laryngeal leukoplakia

1. Nassr Saif ALBarhi

2. Outline
 Introduction.
 Aim of study.
 Methods.
 Discussion
 Epidemiology.
 Risk factors.
 Pathology.
 Diagnosis.
 Treatment.
 New direction.

3. Introduction
 Its descriptive term “white plaque’’ on the vocal fold that can correspond to
a variety of pathologies:
 Benign keratosis.
 Dysplasia.
 Carcinoma in situ.
 Squamous carcinoma.
 A proper diagnosis is the first step toward determining prognosis and a
treatment plan.

4.  Managing this problem is especially challenging due to:
 The variety of pathology.
 Degree of dysplasia.
 Predicting prognosis.
 Balancing voice preservation with surgical excision of the disease.
 Management relates to the lesions’ frequent position along the vibratory edges of
the vocal folds, where scarring may have functionally important consequences to
voice quality.

5. The aim of this study to
 Describe the epidemiology, diagnosis, and management of vocal fold
leukoplakia, with focus on recent advances.
 In the interest of focusing on the distinct clinical entity of leukoplakia, they
excluded squamous papilloma and verrucous hyperplasia.
 Dilemmas and controversies will be discussed, and the techniques and
philosophies reviewed are applicable to the general otolaryngologist as well
as the laryngology specialist.

6. Methods
 A detailed literature search was performed in the PubMed/ MEDLINE database
for publications related to :
 Vocal cord and laryngeal leukoplakia, dysplasia, hyperkeratosis, leukoplakia
endoscopy, and leukoplakia management.
 Search based on certain criteria:
 Literature was chosen based on current practices and techniques for management
of leukoplakia, with specific regard to voice preservation and functional outcomes.
 A literature search was performed to include studies that focused on epidemiology,
oncologic follow-up, and long-term outcomes.

7. Discussion

8. Epidemiology
 In the United States, the annual incidence of vocal fold leukoplakia and
keratosis is:
 4.2 per 100,000, with a male predilection of 10.2 incidences per 100,000
compared to 2.1 in females in 1 study and an estimated 70% to 76% of male
predominance in others.
 About median age of leukoplakia incidence from 61.7 to 63 years old suggests
a temporal relationship between leukoplakia and laryngeal carcinoma whose
median age is 10 to 15 years older.
 Most lesions tend to occur on the medial and superior edges of the mid-true
vocal fold and anterior commissure;
 lesions are unilateral in 78% to 84% of cases.
 Posterior glottis nor the false vocal folds are typically not involved

9. Risk factors
 Cigarette smoking is the major risk factor for development of laryngeal
squamous intraepithelial lesions and laryngeal malignancy.
 The incidence of cigarette smoking in patients with leukoplakia and keratosis
is 67%, and increased duration of smoking has been associated with higher
rates of malignant transformation.
 A recent large retrospective review of 1184 patients in Germany with
leukoplakia revealed increased risk for malignancy with advanced age and
male sex, with odds ratio:
 4.90 for patient more than 65 years of ages.
 2.55 for patients ages 50 to 65.
 OR of 4.09 for men.

10.  The increased association of human papillomavirus (HPV)–positive oropharyngeal cancers
may explain a similar increase in glottic cancer patients who are presenting younger and
without smoking histories.
 It is not clear at this time if there will be an impact of the HPV vaccine on the
development of laryngeal leukoplakia, but classic leukoplakia very rarely presents with
laryngeal papillomatosis.

11.  GERD is also hypothesized to be a risk factor for development of laryngeal leukoplakia
and malignancy.
 Well-performed meta-analyses controlling for smoking and drinking do suggest reflux is
related to laryngeal cancer, although this has not been extended to leukoplakia.
 However, a limitation of these meta-analyses is how sources assess exposure to reflux.
 Most epidemiological studies use patient survey or history of esophagitis as proxy measures
for laryngopharyngeal reflux exposure.
 Some reports also suggest that treatment of reflux may lead to some improvement in
laryngeal leukoplakia for some patients

12. Pathology, Grading, and Risk of
Malignant Transformation
 It is important to note that both benign and dysplastic vocal fold leukoplakia
lesions carry some risk of malignant transformation.

17.  In a comprehensive review and meta-analysis of laryngeal leukoplakia, 33.5% of
leukoplakia patients were noted to have mild to moderate dysplasia, and 15.2% had
severe dysplasia or carcinoma in situ.
 Following these patients over time, squamous cell carcinoma developed in:
 3.7% of those with no dysplasia on initial biopsy.
 10.1% of those with mild to moderate dysplasia.
 18.1% of patients whose initial biopsies demonstrated severe dysplasia.

