nach oben

Head and Neck Pathology

Erschienen in:

28.02.2017 | Original Paper

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland

verfasst von: Raja R. Seethala, Göran Stenman

Erschienen in: Head and Neck Pathology | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

The salivary gland section in the 4th edition of the World Health Organization classification of head and neck tumors features the description and inclusion of several entities, the most significant of which is represented by (mammary analogue) secretory carcinoma. This entity was extracted mainly from acinic cell carcinoma based on recapitulation of breast secretory carcinoma and a shared ETV6-NTRK3 gene fusion. Also new is the subsection of “Other epithelial lesions,” for which key entities include sclerosing polycystic adenosis and intercalated duct hyperplasia. Many entities have been compressed into their broader categories given clinical and morphologic similarities, or transitioned to a different grouping as was the case with low-grade cribriform cystadenocarcinoma reclassified as intraductal carcinoma (with the applied qualifier of low-grade). Specific grade has been removed from the names of the salivary gland entities such as polymorphous adenocarcinoma, providing pathologists flexibility in assigning grade and allowing for recognition of a broader spectrum within an entity. Cribriform adenocarcinoma of (minor) salivary gland origin continues to be divisive in terms of whether it should be recognized as a distinct category. This chapter also features new key concepts such as high-grade transformation. The new paradigm of translocations and gene fusions being common in salivary gland tumors is featured heavily in this chapter.

Eveson JW, Auclair PL, Gnepp DR, El-Naggar AK. Tumours of the salivary gland. In: Barnes L, Eveson JW, Reichart P, Sidransky D, (Eds.). World Health Organization classification of tumours: pathology and genetics of head and neck tumours. Lyon: IARC; 2005. p. 164.

Stenman G. Fusion oncogenes in salivary gland tumors: molecular and clinical consequences. Head Neck Pathol. 2013;7(Suppl 1):S12–9. doi:10.1007/s12105-013-0462-z.CrossRefPubMed

Chiosea SI, Griffith C, Assaad A, Seethala RR. The profile of acinic cell carcinoma after recognition of mammary analog secretory carcinoma. Am J Surg Pathol. 2012;36(3):343–50. doi:10.1097/PAS.0b013e318242a5b0.CrossRefPubMed

Skalova A, Vanecek T, Sima R, Laco J, Weinreb I, Perez-Ordonez B, et al. Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol. 2010;34(5):599–608. doi:10.1097/PAS.0b013e3181d9efcc.PubMed

Bishop JA, Yonescu R, Batista D, Eisele DW, Westra WH. Most nonparotid “acinic cell carcinomas” represent mammary analog secretory carcinomas. Am J Surg Pathol. 2013;37(7):1053–7. doi:10.1097/PAS.0b013e3182841554.CrossRefPubMedPubMedCentral

Chenevert J, Duvvuri U, Chiosea S, Dacic S, Cieply K, Kim J, et al. DOG1: a novel marker of salivary acinar and intercalated duct differentiation. Mod Pathol. 2012;25(7):919–29. doi:10.1038/modpathol.2012.57.CrossRefPubMed

Skalova A, Vanecek T, Simpson RH, Laco J, Majewska H, Baneckova M, et al. Mammary analogue secretory carcinoma of salivary glands: molecular analysis of 25 ETV6 gene rearranged tumors with lack of detection of classical ETV6-NTRK3 fusion transcript by standard RT-PCR: report of 4 cases harboring ETV6-X gene fusion. Am J Surg Pathol. 2016;40(1):3–13. doi:10.1097/PAS.0000000000000537.CrossRefPubMed

Chiosea SI, Griffith C, Assaad A, Seethala RR. Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands. Histopathology. 2012;61(3):387–94. doi:10.1111/j.1365-2559.2012.04232.x.CrossRefPubMed

Skalova A, Vanecek T, Majewska H, Laco J, Grossmann P, Simpson RH, et al. Mammary analogue secretory carcinoma of salivary glands with high-grade transformation: report of 3 cases with the ETV6-NTRK3 gene fusion and analysis of TP53, beta-catenin, EGFR, and CCND1 genes. Am J Surg Pathol. 2014;38(1):23–33. doi:10.1097/PAS.0000000000000088.CrossRefPubMed

10.

