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Early or Small Hepatocellular Carcinoma

ICD-O code 8170/3

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Tumors and Tumor-Like Lesions of the Hepatobiliary Tract

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Abstract

At the time point of diagnosis, subsets of hepatocellular carcinoma (HCC) show a small size. Part of these lesions are early cancers, but there are also small HCCs with a distinct histologic pattern. Lesions with a diameter of 3.5 cm or less were formerly termed minute HCC. Today, early HCC is frequently identified as a nodular HCC measuring 2 cm or less in diameter, the limit of 2 cm having been settled in an international consensus conference. These small neoplasms come in two basic growth patterns, one characterized by vaguely nodular, well-differentiated tumors (small HCC with indistinct margins or vaguely nodular small HCC) and the other by distinctly nodular tumor with the histology of ordinary HCC. Early and small HCCs are usually asymptomatic, but are associated with liver cirrhosis in most patients. At least part of early HCCs show a histological presentation that differs in several respects from that of larger ordinary HCCs, suggesting that some of these small tumors are not simply early stages of a classical HCC progression pathway, but rather represent a distinct variant of HCC.

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References

  • Adachi E, Maeda T, Matsumata T, Shirabe K, Kinukawa N, Sugimachi K, Tsuneyoshi M (1995) Risk factors for intrahepatic recurrence in human small hepatocellular carcinoma. Gastroenterology 108:768–775

    Article  CAS  PubMed  Google Scholar 

  • An FQ, Matsuda M, Fujii H, Tang RF, Amemiya H, Dai YM, Matsumoto Y (2001) Tumor heterogeneity in small hepatocellular carcinoma: analysis of tumor cell proliferation, expression and mutation of p53 and beta-catenin. Int J Cancer 93:468–474

    Article  CAS  PubMed  Google Scholar 

  • Barbara L, Benzi G, Gaiani S, Fusconi F, Zironi G, Siringo S, Rigamonti A, Barbara C et al (1992) Natural history of small untreated hepatocellular carcinoma in cirrhosis: a multivariate analysis of prognostic factors of tumor growth rate and patient survival. Hepatology 16:132–137

    Article  CAS  PubMed  Google Scholar 

  • Bartolozzi C, Battaglia V, Bozzi E (2011) Hepatocellular nodules in liver cirrhosis: contrast-enhanced MR. Abdom Imaging 36:290–299

    Article  PubMed  Google Scholar 

  • Bhattacharjya S, Bhattacharjya T, Quaglia A, Dhillon AP, Burroughs AK, Patch DW et al (2004) Liver transplantation in cirrhotic patients with small hepatocellular carcinoma: an analysis of pre-operative imaging, explant histology and prognostic histologic indicators. Dig Surg 21:152–159

    Article  PubMed  Google Scholar 

  • Boix L, Bruix J, Campo E, Sole M, Castells A, Fuster J, Rivera F, Cardesa A, Rodes J (1994) nm23-H1 expression and disease recurrence after surgical resection of small hepatocellular carcinoma. Gastroenterology 107:486–491

    Article  CAS  PubMed  Google Scholar 

  • Bolondi L, Gaiani S, Celli N, Golfieri R, Grigioni WF, Leoni S, Venturi AM, Piscaglia F (2005) Characterization of small nodules in cirrhosis by assessment of vascularity: the problem of hypovascular hepatocellular carcinoma. Hepatology 42:27–34

    Article  PubMed  Google Scholar 

  • Bruix J, Sherman M (2005) Diagnosis of small HCC. Gastroenterology 129:134

    Article  Google Scholar 

  • Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E et al (2001) Clinical management of hepatocellular carcinoma: conclusions of the Barceloma-2000 EASL conference. J Hepatol 35:421–430

    Article  CAS  PubMed  Google Scholar 

  • Caroli-Bottino A, Nascimento CM, Basto S, Ribeiro J, Silveira V, Carvalho AM, Castro PN et al (2005) Hepatocellular carcinoma: incidental finding in cirrhotic explanted livers. Transplant Proc 37:2791–2792

    Article  CAS  PubMed  Google Scholar 

  • Carr BI, Lu SN, Pancoska P (2011) Small hepatocellular carcinoma in Chinese patients. Hepatogastroenterology 58:1334–1342

    Article  PubMed  Google Scholar 

  • Chen DS, Sheu JC, Sung JL, Lai MY, Lee CS, Su CT, Tsang YM, How SW, Wang TH et al (1982) Small hepatocellular carcinoma – a clinicopathological study in thirteen patients. Gastroenterology 63:1109–1119

    Google Scholar 

  • Chen DS, Sung JL, Sheu JC, Lai MY, How SW, Hsu HC, Lee CS, Wei TC (1984) Serum a-fetoprotein in the early stage of human hepatocellular carcinoma. Gastroenterology 86:1404–1409

    CAS  PubMed  Google Scholar 

  • Chen CL, Huang SM, Chien CH, Chang TT, Yu CY, Lee JC (1994) Successful resection of a minute icteric hepatocellular carcinoma – case report. Hepatogastroenterology 41:503–505

    CAS  PubMed  Google Scholar 

  • Chen MH, Dai Y, Yan K, Fan ZH, Yin SS, Yang W, Wu W, Wang YB, Li JY (2006) The role of contrast-enhanced ultrasound on the diagnosis of small hepatocellular carcinoma (</=3 cm) in patients with cirrhosis. Hepatol Res 35:281–288

    Article  PubMed  Google Scholar 

  • Chen ZY, Wei W, Guo ZX, Lin JR, Shi M, Guo RP (2011a) Morphologic classification of microvessels in hepatocellular carcinoma is associated with the prognosis after resection. J Gastroenterol Hepatol 26:866–874

    Article  PubMed  Google Scholar 

  • Chen YL, Ko CJ, Chien SY, Chen LS, Chen ML, Chi CW, Lai HW (2011b) Tumor size as a prognostic factor in resected small hepatocellular carcinoma: a controversy revisited. J Gastroenterol Hepatol 26:851–857

    Article  PubMed  Google Scholar 

  • Choi BI, Kim CW, Han MC, Kim CY, Lee HS, Kim ST, Kim YI (1989) Sonographic characteristics of small hepatocellular carcinoma. Gastrointest Radiol 14:255–261

    Article  CAS  PubMed  Google Scholar 

  • Choi BI, Takayasu K, Han MC (1993) Small hepatocellular carcinomas and associated nodular lesions of the liver: pathology, pathogenesis, and imaging findings. AJR Am J Roentgenol 160:1177–1187

    Article  CAS  PubMed  Google Scholar 

  • Choi D, Kim S, Lim J, Lee W, Jang H, Lee S, Lim H (2001) Preoperative detection of hepatocellular carcinoma: ferumoxides-enhanced mr imaging versus combined helical CT during arterial portography and CT hepatic arteriography. AJR Am J Roentgenol 176:475–482

    Article  CAS  PubMed  Google Scholar 

  • Colombo M (2008) Natural history of hepatocellular carcinoma. Ann Ital Chir 79:91–97

    PubMed  Google Scholar 

  • Dahiya D, Wu TJ, Lee CF, Chan KM, Lee WC, Chen MF (2010) Minor versus major hepatic resection for small hepatocellular carcinoma (HCC) in cirrhotic patients: a 20-year experience. Surgery 147:676–685

    Article  PubMed  Google Scholar 

  • Dhillon AP, Colombari R, Savage K, Scheuer PJ (1992) An immunohistochemical study of the blood vessels within primary hepatocellular tumours. Liver 12:311–318

