eMedicine Specialties > Dermatology > Diseases of the Oral Mucosa

Oral Florid Papillomatosis

Author: Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Coauthor(s): Channing R Barnett, MD, Staff Physician, Department of Dermatology, University of Medicine and Dentistry of New Jersey
Contributor Information and Disclosures

Updated: Jun 12, 2009

Introduction

Background

Oral florid papillomatosis is a type of verrucous carcinoma (VC) that is clinically evident as multiple squamous papillary nodules in the oral cavity and, less commonly, in the larynx, the pharynx, the esophagus, the middle ear, the maxillary antrum, the nasal fossa, and the bronchus. Verrucous carcinoma usually appears in 3 main sites: the oropharynx, the genital tract, and the soles of the feet. However, verrucous carcinoma can also occur on the cutaneous surface. Accordingly, verrucous carcinoma is known by a number of names.

Oral florid papillomatosis is best defined as a type of verrucous carcinoma, although some consider it a separate entity. Still others consider it a disease on a continuum between viral warts and verrucous carcinoma, rather than a verrucous carcinoma per se.1 Lauren V. Ackerman2 described oral verrucous carcinoma and coined the term verrucous carcinoma. Oral, laryngeal, pharyngeal, and esophageal lesions of this type are generally known as a verrucous carcinoma or an Ackerman tumor.
 
Although the term verrucous carcinoma followed by its anatomical site would be the most comprehensive name, the historical name justifiably favors honoring 2 eminent physicians, Abraham Buschke (1868-1943) of Berlin and Ackerman (1905-1993). Buschke was a legendary professor of dermatology, and Ackerman, the renowned professor of pathology, developed the concept of verrucous carcinoma. However, the descriptive name oral florid papillomatosis is also used.

In recent years, the term multifocal papillomavirus epithelial hyperplasia has been used to define the variant that usually occurs in childhood; this variant is characterized by diffuse confluent papillomatous lesions in the oral mucosa.3

See also Verrucous Carcinoma, Proliferative Verrucous Leukoplakia, Cancers of the Oral Mucosa and Smokeless Tobacco Lesions.

Pathophysiology

In 1934, Kren et al4 observed condylomatous neoplasms of the tongue, the palate, and the uvula. In 1941, Friedell and Rosenthal5 described verrucous tumors of the buccal mucosa and the lower gingivae in 8 patients who chewed tobacco; these lesions developed in the area in which the quid of tobacco was held. Verrucous carcinoma can affect various oroaerodigestive sites, including the esophagus,6 the middle ear,7 the maxillary antrum,8,9 the nasal fossa,10 the lacrimal duct,11 and the bronchus.12

Verrucous carcinoma of both the skin and the mucosa is an uncommon low-grade squamous cell carcinoma that is clinically evident as a slowly but relentlessly enlarging warty tumor, histologically characterized by local invasion with minimal dysplasia, if any, and biologically characterized by a low incidence of metastases.1 Even when the tumor is large, when it has been present for many years, and when it penetrates the bone, distant metastases are rare.

The typical microscopic section shows a well-differentiated typical squamous cell carcinoma with verrucous clinical morphology.1 Ackerman initiated the clinicopathologic concept of verrucous carcinoma and described similar neoplasms of the oral cavity in 31 patients; Ackerman used the term verrucous carcinoma to denote the concept of a locally aggressive exophytic low-grade squamous cell carcinoma with little metastatic potential.13 This tumor has also been known as florid papillomatosis, a term Rock and Fisher14 coined in 1960. They observed multiple confluent nodules of the oral cavity and the larynx in 3 patients. In 1962, Wechsler and Fisher15 emphasized the locally aggressive but clinically benign nature of the disease by using the term oral florid papillomatosis.

The 4 clinicopathologic types of verrucous carcinoma are as follows: (1) the anourogenital type, which includes giant condyloma acuminatum, Buschke-Löwenstein tumor, giant malignant condyloma, verrucous carcinoma of the anogenital mucosa, carcinomalike condyloma, and condylomatoid precarcinosis; (2) the oroaerodigestive type, which includes the Ackerman tumor, verrucous carcinoma of Ackerman, and oral florid papillomatosis; (3) the foot type, epithelioma cuniculatum; and (4) other cutaneous types, which include cutaneous verrucous carcinoma, papillomatosis cutis carcinoides, and papillomatosis cutis.

