Amyloidosis
amyloidosis diagnosis treatment
amyloidosis Congo red apple green birefringence histology

Light microscopy image of a lymph node biopsy stained with Congo Red and examined under polarized light. The tissue reveals extracellular, amorphous eosinophilic deposits distributed throughout nodal architecture consistent with amyloid. The deposits assume a dense, granular to plaque-like appearance on routine brightfield, and demonstrate distinctive apple-green birefringence when illuminated with polarized light, confirming the beta-pleated sheet rich configuration of amyloid fibrils. Congo Red positivity with birefringence distinguishes amyloid from other PAS-positive glycoprotein material and helps differentiate from non-amyloid nodal deposits. The beta-pleated sheet conformation accounts for the characteristic staining behavior and optical properties used in diagnosis. Clinically, identification of nodal amyloid supports systemic or localized amyloidosis and prompts workup for light-chain (AL) or serum amyloid A (AA) subtypes, including serum free light chains, immunofixation, and mass spectrometry-based typing. This image is relevant for educational illustrations of amyloid histology, pathophysiology, and diagnostic pathology workflows, including differential diagnosis with glycoprotein-rich PAS-positive deposits that are Congo Red negative. Potential clinical scenarios include workup of lymphadenopathy in patients with chronic inflammatory states, plasma cell dyscrasias, and lymphoproliferative disorders. High quality images like this support interdepartmental communication, teaching, and reproducible reporting of amyloid histology for junior pathologists and medical trainees in pathology education programs.

Renal biopsy histology of a patient with multiple myeloma showing AL-type amyloid deposition within the kidney. Congo red–stained sections reveal extracellular, eosinophilic, acellular deposits in the glomerular mesangium and throughout the tubulointerstitium; these deposits are salmon-pink on routine light microscopy. When viewed under polarized light, the Congo red positive material displays the diagnostic apple-green birefringence, confirming amyloid. The deposits disrupt normal glomerular architecture, with mesangial expansion, thickened capillary loops, and variable involvement of the tubules and interstitium; vascular involvement may be appreciated as deposition in arterioles. The lamina appears to be produced by a monoclonal immunoglobulin light chain (AL type) associated with underlying plasma cell dyscrasia; in the setting of myeloma, AL amyloidosis accounts for this pattern. Clinically, such renal amyloid deposition commonly correlates with nephrotic-range proteinuria, hypoalbuminemia, edema, and progressive renal insufficiency leading to chronic kidney disease if untreated. The image illustrates Congo red positivity and apple-green birefringence, the gold-standard histologic features used to diagnose systemic AL amyloidosis. Confirmatory typing by immunohistochemistry or mass spectrometry is often pursued. This histology is critical for prognosis and guides therapy targeting the plasma cell clone rather than only symptomatic management. This pattern supports systemic evaluation for underlying plasma cell dyscrasia.

This renal cortical histology specimen demonstrates AL-type amyloidosis with kidney involvement in a patient with multiple myeloma. The left panel shows hematoxylin and eosin–stained tissue with amorphous, eosinophilic extracellular deposits within the glomerular mesangium and extending into the tubulointerstitium, causing mesangial expansion and variable basement membrane thickening. The right panel uses Congo Red staining to highlight the amyloid deposits, which appear salmon-pink on bright-field examination. Under polarized light, the same deposits display the diagnostic apple-green birefringence, a hallmark of Congo Red–positive amyloid. The deposits are diffuse, involving multiple glomeruli and extending into the tubulointerstitium, sometimes outlining capillary walls. In AL amyloidosis associated with plasma cell dyscrasia, the deposited light-chain–derived proteins disrupt normal renal architecture and contribute to proteinuria and progressive renal impairment. Differential considerations include AA (secondary) amyloidosis and other renal amyloidoses, but the combination of a known plasma cell disorder, Congo Red positivity, and apple-green birefringence strongly supports AL-type amyloidosis. This image serves as a valuable teaching reference for renal pathology, nephrology, and hematology-oncology, illustrating classic Congo Red histology, amyloid distribution patterns within glomeruli and interstitium, and the polarizing light signature. Correlates with proteinuria and renal dysfunction in many myeloma patients, guiding targeted therapy and monitoring of clonal plasma cell burden.

This histology image depicts human cardiac tissue (myocardium) stained with Congo Red and examined under bright-field microscopy. The image highlights extracellular, eosinophilic amyloid deposits that encircle and encroach upon individual cardiomyocytes (perimyocytic/interstitial deposition). The deposits appear as amorphous, orange to salmon-pink material on Congo Red, consistent with amyloid. When the same tissue is examined under polarized light, Congo Red–positive material exhibits characteristic apple-green birefringence, a pathognomonic feature of amyloidosis. The prevailing pattern is perimyocytic, with amyloid accumulating in the interstitium around myocytes and near small vessels, potentially contributing to myocardial stiffness and diastolic impairment. Histologic architecture shows preserved cellular morphology of myocytes with basophilic nuclei contrasted against the pink-red amyloid matrix. This image is diagnostic for cardiac amyloidosis on biopsy and would typically prompt typing (AL vs ATTR) by immunohistochemistry or mass spectrometry, as well as correlation with serum free light chains or transthyretin testing. Clinically, such infiltration predisposes to restrictive cardiomyopathy, diastolic dysfunction, arrhythmias, and heart failure symptoms. This slide underscores the utility of Congo Red staining in identifying myocardial amyloid deposits and the diagnostic value of polarized light birefringence for definitive confirmation. Useful for teaching, differential diagnosis, and research into infiltrative cardiomyopathies and treatment monitoring.


| Type | Fibril Protein | Precursor | Clinical Setting |
|---|---|---|---|
| AL | Immunoglobulin light chains (chiefly λ) | Monoclonal plasma cells | Multiple myeloma, plasma cell dyscrasias |
| AA | Serum amyloid A (SAA) protein | SAA (acute-phase reactant) | Chronic inflammation (RA, Crohn, TB, FMF) |
| ATTRwt | Wild-type transthyretin | TTR (liver) | Aging males >70 years; cardiac predominant |
| ATTRv | Mutant transthyretin | TTR variant | Hereditary; cardiomyopathy + neuropathy |
| Aβ2M | β2-microglobulin | MHC class I component | Long-term hemodialysis; periarticular |
| Aβ | Amyloid β protein | Amyloid precursor protein (APP) | Alzheimer disease (localized cerebral) |
| ACal | Calcitonin | Calcitonin | Medullary thyroid carcinoma |
| AIAPP | Islet amyloid polypeptide | IAPP | Type 2 diabetes mellitus |
| Feature | AL | AA | ATTRwt | ATTRv |
|---|---|---|---|---|
| Fibril | Light chain | SAA protein | Wild-type TTR | Mutant TTR |
| Cause | Plasma cell dyscrasia | Chronic inflammation | Aging | Inherited mutation |
| Age | Any, usually >50 | Any | Males >70 | Variable |
| Heart | +++++ | + | +++++ | ++ to +++++ |
| Kidney | +++++ | +++++ | + | Variable |
| Nerve | + | - | - | +++++ |
| Treatment | Daratumumab/bortezomib ± SCT | Treat underlying disease | Tafamidis | Patisiran/inotersen/tafamidis |