Effects of smoking on the oral mucosa

HE effect of excessive sm&ing on the bueeal mucosa, of persons with an inherent tendency to hyperkeratosis has been described variously a,s smoker’s pa.tch, stomatitis nicotina, hypcrkcrstosis, leukoplakia buccalis, leukoma, leukopla,kia nicotma, ichthyosis butrcalis, etc. The clinical and experimental evidence demonstrating the irritating and carcinogenic possibilites of the chemical byproducts of smoking is being compiled in various parts of the world. %:arly conclusions of these studies bear out facts long known to dental clinicians. It is generally agreed that the degree of pathologic changes in the oral mucosa depends chiefly upon (I) the susceptibility of the individual and (2) the amount of tobacco used, regardless of the method of use. It must be borne in mind tha.t this same “hyperkeratot,ic response” reacts to other irritating agents, such as bacteria, foods, allergies, chemicals, and mcchanical-psychoprovides most of these stimuli in one neurotic habits. Smoking, rnnfortunatcly, small ’ ‘ package deal ’ ’ by furnishing both mechanical and chemical stimuli. Merritt1 enumcrat,es some of the chemical constituents and by-products of tobacco, among which are a number of salts, sulfates, nitrates, chlorides and phospha.tes, malates of potassium, calcium and ammonium, albumin, resin, tannin, citric acid, nicotianine, nicotine, collodine, pyridinc, picoline, ammonia, and carbon monoxide Many of these drugs act as vasoconstrictors of the peripheral blood vessels of the oral mucous mcmbrancs, thereby resulting in a restricted circulation of these tissues. Eichenlaub2 examined 16,802 veterans and found 327 with leukoplakia on the oral mucosa. Only five stated that they did not use tobacco. Tn this same study correlation was made between constitutional disease and leukoplakia, and the conclusion reached was that the inherent tendency to hyperkeratosis was more important than the organic disease. Wynde9 reports a 90 per cent or better relationship between tobacco and lung cancer. McCarthy* correlates the localization of the lesions with the method of smoking, which provides a constant mutation, thereby agreeing with Wynder ‘s3 animal experiments with tar and nicotine, which produced hyperkeratotic and papillomatous lesions.

Classification Thorna’@

with .---

the

histopathologie descriptions of these lesions coincide quite well Essentially, recent ICollar group ‘9 microscopic classification.

*Periodontist, Providence, Rhode

Rhode Island.

island

Hospital,

consultant

in

pcriodontia,

Veterans

Hospital,

El?FE:CTS OF SMOKING

1027

ON ORAL MUCOSA

McCartl~y,4 Bernier,7 and Prinz” all agree as to various clinical and pathologic stages of the disease, even though there is a wide variance in clinical findings removal of 0~ and a decided diffcrcnce in manner of rcsponsc following irritant factor. Rotlunan” claims that the degree of diffcrcnce is related to the &tare of the germinative epithclium. A composite classification of these epithclial responses or changes might bc summed up as follows: 1. Hyperplasia.----The initial reaction of ly~~mms, membrane to irrita.tion. This is only an overgrowth of the prickle-cell layer. 2. H$perkeratosis.-The development of a definite, sharply outlined, white patch. Microscopically there is an increase in thickness in the keratin and granular layer, with no inflammatory or invasive activity. 3. Leukoplakia.-This stage has been graded by various pathologists, but essentially it can be diagnosed as present when hyperkeratosis with inflammation appears. Here the plaques are indurated and ra.ised, and wrinkling and fissuring may occur. MUCOL~S glands may be raised and papular nodules noted. Microscopically there is definite bypkeratosis, acanthosis, and a marked rouncl-cell infiltration in the corium. Invasive activity of epithelial elements may or may not bc present and it is almost impossible to determine clinically whether this a.ctivity is present. 4. Dyskeratosis or Neoplastic Stage.-These lesions may bc verrucous and papillomatous; sometimes ulceration and spontaneous desquamation may occur. The downgrowth of the epithclium, extreme dyskcratosis, and pronounced lymphocytic infiltration are the most prominent microscopic features. 5. Early Epidermoid Carcinoma.---Clinically these lesions cart a.pall stages of so-called pear like the ones just described. Microscopically leukoplnkia are found, plus cpithelial pearl formations. Infrequent mitotic figures are typical and there is marked inflammatory activity in the connective tissue. Five cases have been selected to demonstra.te: (1) severe Icukoplakia directly due to heavy smoking (these lesions showed a dramatic improvement by simply removing the causative irritant) ; (2) less severe lesions, which did not improve by removing the irritant factor but eventuadly degenerated or mutated into a malignancy; and (3) the effect of a constitutional background. Case Reports* Cam L-J. W., EL 76.yenr-old white man who CVELRart inveterate pipe smoker, was presented at the Tumor Clinic with 8. lesion of several months duration. Serology was negative. There was a history of epilepsy with no dilantin medication. FIis admission notes describe an “extensive leukoplakia involving the left bu~cal MUCOS~ and oxtending to tlx *Cases presented at the Tumor Clinic, Rhode Island Hospital. Rhode through the courtesy of Dr. Herbert Fanger, Chief of Pathology, photographs by Photo Lab, Rhode Island Hospital.

