How to cite: Martínez-Martínez A, Díaz Caballero A, Quintero-Echenique N,. Malignant and premalignant lesions of the tongue, clinical and

histopathological findings for their early detection. Study of two cases. Ciencia e Innovación en Salud. 2020. e73:59-67.

DOI 10.17081/innosa.73

Malignant and premalignant lesions of the tongue, clinical and

histopathological findings for their early detection. Study of two cases

Adel Martínez-Martínez

*, Antonio Diaz-Caballero

, Natalia Quintero-Echenique

University of Cartagena. Cartagena, Colombia.

Address correspondence to: amartinezm4@unicartagena.edu.co

ABSTRACT

Background: Squamous cell carcinoma affects subjects between the sixth and seventh decade of life.

However, there are growing reports on the involvement of young adults. Clinical Cases: Two male patients

aged 40 and 55, with no history of tobacco consumption and occasional alcohol consumption. They

presented an exophytic ulcer and a white plaque on the lateral border of the tongue, the first diagnosed as

moderately differentiated squamous cell carcinoma without HPV DNA genotypes and the second as

leukoplakia without dysplasia. Conclusions: Risk factors commonly associated with potentially malign

disorders and oral cancer, such as smoking and alcohol consumption, were not involved in the present

cases. Therefore identify clinical, histopathological and molecular findings, allows the early detection of

them, improving the prognosis of these patients.

Keywords: Carcinoma, Squamous Cell; Mouth Neoplasms; Oncovirus; Papillomaviridae; Leukoplakia,

Oral; young adult.

Article History

Received: 15 10 19

Accepted: 09 03 20

Published: 05 06 20

I. INTRODUCTION

Oral cancer is the 11th most common cancer in the world; this includes

cancers of the lips, tongue, gum, floor of the mouth, palate, and mouth.

The squamous cell carcinoma (SCC) is the most frequent of the

malignant neoplasms of the oral cavity, according to WHO corresponds

to more than 90% of all malignant lesions in the mouth and the 3% of all

cancers (1,2). This is a significant cause of morbidity and mortality in

patients with head and neck cancer. This neoplasm is generally more

frequent in male than in the female. In general, SCC affects subjects

after their fifth decade of life (3). A significant increase in pathology has

been reported in young adults (4), among whom patients < 30 years old

are considered (5), some authors have as criteria to define young

patients those under 45 years old (6). The incidence in this population

ranges from 0.4% to 13% (7-9), although the data varies according to

the country, in the UK it is reported 6% (10) and India between 16 and

28%(11). Its worldwide distribution is unequal, being more incident in

Eastern Europe and South Asia, in the United Kingdom, it is rare cancer.

In Latin America, it occurs in countries such as Uruguay, Brazil and

Argentina. In Colombia, there are around 100 to 120 new cases of oral

cancer for a year, mainly affecting men, patients over 60 years of age

and associated with common risk factors (12). The most common sites

of SCC is the lateral border of the tongue, 70% of these neoplasms

involved the lateral border, followed by the floor of the mouth and a lower

frequency by the soft palate, gingiva and buccal mucosa (13,14).

DOI10.17081/innosa.73

Martínez-Martínez

et al.

The consumption of tobacco (70%) and alcohol (36%) are the main risk factors among older

patients, however in the young population, less than half of the patients consume tobacco or

alcohol, which suggests the presence of other etiological factors (15). Other habits have also

been associated with SCC, such as chewing betel leaves, inverted smoking, oral thrush, use of

mouthwash and mate. Factors such as diet and nutrition, radiation, ethnicity, familial and genetic

predisposition, immunosuppression, syphilis, dental factors, occupational risks and infectious

proliferative process caused by human papillomavirus (HPV) are also considered

(16,17,18,19,20). The International Agency for Research on Cancer in 2007 accepted that human

papillomavirus (HPV) type 16 was a risk factor for tongue and tonsillar cancer (21). The clinical

characteristics vary from the case and include the exophytic forms such as verrucous or papillary

form when it starts its growth stage. In early stages, it presents as ulcerous lesions, keratosic

plaques: erythroplasia, leukoplasic, or erythroleukoplakia forms. These lesions may cause painful

symptoms depending on their extent and/or location, usually they are painless when they affect

the ventral side and lateral edges of the tongue, so they can go unnoticed by the patient (22).

