Derived from the Greek words leukos, meaning “white,” and plakoeis, meaning “flat” to describe white patches on the surface of the vocal folds, laryngeal leukoplakia is a purely descriptive term that does not denote a pathologic diagnosis ( Fig. 40.1 ). These white lesions can harbor a wide range of pathologic conditions, from keratosis to infections to cancer. Unfortunately, the macroscopic appearance of these lesions does not reliably predict the underlying histopathology. More than half of leukoplakic lesions show no evidence of dysplasia. The malignant transformation rate for vocal fold leukoplakia in the literature ranges from 1% to 40%, with a tendency for increasing risks as dysplasia grades increase. Due to this relatively high variability in the risk of dysplasia and malignant transformation, the management and timing of surveillance for vocal fold leukoplakia can vary significantly based on the experience and practice pattern of the individual otolaryngologist.

Laryngeal leukoplakia.

(A) White light examination of glottic leukoplakia. This example involves nearly the entire superior and medial edges of the true vocal folds, where it causes hoarseness. The pathologic diagnosis can rarely be determined by visual inspection alone–definitive diagnosis is given at the time of pathologic analysis of the biopsy sample. (Courtesy Ramon A Franco Jr.)

(B) Narrow-band imaging (NBI) of image (A). Filtering the white light to enhance certain wavelengths of light can help to better define the true extent of the leukoplakic changes. NBI is the name of the light filtering technology from Olympus. Similar technology goes by the names i-Scan (Pentax) and Storz Professional Image Enhancing System (SPIES). (Courtesy Ramon A Franco Jr.)

(C) White light examination of glottic dysplasia that appears to mainly affect the right true vocal fold and superior anterior commissure. (Courtesy Ramon A Franco Jr.)

(D) Narrow-band imaging of (C). The borders between diseased and nondiseased tissue are better delineated with the filtering technology. There also appear to be changes that were not noticed on the white light image (C) along the medial left true vocal fold that are seen on NBI. (Courtesy Ramon A Franco Jr.)

(E) White light examination of right true vocal leukoplakia on a bed of erythema. We see scattered patches of leukoplakia along the right true vocal fold (superior and medial edges) that are mainly concentrated in the mid-musculomembranous region. Disease extends laterally to the edge of the visible vocal fold (could be extending into the ventricle) and onto the arytenoid cartilage posteriorly. The erythema under and surrounding the white patches could represent a reaction to whatever is causing the white patches (fungal infection vs. cancer vs. another inflammatory process). (Courtesy Ramon A Franco Jr.)

The patterns of management of these lesions often mirror the treatment of early glottic cancer, including conventional cold-steel excision, transoral laser microsurgery, and radiotherapy. Angiolytic lasers such as the 585 nm pulsed-dye laser (PDL), 532 nm potassium titanyl phosphate (KTP), and various diode lasers (445 and 635 nm) have been reported in the treatment of laryngeal leukoplakia. ^, These pulsed angiolytic lasers are either at or are close to peaks in the absorption spectrum of oxyhemoglobin, allowing them to target the subepithelial vasculature in addition to the lesion. Pulsing of the laser energy allows time for the dispersion of heat, which spares the normal surrounding tissue from thermal damage. These lasers create a cleavage plane between the layers of the basement membrane, allowing easy removal of the epithelial lesion alone, sparing the superficial lamina propria. A comparison of the management of vocal fold leukoplakia with CO ₂ laser transoral surgery to 532 nm KTP laser revealed that the KTP laser had comparable disease control and better vocal function preservation. The 585 nm Pulsed Dye Laser and the 532 nm Aura XP are not commercially available any longer. The Wolf 445 nm TruBlue laser (A.R.C. Laser GmbH, Nurnberg, Germany) is the currently available angiolytic laser for laryngeal use ( Fig. 40.2 ). Ideal treatment outcomes for vocal fold leukoplakia include the complete treatment of diseased epithelium with no vocal fold scarring and preservation of vocal quality. Photodynamic therapy (PDT) has been a promising novel technique introduced over the past few decades that may better realize these ideal treatment outcomes.

