Papillary (pebbled) masses of the oral mucosa: more than simple papillomas


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A Review Paper Published in Practical Periodontics & Aesthetic Dentistry in 1996; 8:533-543.

Authors

J. E. Bouquot D.D.S., M.S.D., Director of Research, The Maxillofacial Center for Diagnostics and Research, Morgantown, West Virginia; Dental Director, West Virginia Bureau for Public Health (Office of Child and Maternal Health), Charleston, West Virginia; and G. J. Wrobleski D.D.S., Private practice (oral & maxillofacial surgery), Morgantown, West Virginia; Clinical Advisor, The Maxillofacial Center for Diagnostics and Research, Morgantown, West Virginia


ABSTRACT

Soft tissue masses are found in almost 4% of your adult patients, and we must assume that most of these will never be biopsied. Your clinical impression, then, is of paramount importance. Oral mucosal masses with irregular or nodular surface alterations are of special concern. To the less informed health professional these all appear to be papillomas, but there are several types of papillomas, and among the lesions which present with a papilloma-like appearance are divers malignancies, contagious infections, sexually transmitted diseases, vascular and reparative lesions, and viral proliferations associated with a wide range of different types of human papillomavirus. The present paper presents a clear, clinically-oriented approach to the diagnosis and management of pebbled and lobulated masses of the mouth in order that you, the clinician, can provide your patient with a more meaningful clinical diagnosis and prognosis. The authors have selected for the differential diagnosis discussion only those entities which have been referred to them by health professionals with the preliminary diagnosis of "papilloma."


INTRODUCTION

When an anxious patient calls to report the recent discovery of a soft tissue mass in his mouth, chances are very good that he's been aware of it for several months, has been worrying about cancer, and has been trying to ignore it under the irrational and subconscious assumption that it is not a real disease until a health professional gives it a diagnosis. If the mass is not located on the gingiva he is also likely to have consulted his family physician before even thinking to give your office a call. And it is a clear certainty that the primary care physician could do no more than indicate whether or not the thing was, in his or her opinion, a malignancy. Very few primary care physicians have had so much as an hour of clinical oral pathology training, and the relative "scarcity" of oral lesions in medical practices without appropriate lighting or thorough oral examinations does not naturally tend to enhance this early training.

The real question becomes, then, what will you do with the lesion, because you will get little help from your medical colleagues. Unfortunately, experience has shown that you, also, are likely to spend little time or effort on an oral mass; you are probably going to do no more than assure your patient that it certainly looks benign. Under the circumstances you have done nothing more than the family physician unless you have a good understanding of the differential diagnosis of oral masses.

Can any mass in the mouth be ignored without a firm diagnosis? The truth is a bit surprising. While it may not be good practice to avoid microscopic confirmation of an oral lesion, population studies have shown that, in fact, the majority of oral soft tissue masses are probably never biopsied,1 and the majority of patients are therefore not given a specific diagnosis.

The result of this "neglect" is that at any given time almost 4% of U.S. adults, males and females, have at least one exophytic lesion in their mouths, excluding common bony growths such as tori and buccal exostoses.2,3 This being the case, it becomes extremely important for each and every dentist to be as familiar with the clinical characteristics of the various oral soft tissue lesions as possible in order to be able to give a reasonably specific and reliable clinical diagnosis to the patient.

Oral masses come in many sizes, shapes, colors and consistencies (Figure 1). Soft or nonbony masses with smooth, even surfaces are usually benign and have minimal potential for continued growth or very large size, especially those lesions resting on a narrow stalk or pedicle (pedunculated). The lowly irritation fibroma is a prime example of this, but even clinically obvious fibromas will occasionally have surface lobulations and reach alarming dimensions (Figure 2). Moreover many low-grade malignancies of salivary glands and nerves have smooth, dome-shaped surfaces.

Lesions without smooth surfaces are inherently more suspicious because sarcomas and carcinomas typically present with such surface changes, but so also do common benign entities like the giant cell fibroma (Figure 3). It is very important for the dentist to be able to at least distinguish between the various benign "pebbled" masses ("lumps with bumps," "bumpy lumps") and the more consequential lesions. It also seems logical to be able to differentiate these lesions in order to intelligently discuss such aspects as potential size, probable cause, contagion, potential for hemorrhage when traumatized, extent of excisional removal, risk of recurrence after removal, and risk of malignant transformation.