Pathology repo~ri Island Hospital.

:tdjacetit soft x11(1 hard palates. ’ ’ Clinically the lesion cotlld be gra.ded by Prinz or ‘ChoIrPA 2~ a grade 3 or 4, by ReGor as dyslroratotit. Ieukoplakia, by Xollar as a verrucous, papilinixttont;, fissured type referred to as i ‘ hyperkeratosis complex. ’ * The leathery, heaped-up layers of keratinizrd eyitbetinnt formed lnrge nodules coated over with heavy fur (Fig. J )~ Xnme badly broken-dowr-I teeth in the area were: causing additional irritation. There w& .yo~‘fmess and active desquamation. Neoplastic leukoplakia was strongly suspected. There were questionable palp;thle lyruph nodes. The lesion was so extensive that it was felt that elect.rodesiccation and fulguration should be postponed. until the earious teeth had been removed and improved oral hygiene xttxined. The patient was told to stop smoking entirely and to return in six wnoks. The enrious t,ecth wore extracted in the outpatient department.

Fig. 1. Fig. I.-Case Fig. 2.-Case

Rig. 2.

1. Heavy pipe smoker for a period of about forty years. 1. Two months after complete cessation of smoking.

The patient reported back to the Tumor Clinic five lveeks later, when a very dramatic improvement was noted (Fig. 2). He had given up smokiug entirely. The papillomatous formation had.‘disappoa.rod and there was but very slight evidence of marginal involvement. Five months later there was no recurrence of the original lesion. Case 2.-J. P., a white Italian man, aged 60 years, was referred to the Tumor Clinic for diagnosis and treatment of a painful lesion on the buecal mucosa of two to three months’ duration. He was a diabetic, controlled by diet. Serology was negative. He was a heavy smoker of strong “stagy” cigars. There was no palpable lymphadenopathy. Teeth were all present and in good condit.ion. The lesions extended over the surfaces of the lower lip, and involved both cheeks and the gingival margins of some of the molar teeth (Fig. 3). The leukoplakia could be classified as grade 3 by Prinz beca.use of the horny, wrinkled surface. Bernier might consider this clinically as hypcrkeratosis mutating to leukoplakia. Kollar and his co-workers could possibly suspect hyperkeratosis, dyskeratosis, and inflammation, and thereby classify the lesion under their No. 4 group. This case was also considered too extensive for desiccation, but the patient was advised to stop smoking entirely and return for follow-up examinations. Five months later, after missing several appointments, he returned and reported that ho had stopped smoking completely. The improvement of the lesion was dramatic and remarkable (Fig. 4).

Fig. Fig. Fig.

Fig. Fig,

3.-Case 4.-Case

5.--ca.se G.---Case

3.

2. Heavy 2. Four

3. 3.

Heavy Cheek

Fig.

“stagy” months

cigar smoker after completely

pipe and following

Fig.

5.

Fig.

