LARYNGEAL PRECANCER: A REVIEW OF THE LITERATURE, COMMENTARY, AND COMPARISON WITH ORAL LEUKOPLAKIA Jerry E. Bouquot, DDS, MSD, and Douglas R. Gnepp, MD

Laryngeal keratosis (LK) is a precancerous mucosal change with great similarity to oral leukoplakia. Its malignant transformation rate varies from 1% to 40%, with the highest rates being found in patients microscopically diagnosed as “keratosis with atypia” (KWA). Recent evidence indicates that even cases with only mild or moderate epithelial dysplasias are at increased risk for malignant transformation, with the highest rates occurring in patients with more severe dysplasia or carcinoma in situ. Approximately 81Yoof LK patients are men and the average age at diagnosis is 50 years, a decade younger than that for laryngeal carcinoma patients. A high proportion of LK patients are tobacco smokers (84%) and alcohol abusers (at least 35%). LK is almost always found on the true vocal cords and is usually bilateral (67%). Clinical signs of high risk include, in decreasing order of importance: erythroplakia, surface granularity, increased keratin thickness, increased size, recurrence after conservative removal, and long duration. The annual incidence of LK in the United States is 10.2 and 2.1 lesions per 100,000 males and females, respectively. HEAD & NECK 1991;13:488-497

Tremendous advances have been made in the understanding of oral leukoplakia (OL), since Schwimmer’ first coined the clinical expression

From the Department of Oral Pathology West Virginia University School of Dentistry and Department of Pathology (Dr Bouquot), West Virginia University School of Medicine. Morgantown West Virginia, and Departments of Pathology and Otolaryngology-Head and Neck Surgery (Dr Gnepp), St Louis University School of Medicine, St Louis, Missouri

in 1877. Today, such lesions are successfully evaluated and managed as a routine facet of oral health care. A parallel but completely independent research effort has led to a less advanced state relative to laryngeal leukoplakia or “keratosis” (LK). Investigators and clinicians from either field, however, seldom use or assimilate hard-won facts and conclusions from the other parallel field. This is due, in part, to an early and erroneous assumption that keratotic plaques from 1 anatomic site bear no significant similarity to identical lesions of the other ~ i t e . ~It - ~ seems also a natural consequence of the simple fact that benign lesions of each site have been considered to be within the purview of 2 different health professions, dentistry and medicine. While several reviews are available for laryngeal precancers, none broadly synopsizes the varied historical, clinicopathologic, histopathologic, epidemiologic, and follow-up data available. The present paper is an attempt to fill this void by summarizing and analyzing past and current concepts of laryngeal keratosis (LK), dysplasia, and carcinoma in situ. It also provides comparisons with OL, because OL has been more extensively studied and because there appears to be, in fact, a marked similarity between OL and

LK.5-10

Address reprint requests to Dr Bouquot at the Department of Oral Pathology, WVU Health Sciences Center- North, Morgantown WV 26506 Accepted for publication May 20, 1991 CCC 0148-6403/91/060488-010 0 1991 John Wiley & Sons, Inc

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$04 00

DEFINITIONS

The term “laryngeal keratosis” is used herein according to the WHO “leukoplakia” definition,”

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that is, a clinical white keratotic plaque that cannot be given another diagnostic name. It is used interchangeably with leukoplakia and has no implication relative to the presence or absence of underlying microscopic atypia or dysplasia. “Erythroplakia” is used as a clinical term to define a red mucosal plaque which does not appear to arise from an obvious mechanical or inflammatory etiology or which persists after removal of obvious etiologic factors. “Erythrokeratosis,” also known as speckled keratosis, is a clinical term used to define a mucosal plaque with areas of erythroplakia and leukoplakia intermixed. A thin layer of surface keratin is accepted by many authors under the definition of carcinoma in situ (CIS), which otherwise requires “top-tobottom” epithelial dysplasia with little or no other evidence of maturation and no invasion through the basement membrane. The acceptance of surface keratin and/or maturation in this lesion is neither encouraged nor espoused by the present authors, but has been allowed by so many investigators as t o make it a de fact0 feature of some CISs. It must be emphasized, therefore, that a strict separation of CIS from severe epithelial dysplasia could not be attained in the present review, and that the majority of lesions reported as CIS may in reality be severe dysplasias. This is of some concern, as CIS is considered to be a preinvasive malignancy, whereas severe dysplasia is a precancer. The terms “precancer” and “premalignancy”define a physically or physiologically altered tissue, benign in itself but thought to carry a greater than normal risk of transforming into malignancy.

