Liver & intrahepatic bile ducts
Benign / nonneoplastic
Donor liver frozen section evaluation
Author: Kimberley J. Evason, M.D., Ph.D.
Editorial Board Member: Danielle Hutchings, M.D.
Deputy Editor-in-Chief: Aaron R. Huber, D.O.
Last author update: 6 February 2024
Last staff update: 17 April 2024
Copyright: 2023-2024, PathologyOutlines.com, Inc.
PubMed Search: Donor liver frozen section evaluation
Table of Contents
Definition / general | Essential features | Terminology | Sites | Diagrams / tables | Clinical features | Diagnosis | Prognostic factors | Case reports | Frozen section description | Frozen section images | Microscopic (histologic) description | Microscopic (histologic) images | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Evason KJ. Donor liver frozen section evaluation. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/liverfatindonorbiopsies.html. Accessed April 29th, 2024.
Definition / general
- Click here for the frozen section procedure topic
- Frozen section evaluation of donor liver biopsies, including assessment of fat, fibrosis, necrosis and inflammation, is a key component in determining if a donor liver is suitable for transplantation
Essential features
- Exclusion of potential donor livers based on frozen section findings of severe steatosis, ischemic necrosis, prominent portal inflammation or fibrosis or malignancy reduces the rate of primary nonfunction of transplanted livers (Transplantation 1993;56:1403)
- Amount of large droplet macrovesicular fat is a key factor in determining suitability of liver for transplantation and should be assessed first (Hepatology 2022;75:1014)
- Other histologic features including amount of small droplet macrovesicular fat and presence of fibrosis, inflammation, necrosis and granulomas should also be reported, as these may affect the transplant surgeon's decision to use the graft
- True microvesicular steatosis is essentially never seen in donor liver frozen sections, though some donor network forms include this feature
Terminology
- Liver allograft biopsy
Sites
- Liver
Diagrams / tables
Contributed by Kimberley J. Evason, M.D., Ph.D.
Large droplet fat determination
Small droplet fat determination
Clinical features
- Multiple donor related factors are considered when surgeon determines whether to use a donor liver, including (Front Med Technol 2023:5:1079003)
- Age
- Body mass index (BMI)
- Clinical history of alcohol or intravenous (IV) drug use
- Laboratory values
- Warm and cold ischemia time
- Gross appearance of the liver
- Histologic features on frozen section
- Transplant surgeons also consider recipient status
- Healthier recipients may be better able to tolerate marginal organs
- Extended donor criteria may be utilized for select recipients (Clin Liver Dis 2017;21:289)
- Includes donor organs from patients with advanced age, steatosis, viral hepatitis, certain other transmissible infections, cardiac death or prolonged ischemia time
- Intended to increase the number of available donor organs
Diagnosis
- Selection of donor livers for transplantation is entirely at the discretion of the transplant surgeon (see Clinical features)
- Pathologists typically receive very limited information about the donor and no information about the recipient
- Amount of large droplet macrovesicular fat in donor liver is one of the key histologic features that define suitability for transplantation (Hepatology 2022;75:1014)
- < 30% large droplet macrovesicular fat generally does not preclude transplantation
- > 60% large droplet macrovesicular fat generally considered unsuitable for transplantation
- 30 - 60% large droplet macrovesicular fat generally considered borderline and other features including small droplet macrovesicular fat may be considered
- Fibrosis and inflammation are also important, particularly for extended criteria donors
- Organs with advanced fibrosis, bridging or greater, are typically excluded
- Inflammation should be moderate or less (Clin Liver Dis 2017;21:289)
- Other histologic features including amount of small droplet macrovesicular fat and presence of necrosis and granulomas should also be reported, as these may affect the transplant surgeon's decision to use the graft
