In Brazil, incidence of malignant neoplasias of the oral cavity is substantially varied in different regions and this fact is probably due to local features concerning prevalence of risk factors1. Many risk factors are related to oral squamous cell carcinoma etiology, among which tobacco, betel, alcohol, virus and diet are included. These factors are associated with genetic inheritance and may have a carcinogenic effect on normal cells of respiratory and digestive systems2. Oral squamous cell carcinoma may occur anywhere in the mouth, although the most affected sites are tongue, lower lip and floor of the mouth. Features of these regions greatly facilitate carcinoma spreading to regional lymph nodes and/or distant organs3.

In patients with head and neck carcinoma, the prognosis is usually obtained based on TNM clinical classification, which is highly useful, specially to assess essential features of cancer, such as local extension, regional dissemination and distant metastasis4.

Patient's prognosis and survival5 may be determined with this system, which must include details of local anatomical characteristics to obtain data on grade of tumor involvement, as well as on distant metastases. However, the use of other prognostic markers is fundamental, once it helps to plan treatment and estimate patient's survival, which most of the times is reduced due to local recurrence or early lymph node metastases, added to existence of inaccurate prognostic factors6,7. Histological staging of the deepest parts of oral squamous cell carcinoma directly influences patient's survival, once neoplastic cells in this site appear to be undifferentiated when compared to other tumor regions, constituting a valuable prognostic mean. Histological staging systems are very important, once they highlight the histopathological characteristics and the immunological relationship between tumor and host, predicting lesion's behavior in face of patient's response8,9. Many studies were carried out to confirm correlation between clinical and histological parameters and prognosis. Keratinization grade, nuclear pleomorphism, number of mitoses, invasion mode and lymphatic infiltration were used by many authors as histopathological characteristics studied in superficial areas of tumor11. Byrne, in 1989, using the same histological markers (except for number of mitoses), suggested histological staging in invasive margins of lesion once he considered it to be the most representative region of neoplasia11.

Dib, Sabba (1994)10 have studied the medical records of 59 patients with oral squamous cell carcinoma between the period of 1960 and 1980. Histological and clinical variables such as sex, age, clinical staging (TNM) and presence of palpable lymph nodes were observed. These authors verified that clinical stage I patients presented higher overall survival rate, while those of clinical stage IV had lower survival. Moreover, tendency to keratinization and tumor thickness presented statistically significant correlation with overall survival10. On the other hand, other authors in similar studies - except for the idea that only the most invasive parts were to be graded - concluded that the invasion pattern was the histological staging system that had the most important correlation with clinical parameters, such as metastasis and recurrence7,11.

Therefore, it was verified that this type of staging studies is more complex due to the heterogeneous features between oral squamous cell carcinoma subtypes and different behaviors this tumor has in different areas of oral mucosa. Furthermore, some clinical variables are not taken into account or investigated by the professional that performs the anamnesis of cancer patient. Considering that, this research study aimed at correlating TNM clinical classification with histopathological characteristics (keratinization grade, nuclear pleomorphism, invasion pattern and lymphoplasmocitary infiltrate) and the histological malignancy scores in 38 cases of oral squamous cell carcinoma in deep areas of the lesion, as described by Bryne (1998)9.

Based on data analysis of 38 patients with oral squamous cell carcinoma presented in this study, the sample consisted of: 55.26% (21 cases) of men and 44.75% (17 cases) of women (Figure 1) between the ages of 40 and 93 years. The most prevalent age range was 51 to 60 years, represented by 57% of the cases (12 patients) (Figure 2).

Figure 1.

Number of patients distributed by gender.

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Figure 2.

Number of patients distributed by age range.

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Regarding the anatomical site of the lesion, it was observed that the side border of tongue was the most affected region in 50% of the sample (19 cases), followed by the lower lip - 26.31% (10 cases), and floor of the mouth - 13.15%, (5 cases). Other areas such as the upper lip (2.63%), jugal mucosa (2.63%), oral pharynx (2.63%), and tongue center (2.63%) were also affected, summing 10.52% (4 cases) of the sample (Figure 3).

Figure 3.

Number of patients distributed by anatomical site.

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Concerning TNM clinical staging, 14 patients were classified as stage IV, 11 as stage III, 5 as stage II and 8 as stage I (Figure 4).

Figure 4.

Number of patients distributed by TNM clinical stage.

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As results using Tukey's statistical test were analyzed, a significant correlation was observed among combinations of TNM clinical stages when related to the following histopathological parameters: degree of keratinization (p = 0.05) and nuclear pleomorphism (p = 0.02). The same correlation was also verified with the average histological score (p = 0.01) (Table 2).