paratory to invasion,”15 and pathologists of the stature of James Ewing considered his cases to represent the “earliest form” of laryngeal cancer.14It is perhaps significant that the long literature debate initiated by him commenced within a decade of the ready availability and rapid popularity of inexpensive, mass-produced cigarettes. 19,20 By 1942 Graham21 was able to report, after review of the literature, that the precancerous nature of LK was well established. The first comprehensive follow-up investigation, a decade later, confirmed his assumption, finding that almost 40% of LK cases eventuated in car~inoma.~ Subsequent studies determined a much smaller proportion of transforming cases (Figure 1).The only population-based analysis of this question found only 0.9%of LK lesions transforming after diagnosis, although 17% contained carcinoma at the time of diagnosis.23OL has demonstrated an equally varied malignant transformation rate (1%to 36%;average 4%)32and the single extant population-based study has found that more than 10%become malignant after diagnosis.33 Acceptance of the precancerous nature of OL preceded LK acceptance by several deCades,4,32,34-36partly because OL has been noted adjacent to as much as 100% of oral cancers,37 but also because of confusion resulting from a lack of appropriate LK diagnostic criteria and terminology. This has lead, literally, to chaos and has prevented meaningful comparison between various research efforts and conclusions. More than 20 different classification systems have thus far been o h n using similar terms but with different meanings. Pierce13

ASSOCIATION WITH CANCER

The first reported case of LK appears to be Durant’s12 1880 description of “white cicatrices” adjacent to an assumed malignancy of the true vocal cords. However, it was not until 1920 that Pierce13 published the first English-language paHELLQUIST (1982) per dealing specifically with “leukoplakia larynGABRIEL, JONES (1973) gis.” Shortly thereafter, Chevalier J a c k ~ o n l ~ ’ ~ ~NORRIS, PEALE (1963) suggested an association between LK and carciBOSATRA(1977) noma of the larynx, a remarkable conclusion in light of the fact that the very concept of premaKLEINSASSER (1959) lignancy was not yet accepted and such terms as 9 ’UTNEY, OKEEFE (1953) dysplasia and CIS had not yet been used to identify cells with a potential for malignant transfor0 5 10 15 20 25 30 35 40 % LK WITH CARCINOMA AFTER DIAGNOSIS mation or invasion.16-ls Jackson metaphorically equated epithelial FIGURE 1. Reported malignant transformation rates for 3,423 treated and followed LK case^?^**-^' atypia t o the “mobilization of a foreign army pre-

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believed that leukoplakia was the same as pachyderma, a dermatologic term long used in otolaryngology to describe a pebbled keratosis of the posterior glottis. Jackson14 preferred the term keratosis for the precancerous or suspicious lesions, reserving leukoplakia for the much more common thin keratotic plaques. Graham2’ preferred to use leukoplakia as a strictly microscopic term and several authors have used leukoplakia and keratosis Since 1959 there has been a trend toward the use of 2 mutually exclusive microscopic names dependent entirely on the presence or absence of atypical epithelial cells: “keratosis without atypia” (KWOA) and “keratosis with atypia” (KWA).8*9*28930,3’ Such terms have true prognostic significance. Treated KWA has been shown t o transform into carcinoma in 5.6% to 40% of hospital-based follow-up studies. This is considerably more than the 0.0% to 16% rates for KWOA (Figure 2). The great variability of these rates, however, damages the credibility of any individual data and is probably as much dependent on patterns of patient referral and selection as on true differences between populations served by hospitals. Such referral patterns tend to select for more seriously affected patients, a feature readily demonstrated by comparing the transformation rates of the 2 investigations which have followed large numbers of untreated LK cases: 22.2% of such lesions became malignant in a patient cohort derived from a teaching hospital, whereas only 0.9% did so in a general population.23,41 The KWONKWA segregation has helped to clarify the risk of malignant transformation in SABRIEL, JONES (1962)

5.6

W A

GABRIEL. JONES (1973)

73

McGAVRAN et al(l960)

NORRIS. PEALE (1963) VELASCO el al (1987)

KWOA

11.1

h33

12.8

&

HENRY (1979)

19.5 28,6

HOJSLET et al(1989)