18.  Analysis of patients with recurrent leukoplakia demonstrates that even patients with
initial pathologic diagnosis of benign hyperkeratosis or no histopathologic dysplasia
still carry risk for recurrence and progression to malignancy, with a 14% malignant
transformation rate on biopsy with direct laryngoscopy.
 A pooled meta-analysis shows that overall risk of progression to malignancy among
patients with vocal cord dysplasia is 14.1%

19.  Ability to rely on degree of dysplasia as a prognostic factor may be further
limited by difficult pathologic assessment of those features that lead to
categorization as mild, moderate, or severe dysplasia.
 Despite difficulties in pathologic staging, general trends suggest that while all
severities of dysplasia may ultimately progress to malignancy, mild dysplasia
does so at lower rate than moderate dysplasia and severe dysplasia.

20.  Difficulties with consistency among these 3 tiers led the World Health
Organization (WHO) to collapse assessment of vocal cord dysplasia severity
into a 2-tiered system in 2017, and now pathologists are encouraged to grade
things simply as low grade or high grade.
 Consistent rating of severity of dysplasia within these laryngeal lesions
remains difficult even in this 2-tier system, and data correlating this 2-tiered
approach to pathologic staging with clinical behavior are not yet available.

21. Diagnosis
 Leukoplakia is a clinical diagnosis made by physical inspection of the larynx,
and laryngoscopy remains the workhorse for otolaryngology recognition of a
leukoplakic lesion.
 Indirect mirror laryngoscopy.
 Trans-nasal flexible laryngoscopy.
 70-degree rigid laryngoscopy traditionally followed by direct microlaryngoscopy
(DML) in the operating room.
 Early detection is the strongest prognostic factor in determining the survival
of patients with vocal cord leukoplakia, presumably a premalignant disease.

22.  Laryngeal stroboscopy has been demonstrated to be helpful in:
 Determining progressive thickness of laryngeal epithelium as the dysplasia stage progresses,
increasing mass effect, as well as infiltrating disease that affects the mucosal wave. (this is
not always true).
 Good for Leukoplakic lesions at the medial border of the vocal folds compare to FOL scope.
 The ability to archive and compare exams over time, and the ability to play back with slow
motion or frame-by-frame analysis, which permits detailed analysis of the medial edge of the
vocal fold.

23.  Narrow-band imaging (NBI) and other versions of blue light wavelength
filtering visually highlight blood vessels of the vocal folds, allowing
identification of neoplastic lesions.
 Multiple studies demonstrate improved identification of lesions and their
associated effects on the vocal fold microcapillary network within the
superficial lamina propria.

24.  Office biopsy, if performed correctly using a channeled flexible laryngoscope,
can be cost-effective, potentially providing earlier diagnosis.
 Surgeons consider office biopsy for tissue sampling for pathologic diagnosis in
an awake patient at the time of presentation without general anesthesia.
 However, it is important to note that office biopsy often under-stages the
severity of the lesion.

25.  A study by Cohen et al of 102 in-office biopsies demonstrated a high false-negative
rate of 33.0%, essentially not recognizing the severity of disease.
 After obtaining repeat biopsy/excision under micro-laryngoscopy, 30 of 91 patient
samples had underestimated the presence of dysplasia or malignancy.
 This discrepancy was again noted by Richards et al in a study of 76 in-office
biopsies followed by biopsy/excision in the operating room, demonstrating
sensitivity of 60% and specificity of 87%.

26.  Major limitations are related to:
 Small tissue sample in large islands of leukoplakia that have heterogeneous
pathology.
 Poor depth of biopsy that excludes the basement membrane.
 Inability to visualize or biopsy lesions in difficult areas to access in an awake
patient.

27.  Laryngeal contact endoscopy uses a rigid endoscope to illuminate and magnify
tissue in areas suspected of malignancy, noting the ability to visualize
patterns of cells and nuclear to cytoplasm ratios in more suspicious areas.
 Has the greatest potential to target areas of biopsy or excision in a patient
under general anesthesia undergoing direct microlaryngoscopy.
 Has limitations in an awake patient due to access of the scope to the larynx,
movement of the patient, and the ability to tolerate laryngeal manipulation.

28. Treatment
 The mainstay of treating laryngeal leukoplakia is:
 Determining the severity of pathology and risk of progression to malignancy.
 Eradicating disease that demonstrates at least severe dysplasia in an oncologic
procedure.
 Respecting or improving the voice.

29.  DML under general anesthesia in the operating room offers advantages of
phonomicrosurgical technique that appreciates the multilayered vocal fold
histology and has as its goal the preservation of vibratory function.
 Microflap techniques with removal of the epithelial disease and preservation
of underlying superficial lamina propria (SLP) are preferred.
 This approach can be done with or without injection of saline or adrenaline to
expand the SLP prior to epithelial resection, and it can be done with or without
laser use in the operating room.