Some authors report about the changing epidemiology of tongue squamous cell carcinoma

(TSCC), recent reports indicating an increasing incidence in young women. These authors

reported that most areas experienced an incidence increase ranging from 0.4% to 3.3% per year

and in patients under 45 years old the incidence of TSCC was higher, compare with patients over

that age (23). Comparing some industrial countries such as UK, Denmark and Netherlands with

USA, France, Italy, Germany and Hong Kong, the firsts one the prevalence of squamous cell

carcinoma was expanded (24). The World Health Organization in 2010 reported that 2 per

100,000 people died in the Middle East, but in USA and India the rate was not that high (25). The

radical primary surgery is the treatment of choice, using a free tissue transfer reconstruction

where indicated. When the tumor invasion is over 3 mm, a selective neck dissection must be

done, with a 0.5 cm margin of normal tissue. In elderly patients, who usually have some

associated co-morbidity and even their lifestyle, based in nowadays oral cancer treatment makes

difficult to have a prognosis, although those patients can die for a different reason than cancer

(26,27).

II. CLINICAL CASES

First case. A 40-year-old male was seen at the Stomatology Clinic, Department of Oral

Medicine, University of Cartagena Dental School, for presenting a tumoral growth in the tongue.

The patient reported a tumoral growth in lateral edges of the tongue for the last 6 months,

without smoking habit and alcohol consumption. Sexual habits that include oral sex are

reported. The patient reports a history of cancer in the family, a maternal grandmother died

from cancer of the cervix as well as a paternal uncle due to gastric cancer. The patient said

have noticed a white plaque, of unknown evolution, asymptomatic, on the lateral border of the

tongue, which did not receive treatment. The physical examination was found a patient with a

good nutritional status, oriented in person, space and time, good health condition with controlled

arterial hypertension. When palpating the ganglion chains no affected lymph nodes were

evident. Intraoral clinical examination showed ulcer with exophytic borders located on the left

side of the tongue, which extends to ventral and dorsal surfaces, with raised and indurated

edges, asymptomatic, 1.0 x 1.0 cm. Whitish plaques are observed on the ventral surface and

ipsilateral mouth floor, there is evidence of vegetations in areas near the edge of the ulcerative

lesion. With six months of evolution, other mucous membranes were within the normal range

(figures 1a and b).

Figure 1a: A localized ulcer is observed on the lateral border of the tongue, left side, with extends to

the ventral surface and the dorsal surface, with raised and indurated edges, asymptomatic, of 1.0 x

1.0 cms. Note the white plaques in the tongue ventral face and the ipsilateral mouth floor, there is

evidence of vegetations near the edge of the ulcerative lesion. 1b: On the tongue ventral side adjacent

to the ulcer, white and asymptomatic plaques are observed, with do not detach from shaving and from

unknown evolution. In the exophytic edge of ulcerative lesion, vegetation is observed, in the form of

cauliflower, white, asymptomatic with a rough surface.

No presence of palpable ganglion chains in the neck and submaxillary and submental region.

An incisional biopsy of the lesion is performed, including in the sample apparently healthy

margins. A part of the sample is sent for detection of HPV genotypes by real-time PCR and

another part for anatomopathological study. The histopathological result reveals ulcerated oral

mucosa with tumor lesion of epithelial lineage characterized by a proliferation of large cells of

hyperchromatic nuclei that are arranged in solid and infiltrating nests, with individual

keratinization, surrounded by a fibrous stroma with chronic inflammatory infiltrate. The

histopathological diagnosis was squamous cell carcinoma of large cells, moderately

differentiated, infiltrating and ulcerated (figure 4). The pathological study reported cellular

changes compatible with dysplasia, nuclear hyperchromatism, pleomorphism and atypical

mitosis (figures 2 a, b and c).

