|Year : 2018 | Volume
| Issue : 3 | Page : 242-247
Role of narrow band imaging in the diagnosis of laryngeal lesions: Pilot study from India
Pirabu Sakthivel1, Kapil Sikka1, Alok Thakar1, Chirom A Singh1, Suresh C Sharma1, Madhu Rajeshwari2, Aanchal Kakkar2
1 Department of Otorhinolaryngology and Head and Neck Surgery, All India Institute of Medical Sciences, New Delhi, India
2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
|Date of Web Publication||28-Jan-2019|
Dr. Kapil Sikka
Department of Otorhinolaryngology and Head and Neck Surgery, All India Institute of Medical Sciences, New Delhi
Source of Support: None, Conflict of Interest: None
INTRODUCTION: Narrow band imaging (NBI) is a new imaging technique developed to improve the diagnostic accuracy of head and neck cancers by depiction of tumor-specific neo-angiogenesis. The purpose of this study was to assess the value of NBI in the diagnosis of laryngeal lesions. AIM: To assess the sensitivity and specificity of combined white light endoscopy (WLE) and NBI compared with WLE alone in the diagnosis of laryngeal lesions. SETTINGS AND DESIGN: Prospective study. MATERIALS AND METHODS: Thirty consecutive patients with various laryngeal lesions scheduled for microlaryngoscopic evaluation underwent WLE followed by NBI. Endoscopic NBI findings were classified into five types (I–V) according to the intraepithelial papillary capillary loop features. Types I–IV are considered benign, whereas type V is considered malignant. The observations were compared with histopathology. STATISTICAL ANALYSIS: Sensitivity, specificity, and positive and negative predictive values for the diagnosis of malignancy (i.e., invasive carcinoma and carcinoma in situ) by means of NBI with WLE were calculated. RESULTS: The sensitivity of WLE combined with NBI (100%) was higher than WLE alone (82.6%) in detecting laryngeal cancers. NBI helped in identifying four malignant lesions missed by WLE alone. Two children with respiratory papillomatosis also demonstrated type V pattern, a potential pitfall, leading to an overall positive predictive value of 92% and a negative predictive value of 100%. CONCLUSION: Combining NBI with WLE increases the sensitivity of detection of laryngeal cancer and its precursor lesions. NBI is also useful in some benign lesions as well as in post-radiotherapy patients.
Keywords: Endoscopy, laryngeal cancer, laryngoscopy, narrow band imaging
|How to cite this article:|
Sakthivel P, Sikka K, Thakar A, Singh CA, Sharma SC, Rajeshwari M, Kakkar A. Role of narrow band imaging in the diagnosis of laryngeal lesions: Pilot study from India. Indian J Cancer 2018;55:242-7
|How to cite this URL:|
Sakthivel P, Sikka K, Thakar A, Singh CA, Sharma SC, Rajeshwari M, Kakkar A. Role of narrow band imaging in the diagnosis of laryngeal lesions: Pilot study from India. Indian J Cancer [serial online] 2018 [cited 2019 Feb 15];55:242-7. Available from: http://www.indianjcancer.com/text.asp?2018/55/3/242/250893
| » Introduction|| |
The visualization of laryngeal and hypopharyngeal lesions has been significantly enhanced with the advent of technological advancements in endoscopes, lighting systems, and camera systems. Accurate recognition of the exact pathology by non-invasive means, however, has remained a considerable challenge. The detection of lesions that are small, recurrent, or in post-treatment settings, and the differentiation of benign versus malignant lesions in certain situations present formidable challenges to clinicians.
Narrow band imaging (NBI) is an optical image enhancement technology that enhances the vessels in the surface of the mucosa using light absorption characteristics of hemoglobin at a specific wavelength. This technique alleviates the need for microscope or any special dyes. In the NBI mode, an optical filter allows a narrow-band low-penetration blue light, centered at 415 nm (range, 400–430 nm), to penetrate only the superficial layer where it is absorbed by the capillary vessels in the surface layer of mucosa. In parallel, a narrowband deep penetration green light, centered at 540 nm (range, 525–555 nm), is applied, which penetrates deeper into the tissue and specifically illustrates the vessels in the submucosa. This results in contrast of the images obtained by the 415-nm light (brown) and 540-nm light (cyan) depicting tumor-specific neoangiogenesis.,,
Because neoangiogenesis accompanies upper aerodigestive tract mucosal squamous cell carcinomas (SCCs), NBI has the potential to detect dysplastic tissue at an earlier stage compared to conventional white light endoscopy (WLE).,,,
The characteristic patterns of changes in morphology of intraepithelial papillary capillary loop (IPCL) in the superficial mucosa of normal, inflammatory, precancerous, and cancerous tissues have been studied extensively under NBI. IPCL changes signifying malignancy are dilatation, meandering, change in caliber, and non-uniformity (variation in shape) of the vessels., Through this study, we have evaluated the diagnostic potential of NBI compared with WLE in identifying laryngeal lesions.
