Leukoedema of the Oral Mucosa

Leukoedema of the Oral Mucosa

L eu ko ed em a of the oral m ucosa This report concerns itself with the first two of those three activities. Roy T. Durocher, DD S, P itts b u rg h R...

3MB Sizes 0 Downloads 113 Views

L eu ko ed em a of the oral m ucosa This report concerns itself with the first two of those three activities. Roy T. Durocher, DD S, P itts b u rg h Roger Thalman, D M D Giuseppe Fiore-Donno, M D, D M D , G eneva, S w itz e rla n d

A n e x tre m e ly h ig h in c id e n c e o f le u k o e d e m a o f th e o ra l m u c o s a w a s fo u n d c lin ic a lly in th is s tu d y o f 430 p a tie n ts . L e u k o e d e m a o n th e b u c c a l m u c o s a w a s c lin ic a lly o b s e rv e d in 400 p a tie n ts , a n d a ls o on th e la b ia l m u c o s a in 131 p a tie n ts . In m o s t p a ­ tie n ts b u c c a l in v o lv e m e n t w a s b ila te ra l. In te n s ity o f th e e x a m in a tio n la m p p ro v e d to be a c ritic a l fa c to r in th e id e n tific a tio n o f m ild fo rm s o f le u k o ­ e d e m a . B e c a u s e o f th e h ig h in c id e n c e o f le u k o ­ e d e m a fo u n d in th e s tu d y s a m p le , th e p o s s ib ility th a t it is a v a ria tio n o f n o rm a l s h o u ld be c o n s id ­ ere d.

In 1953, Sanstead and L ow e1 reported on an in­ teresting phenomenon that they had observed in the buccal mucosa o f 43% o f the white and 90% of the black patients of 646 individuals in a psy­ chiatric hospital. These investigators described what they saw as “ a generalized, whitish gray lesion” ; the biopsy specimens o f the lesions re­ vealed intracellular edema and epithelial hyper­ plasia. They further said that “ the mucosa ap­ peared edematous” and “ the degree of involve­ ment ranged from a filmy opalescence to a whitish-gray or ‘waterlogged’ appearance” and that the condition was asymptomatic. They termed the lesion leukoedema. A 1954 study by Sandstead and co-workers, reported by others2 in 1968, indicated that the condition was diagnosed in 45% of the patients 'in a hospital population of 1,017; there was a much higher incidence o f the condition among black patients than among white patients. Others have reported on leukoedema, but mostly it has been mentioned as only one finding among others in general epidemiological surveys of the oral cavity.3'8 Our objectives were to conduct a systematic study of the clinical incidence of leukoedema, to analyze its possible correlation with several factors, and .to investigate its histochemistry.

D iagnostic crite ria We made a clinical diagnosis of leukoedema of the buccal mucosa when these characteristics were observable. The lesion was diffuse, whit­ ish to whitish-gray, frequently folded into wrin­ kles or whitish streaks, and asymptomatic (Fig 1). At times, however, the wrinkles and streaks were absent, but a filmy opalescence was pres­ ent and continued to obliterate, at least in part, the fine vascular network usually observed in the nonkeratinized portions o f the oral mucosa. Unless the mucosa is heavily wrinkled, the whit­ ishness or whitish-grayness can be made to dis­ appear by stretching the tissue. A s the stretched mucosa is relaxed, the original opalescence re­ turns. H owever, if the opalescence is heavy, the film may not disappear com pletely. In in­ stances of doubt at first glance, extremely fine whitish streaks can be caused to appear if the mucosa is gently compressed on itself. The sur­ face is soft to the touch and cannot be scraped off without surgical manipulation. (The last cri­ terion does not seem to agree with observations of some other investigators.5'7) These criteria were necessarily modified in the examination o f nonbuccal sites o f the oral mucosa. So that the mucosa o f the upper lip could be seen with the patient in the standard­ ized position to be described, a turning back of the lip and, thus, a stretching o f the mucosa was necessary. A t other sites, it was impossible to manipulate the mucosa. Consequently, at non­ buccal sites clinical diagnosis was made only on the basis of the filmy opalescense with or without streaking; otherwise, the lesions were typical o f those seen in the buccal mucosa. ■ Clinical examination: Two dental operator­ ies were used. The various positions o f each chair were adjusted and calibrated so that pa­ tients were positioned as similarly as possible. The back was about at a 45° angle to the seat and the headrest was adjusted so that the head and neck were in a straight line with the upper part o f the patient’s body. The only variable in each chair was the height o f the headrest which was JADA, Vol. 85, Novem ber 1972 ■ 1105

