Laser Management of Oral Leukoplakias: A Follow-up Study of 70 Patients

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1 The Laryngoscope Lippincott Williams & Wilkins, Inc., Philadelphia 1999 The American Laryngological, Rhinological and Otological Society, Inc. Laser Management of Oral Leukoplakias: A Follow-up Study of 7 Patients Michael L. Schoelch, D; Nahid Sekandari, DDS; Joseph A. Regezi, DDS, MS; Sol Silverman, Jr., MA, DDS Objectives/Hypothesis: To assess the efficacy of laser therapy for the management of premalignant oral lesions. Study Design: The study group consisted of seventy consecutive laser-treated patients with oral leukoplakia. The microscopic diagnosis included idiopathic focal keratosis, dysplasias of all grades, and verrucous hyperplasia (proliferative verrucous leukoplakia). Thirty-nine patients had some degree of microscopic dysplasia and six demonstrated highrisk proliferative verrucous leukoplakia. The clinical appearances of the lesions were white (homogeneous leukoplakia) in 48, red and white (erythroleukoplakia) in 8, and verrucous in 14. There were 8 men and women in this group. The average age was years (range, 1-9 y). Methods: Lasers employed were the C and Nd:YAG lasers, and standard laser safety protocols were used. Results: There was no postoperative infection, hemorrhage, or paresthesia. Two patients developed pyogenic granulomas in their surgical sites. Fifty-five of 7 patients were followed for more than months; follow-up averaged months (range -178 mo). Twenty-nine patients had complete control of their lesions; 19 patients had small recurrences removed with subsequent laser surgeries, leading to control; patients had complete recurrences; and patients developed squamous cell carcinoma at the lesion site. Verrucous lesions had an especially high rate of recurrence (8%), with 9 of 1 ultimately controlled with subsequent surgeries. Conclusions: Laser surgery of oral leukoplakia is an effective tool in a complete management strategy that includes careful clinical follow-up, patient education to eliminate risk factors and report suspicious lesions, and biopsy of suspicious lesions when appropriate. However, recurrence and progression to cancer remain a risk. Key Words: oral cancer, laser, C, Nd:YAG, leukoplakia. Laryngoscope, 19:949-9, 1999 From the University of California, Department of Stomatology, School of Dentistry, San Francisco, California. Editor's Note: This Manuscript was accepted for publication February 1, Send Reprint Requests to Michael L. Schoelch, D, 1 Lakeshore Drive, Pleasant Prairie, WI 18, U.S.A. msonnet@ acronet.net Laryngoscope 1 9: June 1999 INTRODUCTION Oral idiopathic leukoplakia is well established as being at risk of transforming to carcinoma. 1 - Other related oral lesions, erythroleukoplakia (red and white lesion) and proliferative verrucous leukoplakia (exophytic and expanding lesion), carry an even greater risk for malignant transformation. 1 - Therefore, proper diagnosis and effective removal might aid in the prevention of some oral cancers. Since its introduction in the early 197s in endoscopic surgery of the larynx, 7 the C laser has become useful in a variety of soft tissue surgical procedures, including the excision of malignant and leukoplakic lesions of the oral cavity. 8-1 The Nd:YAG laser has also been applied with success to the treatment of other oral mucosal lesions In a previous study the safety and efficacy of the C and Nd:YAG lasers were demonstrated in a variety of oral mucosal pathologies. 1 Laser surgery is associated with little morbidity, low intraoperative and postoperative complication rates, and disease control comparable to or better than conventional methods of management. The purpose of this current study was to further evaluate the use and outcome oflaser energy as a surgical modality in the management of oral premalignant lesions. MATERIALS AND METHODS The study group comprised 7 patients treated in a university-based outpatient oral medicine clinic. Inclusion criteria were the following: 1) Clinical presentation of idiopathic lesions with white (homogeneous leukoplakia), red and white (erythroleukoplakia), or proliferative verrucous leukoplakia; ) a biopsy prior to laser removal; and ) no prior history of oral carcinoma. Microscopic degrees of dysplasia were calibrated on the basis of the World Health Organization guidelines.17 Prior to both biopsy and laser removal, vital staining with 1% aqueous toluidine blue and decolorization with 1% acetic acid were used to aid in biopsy sampling and detection of surgical margins. 1 s All surgeries were performed under local anesthesia on an outpatient basis by trained laser dentists following the educational standards established by the Curriculum Guidelines and Standards for Dental Laser Education. 1 9 Surgical intent was to remove the lesions with margins of clinically healthy-appearing mucosa. Two laser emission wavelengths were utilized: 1, nm (C ) and 1,4 nm (Nd:YAG). The C laser device utilized was an articulated arm-delivered surgical C laser equipped with an intra-oral handpiece (Xanar, 949