Drilon A, Li G, Dogan S, Gounder M, Shen R, Arcila M, et al. What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC). Ann Oncol. 2016;27(5):920–6. doi:10.1093/annonc/mdw042.CrossRefPubMedPubMedCentral

11.

Smith BC, Ellis GL, Slater LJ, Foss RD. Sclerosing polycystic adenosis of major salivary glands. A clinicopathologic analysis of nine cases. Am J Surg Pathol. 1996;20(2):161–70.CrossRefPubMed

12.

Skalova A, Gnepp DR, Simpson RH, Lewis JE, Janssen D, Sima R, et al. Clonal nature of sclerosing polycystic adenosis of salivary glands demonstrated by using the polymorphism of the human androgen receptor (HUMARA) locus as a marker. Am J Surg Pathol. 2006;30(8):939–44.CrossRefPubMed

13.

Skalova A, Michal M, Simpson RH, Starek I, Pradna J, Pfaltz M. Sclerosing polycystic adenosis of parotid gland with dysplasia and ductal carcinoma in situ. Report of three cases with immunohistochemical and ultrastructural examination. Virchows Arch. 2002;440(1):29–35.CrossRefPubMed

14.

Canas Marques R, Felix A. Invasive carcinoma arising from sclerosing polycystic adenosis of the salivary gland. Virchows Arch. 2014;464(5):621–5. doi:10.1007/s00428-014-1551-4.CrossRefPubMed

15.

Weinreb I, Seethala RR, Hunt JL, Chetty R, Dardick I, Perez-Ordonez B. Intercalated duct lesions of salivary gland: a morphologic spectrum from hyperplasia to adenoma. Am J Surg Pathol. 2009;33(9):1322–9. doi:10.1097/PAS.0b013e3181a55c15.CrossRefPubMed

16.

Montalli VA, Martinez E, Tincani A, Martins A, Abreu Mdo C, Neves C, et al. Tubular variant of basal cell adenoma shares immunophenotypical features with normal intercalated ducts and is closely related to intercalated duct lesions of salivary gland. Histopathology. 2014;64(6):880–9. doi:10.1111/his.12339.CrossRefPubMed

17.

Chetty R. Intercalated duct hyperplasia: possible relationship to epithelial-myoepithelial carcinoma and hybrid tumours of salivary gland. Histopathology. 2000;37(3):260–3.CrossRefPubMed

18.

Brandwein MS, Huvos AG. Oncocytic tumors of major salivary glands. A study of 68 cases with follow-up of 44 patients. Am J Surg Pathol. 1991;15(6):514–28.CrossRefPubMed

19.

McHugh JB, Hoschar AP, Dvorakova M, Parwani AV, Barnes EL, Seethala RR. p63 immunohistochemistry differentiates salivary gland oncocytoma and oncocytic carcinoma from metastatic renal cell carcinoma. Head Neck Pathol. 2007;1(2):123–31. doi:10.1007/s12105-007-0031-4.CrossRefPubMedPubMedCentral

20.

Daniels TE. Benign lymphoepithelial lesion and Sjögren’s syndrome. In: Ellis GL, Auclair PL, Gnepp DR, (Eds.). Surgical pathology of the salivary glands. Philadelphia: W.B. Saunders Company; 1991. p. 83–106.

21.

Kreisel FH, Frater JL, Hassan A, El-Mofty SK. Cystic lymphoid hyperplasia of the parotid gland in HIV-positive and HIV-negative patients: quantitative immunopathology. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(4):567–74. doi:10.1016/j.tripleo.2009.12.008.CrossRefPubMed

22.

