Clinico-pathological spectrum of oral cavity lesions with their radiological, histopathological, and immuno-histochemistry correlation at a tertiary care teaching hospital: A study of 200 cases

Introduction

The oral cavity is the beginning point of the aero-digestive tract, starting from the lips, which terminates into the oro-pharyngeal isthmus and it is the opening of the oropharynx.1 Oral cavity includes lip, hard palate, soft palate, tongue (anterior two-third), gum (gingiva), buccal mucosa, teeth, retromolar trigone, tonsillar fossa with tonsils, floor of the mouth and minor salivary glands. Oral cavity is more prone and vulnerable to different types of environmental insults, including physical injury (trauma or continuous friction for prolonged duration, e.g., due to ill-fitting dentures) and chemical injury, which initially leads to reversible cell injury, followed by irreversible cell injury to the lining epithelium. Among the chemical injuries, alcohol and tobacco are major risk factors, which release the carcinogenic cytotoxic substance, causing the cancer development with a dose-risk relationship.2

Oral cavity lesions are divided into non-neoplastic lesions and neoplastic lesions, while neoplastic lesions again are further subdivided into benign, premalignant and malignant lesions. Non-neoplastic lesions includes the cases of radicular cyst, dentigerous cyst, odontogenic cyst, tonsillitis, tonsillar hypertrophy. Neoplastic lesions include the cases of pyogenic granuloma (lobular capillary haemangioma), fibroma, mucocele, squamous papilloma, squamous hyperplasia, squamous dysplasia, leukoplakia, squamous cell carcinoma (SCC), verrucous carcinoma.

Among these various oral cavity lesions, oral cancer, specifically SCC, is a major burden in developing countries, including India. It is the third most common cancer in India.3 In India, around 77,000 new cases and 52,000 deaths are reported annually, and day by day the numbers are still increasing.4 As in comparison with western countries, the incidence of oral cancers is quite high in India due to the habit of tobacco chewing.5 Specifically, the low-income population is at high risk and even the cases of females getting oral cancer are increasing. The important thing is that the cases of oral cancer are increasing in the young generation due to various ecological factors, socio-economic status and locality.6

In the present scenario, the majority of the oral cancer patients presented with single or multiple non-healing or refractory oral ulcers and some others had ulcero-proliferative lesions. Early-stage oral carcinoma is often painless and asymptomatic, resulting in a delay in seeking treatment due to delay in diagnosis. This resulted in more than half of oral carcinoma cases being advanced at the time of diagnosis.

Histopathological examination is the gold standard for the diagnosis of oral cavity lesions. Sometimes the biopsy received is very superficial with a lesser amount of deeper stroma hence commenting upon invasion is a difficult task for pathologists and some malignancies cannot be categorized based on light microscopy alone. Immunohistochemistry is helpful in such cases to confirm the diagnosis as well as in certain poorly differentiated carcinomas to confirm an epithelial lineage.

Some of the neoplastic lesions of the oral cavity were very small and deep-seated and were only identified by cross-sectional images of CT or MRI, so in these types of scenarios, radiological investigations were very helpful for early diagnosis and staging of the tumors with a perfect picture of their extension in surrounding structures.7 A chest x-ray was used to detect metastatic lung lesions due to oral SCC. A panoramic x-ray of the mouth (OPG-orthopentogram) was done to assess the teeth and see if cancer had spread to the jaw. Ultrasound was used to assess metastatic lymphadenopathy in the neck. In cases of tongue SCC, MRI with contrast was obtained in various anatomical planes which was the optimal modality, displaying exquisite anatomical detail including intrinsic and extrinsic muscles, the floor of the mouth, and the lingual vascular bundle. An MRI scan can detect whether oral cancer has spread to the soft tissue of the head and neck, including brain tissue. A special dye may be used to enhance the images. Thus, thorough radiological analysis further guides the treatment needed for the patient.

In the cases of late diagnosis of oral malignancies, the surgical treatment option may be the local wide excision with radical neck dissection, which has a bad impact on the patient’s personal, social and professional life. So early diagnosis and treatment are very important for the good quality of life and thus reduce the overall morbidity and mortality associated with the oral cavity lesions & specially cancers.

