Updated: Nov 28, 2022
Author: Kondal Rao Kyanam Kabir Baig, MD; Chief Editor: Kurt E Roberts, MD 



Chromoendoscopy is an endoscopic technique that uses stains during endoscopy to highlight differences in mucosa, as well as dysplastic and malignant changes that are not apparent in white light. Chromoendoscopy is used to increase the detection rates for various pathologic processes during endoscopy. Chromoendoscopy is often used in surveillance of the esophagus for Barrett esophagus, evaluation of polyps in the colon, and surveillance of dysplasia in inflammatory bowel disease (IBD).[1, 2, 3, 4, 5]

Initial evaluations of computerized virtual chromoendoscopy for screening colonoscopy showed efficacy similar to that of chromoendoscopy, without the logistical difficulties or preparing and applying vital dyes.[6, 7, 8]  Magnification endoscopy, spectroscopy, confocal laser endomicroscopy and endocytoscopy have important roles in the evaluation of IBD and surveillance of chronic ulcerative colitis (UC).[9, 10, 11]  Use of these techniques in Barrett esophagus has also led better detection of dysplasia, particularly in the absence of discrete lesions.[12]


Chromoendoscopy has been used in the evaluation of Barrett esophagus,[13, 14, 15]  esophageal adenocarcinoma,[16]  gastric metaplasia and adenocarcinoma,[17, 18, 19, 20, 21]  colon polyps,[22, 23]  colon cancer,[24, 25, 26, 27, 28]  and surveillance in IBD.[29, 30]


Contraindications for chromoendoscopy would be any of the usual contraindications for endoscopy or a history of an allergic reaction to the dye or stain used in the specific clinical situation.

Chromoendoscopy is not routinely performed during general endoscopy. It is performed in centers that specialize in this field or on a case-by-case basis as indicated by the clinical situation and dictated by the experience of the endoscopist and the center.


Periprocedural Care

Preprocedural Planning

Barrett esophagus and esophageal adenocarcinoma

The increasing prevalence of Barrett esophagus and its recognition as a premalignant lesion has engendered a great deal of interest in recognizing metaplastic and dysplastic changes.[31] The increasing use of endoscopic therapy for dysplasia and adenocarcinoma has given further impetus to this concept. Chromoendoscopy is considered by some as a tool for recognizing high-risk lesions within Barrett esophagus and for facilitating definitive therapy.[13] The most commonly used dye is methylene blue.

Magnification chromoendoscopy is an important adjunctive technique that enhances the sensitivity and specificity.[32] Evaluating lesions in the absence of biopsies based on staining has also been shown to be useful.[33] Unfortunately, the sensitivity and specificity are wide-ranging. Randomized controlled trials have shown conflicting results and also equivalency to routine endoscopy.[34]

Esophageal squamous cancer

Lugol iodine is most commonly used to survey patients at risk for squamous cell carcinoma, including patients with tobacco abuse, alcohol abuse, or past head and neck cancer.[35] The sensitivity exceeds 90%, but the specificity is variable.[1] The dye may also be used to guide resection of early lesions.

Gastric metaplasia and cancer

Chromoendoscopy has been used to detect and demarcate dysplasia, intestinal metaplasia, or malignancy.[18, 36, 12] Methylene blue and congo red are used in a combination to differentiate abnormal gastric mucosa (which does not stain) from normal mucosa (which stains red or blue).[37] This may be of utility in high-risk groups targeted for intensive surveillance.[38]

There has been some evidence to suggest that Helicobacter pylori detection in the stomach is better with phenol red chromoendoscopy, though this concept has not been evaluated in clinical trials.[39, 40] Phenol red staining is being studied in assessing the functional recovery of gastric mucosa after H pylori eradication therapy.[41]

Colorectal adenoma

There have been many randomized trials for enhanced adenoma detection with chromoendoscopy using indigo carmine staining.[22, 42, 43] Pohl et al conducted a large randomized controlled trial comparing standard endoscopy with pancolonic chromoendoscopy and showed that chromoendoscopy significantly increased the detection rate for adenomas, flat lesions, and serrated lesions. There was an increase in the mean withdrawal time.[22] Other trials have shown mixed results.[44]

There may be a advantage to chromoendoscopy in detecting flat lesions.[45]  An increased cancer detection rate or survival rate has not been demonstrated. Chromoendoscopy is currently not of significant utility in screening or surveillance colonoscopy.

