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24888 Iron, Liver Tissue (FET)

Iron, Liver Tissue (FET)
Test Code: FELVRSO
Synonyms/Keywords
Fe (Iron), Hemochromatosis, Hepatic Iron Concentration, Hepatic Iron Index, Iron (Fe), Iron, Tissue Liver, Metals, Tissue,
Quantitative Iron, Total Iron, Liver Tissue
Useful For
Diagnosis of hemochromatosis using liver tissue specimens
Specimen Requirements
Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
Liver Tissue​ ​Mayo metal-free specimen vial (blue label) Paraffin block, if not more than 1 or 2 cuts have been made to it for slides. 2 mg​
2 cm (22-gauge needle), 1 cm (18-gauge needle), or 2 mm x 2 mm (punch) 0.3 mg by dry weight​
Collection Processing Instructions
1. 2 mg of liver tissue is required. This is typically a piece of tissue from a 22-gauge needle biopsy at least 2 cm long. If an 18-gauge needle is used, the tissue must be at least 1 cm in length.
2. Any specimen vial other than a Mayo metal-free vial used should be plastic, leached with 10% nitric acid for 2 days, rinsed with redistilled water, and dried in clean air.
Additional Information:
1. Patient's date of birth is required to calculate iron index.
2. Paraffin blocks will be returned 3 days after analysis.​
Specimen Stability Information
Specimen Type Temperature
​Liver Tissue ​ ​ ​Refrigerated (preferred)
​Ambient
​Frozen
Interference

​Formalin-fixed, paraffin-embedded tissue can be used when histologic examination (including iron stains) is requested, in addition to the hepatic iron concentration and calculated hepatic iron index. However, fresh or frozen tissue is preferred.

Paraffin blocks from which many slides have been previously cut often appear to contain sufficient quantity of tissue, however, the specimen is often very thin and less than 2 mg in weight.

Performing Laboratory Information
Performing Location Day(s) Test Performed Analytical Time Methodology/Instrumentation
Mayo Clinic Laboratories​ ​Monday, Wednesday,  Friday ​2-5 days
Inductively Coupled Plasma-Mass Spectrometry (ICP-MS)​
Reference Lab
Test Information

Hemosiderosis is the condition of excessive iron accumulation in tissues. Liver is the first organ affected in iron-overload diseases. Transient increases in iron first appear in Kupffer cells. This finding is commonly related to sideroblastic anemia, excessive iron consumption, or chronic alcohol ingestion. Persistent hemosiderosis, as seen in hemochromatosis, causes iron accumulation in hepatocytes, and is usually concentrated in biliary cells.

Hereditary hemochromatosis is an autosomal recessive disease with estimated prevalence in the population of 2 in 1,000 in Caucasians, with lower incidence in other races. The gene responsible for hereditary hemochromatosis (HFE) is located on chromosome 6; the majority of hereditary hemochromatosis patients have variants in this HFE gene. Hereditary hemochromatosis is characterized by an accelerated rate of intestinal iron absorption and progressive iron deposition in various tissues that typically begins to be expressed in the third to fifth decades of life, but may occur in children. The most common presentation is hepatic cirrhosis in combination with hypopituitarism, cardiomyopathy, diabetes, arthritis, or hyperpigmentation. Because of the severe sequelae of this disease if left untreated and recognizing that treatment is relatively simple, early diagnosis before symptoms or signs appear is important. 