2 Coherent Medical Group, Palo Alto, CA), a power range of 1 to W, continuous wave, and a beam diameter.8 to 1. mm. Two pulsed fiber-optic-delivered Nd:YAG lasers were utilized: 1) the dlase (manufactured for American Dental Laser of Troy, MI by Sunrise Technologies, Inc., Fremont, CA), with a power range of. to W and a repetition rate of 1 to Hz, and ) the Sunlase Master (Sunrise Technologies), with a power range of. to 1 W and a repetition rate of 1 to 1 Hz. The C laser was used for more extensive lesions owing to its larger spot size and continuous mode. The Nd:YAG laser was used in lesions adjacent to hard tissue, owing to its smaller spot size and fiberoptic contact delivery, which offer more precise control of laser energy adjacent to noninvolved tooth structures. The C laser was used in a noncontact mode with a range of power from to 1 W. The Nd:YAG was used in both a contact mode (for excision) and a noncontact mode (for coagulation), with a range of to 8 W at to Hz. Laser power settings were selected by the dentist operator according to the extent of the lesion and the treatment objective (coagulation, excision, or vaporization). The excision sites were left to granulate and undergo healing by secondary intention. Large(> em) lesions were treated in planned serial visits to reduce postsurgical dysfunction and pain. For each surgical procedure, the clinical extent of the lesion treated was documented by either photograph and/or drawings in the patient record. Clinical examination and postoperative photography were utilized to monitor changes during the follow-up period. Appropriate postoperative instructions, including use of analgesics, management of postoperative complications such as edema and hemorrhage, oral hygiene, and diet were provided to each patient. In selected cases of medically compromised patients or treatment of extensive lesions, postoperative antibiotics were prescribed. Nonnarcotic or narcotic analgesics were prescribed as needed for postoperative pain. Patients were followed at 1 week after surgery, and at monthly intervals thereafter. At all times during treatment and follow-up, patients were instructed to report any change in signs and symptoms, and if necessary, additional follow-up examinations were scheduled. RESULTS Some lesions involved multiple sites; the locations were as follows: tongue, 9; gingiva, 1; buccal mucosa, 1; floor of mouth, 1; lower lip, 8; palate, ; lower labial mucosa, 1. The clinical and microscopic findings for the 7 patients at the time of initial presentation for laser management showed that 9 had some degree of microscopic dysplasia, and had proliferative verrucous leukoplakia (Table 1). Lesions with a red component showed dysplasia more frequently than leukoplakias (88% vs. %, respectively). Twenty-eight patients complained of pretreatment pain described most often as soreness or burning. In some cases, the differential diagnosis included vesiculoerosive inflammatory disease and/or candidiasis, and empiric therapy with topical steroids and/or antifungals failed to resolve the lesion. Forty-five of 7 patients had a histologic diagnosis of dysplasia (mild, moderate), severe (carcinoma in situ), or atypical verrucous proliferation. Table II outlines the treatment parameters for all three types of lesions. In several cases, the C laser was utilized after the Nd:YAG failed to control a proliferative verrucous leukoplakia, since more laser energy was required to control the spread of the lesion. As expected, proliferative verrucous leukoplakias required the largest number of treatments to effectively control the lesion, owing to this lesion's tendency to spread as well as recur at a rapid rate. Although 1 patients complained of pain of longer than 1 week in duration, in no case was pain of more than a moderate level at weeks after surgery, and no patient required analgesics of any kind after weeks. Eleven of 1 patients complained of moderate pain involving lesions on the lateral tongue. No cases of postoperative infection or paresthesias were reported, and no cases of severe hemorrhage intraoperatively. Two pyogenic granulomas developed after surgery in two patients, and both healed uneventfully. Fifty-five patients were available for follow-up analysis (Table III). Follow-up was limited in 1 patients because of the following: 7 could not be located; were contacted but unable to return, although