adjusted to accommodate the height of each in­ dividual. Illumination was provided by a Ritter dental overhead light, model J, with lamp number 141160. This unit provides an adjustment for light intensity. The intensity was calibrated for each o f the two lamps at 32,000 lux at a distance of 61.5 cm from the center of the lamp shield to a point on the patient’s upper lip overlying the notch inferior to the anterior nasal spine. This distance was maintained for each patient. Two standard no. 4 dental mirrors were used to examine the oral cavity. Stretching and re­ laxation of the buccal and labial mucosa were accomplished by the use of the mirrors or fin­ gers, or both. The submaxillary glands were pal­ pated. A specially designed form was used to record the findings o f the clinical examination of the lips, tongue, floor of the mouth, submaxillary glands, hard and soft palates, uvula, tonsils, glosso- and pharyngopalatine walls, posterior oropharyngeal wall, edentulous ridges, alveolar mucosa, gingiva, metallic restorations, labial mucosa, and buccal mucosa. The absence or presence of prostheses was documented also. Leukoedema was recorded as being adjacent to natural teeth, prostheses, edentulous spaces, or a combination of these. The name of the exam­ iner was noted. The clinical examinations were conducted by two of us, one examiner in each of the two operatories. Negative and doubtful clinical impres­ sions relative to leukoedema were confirmed by a second examiner. ■ H istologic review: Incisional biopsy speci­ mens were taken for definitive diagnostic pur­ poses if both investigators had doubtful clinical impressions o f the region. In some instances, tissue of buccal mucosa clinically judged by both clinicians to be free of leukoedema was. submitted for histologic review also. Biopsies were performed with a 0.5-cm round punch instrument and a scalpel to free the base o f the specimen. Local anesthesia was infiltrat­ ed in regions away from the site of the tissue to be removed. The specimen was placed, with the epithelial surface downward, on coarse filter paper and immediately immersed, with the con­ nective tissue surface downward, in a bottle containing a 10% Formalin fixative. (The speci­ men was placed on the bottom of the bottle.) Sections were stained with hematoxylin and eosin. 1106 ■ JADA, Vol. 85, November 1972

Fig 1 ■ A rrow s outline more prom inent area of leukoedema.

■ Interexaminer reliability: These steps were taken before the study to establish reliability be­ tween examiners. Single biopsy specimens were taken from the buccal mucosa o f each of three persons for whom a clinical diagnosis of leukoedema had been made by the investigator having the most clinical experience with leukoedema. A review of the sections revealed the presence of epi­ thelial intracellular edema. This was accepted, in accordance with the Sanstead and Lowe study, as a confirmation of the clinical impres­ sion. The principal investigator double-checked clinically the second investigator’s clinical diag­ noses of leukoedema in five patients who had the typical whitish-gray wrinkling or streaks. The second investigator then was required to agree, without previous knowledge, with the first on a mixture of normal and abnormal find­ ings in several other patients. Biopsies were performed in two additional patients who were thought after clinical exam­ ination to be free of leukoedema and in one other patient whose condition was in doubt—inasmuch as there was a faint filmy opalescence, but no wrinkles or streaks. (The specimen from the lat­ ter patient proved to show epithelial intracellu­ lar edema as did one of the first two specimens thought to be normal clinically. The section from the third patient exhibited only an occa­ sional cell containing a space, and therefore, it was judged to be representative of normal tis­ sue.)

Table ■ The d istrib u tio n of find in gs at various sites. Site Buccal mucosa Unilateral Bilateral Labial mucosa Uvula Tongue Other

No. cases

% cases

400 14 386 131 42 6 9

100 3 97 32 10 1.5 2.5

A t the completion of the study, we tried to de­ termine if any actual differences in performance existed between the two examiners in the iden­ tification o f leukoedema. A 2 x 2 chi-square test was performed on the clinical findings in the study sample. The results showed no statistical difference. ■ Sam ple selection: During April, May, and June 1971, 430 patients (more than 15 years old) were examined immediately after, and in the order of, their registration at the polyclinic of the section o f dental medicine o f the Faculty of Medicine, University o f Geneva. Children were excluded because registration and care of this group of patients is provided in another clinic. Oral findings for all o f the patients were record­ ed. ■ Survey questionnaire: A self-administered questionnaire, available in French, Italian, or Spanish, was used at the time of examination to determine the possible correlation o f leuko­ edema with other factors selected on the basis o f subjective hypotheses. It consisted of three parts. Part one included the statistics of name, age, race, sex, parental nationality, and occupa­ tion. Another part, permitting space for an openended response, concerned the patient’s spe­ cific history o f dermatitis, allergy, hormonal disturbance, pregnancy, diabetes, anemia, ner­ vousness, and drug use. The third section in­ cluded questions about diet and alcohol habits and tobacco, wafer, toothpaste, and mouth­ wash usage.