Screening for hemochromatosis is best done by measuring serum iron and transferrin saturation (FEC / Iron and Total Iron-Binding Capacity, Serum). If the serum iron concentration is above 175 mcg/dL and the transferrin saturation is above 55%, analysis of serum ferritin concentration (FERR / Ferritin, Serum) is indicated. A ferritin concentration above 400 ng/mL is suggestive of hemochromatosis, but also can indicate other forms of hepatocyte injury such as alcoholic or viral hepatitis, or other inflammatory disorders involving the liver. HFE analysis (HFE / Hemochromatosis HFE Gene Analysis, Blood) may be used to confirm the clinical diagnosis of hemochromatosis, to diagnose hemochromatosis in asymptomatic individuals with blood tests showing increased iron stores, or for predictive testing of individuals who have a family history of hemochromatosis. The alleles evaluated by HFE gene analysis are evident in approximately 80% of patients with hemochromatosis; a negative report for HFE gene does not rule-out hemochromatosis. In a patient with negative HFE gene testing, elevated iron status for no other obvious reason, and family history of liver disease, additional evaluation of liver iron concentration is indicated. 

Diagnosis of hemochromatosis may also be based on biochemical analysis and histologic examination of a liver biopsy. In this assay, results are reported as the hepatic iron index (HII) and dry weight of iron. The HII is considered the "gold standard" for diagnosis of hemochromatosis. This test is appropriate when:

-Serum iron is above 160 mcg/dL

-Transferrin saturation is above 55%

-Ferritin is above 400 ng/mL in males or above 200 ng/mL in females

-HFE gene test is negative for HFE variants

Reference Range Information
Iron:
    Males: 200-2,400 mcg/g dry weight
    Females: 200-1,800 mcg/g dry weight
Iron Index: <1.0 mcmol/g/year (> or =13 yr)
Reference values have not been established for patients that are less than 13 years of age.
Interpretation

A hepatic iron concentration above 10,000 mcg/g dry weight is diagnostic for hemochromatosis.

Hepatic iron concentrations above 3,000 mcg/g are seen when there is iron overload without cellular injury and cirrhosis. Hepatic iron concentrations greater than the reference range are associated with hemosiderosis, thalassemia, and sideroblastic anemia. Some patients with hepatitis or cirrhosis without significant fibrosis will have hepatic iron concentrations at the top end of normal or just slightly above the normal range.

Iron accumulates in the liver normally with aging. The hepatic iron index (HII) normalizes hepatic iron concentration for age. The HII is calculated from the hepatic iron concentration by converting the concentration from mcg/g to mcmol/g dry weight and dividing by years of age. The normal range for HII is less than 1.0.

-Patients with homozygous hemochromatosis have an HII above 1.9.

-Patients with heterozygous hemochromatosis often have an HII ranging from 1.0 to 1.9.

-Patients with hepatitis and alcoholic cirrhosis usually have an HII below 1.0, although a small percentage of patients with alcoholic cirrhosis have an HII in the range of 1.0 to 1.9.

-Patients with hemochromatosis who have been successfully treated with phlebotomy will have an HII below 1.0.

Liver specimens collected from patients with cirrhosis containing a high degree of fibrosis have results near the low end of the reference range, even though they will show significant iron staining in hepatocytes. While it is true that iron accumulates in hepatocytes in advanced alcoholic cirrhosis with fibrosis, there are relatively few hepatocytes compared to other inert (fibrotic) tissue, so the quantitative iron determination, which is expressed as mcg of iron per gram of dry weight tissues, yields a low result. Histologic examination of all tissue specimens should be performed to facilitate correct interpretation. When structural heterogeneity is apparent histologically, variation in measured iron should be anticipated. We have observed, in approximately 2% of cases, a high degree of hepatic heterogeneity that makes quantitation highly variable.

Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
​83540
Synonyms/Keywords
Fe (Iron), Hemochromatosis, Hepatic Iron Concentration, Hepatic Iron Index, Iron (Fe), Iron, Tissue Liver, Metals, Tissue,
Quantitative Iron, Total Iron, Liver Tissue
Ordering Applications
Ordering Application Description
​Centricity ​Iron, Liver Tissue (8350)
​Cerner ​Iron Level Liver Tissue (8350)
If the ordering application you are looking for is not listed, contact your local laboratory for assistance.
Specimen Requirements
Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
Liver Tissue​ ​Mayo metal-free specimen vial (blue label) Paraffin block, if not more than 1 or 2 cuts have been made to it for slides. 2 mg​
2 cm (22-gauge needle), 1 cm (18-gauge needle), or 2 mm x 2 mm (punch) 0.3 mg by dry weight​
Collection Processing
1. 2 mg of liver tissue is required. This is typically a piece of tissue from a 22-gauge needle biopsy at least 2 cm long. If an 18-gauge needle is used, the tissue must be at least 1 cm in length.
2. Any specimen vial other than a Mayo metal-free vial used should be plastic, leached with 10% nitric acid for 2 days, rinsed with redistilled water, and dried in clean air.
Additional Information:
1. Patient's date of birth is required to calculate iron index.
2. Paraffin blocks will be returned 3 days after analysis.​
Specimen Stability Information
Specimen Type Temperature
​Liver Tissue ​ ​ ​Refrigerated (preferred)
​Ambient
​Frozen
Interference

​Formalin-fixed, paraffin-embedded tissue can be used when histologic examination (including iron stains) is requested, in addition to the hepatic iron concentration and calculated hepatic iron index. However, fresh or frozen tissue is preferred.

Paraffin blocks from which many slides have been previously cut often appear to contain sufficient quantity of tissue, however, the specimen is often very thin and less than 2 mg in weight.

Useful For
Diagnosis of hemochromatosis using liver tissue specimens
Reference Range Information
Iron:
    Males: 200-2,400 mcg/g dry weight
    Females: 200-1,800 mcg/g dry weight
Iron Index: <1.0 mcmol/g/year (> or =13 yr)
Reference values have not been established for patients that are less than 13 years of age.
Interpretation

A hepatic iron concentration above 10,000 mcg/g dry weight is diagnostic for hemochromatosis.

Hepatic iron concentrations above 3,000 mcg/g are seen when there is iron overload without cellular injury and cirrhosis. Hepatic iron concentrations greater than the reference range are associated with hemosiderosis, thalassemia, and sideroblastic anemia. Some patients with hepatitis or cirrhosis without significant fibrosis will have hepatic iron concentrations at the top end of normal or just slightly above the normal range.

Iron accumulates in the liver normally with aging. The hepatic iron index (HII) normalizes hepatic iron concentration for age. The HII is calculated from the hepatic iron concentration by converting the concentration from mcg/g to mcmol/g dry weight and dividing by years of age. The normal range for HII is less than 1.0.

-Patients with homozygous hemochromatosis have an HII above 1.9.

-Patients with heterozygous hemochromatosis often have an HII ranging from 1.0 to 1.9.

-Patients with hepatitis and alcoholic cirrhosis usually have an HII below 1.0, although a small percentage of patients with alcoholic cirrhosis have an HII in the range of 1.0 to 1.9.

-Patients with hemochromatosis who have been successfully treated with phlebotomy will have an HII below 1.0.

Liver specimens collected from patients with cirrhosis containing a high degree of fibrosis have results near the low end of the reference range, even though they will show significant iron staining in hepatocytes. While it is true that iron accumulates in hepatocytes in advanced alcoholic cirrhosis with fibrosis, there are relatively few hepatocytes compared to other inert (fibrotic) tissue, so the quantitative iron determination, which is expressed as mcg of iron per gram of dry weight tissues, yields a low result. Histologic examination of all tissue specimens should be performed to facilitate correct interpretation. When structural heterogeneity is apparent histologically, variation in measured iron should be anticipated. We have observed, in approximately 2% of cases, a high degree of hepatic heterogeneity that makes quantitation highly variable.

For more information visit:
Performing Laboratory Information
Performing Location Day(s) Test Performed Analytical Time Methodology/Instrumentation
Mayo Clinic Laboratories​ ​Monday, Wednesday,  Friday ​2-5 days
Inductively Coupled Plasma-Mass Spectrometry (ICP-MS)​
Reference Lab
For billing questions, see Contacts
Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
​83540
For most current information refer to the Marshfield Laboratory online reference manual.