    Article  CAS  PubMed  Google Scholar 

  • Di Martino M, Di Miscio R, De Filippis G, Lombardo CV, Saba L, Geiger D, Catalano C (2013) Detection of small (<= 2 cm) HCC in cirrhotic patients: added value of diffusion MR-imaging. Abdom Imaging 38:1254–1262

    Google Scholar 

  • Di Tommaso L, Destro A, Fabbris V, Spagnuolo G, Laura Fracanzani A, Fargion S et al (2011) Diagnostic accuracy of clathrin heavy chain staining in a marker panel for the diagnosis of small hepatocellular carcinoma. Hepatology 53:1549–1557

    Article  PubMed  CAS  Google Scholar 

  • Dong H, Cong WM, Xian ZH, Zhu ZZ (2011) Using loss of heterozygosity of microsatellites to distinguish high-grade dysplastic nodule from early minute hepatocellular carcinoma. Exp Mol Pathol 91:578–583

    Article  CAS  PubMed  Google Scholar 

  • Doyonnas R, Nielsen JS, Chelliah S, Drew E, Hara T, Miyajima A, McNagny KM (2005) Podocalyxin is a CD34-related marker of murine hematopoietic stem cells and embryonic erythroid cells. Blood 105:4170–4178

    Article  CAS  PubMed  Google Scholar 

  • Dusheiko GM, Conradie JC, Bowyer SM, Simjee A, Epstein B, Levien LJ, Beale P, Kew MC (1986) Small and asymptomatic hepatocellular carcinoma detected by alpha-fetoprotein screening in black hepatitis B carriers. A report of 2 cases. S Afr Med J 69:129–132

    CAS  PubMed  Google Scholar 

  • Ebara M, Ohto M, Watanabe Y, Kimura K, Saisho H, Tsuchiya Y, Okuda K, Arimizu N et al (1986a) Diagnosis of small hepatocellular carcinoma: correlation of MR imaging and tumor histologic studies. Radiology 159:371–377

    Article  CAS  PubMed  Google Scholar 

  • Ebara M, Ohto M, Shinagawa T, Sugiura N, Kimura K, Matsutani S, Morita M, Saisho H et al (1986b) Natural history of minute hepatocellular carcinoma smaller than three centimeters complicating cirrhosis. A study in 22 patients. Gastroenterology 90:289–298

    Article  CAS  PubMed  Google Scholar 

  • Ebara M, Watanabe S, Kita K, Yoshikawa M, Sugiura N, Ohto M, Kondo F, Kondo Y (1991) MR imaging of small hepatocellular carcinoma: effect of intratumoral copper content on signal intensity. Radiology 180:617–621

    Article  CAS  PubMed  Google Scholar 

  • Ebara M, Okabe S, Kita K, Sugiura N, Fukuda H, Yoshikawa M, Kondo F, Saisho H (2005) Percutaneous ethanol injection for small hepatocellular carcinoma: therapeutic efficacy based on 20-year observation. J Hepatol 43:458–464

    Article  CAS  PubMed  Google Scholar 

  • Effendi K, Sakamoto M (2010) Molecular pathology in early hepatocarcino-genesis. Oncology 78:157–160

    Article  CAS  PubMed  Google Scholar 

  • Efremidis SC, Hytiroglou P, Matsui O (2007) Enhancement patterns and signal-intensity characteristics of small hepatocellular carcinoma in cirrhosis: pathologic basis and diagnostic challenges. Eur Radiol 17:2969–2982

    Article  PubMed  Google Scholar 

  • Ferrari FS, Stella A, Pasquinucci P, Vigni F, Civeli L, Pieraccini M, Magnolfi F (2006) Treatment of small hepatocellular carcinoma: a comparison of techniques and long-term results. Eur J Gastroenterol Hepatol 18:659–672

    Article  PubMed  Google Scholar 

  • Fong Y, Sun RL, Jarnagin W, Blumgart LH (1999) An analysis of 412 cases of hepatocellular carcinoma at Western center. Ann Surg 229:790–799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fukii T, Zen Y, Nakanuma Y (2007) Minute scirrhous hepatocellular carcinomas undergoing different carcinogenetic processes. Pathol Int 57:443–448

    Article  Google Scholar 

  • Fukuda S, Itamoto T, Nakahara H, Kohashi T, Ohdan H, Hino H, Ochi M, Tashiro H, Asahara T (2005) Clinicopathologic features and prognostic factors of resected solitary small-sized hepatocellular carcinoma. Hepatogastroenterology 52:1163–1167

    PubMed  Google Scholar 

  • Gandolfi L, Solmi L, Bertoni F, Muratori R, Stasi G (1987) Small hepatocellular carcinoma: an Italian experience. Hepatogastroenterology 34:100–102

    CAS  PubMed  Google Scholar 

  • Golfieri R, Marini E, Bazzocchi A, Fusco F, Trevisani F, Sama C, Mazzella G, Cavuto S et al (2009) Small (<or= 3 cm) hepatocellular carcinoma in cirrhosis: the role of double contrast agents in MR imaging vs. multidetector-row CT. Radiol Med 114:1239–1266

    Article  CAS  PubMed  Google Scholar 

  • Grigioni WF, D’Errico A, Bacci F, Carella R, Macini AM (1989) Small liver masses in cirrhotic patients. A pathological clue for the morphogenesis of human hepatocellular carcinoma. Acta Pathol Jpn 39:520–527

    CAS  PubMed  Google Scholar 

  • Grigioni WF, D’Errico A, Fortunato C, Cassisa A, Carella R, Mancini AM (1991) The morphogenesis of human hepatocellular carcinoma. Ital J Gastroenterol 23:594–596

    CAS  PubMed  Google Scholar 

  • Haratake J, Horie A, Nakashima A, Takeda S, Mori A (1986) Minute hepatoma with excessive copper accumulation. Report of two cases with resection. Arch Pathol Lab Med 110:192–194

    CAS  PubMed  Google Scholar 

  • Haratake J, Hisaoka M, Yamamoto O, Horie A (1992) An ultrastructural comparison of sinusoids in hepatocellular carcinoma, adenomatous hyperplasia, and fetal liver. Arch Pathol Lab Med 116:67–70

    CAS  PubMed  Google Scholar 

  • Hayashida M, Ito K, Fujita T, Shimizu A, Sasaki K, Tanabe M, Matsunaga N (2008) Small hepatocellular carcinomas in cirrhosis: differences in contrast enhancement effects between helical CT and MR imaging during multiphasic dynamic imaging. Magn Reson Imaging 26:65–71

    Article  PubMed  Google Scholar 

  • Heukamp LC, Fischer HP, Schirmacher P, Chen X, Breuhahn K, Nicolay C, Buttner R et al (2006) Podocalyxin-like protein 1 expression in primary hepatic tumours and tumour-like lesions. Histopathology 49:242–247

    Article  CAS  PubMed  Google Scholar 

  • Higashi T, Tobe K, Asano K, Ikeda H, Ohsawa T, Iwasaki Y, Nouso K, Shinji N, Morimoto Y et al (1988) Ultrasonographic characteristics of small hepatocellular carcinoma. Acta Med Okayama 42:151–157

    CAS  PubMed  Google Scholar 

  • Hirai K, Aoki Y, Majima Y, Abe H, Nakashima O, Kojiro M, Tanikawa K (1991) Magnetic resonance imaging of small hepatocellular carcinoma. Am J Gastroenterol 86:205–209

    CAS  PubMed  Google Scholar 

  • Hosaka T, Ikeda K, Kobayashi M, Hirakawa M, Kawamura Y, Yatsuji H, Sezaki H, Akuta N et al (2009) Predictive factors of advanced recurrence after curative resection of small hepatocellular carcinoma. Liver Int 29:736–742