they reported no recurrent disease; and required additional treatment. Disease was controlled in 9 (%) with one to five planned surgeries, with no recurrence, and showed some clinical control in 19 (%), with small areas of recurrence (usually less than mm in diameter) that were controlled with subsequent surgery, or clinically monitored with no progression of disease. Complete recurrence was seen in of patients (4%), and no further laser surgery was attempted. In examining the patients with recurrences after laser excision, no associations could be found with either the TABLE I. Clinical Characteristics of 7 Patients at Time of Presentation for Laser Management of Premalignant Oral Epithelial Lesions. Age (y) Sex Duration of Lesion (mo) Tobacco Clinical Appearance No. Range Mean M F Uset Range Mean Pain:j: Lesion Size (em) Histopathology 1- > FK AVP Leukoplakia Erythroleukoplakia Proliferative verrucous leukoplakia Characteristics tabulated according to clinical appearance. ttobacco use: history of the equivalent of > 1 pack of cigarettes per day for a minimum of 1 year. :j:patient complained of painful symptoms associated with the lesion at the time of initial presentation. FK = focal keratosis; = mild to moderate dysplasia; - severe dysplasia to carcinoma in situ; AVP = atypical verrucous proliferation. Laryngoscope 1 9: June

3 TABLE II. Treatment Parameters of 7 Patients With Premalignant Oral Epithelial Lesions. Postoperative Laser Therapy Treatments (n) Post-Laser Medications Paint Clinical Appearance No. ND:YAG co, Both:j: Serial Range Mean Antibiotic Analgesic Leukoplakia H Erythroleukoplakia Proliferative verrucous leukoplakia HO Antibiotic was used prophylactically; analgesic varied from nonsteroidal to acetaminophen-codeine; some patients used analgesics prophylactically. tpain: - minimal or no pain during first postoperative week; 1 = minimal to moderate pain of less than 1 week's duration; ~ moderate to severe pain of greater than 1 week's duration. :j:based on availability of unit or Nd:YAG failure to control lesion. Planned serial laser surgeries. location of the lesion or type oflaser utilized. Recurrences typically occurred adjacent to the surgical site, and appeared to develop from clinically normal-appearing mucosa in a range of 1 to more than 1 months after surgery. As might be expected, lesions with a histologic diagnosis of some degree of dysplasia had a greater risk for recurrence than those with no dysplasia; but the proliferative verrucous leukoplakias had the highest frequency of recurrence (Table Ill). Although initial treatment success was poorest in patients with proliferative verrucous leukoplakia, eventually control of disease progression was obtained in 9 of 1 patients, following periodic subsequent minor laser surgeries to eradicate small recurrences, typically adjacent to the previous surgical site. There was progression to squamous cell carcinoma in cases (9%) at the lesion site (Table III). In the proliferative verrucous leukoplakia group, of 1 patients (17%) developed a carcinoma, and in the combined leukoplakias TABLE Ill. Clinical Outcome Results for Patients Followed for More Than Months After Laser Management of Oral Premalignant Epithelial Lesions.* Length of Postoperative Follow-up (mo) Lesion Control With Clinical Outcome Failure Due to Clinical Appearance/Histology Leukoplakia FK Erythroleukoplakia FK One No. Range Mean Surgery Proliferative verrucous leukoplakia FK AVP Planned Serial Surgeries Small Recurrences Removed With Subsequent Surgeries Complete Recurrence Disease Progression (Malignant Conversion) Total Results tabulated according to clinical appearance and histologic diagnosis. FK - focal keratosis; = mild to moderate dysplasia; = severe dysplasia to carcinoma in situ; AVP = atypical verrucous proliferation. Laryngoscope 19: June

4 TABLE IV. Clinical Features of Five Patients With Malignant Transformation to Squamous Cell Carcinoma. Patient No. Age (y) Sex Smoker Clinical Appearance 71 F N Verrucous leukoplakia 7 F y Erythroleukoplakia 7 M y Leukoplakia 4 M y Leukoplakia 1 M y Leukoplakia lime After Laser Location Histology Surgery (mo)t Gingiva, mandibular Severe dysplasia 1 Up, lower Aty~ical verrucous 78 pro iteration Tongue, lateral Severe dysplasia 4 Lip, lower Moderate 19 dysplasia Tongue, ventral Moderate 17 dysplasia *Site of premalignant lesion and carcinoma the same. tcarcinomas controlled with surgery and/or radiation. and erythroleukoplakias group, of 4 (7%) transformed into carcinoma (Table IV). In all five patients carcinoma developed in the site of previous laser surgery in an average of months (range, 4-78 mo) after the time of surgery. DISCUSSION Laser excision of precancerous oral epithelial lesions offers