Prognostic factors
- Exclusion of potential donor livers based on frozen section findings of severe steatosis, ischemic necrosis, prominent portal inflammation or fibrosis or malignancy reduces the rate of primary nonfunction of transplanted livers (Transplantation 1993;56:1403)
- Amount of large droplet macrovesicular fat is key factor in determining suitability of liver for transplantation (Hepatology 2022;75:1014)
- Severe large droplet macrovesicular steatosis (> 60%) in donor liver is associated with adverse outcomes including primary nonfunction, early allograft dysfunction and postreperfusion syndrome (Hepatology 1994;20:829, Transplantation 1989;47:903, Transplantation 1993;56:1403, Transplant Proc 1991;23:1536)
- Moderate to severe small droplet macrovesicular steatosis (> 30%) in graft is associated with increased risk for acute cellular rejection and bile duct loss in recipient (Am J Surg Pathol 2017;41:365)
Case reports
- 16 year old liver donor used for split liver transplant wherein one recipient developed fatty liver disease and one did not (World J Hepatol 2016;8:659)
- 56 and 58 year old men who received steatotic donor livers (Am J Transplant 2019;19:2640)
- 100 year old female liver donor with graft; recipient functioning well 9 months posttransplant (Am J Transplant 2023 Sep 25 [Epub ahead of print])
Frozen section description
- 2.0 cm long core needle biopsy or 1.5 cm² subcapular wedge biopsy from the anterior inferior edge of the liver are recommended for evaluation (Arch Pathol Lab Med 2013;137:270)
- Large droplet fat (Hepatology 2022;75:1014)
- Subtype of macrovesicular steatosis
- Single droplet distending the hepatocyte
- At least slightly larger than nearby hepatocytes lacking fat
- Hepatocyte nucleus, if present, displaced to cell periphery
- Assessed in 3 step process (Hepatology 2022;75:1014)
- At low power, determine % of parenchyma that stands out as white = LP%
- At high power, determine what % of these areas are truly large droplet fat = HP%
- Determine actual large droplet fat amount as percentage of total hepatocyte parenchyma by calculating HP% of LP% = large droplet fat percentage (LDF%)
- Small droplet fat
- Subtype of macrovesicular steatosis
- All fat droplets that do not meet criteria of large droplet fat or microvesicular steatosis (Hepatology 2022;75:1014)
- Assessed at high power after assessment of LDF%
- At high power, determine % of hepatocytes not involved by large droplet fat that contain small droplet fat = sHP%
- Determine actual small droplet fat amount as percentage of total hepatocytes by calculating sHP% of total hepatocytes (estimate total number of hepatocytes as 100% - LDF%)
- Scored based on percent of hepatocytes involved, not on percent of parenchyma
- Small droplet fat plus large droplet fat cannot exceed 100%
- Microvesicular fat
- Tiny fat droplets that impart a foamy appearance to hepatocytes
- Essentially never seen in liver donor biopsies
- Some standardized donor network forms may incorrectly refer to small droplet fat as microvesicular fat
- Fibrosis
- Appears as dense, eosinophilic material that may extend out from central veins or portal tracts entrapping adjacent hepatocytes
- Clues to advanced fibrosis include distortion of normal architecture, including loss of regular spacing of portal tracts and central veins, as well as presence of bridging septa (Surg Pathol Clin 2018;11:453)
- Other abnormalities including inflammation, granulomas and necrosis should also be reported if applicable
Frozen section images
Microscopic (histologic) description
Microscopic (histologic) images
Sample pathology report
- Donor liver, biopsy:
- Mild steatosis (see frozen section diagnosis and comment)
- Frozen section diagnosis
- Specimen type / size / description: liver core
- Fibrosis: none
- Portal infiltrates: mild, some or all portal areas
- Large droplet fat, % of hepatic parenchyma involved: 10%
- Small droplet fat, % of hepatocytes involved: 10%
- Centrilobular necrosis: no
- Evidence of cholestasis: no
- Evidence of lipofuscin: yes
- Evidence of active lobular inflammation: no
- Other pathology: no
- Comment: Frozen sections correlate with permanent sections.
