Odd tongues (Prevalence of lingual disease). Bouquot JE, Gundlach KKH, West Virginia University and University of Hamburg, Hamburg, West Germany.

Presented to the American Academy of Oral Pathology, Toronto, Canada, May, 1986.
Reference: Dent Abst 32:89-90, 1987.

Data collected from oral cancer screening examinations of 23,616 adults age 35 and older in Minnesota between 1957 and 1973 were analyzed to produce prevalence rates of lingual disease in 1,000 persons.

Because there were no statistically significant age, race, or gender differences between the various groups of examinees, this group can be considered to have been examined in a single, massive oral screening. (A summary of larger prevalence of tongue lesions worldwide is shown in the Table.)

The sample population was deliberately biased toward older persons. More than 91% were age 40-79. Males were also under-represented. Only 35.9% of participants were males, while the collective proportion of males over age 30 in these communities was 46.9%.

Of a total of 3,783 reported lesions of the oral mucosa and connective tissue, 628 (16.6%) were located on the tongue, providing an overall point prevalence rate of 26.6 tongue lesions per 1,000 persons examined. Exclusion of lesions reported in such ambiguous terms as "lesions" or erythematous patch" (10.2% of lingual diagnoses) resulted in a corrected prevalence rate of 23.9 specific lesions per 1,000 population.

Lingual disease was somewhat more prevalent in males (27.3/1,000) than females (22/1,000), predominantly due to higher frequencies of squamous papillomas, hyperplastic lingual tonsils, and hairy tongues. Altered mucosal surface was the most common clinical presentation, representing 51.4% of all lesions. Almost 27% of lesions were exophytic, nonvascular soft tissue masses. Vascular lesions, exophytic or otherwise, accounted for 18.8% of all lesions. Only 2.1% of lesions were ulcerative or vesiculobullous in nature and 1.4% were cystic. A surprisingly small number of different diagnoses were rendered (no. = 27) and the five most common entities represented 62.9% of lesions.

Rates determined from this analysis are, as a rule, lower than those from other disease-specific studies. The best explanation is related to a lower level of suspicion from the use of general practitioners as examiners and from the basic function of the screenings themselves. It is likely that only the more remarkable or severe cases of these common abnormalities were reported by examiners. However, these rates are probably more indicative of disease frequency as perceived in the general practice of dentistry, because a general practitioner would be unlikely to record very small or borderline lesions of such innocuous entities.

Common oral lesions found during a mass screening examination. Bouquot JE. West Virginia University, Morgantown, WV.

Reference: Year Book of Dent 1987:275-277.

The results of oral examination of more than 32,000 adults seen at 17 mass oral screenings in Minnesota from 1957-1972 were reviewed. A total of 23,616 examinations were available for review. Most subjects were aged 35 years and older and were attending oral cancer screening clinics voluntarily. The mean age was 56 years. All but 0.5% of the ample were white; 36% were men.

A total of 3,783 oral mucosal and connective tissue lesions were reported (Table 1). The most frequent lesions are ranked by location-specific and gender-specific prevalence rates in Table 2. About 10% of the study population had oral and connective tissue lesions. A single exophytic mass accounted for more than one third of all lesions. White keratotic lesions accounted for more than one third of mucosal surface alterations. Fourteen percent of leukoplakias were epithelial dysplasias, and 12% were early invasive squamous cell carcinomas. About half other inflammatory ulcers were considered traumatic ulcers, often related to denture wear, but 40% were aphthous ulcers. Two of the 16 ulcers biopsied showed squamous cancer. Squamous cell carcinoma ranked 24^th overall among all types of lesions. Just over 30% of lesions described clinically as probable or possible carcinomas were confirmed as neoplastic.

About 10% of this screening population were found to have oral mucosal and connective tissue lesions. An exophytic mass was the most frequent clinical finding. The most common oral connective tissue-mucosal lesions was leukoplakia. Very mild common oral lesions are probably not reported in mass screenings.

Bouquot and Gorlin (Oral Surg. Oral Med, Oral Pathol. 61:373-381, April, 1986) reported in more detail some aspects of this study. They recognize as shortcomings of the study using multiple examiners who were not specialists in diagnosis and excluding equivocal and ambiguous diagnoses which may have led to underreporting. They suggest that the use of volunteers who come to cancer clinics because of unusual physical changes may compensate for underreporting by the examiners.

