- Email: [email protected]
Mode of invasion and outcome in squamous cell carcinoma of the oral tongue
International Congress Series 1240 (2003) 695 – 700
Mode of invasion and outcome in squamous cell carcinoma of the oral tongue Roge´rio A. Dedivitis * Department of Otorhinolaryngology, Head and Neck Surgery of Universidade Metropolitana de Santos ‘Unimes’, Rua Olinto Rodrigues Dantas, 343 conjunto 92, 11050-220 Santos, SP., Brazil
Abstract Background: Histologic parameters concerning the tumor-host relation of squamous cell carcinoma (SCC) are supposed to be important for prediction of future metastases to regional lymph nodes and prognosis. The mode of invasion of squamous cell carcinoma is graded into the following groups: grade 1—well-defined borderline; grade 2—less-marked borderline; grade 3—no distinct borderline; grade 4C—diffuse growth cord-like type; and grade 4D—diffuse type. Objectives: To investigate retrospectively the relationship between the mode of invasion of squamous cell carcinoma of the oral tongue and the occurrence of regional lymph node metastasis and outcome of the patients. Patients and methods: Twenty-two surgical specimens of histologically proven squamous cell carcinoma of the oral tongue were retrospectively studied from 1994 to 2000. All of them underwent partial glossectomy. Patients ranged from 52 to 78 years old with median of 62. There were 18 males and four females. The factors investigated in relation to the mode of invasion were pathological neck metastasis (pN) and survival rates. The pathological neck status was achieved in the medical records. The follow-up varied from 24 to 62 months after the surgical treatment. Fischer Exact Test was applied. Results: There were 10 specimens classified as grades 1 and 2, and 12 classified as grades 3, 4C and 4D. There were no metastasis in grades 1 and 2 (0/10), while the frequency of metastasis was high in grades 3, 4C and 4D (7/12) ( p = 0.005). All the 10 patients classified as grades 1 and 2 were alive without disease. From the 12 patients classified as grades 3, 4C and 4D, five died. Conclusions: The more invasive the tumor (grades 3, 4C and 4D), the more frequent regional metastasis are and the poorer the prognosis is. The mode of invasion of squamous cell carcinoma of the oral tongue has prognostic value. D 2003 International Federation of Otorhinolaryngological Societies (IFOS). All rights reserved. Keywords: Basement membrane; Carcinoma of the tongue; Mouth neoplasms; Prognosis; Malignancy grading; Diagnosis; Invasive cells
* Tel.: +55-13-3223-5550; fax: +55-13-3221-1514. E-mail address: [email protected] (R.A. Dedivitis). 0531-5131/ D 2003 International Federation of Otorhinolaryngological Societies (IFOS). All rights reserved. doi:10.1016/S0531-5131(03)00804-5
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R.A. Dedivitis / International Congress Series 1240 (2003) 695–700
1. Introduction Many investigators have reported histologic factors relating to the prognosis of cancer patients. The mode of invasion of squamous cell carcinoma (SCC) is graded into four groups [1]. Grade 1 has a well-defined borderline, grade 2 has a less-marked borderline and grade 3 has groups of cells with no distinct borderline. Grade 4 presents a diffuse growth and was sub classified into cord-like type (grade 4C) and diffuse type (grade 4D) [2]. Some authors used a multifactorial grading system, which score value (degree of malignancy) revealed a statistically significant correlation with the frequency of regional metastases. As this was particularly marked in the T1 and T2 groups, it seems to be an important supplement to the clinical evaluation of risk groups [3]. The presence of lymph node metastasis affects the prognosis of the tongue cancer patient [4]. It is fundamental to try to find objective criteria for the histologic classification of SCC of the mouth so that prognosis can be better evaluated in individual cases. In the present study, we retrospectively investigated the relationship between the mode of invasion and the frequency of lymph node metastasis and the outcome in cases of squamous cell carcinoma of the tongue.