    Article  PubMed  Google Scholar 

  • Hosoki T, Chtani M, Mori S (1982) Dynamic computed tomography of hepatocellular carcinoma. AJR Am J Roentgenol 139:1099–1106

    Article  CAS  PubMed  Google Scholar 

  • Hsu HC, Sheu JC, Lin YH, Chen DS, Lee CS, Hwang LY, Beasley RP (1985) Prognostic histologic features of resected small hepatocellular carcinoma (HCC) in Taiwan. A comparison with resected large HCC. Cancer 56:672–680

    Article  CAS  PubMed  Google Scholar 

  • Huang GT, Lee PH, Tsang YM, Lai MY, Yang PM, Hu RH, Chen PJ, Kao JH et al (2005) Percutaneous ethanol injection versus surgical resection for the treatment of small hepatocellular carcinoma: a prospective study. Ann Surg 242:36–42

    Article  PubMed  PubMed Central  Google Scholar 

  • Hung HH, Su CW, Lai CR, Chau GY, Chan CC, Huang YH, Huo TI, Lee PC et al (2010) Fibrosis and AST to platelet ratio index predict post-operative prognosis for solitary small hepatitis B-related hepatocellular carcinoma. Hepatol Int 4:691–699

    Article  PubMed  PubMed Central  Google Scholar 

  • Hwang SH, Yu JS, Kim KW, Kim JH, Chung JJ (2008) Small hypervascular enhancing lesions on arterial phase images of multiphase dynamic computed tomography in cirrhotic liver: fate and implications. J Comput Assist Tomogr 32:39–45

    Article  PubMed  Google Scholar 

  • Hwang J, Kim SH, Lee MW, Lee JY (2012) Small (<- 2 cm) hepatocellular carcinoma in patients with chronic liver disease: comparison of gadoxetic acid-enhanced 3.0 T MRI and multiphasic 64-multirow detector CT. Br J Radiol 85:e314–e322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hytiroglou P (2004) Morphological changes of early human hepatocarcinogenesis. Semin Liver Dis 24:65–75

    Article  PubMed  Google Scholar 

  • Ikeda K, Saitoh S, Koida I, Tsubota A, Arase Y, Chayama K, Kumada H (1994) Imaging diagnosis of small hepatocellular carcinoma. Hepatology 20:82–87

    Article  CAS  PubMed  Google Scholar 

  • Ikeda K, Kobayashi M, Kawamura Y, Imai N, Seko Y, Hirakawa M, Hosaka T, Sezaki H et al (2011) Stage progression of small hepatocellular carcinoma after radical therapy: comparison of radiofrequency ablation and surgery using the Markov model. Liver Int 31:692–699

    Article  PubMed  Google Scholar 

  • Imaeda T, Kanematsu M, Mochizuki R, Goto H, Saji S, Shimokawa K (1994) Extracapsular invasion of small hepatocellular carcinoma: MR and CT findings. J Comput Assist Tomogr 18:755–760

    Article  CAS  PubMed  Google Scholar 

  • Imai K, Beppu T, Nakayama Y, Ishiko T, Horino K, Komori H, Masuda T, Hayashi H et al (2009) Preoperative prediction of poorly differentiated components in small-sized hepatocellular carcinoma for safe local ablation therapy. J Surg Oncol 100:121–126

    Article  PubMed  Google Scholar 

  • Inamoto K, Tanaka S, Yamazaki H, Okamoto E (1983) Computed tomography in the detection of small hepatocellular carcinomas. Gastrointest Radiol 8:321–326

    Article  CAS  PubMed  Google Scholar 

  • Inoue E, Kuroda C, Fujita M, Narumi Y, Kadota T, Kuriyama K, Ishiguro S, Kasugai H et al (1993) MR features of various histological grades of small hepatocellular carcinoma. J Comput Assist Tomogr 17:75–79

    Article  CAS  PubMed  Google Scholar 

  • Inoue K, Takayama T, Higaki T, Watanabe Y, Makuuchi M (2004) Clinical significance of early hepatocellular carcinoma. Liver Transpl 10(2 suppl 1):S16–S19

    Article  PubMed  Google Scholar 

  • International Consensus Group for Hepatocellular Neoplasia (2009) Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. Hepatology 49:658–664

    Article  Google Scholar 

  • International Working Party (1995) Terminology of nodular hepatocellular lesions. International Working Party. Hepatology 22:983–993

    Article  Google Scholar 

  • Ise N, Andoh H, Sato T, Yasui O, Kurokawa T, Kotanagi H (2004) Three cases of small hepatocellular carcinoma presenting as obstructive jaundice. HPB (Oxford) 6:21–24

    Article  CAS  Google Scholar 

  • Itai Y, Ohtomo K, Ohnishi S, Atomi Y, Itoh T, Fukuhisa K, Iinuma T (1987) Ultrasonography of small hepatic tumors. Radiat Med 5:14–19

    CAS  PubMed  Google Scholar 

  • Ito K, Fujita T, Shimizu A, Koike S, sasaki K, Matsunaga N, Hibino S, Yuhara M (2004) Multiarterial phase dynamic MRI of small early enhancing hepatic lesions in cirrhosis or chronic hepatitis: differentiating between hypervascular hepatocellular carcinomas and pseudolesions. AJR Am J Roentgenol 183:699–705

    Article  PubMed  Google Scholar 

  • Jang HJ, Kim TK, Wilson SR (2009) Small nodules (1–2 cm) in liver cirrhosis: characterization with contrast-enhanced ultrasound. Eur J Radiol 72:418–424

    Article  PubMed  Google Scholar 

  • Jeong YY, Mitchell DG, Kamishima T (2002) Small (<20mm) enhancing hepatic nodules seen on arterial phase MR imaging of the cirrhotic liver. Clinical implications. AJR Am J Roentgenol 178:1327–1334

    Article  PubMed  Google Scholar 

  • Jiang J, Wu C, Shen Y, Xu B, Zheng X, Li X, Xu N (2011) Clinical application of determining serum AFP-IgM complexes for diagnosis of small hepatocellular carcinoma. Anticancer Res 31:687–691

    CAS  PubMed  Google Scholar 

  • Jing-Dong L, Yun-Hong T, Kanduri HK, Quan-Lin L, De-Xing L, Qiang L (2011) Prognosis in patients with small hepatocellular carcinoma. A meta-analysis. Hepatogastroenterology 58:110–111

    Article  Google Scholar 

  • Kammula US (2006) Predicting outcomes after percutaneous ethanol injection for small hepatocellular cancer. Cancer J 12:175–177

    Article  PubMed  Google Scholar 

  • Kanai T, Hirohashi S, Upton MP, Noguchi M, Kishi M, Makuuchi M, Yamasaki S, Hasegawa H et al (1987) pathology of small hepatocellular carcinoma. A proposal for a new gross classification. Cancer 60:810–819

    Article  CAS  PubMed  Google Scholar 

  • Kanematsu T, Takenaka K, Matsumata T, Furuta T, Sugimachi K, Inokuchi K (1983) Small liver cancer. Jpn J Surg 13:32–36

    Article  CAS  PubMed  Google Scholar 

  • Kanematsu T, Sonoda T, Takenaka K, Matsumata T, Sugimachi K, Inokuchi K (1985) The value of ultrasound in the diagnosis and treatment of small hepatocellular carcinoma. Br J Surg 72:23–25

    Article  CAS  PubMed  Google Scholar 

  • Kanematsu M, Hoshi H, Yamada T, Murakami T, Kim T, Kato M, Yokoyama R, Nakamura H (1999) Small hepatic nodules in cirrhosis: ultrasonographic, CT, and MR imaging findings. Abdom Imaging 24:47–55

