ARTÍCULO CLÍNICO

 

Tumor depth in squamous cell carcinoma of the tongue. Diagnostic repercussions

Profundidad tumoral en el carcinoma epidermoide lingual. Repercusiones diagnósticas

 

 

J.D. Sánchez López², M.A. Sicilia Gutiérrez¹, L.M. Capitán Cañadas¹, I. Labrot Moleón¹,
S. Martínez-Villalobos Castillo², E. Valencia Laseca³

1 Médico Especialista en Formación.
2 Médico Adjunto.
3 Jefe de Servicio.
Servicio de Cirugía Oral y Maxilofacial. Hospital de Rehabilitación y Traumatología. Granada, España

Dirección para correspondencia

 

 

---

ABSTRACT

Objective. To determine the degree of concordance between clinical (cT) and histopathological (pT) values for tumor size in squamous cell carcinoma when introducing "tumor thickness" as a diagnostic marker.
Materials and methods. 1) Design: A retrospective hospital study of 60 patients evaluated between January 1990 and July 1997 was carried out. 2) Variables: Patient dates, clinical and histopathological parameters. 3) Statistics: Correlation assessment by Kappa Index (p<0.05).
Results. After the use of "tumor thickness" as a diagnostic indicator the following can be appreciated:
• Correlation between cT and ppT: Reduction in the degree of concordance between cT and pT in relation to ppT (23.3 /12.5%).
• Correlation between pT and ppT: 100% concordance between pT4 and ppT4. All tumors diagnosed as pT3 were changed to ppT4.
Conclusion. When the parameter "tumor thickness" is used, a change can be appreciated in the early stage clinical and histopathological diagnosis, as tumor size (T) becomes advanced.

Key words: Tongue tumor; Prognostic factors.

---

RESUMEN

Objetivo. Determinar el grado de concordancia entre la valoración clínica (cT) e histopatológica (pT) del tamaño del carcinoma epidermoide lingual en relación a la introducción del parámetro de profundidad tumoral (ppT).
Material y métodos. 1) Diseño: Estudio retrospectivo de base hospitalaria constituido por 60 pacientes evaluados desde Enero de 1990 a Julio de 1997 (Seguimiento mínimo de 8 años). 2) Variables: Filiación del paciente, parámetros clínicos y parámetros histopatológicos. 3) Método estadístico: Correlación mediante el Indice Kappa (p< 0,005).
Resultados. Tras la aplicación del parámetro "profundidad tumoral" se aprecia:
• Correlación entre cT y ppT: Disminución del grado de concordancia entre cT y pT en relación con ppT (23,3 y 12,5%).
• Correlación entre pT y ppT: Concordancia del 100% entre pT4 y ppT4. Todos los tumores pT3 pasaron al estadío ppT4.
Conclusión. Cuando se aplica el parámetro de profundidad tumoral se aprecia un desplazamiento del diagnóstico clínico e histopatológico hacia estadíos más avanzados.

Palabras clave: Carcinoma lingual; Factores pronósticos.

---

 

Introduction

Epidermoid carcinoma, or squamous cell carcinoma, is an entity that most commonly presents in the oral cavity or oropharynx. Although it has a lower incidence than other cancers of the body, its importance lies in the high level of mortality it causes, and the serious disturbance produced in the patient as a result of either the tumor itself or the treatment. ¹

In the series published in the United States, the tongue is the area where half of all intraoral carcinomas arise. This is followed by the floor of the mouth with a prevalence of 35%.² Sixty-sixpercent of lingual carcinomas will affect the posterolateral portion of the tongue, while the ventral and anterior portion is affected in approximately 20% of cases. Although most patients are men, the incidence of lingual carcinoma in women has increased considerably from 15% in the 30’s to 40% in the 80’s.

Oral carcinoma is a typical disease of middle age, although when it affects young people, it will arise most commonly in the tongue. Over recent years an increased tendency can be appreciated in this respect,³ in particular in Belgium, Germany, Spain and in Eastern European countries. ⁴

Recent studies⁵ have shown the limited global survival rate at five years, which is lower than 50%, as a result of late diagnosis. Also, uncontrolled metastatic dissemination to the neck has a mortality of 85%, and it should be kept in mind that in its clinical evaluation, even with the support of imaging studies, only 68% of cases are detected.^6,7 Tumor location,⁸ tumor size,⁹ and tumor depth¹⁰ are the principal factors that will ascertain the risk of neck involvement.