Oh

0 5 10 15 20 25 30 35 40 LK WITH CARCINOMA AFTER DIAGNOSIS

45

FIGURE 2. Comparison of malignant transformation rates for laryngeal keratosis with (KWA) and without (KWOA) atypia or dy~plaSia.”.27.28.30’38-40

490

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LK, but has several major flaws. First, it requires a biopsy specimen and, therefore, does not take into account the 53% of LK lesions which are never b i ~ p s i e d Second, .~~ the word “atypia” encompasses a number of histologic changes not associated with malignancy or premalignancy ;in this light, “keratosis with dysplasia” would be preferred. Third, a thin parakeratin layer is normal to the vocal cords, where most LK occurs, and a white plaque of this site is, therefore, indicative of a n excessive amount of keratin rather than the mere presence of keratin. The term “hyperkeratosis” is more accurate as a histologic descriptor. Finally, the term KWA does not take into account the degree of cellular dysplasia present . . . a feature that has long been considered to be among the most important aspects of risk assessment for leukoplakias of other upper aerodigestive tract (UAT) ~ i t e s ,and ~ ,one ~ ~that ~ ~ will be discussed in a subsequent section of this review. CLINICAL FEATURES OF HIGH RISK

The emphasis on a simplistic, purely microscopic lexicon for LK has resulted in a rather poor understanding of the clinical aspects of the disease. In light of the large number of cases never biopsied and the great stress placed on frequent clinical follow-up of treated cases, this emphasis as early as is surprising. P ~ t n e ydid~ suggest, ~ 1955,that LK lesions with surrounding inflammation (erythroplakia?), surface granularity or “papillarity,” long duration, or recurrence after surgical removal were most likely to “degenerate” into malignancy. Other authorities have occasionally agreed with him and added additional high-risk It wasn’t until the 1970s that Gabriel and Jones27 successfully turned prevailing sentiment toward the concept that the clinical appearance of LK was as important as the microscopic appearance in determining treatment protocols. These authorities recommended an international committee to establish standards in both arenas. Attempts to do so, unfortunately, have failed to bring consensus and rather emphasize than diminish d i s p a r i t i e ~ . ~This ~~.~ ~ , ~ ~ forces difficulty the present authors to emphasize the importance of microscopic evaluation of multiple LK sites. Erythroplakia and erythrokeratosis, long considered the oral mucosal changes with the highest risk of malignant have been largely ignored in the laryngeal literature because they were confounded by the inflamma-

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tory hyperemia which is an almost constant feaindicated are only estimated and it is possible, ture of “smoker’s l a r y n ~ . ” Ironically, ~ ~ - ~ ~ a few although unlikely, that dysplastic epithelium authorities have actually included mucosal could be found beneath all depicted clinical changes. An identical model has been proposed erythema as a routine or required part of their for OL as part of a precancer staging protocol definition of LK.38 Several authors have warned that the more heavily “inflamed LKs were at (J.E. Bouquot et al., submitted for publication). Clinical signs are seldom noticed before greatest risk of malignant or dysplastic change,4,10,21,43,48but only recently has the redsymptoms cause a patient to seek medical consultation. Few papers, however, mention sympness associated with LK been considered to be a tomatology beyond broad introductory comfeature of a dysplastic process rather than eviThose few have indicated that the major dence of differing intensities of i n f l a m m a t i ~ n . ~ ’ ~ments. ~ presenting symptom, found in 50.9%to 97.7% of Erythroplakia in OL, by contrast, has long been affected individuals, is hoarseness o r dysphonia considered to be a high-risk precancer change rather than an inflammatory ~ h a n g e . This ~ ~ . ~ ~of less than 7 months duration (range: 1 month to 25 sign is noted in approximately 16%of LK lesions Duration of hoarseness apand 1%to 3% of OL lesions.8*23*33,42 pears to have little prognostic significance. Figure 3 represents a composite illustration Almost all LK cases are found on the true voof the various clinical appearances of LK with cal cords and a large proportion, perhaps a maexpected underlying microscopic changes. Lejority, involve both cords.23 The average lesion sions become progressively more “severe” toward size at diagnosis is 1.2 cm and involves a large the right, culminating in erythrokeratosis and portion of the affected cord, usually the central erythroplakia, which most frequently demonand anterior lateral borders.23 There is no strate severe epithelial dysplasia and CIS when present proof that LK of nontrue cord mucosa carries a higher risk for malignant transformastudied histologically. It should be emphasized that Figure 3 does not necessarily represent a tion, but 1 site, the aryepiglottic fold, appears to chronological change, but rather the potential carry an extremely low a situation presentations of LK. It is not unusual for LK to somewhat analogous to gingival leukoplakias, present with multiple appearances, in which which are most frequently simple frictional keracase the clinician should attempt to sample tist~ses.~’ sue with the greatest chance of containing dysEPIDEMIOLOGY plastic cells, that is, those appearances to the The prevalence (proportion of persons affected) of right in Figure 3 (right-shifted). It should furLK is not known. Autopsy investigations have ther be mentioned that the microscopic changes