A systematic approach to the diagnosis of pebbled masses is not difficult. One must firstly determine whether or not the lesion is single or multiple. If multiple, the diagnostic choices are limited (Table 1). If single, the mass should be characterized as to the nature of the surface irregularities or projections, using the following categories (Figure 1):

Masses with regular or uniformly distributed surface nodules are more common, but masses with irregular surfaces are more likely to be serious problems, as has been mentioned. Fungating is a term routinely applied, for example, to exophytic ("growing outward") malignancies (Figure 4), although fungating masses may also have serious infectious or other etiologies. The classic gumma of tertiary syphilis is one such mass, as are the masses seen as oral manifestations of tuberculosis, deep fungal infections and sarcoidosis.

An important feature of "bumpy lumps" of the mouth is the width of the base. As a general rule, the more narrow the base the less likely a mass is to be malignant. A narrow stalk can help the dentist to distinguish a papilloma, which may be justifiably left alone, from the typically broad-bases (sessile) condyloma accuminatum, which is contagious enough to spread to you, your staff or your next patient. Sometimes stalks can be extremely long (Figure 5), but they are usually only a fraction of a mm. high.

All oral masses should be evaluated by palpation. This is especially true for those which will not be biopsied. Carcinomas are typically more firm than benign soft tissue lesions, often being so hard (indurated) that they literally mimic the feel of wood. It is not unheard of for a physician to refer a "sore throat" patient to the dentist for extraction of an "infected wisdom tooth" which is, in fact, a white (keratotic), hard, squamous cell carcinoma of the retromolar pad region.

The opposite may also be diagnostically helpful. Pebbled lesions with unusual softness are most likely to be hemangiomas or lymphangiomas. Most other lesions have intermediate firmness on palpation.

Additional features may aid in the clinical diagnosis of specific pebbled oral masses. Lymphangioma often has a clear or transparent appearance to the surface nodules, as does the condyloma in some cases. The mucocele is, of course, the classic transparent mass of the oral mucosa, but its smooth dome-shaped appearance allows it to be easily differentiated from lymphangioma.

A mass which is red is most likely to be an hemangioma or pyogenic granuloma, although peripheral giant cell granuloma and peripheral ossifying fibroma must also be considered for gingival lesions. A red lesion which blanches under palpation can only be an hemangioma, while one which bleeds when palpated is more likely to be a pyogenic granuloma or carcinoma, although any gingival mass may bleed because of gingivitis developing on the crevicular epithelium behind the lesion.

To help the clinician make a high-quality clinical diagnosis of pebbled oral masses, the following discussion reviews the germane features of specific lesions, all of which have at one time or another been referred to the authors by physicians or dentists with a preliminary diagnosis of papilloma. Prior to this discussion, however, the confusing concept of papillomatosis should be clarified. This term is used quite legitimately for mucosal involvement with numerous papillomas or papillary lesions, as occurs, for example, in laryngeal papillomatosis. But in the mouth this term is often used improperly for a type of lesion which is nothing more than clustered individual nodules or papules (Figure 6). Perhaps the most common of these is papillary hyperplasia of the palate, often called denture papillomatosis (Figure 7). This is a lesion comprised entirely of multiple nodules resulting from retained fluids (edema) or fibrous overgrowth of connective tissue papillae, the tissues between the rete ridges of the epithelium.4 Papillary hyperplasia may also occur along the edges of leaf-shaped fibromas, the flattened irritation fibromas which occasionally develop under maxillary dentures. This response to chronic trauma or infection has no finger-like projections in the papillary sense, but many clinicians nevertheless refer to it as a papilloma-producing lesion.

True papillomatosis with multiple papillomas does occurs in the mouth, especially in the precancerous lesion, proliferative verrucous leukoplakia, in the viral infection, focal epithelial hyperplasia, and in developmental anomalies such as the Goltz-Gorlin syndrome (Table 1). In the head and neck region, the most common form of true papillomatosis occurs in the larynx, where it can be so proliferative that it may result in death from asphyxiation. In the mouth, the most common presentation is much less extensive and less frightening, being two to five common warts or venereal warts.