The purpose of establishing a universally accepted oral cancer classification, is that of obtaining groups of similar patients, that are therefore equivalent from the statistical point of view, which will permit unifying criteria when diagnosing and treating these cases.

The first classification of malignant tumors was the TNM classification by Pierre Denoix (1944) based on the extension of the primary tumor (T), regional node involvement (N) and the presence of distant metastasis (M).

It is currently accepted that the two systems for classifying TNM were developed by the IUAC (International Union Against Cancer)¹¹ and the AJCC (American Joint Committee on Cancer),¹² both being similar. The TNM system is a valid tool for elaborating a diagnostic and treatment approach. It includes a classification prior to therapy (cTNM) based on clinical examination and imaging techniques, and another postsurgical classification (pTNM), that includes the data obtained after the histopathologic study of the surgical specimen.

Tumor depth is the parameter that has acquired over the last decade the greatest relevance as a predictive factor for prognosis, ever since its importance was demonstrated in studies that were considered "classic".¹³

The importance of these parameters was emphasized in 1969 by the German- Austrian-Swiss group (DÖSAK). In the year 1986, Platz¹⁴ and in 1992, Howaldt¹⁵ established by means of multivariate analysis statistically significant differences in patients with primary tumors that were greater than 5 mm in depth, regardless of their anatomic location and size. In 1992, Howaldt et al,¹⁵ in the name of the DÖSAK group, and based on a multivariate analysis of 2806 patients, proposed a new classification of the T category defining four sizes (Table 1).

 

The importance of the DÖSAK database was noted by the TNM World Committee, as this classification was included in the new TNM classification proposals in 1993¹⁶ (Table 2). In the new TNM classification of the AJCC,¹⁷ registering maximum tumor thickness is recommended, although to date this has not been incorporated into the staging classification. In the future, when confirmatory multicentric studies are more numerous, this could be recognized as one of the specific and unique aspects of the TNM system for the oral cavity, and its prognostic capacity will be perfected.

 

 

In consonance with this tendency, our study shows this diagnostic discrepancy, which is therefore also contained in the classification of squamous cell carcinomas of the tongue, when the tumor depth parameter is introduced.

 

Objectives

Principal objectives

To determine the degree of concordance between the clinical evaluation (cT) and the histopathologic evaluation (pT) of squamous cell carcinoma of the tongue in relation to the introduction of the variable "tumor depth" (ppT).

Secondary objectives

1. To evaluate the diagnostic and prognostic repercussions of tumor depth.

2. To consider the introduction of the parameter tumor depth as a diagnostic and prognostic element in every day clinical practice.

 

Material and method

Design

This was a hospital-based retrospective study with a cohort made up of patients diagnosed and treated for squamous cell carcinoma of the tongue between January 1990 and July 1997, with 1997 taken to be the final year of the study (minimum follow-up period of 8 years).

For this 120 clinical records were revised, and 60 were selected according to the following criteria:

1. Patients with squamous cell carcinoma of the tongue as first intraoral tumor.
2. Surgery was initial treatment.
3. Established tumor-free surgical margins.
4. Access to the medical records and paraffin block of the tumor.

The gathering of data obtained from the corresponding medical records was carried out by a single observer and the histopathologic evaluation of the surgical specimen was supervised independently by two pathology specialists, who had no previous knowledge of the characteristics of the patient nor of the tumor.

Variables

Characteristics of the patient: age (quantitative variable) and sex (dichotomic variable). The age of the patient relates to their age on their first visit to the department of Oral and Maxillofacial surgery, which is the age given to the member of the department carrying out the clinical records, or the age given by one of the members of the Oncological committee.

Clinical parameters: Pre- and post-surgical size of the primary tumor (cT and pT) and postsurgical tumor size after the introduction of the tumor depth variable (ppT) considered ordinal variables.

The parameters that make up tumor size (cT and pT) were taken according to the nomenclature published by the UICC and AJCC jointly in 1993, and the resulting parameter after the introduction of maximum tumor thickness (ppT), according to the modifications obtained after the application of the multivariate system of the DÖSAK group.

Histopathologic parameters: Tumor depth, considered a quantitative variable. Maximum tumor thickness was taken to be the measurement by the pathologist, in his description of the surgical specimen or, in those cases (especially before 1994) in which this parameter was not included in the histopathologic analysis, this was reevaluated by the same pathologist for inclusion in the study. The measurements were taken in a vertical sense from the surface of the tumor, and those areas corresponding to inflammation or keratinization were excluded.

