Download PDF
Z Gastroenterol 2009; 47(1): 30-36
DOI: 10.1055/s-0028-1109088
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Neue Entwicklungen in der Biopsiediagnostik früher und unklarer Lebertumoren

Recent developments in Biopsy Diagnosis of Early and Undefined Liver TumorsT. Longerich1 , P. Schirmacher1
  • 1Pathologisches Institut, Universität Heidelberg
Further Information

Publication History

Manuskript eingetroffen: 14.10.2008

Manuskript akzeptiert: 11.12.2008

Publication Date:
20 January 2009 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die bioptische Diagnostik früher und hochdifferenzierter Lebertumoren stellt besondere Anforderungen, denen die moderne Pathologie in vielfältiger Weise gerecht wird. So wurden differenzierte morphologische Algorithmen und neue immunhistologische Marker zur Differenzialdiagnose des hochdifferenzierten HCC und eine neue prognostisch relevante, molekularpathologische und histologische Klassifikation des Leberzelladenoms entwickelt. Durch diese neuen diagnostischen Werkzeuge gelingt es heute unter Einbeziehung der „Matrixdiagnostik” bei fast allen dieser schwierigen Fälle eine zuverlässige diagnostische Einstufung zu erreichen.

Abstract

Biopsy diagnosis of early and highly differentiated liver tumors is difficult and complex. Modern pathology has met this challenge by several different means; elaborate morphological algorithms and novel immunohistological markers support the differential diagnosis of highly differentiated HCC and a new, predictive molecular pathological and histological classification of liver cell adenoma was developed. By these new diagnostic tools together with the so-called ‘matrix diagnosis’ a reliable diagnostic classification is now feasible in the vast majority of these difficult cases.