Individual Lesions

Squamous papilloma. There are several different types of papillomas but the ones which occur in the mouth are almost always squamous papillomas.4,6 The oral papilloma is often thought by clinicians to be childhood lesions but, in fact, is most commonly diagnosed in persons 30 to 50 years of age.1,3 It is the fourth most common mass found in the mouths of adults (Table 2).2 The typical lesion is a soft, pedunculated mass with numerous finger-like surface projections (a papilla is a "nipple-shaped projection," i.e. rounded at the tip; Figure 8). Projections may be pointed (Figure 9) and the surface may be covered with a considerable amount of keratin, producing a white surface change. Heavily keratinized lesions with short rounded projections are often describes as cauliflower-like, while similar but less keratinized lesions look more like raspberries or mulberries with a pink or red coloration. A yellow/white, pedunculated, lobulated mass resembling papilloma occasionally occurs on the palatine tonsils and may be responsible for extremely foul breath (Figure 10). This keratin plug is easily differentiated from a papilloma because it can be removed with a tongue blade or spatula. It is comprised of packed keratin sloughed from the epithelium within a tonsillar crypt.

The papilloma is usually solitary and reaches its maximum size rather quickly, probably within a few weeks. While most lesions are no more than 0.5 cm. in greatest diameter, some have become as large as 3.0 cm (Figure 11). Microscopically, each surface projection contains a connective tissue core, often mildly inflamed, and the entire mass usually sits upon a rather narrow base. The shape of a papilloma is quite an engineering feat. Whatever is producing the individual lesion must control not only the proliferation of epithelium but must shape it into projections and must somehow, probably through inductive influences, convince the underlying connective tissues to proliferate into each projection.

First reported as a gingival "wart" by Tomes 7 in 1848, the oral papilloma is now known to be a localized epithelial hyperplasia induced by human papillomavirus (HPV), a group of double-stranded DNA viruses which can become completely integrated with the DNA of the host cell. Evidence of virus change may be microscopically visible within the upper reaches of the epithelial covering, but special staining and processing are normally required to find the virus. Of the more than 70 subtypes of HPV, HPV-6 and HPV-11 are most often isolated from oral papillomas.8 These virus subtypes are not among those associated with malignancy or precancer and, of course, clinical experience has taught us not to expect malignant transformation of oral papillomas. Theoretically all HPV lesions are infective but the oral papilloma appears to have an extremely low virulence and infectivity rate; it does not seem to be contagious.

The best treatment for an oral papilloma is conservative but complete surgical removal. Some advocate removing a mm. or more of normal surrounding mucosa, but recurrence is unlikely with or without this precaution. Destruction by laser or electrocautery is an acceptable alternative therapy, although a portion of the lesion should be removed first in order to obtain a definitive diagnosis via biopsy. Untreated lesions do not normally change over time and should not be expected to disappear on their own.

One of the fascinations of the oral papilloma is how differently it behaves from the more aggressive nasal, paranasal and laryngeal papillomas. For example, the latter lesions are clinically and microscopically identical to their oral counterparts but have a very high recurrence rate, are almost always multiple and continuously proliferate over time. Age at onset is also quite different, being diagnosed usually in children. As already mentioned, laryngeal papillomas may be so relentlessly proliferative that they cause life-threatening asphyxiation, and some worry about malignant transformation in long-standing cases.9,10

Verruca vulgaris (common wart). Verruca vulgaris is rare in the mouth but, of course, quite common on the skin, especially in children.4 Fresh lesions occasionally occur in middle-aged persons. Unlike papilloma, verruca vulgaris is contagious and can spread to other people as well as to other parts of a patient's body, either by local spread or by self-inoculation after biting a lesion. On the skin, the hands are most often involved. In the mouth, almost all lesions are found on or near the lip vermilion (Figure 12), although it is not unheard of for lesions to affect the tip of the tongue, the gingiva, or even the soft palate. As with papillomas, lesions rapidly enlarge to their maximum size and remain unchanged for months or years thereafter. Few oral verrucae become larger than 0.5 cm. in size and most present as painless papules or nodules with white, pointed (verruciform) surface projections. A very thin stalk is typical and is a feature which is somewhat different from the often broad-based verruca vulgaris of the skin.