| » Materials and Methods|| |
NBI equipment included a xenon light source with integrated NBI filter, a high-definition videoendoscope with chip-on-the-tip technology, and a video system unit. Switching between the conventional mode (white light) and NBI mode is achieved by pressing a button on the endoscope or at the unit less than a second during the procedure. In this study, we used Olympus Medical Systems (Tokyo, Japan) with their standard settings.
Patients and procedure
This study was conducted between September 2016 and December 2016 in the Department of Otorhinolaryngology, All India Institute of Medical Sciences, New Delhi. Thirty consecutive patients with a laryngeal lesion scheduled for micro laryngoscopic evaluation underwent conventional WLE in the outpatient clinic under local anesthesia (using 10% lidocaine hydrochloride spray) in the sitting position. In the WLE mode, suspicious lesions were identified by color change (leukoplakia, demarcated red lesions) and irregularity of mucosal surface (growth, bulging, and ulceration). NBI was performed immediately after WLE in the preoperative setting with the images of all examinations recorded and saved on a computer for further evaluation. NBI findings were classified into five types (I–V) according to IPCL features, as recommended by Ni et al., as follows:
Type I lesions correspond to thin, oblique, and arborescent vessels without any IPCL.
Type II lesions show enlarged, oblique, and arborescent vessels without any IPCL.
In type III lesions, vessels are obscured or seen indistinctly by white mucosa.
In type IV lesions, IPCL can be recognized as regular, small, and dark brown spots.
In type V lesions, IPCL appears solid or hollow, with a brownish, speckled pattern, and of various shapes (type Va), or as irregular, tortuous, line-like shapes (type Vb), or as brownish speckles or tortuous, line-like shapes with irregular distribution, scattered on tumor surface (type Vc). Thus, type I–IV lesions are considered benign and V lesions as malignant.
Informed written consent was obtained from each patient before the procedure. All biopsies were performed after obtaining NBI images. The biopsy specimens were fixed in 10% formalin and submitted for histopathological examination. The pathologist was blinded to the results of WLE and NBI. The histopathologic results were analyzed retrospectively with NBI and WLE images. Sensitivity, specificity, and positive and negative predictive values for diagnosis of malignancy [i.e., invasive carcinoma and carcinoma in situ (CIS)] were calculated separately for WLE and WLE with NBI.
| » Results|| |
All the patients (n = 30) tolerated the procedure of endoscopy well. The clinical characteristics of the patients are depicted in [Table 1]. The average time taken for complete procedure of endoscopy (both WLE + NBI) was 2–3 min. Histopathological examination revealed a malignant/pre-malignant lesion in 23 patients [19 cases of SCC; 2 cases of CIS, and 2 cases of adenoid cystic carcinoma (ACC)]. Of these, all the 21 surface epithelial lesions were correctly classified as malignant by NBI only on the basis of abnormal intraepithelial microvascular changes [Table 2]. In contrast, WLE was able to pick up only 17 (of 21) cases. NBI, through its enhanced optics and contrast, picked up these four early malignant lesions which were barely suspicious for malignancy under WLE [Figure 1]. Both the cases of ACC did not reveal any abnormal IPCL on NBI-only view. However, these could be visualized as submucosal growth by WLE. Thus, combining NBI with WLE increased the diagnostic sensitivity to 100% for identification of malignant lesions [Table 3].