    Article  CAS  PubMed  Google Scholar 

  • Kenmochi K, Sugihara S, Kojiro M (1987) Relationship of histologic grade of hepatocellular carcinoma (HCC) to tumor size, and demonstration of tumor cells of multiple different grades in single small HCC. Liver 7:18–26

    Article  CAS  PubMed  Google Scholar 

  • Kikuchi LO, Paranagua-Vezozzo DC, Chagas AL, Mello ES, Alves VA, Farias AQ et al (2009) Nodules less than 20 mm and vascular invasion are predictors of survival in small hepatocellular carcinoma. J Clin Gastroenterol 43:191–195

    Article  PubMed  Google Scholar 

  • Kim SR, Hayashi Y, Matsuoka T, Park SY, Shintani S, Sasaki K, Asano J, Kim JH et al (1998) A case of well-differentiated minute hepatocellular carcinoma with extrahepatic metastasis. J Gastroenterol Hepatol 13:892–896

    Article  CAS  PubMed  Google Scholar 

  • Kim SR, Ikawa H, Ando K, Mita K, Fuki S, Imoto S, Shimizu K, Kanbara Y, Sugimoto K et al (2007) Small hepatocellular carcinoma presenting with massive metastasis in the peritoneum, mimicking sarcomatous tumor. Hepatol Res 37:885–889

    Article  PubMed  Google Scholar 

  • Kim TK, Lee KH, Khalili K, Jang HJ (2011) Hepatocellular nodules in liver cirrhosis: contrast-enhanced ultrasound. Abdom Imaging 36:244–263

    Article  PubMed  Google Scholar 

  • Kim MJ, Lee M, Choi JY, Park YN (2012) Imaging features of small hepatocellular carcinomas with microvascular invasion on gadoxetic acid-enhanced MR imaging. Eur J Radiol 81:2507–2512

    Article  PubMed  Google Scholar 

  • Kin M, Torimura T, Ueno T, Inuzuka S, Tanikawa K (1994) Sinusoidal capillarization in small hepatocellular carcinoma. Pathol Int 44:771–778

    Article  CAS  PubMed  Google Scholar 

  • Kitagawa K, Matsui O, Kadoya M, Takashima T, Kawamori Y, Yamahana T, Kidani H et al (1991) Hepatocellular carcinomas with excessive copper accumulation: CT and MR findings. Radiology 180:623–628

    Article  CAS  PubMed  Google Scholar 

  • Kitamoto M, Nakanishi T, Kira S, Kawaguchi M, Nakashio R, Suemori S, Kajiyama G et al (1993) The assessment of proliferating cell nuclear antigen immunohistochemical staining in small hepatocellular carcinoma and its relationship to histologic characteristics and prognosis. Cancer 72:1859–1865

    Article  CAS  PubMed  Google Scholar 

  • Ko CJ, Chien SY, Chou CT, Chen LS, Chen ML, Chen YL (2011) Factors affecting prognosis of small hepatocellular carcinoma in Taiwanese patients following hepatic resection. Can J Gastroenterol 25:485–491

    Google Scholar 

  • Koda M, Murawaki Y, Mitsuda A, Ohyama K, Horie Y, Suou T, Kawasaki H, Ikawa S (2000) Predictive factors for intrahepatic recurrence after percutaneous ethanol injection therapy for small hepatocellular carcinoma. Cancer 88:529–537

    Article  CAS  PubMed  Google Scholar 

  • Köhn K (1956) Über das Vorkommen von Mikrocarcinomen in cirrhotischen Lebern. Z Krebsforsch 61:350–363

    Article  PubMed  Google Scholar 

  • Kojiro M (1998) Pathology of early hepatocellular carcinoma: progression from early to advanced. Hepatogastroenterology 45(suppl 3):1203–1205

    PubMed  Google Scholar 

  • Kojiro M (2000) Premalignant lesions of hepatocellular carcinoma: pathologic viewpoint. J Hepatobiliary Pancreat Surg 7:535–541

    Article  CAS  PubMed  Google Scholar 

  • Kojiro M (2004) Focus on dysplastic nodules and early hepatocellular carcinoma: an Eastern point of view. Liver Transpl 10(suppl 1):S3–S8

    Article  PubMed  Google Scholar 

  • Kojiro M (2005) Histopathology of liver cancers. Best Pract Res Clin Gastroenterol 19:39–62

    Article  PubMed  Google Scholar 

  • Kojiro M (2010) Pathological diagnosis at early stage: reaching international consensus. Oncology 78(suppl 1):31–35

    Article  PubMed  Google Scholar 

  • Kojiro M, Roskams T (2005) Early hepatocellular carcinoma and dysplastic nodules. Semin Liver Dis 25:133–142

    Article  PubMed  Google Scholar 

  • Kojiro M, Yano H, Nakashima O (1996) Pathology of early hepatocellular carcinoma: progression from early to advanced. Semin Surg Oncol 12:197–203

    Article  CAS  PubMed  Google Scholar 

  • Komatsu S, Murakami M, Fukumoto T, Hori Y, Hishikawa Y, Ku Y (2011) Risk factors for survival and local recurrence after particle radiotherapy for single small hepatocellular carcinoma. Br J Surg 98:558–564

    Article  CAS  PubMed  Google Scholar 

  • Kondo Y, Niwa Y, Akikusa B, Takazawa H, Okubayashi A (1983) A histopathologic study of early hepatocellular carcinoma. Cancer 52:687–692

    Article  CAS  PubMed  Google Scholar 

  • Kondo F, Hirooka N, Wada K, Kondo Y (1987) Morphological clues for the diagnosis of small hepatocellular carcinoma. Virchows Arch A Pathol Anat Histopathol 411:15–21

    Article  CAS  PubMed  Google Scholar 

  • Kondo F, Kondo Y, Nagato Y, Tomizawa M, ada K (1994) Interstitial tumour cell invasion in small hepatocellular carcinoma. Evaluation in microscopic and low magnification views. J Gastroenterol Hepatol 9:604–612

    Article  CAS  PubMed  Google Scholar 

  • Korpraphong P, Leyendecker JR, Hildebolt CF, Narra V, Bae KT, Brown JJ (2009) Serial MR imaging of small arterially-enhancing liver lesions in patients with chronic liver disease. J Med Assoc Thai 92:548–555

    PubMed  Google Scholar 

  • Kudo M, Hirasa M, Takakuwa H, Ibuki Y, Fujimi K, Miyamura M, Tomita S, Komori H et al (1986) Small hepatocellular carcinomas in chronic liver disease: detection with SPECT. Radiology 159:697–703

    Article  CAS  PubMed  Google Scholar 

  • Kumagi T, Horiike N, Abe M, Kurose K, Iuchi H, Matsumoto T, Joko K, Akbar SF et al (2005) Small hepatocellular carcinoma associated with Wilson’s disease. Intern Med 44:439–443

    Article  PubMed  Google Scholar 

  • Larsson A, Johansson ME, Wangefjord S, Gaber A, Nodin B, Kucharzewska P, Welinder C et al (2011) Overexpression of podocalyxin-like protein is an independent factor of poor prognosis in colorectal cancer. Br J Cancer 105:666–672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lencioni R, Cioni D, Crocetti L, Franchini C, Pina CD, Lera J, Bartolozzi C (2005) Early-stage hepatocellular carcinoma in patients with cirrhosis: long-term results of percutaneous image-guided radiofrequency ablation. Radiology 234:961–967

    Article  PubMed  Google Scholar 

  • Leoni S, Piscaglia F, Righini R, Bolondi L (2006) Management of small hepatocellular carcinoma. Acta Gastroenterol Belg 69:230–235

    CAS  PubMed  Google Scholar 

  • Liao CS, Yang KC, Yen AM, Chen LS, Chen TH (2006) Remission, relapse, and metastasis/death of small hepatocellular carcinoma treated with percutaneous ethanol injection. Cancer J 12:194–200