Verruca vulgaris is another epithelial hyperplasia induced by HPV, usually HPV-2, HPV-4 or HPV-40.4,11 The virus lives within the epithelium of the lesion and can be seen microscopically as intranuclear viral inclusions and specially altered clear cells with small, pyknotic nuclei (koilocytes). The resulting mass has absolutely no malignant transformation potential and, in fact, most cases eventually disappear spontaneously after a year or two. There have been cases which disappeared after hypnotic suggestion. When removal is elected, conservative surgical excision is the treatment of choice, but cryotherapy, laser and electrosurgery are all effective. The base of the lesion and a small extent of surrounding mucosa should be removed or destroyed, as the virus is also seen in adjacent normal epithelium. Recurrence after conservative removal is not uncommon. Accum

Condyloma accuminatum (venereal wart). Yet another virus-induced epithelial proliferation is seen as a sexually transmitted disease (STD), condyloma accuminatum (condyloma = "knuckle or knob"), which develops at a site of sexual contact or trauma.4,12,13 This is, as expected, a lesion which is much, much more common in the anogenital region, where it represents approximately 20% of all STDs. It is not unusual for a patient with a condyloma to have multiple STDs and so caution is advised relative to infection control procedures in the dental office. This multi-disease feature is so strong, in fact, that genital condyloma was once thought to be a characteristic feature of syphilis rather than a separate entity. Condylomas are very contagious and may spread by autoinoculation to other sites of trauma.

Condyloma accuminatum is usually diagnosed in teenagers and young adults, but no age is immune (Figure 13). In the mouth, lesions occur most frequently on the lip mucosa, the lingual frenum and the soft palate, all points of potential trauma during cunnilingus and fellatio (Figure 14). The lesion presents as a broad-based, pink mass with the surface covered by short, blunted projections, giving it a raspberry or mulberry appearance. Many lesions have a mild semitransparency to the surface nodules. The typical condyloma is 1.0-1.5 cm. in greatest dimension but may be as much as 3.0 cm. in size. In addition to being larger than papillomas and verrucae vulgaris, condylomas are characteristically multiple and clustered, perhaps because of the autoinoculation phenomenon resulting from repeated sexual trauma.

Not surprising, the virus involved with condyloma accuminatum is HPV, especially subtypes HPV-6, HPV-11, HPV-16, and HPV-18.13 The later two subtypes are among those associated with carcinoma and epithelial dysplasia of genital mucosa, explaining why the condyloma is considered a premalignant lesion by many. For reasons unknown, this precancerous character does not seem to be a part of the condylomas which occur in the mouth.

Focal epithelial hyperplasia (Heck's disease). One of the most contagious of the oral papillary lesions is focal epithelial hyperplasia, another HPV-induced epithelial proliferation first described in Eskimos and Native Americans.14-16 It has now been seen in most population subtypes and is thought to be induced by the HPV subtype HPV-13. Children are predominantly affected, but lesions may occur in young and middle-aged adults. The level of this lesion's contagion is exemplified by the fact that in some isolated populations up to 40% of children have been affected. In communities where the infection is endemic among the young, adults seem to have minimal evidence of residual oral lesions and so the lesions are presumed to eventually disappear on their own.

Focal epithelial hyperplasia is somewhat different from other HPV infections in that it is able to produce extreme hyperplasia of the prickle cell layer of the epithelium (acanthosis) with minimal production of surface projections or induction of connective tissue proliferation. The mucosa may be 8-10 times thicker than normal.

Individual lesions are always broad based and multiple masses are scattered over a localized area (Figure 15). Lesions are frequently papillary in nature, but relatively smooth-surfaced, flat-topped lesions are more commonly seen. A biopsy may be necessary to establish the proper diagnosis but additional treatment is not required or recommended, except perhaps for aesthetic reasons relating to visible labial lesions. No case of focal epithelial hyperplasia has been reported to transform into carcinoma.

