Stains & CD markers
Congo red

Editor-in-Chief: Debra L. Zynger, M.D.
Huiya Huang, M.D., Ph.D.
Kenneth A. Iczkowski, M.D.

Topic Completed: 13 August 2019

Minor changes: 21 June 2021

Copyright: 2003-2022,, Inc.

PubMed Search: Congo red[TI] pathology full text[sb]

Huiya Huang, M.D., Ph.D.
Kenneth A. Iczkowski, M.D.
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Cite this page: Huang H, Iczkowski KA. Congo red. website. Accessed January 21st, 2022.
Definition / general
  • Congo red is an organic compound used for staining amyloid in tissue sections
Essential features
  • Congo red stain is the gold standard for the demonstration of amyloid in tissue sections
  • It is used to evaluate the presence and extent of amyloidosis in different organs
  • Common diseases for Congo red stain include primary amyloidosis, AL amyloid seen in plasma cell dyscrasias, AA amyloid associated with inflammatory conditions
  • Also called amyloid stain
  • Amyloidosis is a rare disease characterized by the deposition of insoluble misfolded proteins in various tissues and organs
  • Key event in the development of AL amyloidosis is the change in the secondary or tertiary structure of an abnormal monoclonal light chain, which results in unstable conformation
  • This conformational change is responsible for abnormal folding of the light chain, rich in β leaves, which assemble into monomers that stack together to form amyloid fibrils (Orphanet J Rare Dis 2012;7:54)
  • Amyloid fibril Congo red complex demonstrates green birefringence owing to the parallel alignment of dye molecules along the β pleated sheath
Clinical features
  • Mostly used for systemic or localized amyloidosis, such as AL amyloid seen in plasma cell dyscrasias, AA amyloid associated with inflammatory conditions, Aβ amyloid fibrils in Alzheimer disease and TTR amyloidosis due to either familial gene mutation or wild type protein, formerly called senile amyloidosis
  • Amyloids can be detected in the kidney, liver, heart, brain and other organs
  • Amyloid deposits in tissue exhibit a deep red or salmon color, whereas elastic tissue remains pale pink
  • When viewed under polarized light, amyloid deposits exhibit apple green birefringence
  • Thickness of the section is critical (8 - 10 μm) (Gattuso: Differential Diagnosis in Surgical Pathology, 2nd Edition, 2010)
  • Rotating the slide or the polarizing filter is important for visualizing the birefringence (Diagn Pathol 2019;14:57)
  • Improved sensitivity is reported by using a metallurgical polarized microscope (Diagn Pathol 2019;14:57)
  • Tissue elements such as collagen, elastin and others may display birefringence of varying colors that may be misinterpreted as amyloid (Hum Pathol 2014;45:1766)
    • Do not mistake the blue-green of collagen for the lime green of amyloid
Uses by pathologists
  • Evaluate the presence and extent of systemic or localized amyloidosis
  • Evaluate the progression of multiple myeloma and other plasma cell dyscrasias
Prognostic factors
Microscopic (histologic) images

Contributed by Kenneth A. Iczkowski, M.D.

Distinguishing the correct color

Rotation to visualize Congo red

Optimized AL amyloid imaging

Positive staining - normal
  • None
Positive staining - disease
Negative staining
Board review style question #1
Which of the following lesions should be negative for Congo red?

  1. Bone marrow in a patient with multiple myeloma
  2. Hyalinizing trabecular adenoma of the thyroid gland
  3. Kidney in a patient with systemic lupus erythematosus
  4. Liver in a patient with systemic light chain amyloidosis
  5. Medullary thyroid carcinoma
Board review style answer #1
B. Hyalinizing trabecular adenoma of the thyroid gland. Typical features of hyalinizing trabecular adenoma of the thyroid gland include oval and elongated nuclei, perinucleolar vacuoles, acidophilic nuclear inclusions, fine nuclear grooving and infrequent mitotic figures. Perivascular hyaline fibrosis and cell degeneration can mimic amyloid but these tumors are Congo red negative (Am J Surg Pathol 1987;11:583).

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