30.  Schweinfurth et al established the efficacy of microflap excision in 20
patients with laryngeal dysplasia, with only 1 patient progressing to invasive
disease and an overall reduction in severity of dysplasia with each additional
procedure.
 Benefits of the microflap approach include preservation of epithelium not
involved with leukoplakia, thereby preserving or improving voice function.

31.  The carbon dioxide (CO2) laser has a role in managing vocal fold leukoplakia.
 Its use as a ‘‘coagulating scalpel’’ allows for hemostatic cutting of the
epithelium through the basement membrane at the time of microflap
excision.
 This laser is also the mainstay for the varying degrees of cordectomy that
are performed for the progression of micro-invasive squamous carcinoma
to more invasive disease.

32.  A prospective randomized controlled trial by Benninger:
 Demonstrated this point, following 37 patients who underwent CO2
microsurgery vs traditional phonosurgical resection of benign vocal fold
lesions, revealing no significant difference in recovery or voice outcomes.
 Angiolytic therapy, previously 585-nm pulsed dye lasers (PDLs) and
more recently 532-nm potassium titanyl phosphate (KTP) lasers,
target oxyhemoglobin as their chromophore and therefore are
designed for superficial treatment of epithelial disease.

33.  These lasers are fiber based, allowing the surgeon to vary distance between
the tip of the fiber and target tissue, to achieve a variety of treatment
effects, ranging from gentle blanching of superficial lesions to more thorough
ablation as needed.
 In the case of leukoplakia, the laser can be used to photocoagulate hyper-
vasculature associated with tumor-related angiogenesis and do so without
associated thermal damage to vibratory tissue

34.  Radiotherapy is rarely used for leukoplakia in the absence of an established
invasive cancer diagnosis.
 However, it may play a role under certain conditions for patients with severe
dysplasia/carcinoma in situ.
 Recurring and pathologically advancing disease despite multiple excisions.
 The potential for insufficient demonstration of microinvasion due to a near-margin
dissection or tissue destruction from a laser margin.

35.  Observation may be reasonably performed without treatment of the lesion
only if the lesion has been histopathologically proven nonmalignant, which
should be performed with DML if feasible.
 While the authors do not recommend biopsy that does not also excise the
lesion, as this leaves ‘‘untreated disease’’ behind that might then progress to
malignancy, this may be a reasonable option if a surgeon doubts their ability
to preserve voice quality by offering an appropriate microflap resection
rather than ‘‘stripping.

36. New Directions
 Biomarkers of nuclear mutations and their cellular phenotypic destiny would
be an ideal way of determining prognosis in patients with leukoplakia.
 The cumulative effect of genetic mutations is thought to be associated with
progression of dysplasia in the head and neck to invasive carcinoma.
 Identification of biomarkers and genetic mutations may also support the
theory of field cancerization; while macroscopic disease and microscopic
disease may not be present in certain tissue, genetic alterations and
mutations of apparently normal tissue may lead to disease progression and
recurrence

37.  Identification of these abnormalities in adjacent tissues to the index lesion
and other normal mucosa may provide guidance for mapping the treatment
area.

38. Conclusion
 There has been a paradigm shift away from performing ‘‘vocal cord stripping’’
procedures that can cause irreversible hoarseness toward voice preservation
surgery while achieving comparable oncologic control.
 Surgical technical and instrumental developments have been designed to
maximally treat superficial disease while preserving underling vibratory
mucosa.

39.  Recent improvements in histopathological grading systems and advances in
biomarker classification may allow for improved oncologic risk stratification.
 Furthermore, improvements in endoscopic imaging capabilities and contact
endoscopy are currently being studied for their potential diagnostic
significance.

40. Implications for Practice
 To optimally manage vocal fold leukoplakia, the otolaryngologist should
become familiar with the oncologic implications of the disease and the
importance of obtaining pathologic diagnosis to rule out malignancy.
 In addition, the surgeon should maintain surgical techniques and knowledge of
available instruments and lasers that can assist in surgical management while
prioritizing the preservation of vibratory tissue and voice quality.
 Finally, the surgeon and the patient should understand the clinical
importance of routine endoscopic surveillance.

42.  In conclusion:
 This representative nationwide study of otorhinolaryngology practices in Germany
revealed that approximately 1 in 5 patients with vocal cord leukoplakia exhibited either
carcinoma at diagnosis or malignant transformation within 5 years.
 A high index of suspicion by physicians is required in older patients, particularly in men.
 A close follow-up of high-risk patients is recommended, even if the results of the initial
biopsy were negative.

43. Thank you