The real-time PCR evaluated the presence of 29 genotypes in the sample sent, 19 of high risk,

among which genotypes 16 and 18 were evaluated and nine of low risk (genotypes 6,11,42,54),

were not identified HPV genotypes in the sample sent. The patient is referred to oncological

surgery of head and neck who performs partial hemiglosectomy with superficial ipsilateral neck

emptying. The patient in the six months control after the surgical procedure is without clinical

signs of recurrence of the neoplasm, the figures 5a and b show the immediate and six months

postoperative (figure 3 a and b).

Figures 2: 2a. The histopathological section shows the cellular characteristics of the malignancy:

nuclear hyperchromatism, pleomorphism and atypical mitosis. 2b. Observe the loss of the normal

architecture of the oral epithelium. 2c. The invasion of the epithelial cells within the connective, with

zones of keratinization around these, is visible in this section.

Figure 3: 3a. Immediate postoperative, of incisional biopsy, showing adequate opposition of tissues

in the intervened area. 3b. 6-month control. Observe the adequate healing of the intervened tissue. It

is evident the plaque of whitish border, center hypochromic, asymptomatic, with no induration,

compatible with leukoplakia.

Second case. A 55-year-old male was seen at the Stomatology Clinic, Department of Oral

Medicine, University of Cartagena Dental School, for presenting a white plaque in tongue. The

patient reported a tumoral growth in lateral edges of the tongue for the last six months, without

smoking habit and alcohol consumption. The physical examination was found a patient with a

good nutritional status, oriented in person, space and time, good health condition without any

clinical background. When palpating the ganglion chains no affected lymph nodes were evident.

Intraoral clinical examination showed ulcer with exophytic borders located on the right ventral

surface side of the tongue, with raised and indurated edges, asymptomatic, 3 mm x 3 mm.

There is evidence of white plaque in areas near the edge of the ulcerative lesion, with 6 months

of evolution, other mucous membranes were within the normal range (figure 4a).

An incisional biopsy of the lesion was performed, including in the sample apparently healthy

margins for an anatomopathological study. The histopathological result reveals oral mucosa

with an intraepithelial lesion with gout shaped epithelial ridges, hyperplasia and hypercellularity

in the basal stratum, without dysplasia, and with hyperkeratosis and papillomatosis. The own

sheet shows chronic inflammation. The histopathological diagnosis was leukoplakia without

dysplasia (figure 4b). A surgical excision was practiced, keeping the patient in controls for 1

year without showing recurrence.

Figure 4: 4a. localized ulcer is observed on the ventral surface of the tongue, right side, with raised

and indurated edges, asymptomatic, of 3 x 3 mm. Note the white plaque in areas near the edge of

the ulcerative lesion. 4b. The histopathological section does not show the cellular characteristics of

the malignancy: Intraepithelial lesion with gout shaped epithelial ridges, hyperplasia and

hypercellularity in the basal stratum, without dysplasia, and with hyperkeratosis and papillomatosis.

III. DISCUSSION

Oral squamous cell carcinoma corresponds to more than 90% of oral cancer diagnoses, is

commonly associated with risk factors such as smoking and alcohol, without ignoring the

hereditary factor. The tongue cancer nowadays has increased, significantly between 1973 and

2012 (0.6% annual increase), more specifically in young white women even though the used of

tobacco decreased in the USA.(28). Regarding the age group, squamous cell carcinoma is a

rare disease in patients under 45 year of age, mainly affecting subjects between the fifth and

sixth decade of life However, there are reports of cases of oral carcinomas in young adults,

without the risk factors commonly associated with neoplasia (29-30). Adorno-Farías et al (31),

report a case of verrucous carcinoma in the tongue in a 60-year-old patient without known risk

factors, just like in the present report. These authors also conducted a review of cases in the

period between January 1984 and October 2010, reporting 20 cases of warty carcinoma in

patients with an average age of 70.7 years, verrucous carcinoma with clinical and histological

particular characteristics, affects primarily the male sex between the fifth and seventh decade

of life, with is why it differs from the present report. In young adults relationship between

malignancy and HPV infection associated with sexual contact pathway (orogenital) has been

reported, without conclusive data considering the virus as an etiological factor (32,33). Many

studies show that HPV DNA is present in a considerable number of squamous cell carcinomas

but it represents a distinct entity with many doubts to be solved regarding the casual relationship

between the virus and carcinoma (34). Chen X et al, recommend the use of makers such as