2. Patients and methods We retrospectively studied 22 surgical specimens from patients treated from 1994 to 1999. All of them had histologically proven SCC of the oral tongue and underwent partial glossectomy as the main therapeutic modality for the primary tumor. Patients ranged from 52 to 78 years old with median of 62. There were 18 males and four females. According to UICC classification [5], there were 11 patients classified as T2, 10 as T3 and one as T4. All the patients were classified as N0, with exception to one, classified as N2b. The factors investigated in relation to the mode of invasion were pathological neck metastasis (pN) and survival rates. The pathological neck status was achieved in the medical records. Surgery alone and combined treatment with postoperative radiation therapy have both been applied. The follow-up varied from 24 to 62 months after the surgical treatment. Fischer Exact Test was applied for analysis of both relationships. The specimens were preserved in paraffin. The slides were stained with hematoxylin – eosin (HE). The pathologist examining the specimens was blinded to further information of the patient prior to histological examination. The mode of invasion in our material was classified by employing the surgical specimens, according to criteria of Jakobsson et al. [1] and Willen et al. [6] modified by Yamamoto et al. [2].
3. Results The histological grading of mode of invasion is shown in Fig. 1. When more than one type of histologic grade was found in the same specimen, the higher one was considered as
R.A. Dedivitis / International Congress Series 1240 (2003) 695–700
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R.A. Dedivitis / International Congress Series 1240 (2003) 695–700
Fig. 1. A—Grade 1: well-defined borderline, HE 200. B—Grade 2: less marked borderline, with cords, HE 200. C—Grade 3: no distinct borderline, with groups of cells invading, HE 200. D—Grade 4C: diffuse type, with cord-like invasion, HE 200. E—Grade 4D: diffuse invasion, HE 200.
the prevalent. There were 10 specimens classified as grades 1 and 2, and 12 classified as grades 3, 4C and 4D. The relationship between the mode of invasion and the frequency of metastasis is shown in Table 1. We had no metastasis in grades 1 and 2 (0/10), while the frequency of metastasis was high in grades 3, 4C and 4D (7/12) ( p = 0.005). Table 1 Relation between mode of invasion and regional lymph node metastasis Mode of invasion
pN0
pN +
Grades 1 and 2 Grades 3, 4C and 4D
10 5
0 7
p = 0.005.
R.A. Dedivitis / International Congress Series 1240 (2003) 695–700
699
Table 2 Relation between mode of invasion and outcome of the patients Mode of invasion
Tumor-free survival
Deaths
Grades 1 and 2 Grades 3, 4C and 4D
10 7
0 5
p = 0.04.
The relationship between the mode of invasion and the outcome is shown in Table 2. We classified the patients into two groups: alive with no evidence of disease and dead before the disease. All the 10 patients classified as grades 1 and 2 were alive without disease. From the 12 patients classified as grades 3, 4C and 4D, five died at the moment of this study.
4. Discussion The more invasive the tumor tissues were, the more frequent metastasis formation was and it is indicative of a poorer prognosis. The prognosis of grades 3 and 4 was poor, while the outcome was good in the other grades. Tumor cells of most invasive types can metastasize resulting in a poorer prognosis. The more invasive the tumor cells are to the host, the more frequent metastasis formation is found [7]. Invasive cell grading is of value as a supplement to clinical staging in treatment planning [8]. The patients who belong to these groups should undergo more aggressive therapy, including prophylactic neck dissection and postoperative concomitant chemoradiation therapy. Preliminary investigations [1,2] suggest that the initial diagnostic biopsy can classify the tumor according to its mode of invasion. So the prognosis could be determined earlier. We found various types of grades of invasion in the same specimen. We consider the typical grade the most advanced in the specimen. So the initial biopsy possibly would not be able to determine the exact grade of the complete specimen.
5. Conclusions We conclude that: the more invasive the tumor (grades 3, 4C and 4D), the more frequent regional metastasis are; the more invasive tumors (grades 3, 4C and 4D) are indicative of a poorer prognosis; the mode of invasion of the deep invasive margins of SCC of the oral tongue has prognostic value.