The American Dental Association has conducted a health assessment program for dentists registered at its annual meetings for several years. For 7 years (1977-1983) 7,041 head, neck, and oral examinations were made by the dental staff of the Veterans Administration. A total of 484 abnormalities were detected (354 intraoral and 130 extraoral), including 35 leukoplakias, 14 lichen planus, 6 pleomorphic adenomas, 2 melanomas, and 6 myoblastomas intraorally. Extraorally 33 lesions appeared as basal cell carcinomas, 1 as squamous cell carcinoma of the lip, 12 as actinic keratoses, and 2 as melanomas. Seven lesions were confirmed as carcinomas (Goltry and Ayer: JADA 112:338-341, March 1986). -abstracted by H.B.G. Robinson, DDS, MS

Table 1. - The 3,783 oral mucosal and connective tissue lesions found in 23,616 adults are categorized according to each lesion's clinical appearance, and gender-specific prevalence rates per 1,000 people are reported for each category.

Table 2. - The most common oral connective tissue and mucosal lesions are ranked according to location- and gender-specific prevalence rates.

Epidemiology of carcinoma in situ of the upper aerodigestive tract. Bouquot J, Gnepp D. West Virginia University, Morgantown, WV, and St. Louis University, St. Louis, MO, U.S.A.

Reference: J Oral Pathol 1988; 17:433.

Epidemiological analyses of upper aerodigestive tract (UAT) carcinoma in situ are non-existent, hence only hospital records and surgical pathology resources are available for its descriptive characterization. The National Cancer Institute's Surveillance, Epidemiology and End Results investigation has, however, published valuable raw data pertaining to CIS of the UAT. This information is analyzed here and summarized for the first time, demonstrating the following: a male incidence rate which is 4 times greater than the female rate (0.8/1000,000 males versus 0.2/100,000 females); similar ages at diagnosis for both sexes (62.7 and 60.0 years of age for males and females, respectively); no significant urban/rural incidence differences; that CIS represents 2.8% of all UAT malignancies; that 2.0% of all CIS lesions in humans are found at UAT sites; and that CIS of the uterine cervix is not a good model for CIS of the UAT.

Incidence, time trends and follow-up of oral/pharyngeal carcinoma in situ, 1935-1984. Bouquot JE, Kurland LT, Weiland LH. West Virginia University, Morgantown, WV; Mayo Clinic, Rochester, MN

Presented to the International Association of Oral Pathologists in Toronto, Canada, 1986.

The dearth of epidemiologic studies relating to carcinoma in situ (CIS) of the mouth and pharynx has lead to the acceptance of clinicopathologic data for the descriptive characterization of this disease. Such data, however, cannot be said to represent any population beyond that of the particular hospital from which a study originated. Hence, our understanding of this disease is necessarily skewed to the more difficult or unusual cases. The present investigation is the first to offer a clinical characterization of CIS from a pool of patients known to represent virtually all cases of CIS and invasive carcinoma in a stable population (Rochester, Minnesota, 1935-84). The annual incidence of CIS in this population was 2.0/100,000 (3.7 for males; 0.7 for females), compared to a rate of 12.6 invasive carcinomas/100,000 (20.7 for males and 6.8 for females). Incidence of CIS increased with increasing age, to a maximum of 28.3/100,000 for males 75 years of age and older. Time trends of CIS incidence showed no significant change over 50 years. Clinical features and follow-up results will be reported.

This study was supported in part by NIH grand AM30582.

Leukoplakia and carcinoma in situ synchronously associated with invasive oral and oropharyngeal carcinomas in Rochester, Minnesota.

Presented to the American Academy of Oral Pathology, May, 1986.

Gender-specific lip lesion occurrence. Bouquot JE, Gundlach KKH, West Virginia University, Morgantown, WV; University of Hamburg, Hamburg, West Germany.

Reference: Dent Abst 1987; 32:423.

The prevalence of common lip lesions in a Minnesota population of 23,616 white adults older than 35 years of age is reported. Lips were the site of approximately 18.5% of oral mucosal and connective tissue lesions, a point prevalence of 29.6 lip lesions per 1,000 persons examined. Leukoplakia was the most frequent diagnosis (14.5 per 1,000 persons overall; 21.8 per 1,000 males). Labial carcinomas presenting as leukoplakias with or without ulceration occurred in 0.8 per 1,000 persons overall (2.1 per 1,000 males).

The population was biased for age (91% aged 40-70 years), gender (64.1% females), and race (99.5% Caucasians). Gender-specific prevalence rates for 698 labial lesions ranked by frequency of diagnosis are shown in the Table.