    Article  PubMed  Google Scholar 

  • Libbrecht L, Severi T, Cassiman D, Borght SV, Pirenne J, Nevens F, Verslype C et al (2006) Glypican-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules. Am J Surg Pathol 30:1405–1411

    Article  PubMed  Google Scholar 

  • Lim JH, Choi D, Cho SK, Kim SH, Lee WJ, Lim HK, Park CK, Paik SW, Kim YI (2001) Conspicuity of hepatocellular nodular lesions in cirrhotic livers at ferumoxides-enhanced MR imaging: importance of Kupffer cell number. Radiology 220:669–676

    Article  CAS  PubMed  Google Scholar 

  • Liu QY, Huang SQ, Chen JY, Li HG, Gao M, Liu C, Liang BL (2010) Small hepatocellular carcinoma with bile duct tumor thrombi: CT and MRI findings. Abdom Imaging 35:537–542

    Article  PubMed  Google Scholar 

  • Liu QY, Lai DM, Liu C, Zhang L, Zhang WD, Li HG, Gao M (2011) A special recurrent pattern in small hepatocellular carcinoma after treatment: bile duct tumor thrombus formation. World J Gastroenterol 17:4817–4824

    Article  PubMed  PubMed Central  Google Scholar 

  • Livraghi T, Sangalli G, Giordano F, Ravetto C, Solbiati L, Fornari F, Cavanna L, Matricardi L et al (1987) 240 hepatocellular carcinomas: ultrasound features, tumor size, cytologic and histologic patterns, serum alpha-fetoprotein and HBs Ag. Tumori 73:507–512

    CAS  PubMed  Google Scholar 

  • Llovet JM, Bruix J, Gores GJ (2000) Surgical resection versus transplantation for early hepatocellular carcinoma: clues for the best strategy. Hepatology 31:1019–1021

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Chen Y, Wurmbach E, Roayaie S, Fiel MI, Schwartz M, Thung SN et al (2006) A molecular signature to discriminate dysplastic nodules from early hepatocellular carcinoma in HCV cirrhosis. Gastroenterology 131:1758–1767

    Article  CAS  PubMed  Google Scholar 

  • Long J, Lang ZW, Wang HG, Wang TL, Wang BE, Liu SQ (2010) Glutamine synthetase as an early marker for hepatocellular carcinoma based on proteomic analysis of resected small hepatocellular carcinomas. Hepatobiliary Pancreat Dis Int 9:296–305

    CAS  PubMed  Google Scholar 

  • Lu XY, Xi T, Lau WY, Dong H, Xian ZH, Yu H, Zhu Z, Shen F, Wu C, Cong WM (2011) Pathobiological features of small hepatocellular carcinoma: correlation between tumor size and biological behavior. J Cancer Res Clin Oncol 137:567–575

    Article  PubMed  Google Scholar 

  • Lv P, Lin XZ, Li J, Li W, Chen K (2011) Differentiation of small hepatic hemangioma from small hepatocellular carcinoma: recently introduced spectral CT method. Radiology 259:720–729

    Article  PubMed  Google Scholar 

  • Maeda T, Adachi E, Kajiyama K, Takenaka K, Honda H, Sugimachi K, Tsuneyoshi M (1995) CD34 expression in endothelial cells of small hepatocellular carcinoma: its correlation with tumour progression and angiographic findings. J Gastroenterol Hepatol 10:650–654

    Article  CAS  PubMed  Google Scholar 

  • Maeda T, Takenaka K, Taguchi K, Kajiyama K, Shirabe K, Shimada M, Honda H, Sugimachi K (2000a) Small hepatocellular carcinoma with minute satellite nodules. Hepatogastroenterology 47:1063–1066

    CAS  PubMed  Google Scholar 

  • Maeda T, Takenaka K, Taguchi K, Kajiyama K, Shirabe K, Shimada M, Tsuneyoshi M et al (2000b) Clinicopathological characteristics of surgically resected minute hepatocellular carcinomas. Hepatogastroenterology 47:498–503

    CAS  PubMed  Google Scholar 

  • Mahmood K, Schatzki PF (1976) Solitary small hepatocellular carcinoma. Am J Dig Dis 21:496–502

    Article  CAS  PubMed  Google Scholar 

  • Makuuchi M, Hasegawa H, Yamazaki S, Bandai Y, Watanabe G, Ito T (1983) Ultrasonic characteristics of the small hepatocellular carcinoma. Ultrasound Med Biol (suppl.2): 489–491

    Google Scholar 

  • Mas VR, Maluf DG, Archer KJ, Yanek K, Williams B, Fisher RA (2006) Differentially expressed genes between early and advanced hepatocellular carcinoma (HCC) as a potential tool for selecting liver transplant recipients. Mol Med 12:97–104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyaaki H, Fujimoto M, Kurogi M, Nakashima O, Eguchi K, Kojiro M (2005) Pathomorphological study on small nodular lesions in hepatitis C virus-related cirrhosis. Oncol Rep 14:1469–1474

    PubMed  Google Scholar 

  • Moribata K, Tamai H, Shingaki N, Mori Y, Enomoto S, Shiraki T, Deguchi H, Ueda K et al (2011) Assessment of malignant potential of small hypervascular hepatocellular carcinoma using B-mode ultrasonography. Hepatol Res 41:233–239

    Article  PubMed  Google Scholar 

  • Muramatsu Y, Moriyama N, Takayasu K, Yamada T, Hasegawa H, Kishi K (1985) A case of minute hepatocellular carcinoma with calcification (in Japanese). Ronsho Hoshasen 30:129–132

    CAS  Google Scholar 

  • Nagasue N, Kohno H, Chang YC, Galizia G, Hayashi T, Yukaya H, Nakamura T (1989) Intraoperative ultrasonography in resection of small hepatocellular carcinoma associated with cirrhosis. Am J Surg 158:40–42

    Article  CAS  PubMed  Google Scholar 

  • Nakano M, Saito A, Takasaki K, Obata H, Kobayashi S (1990) A histopathologic study of early hepatocellular carcinoma: portal tract invasion and progression to advanced hepatocellular carcinoma. Acta Hepatol Jpn 31:754–762

    Article  Google Scholar 

  • Nakanuma Y, Ohta G (1984) Small hepatocellular carcinoma containing many Mallory bodies. Liver 4:128–133

    Article  CAS  PubMed  Google Scholar 

  • Nakashima T, Sakamoto K, Okuda K (1977) A minute hepatocellular carcinoma found in a liver with Clonorchis sinensis infection: report of two cases. Cancer 39:1306–1311

    Article  CAS  PubMed  Google Scholar 

  • Nakashima T, Okuda K, Kojiro M, Jimi A, Yamaguchi R, Sakamoto K, Ikari T (1983) Pathology of hepatocellular carcinoma in Japan. 232 consecutive cases autopsied in ten years. Cancer 51:863–877

    Article  CAS  PubMed  Google Scholar 

  • Nakashima O, Sugihara S, Kage M, Kojiro M (1995) Pathomorphologic characteristics of small hepatocellular carcinoma: a special reference to small hepatocellular carcinoma with indistinct margins. Hepatology 22:101–105

    CAS  PubMed  Google Scholar 

  • Nakashima Y, Nakashima O, Tanaka M, Okuda K, Nakashima M, Kojiro M (2003) Portal vein invasion and intrahepatic micrometastases in small hepatocellular carcinoma by gross type. Hepatol Res 26:142–147

    Article  PubMed  Google Scholar 

  • Nathan H, Schulick RD, Choti MA, Pawlik TM (2009) Predictors of survival after resection of early hepatocellular carcinoma. Ann Surg 249:799–805