GRANULAR. VERRUCIFORM KERATOSIS

1

I

1

-

-

Bulbous. elongated rele pegs

ERYTHROKERATOSIS (SPECKLED KERATOSlSl

Epithstidl atrophy Ion right1

Moderaleiseveie dvsplasta

*Congested vessels

* Candida hyohae lmaybei

FIGURE 3. Representationof the various clinical presentations of LK, progressing from low-risk to high-risk malignant transformation potential from the left to the right side. Probable underlying microscopic appearances are also depicted for each clinical presentation. Fissured, nodular, and verruciform appearances are exaggerated for clarity. This model is derived from the LK literature and the authors’ personal experience.

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concluded that 19.6% of men, 80.7% of whom Even in nonwere smokers, had LK at smokers, 4.2% demonstrate LK. The incidence (number of new cases per annum per 100,000 persons) of clinically diagnosed LK has only recently been shown to be 10.2 for men and 2.1 for women.23This compares to OL incidence rates of 16.0 and 8.6, respectively, in the same populat i ~ n . ~ ~ The incidence rate for LK does not continue to increase throughout life, as it does for OL,23950 but rather decreases after a peak in the 45- to 64-year age group (Figure 4). Bouquot et al.23 have demonstrated that laryngeal carcinomas are actually diagnosed more frequently than LK after 64 years of age. Overall, however, LK is diagnosed 2.1 to 5.4 times more frequently than invasive carcinoma of the larynx, depending on whether or not affected patients are taken from the general population or a teaching hospital.22*23 The annual incidence rate of diagnosed LK is increasing much more rapidly than that for laryngeal carcinoma (Figure 5), predominantly because of changing LK rates in women.23 Most patients with LK are men, accounting This for 63.5% to 93.6% of affected male predilection becomes even more pronounced with increasing dysplasia. Norris and Peale28 reported that 82% of KWOA patients were males, whereas 91% of KWA were male. Bouquot et al.23reported that 80.6% of 1community's LK cases arose in males, whereas 83.3% of its laryngeal CIS cases and 94.3% of its invasive laryngeal carcinomas were male. A strongly pos-

''v)

16-

g

14-

n

10-

2 s

8-

8

2

KERATOSIS CARCINOMA

6-

0 4-

z*3

20

7

0-14

1

I

1

1524 25-34 35-44 45-54 55-64

I

1

65+

AGE IN YEARS

FIGURE 4. Age-specific average annual incidence rates for LK and laryngeal carcinoma, both genders i n ~ l u q d e d . ~ ~

492

KERATOSIS CARCINOMA

,---d 193544 1945-54 195564 1965-74 1975-84

TIME PERIOD (DECADES)

FIGURE 5. Time trends in average annual incidence rates for LK and laryngeal carcinoma in a white population, both genders in~luded.'~

itive correlation between the proportion of men and increasing lesion severity has recently been demonstrated for OL lesions as well.50 There appears to be an additional positive correlation between age at diagnosis and laryngeal lesion severity or dysplasia.40 Mean ages for first LK diagnosis vary from 48.0 to 56.5 years,4,17,2224,39.40,51 10 to 15 years younger than patients with laryngeal carcinoma (see also Figure 4).9,23Norris and Peale,28 moreover, determined that the mean age of patients with KWOA is less than that for patients with KWA, 48 and 53 years of age, respectively, although no test for statistical significance was made by them. ETIOLOGY

12-

8

0

Laryngeal Precancer

Gender and age appear to be significant highrisk features for LK but are not etiologic factors per se. Virchow was probably the first to suggest that voice and/or alcohol abuse could produce pachyderms," and Jackson14 presumed that LK was primarily produced by voice abuse. Surprisingly few investigators, however, have addressed etiology in their research. Graham21 was first to report LK disappearance afier vitamin A therapy, and W a l l n e ~ first - ~ ~ reported LK disappearance after smoking cessation; however, there have been no follow-up investigations that have specifically addressed vitamin therapy or habit cessation. Current suggestions that carotene and/or retinoids are efficacious in reducing oral 1eukoPlakia O r dYsPlasia tend to validate the use of beta-carotenes or cis-retinoic acid for LK.53*54