Abbondanzo SL. Extranodal marginal-zone B-cell lymphoma of the salivary gland. Ann Diagn Pathol. 2001;5(4):246–54. doi:10.1053/adpa.2001.26980.CrossRefPubMed

23.

Agaimy A, Ihrler S, Markl B, Lell M, Zenk J, Hartmann A, et al. Lipomatous salivary gland tumors: a series of 31 cases spanning their morphologic spectrum with emphasis on sialolipoma and oncocytic lipoadenoma. Am J Surg Pathol. 2013;37(1):128–37. doi:10.1097/PAS.0b013e31826731e0.CrossRefPubMed

24.

Erickson-Johnson MR, Chou MM, Evers BR, Roth CW, Seys AR, Jin L, et al. Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Lab Invest. 2011;91(10):1427–33. doi:10.1038/labinvest.2011.118.CrossRefPubMed

25.

Brandwein-Gensler MS, Gnepp DR. Low Grade Cribriform Cystadenocarcinoma. In: Barnes L, Eveson JW, Reichart P, Sidransky D, editors. World Health Organization classification of tumours: pathology and genetics of head and neck tumours. Lyon: IARC; 2005. p. 233.

26.

Gnepp DR, Cheuk W, Chan JKC, Nagao T. Lymphadenomas: Sebaceous and Non-Sebaceous. In: Barnes L, Eveson JW, Reichart P, Sidransky D, (Eds.). World Health Organization classification of tumours: pathology and genetics of head and neck tumours. Lyon: IARC; 2005. p. 269.

27.

Brannon RB, Sciubba JJ. Ductal Papillomas. In: Barnes L, Eveson JW, Reichart P, Sidransky D, (Eds.). World Health Organization classification of tumours: pathology and genetics of head and neck tumours. Lyon: IARC; 2005. pp. 270–2.

28.

Seethala RR, Thompson LD, Gnepp DR, Barnes EL, Skalova A, Montone K, et al. Lymphadenoma of the salivary gland: clinicopathological and immunohistochemical analysis of 33 tumors. Mod Pathol. 2012;25(1):26–35. doi:10.1038/modpathol.2011.135.CrossRefPubMed

29.

Brannon RB, Sciubba JJ, Giulani M. Ductal papillomas of salivary gland origin: a report of 19 cases and a review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;92(1):68–77. doi:10.1067/moe.2001.115978.CrossRefPubMed

30.

Auclair PL. Cystadenocarcinoma. In: Barnes L, Eveson JW, Reichart P, Sidransky D, (Eds.). World Health Organization classification of tumours: pathology and genetics of head and neck tumours. Lyon: IARC; 2005. p. 232.

31.

Sun KH, Gao Y, Li TJ Mucinous Adenocarcinoma. In: Barnes L, Eveson JW, Reichart P, Sidransky D, (Eds.). World Health Organization classification of tumours: pathology and genetics of head and neck tumours. Lyon: IARC; 2005. pp. 233–4.

32.

Gnepp DR. Malignant Sebaceous Tumours. In: Barnes L, Eveson JW, Reichart P, Sidransky D, (Eds.). World Health Organization classification of tumours: pathology and genetics of head and neck tumours. Lyon: IARC; 2005. p. 231.

33.

Bradley PJ. ‘Metastasizing pleomorphic salivary adenoma’ should now be considered a low-grade malignancy with a lethal potential. Curr Opin Otolaryngol Head Neck Surg. 2005;13(2):123–6.CrossRefPubMed

34.

Evans HL, Batsakis JG. Polymorphous low-grade adenocarcinoma of minor salivary glands. A study of 14 cases of a distinctive neoplasm. Cancer. 1984;53(4):935–42.CrossRefPubMed

35.

Castle JT, Thompson LD, Frommelt RA, Wenig BM, Kessler HP. Polymorphous low grade adenocarcinoma: a clinicopathologic study of 164 cases. Cancer. 1999;86(2):207–19.CrossRefPubMed

36.