    Article  PubMed  Google Scholar 

  • Noguchi H, Hirai K, Itano S, Ijuin H, Kajiwara M, Sakata K, Ono N, Hidaka R, Aritaka T et al (1994) Small hepatocellular carcinoma with intravascular tumor growth into the right atrium. J Gastroenterol 29:41–46

    Article  CAS  PubMed  Google Scholar 

  • Nonomura T, Masaki T, Morishita A, Jian G, Uchida N, Himoto T, Izuishi K, Iwama H et al (2007) Identification of c-Yes expression in the nuclei of hepatocellular carcinoma cells: involvement in the early stages of hepatocarcinogenesis. Int J Oncol 30:105–111

    CAS  PubMed  Google Scholar 

  • O’Malley ME, Takayama Y, Sherman M (2005) Outcome of small (10–20 mm) arterial phase-enhancing nodules seen on triphasic liver CT in patients with cirrhosis or chronic liver disease. Am J Gastroenterol 100:1523–1528

    Article  PubMed  Google Scholar 

  • Ohnishi K, Tanabe Y, Ryu M, Isono K, Yamamoto Y, Usui S, Hiyama Y, Goto N, Iwama S et al (1987) Prognosis of hepatocellular carcinoma smaller than 5 cm in relation to treatment: study of 100 patients. Hepatology 7:1285–1290

    Article  CAS  PubMed  Google Scholar 

  • Ohnishi H, Sakaguchi K, Nouso K, Kobayashi Y, Nakamura S, Tanaka H, Miyake Y et al (2010) Outcome of small liver nodules detected by computed tomographic angiography in patients with hepatocellular carcinoma. Hepatol Int 4:562–568

    Article  PubMed  PubMed Central  Google Scholar 

  • Ohno Y, Shiga J, Machinami R (1990) A histopathological analysis of five cases of adenomatous hyperplasia containing minute hepatocellular carcinoma. Acta Pathol Jpn 40:267–278

    CAS  PubMed  Google Scholar 

  • Okazaki N, Yoshino M, Yoshida T, Suzuki M, Moriyama N, Takayasu K, Makuuchi M et al (1989) Evaluation of the prognosis for small hepatocellular carcinoma based on tumor volume doubling time. A preliminary report. Cancer 63:2207–2210

    Article  CAS  PubMed  Google Scholar 

  • Okita K (2006) Clinical aspects of hepatocellular carcinoma in Japan. Intern Med 45:229–233

    Article  PubMed  Google Scholar 

  • Okuda K, Kotoda K, Obata H, Hayashi N, Hisamitsu T (1975) Clinical observations during a relatively early stage of hepatocellular carcinoma, with special reference to serum alpha-fetoprotein levels. Gastroenterology 69:226–234

    CAS  PubMed  Google Scholar 

  • Okuda K, Nakashima T, Obata H, Kubo Y (1977) Clinicopathological studies of minute hepatocellular carcinoma. Analysis of 20 cases, including 4 with hepatic resection. Gastroenterology 73:109–115

    CAS  PubMed  Google Scholar 

  • Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H, Nakajima Y, Ohnishi K (1985) Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 56:918–928

    Article  CAS  PubMed  Google Scholar 

  • Pancoska P, De Giorgio M, Fagiulo S, Carr BI (2011) Small HCCs identified by screening. Dig Dis Sci 56:3078–3085

    Article  PubMed  Google Scholar 

  • Park YN (2005) Pathology of hepatocellular carcinoma: recent update (in Korean). Korean J Gastroenterol 45:227–233

    PubMed  Google Scholar 

  • Park YN (2011) Update on precursor and early lesions of hepatocellular carcinomas. Arch Pathol Lab Med 135:704–715

    Article  PubMed  CAS  Google Scholar 

  • Pauleit D, Textor J, Bachmann R, Conrad R, Flacke S, Layer G, Kreft B, Schild H (2002) Hepatocellular carcinoma: detection with gadolinium-and ferumoxides-enhanced MR imaging of the liver. Radiology 222:73–80

    Article  PubMed  Google Scholar 

  • Pompili M, Rapaccini GL, Covino M, Pignataro G, Caturelli E, Siena DA, Villani MR et al (2001) Prognostic factors for survival in patients with compensated cirrhosis and small hepatocellular carcinoma after percutaneous ethanol injection therapy. Cancer 92:126–135

    Article  CAS  PubMed  Google Scholar 

  • Rim KS, Sakamoto M, Watanabe H, Matsuno Y, Nakanishi Y, Mukai K, Hirohashi S (1993) Pathology and DNA cytophotometry of small hepatocellular carcinoma with a nodule-in-nodule appearance- evidence for stepwise progression of hepatocellular carcinoma. Jpn J Clin Oncol 23:26–33

    CAS  PubMed  Google Scholar 

  • Roncalli M, Park YN, Di Tommaso L (2010) Histopathological classification of hepatocellular carcinoma. Dig Liver Dis 42(suppl 3):S228–S234

    Article  PubMed  Google Scholar 

  • Roncalli M, Terracciano L, Di Tommaso L, David E, Colombo M, Gruppo Italiano Patologi Apparato Digerente (GIPAD) et al (2011) Liver precancerous lesions and hepatocellular carcinoma: the histology report. Dig Liver Dis 43(suppl 4):S361–S372

    Article  PubMed  Google Scholar 

  • Roskams T, Kojiro M (2010) Pathology of early hepatocellular carcinoma: conventional and molecular diagnosis. Semin Liver Dis 30:17–25

    Article  PubMed  Google Scholar 

  • Sakamoto M (2009) Early HCC: diagnosis and molecular markers. J Gastroenterol 44(suppl 19):108–111

    Article  CAS  PubMed  Google Scholar 

  • Sanuki-Fujimoto N, Takeda A, Ohashi T, Kunieda E, Iwabuchi S, Takatsuka K, Koike N et al (2010) CT evaluation of focal liver reactions following stereotactic body radiotherapy for small hepatocellular carcinoma with cirrhosis: relationship between imaging appearance and baseline liver function. Br J Radiol 83:1063–1071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sasaki Y, Imaoka S, Ishiguro S, nakano H, Kasugai H, Fujita M, Inoue E, Ishikawa O et al (1996) Clinical features of small hepatocellular carcinomas as assessed by histologic grades. Surgery 119:252–260

    Article  CAS  PubMed  Google Scholar 

  • Seki S, Sakaguchi H, Kawakita N, Yanai A, Tamori A, Yabusako T, Nishiguchi S, Kuroki T et al (1993) Detection of the preneoplastic lesions of small hepatocellular carcinoma in cirrhotic livers. J Gastroenterol Hepatol 8:582–589

    Article  CAS  PubMed  Google Scholar 

  • Seror O, N’kontchou G, Tin Tin Htar M, Durand-Zaleski I, Trinchet JC, Sellier N, Beaugrand M (2006) Ethanol versus radiofrequency ablation for treatment of small hepatocellular carcinoma in patients with cirrhosis. Gastroenterol Clin Biol 30:1265–1273

    Article  PubMed  Google Scholar 

  • Sherman M (2005) Diagnosis of small hepatocellular carcinoma. Hepatology 42:14–16

    Article  PubMed  Google Scholar 

  • Sherman M (2010) Optimum imaging for small suspected hepatocellular carcinoma. Gut 59:570–571

    Article  PubMed  Google Scholar 

  • Shinagawa T, Ohto M, Kimura K, Tsunetomi S, Morita M, Saisho H, Tsuchiya Y, Okuda K et al (1982) Clinical features of small hepatocellular carcinoma (in Japanese). Nihon Shokakibyo Gakkai Zasshi 79:2277–2284