Aims and Objectives

Materials and Methods

Results

The present study was conducted on 200 cases of the oral cavity lesions.

The most involved age group was 41 to 50 years, followed by 31 to 40 years. The age of oral cavity lesions ranged from 4 years to 84 years. In the less than 20-year-old age group, many of the lesions were non-neoplastic (Table 1).

Out of total 200 cases, 139 (69.5%) were males and the remaining 61 (30.5%) were females, with a male-to-female ratio of 2.27:1 (Table 2).

The most common site of the oral cavity lesion was buccal mucosa (46.5%), followed by the tongue (19.5%) (Table 3).

The oral cavity lesions were classified as non-neoplastic and neoplastic lesions and neoplastic lesions were further subdivided into benign, premalignant and malignant lesions based on the histopathological diagnosis. Out of 200 cases, 19 cases (9.5%) were of non-neoplastic lesions, 29 cases (14.5%) were of benign lesions, 50 cases (25%) were of pre-malignant lesions and 102 cases (51%) were of malignant lesions of the oral cavity. Neoplastic lesions specifically malignant lesions were more common as compared to non-neoplastic lesions in the oral cavity (Table 4).

In the non-neoplastic lesions, out of 19 cases, most of the cases were of radicular cysts (total 05 cases). In the benign lesions, many of the cases were of squamous hyperplasia (total 05 cases). In the premalignant lesions, 42 cases of dysplasia, 07 cases of leukoplakia, and 1 case of dysplastic leukoplakia were seen. In the malignant lesion, the most common malignancy was oral SCC (total 99 cases), followed by two cases of verrucous carcinoma (Table 5).

The youngest case was of a 4-year-old female child diagnosed with bilateral tonsillar hypertrophy. The oldest case was of an 84-year-old male who was diagnosed with the well-differentiated SCC of the tongue.

The most common presentation of malignant lesions of the oral cavity was ulcero-proliferative growth in the buccal mucosa (Figure 1).

Figure 1

Ulcero-proliferative growth of oral SCC on the left buccal mucosa

An MRI and CT scan of the oral cavity showed extensive thickening and enhancement of the buccal mucosa (Figure 2).

Figure 2

MRI and CT image of the oral cavity show extensive thickening and irregular enhancement of the right buccal mucosa

Almost all cases of oral SCC were associated with some form of addiction, either alcohol and/or tobacco consumption in the form of gutka, pan masala, betel nuts, smoked tobacco (Table 6).

In the present study, the maximum number of oral SCC cases were seen in the 41 to 50-years-old age group, but the overall age range for oral SCC was very wide, which was 21 to >80 years. Six cases of oral SCC were seen in the 21–30-year age group, and 25 cases of oral SCC were seen in the 31-to-40-year age group. Table 6 shows many cases of oral SCC in the younger age group & these were associated with addiction of long duration.

In one case, the H&E-stained slide showed large pleomorphic cells in sheets with a hyperchromatic nucleus and moderate eosinophilic cytoplasm, suggestive of poorly differentiated SCC (Figure 3).

Figure 3

Poorly differentiated SCC (H & E * 10X)

IHC for p63 was done and was positive, confirming the diagnosis of poorly differentiated SCC (Figure 4).

Figure 4

p63 positivity in oral poorly differentiated SCC (IHC *40X)

In one case, the H&E-stained slide shows acantholysis, multinucleation, moulding, intranuclear inclusions and nuclear margination, which was suggestive of herpes simplex infection (Figure 5).

Figure 5

HSV infection in oral cavity (H & E *10X)

In one case, the H&E-stained slide shows hypercellular Antoni A areas and hypocellular Antoni B areas with Verocay bodies formation, which was suggestive of Schwannoma (Figure 6).

Figure 6

Histopathology of Schwannoma (H & E * 40X)

In another case CT scan of soft palate showing growth (Figure 7).

Figure 7

CT image of non-Hodgkin’s lymphoma of the soft palate

The H&E-stained slide shows infiltrative atypical cells, which were mononuclear, having clumped chromatin, inconspicuous nucleoli and scant cytoplasm with areas of inflammation. These findings were suspicious for non-Hodgkin’s lymphoma of the soft palate. IHC was positive for CD45, CD 19 and CD 20, which confirmed the diagnosis of NHL (Figure 8).