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altered cells. However, analysis of HPV-inocuEpidemiologic evidence has strongly implilated normal cervical mucosa cells grown t o full cated tobacco smoking in the etiology of laryndifferentiation and maturity on collagen gels geal and autopsy studies have seems to strongly suggest that HPV causes epidemonstrated a strong correlation between the thelial dysplasias.66 daily amount of tobacco consumed and the preskeratosis has a multifactorial etience of LK or laryngeal d y ~ p l a s i a . ~ Per~ , ~ ~ , ~ ~Laryngeal ,~~ ology with tobacco smoking being of prime imsons smoking more than 20 cigarettes daily have p ~ r t a n c e $ ~ ~ , ~followed ~ * ~ ~closely , ~ ~ ,by ~ ~ ~ ~ ~ , a 44.4% chance of developing LK and an even chronic mechanical trauma (voice greater chance, 47.2%, of developing dysplastic and more distantly by alcohol abuse10*23,30p51 vocal cord m u ~ o s a Light . ~ ~ smokers (fewer than and/or nutritional d e f i c i e n ~ i e s . ’ ~ ~It~ ~ is ~~~*~~ 10 cigarettedday) have a 12.4% risk of dysplastic change, compared to 4.2% for nonsmokers. Tolikely that LK lesions diagnosed in otolaryngolbacco chewing appears to contribute significantly ogy clinics of large teaching hospitals have an to the risk of developing laryngeal cancer in Inartificially high proportion of smoke-related ledia58 and to a much lesser extent in the United sions, as voice-related LK lesions would tend to but data are not detailed enough to be selected out by the referral process. It should quantitate the relative risk of acquiring LK from also be emphasized that LK lesions without identhis habit. tifiable etiologies are considered more likely to become dysplastic or malignant than other LK Whether or not stopping the smoking habit routinely returns the laryngeal mucosa to its lesions,* a characteristic of OL as well.’ normal histology is uncertain,26*38*46*47*51,60 but DYSPLASIA AND CIS certainly many LK lesions are reversible if etioThe clinical presence of white keratosis, red logic habits, such as tobacco, alcohol, and voice abuse, are eliminated or if potential nutritional erythroplakia, verrucous hyperplasia, or surface deficiencies, especially vitamin A deficiencies, granularity is extremely important for identifyare corrected. Occasional lesions disappear withing and pin-pointing laryngeal mucosa at greatout a change in smoking or other etiologic est risk for containing or developing neoplastic habits61; re-biopsy of previously excised lesions cells, but only the most innocuous LK lesions demonstrates normal mucosa in two thirds of should be exempt from biopsy, since the microcases.4o scopic appearance of the epithelial cells, with or Alcohol abuse has been shown to have a synwithout overlying keratin, is the single most influential predictor of future transformation into ergistic association with tobacco abuse in the production of laryngeal carcinoma,s5 but no sim2 emphasizes the imporm a l i g n a n ~ y Figure .~~ ilar effect has been examined relative to laryntance of histologic evaluation using a simple geal precancers. Only 1 investigation has proKWOMKWA classification. One should keep in vided statistics for this parameter, reporting that mind, however, that many authors have not pre35.2% of all LK patients are alcohol abusers sented clear microscopic definitions of atypia, es(listed in the medical records as heavy drinkers, pecially with regard to the proper classification of mild and moderate dysplasias. Most investigaalcoholics, or having a “drinking problem”).23 tors, we believe, have included the latter diagHuman papillomaviruses (HPV) have been noses under the KWA terminology, but several demonstrated in laryngeal carcinomas and precancerous p a p i ~ l o m a s ,as ~ ~well ’ ~ ~as in oral carhave only included severe (“precancerous”) epitheilal dysplasia in this ~ a t e g o r y , ~ , ~ ~and @ *a~ ’ cinomas and l e ~ k o p l a k i a s . ~Such ~’~~ data are few have included CIS as a KWA l e ~ i o n . ~ ~ , ~ ~ based on immunohistochemical demonstration of Recent studies have concluded that there is, HPV-antigen expression in such lesions, and on DNA hybridization studies. The “high risk” HPV in fact, significant risk of malignant transformation in moderate epithelial dysplasia of laryntype 16 DNA has been found in laryngeal verrugeal mucosa. Hojslet et al.40found that risk to be cous carcinomas and HPV 6, 11, and 16 in nonthe same (40%) as that of the combined group of verrucous laryngeal carcinomas; 12.9% of the latter contained the DNA of at least 1 HPV severe dysplasidCIS lesions. Investigations by type.“ No investigation has yet examined the Hellquist et a1.26and Velasco et al.39 corroborate role of HPV in LK, nor do we know whether this similarity of risk, although their transforHPV actually causes epithelial dysplasias rather mation rates are lower (20%). Hojslet et al. cauthan being a secondary infection in previously tioned that even mild epithelial dysplasia bears

