The Maxillofacial Center for Diagnostics & Research
| Leukoplakia | Epithelial Dysplasia | Smokeless Tobacco Keratosis | Oral Cancer |
Oral & pharyngeal erythroplakia
Laryngeal erythroplakia
Erythroleukoplakia
Histopathology of eryhtroplakia
Epidemiology of oral erythroplakia
Erythroplakia treatment
Malignant transformation of erythroplakia, dysplasia & CIS
Etiology & biological behavior of erythroplakia
Precancers of the mouth & throat, listing of clinical terms
& ranking of transformation potential
Broders AC. Carcinoma in situ contrasted with benign penetrating epithelium. J Am Med Assoc 1932; 99:1670-1674.
Gorlin RJ. Bowen's disease of mucous membrane of the mouth; review of literature and presentation of cases. Oral Surg Oral Med Oral Pathol 1950; 50; 3:35-51.
Shedd DP, Hukill PB, Kigerman MM, et al. A clinicopathologic study of oral carcinoma in situ. Am J Surg 1963; 106:791-796.
Waldron CA. Oral epithelial tumors. In: Gorlin RJ, Goldman HM (editors). Thoma's oral pathology, 6th ed. St. Louis: C. V. Mosby; 1970, pp. 824-826.
Shafer WG, Hine MK, Levy BM. A textbook of oral pathology, 3rd edition. Philadelphia: W. B. Saunders, 1972.
Shafer WG, Waldron CA. Erythroplakia of the oral cavity. Cancer 1975; 36:1021-1028.
Shafer WG. Oral carcinoma in situ. Oral Surg Oral Med Oral Pathol 1975; 39:227-238.
Crissman JD, et al. Preinvasive lesions of the upper aerodigestive tract: histologic definitions and clinical implications (a symposium). Pathol Annu 1987; 22:311-352.
Mashberg A, Samit AM. Early detection, diagnosis, and management of oral and oropharyngeal cancer. CA 1989; 39:67-88.
Mincer HH, Coleman SA, Hopkins KP. Observations on the clinical characteristics of oral lesions showing histologic epithelial dysplasia. Oral Surg Oral Med Oral Pathol 1972; 33: 389-399.
Bouquot JE. Leukoplakia and erythroplakia: a review and update. Pract Perio Aesth Dent 1994; 6:1-10.
Bouquot JE, Ephros H. Erythroplakia: the dangerous red mucosa. Prac Perio Aesth Dent 1995; 7:59-68.
Neville B, Damm D, Allen C, et al. Oral and maxillofacial pathology. Philadelphia: W. B. Saunders, 1995: 284-288.
Graham HB. Keratosis of the larynx. Arch Otolaryngol 1942; 36:735-739.
Myerson MC. Smoker's larynx: clinical pathologic entity. Ann Otol Rhin Laryng 1950; 59:541-546.
Miller AH. Carcinoma-in-situ of the larynx: a 20 year study of the results of management. Am J Surg 1970; 120:492-494.
Bauer WC. Concommitant carcinoma in situ and invasive carcinoma of the larynx. Can J Otolaryngol 1974; 3:533-542.
Kambic V. Difficulties in management of vocal cord precancerous lesions. J Laryngol Otol 1978; 92:305-315.
Altman F, Ginsberg I Stout AP. Intraepithelial carcinoma (carcinoma in situ) of the laryngx. Arch Otolaryngol 1952; 56:121-133.
Pene F, Fletcher GH. Results in irradiation of the in situ carcinoma of the vocal cords. Cancer 1976; 37:2586-2590.
Doyle PJ, Flores A, Douglas GS. Carcinoma in situ of the larynx. Laryngoscope 1977; 87:310-316.
Gabriel CE, Jones DG. Hyperkeratosis of the larynx. J Laryngol Otol 1973; 87:129-134.
McGavran MH, Bauer WC, Ogura JH. Isolated laryngeal keratosis--its relation to carcinoma of the larynx based on a clinicopathologic study of 87 consecutive cases. Laryngoscope 1960; 70:932-951.