Evans HL, Luna MA. Polymorphous low-grade adenocarcinoma: a study of 40 cases with long-term follow up and an evaluation of the importance of papillary areas. Am J Surg Pathol. 2000;24(10):1319–28.CrossRefPubMed

37.

Seethala RR, Johnson JT, Barnes EL, Myers EN. Polymorphous low-grade adenocarcinoma: the University of Pittsburgh experience. Arch Otolaryngol Head Neck Surg. 2010;136(4):385–92. doi:10.1001/archoto.2010.39.CrossRefPubMed

38.

Rooper L, Sharma R, Bishop JA. Polymorphous low grade adenocarcinoma has a consistent p63+/p40- immunophenotype that helps distinguish it from adenoid cystic carcinoma and cellular pleomorphic adenoma. Head Neck Pathol. 2015;9(1):79–84. doi:10.1007/s12105-014-0554-4.CrossRefPubMed

39.

Skalova A, Sima R, Kaspirkova-Nemcova J, Simpson RH, Elmberger G, Leivo I, et al. Cribriform adenocarcinoma of minor salivary gland origin principally affecting the tongue: characterization of new entity. Am J Surg Pathol. 2011;35(8):1168–76. doi:10.1097/PAS.0b013e31821e1f54.CrossRefPubMed

40.

Michal M, Skalova A, Simpson RH, Raslan WF, Curik R, Leivo I, et al. Cribriform adenocarcinoma of the tongue: a hitherto unrecognized type of adenocarcinoma characteristically occurring in the tongue. Histopathology. 1999;35(6):495–501.CrossRefPubMed

41.

Simpson RH, Pereira EM, Ribeiro AC, Abdulkadir A, Reis-Filho JS. Polymorphous low-grade adenocarcinoma of the salivary glands with transformation to high-grade carcinoma. Histopathology. 2002;41(3):250–9.CrossRefPubMed

42.

Weinreb I, Zhang L, Tirunagari LM, Sung YS, Chen CL, Perez-Ordonez B, et al. Novel PRKD gene rearrangements and variant fusions in cribriform adenocarcinoma of salivary gland origin. Genes Chromosomes Cancer. 2014;53(10):845–56. doi:10.1002/gcc.22195.CrossRefPubMed

43.

Weinreb I, Piscuoglio S, Martelotto LG, Waggott D, Ng CK, Perez-Ordonez B, et al. Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands. Nat Genet. 2014;46(11):1166–9. doi:10.1038/ng.3096.CrossRefPubMed

44.

Weinreb I, Chiosea SI, Seethala RR, Reis-Filho JS, Weigelt B, Piscuoglio S, et al. Genotypic and phenotypic comparison of polymorphous and cribriform adenocarcinomas of salivary gland. Mod Pathol. 2015;28(S2):333.

45.

Goode RK, El-Naggar AK Mucoepidermoid Carcinoma. In: Barnes L, Eveson JW, Reichart P, Sidransky D, (Eds.) World Health Organization classification of tumours: pathology and genetics of head and neck tumours. Lyon: IARC; 2005. pp. 219–20.

46.

Goode RK, Auclair PL, Ellis GL. Mucoepidermoid carcinoma of the major salivary glands: clinical and histopathologic analysis of 234 cases with evaluation of grading criteria. Cancer. 1998;82(7):1217–24.CrossRefPubMed

47.

Brandwein MS, Ivanov K, Wallace DI, Hille JJ, Wang B, Fahmy A, et al. Mucoepidermoid carcinoma: a clinicopathologic study of 80 patients with special reference to histological grading. Am J Surg Pathol. 2001;25(7):835–45.CrossRefPubMed

48.

Batsakis JG, Luna MA. Histopathologic grading of salivary gland neoplasms: I. Mucoepidermoid carcinomas. Ann Otol Rhinol Laryngol. 1990;99(10 Pt 1):835–8.CrossRefPubMed

49.

