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| REVIEW ARTICLE |
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| Year : 2012 | Volume
: 2
| Issue : 2 | Page : 53-59 |
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Contact Endoscopy - A promising tool for evaluation of laryngeal mucosal lesions
Awadhesh Mishra1, Ajith Nilakantan2, Rakesh Datta1, Kavita Sahai3, Satwinder P Singh1, Ashwani Sethi1
1 Department of ENT-HNS, Base Hospital, Delhi Cantt, India
2 Department of ENT-HNS, Army Hospital (R&R), Delhi Cantt, India
3 Department of Pathology, Base Hospital, Delhi Cantt, India
| Date of Web Publication | 5-Feb-2013 |
Correspondence Address:
Awadhesh Mishra
Department of ENT-HNS, Base Hospital, Delhi Cantt, New Delhi-110010
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2230-9748.106978
 Abstract | | |
Early diagnosis of laryngeal cancer is important for favourable treatment outcome. Due to morbidity and difficulties associated with surgical biopsy, a need has always been felt for an easy, non invasive yet accurate tool for knowing histopathological nature of mucosal lesions. Contact Endoscopy (CE) is one such technique which is capable of providing real time and magnified images of cellular structure of superficial layers of various mucosal surfaces with obvious advantages and potential for wide clinical application. In this review, a summary of role and efficacy of CE in diagnosis, treatment and follow up of various laryngeal mucosal lesions is presented. We searched Pubmed, Medline, Cochrane and Google scholar for articles on CE for mucosal lesions of larynx. For better understanding of the technique, articles on CE of other non-laryngeal sites of head and neck were also reviewed. Article selection was limited to human studies without restriction to language and year of publication. Reference lists from identified articles were also searched. Six prospective original articles, three descriptive studies and one review article on CE of laryngeal lesions are included in this review and their findings summarized. Common findings on examination of cellular architecture and vascular patterns described by various authors are also tabulated. The literature revealed high sensitivity (90-94.7%), specificity (81-100%) and accuracy (88-94%) of CE in diagnosis of laryngeal lesions across the published studies. CE is a promising non invasive tool for evaluation of laryngeal mucosal lesions. However, further prospective, randomized, double blinded studies as well as research to improve the technique to overcome the existing limitations are required before defining its precise role in clinical practice. Keywords: Contact endoscopy, laryngeal, larynx, mucosal lesions, malignant, non invasive, pre malignant, vocal cord
How to cite this article:
Mishra A, Nilakantan A, Datta R, Sahai K, Singh SP, Sethi A. Contact Endoscopy - A promising tool for evaluation of laryngeal mucosal lesions. J Laryngol Voice 2012;2:53-9 |
| Introduction | |  |
Mucosal lining of Head and Neck area is exposed to a variety of carcinogens rendering it prone to develop malignancy. Squamous cell carcinoma of head and neck is ranked 6 th in occurrence among all cancers in the world, [1] while incidence of laryngeal cancer is reported as 5.7 per 100,000 in males and 0.7 per 100,000 in females. [2] Clinicians encounter various mucosal lesions ranging from mild changes in appearance of the mucosa to frank ulcero-proliferative growths. Many of these lesions, which on inspection may not appear to be 'ulcers' or 'growths', are known to harbour malignancy or undergo malignant transformation later on. Early detection and diagnosis of such suspicious mucosal lesions is very important for favourable outcome of the treatment. At present, the gold standard of diagnosis of such lesions is the histopathological examination by surgical biopsy which has, particularly in larynx, many disadvantages like risk of bleeding, infection, change in quality of voice and painful swallowing. The diagnosis may not be ascertained on single biopsy and the lesion may require follow up with multiple biopsies which can cause significant morbidity and delay in commencing treatment. Interpretation of biopsy taken subsequently may be difficult due to scarring and other changes resulting from previous biopsies. Further, in case of residual or recurrent lesion after surgery and/or radiotherapy, differentiation of cancerous lesion from oedema and scarring is quite difficult.