|Table 2: Correlation between histopathology and NBI findings according to ICPL patterns|
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|Figure 1: (a) Erythroleukoplakic patch, bilateral cords. (b) NBI image, right cord, Va pattern (arrow). Inset- Close view. (c) WLE: Vocal cords in a case of recurrent respiratory papillomatosis. (d) NBI, depicting abnormal IPCL pattern (type Vb pattern in inset). Biopsy revealed squamous cell carcinoma. (e) WLE of vocal cords showing a leukoplakic patch whereas in (f) NBI vascular atypia was noted in a small area (Type Va arrow and inset). (g) WLE of vocal cords showing a small area of irregularity (arrow) where as in (h) NBI scattered brown dots were seen (inset- type Va) and biopsy in last two cases revealed CIS|
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Among benign lesions, vocal nodule (n = 2) and tuberculosis (n = 1) displayed type II pattern. NBI was particularly helpful in the latter case, in which the patient had a slough-like growth over true vocal cords with WLE mimicking malignancy. NBI findings also helped in a patient who had previously undergone radiotherapy for stage Ia carcinoma of the left true vocal cord [Figure 2]. On WLE, there was a lesion at the same site, suspicious for recurrence but on NBI type III pattern was noted and the biopsy revealed mild to moderate dysplasia without any invasive malignancy. However, respiratory papilloma cases (n = 2) were falsely positive for malignancy in NBI with type V pattern [Figure 3].
|Figure 2: False positives with WLE. (a) WLE showing a slough covered growth and (b) on NBI only dilated vessels were seen with no abnormal IPCL patterns and the biopsy was suggestive of tuberculosis (c) WLE showing a growth in a post radiotherapy patient for carcinoma left vocal cord whereas in (d) NBI no scattered brown spots were not noticed over the entire lesion and the biopsy report ruled out invasive carcinoma|
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|Figure 3: False negatives and false positives with NBI. (a) WLE revealing a large submucosal bulge in the supraglottis and on (b) NBI, no IPCL patterns were noted except for increased vasculature. Biopsy revealed Adenoid Cystic Carcinoma. (c) WLE view of papillomas and on (d) NBI type Va pattern was noted with biospy suggestive of benign papillomas|
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Sensitivity, specificity, and positive predictive value and negative predictive values for diagnosis of malignancy by means of combining WLE + NBI images calculated from these results were 100%, 71.43%, 92%, and 100%, respectively [Table 4].
NBI findings are particularly useful in many cases for guiding the site of biopsies [Figure 4].
|Figure 4: NBI guidance for targeted biopsy to increase the yield. (a) WLE: Large bulge with no ulcerated area (b) NBI: Afferent vessels (black arrows) and scaterred brown dots (white arrows) seen in the right ventricle. (c) WLE showing leukoplakia with raised lesion on both vocal cords (d) NBI: Clear areas of scattered brown dots with vascular atypias (Type Vb) seen on the right vocal cord with involvement of anterior commissure. (e) WLE showing a large bulge (f) NBI: Snake like vessels on the medial surface of the bulge. Targeted biopsies from these areas in all three cases revealed invasive SCC|
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| » Discussion|| |
As early malignant disease of larynx has a favorable prognosis, it is mandatory for the treating otolaryngologist to have a clear understanding of the clinical features of premalignant and early malignant changes in the larynx.,
Because of the current availability of thin high-definition videoendoscopes, indirect NBI is practical for use in the outpatient setting. Furthermore, this promising method can be performed with rigid endoscopes during micro-laryngoscopy. As no drug administration is required (except for local anesthetic spray), one need not be concerned with side effects or complications. Other advantages of NBI are convenient handling of its equipment, excellent image quality, and photo documentation.,
Although there are several studies assessing the value of NBI in head and neck cancers, there are only a few publications on its exclusive use in laryngology [Table 5].,,,,,,,
The early diagnosis of laryngeal carcinoma relies on the characteristic type Va IPCL pattern in NBI. The sensitivity and specificity of type Va pattern in diagnosing severe dysplasia and CIS are very high. The sensitivity and specificity of NBI in our study was 100% and 71%, respectively. NBI is also useful in the setting of recurrent disease after surgery or radiotherapy, where proper identification of IPCL patterns (type Va or Vb) will help differentiate from post-therapy changes.,,, Although there is little advantange of NBI in identifying advanced tumors which are readily seen with WLE, NBI shows their exact extension, infiltration of neighboring structures, and also provides guidance for the site of biopsy. Often, malignant portions of lesions cannot be readily identified under WLE especially when the surrounding background mucosa is abnormal, as in post-radiotherapy patients, extensive leukoplakia, and tissue necrosis. NBI is particularly helpful in these situations for identifying the exact site of pathology. As NBI can be performed with rigid endoscopes during microlaryngoscopy, there is an exciting role for identifying margins before resection.,
Chang et al. advised that office-based NBI-guided flexible laryngoscopic biopsy is an effective and efficient technique with high diagnostic accuracy, and overall sensitivity and specificity were 97.2% and 100%, respectively, with a diagnostic accuracy of 98.9%. Accuracy in their study was not affected by tumor size, location, learning curves, or previous head and neck cancer history, indicating that NBI can aid in targeting specific site biopsies. In our study too, none of the patients needed a second biopsy for confirmation of malignancy.