Katabi N, Ghossein R, Ali S, Dogan S, Klimstra D, Ganly I. Prognostic features in mucoepidermoid carcinoma of major salivary glands with emphasis on tumour histologic grading. Histopathology. 2014;65(6):793–804. doi:10.1111/his.12488.CrossRefPubMed

50.

Seethala RR, Dacic S, Cieply K, Kelly LM, Nikiforova MN. A reappraisal of the MECT1/MAML2 translocation in salivary mucoepidermoid carcinomas. Am J Surg Pathol. 2010;34(8):1106–21. doi:10.1097/PAS.0b013e3181de3021.CrossRefPubMed

51.

Costa AF, Altemani A, Hermsen M. Current concepts on dedifferentiation/high-grade transformation in salivary gland tumors. Patholog Res Int. 2011;2011:325965. doi:10.4061/2011/325965.PubMedPubMedCentral

52.

Roy P, Bullock MJ, Perez-Ordonez B, Dardick I, Weinreb I. Epithelial-myoepithelial carcinoma with high grade transformation. Am J Surg Pathol. 2010;34(9):1258–65. doi:10.1097/PAS.0b013e3181e366d2.CrossRefPubMed

53.

Williams L, Thompson LD, Seethala RR, Weinreb I, Assaad AM, Tuluc M, et al. Salivary duct carcinoma: the predominance of apocrine morphology, prevalence of histologic variants, and androgen receptor expression. Am J Surg Pathol. 2015;39(5):705–13. doi:10.1097/PAS.0000000000000413.CrossRefPubMed

54.

Lewis JE, Olsen KD, Sebo TJ. Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases. Hum Pathol. 2001;32(6):596–604. doi:10.1053/hupa.2001.25000.CrossRefPubMed

55.

LiVolsi VA, Perzin KH. Malignant mixed tumors arising in salivary glands. I. Carcinomas arising in benign mixed tumors: a clinicopathologic study. Cancer. 1977;39(5):2209–30.CrossRefPubMed

56.

Katabi N, Ghossein R, Ho A, Dogan S, Zhang L, Sung YS, et al. Consistent PLAG1 and HMGA2 abnormalities distinguish carcinoma ex-pleomorphic adenoma from its de novo counterparts. Hum Pathol. 2015;46(1):26–33. doi:10.1016/j.humpath.2014.08.017.CrossRefPubMed

57.

Katabi N, Gomez D, Klimstra DS, Carlson DL, Lee N, Ghossein R. Prognostic factors of recurrence in salivary carcinoma ex pleomorphic adenoma, with emphasis on the carcinoma histologic subtype: a clinicopathologic study of 43 cases. Hum Pathol. 2010;41(7):927–34. doi:10.1016/j.humpath.2009.12.011.CrossRefPubMed

58.

Gnepp DR, Brandwein-Gensler MS, el-Naggar AK, Nagao T. Carcinoma ex Pleomorphic Adenoma. In: Barnes L, Eveson JW, Reichart P, Sidransky D, (Eds.) World Health Organization classification of tumours: pathology and genetics of head and neck tumours. Lyon: IARC; 2005. pp. 242–3.

59.

Di Palma S. Carcinoma ex pleomorphic adenoma, with particular emphasis on early lesions. Head Neck Pathol. 2013;7(Suppl 1):S68–76. doi:10.1007/s12105-013-0454-z.CrossRefPubMed

60.

Griffith CC, Thompson LD, Assaad A, Purgina BM, Lai C, Bauman JE, et al. Salivary duct carcinoma and the concept of early carcinoma ex pleomorphic adenoma. Histopathology. 2014;65(6):854–60. doi:10.1111/his.12454.CrossRefPubMed

61.

Weiler C, Zengel P, van der Wal JE, Guntinas-Lichius O, Schwarz S, Harrison JD, et al. Carcinoma ex pleomorphic adenoma with special reference to the prognostic significance of histological progression: a clinicopathological investigation of 41 cases. Histopathology. 2011;59(4):741–50. doi:10.1111/j.1365-2559.2011.03937.x.CrossRefPubMed

62.