Schlüsselwörter

Leberbiopsie - Diagnose - Klassikation - Marker - Lebertumoren

Key words

liver biopsy - diagnosis - classification - marker - liver tumor

Literatur

  • 1 Giorgio A, Tarantino L, Stefano de G. et al . Complications after interventional sonography of focal liver lesions: a 22-year single-center experience.  J Ultrasound Med. 2003;  22 193-205
    Google Scholar
  • 2 Stigliano R, Marelli L, Yu D. et al . Seeding following percutaneous diagnostic and therapeutic approaches for hepatocellular carcinoma. What is the risk and the outcome? Seeding risk for percutaneous approach of HCC.  Cancer treatment reviews. 2007;  33 437-447
    Google Scholar
  • 3 Navarro F, Taourel P, Michel J. et al . Diaphragmatic and subcutaneous seeding of hepatocellular carcinoma following fine-needle aspiration biopsy.  Liver. 1998;  18 251-254
    Google Scholar
  • 4 Fattovich G, Stroffolini T, Zagni I. et al . Hepatocellular carcinoma in cirrhosis: incidence and risk factors.  Gastroenterology. 2004;  127 S35-S50
    Google Scholar
  • 5 Bruix J, Sherman M. Management of hepatocellular carcinoma.  Hepatology. 2005;  42 1208-1236
    Google Scholar
  • 6 Bruix J, Sherman M, Llovet J M. et al . Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver.  J Hepatol. 2001;  35 421-430
    Google Scholar
  • 7 Kudo M, Okanoue T. Management of hepatocellular carcinoma in Japan: consensus-based clinical practice manual proposed by the Japan Society of Hepatology.  Oncology. 2007;  72 (Suppl 1) 2-15
    Google Scholar
  • 8 Ferrell L, Wright T, Lake J. et al . Incidence and diagnostic features of macroregenerative nodules vs. small hepatocellular carcinoma in cirrhotic livers.  Hepatology. 1992;  16 1372-1381
    Google Scholar
  • 9 Theise N D, Schwartz M, Miller C. et al . Macroregenerative nodules and hepatocellular carcinoma in forty-four sequential adult liver explants with cirrhosis.  Hepatology. 1992;  16 949-955
    Google Scholar
  • 10 Roncalli M, Roz E, Coggi G. et al . The vascular profile of regenerative and dysplastic nodules of the cirrhotic liver: implications for diagnosis and classification.  Hepatology. 1999;  30 1174-1178
    Google Scholar
  • 11 Quaglia A, Bhattacharjya S, Dhillon A P. Limitations of the histopathological diagnosis and prognostic assessment of hepatocellular carcinoma.  Histopathology. 2001;  38 167-174
    Google Scholar
  • 12 Schrimacher P, Prange W, Dries V. et al . Highly differentiated hepatocellular tumors. Concepts, criteria, and differential diagnosis.  Pathologe. 2001;  22 407-416
    Google Scholar
  • 13 Roncalli M. Hepatocellular nodules in cirrhosis: Focus on diagnostic criteria on liver biopsy. A Western experience.  Liver Transpl. 2004;  10 S9-S15
    Google Scholar
  • 14 Libbrecht L, Desmet V, Roskams T. Preneoplastic lesions in human hepatocarcinogenesis.  Liver Int. 2005;  25 16-27
    Google Scholar
  • 15 International Working Party . Terminology of nodular hepatocellular lesions. International Working Party.  Hepatology. 1995;  22 983-993
    Google Scholar
  • 16 Wanless I R, Mawdsley C, Adams R. On the pathogenesis of focal nodular hyperplasia of the liver.  Hepatology. 1985;  5 1194-1200
    Google Scholar
  • 17 Paradis V, Benzekri A, Dargere D. et al . Telangiectatic focal nodular hyperplasia: a variant of hepatocellular adenoma.  Gastroenterology. 2004;  126 1323-1329
    Google Scholar
  • 18 Bioulac-Sage P, Rebouissou S, Sa Cunha A. et al . Clinical, morphologic, and molecular features defining so-called telangiectatic focal nodular hyperplasias of the liver.  Gastroenterology. 2005;  128 1211-1218
    Google Scholar
  • 19 Yen Y H, Wang J H, Lu S N. et al . Contrast-enhanced ultrasonographic spoke-wheel sign in hepatic focal nodular hyperplasia.  European journal of radiology. 2006;  60 439-444
    Google Scholar
  • 20 Hussain S M, Terkivatan T, Zondervan P E. et al . Focal nodular hyperplasia: findings at state-of-the-art MR imaging, US, CT, and pathologic analysis.  Radiographics. 2004;  24 3-17; discussion 18 – 19
    Google Scholar
  • 21 Wanless I R, Albrecht S, Bilbao J. et al . Multiple focal nodular hyperplasia of the liver associated with vascular malformations of various organs and neoplasia of the brain: a new syndrome.  Mod Pathol. 1989;  2 456-462
    Google Scholar
  • 22 Ohmoto K, Honda T, Hirokawa M. et al . Spontaneous regression of focal nodular hyperplasia of the liver.  J Gastroenterol. 2002;  37 849-853
    Google Scholar
  • 23 Ishak K G, Goodman Z D, Stocker J T. et al .Benign Hepatocellular Tumors. Tumors of the Liver and Intrahepatic Bile Ducts Washington; Armed Forces Institute of Pathology 2001: 9-48
    Google Scholar
  • 24 Gyorffy E J, Bredfeldt J E, Black W C. Transformation of hepatic cell adenoma to hepatocellular carcinoma due to oral contraceptive use.  Ann Intern Med. 1989;  110 489-490
    Google Scholar
  • 25 Foster J H, Berman M M. The malignant transformation of liver cell adenomas.  Arch Surg. 1994;  129 712-717
    Google Scholar
  • 26 Ito M, Sasaki M, Wen C Y. et al . Liver cell adenoma with malignant transformation: a case report.  World J Gastroenterol. 2003;  9 2379-2381
    Google Scholar
  • 27 Zucman-Rossi J, Jeannot E, Nhieu J T. et al . Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC.  Hepatology. 2006;  43 515-524
