Oral squamous cell carcinoma arising in a patient with long-standing lichen planus

Oral squamous cell carcinoma arising in a patient with long-standing lichen planus

oral medicine Editor: H. DEAN MILLARD, DDS, MS 1205 Glen Leven Road Ann Arbor, Michigan Oral squamous cell carcinoma arising in a patient with long-...

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oral medicine Editor: H. DEAN MILLARD, DDS, MS

1205 Glen Leven Road Ann Arbor, Michigan

Oral squamous cell carcinoma arising in a patient with long-standing lichen planus A case report Ronald W. Katz, DiUD,a Jaime S. Brahim, DDS, iUS,b and William D. Travis, IUD,~ Bethesda, Md. NATIONAL

INSTITUTE

OF DENTAL

RESEARCH

AND NATIONAL

CANCER

INSTITUTE

The risk of malignant transformation of oral lichen planus remains a controversial point. Many previous reports have been discounted on the basis of inadequate information or lack of histologic confirmation of lichen planus. We report a well-documented case of long-standing cutaneous and oral lichen planus in which squamous cell carcinoma of the dorsal portion of the tongue occurred. There is an apparent difference in the sites of oral carcinomas in patients with lichen planus compared with the general population. This suggests that lichen planus increases the risk of oral cancer in affected sites. (ORAL SURC ORAL MED ORAL PATHOL 1990;70:282-5)

L

ichen planus is a well-recognized mucocutaneous diseaseof unknown cause with a characteristic histopathologic appearance. It is predominantly a disease of the later decades,and most surveys suggest that a greater proportion of cases occur in women.’ Most patients with cutaneous lesions exhibit remission within 2 years, although relapse is also common.2-5 Oral lesions seemto be more chronic, and erosive lesions tend to be long standing and symptomatic.5-7 The prevalence in the general population of this disease ranges from 0.02% to 1.2%.3,4,*-12There have been several attempts to determine what percentage of oral casessubsequently developed into squamous cell carcinoma; reported transformation frequencies range from 0.3% to lo%, with a 1% to 2% transformation rate a likely actual value.6$13,I4 There is a continuing controversy over whether oral lichen planus can be considered a precancerous

‘Winical Staff Fellow, National Institute of Dental Research. “Senior Staff Oral and Maxillofacial Surgeon, Clinical Investigations and Patient Care Branch, National Institute of Dental Research. %enior Surgical Pathologist, Laboratory of Pathology, National Cancer Institute. 7/13/14x9 282

condition.6, ’ 5,l 6It has beensuggestedthat the erosive or atrophic forms of oral lichen planus undergo malignant transformation more commonly than other variants of lichen planus. 13,I7 Many investigators favor the concept that the atrophic or erosive forms of oral lichen planus predispose the mucosa to damage from other carcinogenic agents.18-23 According to this view, the lesions themselves are not considered premalignant in the sensethat erythroplakias of the oral cavity are.17,24Other investigators believe that coincidence has led to an erroneous association of the two diseases.11,I4325 Krutchkoff and coworkers25critically reviewed the literature on the association of oral lichen planus and carcinoma. According to their strict criteria, only 15 casesfrom a total of 223 reported casesin the literature were accepted. They noted eight casesin which known carcinogenic factors were present in the medical histories and no case that could have such exposure ruled out. They argued that there was insufficient evidence to prove that lichen planus is premalignant as such, yet they accept the idea that persons with lichen planus may be more susceptible to transformation of their mucosa by other carcinogens. Subsequently, there have been somereports of malignant transformation of lichen planus in the absence of known carcinogenic exposure.*O,23*26Because of the

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283

Fig. 1. Photograph of erosive lesion of dorsal portion of tongue noted in July 1980.

2. Photomicrograph of skin biopsy specimen. Note the loss of basal cells, hyperkeratosis, separation of the epidermis from the dermis, and bandlike lymphocytic infiltrate in the upper dermis typical of lichen planus. (Original magnification, X 125.) Fig.

apparent rarity of well-documented casereports in the literature, we report a case of long-standing lichen planus with transformation to oral squamous cell carcinoma. CASEREPORT