Verruciform xanthoma. One of the more recently delineated of the oral papillary lesions is the verruciform xanthoma, an exact papilloma look-alike which seems not to be associated with HPV but is perhaps a response to local trauma.4,17,18 This unique lesion typically occurs in middle-aged and older individuals, usually women and usually on the gingival or alveolar mucosa. It usually remains smaller than 2 cm. and is a broad-based mass with either a papillary or a "roughen" surface appearance (Figure 16). The roughened surface change proves to be verruciform under the microscope but the most interesting histopathologic feature is that each connective tissue papilla is filled with foamy or fat-filled histiocytes called xanthoma cells ("xanthos" = yellow). These cells never extend below the level of the adjacent rete ridges. We have no plausible explaination as to why this strange localization should occur but xanthoma cells may be so numerous as to actually become visible clinically as a cluster of small yellow surface nodules resembling fish eggs.

Initially thought to be related to a high blood level of lipids or to a systemic process such as histiocytosis X, these lesions are now considered to be unrelated to systemic diseases. Conservative surgical removal is recommended, as some lesions have grown to as much as 4 cm. in diameter; without surgery they are likely to remain indefinitely. There is no malignant transformation potential to this lesion.

Lymphangioma. The lymphangioma is a developmental anomaly rather than a true neoplasm, but it can nevertheless be life-threatening when it occurs in a vital area such as the neck.4 A particularily persistent congenital form, called cystic hygroma because of very large, lymph-filled cystic spaces, may be as large as the affected child's head at birth and may produce death from asphyxiation, infection or hemorrhage into the cystic spaces. The type of lymphangioma with a raspberry or papillary appearance is called lymphangioma simplex or capillary lymphangioma (Figure 17). It most commonly is seen on the tongue and may produce macroglossia because the abnormal or proliferative lymphatic vessels spread deeply and extensively throughout the surrounding tissues without the slightest attempt at encapsulation. These vessels extend from the primary mass, burrowing beneath the adjacent mucosa to surface several mm. away in a fashion similar to a worm tunneling underground to occasionally surface and expose itself. The resulting satellite lesions look very much like vesicles.

Lymphangiomas of the mouth are often superficial and the surface nodules are often semitransparent in appearance, a feature which once led them to be called "chronic clustered vesicles."7 Secondary hemorrhage into the vessels may result in a mixture of hematoma-like "blood blisters" intermixed with the clear vesicles. Microscopically, these lesions appear as nothing more than an excess number of vascular channels filled with lymph instead of cellular blood elements.

Lymphangioma is typically treated by surgical excision, but the surgeon is almost always forced to leave lymphatic channels behind rather than risk disability or disfigurement from the removal of too much normal tissue with the abnormal tissue. This results in a very high recurrence rate and the typical lymphangioma must be removed three or four times before it is finally controlled. While there is a malignant lymphangioma (lymphangiosarcoma), benign lesions are not known to present a threat of malignant transformation.

Pyogenic granuloma. After injury or infection the healing process may be defective in such a way that a considerable excess of granulation tissue is produced.4 The resulting pyogenic granuloma, which is neither pus-producing (pyogenic) nor a true granuloma, can occur at any age but is usually seen in teenagers and young adults. It may exhibit rapid, even alarming growth and may reach a size of several cm., although most remain smaller than 0.5 cm. in size. The lesion typically has an irregular or lobulated surface with coloration varying from pink to red to white. The white represents surface ulceration rather than excess keratin. Palpation reveals minimal tenderness and often produces hemorrhage.

This lesion is most often seen on the gingiva, although no area of the mouth is immune. Certain situations seem to predispose toward the development of pyogenic granuloma, especially pregnancy gingivitis and recent extraction. In the latter case, the term epulis granulomatosum is used as a clinical diagnosis for pyogenic granulomas protruding from a socket (Figure 18).

Pyogenic granuloma is comprised of edematous fibrovascular connective tissue admixed throughout with acute and chronic inflammatory cells. Ulceration of the surface epithelium is often seen. Treatment consists of conservative surgical removal. Root surfaces adjacent to a gingival lesion should be thoroughly scaled at the time of surgery in order to avoid recurrence, a not uncommon event with pyogenic granuloma.

