Definition/General
Introduction:
Small intestinal amyloidosis involves extracellular deposition of misfolded proteins in the small bowel wall
It shows characteristic Congo red positivity and apple-green birefringence
It can be primary (AL) or secondary (AA)
It causes malabsorption and motility disorders.
Origin:
Results from protein misfolding and aggregation
AL amyloidosis: immunoglobulin light chains
AA amyloidosis: serum amyloid A protein
AH amyloidosis: heavy chains
AFib amyloidosis: fibrinogen A
Systemic disease with GI involvement.
Classification:
AL amyloidosis (primary): lambda or kappa light chains
AA amyloidosis (secondary): chronic inflammatory diseases
AH amyloidosis: heavy chain disease
Hereditary amyloidosis: various proteins
Based on distribution: localized vs systemic.
Epidemiology:
GI involvement in 60-70% of systemic amyloidosis
AL type most common in developed countries
AA type more common in developing countries
Male predominance (1.5:1)
Peak incidence: 50-70 years.
Clinical Features
Presentation:
Malabsorption syndrome
Chronic diarrhea
Weight loss and malnutrition
Intestinal pseudo-obstruction
GI bleeding
Protein-losing enteropathy.
Symptoms:
Bulky, greasy stools (steatorrhea)
Abdominal distension
Crampy abdominal pain
Early satiety
Peripheral edema (hypoproteinemia)
Fatigue and weakness.
Risk Factors:
Plasma cell dyscrasias (AL type)
Chronic inflammatory diseases: rheumatoid arthritis, inflammatory bowel disease (AA type)
Chronic infections: tuberculosis, osteomyelitis
Familial Mediterranean fever
Advanced age.
Screening:
Small bowel biopsy (definitive diagnosis)
Congo red staining
Serum free light chains
Serum amyloid A levels
Bone marrow biopsy
Echocardiography (cardiac involvement).
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Gross Description
Appearance:
Thickened bowel wall
Rigid, pipe-like bowel
Mucosal nodularity
Loss of normal fold pattern
Waxy appearance
Friable mucosa.
Characteristics:
Diffuse wall thickening
Loss of peristalsis
Rubbery consistency
Pale, waxy cut surface
Mucosal ulcerations possible
Luminal narrowing.
Size Location:
Duodenum and jejunum most commonly affected
Entire small bowel involvement possible
Mesenteric involvement
Concurrent colonic involvement
Variable extent.
Multifocality:
Diffuse involvement pattern
Progressive deposition over time
Multiorgan involvement (systemic)
Concurrent cardiac, renal involvement
Lymph node involvement.
Microscopic Description
Histological Features:
Homogeneous eosinophilic deposits in vessel walls and interstitium
Congo red positivity
Apple-green birefringence under polarized light
Vascular wall thickening
Smooth muscle replacement.
Cellular Characteristics:
Acellular eosinophilic material
Amorphous deposits
Vessel wall involvement
Smooth muscle atrophy
Chronic inflammation
Giant cell reaction (rare).
Architectural Patterns:
Submucosal deposition
Muscularis propria involvement
Vascular wall deposits
Neural plexus involvement
Villous architecture preservation initially
Progressive architectural distortion.
Grading Criteria:
Extent of deposition: mild, moderate, severe
Layer involvement: mucosal, submucosal, muscular, serosal
Vascular involvement: present/absent
Functional impact assessment.
Immunohistochemistry
Positive Markers:
Congo red (diagnostic stain)
Thioflavin T (fluorescent)
Anti-AA antibody (AA amyloidosis)
Anti-AL antibodies (kappa/lambda)
Anti-transthyretin (hereditary).
Negative Markers:
Cytokeratins (excludes carcinoma)
Smooth muscle markers (in areas of replacement)
Endothelial markers (in occluded vessels).
Diagnostic Utility:
Congo red staining: gold standard for diagnosis
Polarization microscopy: apple-green birefringence
Amyloid typing: determines treatment
Electron microscopy: fibrillary structure
Essential for diagnosis.
Molecular Subtypes:
AL amyloidosis: lambda or kappa light chains
AA amyloidosis: serum amyloid A
AH amyloidosis: heavy chains
Hereditary forms: various proteins.
Molecular/Genetic
Genetic Mutations:
Immunoglobulin gene rearrangements (AL type)
SAA gene variants (AA type)
TTR mutations (hereditary transthyretin)
FGA mutations (fibrinogen A)
APOA1 mutations (apolipoprotein A1).
Molecular Markers:
Serum free light chains (AL type)
SAA levels (AA type)
Proteomic analysis
Mass spectrometry (protein identification)
Fibrillary structure on electron microscopy.
Prognostic Significance:
AL amyloidosis: worse prognosis
Cardiac involvement: poor prognosis
Extent of deposition: affects outcome
Response to treatment: variable
Organ involvement number: prognostic factor.
Therapeutic Targets:
Chemotherapy (AL type): melphalan, dexamethasone
Anti-inflammatory therapy (AA type)
Colchicine (familial Mediterranean fever)
Supportive care
Organ transplantation (selected cases).
Differential Diagnosis
Similar Entities:
Hyalinosis
Fibrosis
Immunotactoid glomerulopathy
Light chain deposition disease
Colloid carcinoma
Signet ring cell carcinoma.
Distinguishing Features:
Amyloidosis: Congo red positive, apple-green birefringence
Hyalinosis: Congo red negative
LCDD: Congo red negative, granular deposits
Carcinoma: epithelial markers positive, cellular.
Diagnostic Challenges:
Early recognition of amyloid deposits
Adequate Congo red staining
Proper polarization technique
Amyloid typing
Distinguishing from other protein deposits.
Rare Variants:
Localized GI amyloidosis
Amyloidoma
Multiple amyloid types (mixed)
Drug-induced amyloidosis
Dialysis-related amyloidosis.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Small bowel biopsy from [duodenum/jejunum], [number] fragments
Diagnosis
Small intestinal amyloidosis
Congo Red Stain
Congo red stain: positive with apple-green birefringence under polarized light
Distribution
Amyloid deposits present in: [blood vessels/smooth muscle/interstitium]
Extent
Extent of deposition: [mild/moderate/severe]
Amyloid Type
Amyloid typing: [AL/AA/AH/other] type
Special Studies
Congo red: positive with apple-green birefringence
Immunohistochemistry for amyloid typing: [result]
Electron microscopy: [if performed] shows fibrillary deposits
Recommendations
Clinical correlation, systemic evaluation for amyloidosis, hematology consultation
Final Diagnosis
Small intestinal [type] amyloidosis with [extent] deposition