P16 and HPV genotypes as test for the detection of HPV in patients with squamous cell

carcinoma. The human papillomavirus is considered an etiological factor of this pathology an

even for oral premalignant disorders (34). Kouketsu A et al, reported and expression in 24

subjects of the P16 protein of 174 subjects evaluated with squamous cell carcinoma, with the

most prevalent subtypes being 16 and 18. This authors conclude that HPV has a minor role in

oral oncogenesis in patients Japanese in this report, HPV genotypes associated with neoplasia

were not found (35). Falaki F et al. in 2011 published a retrospective study of patients diagnosed

with squamous cell carcinoma, received in the last 13 years in a health care center in Iran. of

the 158 cases of squamous cell carcinoma diagnosed, 21 patients were young adults under 40

years of age, 12 of them males. In the group of patients studied there were no significant risk

factors associated, the tongue was the most common site of presentation, with exophytic ulcer

being the most common clinical lesion. HPV DNA was not detected in these patients. All the

data of the studied population are coincident with the case in this report, highlighting the non-

presence of common risk factors and the non-detection of HPV DNA (12) (36).

IV. CONCLUSIONS

Associated findings at the white plaques or erosive lesions in the lateral borders of the tongue,

must caught the attention of the clinical professional when are present in young patients without

the habits that are commonly associated with oral squamous cell carcinoma.

It is important a well detailed clinical history that reveal data of the background of this lesions,

how they have been treated and how often do they show up, furthermore it has to be considered

the biopsy to determinate the presence of dysplasia changes in the evaluated tissue, not

forgetting the immunohistochemical studies to determinate oncogenesis such as P16 and

stablished a prognosis of the lesions evaluated. The best prognosis of oral cancer it is given by

the early diagnosis.

Ethical revelation. The authors declare that no experiments were performed in humans or

animals for this study.

Confidentiality of data. The authors declare that they have followed the protocols of their work

center on the publication of patient data.

Right to privacy and informed consent. The authors have obtained the written informed

consent of the patients or subjects mentioned in the article.

Authors contribution: "Conceptualization, Adel Martínez-Martínez. Antonio Diaz-Caballero.;

methodology, Adel Martínez-Martínez. Antonio Diaz-Caballero.; software, Antonio Diaz-

Caballero.; validation, Adel Martínez-Martínez.; formal analysis, Adel Martínez-Martínez.

Antonio Diaz-Caballero. Natalia Quintero-Echenique.; research, Adel Martínez-Martínez.

Antonio Diaz-Caballero.; resources, Antonio Diaz-Caballero.; data healing, Antonio Diaz-

Caballero.; writing: preparation of original draft, Adel Martínez-Martínez.; writing: review and

editing, Adel Martínez-Martínez. Natalia Quintero-Echenique.; viewing, Adel Martínez-

Martínez. Natalia Quintero-Echenique.; supervision, Adel Martínez-Martínez project

management, Antonio Diaz-Caballero.; fund acquisition, Antonio Diaz-Caballero. All authors

have read and accepted the published version of the manuscript."Yes”

Acknowledgements. To our patient who today allows us to learn from her case.

Conflicts of interest. The authors declare no conflict of interest.

About the authors.

Adel Martínez-Martínez. Oral Surgeon, Assistant Professor, Department of Oral Medicine, Gitouc

Investigation Group, Faculty of Dentistry, University of Cartagena. Cartagena, Colombia. email:

amartinezm4@unicartagena.edu.co.

Antonio Diaz-Caballero. Periodontist, Titular Professor, Department of Oral Medicine, Director of

the Group Investigation Group, Faculty of Dentistry, University of Cartagena. Cartagena, Colombia.

email: adiazc1@unicartagena.edu.co.

Natalia Quintero-Echenique. Resident, Stomatology and Oral Surgery, Gitouc Investigation Group,

Faculty of Dentistry, University of Cartagena. Cartagena, Colombia. email:

nquinteroe@unicartagena.edu.co.

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