A 60-year-old man with a history of drug and alcohol abuse recently presented to the ER with active upper gastrointestinal bleeding, hypovolemic shock, and possible sepsis. The present liver biopsy was performed seven days after the ER presentation due to the persistently elevated liver enzymes, especially the alkaline phosphatase of over 400 units/L.
The correct answer is ...
The biopsy shows liver parenchyma with acellular eosinophilic amorphous material deposition within the sinusoidal spaces with atrophy of the hepatocytes, characteristic of amyloidosis. Confirmatory Congo Red special stain demonstrated salmon-colored deposits, which showed apple green-birefringence under polarization, confirming amyloid deposits. The subsequent mass-spectrometry analysis identified the deposits to be AL-amyloid.
Amyloidosis is a systemic disorder characterized by extracellular amyloid protein deposition commonly involving the liver.1 Autopsy studies have shown up to 95% of patients with amyloidosis to have hepatic involvement.2
Clinically, patients present with hepatomegaly and elevated serum alkaline phosphatase as the most common laboratory finding associated with hepatic amyloidosis.3
The five most common systemic forms of amyloid that involve the liver are amyloid light chain (AL), acquired amyloidosis (AA), B2 microglobulin amyloidosis (Abeta2M), and the two types of transthyretin amyloidosis (ATTR) (hereditary and non-hereditary). The present subtype, AL-amyloid, is associated with plasma cell dyscrasias, multiple myeloma, B-cell lymphoma, or Waldenstrom disease. The precursor proteins can be Kappa or Lambda immunoglobulin light chains derived from plasma cells.
Amyloid deposits in the liver show similar morphologic findings as other organ sites, as it presents as an acellular eosinophilic amorphous material, which may deposit in the sinusoids, portal tracts, vessel walls, or any mix of the mentioned sites.
Specific subtypes of amyloid may show different patterns of deposition within the liver. For example, some studies have demonstrated that AA amyloidosis shows deposits primarily in the blood vessels of the portal tracts, whereas AL amyloidosis usually shows a “sinusoidal” pattern. However, the distribution pattern alone is not used clinically to subtype amyloid.4 Additionally, the deposit morphology may also help determine the subtypes of amyloid deposits as large round eosinophilic globular deposits within the hepatocytes or reticuloendothelial cells characterize the “globular amyloid deposits,” which are highly specific for leukocyte chemotactic factor (LECT2)-associated amyloidosis.5
Previously, immunostains were utilized to subtype the amyloid. However, due to their challenges in interpretation, laser microdissection with mass spectrometry is now the preferred method that is both sensitive and specific for identifying all amyloid subtypes.6
The differential diagnosis for hepatic amyloid is the presence of other extracellular deposits that can look similar on H&E, such as dense collagen deposits, collection of red blood cells, or light chain deposition. The application of Congo Red Trichrome stain can be helpful for their distinction.
The Light chain deposition disease is a rare monoclonal plasma cell proliferative disorder characterized by the deposition of light chains in the basement membranes. It primarily affects the kidneys, and the liver is the most common site of extrarenal involvement. These typically deposit within the sinusoidal spaces similar to amyloid but are Congo Red stain negative.7
Byoung Uk Park, M.D.
Fellow, Gastrointestinal & Liver Pathology
Chady Meroueh, M.D.
Consultant, Anatomic Pathology
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science