Potentially malignant epithelial oral lesions - Wiley Online Library

Oral Diseases (1997) 3, 148–152  1997 Stockton Press All rights reserved. 1354-523X/97 $12.00

Potentially malignant epithelial oral lesions: discrepancies between clinical and histological diagnosis MA Onofre, MR Sposto, CM Navarro, MESFM Motta, E Turatti, RT Almeida Oral Medicine Service, Department of Diagnosis and Surgery, School of Dentistry of Araraquara, UNESP, 14801–903 Araraquara, SP, Brazil

OBJECTIVE: To evaluate the discrepancy index between the clinical and histological diagnosis and the prevalence of epithelial dysplasia and carcinoma in 45 patients with potentially malignant epithelial oral lesions (PMEL). PATIENTS AND METHODS: We submitted 45 patients with PMEL to clinical examination and obtained a biopsy from each. The results of histological diagnosis were compared to the clinical diagnosis. RESULTS: Clinical diagnosis showed that the most common PMEL was leukoplakia followed by lichen planus and by actinic cheilitis associated with leukoplakia. The most common site was the buccal mucosa. Histological diagnosis revealed that 46.7% of the PMEL were lichen planus. The discrepancy index between clinical and histological diagnosis was 24.4%. The higher discrepancy index occurred among leukoplakias. The prevalence of epithelial dysplasia and carcinoma was 17.8%. CONCLUSIONS: We conclude that all PMEL should be submitted to a microscopic analysis because the discrepancy between clinical and histological diagnosis was present in a quarter of these lesions. Otherwise, the epithelial dysplasia and carcinoma were more frequent in the leukoplakias. Keywords: leukoplakia; lichen planus; diagnostic errors; discrepancy index; oral diagnosis

Introduction According to the World Health Organization (WHO), a precancerous lesion is characterised by morphologically changed tissue in which the occurrence of cancer is more probable. This definition suggests that malignant transformation of changed mucosal sites is statistically more probable, though not necessary (Speight and Morgan, 1993). In our view the term ‘precancerous lesion’ should not be used since not all lesions become malignant. Thus these changes of the mucosa must be referred to as potentially malignant epithelial lesions (PMEL) (Eveson, 1983; Johnson et al, Correspondence: MA Onofre, Department of Diagnosis and Surgery, School of Dentistry of Araraquara, UNESP, Rua Humaita´, 1680, 14801– 903 Araraquara, SP, Brazil Received 17 December 1996; revised 21 and 23 March 1997; accepted 23 March 1997

1993). These lesions include leukoplakia, erythroplakia, lichen planus and actinic cheilitis. The prevalence of oral leukoplakia in the American and Swedish population ranges from 2.9 to 3.6% (Bouquot and Gorlin, 1986; Axe´ll, 1987). Epidemiological data obtained from the rural population of India have shown prevalences of 0.2–4.9% (Pindborg, 1981). The prevalence of lichen planus is lower than the prevalence of leukoplakia and ranges from 0.1–2.2% (Bouquot and Gorlin, 1986; Jungell, 1991). Retrospective studies in which tissue samples were examined in pathology laboratories have shown a prevalence of 5.5–6.2% for leukoplakia (Tinoco and Salazar, 1975; Waldron and Shafer, 1986), and of 3.4% for lichen planus (Moncarz et al, 1993). In a previous clinical study conducted on 512 patients with oral mucosal complaints seen at the Oral Medicine Service of the School of Dentistry of Araraquara, Brazil, during the 1989–1992 period, the prevalence of leukopakia was 6.6%, the prevalence of actinic cheilitis was 2.7%, and the prevalence of lichen planus was 2% (Afonso et al, 1994). Leukoplakias undergo malignant transformation in 0.13– 25% of cases, the average being about 5% (Pindborg, 1981; Bouquot and Gorlin, 1986; Lind, 1987; Bouquot, 1991; Frame, 1992). Clinically, leukoplakia may present the homogeneous form which has a lower risk of malignant transformation and the non-homogeneous form which has a higher risk (Bańoćzy and Csiba, 1976; Pindborg, 1981; Williams, 1990; Bouquot, 1991; Speight and Morgan, 1993). Actinic cheilitis may present areas of leukoplakia associated or not with atrophic areas, fissures and superficial erosions. A biopsy of these areas may reveal dysplastic cellular characteristics and often invasive carcinomas (Pindborg, 1981; Bouquot, 1991). Lichen planus is clinically classified as reticular, erosive/ulcerated, atrophic, papular and plaque-like. Retrospective studies have shown that a small percentage (0.4– 2.7%), of these lesions undergo malignant transformation (Fulling, 1973; Silverman et al, 1985; Sigurgeirsson and Lindelo¨f, 1991; Vouˆte et al, 1992; Moncarz, 1993), which is often associated with the erosive form (Lind et al, 1985; Holmstrup et al, 1988; Moncarz et al., 1993; Barnard et al, 1993). Although the literature shows that PMEL may exhibit dysplasia or malignancy, in practice only 26% of all leukoplakias are biopsied (Bouquot and Gorlin, 1986). The same occurs with lichen planus, whose diagnosis is often defined