Wolf TruBlue 445 nm laser (A.R.C. Laser, Nurnberg, Germany). This angiolytic laser can be used to activate protoporphyrin IX as its 445 nm wavelength is close to the major absorption peak of PpIX around 400 nm. When aminolevulinic acid-treated tissue has been given sufficient time to convert to PpIX and is exposed to laser light, the result is the creation of oxygen radical species that internally attack organelles and nucleic acids, leading to cell death. (Courtesy Ramon A Franco Jr.)

PDT depends on the presence of three factors: a photosensitizing agent, an energy source, and oxygen. The photosensitizing agent is retained in the diseased tissue and activated by an energy source. After exposing the photosensitizing agent to the energy source, oxygen radicals are produced, leading to organelle and DNA damage, eventually killing the cells that were selectively activated. PDT, in theory, is a photochemical reaction that is nonthermal and thus spares neighboring normal tissue. PDT also only affects the cells that have taken up the photosensitizer and have been exposed to the energy source, allowing the physician to target the areas to be treated. Various agents have been used for PDT of the larynx, including porfimer sodium and 5-aminolevulinic acid (ALA). Topical ALA is one of the preferred photosensitizing agents for the upper aerodigestive because it does not leave the patients photosensitive for weeks, as happens with the intravenous administration of porfimer sodium. The use of ALA-PDT to treat laryngeal leukoplakia was first reported in 1999 by Malczewski et al. After topical application of ALA, the exogenous ALA enters the porphyrin-heme biosynthesis pathway and is converted to protoporphyrin IX (PpIX), which results in the accumulation of PpIX in the mitochondria. After a set period (1–3 hours), PpIX is then activated by an energy source of the proper wavelength,which produces oxygen radicals, causing cell death in those cells exposed to the laser energy. It is important to use a light source that targets the PpIX absorption peaks of 400–410 nm and 635 nm to maximally treat laryngeal leukoplakia ( Fig. 40.3 ).

Absorption peaks for Protoporphyrin IX (PpIX). The 445 nm TruBlue laser ( blue lightning bolt ) is better absorbed than the 532 nm Aura XP KTP laser ( green lightning bolt ). This makes the 445 nm blue laser more efficient at activating PpIX to institute photodynamic therapy using aminolevulinic acid. (Courtesy Ramon A Franco Jr.)

This technique treats laryngeal leukoplakia ranging from low-grade dysplasia to the most recalcitrant high-grade dysplastic lesions. Laryngeal leukoplakia tends to recur, requiring multiple biopsies and excisions. Each of these multiple procedures potentially injures the true vocal folds and leaves them susceptible to permanent damage and scarring. When one considers that most glottic leukoplakia is not malignant, these procedures can sometimes lead to overtreatment. However, one should always consider the premalignant nature and possible malignant transformation of these lesions. There should always be careful consideration for how much vocal fold tissue should be treated and/or excised.

PDT is an effective technique in the treatment of glottal dysplasia and spares the superficial lamina propria while creating a cleavage plane that allows the complete removal of the dysplastic epithelium. Because the conversion of ALA to PpIX tends to take place faster in the dysplastic cells, there is an accumulation of PpIX in the visible lesions when compared to the surrounding normal tissue. When laser light is directed to the leukoplakia, this differential accumulation of PpIX leads to preferential creation of reactive oxygen species within the dysplasia, causing cell death. This makes ALA a valuable adjunct to the treatment of these lesions. This mechanism is especially important in the recurrent dysplastic lesions of the vocal folds. The main indication of this technique is recurrent and biopsy-proven dysplasia of the vocal folds. It is important that these lesions be biopsied to exclude possible malignancy. This technique has the benefit of being able to be performed under either local or general anesthesia. Performing the procedure in the office saves the patient from a visit to the operating room and exposure to general anesthesia. This is a major advantage as these lesions tend to recur and require multiple procedures.