Figure 8

Histopathology and IHC marker positivity in a non-Hodgkin’s lymphoma of the oral cavity

Discussion

This was the prospective as well as retrospective study done to analyse the spectrum of the oral cavity lesions.

The age range of the present study was from 4 years to 84 years, while the mean age was 44 years. In the present study most common age group was 41 to 50 years which is quite like other studies including Gupta I et al.,3 Dholakiya Z et al11 and Patro P et al.,12

Oral cavity lesions were more common in males as compared to females, with a male-to-female ratio of 2.27:1, which is quite like the study done by Gupta I et al.3 Male predominance has been noted in most of the studies due to increased tobacco consumption. In this study, the percentage of affected male subjects was 69.5%, and the remaining 30.5% were female, while in the Bhagat R et al.,8 study, the affected males were 60% and females were 40%.

Buccal mucosa (46.5%) was the most common site involved in the present study, followed by the tongue (19.5%), which is quite like many of the other studies, but in the study of Agrawal R et al.,10 the most common site was the tongue (29.32%), followed by buccal mucosa (27%). (Table 7)

The Table 7 shows almost similar observations of the present study with other authors with respect to age group, M:F ratio & most common site of oral cavity lesions.

In the present study, out of 200 cases, 102 cases (51%) were malignant, while in the Bastakoti S et al.,9 study, 55.5% of cases were malignant.

As we look upon the development of the oral SCC, most of them arose from squamous dysplasia or carcinoma in situ and few cases arose from dysplastic leukoplakia if the tobacco consumption was continued.

Oral SCC is classified as well differentiated carcinoma, moderately differentiated carcinoma and poorly differentiated carcinoma, based on the level of differentiation of squamous cells and keratinization. In the case of poorly differentiated SCC, p63 IHC marker was done to confirm an epithelial lineage of squamous cells. Total 10 cases were positive for p63 IHC markers in the present study. We also received 1 case of a sarcomatoid variant of oral SCC.

Total 02 cases of verrucous carcinoma (1%) have been observed in the present study, which was like the Bhagat R et al.,8 study (1.9%). One case of non-Hodgkin’s lymphoma was noted in the present study; similar cases were also observed in the Bhagat R et al., study.8

In the present study, the most common malignant lesion of the oral cavity was oral SCC. Out of 102 cases of oral malignant lesions, 99 cases were of squamous cell carcinoma (SCC), and the most common site was the buccal mucosa for oral SCC. These results were like the Sakpal et al.,13 and Kak M et al.,14 studies, while the most common site for oral SCC in the Pires FR et al.,15 study was the border of the tongue, followed by the alveolar mucosa/gingiva/retromolar area. The maximum number of oral SCC cases were seen in the 41 to 50-year-old age group, but the overall age range for oral SCC was very wide, which was 21 to >80 years.

Conclusions

Any oral cavity lesion in the form of unresolved lesions (patch, thickening, ulcers, and/or non-healing ulcers) or mass found at any age should be thoroughly evaluated (clinical history & examination) and if indicated, a biopsy should be taken for the final diagnosis. Radiological correlation should be done, which is very helpful in many of the deep-seated and small oral cavity lesions and to know the extent of the lesion. Histopathological examination is the gold standard of investigation for the diagnosis. IHC of the oral lesions is helpful in confirming the diagnosis and categorization of the malignant lesions in a few cases.

If the lesion is pre-malignant or malignant, its early detection is good for the patient. For example, if the lesion is premalignant, then early intervention may prevent the development of malignancy. And if the lesion is malignant, then some advanced cancers in the oral cavity need a major operation (like wide local excision with radical neck dissection) as a treatment option that ends with marked disfigurement of the face of the patient, which has a bad impact on the patient’s personal, social, and professional life.

Hence, early and proper diagnosis with appropriate intervention can prevent progression to malignant lesion and reduce the overall morbidity and mortality associated with oral cavity cancer.

Awareness regarding the harmful effects of alcohol and tobacco consumption should be done regularly in the community (in schools, colleges, towns, villages, etc.) in different ways. Health facilities can plan camps for mass screening of oral cavity lesions in society, which should be done regularly.

Source of Funding

None.

Conflict of Interest

None.