During surgery for tumour excision, less removal will leave the disease behind while excessive removal will cause problems in reconstruction and more morbidity. There is, therefore, a need for a non traumatic, repeatable technique which can show histopathological picture of the lesion reliably and in vivo, without biopsy. Many techniques have been described for achieving this goal. These include aminolevulinic acid-induced fluorescence, auto-fluorescence, Narrow Band Imaging Endoscopy, Optical Coherence Tomography, Laser Doppler flowmetry, Confocal Endomicroscopy, and CE. Out of these only confocal endomicroscopy and CE are capable of showing details of cellular architecture and patterns of vascularisation in the lesion.
CE was originally described by Hamou in 1979. He used it as a technique for visualization of cervical and uterine epithelial cells for screening and diagnosis of cervical and uterine pathology. [3] In head and neck, CE was first reported by Andrea et al. as a diagnostic tool in the evaluation of various pathologies in the larynx in 1995. [4],[5] Thereafter its use has been reported in diagnosis of mucosal lesions of oral cavity, [6] oropharynx, hypopharynx, [7] nose, [8] nasopharynx, [9] study of recurrence of cholesteatoma in the ear, [10] per operative identification of parathyroid glands, [11] comparison of fungiform papillae of healthy subjects and patients with transacted Chorda Tympani nerve [12] etc.
The role and efficacy of CE in diagnosis, management and follow up of laryngeal mucosal lesions will be reviewed in this article.
The technique of CE
Contact Endoscopy (also called as Contact Microlaryngoscopy by some) is essentially a non-invasive, optical technique of visualisation which helps real time and in situ examination of the pattern of vascularisation as well as cellular architecture of the superficial layers of the mucosa. For oral cavity and other accessible areas, the contact endoscope can be used in out patient department (OPD) while evaluation of laryngeal mucosa requires passage of contact endoscope through a suspension laryngoscope under anaesthesia. The endoscope used (30°/0°) consists of rod lens system with facility for 60x and/or 150x magnification. For visualisation, it is gently placed over the mucosa and moved slowly over the area of interest after connecting it to a xenon light source as well as to a good quality camera and monitor. Images are digitally captured by the camera and can be stored both as photograph and video [Figure 1]. Vascular patterns [Figure 2], [Figure 3] and [Figure 4] are studied before staining as the dye leads to loss of transparency of mucosa making the blood vessels invisible. Cellular architecture [Figure 5], [Figure 6] and [Figure 7] is studied after staining the mucosal surface with 1% methylene blue which imparts a dark blue colour to the nucleus and light blue colour to the cytoplasm. Excess stain needs to be removed by washing the area with copious amount of normal saline using suction and irrigation. Methylene blue is non toxic and the staining is reversible. The images can be analysed by the Otolaryngologist as well as histopathologist during the procedure and also can be reviewed later on as many times as needed. | Figure 2: CE image of blood vessels on normal vocal cords: Blood vessels are parallel to long axis of vocal cord; bifurcations and anastomoses are few
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 | Figure 3: CE image of blood vessels in early laryngeal cancer: Increased number of blood vessels with increase in bifurcations and anastomoses. Decreased parallelity with long axis of vocal cord is also seen
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 | Figure 4: CE image of blood vessels in advanced laryngeal cancer: Complete loss of parallelity, extensive anastomoses leading to formation of vascular loops
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 | Figure 5: CE image of cellular architecture of normal vocal cord: Homogenous cells with uniform size and shape, Nuclear cytoplasmic ratio uniform and less than 1, nuclei of uniform size and shape and evenly stained, no hyperchromatism or mitotic figures
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 | Figure 6: CE image of cellular architecture of squamous carcinoma 1: Increased number of cells per field, non homogenous distribution, size and shape of cells, nucleus shape and size varying in the same field, nuclei more darkly stained and larger in size, nuclear-cytoplasmic ratio variable among cells, many cells with nuclear - cytoplasmic ratio of more than one (arrow), mitotic figures present
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 | Figure 7: CE image of cellular architecture of squamous carcinoma 2: Multiple mitotic figures are seen (arrows)
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| Materials and Methods | | |
A literature search using the following key terms: "Contact endoscopy", "contact microlaryngoscopy", "larynx", "Vocal cord", "head and neck carcinoma", "leukoplakia", "mucosal lesions" and "non invasive" was conducted. Medline, Cochrane, Pubmed and Google scholar databases were searched. Search was performed by combining search terms using Boolean operators. Article selection was limited to human studies without restriction to language and year of publication. Reference lists from identified articles were also searched and cross referenced to find additional relevant publications.
