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What is an adequate size liver biopsy specimen

What is an adequate size liver biopsy specimen. Puja Sakhuja Professor, Pathology’ GB Pant Hospital. Royal College of Pathologists definition of adequacy of liver core biopsies for medical disease.

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What is an adequate size liver biopsy specimen

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  1. What is an adequate size liver biopsy specimen Puja Sakhuja Professor, Pathology’ GB Pant Hospital

  2. Royal College of Pathologists definition of adequacy of liver core biopsies for medical disease Tissue pathways for liver biopsies for the investigation of medical disease and for focal lesions. The Royal College ofPathologists, 2008.

  3. Impact of the specimen diameter on the number of portal tracts and on grading and staging G. Colloredo et al. / Journal of Hepatology 39 (2003)

  4. Impact of the specimen length on the number of portal tracts and on grading and staging G. Colloredo et al. / Journal of Hepatology 39 (2003)

  5. Grading and staging of liver biopsy in chronic viral hepatitis • use of the fine needle should be discouraged • traditional 1.5 cm long sample should no longer be considered the ‘standard’ size • 2 cm long – 1.4 mm wide sample is recommended to ensure the minimum number of complete portal tracts for reliable grading and staging • biopsies of comparable size should be used in studies aiming to assess disease progression or the effect of antiviral therapy • make the clinician aware of the limitations of histological interpretation - specimen size and the number of complete portal tracts should be clearly indicated in the histological report G. Colloredo et al. / Journal of Hepatology 39 (2003)

  6. Biopsy length of at least 25 mm is necessary to evaluate fibrosis accurately with a semiquantitative score. • No substantial benefit for longer biopsy specimens (Bedossa, HEPATOLOGY 2003;38:1449-1457.)

  7. specimens longer than 15 mm and containing 6 or more portal tracts gave better correlation of histology with biochemical surrogate markers of fibrosis and disease activity than smaller samples.

  8. Transjugular liver biopsy (TJLB) has been proposed as a useful method to obtain “adequate” samples • It allows for more than one pass without any significant risk of bleeding • TJLB with 3 passes - produces optimal biopsies for diagnostic purposes • adequate for staging and grading in 38% (≥25 mm) or 25% (≥11 CP) of cases CholongitasE, et al. Transjugularliverbiopsy: how good is it for accurate histological interpretation? Gut 2006;55:1789–94

  9. ✓ ✓ ✓ ✓ 23% of 464 were >20mm Schiano et al., 2005 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

  10. Specimens with a length of at least 10 mm usually reflect the grade of necroinflammatory activity and the stage of fibrosis reliably in patients with CHC • Relatively little improvement in diagnostic accuracy is afforded with longer specimens • 94% of the 10-mm long specimens were assessed either identically to or within 1 stage difference of the gold standard of 20 mm or greater Schiano et al., 2005 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

  11. Proportion with definite NASH was significantly lower in single core biopsy in comparison to 2 cores (37% vs. 57%, p<0.001) • It was not different between two cores and three cores (57% vs. 61%, p=0.3). • Significantly lower severity in steatosis, lobular inflammation, hepatocellular ballooning and fibrosis were observed when 1 core biopsy was compared to multiple core biopsies.

  12. Biopsy size Vsprobability plots • 90% probability - the virtual biopsy CPA can be expected to be within 5% of the reference CPA22– 28 mm2 of analysable tissue is required depending on aetiology • 75% probability level requires a biopsy with 12–15 mm2 of analysabletissue • Increasing sample size will inevitably increase the reliability of CPA results. Howeverabove 20–25 mm2 biopsy size (16G needle biopsy with 25–31 mm length of specimen, 19G: 33–42 mm length of specimen) the incremental improvement in probability that the biopsy CPA will be within 5% of the actual CPA diminishes

  13. The Effect of Processing on Liver Biopsy Core Size • The mean size of the liver biopsy specimen in the needle cartridge (CS) - 15 ± 2.0 mm. • The mean liver biopsy specimen size outside the needle cartridge on the biopsy tray (TS) - 19.6 ± 3.5 mm. • The mean liver biopsy size after fixation with formalin and before embeddingin paraffin block (FS) - 18.3 ± 2.9 mm Riley III DigDis Sci (2008)

  14. Adequacy of cares • 19.8% - adequate • 56.4% - suboptimal • 23.8% - inadequate. • The increased proportion of adequate biopsies since introduction of the guidelines was statistically significant (p<0.011 • shorter cores are associated with understaging, as also found by Colloredo et al • 40 of the 319 reports on inadequate cores (15%) commented on adequacy (fibrosis and architecture) Fryer E, Wang LM, Verrill C, et al. J ClinPathol 2013;66:1087–1089

  15. GBPH data

  16. Cholongitas et al / QUALITY OF LIVER BIOPSY SPECIMENS Am J ClinPathol 2006

  17. Cholongitas et al / QUALITY OF LIVER BIOPSY SPECIMENS Am J ClinPathol 2006

  18. Audit Standards UK Radiology: Volume 265: Number 3—December 2012

  19. Guidelines for “clinically useful” histology report in CVH 1. Assess the adequacy of the biopsy by measuring the lengthof the specimen and counting the number of portal tracts. Write these data in the final report to make clinicians awareof any potential sampling error in the grading and staging…… …it is important to emphasize the need for biopsies of comparable size when assessing disease progression or the effect of antiviral therapy Guido M, Rugge M. Liver fibrosis: natural history may be affected by the biopsy sample. Gut 2004;53:1878 M. Guido et al. / Digestive and Liver Disease 43S (2011) S331–S343

  20. Thereport for each liver biopsy obtained for the assessment of diffuse disease should contain some mention about the adequacy of the specimen • This judgment should be left to the subjective opinion of the pathologist • Even biopsies containing less than 10–11 portal tracts might contain diagnostic findings and adequate tissue for grading and staging of chronic hepatitis. • Put an absolute limit on the number of portal tracts ????

  21. Liver biopsy size 8mm

  22. RECOMMENDATIONS • Biopsy length of <10mm and/or 6 portal tracts should be considered inadequate for fibrosis staging [Grading of evidence: moderate quality (B); Grading of recommendation: Strong recommendation (1)] • Ideal Biopsies >20mm/11 portal tracts should be considered adequate however a biopsy of 15mm and 10 PT is adequate for routine clinical practice [Grading of evidence: moderate quality (B); Grading of recommendation: Strong recommendation (1)] • Final judgement on adequacy of sample for staging is on the judgement of an experienced pathologist [Grading of evidence: low quality (C); Grading of recommendation: weaker recommendation (2)]

  23. ….RECOMMENDATIONS • All histology reports should mention the sample size, the number of complete portal tracts included and comment on adequacy of the sample [Grading of evidence: moderate quality (B); Grading of recommendation: Strong recommendation (1)] • Clinical trials should specify minimum sample size as an inclusion criteria [Grading of evidence: moderate quality (B); Grading of recommendation: Strong recommendation (1)]

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