Colorectal cancer

Chromoendoscopy also has a limited and experimental role in endoscopically assessing the depth of known colorectal cancer.[24]

Inflammatory bowel disease

The difficulty in identifying dysplasia and carcinoma in chronic ulcerative colitis (UC) has led to the evaluation of chromoendoscopy in this particular high-risk situation. Many trials have shown that dysplasia detection is improved significantly and reproducibly.[30, 46, 47, 48, 49] The accumulation of evidence may have an impact on chronic UC surveillance guidelines.[50] Evidence with regard to carcinoma detection in this setting is equivocal.[51]

Patient Preparation

The usual preparation prior to upper endoscopy or colonoscopy and sedation administration is undertaken in the standard manner. Thereafter, specialized preparation of mucosa is carried out in accordance with the endoscopic procedure to be done, the dye or stain to be used, the suspected lesion, and the planned therapy for that lesion.



Approach Considerations

The agents used in chromoendoscopy are commercially available and inexpensive. They are not specifically made for endoscopy. They are prepared and diluted in accordance with the practices of the chromoendoscopists. Common staining agents used are Lugol solution, methylene blue, toluidine blue, crystal violet, indigo carmine, congo red, and phenol red. Special spray catheters are used to spray a fine mist on to the mucosa.[1]

The agents are classified as absorptive, contrast, or reactive agents. Absorptive stain are absorbed by or diffuse into specific cells. Contrast agents seep between cells and enhance the surface. Reactive agents undergo chemical reactions with specific cell components and undergo color change.[1]

It should be kept in mind that Lugol iodine can cause esophagitis or gastritis in rare cases. Hyperthyroidism or hypersensitivity to iodine should preclude the use of this agent. Methylene blue can cause discoloration of urine and feces. No serious adverse effects of other vital dyes have been described. General precautions should include aspiration and contact precautions.[1]

Virtual chromoendoscopy is increasingly used; it appears to be as effective as standard chromoendoscopy, without the logistical difficulties or preparing and applying vital dyes. The implementation of artificial intelligence systems in this procedure may further improve the reliability of virtual chromoendoscopy.[52]

Use of Staining Agents in Endoscopy

Application of some staining agents requires the application of mucolytic agents such as N-acetylcysteine to remove mucus from epithelium to allow optimal results with staining.

The agent may be applied to a specific area or to the whole mucosal surface of interest. The abnormal mucosa may stain positively (ie, taking up the dye) or negatively (ie, remaining unstained or understained). In general, the minimum amount of dye required is used. Excess dye is suctioned or washed. The time required for optimal staining is variable and depends on the targeted tissue and the stain used.

Table 1 below details the properties and uses of each agent.[1]

Table 1. Properties of and Clinical Indications for Common Stains Used in Endoscopy [1] (Open Table in a new window)



Clinical Indication




Lugol solution (iodine and potassium


Glycogen-containing normal squamous

epithelium is stained dark brown;

inflammation, columnar mucosa, dysplasia,

and cancer remain unstained

Esophageal squamous cell cancer and


Barrett esophagus

Methylene blue (methylthioninium


Absorptive epithelial cells of the small

bowel, colon, and intestinal metaplasia at

any site are stained blue; dysplasia and

cancer is variably stained or unstained

Barrett esophagus

Gastric intestinal metaplasia and cancer

Chronic ulcerative colitis

Toluidine blue (tolonium chloride)

Nuclei of malignant cells are stained blue

Oral and esophageal squamous cell cancer

Crystal violet (methylrosaniline chloride

Absorbed into intestinal and neoplastic

cells; nuclear stain

Barrett esophagus

Colonic neoplasms




Indigo carmine (indigotindisulfonate


Nonabsorbed dark bluish dye highlighting

mucosal topography

Colonic neoplasms

Chronic ulcerative colitis




Congo red (biphenylenenaphthadene

sulfonic acid)

Color change from red to dark blue/black

in presence of acid at pH 3

Ectopic gastric mucosa

Gastric cancer

Adequacy of vagotomy

Phenol red (phenolsulfonephthalein)

Color change from yellow to red in

presence of alkali (eg, from hydrolysis of

urea to ammonia and carbon dioxide by

urease-producing H. pylori)

H. pylori infection

Chromoendoscopy is not an advanced endoscopic technique and is not technically difficult to learn. However, interpretation of the staining patterns requires training and may not always be easy. Evidence suggests that there is significant intraobserver and interobserver variation.[53, 54]