6

cigar smoker. desiccation.

4.

for forty years. eliminating USC of

Epidermoid

all

carcinoma,

1.ypes

of

grade

to ,bacco.

1.

case 3.--F:. G., an Irishman, aged 69 years, presented a sore in the mouth of one ~n~onth’s duration. Kc had had diabetes for about six years. A Uinton test was negutivr. 11.2 mns ii very hmvy pipe ad cigtw smoker. Tlrc lesion appeared as a typical verrucous, papillomatous formation. It was somewhat rxistxl and indurated iu one area about 1 cm. iu diameter. The surrounding muocosa was lwthc~ry and flasurcd, but this was not as marked as in the two previous cases (Fig. 5). There were some questionable nodes at the angle of the jaw on the afIecl,ed side. The biopsy report was ( i typical hyperplasia, suggestive but not diagnostic for malignancy. ’ ’ Thon~sl and Prinz might regard this a neoplastic leukoplakia, grade 4; Bernier, and associates, probably intracpithelial cancer or group 5 in a true leukoplakia ; and Kollar l;hi?ir rlassification. Smoking was discontinued, but one week latcs the soreness persisted, A second microscopic examination showed tumor tissue apparontly &sing from surface epithelium. There were frequent foci of keratin formations and numerous epithelial pearls, atypical cells with variat,ions in sizes and shapes of the nuclei and. mitotic figures. Inflammation. was marked and chronic in nature. Diagnosis : Epidermoid carcinoma, grade 1. Electrosurgerg was performed a.nd the patient was followed monthly,

Fig.

7.-~-Case

4.

Nonsmoker

with

leukoplakia

and

early

malignant

changes.

Ten months later snpcrfieial ulceration had appeared at the site of excision performed by electrocautery. A third biopsy showed epidermoid carcinoma, grade 1. One week later Under superficial ulceration was noted and small lymph nodes were found on palpation. the Wood lamp (ultraviolet), an orange-reddish pink fluorescence was easily discernible. The patient was hospitalized for wide excision and radical no& dissection. Microscopically, the lesion was verified as epidermoid carcinoma., grade 1. The nodes showed chronic lymphadcnitis. Ten months later the patient showed no evidence of recurrence (Fig. 6). Case 4.-M. C., a 55year-old white woman, was presented at the clinic with an extensive lesion of the left buccnl mucosa of several years’ duration. She was a controlled diabetic. She did not admit to smoking or chewing snuff. The lesion was papilliferous and fnngating. There were multiple white, pearly plaques seon on both upper and lower alveolar ridges, widespread over the buccal mucosa (Pig. 7). The biopsy showed leukoplakia of the buccal mucosa with early malignant changes. Occasional mitotic figures were seen. The postoperative diagnosis after desiccation was leulrophtkia, active, premalignant.

lWFJ!XTS

OF SMOKING

Fig. 8.--Case

ON ORhL

4. Recurrence

MUCOSA

two years

later.

Fig. 9.

Fig. 10. Fig. 9.Fig. 10.-

5. Glossitis with luetic e 5. Keratoses eliminated

background. by stopping

Superimposed lee Ikoplakia. heavy smoking.

103 1

Extensive

was noted one month later, and after snother Bvc weeks there was leukop$akic areas. Additional electrodessieation was d.onc, but a war later there was more recIIrrence. This was a,gain treated by &sic&ion, but aftor another vear there was more recurrence. Biopsy at thie time did not show a positive picture of The patient, the~eforo, was treated with mazy de&cation a few we&s -pidermoid carcinoma. later and again five months later when recurrence again was noted. There was no lymphadenopathy present (Fig. 8). This case demonstrates the recurrence of the keratoses without an apparent irritation Fa.c.t;or. The susceptibility of this patient is of primary importance. Case S.-P. D., a 66-year-old white man, wa ,s a very heavy smoker and had a leutic background. There WOE irregular, grayish white, erosive He complained of severe glossitis. lcukoplakie areas on the dorsum of the tongue which were quite painful (Fig. 9). He was told to give up smoking and to return in six months. had Six months later the tongue was the same morpl~ologically, but the leukoplakia lessened appreciably. After another six months the superficial keratosis had disappeard CxtenSive

(Fig.

slo;ghing

reeurrenee

of

10).