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an increased risk (4%) of malignant transformation. Such results are contrary to the OL experience9v70,71 and would seem to dictate a more specific subcategorization of epithelial dysplasias in future LK research. Special emphasis, furthermore, should be placed on nuclear enlargement and hyperchromatism in the assessment of that dysplasia, as photometric analyses have demonstrated that greatly increased DNA content was the single strongest prognostic indicator.72 Laryngeal CIS received special and early attention in the otolaryngologic literature. In fact, the earliest review of nonlaryngeal UAT CIS, by G~rlin'~ specifically emphasized oral and pharyngeal lesions in order to counter the prevalent belief that the larynx was the only UAT site affected by this preinvasive malignancy. Recent epidemiologic studies have justified the concern of Gorlin, demonstrating that only one third to one half of UAT CIS lesions are found in the larynx.74>75 The annual incidence rate for CIS of the larynx is only 0.4 cases per 100,000 persons, a rare neoplasm indeed. Even among total body CIS cases, laryngeal lesions represent only 1%of all cases. They also represent 6.5% of all laryngeal cancers, are much more common in males than in females, and have a peak incidence in the 65- to 69-year-old age group (Figure 6). Although rarely diagnosed, CIS of the larynx has been more extensively followed than CIS of other UAT sites: three fourths of the 468 UAT CIS patients thus far followed after diagnosis have had laryngeal involvement. Table 1 demonstrates that 29.0% of laryngeal CIS lesions eventuate in invasive disease, with untreated cases

-

CT

-

*

4

MALES FEMALES

30-34 4044 5054 60-64 70-74 80-84 2529 35-39 45-49 5559 65-69 75-79 85+

20-24

AGE (IN YEARS) FIGURE 6. Age-specific average annual incidence rates for laryngeal CIS,by gender.75

transforming at the highest rate (33.3% to 90.0%). Because of differences in the definition and criteria of KWA, severe dysplasia and CIS, we strongly recommend a classification system similar to that used for tissue of the uterine cervix: LIN I (laryngeal intra-epithelial neoplasm) for mild epithelial dysplasia; LIN I1 for moderate dysplasia; and LIN I11 for severe dysplasia or CIS. This should ensure a more uniform diagnostic protocol. LK AND OL COMPARISON

By way of conclusion, Table 2 provides a summary of various clinicopathologic and epidemiologic characteristics of LK and compares each characteristic with OL lesions. The similarity be-

Table 1. Results of follow-up investigations of laryngeal CIS (listed by year of publication). Aulhor(s) Altman et al.76 McGavran et a1.22 Norris and Peale2' Klein~asser~~ Miller and Fisher7' Pene and Fletcher7' Doyle et al.'' Elrnan et aL8' Hintz el aLa2 Hellquist el a1.26 Total

Year published

No. of CIS cases

70transformed into invasive carcinoma

1952 1960 1963 1963 1971 1976 1977 1979 1981 1982

29 18' 1st 20t 203 26 28 81* 27t 20' 468

3.5 11.1 33.3 90.0 15.8 4.0 7.1 17.0 63.0 25.0 29.0%*

'Includes severe epithelial dysplasias in addition to CIS tCases were followed without treatment. #Not weighed according to size of patient cohorts.