Diagnosis of potentially malignant epithelial lesions MA Onofre et al

only on the basis of the clinical aspects which can lead to misdiagnosis (Eisenberg and Krutchkoff, 1992). Therefore it is necessary to evaluate through examples the magnitude of the discrepancy between the clinical and histological diagnosis. The objective of the present study was to evaluate the discrepancy index between the clinical and histological diagnosis and the prevalence of epithelial dysplasia and carcinoma associated with the PMEL.

Patients and methods The records of 1888 patients seen at the Oral Medicine Service, Araraquara Dental School, State of Saõ Paulo, Brazil, from 1991 to 1995 were reviewed in a retrospective study. Among the 143 patients with PMEL, 45 who had been submitted to biopsy were selected for the present study. Twenty-two patients were male and 23 females, 39 were white, four were black and one was yellow, the mean age was 53.3 years (range: 15–85). The remaining 98 patients were excluded from the study because they refused to be submitted to a biopsy. A history was taken from each patient and all were submitted to oral examination. The clinical diagnosis were: (a) homogeneous leukoplakia—a predominantly white uniform flat lesion, thin appearance that may exhibit shallow cracks and has a smooth, wrinkled or corrugated surface with a consistent texture throughout; (b) non-homogeneous leukoplakia—a predominantly white or white and red lesion that may be irregularly flat, nodular or exophytic. The nodular lesions have slightly raised, rounded, red and/or white excrescences and the exophytic lesions may have irregular or sharp projections; (c) erythroplakia—a velvety red lesion that could not be diagnosed as any other lesion; (d) reticular lichen planus—a predominantly white lesion with intertwining lines or striae that confer a lacy or annular aspect; (e) erosive and/or ulcerated lichen planus—a predominantly red, irregular, erosive or ulcerated lesion frequently associated with the reticular form, especially in the peripheral region. A fibrinous pseudomembrane may be present, covering the ulcerated areas; (f) actinic cheilitis plus homogeneous leukoplakia— fine or desquamating mucosa lip vermilion with ill defined margins and with a white and uniform plaque in patients with a history of regular and prolonged exposure to sunlight; (g) actinic cheilitis plus non-homogeneous leukoplakia—fine mucosa of the lip vermilion with a white plaque associated with red, nodular, fissured, exophytic, erosive or ulcerated areas covered with a crust in patients with a history of regular and prolonged exposure to sunlight. Small lesions approximately 1 cm in size were submitted to excisional biopsy with a small safety margin. Lesions larger than 1 cm were submitted to incisional biopsy at several sites, preferentially in erythematous, verrucous and indurated areas. The lesions were histologically classified as: (a) benign keratosis: presence of various degrees of keratosis and/or acanthosis with no epithelial dysplasia or cellular atypia; (b) epithelial dysplasia: we used the parameters recommended by the WHO (1978) which include loss of polarity of the basal cells, the presence of more than one