Papillary carcinoma. While most exophytic oral cancers are best described as lobulated or fungating, a small proportion of squamous cell carcinomas present with rather uniformly distributed surface nodules. These are often called papillary carcinomas but they behave in the same fashion as any other carcinoma of the same size and location; the only aspect which is special is the papillary appearance and it is not understood what produces this appearance.

Verrucous carcinoma. One of the strangest of the oral malignancies is the "snuff-dipper's cancer," verrucous carcinoma. As the name implies, this lesion is characterized by the presence of numerous pointed surface projections, usually white from a thick keratin covering (Figure 19), but many cases present as mulberry in appearance and lack the white coloration. Verrucous carcinoma is clearly a malignancy, but it is similar to basal cell carcinoma in that it produces great local destruction with very little tendency to metastasize. It is not unusual for a lesion to be present for years prior to diagnosis.

Almost all cases of verrucous carcinoma occur in the mouths of snuff dippers and tobacco chewers. The cancer seldom occurs before 55 years of age and it is usually a male disease, probably because males have traditionally been the tobacco users in our culture.4,19,20 In users of smokeless tobacco who develop cancer, the cancer usually occurs at the site of long-term tobacco quid placement, but it should be emphasized that only 4% of such cancers are actually verrucous carcinoma. In other words, most cancers developing from this habit are regular squamous cell carcinomas and are, therefore, much worse relative to the extent of treatment and the eventual risk of dying from the disease.

This cancer is treated by conservative local excision, usually a block resection. Some advocate radiation therapy as an alternative therapy but there is some question as to whether this induces the development of a higher grade malignancy within the verrucous carcinoma.21 Even without irradiation, the latter event occurs in a certain number of cases. The overall survival rate, however, is good, usually reported as 90% or better.

Proliferative verrucous leukoplakia (PVL). During the past decade a newly recognized subset of oral leukoplakia, PVL, has proven to have frightening consequences, with extreme resistance to therapy and at least 30% of affected patients eventually dying of oral carcinoma.4,22-24 The diagnosis of this disease is essentially a clinical diagnosis, since the microscopic features of any particular lesion may fall anywhere along the spectrum from hyperkeratosis to epithelial dysplasia to verrucous hyperkeratosis to verrucous carcinoma to invasive carcinoma. In contrast to routine leukoplakia, most cases of PVL occur among older women and in persons without a tobacco or alcohol habit. Almost all PVL lesions are positive for HPV, usually the cancer-associated HPV-16. This disease begins as multiple flat leukoplakias which relentlessly expand and are added to by similar lesions. With time, the flat white macules become roughed or granular on the surface, then verruciform. Scattered individual areas typically develop papillary or verrucous exophytic lesions identical to papillomas, condylomas, and verruciform hyperkeratosis.

Almost every affected patient develops some form of oral carcinoma, hence, very close clinical follow-up is required, with surgical removal of any and all suspicious areas or lesions. Even the benign lesions in PVL have a high rate of recurrence.


Conclusions

Pebbled or papillary masses of the oral mucosa have numerous possible diagnoses, some benign, some malignant and some very contagious. Since most such lesions are not biopsied we all must be as knowledgeable as possible about clinical variations and differences between these lesions in order to provide a meaningful service to our patients. Lesions which are not obvious clinically should be biopsied for microscopic interpretation, or at the very least should be followed in order to assess biological behavior.


References

1. Bouquot JE, Gundlach KKH. Oral exophytic lesions in 23,616 white Americans over 35 years of age. Oral Surg Oral Med Oral Pathol 1986; 62:284-291.

2. Bouquot JE. Common oral lesions found in a large mass screening. J Am Dent Assoc 1986; 112:50-57.

3. Bouquot, J.E. Epidemiology. In: Gnepp, DG: Pathology of the head and neck. New York: Churchill Livingstone, 1987, pp 263-314.