    CAS  PubMed  Google Scholar 

  • Shinagawa T, Ohto M, Kimura K, Tsunetomi S, Morita M, Saisho H, Tsuchiya Y, Saotome N et al (1984) Diagnosis and clinical features of small hepatocellular carcinoma with emphasis on the utility of real-time ultrasonography. A study 0f 51 patients. Gastroenterology 86:495–502

    CAS  PubMed  Google Scholar 

  • Shirabe K, Kanematsu T, Matsumata T, Adachi E, Akazawa K, Sugimachi K (1991) Factors linked to early recurrence of small hepatocellular carcinoma after hepatectomy: univariate and multivariate analyses. Hepatology 14:802–805

    Article  CAS  PubMed  Google Scholar 

  • Sohda T, Kamimura S, Iwata K, Shijo H, Okumura M (1997) Immunohistochemical evidence of insulin-like growth factor II in human small hepatocellular carcinoma with hepatitis C virus infection: relationship to fatty change in carcinoma cells. J Gastroenterol Hepatol 12:224–228

    Article  CAS  PubMed  Google Scholar 

  • Sugihara S, Nakashima O, Kojiro M, Majima Y, Tanaka M, Tanikawa K (1992) The morphologic transition in hepatocellular carcinoma. A comparison of the individual histologic features disclosed by ultrasound-guided fine-needle biopsy with those of autopsy. Cancer 70:1488–1492

    Article  CAS  PubMed  Google Scholar 

  • Suh KS (2005) Systematic hepatectomy for small hepatocellular carcinoma in Korea. J Hepatobiliary Pancreat Surg 12:365–370

    Article  PubMed  Google Scholar 

  • Sumida M, Ohto M, Ebara M, Kimura K, Okuda K, Hirooka N (1986) Accuracy of angiography in the diagnosis of small hepatocellular carcinoma. AJR Am J Roentgenol 147:531–536

    Article  CAS  PubMed  Google Scholar 

  • Sun HY, Lee JM, Shin CI, Lee DH, Moon SK, Kim KW, Han JK, Choi BI (2010) Gadoxetic acid-enhanced magnetic resonance imaging for differentiating small hepatocellular carcinomas (< or = 2 cm in diameter) from arterial enhancing pseudolesions: special emphasis on hepatobiliary phase imaging. Invest Radiol 45:96–103

    Article  CAS  PubMed  Google Scholar 

  • Suriawinata A, Thung SN (2010) Molecular signature of early hepatocellular carcinoma. Oncology 78(suppl1):36–39

    Article  CAS  PubMed  Google Scholar 

  • Takashima T, Matsui O (1980) Infusion hepatic angiography in the detection of small hepatocellular carcinomas. Radiology 136:321–325

    Article  CAS  PubMed  Google Scholar 

  • Takashima T, Matsui O, Suzuki M, Ida M (1982) Diagnosis and screening of small hepatocellular carcinoma. Comparison of radionuclide imaging, ultrasound, computed tomography, hepatic angiography, and alpha 1-fetoprotein assay. Radiology 145:635–638

    Article  CAS  PubMed  Google Scholar 

  • Takayama T, Makuuchi M, Hirohashi S, Sakamoto M, Yamamoto J, Shimada K, Kosuge T et al (1998) Early hepatocellular carcinoma as an entity with a high rate of surgical cure. Hepatology 28:1241–1246

    Article  CAS  PubMed  Google Scholar 

  • Tan Y, Yin P, Tang L, Xing W, Huang Q, Cao D, Zhao X, Wang W, Lu X, Xu Z, Wang H et al (2012) Metabolomics study of stepwise hepatocarcinogenesis from the model rats to patients: potential biomarkers effective for small hepatocellular carcinoma diagnosis. Mol Cell Proteomics 11:M111.010694

    Article  PubMed  CAS  Google Scholar 

  • Tanaka S, Kitamura T, Nakanishi K, Okuda S, Kojima J, Fujimoto I (1989) Recent advances in ultrasonographic diagnosis of hepatocellular carcinoma. Cancer 63:1313–1317

    Article  CAS  PubMed  Google Scholar 

  • Tang ZY, Yu YQ, Zhou XD, Ma ZC, Yang R, Lu JZ, Lin ZY, Yang BH (1989) Surgery of small hepatocellular carcinoma. Analysis of 144 cases. Cancer 64:536–541

    Article  CAS  PubMed  Google Scholar 

  • Tang ZY, Yu YQ, Zhou XD, Yang BH, Ma ZC, Lin ZY (1993) Subclinical hepatocellular carcinoma: an analysis of 391 patients. J Surg Oncol Suppl 3:55–58

    Article  CAS  PubMed  Google Scholar 

  • Tang Y, Yamashita Y, Arakawa A, Namimoto T, Mitsuzaki K, Abe Y, Katahira K, Takahashi M (1999) Detection of hepatocellular carcinoma arising in cirrhotic livers: comparison of gadolinium-and ferumoxides-enhanced MR imaging. AJR Am J Roentgenol 172:1547–1554

    Article  CAS  PubMed  Google Scholar 

  • Terada T, Nakanuma Y (1992) Cell proliferative activity in adenomatous hyperplasia of the liver and small hepatocellular carcinoma. An immunohistochemical study demonstrating proliferating cell nuclear antigen. Cancer 70:591–598

    Article  CAS  PubMed  Google Scholar 

  • Terada T, Nakanuma Y, Kawai K (1989) Small hepatocellular carcinoma presenting as intrabiliary pedunculated polyp and obstructive jaundice. J Clin Gastroenterol 11:578–583

    Article  CAS  PubMed  Google Scholar 

  • Teratani T, Yoshida H, Shiina S, Obi S, Sato S, Koike Y, Hamamura K, Akamatsu M et al (2004) A novel display of reconstruction computed tomography for the detection of small hepatocellular carcinoma. Liver Int 24:619–624

    Article  PubMed  Google Scholar 

  • Than KW, Okayasu I, Akashi T (1995) Histopathological and immunohistochemical analysis of adenomatous hyperplasia and hepatocellular carcinoma: cellularity, thickness of cell cord, and Ki-67 proliferative activity. Bull Tokyo Med Dent Univ 42:67–81

    CAS  PubMed  Google Scholar 

  • Theise ND, Curado MP, Franceschi S, Hytiroglou P, Kudo M, Park YN, Sakamoto M et al (2010) Hepatocellular carcinoma. WHO Classification of tumours of the digestive system. IARC, Lyon, pp 214–215

    Google Scholar 

  • Toyoda H, Kumada T, Nakano S, Takeda I, Sugiyama K, Kiriyama S, Sone Y, Hisanaga Y (2001) Characteristics and course of small hepatocellular carcinomas in patients with hepatitis C virus types 1 and 2. J Med Virol 63:120–127

    Article  CAS  PubMed  Google Scholar 

  • Tremosini S, Forner A, Boix L, Vilana R, Bianchi L, Reig M, Rimola J, Rodriguez-Lope C et al (2012) Prospective validation of an immunohistochemical panel (glypican 3, heat shock protein 70 and glutamine synthetase) in liver biopsies for diagnosis of very early hepatocellular carcinoma. Gut 61:1481–1487

    Article  PubMed  Google Scholar 

  • Tsunetomi S, Ohto M, Iino Y, Shinagawa T, Kimura K, Morita M, Saisho H, Tsuchiya Y et al (1989) Diagnosis of small hepatocellular carcinoma by computed tomography: correlation of CT findings and histopathology. J Gastroenterol Hepatol 4:395–404

    Article  CAS  PubMed  Google Scholar 

  • Uchida T (1995) Small hepatocellular carcinoma: its relationship to multistep hepatocarcinogenesis. Pathol Int 45:175–184

