Multiple and Confluent Lesions of Oral Leukoplakia Proliferative Verrucous
Leukoplakia
J. Michael Hall, DDS; Mark A. Cohen, BDS, MDent, FFD; Adele A. Moreland, MD Medical College of Georgia, Augusta, and the University of Saskatchewan, Saskatoon REPORT OF A CASE
An 80-year-old man with a complaint of ill-fitting dentures was referred for evaluation of extensive oral leukoplakia (Fig 1). He related a 30-year history of this condition, which first appeared as a flat, filmy
Figure
1.
Figure 2.
Figure 3.
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patch on the anterior edentulous mandibular ridge. The white areas slowly spread across the mandibular arch, from the ventral aspect of the tongue onto the buccal and labial mucosa and posteriorly to the tonsilar pillars. The lesions gradually became exophytic and verrucous (Fig 2). Evidence of ulceration or erythema associated with this asymptomatic condition was not present. The patient had sought the advice of numerous physicians and dentists over the years but was never given a diagnosis or received effective treatment. The patient never used tobacco and was in good health otherwise. Representative biopsy specimens are shown in Figs 3 and 4. What is your diagnosis?
Figure
4.
Multiple and Confluent Lesions of Oral Leukoplakia Proliferative Verrucous DIAGNOSIS: Proliferative
verrucous
leukoplakia (PVL).
HISTOLOGIC FINDINGS
Hematoxylin-eosin-stained sections from two sites showed the spectrum of this disease process. Flat areas exhibited only hyperkeratosis (Fig 3), while the exophytic lesions were characterized by broad blunt rete and hyperparakeratosis (Fig 4). This specific type of epithelial hyperplasia borders on verrucous carcinoma and has been termed verrucous hy¬ perplasia. The typical heavy lymphocytic infiltrate can be seen hugging the basement membrane zone.
DISCUSSION Proliferative verrucous leukoplakia was described by Hansen and coworkers' in 1985 as a specific form of leuko¬ plakia that is slowly progressive, has an almost 100% rate of malignant transformation, and carries a high risk of re¬ currence after removal. The condition typically begins as a simple hyperkeratosis that enlarges and becomes multifocal, often over extended periods of 20 years or more, with di¬ agnosis impossible until characteristics such as multifocality and persistence become evident. While some research has shown a link between tobacco use and the development of verrucous carcinoma" this relationship has not been dem¬ onstrated with PVL.' The disease runs a relentless irrevers¬ ible course with flat lesions becoming warty exophytic masses that may harbor areas of verrucous or squamous cell carcinoma. Proliferative verrucous leukoplakia is consid-
ered
a
disease of unknown
cause
Leukoplakia
that represents
a
contin¬
ranging from hyperkeratosis to carcinoma. The spectrum of microscopic features reflects the complex clinical changes. The closely related lesions of verrucous hy¬ perplasia, as described by Shear and Pindborg," verrucous carcinoma, and well-differentiated squamous cell carcinoma may all exist concurrently within PVL. Some authors2 regard verrucous hyperplasia as an early form of verrucous carcinoma, but the former does not exhibit the histologie presence of epithelial rete pushing into the underlying con¬ nective tissue, a characteristic feature of verrucous carci¬ noma. Hansen and associates' reserve the diagnosis of ver¬ rucous carcinoma for solitary lesions, because verrucous carcinoma has fairly definitive margins and is usually responsive to treatment, whereas PVL is not. Leukoplakia that shows severe dysplasia at its first appearance likewise uum