in the inferior labial mucosa, in no patients was it seen in the superior labial mucosa only. The uvula exhibited leukoedema in 42 patients and the tongue in only 6. The condition was ob­ served in the floor o f the mouth in only two per­ sons. In nine patients leukoedema was observed in the pharyngoglossopalatine sites (Table). Several other oral changes were observed and recorded. H owever, since any one variety o f these was minimal in number and inasmuch as the number of patients without leukoedema was so small, correlations could not be made. There­ fore, listing of the additional findings is not per­ tinent to this report. ■ Survey questionnaire: Responses to the ques­ tionnaire were subjected to statistical analysis. The ages of the patients with leukoedema ranged from 16 to 82. O f 60 persons 21 years old or younger who were examined, 57 had the condi­ tion, including the five patients who were age 16. The age distribution of those individuals without leukoedema was wide, from age 19 to 76, and unclustered. Alm ost 100% of the respond­ ents listed their race as white. Sex distribution was nearly even with respect to numbers ex­ amined and incidence o f leukoedema. The par­ ents o f the individuals were mainly of Swiss, Italian, French, or Spanish origin. A side from these observations, little can be said o f the data. Again, in view o f the fact that there were so few patients without leukoedema, it is impossible to make any statistical compar­ isons between the groups with and without leu­ koedema. A lso, it is not possible to make com­ parisons within the leukoedema group because data are not known on the distribution of vari­ ables, such as the percentage of the total pop­ ulation from which the study sample came who drink alcoholic beverages or who have a history of diabetes.

Results D iscussion ■ Clinical examination: Leukoedema was clin­ ically observed in 400, or 93%, of the 430 pa­ tients examined. In each instance o f a positive observation, the lesion was present in the buc­ cal mucosa, although it was frequently present at other sites as well. Except for 14 patients, buccal involvement was bilateral; unilateral in­ cidence was only 3%. The lesion was observed in the labial mucosa in 131 persons, or 32% o f the patients. Although it was seen at times only

The high clinical incidence of leukoedema as de­ termined by this study conducted under care­ fully controlled conditions raises a question concerning data obtained by other investigators, although the data o f Sanstead and L ow e1 for blacks did approach the findings o f this investi­ gation. On the basis o f the clinical descriptions and histologic sections reported by those investiga-

D urocher—Thalm an— Fiore-D onno: LEUKOEDEMA OF ORAL MUCOSA ■ 1107

Fig 2 ■ Buccal mucosa w ith no clinical m anifestation of leuko­ edema.

tors, we believe that they observed the same clinical variations that we did. Sanstead and Lowe referred to a “ bluish cast” to the leukoedemic mucosa among some blacks. A similar color was observed in at least one black in the present study. Undoubtedly, a pigmented back­ ground enhances the ease with which leuko­ edema is observed. Indeed, the optic aspect of leukoedema is critical to the finding of this phe­ nomenon. The intensity of light and the pliabil­ ity of the mucosa are significant factors in the establishment o f a clinical diagnosis. In standardization of the intensity of each of the two adjustable dental lights, quite by acci­ dent it was noticed that mild forms of leuko­ edema could be made to appear and disappear clinically by manipulation of the intensity. Fur­ thermore, in instances in which the clinical ob­ servations about the presence of a change were in doubt, it was frequently possible for the in­ vestigator to bring about fine whitish folds or streaks by gently compressing the mucosa on

1108 • JADA, Vol. 85, November 1972

itself. Moreover, doubtful and negative clinical observations did not necessarily rule out the possibility of the presence of intracellular ede­ ma, either observable only through microscopic examination or manifested clinically under con­ ditions other than those described for this par­ ticular study. The possibility of clinically undetected leuko­ edema was suggested when the biopsies were performed to establish reliability between exam­ iners. Therefore, specimens for histologic re­ view were obtained from the buccal mucosa of seven persons in the survey sample. In five pa­ tients, mucosa clinically judged by both exam­ iners to be free of leukoedema was found to contain intracellular edema of sufficient degree to be diagnosed as leukoedema by the patholo­ gist who studied the specimens without the benefit of any clinical impression (Fig 2, 3). These histologic findings were substantiated later by two of us. In three of the five patients, a biopsy on clinically normal mucosa was per­ formed because the mucosa of the opposite buc­ cal pouch was clinically judged by the two ex­ aminers to indicate leukoedema. In both of the other two patients of the five, the buccal mucosa was clinically normal bilaterally. In one, bilater­ al biopsies were performed and the specimen from one side was positive. In the other indivi­ dual, buccal mucosa obtained from only one side was subjected to microscopic examination. This specimen also was reported to exhibit leu­ koedema. Again, in both instances the path­ ologist offered the diagnosis on the basis of in­ tracellular edema and without benefit of cliniical impressions. The diagnoses also were sub­