Oral verrucous carcinoma should be recognized as an important clinicopathologic variant of squamous cell carcinoma. Its apparent clinical benignity may result in lengthy periods of misdiagnosis, during which it is not likely to spread to distant lymph nodes. Instead, oral verrucous carcinoma is more likely to destroy the nose or the mandible as it slowly but relentlessly extends into the underlying tissue, following what appears to be the path of least resistance that often causes it to develop around regional lymph nodes and not directly involve them. To those unfamiliar with oral verrucous carcinoma, its morphologic warty or verrucous appearance and its relatively bland histologic features often suggest verruca vulgaris or pseudoepitheliomatous hyperplasia rather than squamous cell carcinoma. When the lesion extends into underlying tissues, it may occasionally be mistaken for a benign adnexal tumor or rarely an epidermoid cyst at histologic examination.

Therapy for oral verrucous carcinoma is challenging because recurrences are common, and potential anaplastic transformation after radiation therapy may be a concern.

Cyclin D1 expression in oral squamous cell carcinoma and verrucous carcinoma was found to correlate with lack of histological differentiation.16

Frequency

United States

Oral verrucous carcinoma is a rare neoplasm that occurs in older people. It is diagnosed in only 1-3 of every 1 million persons each year.17 The age-adjusted average annual incidence for oral verrucous carcinoma among residents of Rochester, Minnesota, was 0.1 case per 100,000 person-years (0.2 for males, 0.0 for females), whereas the incidence for all intraoral carcinomas was 3.6 cases per 100,000 person-years (5.4 for males, 2.1 for females).

The Ackerman tumor represents 2-12% of all oral carcinomas.18,19,20,21 In men older than 64 years, the incidence increases to 3.2 cases per 100,000 person-years; the lesion represented only 3% of the oral cancers.17

Verrucous carcinoma of the larynx accounts for about 1-3.8% of all primary laryngeal squamous cell carcinomas.22,23

International

Oral verrucous carcinoma is a rare neoplasm (see Frequency, United States, above). Verrucous carcinoma represents about 400 (5%) of 7988 primary malignancies of the oral cavity in India,18 with most occurring in persons aged 40-50 years or older.21

Mortality/Morbidity

These tumors often cause considerably more morbidity than mortality.

The National Cancer Data Base includes 2350 cases of verrucous carcinoma of the head and the neck.24

  • Most verrucous carcinomas originate in the oral cavity (55.9%) and the larynx (35.2%), and the 5-year relative survival rate is 77.9%.
  • For localized verrucous carcinoma, the survival rate after surgery is 88.9% compared with 57.6% after irradiation.
  • Patients receiving initial surgical treatment have a better survival rate than those treated with irradiation, especially if their lesions originated in the oral cavity.

Sex

A male predisposition is usually observed, although in one study, almost 60% of cases occurred in women.25  

  • In his original series, Ackerman documented 31 cases, 26 of which involved men.
  • Although most patients (60.0%) are men, tumors of the oral cavity are more common among older females, according to the National Cancer Data Base, which includes data on 2350 cases of verrucous carcinoma of the head and the neck.24
  • Verrucous carcinoma of the larynx is more common in men than in women.22,23

Age

  • In Ackerman's original series, the average patient age was 67 years.
  • In another survey, most patients were aged 40-50 years or older.21
  • Most patients with verrucous carcinoma of the larynx are older than 60 years.22,23

Clinical

History

  • The patient may note a bulky tumor.
  • Some patients experience localized pain and difficulty in mastication.
  • Malignant conversion of florid oral and labial papillomatosis during topical immunotherapy with imiquimod was described in one patient.26

Physical

The Ackerman tumor is evident as a confluence of whitish nonulcerated papillomas on the oral mucosa, often on a background of chronic irritation or leukoplakia.

  • The surface may be pebbly or mamillated.2
  • Leukoplakia may be the earliest sign.21
  • The tumor may begin on the vermillion border of the lip or extend onto it.
  • Of the 31 patients that Ackerman described, 18 had verrucous carcinoma on the buccal mucosa; 8, on the lower gingiva; 2, on the hard palate; and 1 each, on the upper gingiva, the tongue, and the tonsil.
  • The most common sites are the inner aspects of the cheek along the bite line and the gingiva.
  • Verrucous carcinoma slowly extends into locally contiguous sites. It may expand into the mandible or to the cheek from the inner buccal surface.
  • Concurrent infection is common, and the resultant enlarged and tender lymph nodes may be mistaken for malignant involvement of the regional lymph nodes.
    • Concurrent infection can create the impression that the tumor is indurated rather than soft.
    • Despite advancement near the lymph nodes, verrucous carcinoma invariably grows around them rather than metastasizing to them.