| Results | | |
Six prospective original articles and three descriptive studies on CE for laryngeal lesions as well as one review article on CE (covering entire head and neck including larynx) are included in this review. Findings from these studies are summarized in [Table 1]. Only four studies have calculated sensitivity, specificity and accuracy indices. [7],[13],[14],[15] Common findings on examination of cellular architecture and vascular patterns described by various authors on CE of larynx are tabulated in [Table 2]. | Table 2: Common findings observed on CE of larynx described in literature
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Warnecke et al. [7] examined 42 consecutive patients with suspicious lesions of larynx and pharynx under general anesthesia. All were biopsied after endoscopy and sample subjected to histopathological examination. They reported high sensitivity and specificity of CE in diagnosing various mucosal lesions in pharynx and larynx but its dependence on the experience of the examiner was also brought out.
Cikojeviæ et al . [13] compared intra-operative utility of CE with frozen section examination in the diagnosis of laryngeal pathology in 142 patients. Paraffin section histopathological examination was taken as gold standard. All lesions identified by CE as malignant were confirmed by histopathology, but CE failed to identify malignancy in 10 patients.
Tarnawski et al. [14] performed CE on 54 patients with various laryngeal pathologies intraoperatively during microlaryngoscopy. Their results were based on computer-assisted analysis of all CE images for certain nuclear morphometric parameters.They reported, on computer-assisted analysis of CE images, 100% sensitivity and specificity for diagnosis of Squamous cell carcinoma and severe dysplasia but overall sensitivity and specificity for all lesions put together was only 91% and 81% respectively.
Arens et al. [15] examined 83 patients using auto fluorescence along with CE during microlaryngoscopy and called it Compact Endoscopy. For CE, the calculated sensitivity was 94.7%, specificity of 95.5% and an accuracy of 94%.
Dedivitis et al. [16] used CE for deciding tumour resection margins in fronto lateral laryngectomy and found 100% agreement of CE results with histopathological findings. Sone et al. [17] carried out vascular evaluation of various laryngeal lesions using Laser Doppler Flowmetry and CE. The variables measured by the two methods were strongly correlated.
Carriero et al. [18] described CE findings in 18 cases of various laryngeal lesions. The cytological findings on CE were consistent with histological findings in all cases. Wardrop etal.[19] and Andrea et al. [4] described the details of cytological characteristics of various laryngeal mucosal lesions on CE.
In their review article Szeto et al. [20] reported overall sensitivity of 79-100%, specificity of 81-100%, and accuracy of 88-94% of CE in diagnosis of mucosal lesions of head and neck (including larynx) based on five prospective studies reviewed by them.
Thus, the literature reveals high sensitivity, specificity and accuracy of CE in diagnosis of laryngeal lesions across the published studies.
| Discussion | | |
Many researchers have reported high efficacy of CE in diagnosis of mucosal lesions of not only larynx but other sites of head and neck as well. [7],[8],[9],[13],[14],[15],[16],[7],[18],[20] These results have been obtained taking the histopathological examination as the gold standard. However, the technique of CE has definite advantages and limitations.
Advantages of CE
Based on reviewed literature, following advantages of CE could be identified:
- Non invasive, simple, quick, repeatable, in vivo examination of cellular architecture and vascular pattern of the mucosa.
- Large and multiple areas can be examined quickly and in the same sitting as compared to limited areas assessed by biopsy.
- Avoids risks associated with biopsy/repeated biopsies. Also avoids tissue damage and changes in cells which can occur due to biopsy and processing of tissue for histopathological examination. Suspicious lesions thus can be followed up serially without antecedent morbidity associated with surgical biopsy.
- Can help in deciding precise site for taking biopsy by identifying areas of cellular atypia which may improve the yield of biopsy.
- Can help in deciding margins of resection during tumour removal by differentiating tumour areas from normal mucosa. The line of demarcation between carcinoma and normal mucosa is not regular.