Kleinsasser O. Uber den Krankheitsverlauf bei Epithelhyperplasien der Kehlkopfscheimaut und die Entstehung von Karzinomen: IV. Mitteilung. Z Laryngol Rhinol Otol 1963; 42:541-558.
Miller AH, Fisher HR. Clues to the life history of carcinoma in situ of the larynx. Laryngoscope 1971; 81:1475-1480.
Elman AJ, Goodman M, Wang CC, et al. In situ carcinoma in the vocal cords. Cancer 1979; 43:2422-2428.
Hintz BL, Kagon AR, Nussbaum H, et al.A "watchful waiting" policy for in situ carcinoma of the vocal cords. Arch Otolaryngol 1981; 107; 746-751.
Hellquist H, Lundgren J, Olofsson J. Hyperplasia, keratosis, dysplasia, and carcinoma in situ of the vocal cords -- a follow-up study. Clin Otolaryngol 1982; 7:11-27.
Norris CM, Peale AR. Keratosis of the larynx. J Laryngol Otol 1973; 77:635-647.
Hojslet et al.[1989, find this]
Bouquot JE, Weiland LH, Kurland LT. Laryngeal keratosis and carcinoma in the Rochester, Minnesota population, 1935-1984. Cancer Detect Prevent 1991; 15:83-91.64.
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Waldron CA, Shafer WG. Leukoplakia revisted: a clinicopathologic study of 3256 oral leukoplakias. Cancer 1975; 36:1386-1392.
Pindborg JJ. Oral precancer. In: Barnes L (ed). Surgical pathology of the head and neck. New York: Marcel Dekker, 1985, pp 279-301.
Bouquot JE. Leukoplakia and erythroplakia: a review and update. Pract Perio Aesth Dent 1994; 6:1-10.
Bouquot JE, Whitaker SB. Oral leukoplakia--rationale for diagnosis and prognosis of its clinical subtypes or "phases". Quint Internat 1994; 25:133-140.
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Broders AC. Carcinoma in situ contrasted with benign penetrating epithelium. J Am Med Assoc 1932; 99:1670-1674.
Kramer IRH. Carcinoma in situ of the oral mucosa. Int Dent J 1973; 23:94-______.
Banoczy J, Csiba A. Occurrence of epithelial dysplasia in oral leukoplakia: analysis and follow-up study of 120 cases. Oral Surg Oral Med Oral Pathol 1976; 42:766-774.
Neville B, Damm D, Allen C, et al. Oral and maxillofacial pathology. Philadelphia: W. B. Saunders, 1995: 284-288.r
WHO Collaborating Centre for Oral Precancerous Lesions. Definitions of leukoplakia and related lesions: an aid to studies on oral precancers. Oral Surg Oral Med Oral Pathol 1978; 46:518-539.
Lumerman H, Freedman P, Kerpel S. Oral epithelial dysplasia and the development of invasive squamous cell carcinoma. Oral Surg Oral Med Oral Pathol 1995; 79:321-329.
Bouquot JE, Kurland LT, Weiland FH. Forty-five years of oral carcinoma in an United States population. J Oral Pathol 1985; 11:81.
Bouquot JE. Common oral lesions found during a mass screening examination. J Amer Dent Assoc 1986; 112:50-57.
Bouquot JE. Epidemiology. In: Gnepp DG. Pathology of the head and neck. New York: Churchill Livingstone, 1987, pp 263-314.
Bouquot JE, Gnepp D. Epidemiology of carcinoma in situ of the upper aerodigestive tract. Cancer 1988; 61: 1685-1690.
Bouquot JE, Kurland LT, Weiland LH. Carcinoma in situ of the upper aerodigestive tract: incidence, time trends and follow-up in Rochester, Minnesota, 1935-1984. Cancer 1988; 61:1691-1698.
Bouquot JE, Weiland LH, Kurland LT. Leukoplakia and carcinoma in situ synchronously associated with invasive oral/pharyngeal carcinoma in Rochester, Minnesota, 1935-1984. Oral Surg Oral Med Oral Pathol 1988; 65:199-207.