References [1] P.A. Jakobsson, G.M. Eneroth, D. Killander, G. Moberger, B. Martensson, Histologic classification and grading of malignancy in carcinoma of the larynx, Acta Radiol. 12 (1973) 1 – 7. [2] E. Yamamoto, G. Kohama, H. Sunakawa, M. Iwai, H. Hiratsuka, Mode of invasion, bleomycin sensitivity, and clinical course in squamous cell carcinoma of the oral cavity, Cancer 51 (1983) 2175 – 2180.
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R.A. Dedivitis / International Congress Series 1240 (2003) 695–700
[3] C. Lund, H. Sogaard, O. Elbrond, K. Jorgensen, A.P. Andersen, Epidermoid carcinoma of the tongue: histological grading in the clinical evaluation, Acta Radiol. 14 (1975) 513 – 520. [4] B. Leipzig, J.A. Hokanson, Treatment of cervical lymph nodes in carcinoma of the tongue, Head Neck Surg. 5 (1982) 3 – 9. [5] J.A. International Union Against Cancer (UICC), TNM Classification of Malignant Tumors, in: L.H. Sobin, Ch. Wittekind (Eds.), 5th ed., Wiley-Liss, Geneva, 1997. [6] R. Wille´n, A. Nathanson, G. Moeberger, G. Anneroth, Squamous cell carcinoma of the gingiva: histological classification and grading of malignancy, Acta Otolaryngol. 79 (1975) 146 – 154. [7] E. Yamamoto, A. Miyakawa, G. Kohama, Mode of invasion and lymph node metastasis in squamous cell carcinoma of the oral cavity, Head Neck Surg. 6 (1984) 938 – 947. [8] M. Bryne, H.S. Koppang, R. Lilleng, A. Kjærheim, Malignancy grading of the deep invasive margins of oral squamous cell carcinoma has high prognostic value, J. Pathol. 166 (1992) 375 – 381.
Mode of invasion and outcome in squamous cell carcinoma of the oral tongue Roge´rio A. Dedivitis * Department of Otorhinolaryngology, Head and Neck Surgery of Universidade Metropolitana de Santos ‘Unimes’, Rua Olinto Rodrigues Dantas, 343 conjunto 92, 11050-220 Santos, SP., Brazil
Abstract Background: Histologic parameters concerning the tumor-host relation of squamous cell carcinoma (SCC) are supposed to be important for prediction of future metastases to regional lymph nodes and prognosis. The mode of invasion of squamous cell carcinoma is graded into the following groups: grade 1—well-defined borderline; grade 2—less-marked borderline; grade 3—no distinct borderline; grade 4C—diffuse growth cord-like type; and grade 4D—diffuse type. Objectives: To investigate retrospectively the relationship between the mode of invasion of squamous cell carcinoma of the oral tongue and the occurrence of regional lymph node metastasis and outcome of the patients. Patients and methods: Twenty-two surgical specimens of histologically proven squamous cell carcinoma of the oral tongue were retrospectively studied from 1994 to 2000. All of them underwent partial glossectomy. Patients ranged from 52 to 78 years old with median of 62. There were 18 males and four females. The factors investigated in relation to the mode of invasion were pathological neck metastasis (pN) and survival rates. The pathological neck status was achieved in the medical records. The follow-up varied from 24 to 62 months after the surgical treatment. Fischer Exact Test was applied. Results: There were 10 specimens classified as grades 1 and 2, and 12 classified as grades 3, 4C and 4D. There were no metastasis in grades 1 and 2 (0/10), while the frequency of metastasis was high in grades 3, 4C and 4D (7/12) ( p = 0.005). All the 10 patients classified as grades 1 and 2 were alive without disease. From the 12 patients classified as grades 3, 4C and 4D, five died. Conclusions: The more invasive the tumor (grades 3, 4C and 4D), the more frequent regional metastasis are and the poorer the prognosis is. The mode of invasion of squamous cell carcinoma of the oral tongue has prognostic value. D 2003 International Federation of Otorhinolaryngological Societies (IFOS). All rights reserved. Keywords: Basement membrane; Carcinoma of the tongue; Mouth neoplasms; Prognosis; Malignancy grading; Diagnosis; Invasive cells