In 1974 a 52-year-old obesewhite man was seen in the National Institute of Health Clinical Center dental clinic for evaluation of oral erosive lichen planus. Examination revealed large areasof reticular lichen planus of the buccal mucosaassociatedwith symptomatic ulcerated areason the buccal mucosa and dorsum of the tongue. Lesions on the floor of the mouth and on the ventrolateral portion of the tongue were asymptomatic. His diseasemanifested as crops of 1 to 2 mm pruritic papules on his genitals which spread to his legs, intertriginous areas of his torso, flexor surfaces of his wrists, hands, mouth, and ears. He had had a chronic course without total remission for more than 10 years. During his dental examination, moderately severe periodontitis was noted, but no rough teeth. During the treatment of his periodontal condition in 1974, a course of tetracycline was given and it was noted that his skin lesions cleared and his oral lesions improved somewhat. Becauseof the presenceof amalgam restorations, a copper patch test was performed with negative findings. He subsequently had cutaneous relapse of his diseasewithin 6 months. In 1979, he was accepted for an experimental treatment protocol testing a vitamin A derivative. His medical history included cutaneous and oral lichen planus since age 42 (Fig. l), treatment for malaria at age 20, hypothyroidism, a 50 pack per year history of smoking up to age 42, and social alcohol ingestion. He was taking 0.1 mg L-thyroxine daily. Biopsy specimens of lesions from the skin and buccal mucosa revealed histologic features consistent with lichen planus (Figs. 2 and 3). In the specimen from the buccal mucosa,ulceration was present adjacent to areastypical for lichen planus, but no dysplastic features were noted (Fig. 3). He started 20 weeks of therapy with an aromatic retinoid (RO-lo-9359), 0.5 mg/kg/day. A secondcourse was instituted and oral symptoms of burning and dysphagia led to a dental consultation in which candidiasis was diagnosed. The patient was successfully treated with antifungals but

Fig. 3. Photomicrograph of biopsy specimen from right buccal mucosa. The acanthosis, basilar degeneration, sawtooth rete pegs, and infiltrate of lymphocytes and plasma cells are characteristic of lichen planus. (Original magnification, X 160.)

his oral lichen planus lesions returned 2 weeks after completing the experimental treatment. By May 1984 he had completed 10 coursesof therapy (at varying doses) without lasting improvement. Side effects

284 Katz, Brahim, and Travis

Fig. 4. Photograph of squamouscell carcinoma noted in August 1984.

noted during the therapy included desquamation of the skin of his fingers, cheilitis, conjunctivitis, fatigue, paronychia, and loss of hair. In July 1984 he was switched to retinoids and etretinate and his skin lesions resolved but ulcerated lesions were noted on the left maxillary ridge, left buccal mucosa,dorsum of tongue, and left floor of mouth. He was then treated with a 2-week course of prednisone (80 mg/day) and azathioprine (Imuran) (20 mg/day), and the oral lesions cleared. Shortly thereafter, a new lesion was noted on the dorsum of the tongue measuring 1.8 X 2.7 cm and extending to the midline (Fig. 4). On reevaluation 2 weeks later, the ulcer had not improved and a biopsy was performed. Histologic analysis revealed a moderately differentiated squamous cell carcinoma, which on clinical evaluation was staged TzNaMc. He was treated in September with an iridium implant delivering 7000 rad to the primary site. Left submandibular swelling and pain subsequently developed. A bilateral radical neck dissection and biopsy of the site of the primary tumor was performed. No residual tumor was observedin the surgical specimens,and only one level IV node in the right side of the neck was positive for metastatic foci. Distant metastasis developed despite follow-up radiotherapy to the neck, and the patient died in December 1985. DISCUSSION

There are very few well-documented casesin which lichen planus underwent transformation to squamous cell carcinoma in the absence of known exposure to other carcinogenic agents.25In this case, two factors known to be associatedwith squamouscell carcinoma were present. The patient was a 50 pack per year smoker who had discontinued his smoking shortly before the onset of his lichen planus. He had been treated for malaria with arsenic compounds. The several-year history of treatment with systemic vitamin

A derivatives may also have had an effect. The case illustrates someof the known adverseside effects seen with the use of vitamin A analogs for the treatment

of lichen planus.27,28 It is difficult to determine to what extent these factors influenced the development