4. Neville B, Damm D, Allen C, Bouquot J. Oral and maxillofacial pathology. Philadelphia: W. B. Saunders; 1995.

5. Gorlin RJ, Cohen MM, Levin LS. Syndromes of the head and neck, 3rd edition. New York: Oxford University Press, 1990.

6. Abbey LM, Page DG, Sawyer DR. The clinical and histopathologic features of a series of 464 oral squamous cell papillomas. Oral Surg Oral Med Oral Pathol 1980; 49:419-428.

7. Bouquot JE, Lense EC. The beginning of oral pathology. Part II: First dental journal reports of nonodontogenic tumors and cysts, 1839-1860, in press.

8. Ward KA, Napier SS, Winter PC, et al. Detection of human papilloma-virus DNA-sequences in oral squamous-cell papillomas by the polymerase chain-reaction. Oral Surg Oral Med Oral Pathol 1995; 80:63-66.

9. Sakakura A, Yamamoto Y, Takasaki T, et al. Recurrent laryngeal papillomatosis developing into laryngeal carcinoma with human papilloma-virus (HPV) Type-18. A case report. J Laryngol Otol 1996; 110:75-77.

10. Bouquot JE, Gnepp DR. Laryngeal precancer--a review of the literature, commentary and comparison with oral leukoplakia. Head Neck 1991; 13:488-497.

11. Green TL, Eversole LR, Leider AS. Oral and labial verruca vulgaris: clinical, histologic, and immunohistochemical evaluation. Oral Surg Oral Med Oral Pathol 1986; 62:410-416.

12. Zunt SL, Tomich CE. Oral condyloma acuminatum. J Dermatol Surg Oncol 1989; 15:591-594.

13. Sykes NL. Condyloma acuminatum. Intnl J Dermatol 1995; 34:297-302.

14. Witkop CJ Jr, Niswander JD. Focal epithelial hyperplasia in Central and South American Indians and Ladinos. 1965; 20:213-217.

15. Padayachee A, van Wyk CW. Human papillomavirus (HPV) DNA in focal epithelial hyperplasia by in situ hybridization. J Oral Pathol Med 1991; 20:210-214.

16. Carlos R, Sedano HO. Multifocal papilloma virus epithelial hyperplasia. Oral Surg Oral Med Oral Pathol 1994; 77:631-635.

17. Neville B. The verruciform xanthoma: a review and report of eight new cases. Am J Dermatopathol 1986; 8:247-253.

18. Huaug JS, Tseng CC, Jin YT, et al. Verruciform xanthoma -- case report and literature review. J Perio 1996; 67: 162-165.

19. McCoy JM, Waldron CA. Verrucous carcinoma of the oral cavity: a review of forty-nine cases. Oral Surg Oral Med Oral Pathol 1981; 52:623-629.

20. Schwartz RA. Verrucous carcinoma of the skin and mucosa. J Am Acad Dermatol 1995; 32:1-21.

21. Thorp ME, Shidnia H. Radiotherapy in the treatment of verrucous carcinoma of the head and neck. Laryngoscope 1995; 105:391-396.

22. Hansen LS, Olson JA, Silverman S. Proliferative verrucous leukoplakia: a long-term study of thirty patients. Oral Surg Oral Med Oral Pathol 1985; 60:285-298.

23. Bouquot JE. Oral leukoplakia and erythroplakia: a review and update. Pract Perio Aesth Dent 1994; 14:9-19.

24. Palefsky JM, Silverman S, Abdelsalaam M, et al. Association between proliferative verrucous leukoplakia and infection with human papillomavirus Type-16. J Oral Pathol Med 1995; 24:193-197.


Table 1. Lesions demonstrating multiple papillary or nodular masses of the oral mucosa, often referred to as papillomatosis.4,5

Inflammatory lesions:

Developmental syndromes:


Table 2: The 15 most common benign moral masses found in U.S. adults, ranked according to prevalence rates per 1,000 population.2