Brandwein-Gensler M, Hille J, Wang BY, Urken M, Gordon R, Wang LJ, et al. Low-grade salivary duct carcinoma: description of 16 cases. Am J Surg Pathol. 2004;28(8):1040–4.CrossRefPubMed

63.

Simpson RH, Desai S, Di Palma S. Salivary duct carcinoma in situ of the parotid gland. Histopathology. 2008;53(4):416–25. doi:10.1111/j.1365-2559.2008.03135.x.CrossRefPubMed

64.

Persson M, Andren Y, Mark J, Horlings HM, Persson F, Stenman G. Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc Natl Acad Sci USA. 2009;106(44):18740–4. doi:10.1073/pnas.0909114106.CrossRefPubMedPubMedCentral

65.

Tonon G, Modi S, Wu L, Kubo A, Coxon AB, Komiya T, et al. t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway. Nat Genet. 2003;33(2):208–13. doi:10.1038/ng1083.CrossRefPubMed

66.

Jo VY, Sholl LM, Krane JF. Distinctive patterns of CTNNB1 (beta-Catenin) alterations in salivary gland basal cell adenoma and basal cell adenocarcinoma. Am J Surg Pathol. 2016;40(8):1143–50. doi:10.1097/PAS.0000000000000669.CrossRefPubMed

67.

Persson F, Andren Y, Winnes M, Wedell B, Nordkvist A, Gudnadottir G, et al. High-resolution genomic profiling of adenomas and carcinomas of the salivary glands reveals amplification, rearrangement, and fusion of HMGA2. Genes Chromosomes Cancer. 2009;48(1):69–82. doi:10.1002/gcc.20619.CrossRefPubMed

68.

Andersson MK, Stenman G. The landscape of gene fusions and somatic mutations in salivary gland neoplasms - Implications for diagnosis and therapy. Oral Oncol. 2016;57:63–9. doi:10.1016/j.oraloncology.2016.04.002.CrossRefPubMed

69.

Antonescu CR, Katabi N, Zhang L, Sung YS, Seethala RR, Jordan RC, et al. EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland. Genes Chromosomes Cancer. 2011;50(7):559–70. doi:10.1002/gcc.20881.CrossRefPubMed

Titel: Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland
verfasst von: Raja R. Seethala
Göran Stenman
Publikationsdatum: 28.02.2017
Verlag: Springer US
Erschienen in: Head and Neck Pathology / Ausgabe 1/2017
Elektronische ISSN: 1936-0568
DOI: https://doi.org/10.1007/s12105-017-0795-0

Neu im Fachgebiet Pathologie

01.04.2024 | Forensische Traumatologie | CME

Springer Medizin

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland

Abstract

Neu im Fachgebiet Pathologie

Theoretische Grundlagen von Explosionen und Explosionsverletzungen

Auswirkungen vorgeschalteter Laborprozesse auf die Digitalisierung histologischer Schnittpräparate

Knochenmarkhistologie bei Zytopenien

Herausforderungen der Automation bei der quantitativen Auswertung von Leberbiopsien

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2017

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What is New in the 2017 WHO Blue Book for Tumours of the Hypopharynx, Larynx, Trachea and Parapharyngeal Space

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Preface

Update From The 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Nasopharynx

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What Is New in the 2017 WHO Blue Book for Tumors and Tumor-Like Lesions of the Neck and Lymph Nodes

Update from the 4th Edition of the World Health Organization of Head and Neck Tumours: Tumours of the Oral Cavity and Mobile Tongue

Update From the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumours of the Ear

Neu im Fachgebiet Pathologie

Theoretische Grundlagen von Explosionen und Explosionsverletzungen

Auswirkungen vorgeschalteter Laborprozesse auf die Digitalisierung histologischer Schnittpräparate

Knochenmarkhistologie bei Zytopenien

Herausforderungen der Automation bei der quantitativen Auswertung von Leberbiopsien