Fig 4 ■ P hotom icrograph revealing epithelial In­ tracellular edema in biopsy specim en obtained from buccal mucosa of do ubtfu l clinical appear­ ance. (Arrows indicate area of qu ite high degree of change.) Leukoedema, however, was clin ica lly o b ­ served in buccal m ucosa of opposite side.

stantiated by the same two examiners. In the re­ maining two of the seven persons subjected to biopsy, the two examiners observed leuko­ edema unilaterally in the buccal mucosa, but they had some doubt about the clinical appear­ ance of the opposite sides. For both patients, the results of the histologic examination were positive for leukoedema on the sides in question (Fig 4). The findings from histologic examination of these seven patients indicate the probability that there are more instances of the intracellular edema characteristic o f leukoedema than those manifested by clinical signs. Furthermore, the findings from the clinical examinations reported in this study indicate the likelihood of a far higher incidence of the clinical signs of leukoedema than would be detected by casual examination.

S u m m ary

Under controlled conditions, leukoedema of the oral mucosa was clinically observed in 400 (93%) of 430 dental clinic patients in Geneva, Switzerland. Tissue specimens, taken from the clinically normal buccal sides o f the mucosa of five of the 400 patients, were found by micro­ scopic examination to contain intracellular edema of a degree characteristic of leukoedema. Histologic specimens taken from two patients of the clinically normal group revealed the same intracellular edema. Because of the optic phenomenon related to the tissue alterations, the conditions under which the clinical examination is conducted are critical for identification of leukoedema. It was not possible to make a statistical cor­ relation of the finding of leukoedema with other

clinical changes, vital statistics, histories, or habits. Because this study suggests an the extremely high incidence of intracellular edema on the oral mucosa, the possibility that this phenomenon is a variation of normal must be considered. This concept is further supported by evidence that intracellular edema is a common finding in “ nor­ mal” vaginal m ucosa.1,9

The authors wish to acknow ledge the assistance of Dr. B. Portmann, pathologist at the Faculty of Medicine, University of Gene­ va, and Dr. T. Zullo o f the University of P ittsburgh School of Dental M edicine fo r his statistical analysis. Dr. D urocher was a visiting professor of stom atology at the section o f dental medicine, Faculty o f M edicine, University of Geneva, Switzerland. His current address is School of Dental Medicine, University o f Pittsburgh, 348 Salk Hall, Pittsburgh, 15213. Dr. Thalman is assistant and Dr. Fiore-Donno is professor and chief, o f the departm ent of stom atology and oral surgery, University of Geneva, Switzerland. 1. Sanstead, H.R., and Lowe, J.W. Leukoedema and kera­ tosis In relation to leukoplakia of the buccal mucosa in man. J Natl Cancer Inst 14:423 Oct 1953. 2. A rchard, H.O.; Carlson, K.P.; and Stanley, H.R. Leukoedema o f the human oral mucosa. Oral Surg 25:717 May 1968. 3. Martin, J.L.: Buenahora, A.M.; and Bolden, T.E. Cyto-histology of leukoedema of the buccal mucosa. J DC Dent Soc 44: 47 March 1969. 4. Hamner, J.E., and Villegas, O.L. The effect of coca leaf chewing on the buccal mucosa o f Aymara and Quechua In­ dians in Bolivia. Oral Surg 28:287 Aug 1969. 5. Pindborg, J.J.; Barmes, D.; Roed-Petersen, B. E pidem i­ ology and histology of oral leukoplakia and leukoedema among Papuans and New Guineans. Cancer 22:379 Aug 1968. 6. Pindborg, J.J., and others. Frequency o f oral w hite lesions among 10,000 individuals in Bangalore, South India. A prelim i­ nary report. Indian J Med Sci 20:349 May 1966. 7. Pindborg, J.J., and others. Frequency o f oral leukoplakias and related conditions am ong 10,000 Bombayites. P relim inary report. J All India Dent Assoc 37:228 July 1965. 8. Pindborg, J.J., and others. Frequency of oral carcinom a, leukoplakia, leukokeratosls, leukoedema, subm ucous fibrosis, and lichen planus in 10,000 Indians in Lucknow , Uttar Pradesh, India; prelim inary report. J Dent Res 44:61 May-June 1965. 9. Portm ann, B. Personal com m unication.

Durocher— Thalm an— Fiore-Donno: LEUKOEDEMA OF ORAL MUCOSA ■ 1109