    Article  CAS  PubMed  Google Scholar 

  • Utsunomiya T, Shimada M, Taguchi KI, Hasegawa H, Yamashita Y, Hamatsu T, Aishima SI et al (2000) Clinicopathologic features and postoperative prognosis of multicentric small hepatocellular carcinoma. J Am Coll Surg 190:331–335

    Article  CAS  PubMed  Google Scholar 

  • Vilana R, Bruix J, Bru C, Ayuso C, Sole M, Rodes J (1992) Tumor size determines the efficacy of percutaneous ethanol injection for the treatment of small hepatocellular carcinoma. Hepatology 16:353–357

    Article  CAS  PubMed  Google Scholar 

  • Wakasa K, Sakurai M, Okamura J, Kuroda C (1985) Pathological study of small hepatocellular carcinoma: frequency of their invasion. Virchows Arch A Pathol Anat Histopathol 407:259–270

    Article  CAS  PubMed  Google Scholar 

  • Wang JH, Lu SN, Hung CH, Chen TY, Chen CH, Changchien CS, Lee CM (2006) Small hepatic nodules (< or = 2 cm) in cirrhosis patients: characterization with contrast-enhanced ultrasonography. Liver Int 26:928–934

    Article  PubMed  Google Scholar 

  • Wang F, Jing X, Wang T, Li G, Zhang Q, Huang Y, Li J, Wang Y, Gao Y, Han T et al (2012) Differential diagnostic value of GPC3-CD34 combined staining in small liver nodules with diameter less than 3 cm. Am J Clin Pathol 137:937–945

    Article  PubMed  Google Scholar 

  • Ward J, Guthrie JA, Scott DJ, Atchley J, Wilson D, Davies MH, Wyatt JI, Robinson PJ (2000) Hepatocellular carcinoma in the cirrhotic liver: double-contrast MR imaging for diagnosis. Radiology 216:154–162

    Article  CAS  PubMed  Google Scholar 

  • Watanabe A, Sakata T, Shiota T, Nagashima H (1984) Hepatocellular carcinoma of small size. Am J Med Sci 288:151–157

    Article  CAS  PubMed  Google Scholar 

  • Watanabe A, Yamamoto H, Ito T, Nagashima H (1986) Diagnosis, treatment and prognosis of small hepatocellular carcinoma. Hepatogastroenterology 33:52–55

    CAS  PubMed  Google Scholar 

  • Wee A (2011) Fine-needle aspiration biopsy of hepatocellular carcinoma and related hepatocellular nodular lesions in cirrhosis: controversies, challenges, and expectations. Pathol Res Int 2011:587936

    Article  Google Scholar 

  • Wu FS, Zhao WH, Liang TB, Ma ZM, Teng LS, Wang M, Zheng SS (2005) Survival factors after resection of small hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 4:379–384

    PubMed  Google Scholar 

  • Yamada N, Shinzawa H, Ukai K, Wakabayashi H, Togashi H, Takahashi T, Seo N et al (1993) Subcutaneous seeding of small hepatocellular carcinoma after fine needle aspiration biopsy. J Gastroenterol Hepatol 8:195–198

    Article  CAS  PubMed  Google Scholar 

  • Yamagata M, Masaki T, Okudaira T, Imai Y, Shiina S, Shiratori Y, Omata M (1999) Small hyperechoic nodules in chronic liver diseases include hepatocellular carcinomas with low cyclin D1 and Ki-67 expression. Hepatology 29:1722–1729

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto T, Ikebe T, Mikami S, Shuto T, Hirohashi K, Kinoshita H, Sakurai M (1996) Immunohistochemistry and angiography in adenomatous hyperplasia and small hepatocellular carcinomas. Pathol Int 46:364–371

    Article  CAS  PubMed  Google Scholar 

  • Yamasaki S, Hasegawa H, Makuuchi M (1981) Clinico-pathological observation of the minute liver cancer and the new methods of hepatectomy – analysis of 27 resected cases. Acta Hepatol Jpn 22:1714–1724

    Article  Google Scholar 

  • Yamashita Y, Tsuijita E, Takeishi K, Fujiwara M, Kira S, Mori M, Aishima S, Taketomi A et al (2012) Predictors for microinvasion of small hepatocellular carcinoma <= 2 cm. Ann Surg Oncol 19:2027–2034

    Article  PubMed  Google Scholar 

  • Yoshida T, Okazaki N, Yoshino M, Kitaoka H, Hirohashi S, Shimozato Y (1982) Minute hepatocellular carcinoma without appreciable change in size for seven years: a case report. Cancer 19:1491–1495

    Article  Google Scholar 

  • Yoshino M (1983) Growth kinetics of hepatocellular carcinoma. Jpn J Clin Oncol 13:45–52

    CAS  PubMed  Google Scholar 

  • Yu YQ, Tang ZY, Zhou XD (1980) Experience in resection of small hepatocellular carcinoma. Chin Med J (Engl) 93:491–494

    CAS  Google Scholar 

  • Yu JS, Lee JH, Chung JJ, Kim JH, Kim KW (2008) Small hypervascular hepatocellular carcinomas: limited value of portal and delayed phases of dynamic magnetic resonance imaging. Acta Radiol 49:735–743

    Article  CAS  PubMed  Google Scholar 

  • Yu JS, Chung JJ, Kim JH, Kim KW (2009) Small hypervascular hepatocellular carcinomas; value of “washout’ on gadolinium-enhanced dynamic MR imaging compared to superparamagnetic iron oxide-enhanced imaging. Eur Radiol 19:2614–2622

    Article  PubMed  Google Scholar 

  • Yu MC, Lee YS, Lin SE, Wu HY, Chen TC, Lee WC, Chen MF, Tsai CN (2012) Recurrence and poor prognosis following resection of small hepatitis B-related hepatocellular carcinoma lesions are associated with aberrant tumor expression profiles of glypican 3 and osteopontin. Ann Surg Oncol 19(suppl 3):S455–S463

    Article  PubMed  Google Scholar 

  • Zeppa P, Vetrani A, Palombini L, Chiacchio R, Zabatta A, De Sio I, Castellano L, Calandra M et al (1993) Evolution of DNA content in small and well-differentiated hepatocarcinoma. Anal Quant Cytol Histol 15:12–22

    CAS  PubMed  Google Scholar 

  • Zhang YJ, Chen MS (2010) Role of radiofrequency ablation in the treatment of small hepatocellular carcinoma. World J Hepatol 2:146–150

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhaoyou T, Yegin Y, Zhiying L, Xinda Z, Binghui Y, Yunzhen C, Jizhen L, Chenlong T (1979) Small hepatocellular carcinoma: clinical analysis of 30 cases. Chin Med J (Engl) 92:455–462

    CAS  Google Scholar 

  • Zhou XD, Tang ZY, Yu YQ, Ma ZC, Yang BH, Lu JZ, Lin ZY, Wang J (1991) Solitary minute hepatocellular carcinoma. A study of 14 patients. Cancer 67:2855–2858

    Article  CAS  PubMed  Google Scholar 

  • Zhou YM, Yang JM, Li B, Yin ZF, Xu F, Wang B, Xu W, Kan T (2010) Risk factors for early recurrence of small hepatocellular carcinoma after curative resection. Hepatobiliary Pancreat Dis Int 9:33–37

    PubMed  Google Scholar 

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    Arthur Zimmermann

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Zimmermann, A. (2017). Early or Small Hepatocellular Carcinoma. In: Tumors and Tumor-Like Lesions of the Hepatobiliary Tract. Springer, Cham. https://doi.org/10.1007/978-3-319-26956-6_8

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