Laboratory procedures

The histological specimens were processed by the department of Pathological Anatomy at the same hospital center by means of fixation in 10% formol for 12-24 hours. A macroscopic description of the sample, and sectioning of the specimen, was carried out and it was stored in paraffin blocks, which were classified according to registry number, block number and year at the time.

The measurement of tumor depth was carried out in a micrometric manner on the specimen, in such a way that if this was completely infiltrated, the measurement of tumor depth coincided with the diameter of the specimen, while if the tumor was excrescent, this measurement would be taken from the baseline, or without infiltrations, to the deepest area or layer.

Statistical procedures

A univariate analysis was first carried out of the whole sample that consisted of a frequency and descriptive analysis (position and dispersion measurements) according to the nature of the variables included. A bivariate analysis was then carried out for determining the degree of correlation, by establishing the Kappa Index (p<0.05).18 The level of statistical significance was p<0.05.

The analysis of the data was carried out by means of the SPSS 11.5 statistical package.

 

Results

Univariate descriptive study

Personal data details: 26.66% were females and 73.34% were males. Mean age 58, age range 67 (88-21) and 14 was the standard deviation.

Tumor size: cT, pT and DÖSAK. The high number of tumors corresponding to T1 (23.3%) and T2 (50%) stands out, and this index remains practically constant after the histopathologic study of the surgical specimen. (Table 3)

Bivariate analytical study

Degree of concordance between cT and DÖSAK (ppT): The introduction of the concept of depth in the analysis of the surgical specimen reveals a notable descent in the clinical- histopathologic concordance of T2 tumors, while only 23.3% of those carcinomas that were classified as cT2 corresponded to this histopathologic category. This was particularly significant in cT3 tumors, with a concordance of only 12.5%. 72.7% of ppT3 tumors, were erroneously diagnosed clinically as cT2.

The cT4 category had the greatest level of concordance (62.5%) after the application of the tumor depth parameter (Table 4).

Degree of concordance between pT and DÖSAK (ppT). In Table 5 those carcinomas that histopathologically were typed as pT4 continued staying in this category after tumor thickness was established. On the other hand, all those that had been classified as pT3 became ppT4.

This change can be appreciated if we observe how the greatest percentage of ppT4a carcinomas (50%) were diagnosed initially as pT3. The pT2 category also underwent a notable change as, after the introduction of the DÖSAK parameter, 64.7% were classified as ppT3. It was also observed that once tumor depth had been determined, all ppT3 were diagnosed erroneously as pT2.

 

Discussion

As has been demonstrated previously in the Introduction, the TNM system, despite being undeniably useful as a method that allows the standardization and unification of the different neoplasms of the head and neck, does not represent a procedure that permits predicting efficiently the prognosis of oral and oropharyngeal carcinoma, as it depends on a series of histopathologic, local clinical, cervical clinical and therapeutic factors that are not included in this classification.¹⁹

The TNM system provides a classification for oral and oropharyngeal carcinomas, as descriptive factors are included such as tumor size (T), neck involvement (N) and distant metastasis (M), which in other words, is a topographic and clinical description of the lesion. On the other hand, tumor staging entails adapting the information provided by the TNM classification to one of the four stages proposed (EI, II, III, IV) with the aim of categorizing the tumor into a series of groups that are as homogenous as possible with regard to tumor behavior, prognosis and treatment. In this sense, the limitations of the TNM system are evident, as it is based on clinical examination and the application of imaging studies in order to evaluate the lesions (CAT, MRI).²⁰

The concept of tumor depth refers to the maximum thickness of the tumor in millimeters, which is determined by means of micrometric perpendicular measurements from the surface of the tumor to the deepest point of the tumor invasion, excluding the keratin area and inflammatory exudate.²¹ It represents a variable that defines tumor quantity, but that at the same time introduces a qualitative aspect with regard to the aggressiveness of local infiltration. This responds to the clinical variability of tumors, as two tumors with the same superficial diameter (10 mm) and with thicknesses that are as different as 5 mm and 20 mm, cannot be considered the same. The first would be a T1 tumor, while the second, after applying the DÖSAK proposal would be a T3 tumor.

In this study we have noted marked discordance in the classical typing of tumor size (cT and pT) in relation to the introduction of maximum tumor thickness (ppT), and an increase in stages ppT3 and ppT4a can be appreciated at the expense of a descent in the cT2 and pT2 stages.