Differential diagnosis
- Mimickers of large droplet fat:
- Dilated sinusoids:
- Elongated, somewhat irregular / wavy appearance
- Not circular
- Medium sized fat droplets:
- Should be counted as small droplet fat
- Smaller than nearby hepatocytes without fat
- Do not distend nucleus
- Dilated sinusoids:
- Mimickers of small droplet fat:
- Frozen section artifact:
- May occur when biopsies are submitted in saline
- May be visible overlying nuclei or sinusoids
- Often diffusely involve entire core or swaths of core
- Often pale pink rather than white
- Frozen section artifact:
- Microvesicular steatosis:
- Outdated terminology for macrovesicular small droplet fat
- Some standardized donor network forms may include this diagnosis
- Essentially never seen in donor liver biopsies
Additional references
Board review style question #1
A 60 year old man with a body mass index (BMI) of 40 suffered severe trauma and his organs are being evaluated for donation. This image is a frozen section from the right lobe of his liver. Assuming this field of view is representative of the entire biopsy, how should the amount of fat be reported?
- 0% large droplet macrovesicular steatosis; 0% small droplet macrovesicular steatosis; frozen section artifact is present
- 5% large droplet macrovesicular steatosis; 90% small droplet macrovesicular steatosis
- 5% macrovesicular steatosis; 90% microvesicular steatosis
- 95% macrovesicular steatosis (medium sized droplets); 0% microvesicular steatosis
Board review style answer #1
B. 5% large droplet macrovesicular steatosis; 90% small droplet macrovesicular steatosis. About 5% of this biopsy is large droplet fat, which comprises large droplets greater than the size of a nonfatty hepatocyte. About 90% of the hepatocytes contain small droplets, which do not significantly distend the hepatocyte cytoplasm or displace the nucleus.
Answer C is incorrect because microvesicular steatosis (tiny droplets that lend a foamy appearance to the hepatocytes) is not seen here. Answer D is incorrect because it is critical to divide macrovesicular steatosis into large and small droplet components, as they have different prognostic implications. Answer A is incorrect because the droplets are white and do not overlap with sinusoids or nuclei, as frozen section artifact droplets typically do.
Comment Here
Reference: Donor liver frozen section evaluation
Comment Here
Reference: Donor liver frozen section evaluation
Board review style question #2
A 30 year old woman with a body mass index (BMI) of 40 suffered severe trauma and her organs are being evaluated for donation. This image is a frozen section from the right lobe of her liver. How should the amount of fat be reported?
- 0% large droplet macrovesicular steatosis; 0% small droplet macrovesicular steatosis; frozen section artifact is present
- 30% large droplet macrovesicular steatosis; 30% small droplet macrovesicular steatosis
- 50% large droplet macrovesicular steatosis; 10% small droplet macrovesicular steatosis; centrizonal fibrosis is present
- 50% macrovesicular steatosis; 10% microvesicular steatosis
- 60% macrovesicular steatosis; 0% microvesicular steatosis
Board review style answer #2
C. 50% large droplet macrovesicular steatosis; 10% small droplet macrovesicular steatosis; centrizonal fibrosis is present. About 50% of this biopsy is large droplet fat, which comprises large droplets greater than the size of a nonfatty hepatocyte. About 90% of the hepatocytes contain small droplets, which do not significantly distend the hepatocyte cytoplasm or displace the nucleus. Fibrosis is seen near the central vein, around 10 o'clock.
Answer B is incorrect because most of the fat in this biopsy is large droplet fat (droplets larger than the size of a nonfatty hepatocyte). Answer D is incorrect because microvesicular steatosis (tiny droplets that lend a foamy appearance to the hepatocytes) is not seen here. Answer E is incorrect because it is critical to divide macrovesicular steatosis into large and small droplet components, as they have different prognostic implications. Answer A is incorrect because the droplets are large, white, round and do not overlap with sinusoids or nuclei, as frozen section artifact droplets typically do.
Comment Here
Reference: Donor liver frozen section evaluation
Answer B is incorrect because most of the fat in this biopsy is large droplet fat (droplets larger than the size of a nonfatty hepatocyte). Answer D is incorrect because microvesicular steatosis (tiny droplets that lend a foamy appearance to the hepatocytes) is not seen here. Answer E is incorrect because it is critical to divide macrovesicular steatosis into large and small droplet components, as they have different prognostic implications. Answer A is incorrect because the droplets are large, white, round and do not overlap with sinusoids or nuclei, as frozen section artifact droplets typically do.
Comment Here
Reference: Donor liver frozen section evaluation
