual report to the nation on the status of cancer, 1975–2012, featuring the increasing incidence of liver cancer. Cancer. 2016;122(9):1312-1337. DOI: 10.1002/cncr.

[3] Schlageter M, Terracciano LM, D'Angelo S, Sorrentino P. Histopathology of hepatocellular carcinoma. World Journal of Gastroenterology. 2014;20(43):15955-15964. DOI: 10.3748/

[4] Mezale D, Strumfa I, Vanags A, Mezals M, Fridrihsone I, Strumfs B, Balodis D. Nonalcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma: The molecular pathways. In: Tsoulfas G, editor. Liver Cirrhosis – Update and Current Challenges. Rijeka:

IntechOpen; 2017. pp. 1-34. DOI: 10.5772/intechopen.68771

, Dainis Balodis1

http://dx.doi.org/10.5772/intechopen.76136

39

,

\*, Andrejs Vanags<sup>2</sup>

Acknowledgements

Author details

Dzeina Mezale<sup>1</sup>

Boriss Strumfs3

References

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, Ilze Strumfa<sup>1</sup>

, Ilze Fridrihsone<sup>1</sup>

\*Address all correspondence to: ilze.strumfa@rsu.lv

3 Latvian Institute of Organic Synthesis, Riga, Latvia

Digestive System. IARC: Lyon; 2010. 417 p

1 Department of Pathology, Riga Stradins University, Riga, Latvia 2 Department of Surgery, Riga Stradins University, Riga, Latvia

Awareness of the risk factors of HCC is helpful both in diagnostics and in order to set up the surveillance. Liver cirrhosis is the main risk factor; surveillance is indicated in these patients. A tumour found in cirrhotic liver is more likely to be HCC than metastasis or liver adenoma. However, the differential diagnosis includes a dysplastic cirrhotic nodule.

The other risk factors act mainly through inducing cirrhosis although a fraction of HCC can precede the development of cirrhosis in a patient affected by chronic liver disease or develop in non-fibrotic liver. Thus, the complete list of the risk factors of HCC includes chronic active hepatitis B or C, liver damage by alcohol and/or aflatoxins, as well as NASH. The risk factors can act synergistically. Evaluating the HCC risk in any patient, the relative risk must be considered in accordance to the risk factors that are identified in that individual. However, to estimate the expected cancer burden in the population, population attributable fractions are of importance; these parameters depend both on relative risk and population frequency of each particular factor.

Non-invasive radiological approach is the gold standard in the diagnostics of HCC in contrast with most of other malignant tumours necessitating confirmation by a biopsy. Biopsy is indicated only in radiologically controversial cases or to prove HCC in non-cirrhotic liver.

Ultrasonography is used for surveillance and the initial step of diagnostics. For surveillance of cirrhotic patient, US is carried out once in 6 months. If a suspicious focus is disclosed, the further approach is based on the size. Either CT or MRI is indicated for mass lesions larger than 20 mm, while both methods are recommended for a nodule measuring between 10 and 20 mm. Nodules that are smaller than 1 cm are followed up by US once in 4 months. Hypervascularity is a characteristic trait of HCC in CT and MRI. PET and CEUS may have additional role in HCC diagnostics.

If biopsy is carried out, HCC can be diagnosed if both signs of hepatocellular differentiation and cellular atypia or invasion are present. Low-grade tumours must be differentiated from dysplastic nodule, focal nodular hyperplasia and adenoma while high-grade HCC must be distinguished from metastasis. Mass lesion in cirrhotic liver is most probably a dysplastic nodule or HCC while adenomas and metastases usually develop in non-cirrhotic liver. In a Western patient, clearly malignant tumour in a non-cirrhotic liver has higher probability to represent a metastatic carcinoma.

Regarding immunohistochemistry, arginase-1 and HepPar antigen are reasonable hepatocellular markers that are used to distinguish HCC from metastases. Novel immunohistochemical markers of HCC include bile salt export pump protein and heavy chain of clathrin. Glypican should be used with caution due to the reported expression in a wide range of extrahepatic tumours. In order to discriminate between low-grade HCC and FNH, reticulin network, glypican-3 and heat shock protein 70 can be assessed. The differential diagnosis between high grade dysplastic nodule and low grade HCC can be very complicated as both processes share several morphological features and can coexist, biologically representing subsequent stages of HCC development. The features favouring malignancy over dysplastic nodule, include (1) expression of at least two markers in a panel consisting from glypican-3, heat shock protein 70 and glutamine synthetase; (2) diffuse expression of CD34 due to higher oxygen tension in HCC and (3) loss of perifocal CK7- and CK19-positive ductular reaction as a sign of invasive growth.

Regarding molecular classification of HCC, reasonable success has been reached by French research group and trans-ancestry study team. However, no unified classification has been established yet. Molecular profile can have both diagnostic and prognostic value.