As previously mentioned, typing tumor size from the clinical point of view is based on visual and tactile analysis, which provide bidimensional information on the size of the tumor. It is because of this that when tumor size is introduced into the evaluation, size is evaluated tridimensionally, with the result that there is a displacement towards stages ppT3 and ppT4 in detriment to stages cT2 and pT2.

The routine use in our center of the imaging studies previously mentioned (CAT and MRI) has numerous limitations given that the muscles of the tongue are hypointense, identifying tissue planes is difficult,²² and extensive tumors frequently exhibit loss of homogeneity. These limitations are more obvious when there is a notable change in clinical tumor size from advanced stage (cT3/cT4) towards early histopathologic stage (pT2/pT3), as on certain occasions, tumor dissemination towards the floor of the mouth with peripheral infiltration of mylohyoid muscles, or involvement of the sublingual gland and obstruction of Wharton’s duct, is indistinguishable from an inflammatory or infectious process associated with the tumor.²³

When tumor depth is considered a diagnostic element, the change in the tumor size classification to more advanced stages corroborates the fact that tumor aggressiveness is an intrinsic characteristic of the tumor itself, as it depends on the extension and depth of the tumor, a factor that is not taken into account in the current TNM classification. Thus, a neoplasm that is clinically limited topographically, with no invasion of adjacent structures, is traditionally classified as early stage (EI-EII), while with the introduction of the tumor thickness parameter, it would be considered as advanced stage, with the resulting therapeutic and prognostic modifications. These results are in consonance with those obtained by the DÖSAK group in 1986, 1991 and 1992, who emphasized the fact that maximum tumor thickness has the capacity for modifying T classification, based on the fact that numerous T2 and T4 would become T3 with the introduction of this parameter. But, at the same time, numerous T3 that are deeply infiltrated, have a worse prognosis than those classified as T4.

What we have exposed clearly shows the need for incorporating "maximum tumor thickness" as a routine diagnostic element in daily clinical practice. For this, unifying measurement criteria is necessary, so that it can be accessed by most centers. In our study, tumor thickness was established by the pathologist in such as way that if the tumor specimen were to be completely infiltrated, the depth measurement would coincide with the diameter of the specimen. When the tumor was excrescent or ulcerated, the distance between the baseline, or line without infiltration, to the deepest layer was taken as a reference. This method is currently used in squamous cell carcinomas of the head and neck by other authors.^7,21

Other methods for determining tumor depth based on imaging procedures such as ultrasound,²⁴ high resolution ultrasonography or RMI,²⁵ have a very limited application in our field as they entail greater diagnostic costs, and highly specialized staff are required, yet greater reliability in tumor depth value is not achieved.

Including tumor depth when classifying tumor size (T) and stage (E) would represent a new therapeutic approach for squamous cell carcinoma of the oral cavity as, when (T) is modified, the treatment given is considerably affected, as is prognosis with regard to survival.⁹

 

Conclusions

1. The introduction of the tumor depth parameter in the diagnosis of squamous cell carcinoma of the tongue modifies the initial diagnosis of tumor size (T) towards more advanced stages.

2. Given the therapeutic and prognostic implications, it should be considered as a routine diagnostic factor in the typing of squamous cell carcinoma.

3. Adopting this in daily practice requires a uniform measuring system that is accessible to pathologists.

 

 

Dirección para correspondencia:
José Darío Sánchez López
C/ Martínez Campos 23, 6ºB
18002 Granada, España
E-mail: dario@fundacionhvn.es

Recibido: 18.04.05
Aceptado: 06.10.06

 

References

1. Boring CC, Squires TS, Tong T. Cancer Statistics. Cancer J Clin 1994;44:7-26.        [ Links ]

2. Neville BW, Damm DD, Allen CM, y cols. Epithelial Pathology. En: Oral and Maxillofacial Pathology. Philadelphia, Wb Saunders 1995; 416-42.        [ Links ]

3. Moore SR, Johnson NW, Pierce AM y cols. The epidemiology of tongue cancer: A review of global incidence. Oral Diseases 2000;6:75-84.        [ Links ]

4. Ferlay J,Bray F, Pisani P, y cols. GLOBOCAN: Cancer incidence mortality and prevalence worldwide, version 1.0. IARC Cancer-Base No. 5 Lyon, IARC 2000.        [ Links ]