layer of cells having a basaloid appearance, an increased nuclear-cytoplasmatic ratio, drop-shaped rete processes, irregular epithelial stratification, increased number of mitotic figures (a few abnormal mitoses may be present), the presence of mitotic figures in the superficial half of the epithelium, cellular pleomorphism, nuclear hyperchromatism, enlarged nucleoli, reduction of cellular cohesion, keratinization of single cells or cell groups in the prickle layer. The dysplasias were classified as mild, moderate and severe; (c) squamous cells carcinoma: severe dysplasias involving the entire extent of the epithelium without invasion of connective tissue (in situ carcinoma) or with invasive of connective tissue (invasive carcinoma: initial or frank) (WHO, 1978; Pindborg et al, 1985); (d) lichen planus: based on indispensable criteria for diagnosis (liquefying degeneration of basal cells, band-shaped lymphocyte infiltrate in the connective tissues intimately mixed with the basal cell region of the epithelium) and on additional aspects (sawtooth-shaped epithelial projections, hyperkeratosis and presence of Civatte bodies, and separation between epithelium and connective tissue) (Krutchkoff and Eisenberg, 1985; Hatchuel et al, 1990); (e) lichenoid dysplasia: this entity includes histological characteristics of epithelial dysplasia associated with the histological characteristics of lichen planus (Krutchkoff and Eisenberg, 1985; Hatchuel et al, 1990). When the multiple biopsies were taken we considered the most severe histological diagnosis as the final result. The results of the histological diagnosis were compared with clinical diagnosis. We established the histological diagnosis incompatible with the clinical diagnosis when the clinical diagnosis was not confirmed. Clinical diagnosis (b), (c) and (g) were suspicious of epithelial dysplasia or squamous cell carcinoma. On the basis of incompatible diagnosis, we calculated a discrepancy index (DI) between the clinical and histological diagnosis. This index and the prevalence of epithelial dysplasia and squamous cell carcinoma were calculated using the following formulae: Discrepancy index (DI) = Prevalence =

number of incompatible diagnosis × 100 total sample

number of cases of epithelial dysplasia and carcinoma × 100 total sample

Results Table 1 shows data about the patients studied. Clinically the leukoplakia (homogeneous and non-homogeneous) were the most frequent lesions followed by lichen planus (reticular and erosive/ulcerated) and actinic cheilitis (plus homogeneous and non-homogeneous leukoplakia). No cases of erythroplakia were observed. The majority of the patients presented lesions at many sites in the oral mucosa and the buccal mucosa was the most common location. A mouth burning sensation was reported in 62.5% of the lichen planus and 37.5% of leukoplakias. The histological diagnosis presented in Table 2 showed that the majority of the lesions were lichen planus. Three initial squamous cells carcinoma and one in situ carcinoma were found in the non-homogeneous leukoplakia and actinic cheilitis plus non-homogeneous leukoplakia. One

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150

Table 1

Distribution of patients with PMELs by clinical diagnosis, sex, and anatomical location

Clinical diagnosis

Patients n

Sex M/F

Anatomical location*

%

Buccal mucosa

Lip vermilion

Palate

Mouth floor

Tongue

n

Gingiva (alveolar mucosa) n

n

n

n

n

– 3 1

– 2 – – –

Homogeneous leukoplakia Non-homogeneous leukoplakia Reticular lichen planus Erosive/ulcerated lichen planus Actinic cheilitis plus homogeneous leukoplakia Actinic cheilitis plus non-homogeneous leukoplakia

12 10 09 08 02

26.7 22.2 20.0 17.8 4.4

4/8 7/3 3/6 2/6 2/0

6 3 7 7 –

8 2 4 2 –

2 1 1 2 2

1 4 – – –

04

8.9

4/0

–

–

4

–

Total

45

100

22/23

23

16

12

5

– 4

2

*In some patients the lesions were present at more than one anatomical location

Table 2

Distribution of PMELs according to histological and clinical diagnosis

Clinical diagnosis

Histological diagnosis Lichen planus

Benign keratosis

Squamous cell carcinoma

Epithelial dysplasia

Lichenoid dysplasia

Ulcerated papilloma

DI

n

%

n

%

n

%

n

%

n

%

n

%

n

%

Homogeneous leukoplakia (n = 12)

3*

25

9

75

–

–

–

–

–

–

–

–

3

(25)

Non-homogeneous leukoplakia (n = 10)

2*

20

3*

30

3

30

2

20

–

–

–

–

5

(50)

Reticular lichen planus (n = 9)

9

100

–

–

–

–

–

–

–

–

–

–

–

–

Erosive/ulcerated lichen planus (n = 8)

7

87

–

–

–

–

–

–

1*

12.5

–

–

1

(12.5)

Actinic cheilitis plus homogeneous leukoplakia (n = 2)

–

–

2

100

–

–

–

–

–

–

–

–

–

–

25

1

25

1

25

–

–

1*

25

2

(50)

33.3

4

8.9

3

6.7

1

2.2

1

2.2

11

(24.4)

Actinic cheilitis plus nonhomogeneous leukoplakia (n = 4) Total (n = 45)

–

–

21

46.7

1* 15

*Cases incompatible with the most probable clinical diagnosis DI = Discrepancy index

case of epithelial dysplasia was mild and two moderate. The DI between clinical and histological diagnosis was 24.4%. The prevalence of epithelial dysplasia and squamous cells carcinoma was 17.8%. The higher DI was found in non-homogeneous leukoplakias and actinic cheilitis plus non-homogeneous leukoplakias.