- Mapping the tumours is easy.
- Results are known immediately.
- Can be employed both in out patient department and operation theatre.
- Can be combined with other techniques like autofluorescence (Compact Endoscopy).
- The CE can be performed just before surgical excision, hence it can be employed even when other surgical techniques like endoscopic laser are used.
- Video and still images can be stored and reviewed as many time as necessary.
Limitations of CE
The two inherent limitations of CE identified in majority of studies include inability to detect very early dysplasia and differentiation of 'carcinoma in situ' from 'invasive carcinoma'. Early dysplasia first appears in the cells near basement membrane which are not seen on CE as the light as well as dye are unable to penetrate deeper than few superficial layers of the mucosa. Consequently, some delay in diagnosis by CE can occur till the dysplastic cells migrate to superficial layers. Similarly, invasive carcinoma is differentiated from carcinoma in situ by angioinvasion/neoangiogenesis at the level of basement membrane which may not be picked up by CE. Hence, absence of angioinvasion/neoangiogenesis on CE should not be taken as absence of invasive carcinoma. CE may not be appropriate tool for evaluation of submucosal lesions for the same reason.
Other limitations of CE include optical artifacts occurring at high magnification which can pose difficulty in image interpretation. Necrosis on the surface of the tumour makes performance of CE difficult due to bleeding and poor uptake of stain. All these factors can cause false negative results. Image interpretation at present is prone to subjective bias on the part of the interpreter. Ancillary techniques like antibody labelling/immunohistochemistry for confirmation of malignancy cannot be used with this technique at present.
Technical difficulties
Technical difficulties reported for CE include the need for anaesthesia for passage of contact endoscope through a suspension laryngoscope, problems with line of sight, stain precipitation causing artefacts, difficulty in achieving optimum staining, stain getting washed away too quickly by secretions, secretions smeared on the mucosa causing artefact/forcing frequent withdrawal of the scope to dry the mucosal surface, need for frequent cleaning of the tip of the scope during the procedure etc.
Training and learning curve
There is always a learning curve in this technique and some amount of training in performing the procedure as well as interpretation of images obtained thereof is desirable.Presence of the histopathologist during initial phase may be rewarding. Earlier studies have emphasised the need for collaboration between endoscopist and pathologist especially at the initial stages. [4],[21]
Current status
Despite the technique of CE of larynx being in existence for almost two decades and many prospective studies revealing it's high sensitivity, specificity and accuracy in diagnosis of laryngeal mucosal lesions, it has not found wide spread use in routine clinical practice. The fact that some malignant lesions can be missed on CE brings hesitation on the part of clinician to substitute CE for biopsy in routine clinical practice at present.
Further prospective randomized doubleblind studies to ascertain its diagnostic accuracy are needed. Present day literature reveals paucity of such studies but abundance of descriptive reports. Also, dedicated future research is warranted in the following areas:
- Improvement in optics of the instruments and staining methods to allow examination of deeper layers.
- Better image capture and enhancement technique to make cellular changes easily detectable.
- Computer software and hardware to allow accurate assessment of various mucosal changes eliminating interpreter bias e.g. automatic counting of number of cells per field, estimation of size of cells and nuclei, assigning numerical value to degree of staining, calculating nuclear cytoplasmic ratio etc.
- Computer assisted estimation of number and calibre of blood vessels per unit area of examination, rate of flow of RBCs inside the vessels etc.
| Conclusion | | |
CE is a promising non invasive tool to know cellular architecture and vascular patterns in vivo without surgical biopsy for evaluation of laryngeal mucosal lesions and has shown high sensitivity, specificity and accuracy. However, further prospective, randomized, double blinded studies as well as research to improve the technique to overcome the existing limitations are required. At present it is not recommended to substitute surgical biopsy but can be useful tool in deciding the most suitable area for obtaining biopsy to reduce sampling error, as an adjunct to frozen section in deciding tumor resection margins during surgery and serial follow up of precancerous lesions as well as post treatment monitoring of mucosal lesions of larynx. We envisage that future research into improvement of the technique and well conducted clinical trials may enable CE findings to be instrumental in deciding the treatment modality both pre operatively as well as during surgery.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2]
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