5. Parkin DM, Whelan SL, Ferlay J, y cols. Cancer Incidence in Five Continents. Vol VIII. IARC Scientific Publications No. 155 Lyon, IARC 2000.        [ Links ]

6. Umeda M, Yokoo S, Take Y, y cols. Lymph node metastases cell carcinoma of the oral cavity: Correlation between histologic features and the prevalence of metastasis. Head Neck 1993;14:263-72.        [ Links ]

7. Woolgar JA. T2 carcinoma of the tongue: The histopathologist´s perspective. Br J Oral Maxillofac Surg 1999;37:187-93.        [ Links ]

8. Million RR, CassiniNJ, Wittes RE. Cancer of the head and neck. En: De Vita VT, Hellman S, Rosenberg SA (eds). Cancer 1990. Principles and Practice of Oncology. Philadelphia: Lippincott, pp. 407-506.        [ Links ]

9. Shah JP, Andersen PE. The impact of patterns of nodal metastasis in modifications of neck dissection. Ann Surg Oncol 1994;1:521-32.        [ Links ]

10. Spiro RH, Huvos AG, Wong GY, y cols. Predictive value of tumor thickness in squamous carcinoma confined to the tongue and floor of the mouth. Am J Surg 1986;152(4):345-50.        [ Links ]

11. Beltrani CA, Desinan L, Rubini C . Prognostic factors in squamous cell carcinoma of the oral cavity. A retrospective study of 80 cases. Pathol Res Pract 1992;188: 510-10.        [ Links ]

12. Ilstad ST, Tollerud DJ, Bigelovw ME. A multivariate analysis of derminants of survival for patiens with squamous cell carcinoma of the head and neck. Ann Surg 1989;209:237-42.        [ Links ]

13. Mohit-Tabatabai MA, Sobei HJ, Rush BF et al. Relation of thickness of floor of mouth stage I and stage II cancers to regional metastasis. Am J Surg 1986; 152:351-53.        [ Links ]

14. Platz H, Fries R, Hudec M. DÖSAK German (Austrian). Swiss Association for Head and Neck Tumors. Prognose of oral cavity carcinomas: results of a multicentric retrospective observational study. Carl Hanser Verlag, München-Wien 1986; pp 12-123.        [ Links ]

15. Howaldt HP, Frenz M, Pitz H. Proposal for a modified T-classification for oral cancer. J Cranio-Maxillo-Facial Surg 1992;21:96-101.        [ Links ]

16. Hermanek P, Henson DE, Hutter RVP, y cols. TNM Suplement. International Union Against Cancer. Springer-Verlag Berlin 1993; pp23-24.        [ Links ]

17. Henson DE, Hutter RVP, Kennedy BJ. Manual for Staging of Cancer. American Joint Committee on Cancer. Fifth ed. JB. Lippincott, Philadelphia 1997; pp34-36.        [ Links ]

18. Altman DG. Practical statistics for medical research. Chapman and Hall: London, 1991.        [ Links ]

19. Urist MM, O’Brien CJ, Soong SJ, y cols. Squamous cell carcinoma of the buccal mucosa: Analysis of prognostic factors. Am J Surg 1987;154: 411-4.        [ Links ]

20. Vokes EE, Weichselbaum RR, Lippman SM. Head and neck cancer. New Engl J Med 1993;328:184-94.        [ Links ]

21. Yuen APW, Lam KY, Chan ACL, y cols. Clinicopathological analysis of local spread of carcinoma of tongue. Am J Surg 1998;175:242-4.        [ Links ]

22. Million RR, Cassini NJ, Mancuso AA. Oral cavity. En Million RR, Cassini NJ (eds): Management of Head and Neck Cancer. ed 2. Philadelphia, JB Lippincott, 1994, pp 321-400.        [ Links ]

23. Mancuso AA. Imaging in patients with head and neck cancer. En: Million RR, Cassini NJ (eds). Management of Head and Neck Cancer. ed 2. Philadelphia, JB Lippincott, 1994, pp 43-59.        [ Links ]

24. Shintani S, Nakayama B, Matsuura H, y cols. Intraoral ultrasonography is useful to evaluate tumor thickness in tongue carcinoma. Am J Surg 1997;173:345-47.        [ Links ]

25. Iwae H, Kyomoto R, Ha-Hawa SK, y cols. Magnetic Resonance determination of tumor thickness as predictive factor of cervical metastasis in oral tongue carcinoma. Laryngoscope 2002;112:457-61.        [ Links ]