The constitutional which can very readily

syphilitic background become precancerous.

predisposed

this

patient,

to

lrerntotic

ct~~gcts

Discussion The cases reported demonstrate ihe clinical variance that can occur when the oral mucous membrane is irritated by the by-products of smoking. Certainly, all leukoplakia type lesions can be considered part of a keratotic process. The keratosis can be a mild, innocent-looking, whitish gray plaque, or it can appear clinically as an advanced, verrucous, papillomatous precancerous lesion. The intensity of the keratotic response to the irritating stimulus of smoki.ng seems directly proportional to the susceptibility of the patient. The tissue changes in the susceptible person are also directly proportional to the amount of tobscco consumed, regardless of the form or method of use. The microscopic examination of the lesion is the essential means to making a diEerentia1 diagnosis. The gross appearance of the tissue does not furnish adequate criteria, and simple grading of the lesion by a clinical examination does not seem positive enough, since there is too much of a variance in t,heir gross Somewha.t simple-looking white plaques have proved premalignant appearance. or malignant after prolonged clinical observation, whereas advanced-appearing lesions have been made to disappear by simply removing the irritating or traumatizing factors. There seems a need for reclassifying these lesions clinically, as well as pathologically. Actually, there is a generalized agreement in the literature that keratoscs in the oral mucosa appear following eonstant irritation or traumatization. LeukoplaRia, the derivation of which means “white patch,” seems like an excellent generalized term. Descriptive terms of this white patch, such as flat, raised, fissured, verrucous, papillomatous, ulcerated, eroded, etc., also seem adequate. The grading and classification of the lesion, however, should be done only aft,er microscopic examination. Summazy 1. Several c&es were sanoking on oral mucosa.

described

and Conclusions to demonstrate

the

kcratotjc

effect of

EBIG!XTS

OF SMOKING

ON ORAL MUCOSA

1033

2. The gross lesion may appear in many forms, ranging from a simple grayish white patch to a large angry-looking, verrucous, papillomatous, mushroom type growth. 3. The lesion, regardless of clinical appearance, may disappear entirely after smoking has been discontinued. 4. The lesion can appear simple and still may he precancerous or cancerous. 5. The lesion may be descrihad grossly hut the diagnosis should be made microscopically. 6. If a person is susceptible to kcratosis, excessive smoking should be avoided. References 1. Merritt, 2. 3. 4. 5. 6. 7. 8. 9.

Arthur H.: Periodontal Diseases and Soft Tissue Lesions of the Oral Cavity, ed. 3, Philadelphia, 1946, The Macmillan Company, p. 176. Arch. Dcrmat. & Syph. 37: 590-596, 1938. Eiehenlaub, F. J.: Wynder, Ernest L.: The Place of Tobacco in the Etiology of Lung Cancer, Paper read before the 7th Annual R. I. Cancer Conference for Phvsieians. Oct. 13. 1954. Etiology, Pathology, and Treatment oi? Loulro’plakia .&ccalis, Arch. McCarthy, F. P.: Dermat. & Syph. 34: 612, 1936. Thoma, Kurt H.: Oral Pathology, ed. 4, St. Louis, 1954, The C. ‘V. Mosby Company, pp. 966-968. Kollar, John A:, Jr., Finley, C. W., Nabers, J. M., Ritchey, B., and Crban, R. J.: Leukoplakia, J. Am. Dent. A. 49: 538-548, 1954. Fascile on Oral Diseases, Washmgton, D. C., 1953, Armed Forces Institute Bernier, J. L.: of Pathology. Prinz, H., and Greenbaum, S. G.: Diseases of the Mouth and Their Treatment, ed. 2, Philadelphia, 1939, Lea & Febiger, p. 246. of Keratinization, ORAL SURG., ORAL MED., AND ORAL PATH. Rothman, Stephan : Physiology 7: 1085, 1954. 183 WATERMAN ST.