does not fit the criteria for PVL. The characteristic bandlike lymphocytic infiltrate at the basement membrane zone in verrucous hyperplasia has lead to the mistaken diagnosis of lichen planus. Treatment of PVL remains unsatisfactory with high recurrence rates, often within months. Only three of 30 pa¬ tients described in the original study1 remained free of dis¬ ease after treatment. Early aggressive therapy with close follow-up is the ideal; however, the disease is usually wide¬ spread, making total excision impossible. Multifocal disease demands frequent biopsy with surgical removal of carcinomatous areas. Treatment with retinoic acid derivatives ap-
Downloaded From: http://archderm.jamanetwork.com/ by a University of Auckland User on 05/14/2015
pears promising and has been reported effective in the
man¬
agement of some oral leukoplakias"; however, other forms of treatment, including radical surgery and radiation, have
been ineffective. The prognosis of PVL is poor, especially in widespread disease, because of the inability to treat all of the involved mucosa. The indolent growth and lack of symptoms may lull both patient and clinician into a false sense of security. Early bland histologie findings may likewise contribute to misdi-
agnosis. Conversely, a biopsy specimen showing dysplasia or
carcinoma within a diffuse leukoplakia requires only local excision rather than radical removal of the entire lesion of
leukoplakia. References 1. Hansen
leukoplakia:
LS, Olson JA, Silverman S Jr. Proliferative verrucous a long-term study of 30 patients. Oral Surg. 1985;
60:285-298. 2. Luna MA, Tortoledo ME. Verrucous carcinoma. In: Gnepp DR, ed. Pathology of the Head and Neck. New York, NY: Churchill Livingstone Inc; 1988:497-515. 3. Shafer WG. Verrucous carcinoma. Int Dent J. 1972;232:451-459. 4. Shear M, Pindborg JJ. Verrucous hyperplasia of the oral mucosa.
Cancer. 1980;46:1855-1862.
5. Silverman S Jr, ed. Oral Cancer. New York, NY: American Cancer Society; 1985:25-26. 6. Hong WK, Endicott J, Itri LM, et al. 13-cis-Retinoic acid in the treatment of oral leukoplakia. N Engl J Med. 1986;315:1501-1505. 7. Shah JP, Strong EW, Decosse JJ, Itri L, Sellers P. Effect of retinoids on oral leukoplakia. Am J Surg. 1983;146:466-470.
Leukoplakia
J. Michael Hall, DDS; Mark A. Cohen, BDS, MDent, FFD; Adele A. Moreland, MD Medical College of Georgia, Augusta, and the University of Saskatchewan, Saskatoon REPORT OF A CASE
An 80-year-old man with a complaint of ill-fitting dentures was referred for evaluation of extensive oral leukoplakia (Fig 1). He related a 30-year history of this condition, which first appeared as a flat, filmy
Figure
1.
Figure 2.
Figure 3.
Downloaded From: http://archderm.jamanetwork.com/ by a University of Auckland User on 05/14/2015
patch on the anterior edentulous mandibular ridge. The white areas slowly spread across the mandibular arch, from the ventral aspect of the tongue onto the buccal and labial mucosa and posteriorly to the tonsilar pillars. The lesions gradually became exophytic and verrucous (Fig 2). Evidence of ulceration or erythema associated with this asymptomatic condition was not present. The patient had sought the advice of numerous physicians and dentists over the years but was never given a diagnosis or received effective treatment. The patient never used tobacco and was in good health otherwise. Representative biopsy specimens are shown in Figs 3 and 4. What is your diagnosis?
Figure
4.
Multiple and Confluent Lesions of Oral Leukoplakia Proliferative Verrucous DIAGNOSIS: Proliferative
verrucous
leukoplakia (PVL).
HISTOLOGIC FINDINGS
Hematoxylin-eosin-stained sections from two sites showed the spectrum of this disease process. Flat areas exhibited only hyperkeratosis (Fig 3), while the exophytic lesions were characterized by broad blunt rete and hyperparakeratosis (Fig 4). This specific type of epithelial hyperplasia borders on verrucous carcinoma and has been termed verrucous hy¬ perplasia. The typical heavy lymphocytic infiltrate can be seen hugging the basement membrane zone.