We believe that NBI is also beneficial in a variety of benign lesions by their better recognition in NBI mode and hence, some benign lesions can readily be detected in a very early stage. NBI allows a better differentiation between bamboo nodes and vocal fold cysts, early respiratory papilloma, venous ectasias, or small hemangiomas, thus helping in several therapeutic occasions such as intraoperative laser vaporization of early respiratory papilloma and microcoagulation of ectatic veins or small hemangiomas., Dippold et al. found that NBI in combination with WLE improves the detection rate of benign lesions of larynx, especially of vocal fold cysts.
In the evaluation of any new method, it should be compared with gold standard technique, which is the histopathological examination in case of laryngeal lesions. We included patients already scheduled for microlaryngoscopy, and hence a few benign lesions were also included in our study. This study design allows for histologic diagnosis of all lesions, which has not been fulfilled in some of the previous studies., Because NBI was performed after WLE in all the cases, our results do not reflect the outcome of NBI alone. This certainly was a limitation of our study, and bias from initial WLE could reasonably exist. However, the same is true for the majority of the NBI literature published earlier. Muto et al. conducted a clinical trial in which 333 patients were randomly assigned to primary WLE followed by NBI and vice versa, thus controlling this problem. This study demonstrated that when WLE was followed by NBI, the diagnostic accuracy was higher than in the alternative order and is unlikely to miss a mucosal lesion.,,
NBI has excellent negative predictive values for identification of primary, recurrent tumors, and carcinoma of unknown primary cases, providing great clinical value for patient reassurance with negative endoscopy.,
Although NBI has many advantages, a few hardships may be encountered. To assess the vessels properly, the videoendoscope is brought close to the lesion, that is, behind the epiglottis deep into the larynx, which at times is difficult in patients with strong gag reflex., In such patients, NBI can be performed after giving regional blocks or under general anesthesia. The cost of the equipment and lack of assessing the vertical extent of the lesion are other significant disadvantages of NBI.
Occasionally, false-negative and false-positive results do occur with NBI. Severe hyperkeratosis may cover a subjacent cancerous lesion, warranting the need for thorough examination of the surrounding areas for any vascular atypias., Similarly, capillary patterns may not be appreciable in submucosal lesions. We had false-negative reports in two patients with ACC, which clinically appeared as a submucosal bulge, masking the IPCL patterns.
Another shortcoming with NBI is the presence of type Va pattern in respiratory papillomas, which also appear as well-demarcated brownish areas with irregular dark spots., However, in most cases, these benign lesions can be distinguished from malignancy by their typical appearance on WLE. In this study, two children with respiratory papillomatosis demonstrated type Va pattern, leading to an overall positive predictive value of 92% and a negative predictive value of 100%. Occasionally, isolated small vocal cord cancers can be confused with isolated respiratory papillomas. There is a learning curve for NBI endoscopy. Regular and smaller brown spots with blurred edges are often caused by inflammatory or post-radiation changes.,
The sample size is too small to accurately determine the diagnostic accuracy of NBI for diagnosis of laryngeal lesions. Because our center is burdened with malignancy patients, only a few benign cases were scheduled for microlaryngoscopy and hence less number of benign cases was included in the study. Ours is the first study on the use of NBI in diagnosis of laryngeal lesions in Indian patients.
| » Conclusion|| |
Combining NBI with WLE increases the sensitivity of identifying laryngeal cancer and its precursor lesions. NBI helps in detection and delineation of suspicious malignant lesions, determination of their horizontal extension, and field cancerization. NBI is also useful in a variety of benign lesions and in post-radiotherapy patients. Despite being a clinically useful tool than WLE in various laryngeal lesions, the possibility of false-positive and false-negative results, though rare, should be kept in mind. Cost-effectiveness requires to be thoroughly evaluated by larger studies taking financial aspects into consideration, especially in developing countries.
Informed consent was obtained from all individual participants included in the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]