Bouquot JE, Gnepp DR. Laryngeal precancer--a review of the literature, commentary and comparison with oral leukoplakia. Head Neck 1991; 13: 488-497.
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Vedtofte P, Holmstrup P, Hjorting-Hansen E, et al. Surgical treatment of premalignant lesions of the oral mucosa. Int J Oral Maxillofac Surg 1987; 16:656-664.
Silverman S Jr, Gorsky M, Lozada F. Oral leukoplakia and malignant transformation: a follow-up study of 257 patients. Cancer 1984; 53:563-568.
Amagasa T, Yakoo E, Sato K, et al. A study of the clinical characteristics and treatment of oral carcinoma in situ. Oral Surg Oral Pathol Oral Pathol 1985; 60:50-55.
Field EA, Field JK, Martin MV. Does Candida have a role in oral epithelial neoplasia? J Med Vet Mycol 1989; 27:277-294.
McCance DJ, Kopan R, Fuchs E, et al. Human papillomavirus type 16 alters human epithelial cell differentiation in vitro. Proc Natl Acad Sci USA 1988; 85:7169-7173.
Gassenmaier A, Hornstein OP. Presence of papillomavirus DNA in benign and precancerous oral leukoplakias and squamous cell carcinomas. Dermatologica 1988; 176:224-233.
Kashima HK, et al. Human papillomavirus in squamous cell carcinoma, leukoplakia, lichen planus, and clinically normal epithelium of the oral cavity. Ann Otol Rhinol Laryngol 1990; 99:55-61.
Murrah V. Human papillomavirus in oral leukoplakia. Proceedings, annual meeting, American Academy of Oral Pathology; Portland, Maine; May, 1994.
Bouquot JE, Young S. Unpublished data: "Human papillomavirus identification in 500 oral leukoplakia cases using polymerase chain reaction."
Erythroplakia of Sites Other than Head & Neck Mucosa
Queyrat L. Erythroplasie du gland. Bull Soc Fr Dermatol Syph 1911; 22:378-382.[vol. 28?]
Rubin IC. The pathologic diagnosis of incipient carcinoma of the uterus. Am J Obstet 1910; 62:668-676.
Darier J, Lemaitre F, Monier L. Les modes de debut des cancers de la bouche et des machiores. Bull Cancer (Paris) 1924; 13:256-272.
Santa Cruz DJ. Skin. In: Henson DE, Albores-Saavedra J. The pathology of incipient neoplasia. Philadelphia: W. B. Saunders, 1986:5-16.
Fu YS, Reagan JW. Pathology of the uterine cervix, vagina, and vulva. Philadelphia: W. B. Saunders, 1989:235-258.
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Table 1: Precancerous lesions of the oral, pharyngeal and laryngeal mucosa (clinical terms only).
MALIGNANT TRANSFORMATION
DISEASE NAME POTENTIAL
Proliferative verrucous leukoplakia (PVC) ******
Nicotine palatinus in reverse smokers # *****
Erythroplakia *****
Oral submucous fibrosis *****
Erythroleukoplakia (Phase IV leukoplakia) ## ****
Granular (Phase III) leukoplakia ## ****
Laryngeal keratosis ***
Actinic cheilosis ***
Smooth, thick (Phase II) leukoplakia ## **
Lichen planus (erosive forms) **
Smooth,red tongue of Plummer-Vinson disease **
Smokeless tobacco keratosis *
Smooth, thin (Phase I) leukoplakia ## +/-
# reverse smoking: smoking with the lit end of the cigarette in one's mouth
## leukoplakia Phases are explained in the papers by Bouquot and Whitaker33 and Bouquot.1
Table 2: Malignant transformation rates (%) for oral carcinoma in situ and/or severe epithelial dysplasia, ranked by rates. Lesions appeared clinically as red, white or combined red and white macules, i.e. not all were pure erythroplakias. Cancers not arising from the site of the precancer are excluded.