Rank Diagnosis Number per 1,000 adults

1 Torus (palatal and mandibular) 27.1

2 Irritation fibroma 12.0

3 Hemangioma 5.6

4 Papilloma 4.6

5 Epulis Fissuratum 4.1

6 Papillary hyperplasia of the palate * 3.0

7 Mucocele 2.5

8 Enlarged lingual tonsil 1.6

9 Hematoma 1.6

10 Buccal exostoses 0.9

11 Hairy tongue * 0.6

12 Epidermoid cyst 0.5

13 Lipoma 0.3

14 Oral tonsils (nonlingual) 0.3

15 Ranula 0.2

Total, oral masses 64.9/1,000 adults

Total, soft tissue masses ** 33.3/1,000 adults

     * not technically a mass, but comprised of numerous small enlargements coalesced together

 ** excludes bony lesions (torus, buccal exostosis) and lesions with multiple papules scattered over broad areas (papillary hyperplasia of the palate, hairy tongue)


Legends for Figures

Figure 1: The basis of a good clinical diagnosis is an accurate determination of the surface appearance of the oral mass. The various surface alterations of oral mucosal masses are depicted here.

Figure 2: Even an irritation fibromas, as seen here on the lingual gingiva, may become quite large and lobulated. Some authorities prefer to call the large lesions fibromatosis.

Figure 3A: Small versions of the irritation fibroma may also occasionally resemble papillary lesions, usually these are the variant called giant cell fibroma.

Figure 3B: The giant cells in giant cell fibroma are unusual fibroblasts which can be alarming to a pathologist not familiar with the lesion.

Figure 4: Most exophytic squamous cell carcinomas of the mouth have a lobulated or fungated appearance. There is often a central necrosis or ulceration, as seen here.

Figure 5: This pedunculated mass (arrow) was on a 2.5 cm. stalk extending from the uvula. It proved microscopically to be a classic papilloma but the surface was covered by saliva, giving it a rather smooth clinical appearance.

Figure 6: Enlargement and fibrosis of individual lingual papillae along the lateral margin has given this lesion the appearance of "papillomatosis." Each nodule is, however, more similar to an irritation fibroma than a papilloma and so a more accurate designation would be "multinodular" or "multipapular."

Figure 7: Papillary hyperplasia of the palate is an inflammatory entity comprised of numerous nodules or papules, rather than multiple papillomas. In this case a leaf-shaped irritation fibroma is also seen (arrow).

Figure 8: This keratinized papilloma of the dorsum of the tongue presents a classic appearance with long, blunted surface projections.

Figure 9: A: On less keratinized oral mucosal surfaces, a papilloma is typically not white. This one presents with pointed projections rather than finger-like projections. B: Gross appearance of a biopsied papilloma illustrates the pointed and blunted shapes of the surface projections.

Figure 10: A keratin plug protruding from a tonsillar crypt may have a stalk and a lobulated or papillary appearance, as seen here. These are easily removed with a tongue blade.

Figure 11: Squamous papillomas can be several cm. in diameter, as seen here on the right mandibular mucosa. Large lesions may be similar in appearance to verrucous carcinoma. (Courtesy of Dr. William Young, Sydney, Australia).

Figure 12: Verruca vulgaris is usually located on the lip vermilion and is so heavily keratinized that it appears white. (Courtesy of Dr. Richard Hart, Morgantown, West Virginia).

Figure 13: Broad-based condyloma accuminatum is a contagious, sexually transmitted disease. Seen here (large arrow) in a chronic alcoholic, there is also a newly developed squamous cell carcinoma of the adjacent soft palate (small arrow). Oral condylomas are not, however, considered to have much risk of malignant transformation.

Figure 14: A condyloma is seen here on a lingual frenum, presumably traumatized during sexual activity.

Figure 15: Multiple papillary or papular masses are characteristic of the childhood infection, focal epithelial hyperplasia (Heck's disease). (Courtesy of Dr. Fin Preatorius, Copenhagen, Denmark).

Figure 16: Verruciform xanthoma often looks exactly like papilloma in the mouth. Here two lesions (arrow) are seen on the soft palate, a common location.

Figure 17: Lymphangioma is often a papillary or pebbled mass (large arrow) with satellite lesions appearing like vesicles (small arrows).

Figure 18: A pyogenic granuloma protruding from an extraction socket may be pedunculated and lobulated, as seen here. The red color makes this lesion similar in appearance to hemangioma.

Figure 19: A verrucous carcinoma of the right oral floor (arrows) demonstrates both pointed and blunted surface projections.