The most frequent clinical presentation (46.1% of lesions) was a nonelevated surface change, followed by exophytic masses (33.3%) and vesicles or ulcerations (13.9%). Keratoses accounted for 34.7% of lip lesions and were the most frequent of surface alterations. Hemangiomas were the most frequent of the exophytic lesions.

Approximately 95% of lip leukoplakias were specifically located on the vermillion border, usually of the lower lip (95%). Microscopically confirmed early invasive squamous cell carcinomas (no. = 18) and severe epithelial dysplasias (no. = 12) accounted for 13.7% of lip leukoplakias. All were vermillion lesions in males. Papilloma was the only benign neoplasm diagnosed in this population.

Hemangiomas were almost twice as prevalent in males. Irritation fibromas were the most frequently diagnosed nonvascular masses of the lips, usually occurring in males and on the mucosal surface rather than on the vermillion.

The 59 cases of herpes labialis included active disease only. No attempt was made to obtain a history of recurrent herpes labialis.

The histopathology of Neuralgia-Inducing Cavitational Osteonecrosis (NICO). Bouquot JE, Roberts AM, Person P, Christian J. West Virginia University, Morgantown, WV; New York University, New York, NY

Presented to the International Association for Dental Research in Dublin, Ireland, June, 1989.
Reference: J Dent Res 1989; 68:952.

Recent research has indicated that trigeminal neuralgia (TN) may be related to lesions external to the CNS. This concept is corroborated by the successful treatment of more than 1,800 TN patients via curettage of unusual cavitating osteomyelitis lesions of the jaws. The present investigation is the first to microscopically evaluate and characterize a large number of such lesions. Tissue samples were collected from 126 NICO lesions in the jaws of medically diagnosed TN or atypical facial neuralgia patients, processed routinely, stained with H&E, and reviewed by a pathologist. All lesions demonstrated unusual microscopic features: a densely fibrotic and avascular central core within a highly vascularized connective tissue capsule; numerous angular fragments of necrotic cancellous bone with no evidence of resorption, involucrum or neutrophils (no suppuration); a complete lack of osteoclastic activity with minimal bony remodeling; occasional (n = 3) traumatic neuromas. Various non-specific anaerobic m/o were cultured. Conclusions: NICO cavities are not typical osteomyelitis lesions - actually, salient features of acute or chronic osteomyelitis are seldom seen in NICO tissues. The generalized avascular fibrosis of NICO lesions is most likely the result of abnormal healing or repair of an initiating intraosseous inflammation (periapical pathoses, periodontitis, trauma?), possibly aggravated by an intrinsic bone factor, focal hypoxia, focal immune suppression, or abnormal macrophage function.

Osteomyelitis in 100% of 190 jawbone samples from patients with trigeminal neuralgia and atypical facial neuralgia. Bouquot J, Roberts R, Person P, Christian J. West Virginia University, Morgantown, WV; New York University, New York, NY

Presented to the American Academy of Oral Pathology, San Diego, CA, April, 1990.
Reference: Proceedings of Annual Meeting, American Academy of Oral Pathology, 1990.

Trigeminal neuralgia (TN) now appears to usually result from injury or lesions external to the CNS, most frequently adjacent to the gasserian ganglion.  A recent theory has postulated more distant peripheral nerve injuries within the maxilla and mandible for at least some TN cases, and numerous TN patients have been successfully treated via curettage of unusual, cavitating areas of chronic, nonsuppurative osteomyelitis.  the present investigation is the first to microscopically evaluate and characterize a large number of such jaw lesions.  Tissue samples were collected from 190 mandibular and maxillary lesions in medically diagnosed TN or atypical facial neuralgia patients, processed and stained routinely (H&E), and reviewed by a single pathologist with special training in bone pathology.  All samples demonstrated an avascular and unusually dense fibrosis of marrow spaces.  Also noted: angular fragments of necrotic bone with minimal attempt at resorption; a sprinkling of mature lymphocytes; a lack of histiocytes and neurtrophils; a lack of osteoblastic and osteoclastic activity; a lack of involucrum formation; a lack of normal bone marrow.  This fibrotic osteomyelitis produced irregular and occasionally hollow cavities within the bone, appears to cause degeneration (demyelination?) of adjacent peripheral nerves, is seldom tender but frequently is found in a trigger-point area, frequently yields varied and nonspecific anaerobes on culture, and is thought to be slowly progressive.  We suggest the diagnostic term Neuralgia-Inducing Cavitational Osteonecrosis (NICO) for this entity.