Causes

The leading possible causes are infection with human papillomavirus (HPV) and tobacco use, especially for the Ackerman tumor. Perhaps, chemical and HPV viral co-carcinogens work together. Other factors may be important as well.

  • In 1967, Barnett and Hyman27 first linked oral florid papillomatosis to HPV on the basis of ultrastructural findings.
    • A number of HPV types are associated with squamous cell carcinoma, including HPV types 6 and 11.
    • Oral verrucous carcinomas may be associated with or caused by HPVs, particularly in individuals who are predisposed. In one study, HPV types 6 and 11 were detected in 7 of 17 cases of oral verrucous carcinoma.28
    • In an analysis of laryngeal verrucous carcinoma, HPV-16 DNA, HPV-18 DNA, or both were present in 13 of 29 cases.20
    • HPV may facilitate the development of verrucous carcinoma because of oncogenic expression.29 The E6 oncoprotein encoded by HPV types 16 and 18 promotes the degradation of p53.30 In addition, alterations of the amino acids in the HPV-6 E7 protein may result in HPV-16 oncoproteinlike transforming activity.31
  • Tobacco chewing may be an etiologic factor. The possibility of chemical carcinogenesis of verrucous carcinoma of the oral cavity from tobacco has long been suggested.
    • Research has indicated that the use of chewing tobacco and snuff is strongly correlated with oral florid papillomatosis in many, but not all, patients. Why verrucous carcinomas develop in some patients and ordinary squamous cell carcinomas develop in other patients is unclear. Perhaps, some patients with oral verrucous carcinoma die from a highly aggressive second primary oral cancer due to the same carcinogenic stimuli rather than a transformation of the verrucous carcinoma.
    • In a study of 37 patients, 11 chewed tobacco and another 11 smoked tobacco.21
    • Among Swedish men who had oral cancer and who used snuff, almost one half had verrucous carcinoma.32
    • Betel nuts may be linked to verrucous carcinoma,33 although the association may be due to the tobacco added to betel chew.
  • Other factors may contribute to the development of verrucous carcinoma.
    • Chronic inflammatory processes may be involved, possibly by lowering the body's mutagenic resistance.1
    • An important issue is whether the development of oral verrucous carcinomas is related to the patient's immune status.
    • Another risk factor is chronic inflammation or irritation such as that caused by poorly fitted dentures.

More on Oral Florid Papillomatosis

Overview: Oral Florid Papillomatosis
Differential Diagnoses & Workup: Oral Florid Papillomatosis
Treatment & Medication: Oral Florid Papillomatosis
Follow-up: Oral Florid Papillomatosis
References
[ CLOSE WINDOW ]

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Further Reading

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Keywords

oral florid papillomatosis, verrucous carcinoma, Ackerman's tumor, Ackerman tumor, carcinoid mucous papillomatosis, oral cavity and aerodigestive tract verrucous carcinoma, oral florid verrucosis, giant mucocutaneous papillomatosis, nonmetastasizing papillomatosis, squamous cell carcinoma, multifocal papillomavirus epithelial hyperplasia

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Contributor Information and Disclosures

Author

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Coauthor(s)

Channing R Barnett, MD, Staff Physician, Department of Dermatology, University of Medicine and Dentistry of New Jersey
Channing R Barnett, MD is a member of the following medical societies: Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Julie C Harper, MD, Assistant Program Director, Assistant Professor, Department of Dermatology, University of Alabama at Birmingham
Julie C Harper, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Stiefel Honoraria Speaking and teaching; Allergan Honoraria Speaking and teaching; Intendis Honoraria Speaking and teaching; Coria Honoraria Speaking and teaching; Sanofi-Aventis Honoraria Speaking and teaching

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Drore Eisen, MD, DDS, Consulting Staff, Department of Dermatology, Dermatology Research Associates of Cincinnati
Drore Eisen, MD, DDS is a member of the following medical societies: American Academy of Dermatology, American Academy of Oral Medicine, and American Dental Association
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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