Discussion Our results agree with the literature by showing that the most common PMEL is leukoplakia (Bouquot and Gorlin,

1986; Bouquot, 1991; Frame, 1992; Afonso et al, 1994). Clinically these lesions represented 48.9% of the sample analysed. The male/female proportion for lichen planus was 2.4/l, in agreement with the literature (Holmstrup and Pindborg, 1979; Silverman et al, 1985), whereas actinic cheilitis occurred exclusively among males. The occurrence of a local burning sensation was more frequent for lichen planus both in its reticular and erosive and/or ulcerated form. The most frequent sites of PMEL were the buccal mucosa, gingiva (alveolar mucosa) and lip vermilion. According to Bouquot and Gorlin (1986), 75% of all leukoplakias are detected in these regions. Lichen planus can be


found anywhere in the oral mucosa, but the most common sites are the buccal mucosa, gingiva and tongue (Silverman and Griffith, 1984; Silverman et al, 1985; Jungell, 1991). The histological diagnosis showed that the lichen planus was the most frequent PMEL. We found a DI of 24.4%. The higher DI was detected among the homogeneous and non-homogeneous leukoplakias. Histological analysis showed five cases clinically diagnosed as leukoplakia were in fact lichen planus. Upon clinical characteristics, these lichen planus appeared as white plaques without a lacy aspect, and therefore were diagnosed as leukoplakias. These lesions presented burning mouth sensation, which may be an important symptom for the differential diagnosis between leukoplakia and plaque-like lichen planus since these two lesions are clinically similar. There was some concern about a particular case with a clinical diagnosis of actinic cheilitis plus non-homogeneous leukoplakia which resembled verrucous carcinoma. This lesion presented a slightly raised, verrucous, ulcerated and indurated surface. These aspects, taken together with the use of tobacco and exposure to the sun, led us to suspect malignancy, but the histological diagnosis was ulcerated papilloma. In four cases with a clinical diagnosis of non-homogeneous leukoplakia and actinic cheilitis plus non-homogeneous leukoplakia, for whom we expected the presence of epithelial dysplasia or squamous cell carcinoma, histological diagnosis revealed benign keratosis only. A case clinically diagnosed as erosive lichen planus and histologically confirmed as lichenoid dysplasia also contributed to the increase in the DI. The differential diagnosis between lichen planus and lichenoid dysplasia is only possible by microscopic analysis since the two conditions share some clinical characteristics (Krutchkoff and Eisenberg, 1985; Eisenberg and Krutchkoff, 1992). The prevalence of epithelial dysplasia and squamous cell carcinoma was 17.8% in PMEL. Waldron and Shafer (1975) observed a prevalence of 19.9%, where Bańoćzy and Csiba (1976) and Bouquot and Gorlin (1986) reported 25%. These differences between the results are probably due to the methodology employed and to the populations analysed in the different studies. Among the 14 cases clinically diagnosed as non-homogeneous leukoplakia and actinic cheilitis plus non-homogeneous leukoplakia, half were epithelial dysplasia or carcinoma. However, epithelial dysplasia and carcinoma were not found in cases of homogeneous leukoplakia and actinic cheilitis plus homogeneous leukoplakia. There was only one lichenoid dysplasia in the 17 cases clinically diagnosed as lichen planus. Our results agree with those reported by Pindborg (1981) and Silverman et al (1976) confirming the non-homogeneous leukoplakia as the main lesion of epithelial dysplasia onset (Bańoćzy, 1977). In summary, the diagnosis of PMEL only based on clinical characteristics may lead to misdiagnosis and therapeutic errors. A biopsy is particularly important in leukoplakias because these lesions present the higher frequency of dysplasia and malignancy. All PMEL should be submitted to a microscopic analysis because the discrepancy between clinical and histological diagnosis was presented in a quarter of these lesions.

Acknowledgements Supported by CNPq, Brazil, Grant No. 523164/96–3 Brazil. We are indebted to the ‘Ma´rio AS Paino’ Laboratory of Clinical Pathology; Mr Antonio Medeiros Filho and Mrs Maria dos Santos Vieira for technical assistance.

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