    Google Scholar
  • 28 Bioulac-Sage P, Rebouissou S, Thomas C. et al . Hepatocellular adenoma subtype classification using molecular markers and immunohistochemistry.  Hepatology. 2007;  46 740-748
    Google Scholar
  • 29 Rebouissou S, Imbeaud S, Balabaud C. et al . HNF1alpha inactivation promotes lipogenesis in human hepatocellular adenoma independently of SREBP-1 and carbohydrate-response element-binding protein (ChREBP) activation.  J Biol Chem. 2007;  282 14437-14446
    Google Scholar
  • 30 Jeannot E, Poussin K, Chiche L. et al . Association of CYP1B1 germ line mutations with hepatocyte nuclear factor 1alpha-mutated hepatocellular adenoma.  Cancer Res. 2007;  67 2611-2616
    Google Scholar
  • 31 Torbenson M, Lee J H, Choti M. et al . Hepatic adenomas: analysis of sex steroid receptor status and the Wnt signaling pathway.  Mod Pathol. 2002;  15 189-196
    Google Scholar
  • 32 Rebouissou S, Bioulac-Sage P, Zucman-Rossi J. Molecular pathogenesis of focal nodular hyperplasia and hepatocellular adenoma.  J Hepatol. 2008;  48 163-170
    Google Scholar
  • 33 Sa Cunha A, Blanc J F, Lazaro E. et al . Inflammatory syndrome with liver adenomatosis: the beneficial effects of surgical management.  Gut. 2007;  56 307-309
    Google Scholar
  • 34 Lepreux S, Laurent C, Le Bail B. et al . Multiple telangiectatic focal nodular hyperplasia: vascular abnormalities.  Virchows Arch. 2003;  442 226-230. Epub 2003
    Google Scholar
  • 35 Marchio A, Terris B, Meddeb M. et al . Chromosomal abnormalities in liver cell dysplasia detected by comparative genomic hybridisation.  Mol Pathol. 2001;  54 270-274
    Google Scholar
  • 36 Le Bail B, Bernard P H, Carles J. et al . Prevalence of liver cell dysplasia and association with HCC in a series of 100 cirrhotic liver explants.  J Hepatol. 1997;  27 835-842
    Google Scholar
  • 37 Tsuda H, Hirohashi S, Shimosato Y. et al . Clonal origin of atypical adenomatous hyperplasia of the liver and clonal identity with hepatocellular carcinoma.  Gastroenterology. 1988;  95 1664-1666
    Google Scholar
  • 38 Park Y N, Yang C P, Fernandez G J. et al . Neoangiogenesis and sinusoidal “capillarization” in dysplastic nodules of the liver.  Am J Surg Pathol. 1998;  22 656-662
    Google Scholar
  • 39 Takayama T, Makuuchi M, Hirohashi S. et al . Malignant transformation of adenomatous hyperplasia to hepatocellular carcinoma.  Lancet. 1990;  336 1150-1153
    Google Scholar
  • 40 Borzio M, Fargion S, Borzio F. et al . Impact of large regenerative, low grade and high grade dysplastic nodules in hepatocellular carcinoma development.  J Hepatol. 2003;  39 208-214
    Google Scholar
  • 41 Nagato Y, Kondo F, Kondo Y. et al . Histological and morphometrical indicators for a biopsy diagnosis of well-differentiated hepatocellular carcinoma.  Hepatology. 1991;  14 473-478
    Google Scholar
  • 42 Sakamoto M, Hirohashi S, Shimosato Y. Early stages of multistep hepatocarcinogenesis: adenomatous hyperplasia and early hepatocellular carcinoma.  Hum Pathol. 1991;  22 172-178
    Google Scholar
  • 43 Di Tommaso L, Franchi G, Park Y N. et al . Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis.  Hepatology. 2007;  45 725-734
    Google Scholar
  • 44 Garrido C, Gurbuxani S, Ravagnan L. et al . Heat shock proteins: endogenous modulators of apoptotic cell death.  Biochem Biophys Res Commun. 2001;  286 433-442
    Google Scholar
  • 45 Chuma M, Sakamoto M, Yamazaki K. et al . Expression profiling in multistage hepatocarcinogenesis: identification of HSP70 as a molecular marker of early hepatocellular carcinoma.  Hepatology. 2003;  37 198-207
    Google Scholar
  • 46 Lai J P, Sandhu D S, Yu C. et al . Sulfatase 2 up-regulates glypican 3, promotes fibroblast growth factor signaling, and decreases survival in hepatocellular carcinoma.  Hepatology. 2008;  47 1211-1222
    Google Scholar
  • 47 Cheng W, Tseng C J, Lin T T. et al . Glypican-3-mediated oncogenesis involves the Insulin-like growth factor-signaling pathway.  Carcinogenesis. 2008;  29 1319-1326
    Google Scholar
  • 48 Moorman A F, Vermeulen J L, Charles R. et al . Localization of ammonia-metabolizing enzymes in human liver: ontogenesis of heterogeneity.  Hepatology. 1989;  9 367-372
    Google Scholar
  • 49 Reitzer L J, Wice B M, Kennell D. Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells.  J Biol Chem. 1979;  254 2669-2676
    Google Scholar
  • 50 Christa L, Simon M T, Flinois J P. et al . Overexpression of glutamine synthetase in human primary liver cancer.  Gastroenterology. 1994;  106 1312-1320
    Google Scholar
  • 51 Schirmacher P, Prange W, Dries V. et al . Highly differentiated hepatocellular tumors. Concepts, criteria, and differential diagnosis.  Pathologe. 2001;  22 407-416
    Google Scholar
  • 52 Rebouissou S, Amessou M, Couchy G. et al . Frequent in-frame somatic deletions activate gp130 in inflammatory hepatocellular tumours.  Nature. 2008;  epub
    Google Scholar

Prof. Dr. Peter Schirmacher

Pathologisches Institut, Universität Heidelberg

Im Neuenheimer Feld 220 / 221

69120 Heidelberg

Phone: ++ 49 / 6221 / 562601

Fax: ++ 49 / 6221 / 565251

Email: peter.schirmacher@med.uni-heidelberg.de

      >