DISCUSSION Proliferative verrucous leukoplakia was described by Hansen and coworkers' in 1985 as a specific form of leuko¬ plakia that is slowly progressive, has an almost 100% rate of malignant transformation, and carries a high risk of re¬ currence after removal. The condition typically begins as a simple hyperkeratosis that enlarges and becomes multifocal, often over extended periods of 20 years or more, with di¬ agnosis impossible until characteristics such as multifocality and persistence become evident. While some research has shown a link between tobacco use and the development of verrucous carcinoma" this relationship has not been dem¬ onstrated with PVL.' The disease runs a relentless irrevers¬ ible course with flat lesions becoming warty exophytic masses that may harbor areas of verrucous or squamous cell carcinoma. Proliferative verrucous leukoplakia is consid-
ered
a
disease of unknown
cause
Leukoplakia
that represents
a
contin¬
ranging from hyperkeratosis to carcinoma. The spectrum of microscopic features reflects the complex clinical changes. The closely related lesions of verrucous hy¬ perplasia, as described by Shear and Pindborg," verrucous carcinoma, and well-differentiated squamous cell carcinoma may all exist concurrently within PVL. Some authors2 regard verrucous hyperplasia as an early form of verrucous carcinoma, but the former does not exhibit the histologie presence of epithelial rete pushing into the underlying con¬ nective tissue, a characteristic feature of verrucous carci¬ noma. Hansen and associates' reserve the diagnosis of ver¬ rucous carcinoma for solitary lesions, because verrucous carcinoma has fairly definitive margins and is usually responsive to treatment, whereas PVL is not. Leukoplakia that shows severe dysplasia at its first appearance likewise uum
does not fit the criteria for PVL. The characteristic bandlike lymphocytic infiltrate at the basement membrane zone in verrucous hyperplasia has lead to the mistaken diagnosis of lichen planus. Treatment of PVL remains unsatisfactory with high recurrence rates, often within months. Only three of 30 pa¬ tients described in the original study1 remained free of dis¬ ease after treatment. Early aggressive therapy with close follow-up is the ideal; however, the disease is usually wide¬ spread, making total excision impossible. Multifocal disease demands frequent biopsy with surgical removal of carcinomatous areas. Treatment with retinoic acid derivatives ap-
Downloaded From: http://archderm.jamanetwork.com/ by a University of Auckland User on 05/14/2015
pears promising and has been reported effective in the
man¬
agement of some oral leukoplakias"; however, other forms of treatment, including radical surgery and radiation, have
been ineffective. The prognosis of PVL is poor, especially in widespread disease, because of the inability to treat all of the involved mucosa. The indolent growth and lack of symptoms may lull both patient and clinician into a false sense of security. Early bland histologie findings may likewise contribute to misdi-
agnosis. Conversely, a biopsy specimen showing dysplasia or
carcinoma within a diffuse leukoplakia requires only local excision rather than radical removal of the entire lesion of
leukoplakia. References 1. Hansen
leukoplakia:
LS, Olson JA, Silverman S Jr. Proliferative verrucous a long-term study of 30 patients. Oral Surg. 1985;
60:285-298. 2. Luna MA, Tortoledo ME. Verrucous carcinoma. In: Gnepp DR, ed. Pathology of the Head and Neck. New York, NY: Churchill Livingstone Inc; 1988:497-515. 3. Shafer WG. Verrucous carcinoma. Int Dent J. 1972;232:451-459. 4. Shear M, Pindborg JJ. Verrucous hyperplasia of the oral mucosa.
Cancer. 1980;46:1855-1862.
5. Silverman S Jr, ed. Oral Cancer. New York, NY: American Cancer Society; 1985:25-26. 6. Hong WK, Endicott J, Itri LM, et al. 13-cis-Retinoic acid in the treatment of oral leukoplakia. N Engl J Med. 1986;315:1501-1505. 7. Shah JP, Strong EW, Decosse JJ, Itri L, Sellers P. Effect of retinoids on oral leukoplakia. Am J Surg. 1983;146:466-470.
