Globular hepatic amyloid is highly sensitive and specific for LECT2 amyloidosis
Vishal S Chandan1, Sejal S Shah, Dora M Lam-Himlin
1*Division of Anatomic Pathology, Mayo Clinic, Rochester, MN †Division of Anatomic Pathology, Mayo Clinic, Scottsdale, AZ ‡Department of Pathology and Laboratory Medicine, Memorial Sloan-Kettering Cancer Center, New York City, NY.
The American Journal of Surgical Pathology
|January 21, 2015
Summary
Globular hepatic amyloid (GHA) is rare, but leukocyte chemotactic factor-associated amyloidosis (ALECT2) specifically shows this pattern. LECT2 immunostaining is a reliable method for diagnosing ALECT2-related GHA.
Area of Science:
- Hepatology
- Pathology
- Immunohistochemistry
Background:
- Globular hepatic amyloid (GHA) is an uncommon finding with unclear clinical significance.
- Leukocyte chemotactic factor-associated amyloidosis (ALECT2) has recently been identified as a cause of hepatic amyloidosis with a globular pattern.
Purpose of the Study:
- To determine the prevalence and morphology of hepatic amyloid subtypes.
- To investigate the association between ALECT2 and GHA.
- To evaluate the utility of LECT2 immunostaining in identifying ALECT2.
Main Methods:
- Review of 70 consecutive hepatic amyloidosis cases for subtype, pattern (globular/linear), and distribution.
- Analysis of 24 additional mass spectrometry-confirmed hepatic ALECT2 cases.
- Immunohistochemistry for LECT2 performed on 49 cases.
Main Results:
- Immunoglobulin light chain (AL) amyloidosis was most common (59%), followed by transthyretin (ATTR) amyloidosis (22%).
- Leukocyte chemotactic factor-associated amyloidosis (ALECT2) accounted for 4% of cases and exclusively showed globular hepatic amyloid (GHA) deposits.
- All mass spectrometry-confirmed hepatic ALECT2 cases (100%) exhibited GHA.
- LECT2 immunostaining was positive in all ALECT2 cases and negative in other amyloid subtypes.
Conclusions:
- Pure GHA is rare (4%) but highly specific for ALECT2.
- LECT2 immunostaining is a valuable diagnostic tool for identifying ALECT2-associated hepatic amyloidosis.
Related Concept Videos
03:03Amyloid Fibrils
7.0K
7.0K
03:03Amyloid Fibrils
13.2K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
13.2K
01:24Cirrhosis II: Pathophysiology
3
Cirrhosis is a progressive chronic liver injury caused by prolonged inflammation, excessive fibrotic remodeling, and impaired regeneration. Over time, repeated hepatic insults disrupt the liver’s architecture and function, leading to reduced blood flow, impaired bile drainage, and diminished metabolic capacity.Pathophysiology of cirrhosisCirrhosis arises from three main responses to chronic liver damage: inflammation, immune activation, and hepatocyte death. These processes lead to...
3
01:29Hepatic Encephalopathy
2
DefinitionHepatic encephalopathy is a reversible neurologic syndrome that results from advanced liver dysfunction or portosystemic shunting. It leads to disturbances in cognition, behavior, and motor function due to the brain’s exposure to gut-derived toxins that the liver fails to detoxify.EtiologyThis condition develops either in the setting of acute fulminant hepatitis or progressively during chronic liver disease, such as cirrhosis and portal hypertension. Portosystemic...
2
01:22Lysosomal Hydrolases
4.8K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
4.8K
01:26Diseases of the Liver and Gallbladder
2.4K
Liver and gallbladder diseases are a significant health concern, with prominent conditions including cirrhosis, hepatitis, non-alcoholic fatty liver disease (NAFLD), and gallstones. Jaundice is a common manifestation of liver and biliary disease.
Cirrhosis is characterized by the scarring of hepatic lobules in the liver, which are replaced by fibrous tissue, affecting the liver's normal functioning. NAFLD, on the other hand, is caused by an excessive build-up of fat in the liver, not...
Cirrhosis is characterized by the scarring of hepatic lobules in the liver, which are replaced by fibrous tissue, affecting the liver's normal functioning. NAFLD, on the other hand, is caused by an excessive build-up of fat in the liver, not...
2.4K