comparative advantages over traditional scalpel excision. These advantages include rapid removal of diseased tissue, control of bleeding, precise removal of lesional tissue, good patient acceptance, low morbidity and complications, and favorable healing. Because of the low morbidity and reasonably effective control, laser removal by vaporization or excision appears useful in oral cancer control. This potential approach to prevention is important, because the mortality from oral cancer is high: about half of those affected with oral cancer will die of their disease. The key element in the success of laser management is its precise ability to remove mutagenic clones from the oral mucosa as they develop. Although it remains unresolved whether control ofleukoplakia by surgical removal prevents the development of cancer in that site, this hypothesis certainly appears logical. Once epithelial cells have shown mutations in tumor suppressor genes or proto-oncogenes, they have an established risk of malignant progression over time. In relatively short-term follow-up, our findings so far indicate a possibility of prevention. Until effective therapies are developed that can either 1) prevent these mutations, ) reverse these mutations or ) arrest further malignant progression, the most definitive method of prevention is the recognition and excision of these mutagenic clones as they are detected. Certainly, attempts at removing dysplastic leukoplakias are important, because the risk for malignant transformation is relatively high. However, even leukoplakias that histologically show microscopic hyperkeratosis are at risk for malignant transformation. But the highest risk appears to be with proliferative verrucous leukoplakia, and these lesions should be removed surgically. In extensive or multifocal lesions, serial removal is reasonable, acceptable, and effective. It should be emphasized, however, as with any destructive modality done without pathologic examination of margins, that there is always the possibility of incomplete removal. Close clinical follow-up is necessary to detect early recurrence. Early detection of premalignant oral lesions is aided by careful clinical examination and thorough follow-up of high-risk patients. This process includes follow-up biopsy when changes in signs or symptoms occur. Exfoliative cytology and vital staining with toluidine blue are useful clinical adjuncts to supplement clinical judgment. Patients should be educated to eliminate the most important risk factors for oral cancer (tobacco and alcohol), and to report in a timely manner any changes in signs or symptoms of premalignant lesions. BIBLIOGRAPHY 1. Silverman S Jr. Diagnosis and management of leukoplakia and premalignant lesions. Oral Maxillofac Surg Clin North Am 1998;1(1):1-.. Silverman S Jr, Gorsky M, Lozada F. 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5 Surg 1989;7: Loh HS. A clinical investigation of the management of oral lichen planus with C laser surgery. J Clin Laser Med Surg 199;1(): White JM, Goodis HE, Rose CL. Use of the pulsed Nd:YAG laser for intra-oral soft tissue surgery. Lasers Surg Med 1991;: Myers TD, Murphy DG, White JM, Gold SI. Conservative soft tissue management with the low powered pulsed Nd:YAG dental laser. Pract Periodontics Aesthet Dent 199;4: White JM, Chaudhry SI, Kudler JJ, Sekandari N, Schoelch ML, Silverman S Jr. Nd:YAG and C laser therapy of oral mucosal lesions. J Laser Clin Med Surg (in press). 17. Wahl PN, Cohen B, Luthra, UK, Torloni H. International Histological Classification of Tumours No. 4: Histologic Typing of Oral and Oropharyngeal Tumours. Geneva: World Health Organization; Silverman S Jr, Migliorati C, Barbosa J. Toluidine blue staining in the detection of oral precancerous and malignant lesions. Oral Surg 1984;7: White JM, ed. Curriculum Guidelines and Standards for Dental Laser Education. Proceedings of Lasers in Orthopedic, Dental, and Veterinary Medicine II. SPIE 199;188: thors are encouraged to submit color photographs to be considered as the over illustration. The photo should relate to the subject of the manuscript subitted for publication but need not be used in the manuscript. If the photo appears as an illustration in the manuscript, please indicate which photo is suggested for the cover. If the photo is not part of the manuscript, please submit it with the manuscript and indicate that an additional photo has been included for possible use as a cover photo. The cover photo must be accompanied by a separate legend written for the interest of the general reader. The cover legend appears on the last page of the Table of Contents. Authors are encouraged to refer to previous issues of The Laryngoscope for examples of cover legends. Laryngoscope 19: June