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Table 2. Comparison of various characteristics of LK and OL.* Characteristict Patient characteristics Average age at diagnosis Yo Males Yo Smokers Yo Alcohol abusers Incidence (casedl 00,00O/yr) Prevalence (casedl ,000) Lesion characteristics Average lesion size Average duration at diagnosis % With erythroplakia at diagnosis % With carcinoma at diagnosis Yo With carcinoma after diagnosis % Recurred after treatment % With dysplasia at diagnosis Yo Carcinomas with adjacent LWOL % Biopsied % Treated Typical histology

Laryngeal keratosisS

Oral IeukoplakiaS

48-56 yrs (50y/o) 64-94% (81%) 84-94% (84%) 35% (35%) 6 (6)

54-63% (60y/o) 58-80% (60%) 66-81% (66%) N/A NIA

N/A§

20- 170 (20)

1-3 crn (1 cm) 7 rno (7rno) 16% (16%) 4-67% (12%) 1-40% (1%) 16-30% (16%) 3-100% (3%) 18-43% (33%) 47% (47%) ’ 46% (46%)

1-2 crn (1 cm) 1-40 rno (26 rno) 18-24% (18%) 0.1-40% (7%) 0.1-6% (4%) 18-42% (18%) 3-54% (14%) 10- 100% (34%) 26% (26%) N/A (20%)

Hyperkeratosis

Hyperkeratosis

*References 4, 5,9. 13, 17. 22-24, 27, 28, 30.32-35, 39-42, 50, 51, 70.71. 83-86. jRepresents 3857 LK and 4117 OL patients. #Numbers in parentheses represent authors’ estimate of the most representative (unbiased) data. §MA, data not available.

tween the 2 lesions would appear to justify the contention that they are, in fact, the same entity. Table 2 also illustrates the unfortunate variation in results arising from clinicopathologic investigations with their considerable patient referral or case-selection biases. The authors recommend

that future investigators make every effort t o minimize or at least identify such biases. In the meantime we have suggested figures (in parentheses in Table 2) which we believe to be the most representative for these lesions.

REFERENCES

1. Schwimmer E. Die idopathisches Schleimhaut-plaques der Mundhohle (Leukoplakia buccalis). Arch Dermtol Syphilol 1877;9:511-570. 2. Fisher HR. The delineation of carcinoma in situ of the larynx. Can J Otolaryngol 1974;3:522-532. 3. Martin H. As quoted in: Gordon GR. Keratosis of the larynx. Laryngoscope 1950;60:1201-1209. 4. Putney FJ, O’Keefe JJ. The clinical significance of keratosis of the larynx as a premalignant lesion. Ann Otol Rhinol Laryngol 1953;62:348-358. 5. Black M, Davis BT, Bond WH, et al. Discussion on the keratoses of the larynx. Proc R SOCMed 1954;47:245254. 6. Grundman E.Classification and clinical consequences of precancerous lesions in the digestive and respiratory tracts. Actn Pathol Jpn 1983;33:195-217. 7. Friedmann I. Precancerous lesions of the larynx. Can J Otolayngol 1974;3:528-532. 8. Crissman JD, Gnepp DR, Goodman ML, et al. Preinvasive lesions of the upper aerodigestive tract histologic definitions and clinical implications (a symposium). Pathol Annu 1987;22:311-352. 9. Bouquot JE.Epidemiology. In: Gnepp DR, ed. Pathology of the head and neck. New York: Churchill-Livingstone, 1988~263-314. 10. Gordon GR. Keratosis and the larynx; report of a case

Laryngeal Precancer

with underlying carcinoma in situ. Laryngoscope 1950;60:1201- 1209. 11. WHO Collaborating Center for Oral Precancerous Lesions. Definition of leukoplakia and related lesions: an aid to studies on oral precancer. Oral Surg 1978;46:518539. 12. Durant G. Case of cancer of the larynx. Arch Laryngol 1880;1:61-62. 13. Pierce NH. Leucoplakia laryngis. Ann Otol Rhinol Laryngol 1920;29:33-56. 14. Jackson C. Cancer of the larynx: is it preceded by a recognizable precancerous condition? Ann Surg 1923;77:114. 15. Jackson C,Colledge L, Thomson S, et al. Discussion on precancerous conditions of the larynx. Proc R Soc Med 1930;24:301-308. 16. Broders AC. Carcinoma in situ contrasted with benign penetrating epithelium. JAMA 1932;99:1670-1674. 17. Von Speiser F. Zur krebsigen Entartung der Pachydermia laryngis. Z Hals- Nasen- Ohrenh 1932;30: 391-409. 18. Weiss P. Perspectives in the field of morphogenesis. Q Rev Bwl 1950;25:177-198. 19. National Cancer Institute. Health implications of smokeless tobacco use. Public Health Reports 1986;101:349354.

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