Jaw NICO (Neuralgia-Inducing Cavitational Osteonecrosis) in facial neuralgias. Bouquot J, Roberts A, Person P, Christian J. West Virginia University, Morgantown, WV; New York University, New York, NY

Presented to the 5th Biennial Congress of the International Association of Oral Pathologists, in
Tokyo, Japan, July, 1990.

A recent etiologic theory for trigeminal and atypical facial neuralgia (N & AFN) presumes neural damage some distance from the brain stem, i.e. low-grade chronic osteomyelitis around peripheral nerves in the jaws. The present study analyses clinical, radiographic and histologic features of 619 jawbone samples in 224 TN and AFN patients from 3 WV hospitals. All patients were examined surgically and all had NICO jaw lesions, characterized by nonresorbing fragments of necrotic bone, lymphocytes, few PMNs, very few histiocytes, and frequent cavity formation. A nonspecific mix of anaerobic bacteria were cultured. Cavities were usually located in the molar and bicuspid areas of the mandible or the molar and cuspid areas of the maxilla, and usually coincided with trigger points. Average patient age at NICO diagnosis was 49 years, but young adults were also affected. The majority of cases were in females. Duration of TN or AFN prior to NICO diagnosis ranged from several months to decades. Radiographic evidence of NICO lesions, noted in a majority of cases, included: generalized loss of trabeculae ("anemia bone") in a nonexpansile area of mild to moderate tenderness, complete radiolucency with "moth-eaten" borders, retention of lamina dura after tooth extraction, or thickened trabeculae in a radiolucent background. Many NICO cavities demonstrated little or no radiographic change.

Leukoplakia and smokeless tobacco keratosis are two separate precancers. Bouquot JE, Glover ED, Schroeder KL. West Virginia University, Morgantown, WV, USA

Presented to the 2nd International Congress on Oral Cancer, New Delhi, India, December, 1991

The object of this paper is to demonstrate the clinical and microscopic differences between the white oral mucosal changes resulting from chronic smokeless tobacco use (ST keratosis) and the WHO-defined leukoplakias. Although both are precancerous, the malignant potential for leukoplakia (4%) is several magnitudes greater than that for ST keratosis in the US population (0.5%). And while both are white surface changes, ST keratosis typically presents as a smooth a (perhaps fissured) gray-white, opalescent, velvety macule with a poorly-defined periphery. After its initial onset it usually remains similar indefinitely. Leukoplakia plaques become very definitely white, with distinct borders, and continue to expand laterally over time. They also tend to change appearances, i.e. become nodular and/or "speckled" (erythroleukoplakia) over time.

Leukoplakia lacks the intracellular edema of the superficial epithelial cells which is so characteristic of ST keratosis, a change recently called "surface etching." Epithelial dysplasia is exceeding uncommon in ST keratosis biopsy samples, but is noted in as many as 40% of leukoplakias. Also, ST keratosis occurs only at areas of ST contact and is usually completely reversible after habit cessation; leukoplakia lacks such features.

It is recommended that ST keratosis and leukoplakia be considered as and reported as separate diagnostic names, and different biological behaviors. Such a separation is similar to the one presently distinguishing another tobacco-induced lesion, nicotine palatinus, from leukoplakia.

Bouquot JE, Glover ED, Schroeder KL. Leukoplakia and smokeless tobacco keratosis are two separate precancers. In: Varma AD (ed). Oral oncology. Delhi: MacMillan India, Ltd, 1991; vol 2:67-69.

White keratotic oral mucosal changes resulting from chronic use of smokeless tobacco (ST) have more often than not been referred to in the literature as leukoplakia. This misuse of terminology defeats the very purpose of having different and distinct diagnostic names for various pathologic entities and is, at best, a questionable practice. The authors feel that it is prudent to consider ST keratosis (STK) and leukoplakia as two separate and distinct oral keratotic plaques. While both are undoubtedly premalignant lesions, they have essential and profound differences in etiology, clinical presentation, microscopic features, and prognosis.

Clinical Differences: STK (snuff pouch, snuff dipper's lesion, tobacco pouch) is localized to areas in direct contact with ST. It is often fissured, and is poorly demarcated from surrounding mucosa, but is otherwise quite uniform in consistency. This lesion typically has a soft velvety feel. Inducation, ulceration and pain are not associated with this lesion, but occasional erythema may be noted. This erythema is inflammatory and unrelated to dysplastic change. Once it occurs, STK typically remains unchanged indefinitely unless the daily ST contact increases, in which case it will gradually become thickened to the point of appearing as a distinctly white, leathery or nodular plaque. The latter lesions become clinically indistinguishable from true leukoplakia.

