Stains & molecular markers
Congo red
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PubMed Search: Congo red[TI] pathology full text[sb]
Congo red
Editor-in-Chief: Debra L. Zynger, M.D.
Topic Completed: 13 August 2019
Minor changes: 25 September 2020
Copyright: 2003-2021, PathologyOutlines.com, Inc.
PubMed Search: Congo red[TI] pathology full text[sb]
Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Clinical features | Interpretation | Uses by pathologists | Prognostic factors | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Board review style question #1 | Board review style answer #1Cite this page: Huang H, Iczkowski KA. Congo red. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainscongored.html. Accessed January 16th, 2021.
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
Terminology
- Also called amyloid stain
Pathophysiology
- 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
Interpretation
- 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
- Amyloid heart disease is the main prognostic factor with an unfavorable outcome (Future Rheumatol 2008;3:369)
- Multiple myeloma associated amyloidosis is an independent high risk prognostic factor (Ann Hematol 2009;88:59)
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
- Primary systemic amyloidosis
- Breast (BMC Surg 2016;16:62)
- Central nervous system (J Clin Neurosci 2006;13:159)
- Heart (Rev Assoc Med Bras 2018;64:787)
- Kidney (J Int Med Res 2019;47:1778, Am J Kidney Dis 2019;74:276)
- Liver (J Int Med Res 2019;47:1778)
- Muscle (Muscle Nerve 1995;18:1016)
- Nerve, gastrointestinal tract, lung and soft tissue (Am J Hematol 2005;79:319)
- Salivary gland (Otolaryngol Head Neck Surg 2006;135:471)
- Skin (J Clin Diagn Res 2017;11:WC01)
- Spleen (Eur J Case Rep Intern Med 2018;5:0001010)
- Stomach (Case Rep Gastroenterol 2018;12:317)
- Testis (Urology 2002;59:201)
- Tongue and eyelid (Clin Chim Acta 2019;494:112)
- Amyloidosis associated with multiple myeloma
- Bone marrow (Ann Hematol 2010;89:469)
- Heart (Rev Med Panama 1994;19:147)
- Joint (Q J Med 1981;50:417)
- Kidney (Recenti Prog Med 1994;85:123)
- Lung (BMC Cancer 2018;18:802)
- Muscle (Int J Hematol 2012;95:716)
- Skin (Oncol Lett 2016;11:3617)
- Stomach (Case Rep Gastrointest Med 2015;2015:320120)
- Thyroid (Arch Pathol Lab Med 1990;114:429)
- Tongue (J Oral Pathol 1988;17:554)
- Secondary systemic amyloidosis
- Kidney in celiac disease (ACG Case Rep J 2018;5:e24)
- Kidney in longterm inflammatory disorder (Rheum Dis Clin North Am 2018;44:585)
- Kidney in systemic lupus erythematosus (Hum Pathol 1981;12:853)
- Kidneys, retroperitoneal lymphoma mass, blood vessels and adrenal glands in non-Hodgkin lymphoma (Hum Pathol 2004;35:1041)
- Secondary corneal amyloidosis in keratoconus (Cornea 2011;30:716)
- Tongue in longterm hemodialysis (Spec Care Dentist 2018;38:434)
- Medullary thyroid carcinoma (Acta Cytol 1992;36:137)
- Alzheimer disease (Uversky: Bio-nanoimaging - Protein Misfolding and Aggregation, 1st Edition, 2014)
- Amyloid tumor of the breast (Surg Case Rep 2019;5:31)
- Amyloid tumor of the parotid gland (Oral Surg Oral Med Oral Pathol 1988;66:466)
- Amyloid insulin bodies at an insulin injection site (Am J Dermatopathol 2018;40:527)
- Lumbar epidural amyloidoma (Neurosurgery 2005;57:E196)
Negative staining
- Hyalinizing trabecular adenoma of the thyroid gland (Am J Surg Pathol 1987;11:583)
- Fibrillary glomerulonephritis (Kidney Int 2003;63:1450)
- Primary central nervous system nonamyloidogenic light chain deposition disease (Int J Surg Pathol 2017;25:755)
Board review style question #1
Which of the following lesions should be negative for Congo red?
- Bone marrow in a patient with multiple myeloma
- Hyalinizing trabecular adenoma of the thyroid gland
- Kidney in a patient with systemic lupus erythematosus
- Liver in a patient with systemic light chain amyloidosis
- 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).
Reference: Congo red
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Reference: Congo red
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