ORAL SURG ORAL MED ORAL PATHOL September 1990

of his cancer, but the medical evaluation provides clear clinical and histologic evidence for the longstanding presenceof cutaneous and oral lichen planus before the development of oral squamous cell carcinoma. A reevaluation of the histologic material agreed with the original diagnosis of lichen planus and the subsequent malignant transformation. The carcinoma in this patient occurred on the dorsal surface of the tongue. Squamous cell carcinomas in this location are unusual.26The distribution of oral carcinoma associated with lichen planus is distinctly different from carcinoma not associated with this disease.13* 20,29This suggeststhat oral lichen planus is a diseasein which there is an increased sensitivity to malignant transformation, and the site of this sensitivity correlates well with the distribution of lichen planus, not with the distribution of oral cancer seenin the general population. Kaplan and Barnes20suggest that there is an increased turnover of basal cells in lichen planus and that this predisposesto the development of a malignant clone in the presenceof initiators or promoters of malignancy. Others have proposed that the ulcerative form of lichen planus increasesthe risk of malignant transformation.19 Krutchkoff and Eisenberg30describe an entity they label lichenoid dysplasia and suggestthat the diagnosis of lichen planus may have been used erroneously in the literature for lesions that are in fact dysplastic (i.e., leukoplakias) and would understandably be prone to malignant transformation. The possibility of an erroneous diagnosis of lichen planus was demonstrated clearly by Reisman and associates.31The well-documented clinical history of long-standing skin and oral lesions typical of lichen planus with histologic findings consistent with that diagnosis would discount the possibility of an erroneous diagnosis in this case. It is a difficult clinical task to distinguish dysplastic areas from the ulcerative and hyperkeratotic areas of lichen planus. It is not reasonable to conduct a biopsy of all lesions of lichen planus on a regular basis, but the identification of dysplastic regions or early malignant changeswould increase the chances of a successful intervention in the development of an oral cancer. Some casesof lichen planus may contain areas of dysplasia, and other lesions may resemble lichen planus superficially. However, in most casesit should be possible to differentiate between lichen planus (with or without dysplastic changes) and lichenoid lesions when the clinical and histologic findings are examined critically. 32 Further studies are needed to prove an increased rate of malignant transformation in patients with lichen planus. However, we believe that erosive lichen planus is a condition that will increase the risk of oral cancer in sites not typically associated with the development of squamouscell carcinoma. Pe-

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riodic thorough oral examinations are recommended in patients with lichen planus to intervene at the earliest time in the event of malignant transformation. REFERENCES 1. Scully C, El-Kom M. Lichen planus: review and update on pathogenesis. J Oral Pathol 1985;14:431-58. 2. Samman PD. A note on the natural history of lichen planus. Br J Dermatol 1956;68:175-81. 3. Ramsey DL, Hurley HJ. Papulosquamouseruptions and exfoliative dermatitis. In: Moschella SL, Hurley HJ, eds. Dermatology. Philadelphia: WB Saunders, 1985:529. 4. Arndt KA. Lichen planus. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF, eds. Dermatology in general medicine; vol. 1, 2nd ed. New York: McGraw-Hill, 1979:655. 5. Altman J, Perry HO. The variations and course of lichen planus. Arch Dermatol 1961;84:47-59. 6. Silverman S, Gorsky M, Lozada-Nur F. A prospective followup study of 570 patients with oral lichen planus: persistence, remission, and malignant association. ORAL SURG ORAL MED ORAL PATHOL 1985;60:30-4.

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27. Ferguson MM, Simpson NB, Hammersley N. The treatment of erosive lichen planus with a retinoid-etretinate. ORAL SURG ORAL MED ORAL PATHOL 1984;58:283-7.

28. Woo TY. Systemic isotretinoin: treatment of oral and cutaneous lichen planus. Cutis 1985;35:385-93. 29. Mashberg A, Meyers H. Anatomical site and size of 222 early asymptomatic oral squamous cell carcinomas. Cancer 1976; 37:2149-57. 30. Krutchkoff DJ, Eisenberg E. Lichenoid dysplasia: a distinct histopathological entity. ORAL SURG ORAL MED ORAL PATHOL 1985;30:308-15.

31. Reisman RJ, Schwartz AE, Friedman EW, Gerry RG. The malignant potential of oral lichen planus-diagnostic pitfalls. ORAL SURG ORAL MED ORAL PATHOL 1974;38:227-32.

32. McClatchey KD, Silverman S, Hansen LS. Studies on oral Iithen planus. ORAL SURG ORAL MED ORAL PATHOL 1975;39:122-9. Reprint requests to:

Dr. R. Katz Bldg. 10, Room lN118 National Institutes of Health 9000 Rockville Pike Bethesda, MD 20892