The statistical analysis of variance revealed that the degree of keratinization (p = 0.025), nuclear pleomorphism (p = 0.016) and average malignancy score (p = 0.001) had statistically significant correlation with TNM clinical staging (Table 3). Pearson's test showed correlation between the average histological scores and the isolated variables of TNM clinical staging (p < 0.005) (Table 4).

When TNM clinical stages were grouped into two series - I/II and III/IV - and related with the histopathological variables using the Q-square test, a correlation between these groups and the lymphoplasmocytic infiltrate (p = 0.016) and nuclear pleomorphism (p = 0.004) (Table 5) was also observed.

Prognosis of patients with oral squamous cell carcinoma is significantly varied due to different histological types and clinical features of this entity. Analysis of the TNM system and the histological staging has been adopted to plan treatment and provide better evaluation of patient's evolution. Patients with advanced tumors have poor prognosis, in which regional metastasis is the most important prognostic indicator12,13.

Some clinical findings are discussed in this study to elucidate the relation between the events and the aspects approached, as well as to give rise to reflections that may contribute for new investigations.

Regarding clinical data, the sample showed that 55.26% of patients (21 cases) were men and that the cases within the 50-70-age range were the most affected ones (25 cases). No patients under 30 years old were registered, which is consistent with the literature available (Figures 1 and 2)4,10,14–17.

Concerning anatomical, the side border of tongue (19 cases) followed by the lower lip (10 cases) were the most affected regions, which is in accordance with the data reported by other studies4,18,19 (Figure 3).

TNM clinical classification is one of the most used systems to predict the prognosis of oral squamous cell carcinoma. However, there are some divergences concerning tumor staging. It is a fact when dealing with primary tumors that advanced cases with infiltration of adjacent structures are hardly accessed at clinical examination20,21. Regardless of the limitation of TNM clinical staging, its accuracy is around 70 to 80%. This percentage is higher when complementary exams, such as computed tomography and magnetic resonance, are used for classification and staging of neoplasias20. It is perfectly feasible to admit that results obtained by histological assessment are more accurate in prognostic settlement than essentially clinical exams, once microscopic findings provide information on events that are previous to those of clinical nature.

In order to assess an eventual correlation of TNM clinical staging with histological malignancy parameters and the average score proposed in our trial, a descriptive statistical analysis was conducted demonstrating statistically significant correlation between them4,9,22–24 (Table 2). However, these results changed when a variance analysis of independent histological parameters was performed in relation to the grade of TNM clinical staging, showing that invasion pattern (p = 0.119) was the only parameter that had no significant statistical relation with TNM clinical stage (Table 3).

The statistical analysis by Pearson's correlation test straightens the results of the statistics of variance, once there was correlation between the average histological scores and the clinical variables of TNM clinical staging (p < 0.005) when observed isolated9,22 (Table 4).

The histological parameter “invasion pattern” is a valuable prognostic factor, once it reflects the capacity of cohesion of neoplastic cells23, suggesting that well-differentiated neoplasias invade within a well-defined margin pattern, while more anaplastic tumors infiltrate as small cell aggregates or isolated cells19. We understand that this explains its correlation with the prognosis.

Regarding TNM clinical stages of 38 cases distributed by I/II and III/IV groups and its relation with histological variables, a significant correlation was observed in these groups with lymphoplasmocytic infiltrate (p = 0.016) and nuclear pleomorphism (p = 0.004). These results may translate the possible effect of TNM clinical staging over tumor histological behavior, once III/IV patients presented poorer histological behavior. Contrary to our findings, Lopes et al. (2002)15 observed that the keratinization degree (p < 00.1) is the best histological parameter to determine the entity's clinical behavior and the risk of developing regional metastasis. In addition, the authors also verified that T1/T2N+ tumors presented high percentage of neoplastic cells with plentiful nuclear pleomorphism (p < 0.05), while T3/T4N0 tumors showed “invasion pattern” histological parameter in small-cell like groups in 65% of the cases (Table 5).

Histological staging of the most invasive margin, as suggested by Bryne (1998)9 and adopted in our trial, provides the best prognostic information on the neoplasm. Differently from former systems in which only the superficial part of the tumor was observed25–27, this author provides the pathologist9 with thorough information on anaplastic cells behavior.

By the end of our study, we concluded that keratinization degree, nuclear pleomorphism and lymphoplasmocytic infiltrate are strongly correlated to TNM clinical staging. The latter is strongly associated with malignancy scores, constituting important prognostic indicator. Therefore, there was statistically significant correlation between clinical staging (TNM), histological staging and malignancy scores.