Number of Cumulative Malignant
Author(s) Country Patients Follow-up Time # Transformation Rate
Lumerman et al (1995)36 U.S.A. 7 11 yrs (m=1.5 yrs) 14.3% *
Bouquot et al (1988)37 U.S.A. @ 32 @@ 346 yrs (m=10.8 yrs) 15.6 **
Mincer et al (1972)35 U.S.A. 16 48 (m=3.0 yrs) @@@ 18.8
Banoczy, Csiba (1976)38 Hungary 23 145 yrs (m=6.3 yrs) 21.8
Vedtofte et al (1987)39 Denmark 14 55 yrs (m=3.9 yrs) 35.7
Silverman et al (1984)40 U.S.A. 22 162 yrs (m=7.4 yrs) 36.0
Amagasa et al (1985)41 Japan 12 @@ 120 yrs (m=10.0 yrs) 50.0 **
TOTAL 126 887 years (m=7.1 yrs) 26.3% ***
# sum total of time which lesions were collectively followed (mean follow-up times are in parentheses)
@ the only population-based study; represents middle-class whites
@@ includes only carcinoma in situ cases
@@@ assumes an average follow-up time of 3 years (range=1-8 years); data not available from the report
* average follow-up time was less than 2 years
** average follow-up time was 10 years or more
*** statistically weighed for different follow-up time periods and sample sizesTable 3: Malignant transformation rates (%) for laryngeal carcinoma in situ, as determined by all English language follow-up studies published to date, ranked by frequency.
NUMBER OF MALIGNANT
AUTHOR(S) COUNTRY PATIENTS TRANSFORMATION
Altman et al (1952)42 U.S.A. 29 ## 3.5% *
Pene & Fletcher (1976)43 U.S.A. 26 ## 4.0
Doyle et al (1977)44 U.S.A. 28 ## 7.1
Gabriel & Jones (1973)45 U.S.A. # 7.3
McGavran et al (1960)46 U.S.A. 18 # 11.1
Miller & Fisher (1971)47 U.S.A. 203 ## 15.8
Elman et al (1979)48 U.S.A. 81 ## 17.0
Hellquist et al (1982)49 Norway 20 # 25.0
Norris & Peal (1963)50 U.S.A. 16 # 33.3 **
Hojslet et al (1989)51 Germany # 40.0
Hintz et al (1981)52 Germany 27 # 63.0 **
Kleinsasser (1963)53 Germany 20 ## 90.0 **
TOTAL, TREATED CASES 486 29.0% ***
TOTAL, UNTREATED CASES 53 60.0% ***
* includes only cancers developing in the anatomic area of the previously recorded dysplastic lesions
** includes only untreated cases of carcinoma in situ and severe epithelial dysplasia
*** weighed for different sample sizes, excludes untreated cases
# includes all epithelial dysplasias: mild, moderate and severe dysplasia, and carcinoma in situ
## includes only severe epithelial dysplasias and carcinomas in situTable 4: Clinical characteristics of carcinoma in situ of the vermilion border and UAT mucosa.37
CHARACTERISTIC VERMILION UAT MUCOSA
% males 88.2% 79.2%
Avg. age at diagnosis 69.8 yrs. 60.1 yrs.
% tobacco smokers 80.0% 93.3%
% alcohol abuse * 6.7% 68.4%
% with outdoor occupation 64.7% 20.0%
Average lesion size 1.3 cm. 1.4 cm.
Average lesion duration 3.4 yrs. 2.1 yrs.
% with erythroplakia 0.0% 38.9%
% with leukoplakia 100.0% 66.7%
% with ulceration ** 56.3% 16.7%
% with invasive carcinoma at diagnosis @ 11.8% 16.7%
% with invasive carcinoma after diagnosis @ 0.0% 8.3%
% recurred after treatment (no cancer) 0.0% 12.5%
* identified as "alcoholic," "heavy drinker," or with a "drinking problem" in medical records
** mucosa ulcers are virtually all invasive carcinomas, while most vermilion ulcers are inflammatory or traumatic in nature
@ invasive squamous cell carcinoma (excluding carcinoma in situ)
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