Early and thin leukoplakia may appear similar to STK, i.e. a gray/white soft mucosal plaque which can be semi-translucent. It typically begins, however, as a distinctly outlined white keratosis which extends laterally over time, perhaps also becoming thickened. Some develop irregular thickening and appear nodular, granular, or verruciform. Others develop areas of dysplastic erythema within the white areas. A few in heavy smokers will exhibit an underlying pigmentation (melanoleukoplia), something not yet reported in tobacco chewers.

Age and Gender: Although STK and leukoplakia in Western populations have a similar average age at diagnosis (48-58 years), STK has a biphasic pattern with increased prevalence in young adults and in persons beyond 65 years of age; this prevalence correlates with ST use. Leukoplakia, on the other hand, continues to increase in prevalence throughout life, regardless of the population's tobacco habits. As with age, gender predilection with STK is dependent on the population's use of ST. This usually means a strong male predilection. Leukoplakia also is typically more prevalent among males, especially in older age groups.

Histology: Squamous epithelium in both lesions is hyperplastic and hyperkeratinized, but STK is characterized by intracellular vacuolization or "edema" of superficial layers (perhaps interspersed with streaks of parakeratinized cells, resulting in the typical translucent or edematous clinical appearance. Leukoplakia, on the other hand, is characterized by thickened layers of flattened superficial keratocytes (i.e. excessive parakeratin or orthokeratin) and lacks vacuolization. Both lesions, however, follow a similar chronological pattern of change from normal to mild to severe epithelial dysplasia prior to actual transformation into invasive carcinoma, although the proportion with dysplasia is much greater for leukoplakia than for STK: 13-54% vs. 0-3%, respectively. Both lesions also demonstrate occasional verruciform or chevron structures of superficial epithelium, but such changes in and of themselves are not significant and only the intensity of dysplasia should be considered when determining lesion ‘severity." Hyaline deposition has been noted within connective tissues and salivary glands beneath STK in India, where betel and ereca nut chewing are common habits. Minimal hyalinization is noted in Western ST users, but leukoplakia, even in heavy smokers, never demonstrates such a change.

Etiology: STK is only seen at the site of ST use and routinely disappears after ST habit cessation. The etiology of leukoplakia, however, is entirely unknown. It is true that a high proportion of leukoplakia patients are tobacco smokers, but many are not. Also, actinic rays can produce leukoplakia of the lip vermilion and microorganisms such as candida and human papillomavirus (HPV) have been identified within lesions, although HPV may be more related to the malignant transformation of STK and leukoplakia than to the initial pro9duction of either lesin. Several systemic disease states, such as tertiary syphilis, are associated with leukoplakia but none with STK, except perhaps a deficiency in beta carotene.

Prognosis: The malignant transformation potential of STK has been determined to be only 0.05% per annum in U.S. female textile workers and 0.1% in male Bombay policemen. Previous investigations suggesting malignant potentials as high as 13.8% were based on too few numbewrs of cases to be valid, and larger investigations suggesting an epithelial dysplasia (moderate or severe) rate greater than 16% have used biopsy service samples with their obvious case-selection biases. The largest U.S. STK prevalence study (15,000 persons examined) found not a single malignancy, and the U.S. state with the highest per capita consumption of ST has an oral cancer mortality rate no higher than the national average. A population-based histologic analysis of 1,466 STK lesions among 20,333 ostensibly normal Swedes found no dysplasia in 114 biopsies, likewise for 92 biopsy samples taken from 1109 ST users who were professional U.S. baseball players. No animal investigation has yet produced carcinoma via contact of ST with oral mucosa.

Oral leukoplakia, on the other hand, has a very well-defined malignant potential, ranging from 1-28% (excluding clinical subtypes), with an average of 4% overall. Case-control studies have strongly implicated smoked tobacco and, to a lesser extent, alcohol abuse in the etiology of oral cancer, but such studies have not further correlated white mucosal plaques with malignant transformation. It is not known, then, whether oral cancers in the smokers in epidemiological studies arise from leukoplakias or note. Various clinicopathologic investigations have, however, found leukoplakia in association with 10=60% of oral carcinomas.

           Table 1: Summary of differences between ST keratosis and true leukoplakia.

   * only if patient increases smokeless tobacco use
 ** in Western populations
   # in Indian populations