* Tel.: +55-13-3223-5550; fax: +55-13-3221-1514. E-mail address: [email protected] (R.A. Dedivitis). 0531-5131/ D 2003 International Federation of Otorhinolaryngological Societies (IFOS). All rights reserved. doi:10.1016/S0531-5131(03)00804-5
696
R.A. Dedivitis / International Congress Series 1240 (2003) 695–700
1. Introduction Many investigators have reported histologic factors relating to the prognosis of cancer patients. The mode of invasion of squamous cell carcinoma (SCC) is graded into four groups [1]. Grade 1 has a well-defined borderline, grade 2 has a less-marked borderline and grade 3 has groups of cells with no distinct borderline. Grade 4 presents a diffuse growth and was sub classified into cord-like type (grade 4C) and diffuse type (grade 4D) [2]. Some authors used a multifactorial grading system, which score value (degree of malignancy) revealed a statistically significant correlation with the frequency of regional metastases. As this was particularly marked in the T1 and T2 groups, it seems to be an important supplement to the clinical evaluation of risk groups [3]. The presence of lymph node metastasis affects the prognosis of the tongue cancer patient [4]. It is fundamental to try to find objective criteria for the histologic classification of SCC of the mouth so that prognosis can be better evaluated in individual cases. In the present study, we retrospectively investigated the relationship between the mode of invasion and the frequency of lymph node metastasis and the outcome in cases of squamous cell carcinoma of the tongue.
2. Patients and methods We retrospectively studied 22 surgical specimens from patients treated from 1994 to 1999. All of them had histologically proven SCC of the oral tongue and underwent partial glossectomy as the main therapeutic modality for the primary tumor. Patients ranged from 52 to 78 years old with median of 62. There were 18 males and four females. According to UICC classification [5], there were 11 patients classified as T2, 10 as T3 and one as T4. All the patients were classified as N0, with exception to one, classified as N2b. The factors investigated in relation to the mode of invasion were pathological neck metastasis (pN) and survival rates. The pathological neck status was achieved in the medical records. Surgery alone and combined treatment with postoperative radiation therapy have both been applied. The follow-up varied from 24 to 62 months after the surgical treatment. Fischer Exact Test was applied for analysis of both relationships. The specimens were preserved in paraffin. The slides were stained with hematoxylin – eosin (HE). The pathologist examining the specimens was blinded to further information of the patient prior to histological examination. The mode of invasion in our material was classified by employing the surgical specimens, according to criteria of Jakobsson et al. [1] and Willen et al. [6] modified by Yamamoto et al. [2].
3. Results The histological grading of mode of invasion is shown in Fig. 1. When more than one type of histologic grade was found in the same specimen, the higher one was considered as
R.A. Dedivitis / International Congress Series 1240 (2003) 695–700
697
698
R.A. Dedivitis / International Congress Series 1240 (2003) 695–700
Fig. 1. A—Grade 1: well-defined borderline, HE 200. B—Grade 2: less marked borderline, with cords, HE 200. C—Grade 3: no distinct borderline, with groups of cells invading, HE 200. D—Grade 4C: diffuse type, with cord-like invasion, HE 200. E—Grade 4D: diffuse invasion, HE 200.
the prevalent. There were 10 specimens classified as grades 1 and 2, and 12 classified as grades 3, 4C and 4D. The relationship between the mode of invasion and the frequency of metastasis is shown in Table 1. We had no metastasis in grades 1 and 2 (0/10), while the frequency of metastasis was high in grades 3, 4C and 4D (7/12) ( p = 0.005). Table 1 Relation between mode of invasion and regional lymph node metastasis Mode of invasion
pN0
pN +
Grades 1 and 2 Grades 3, 4C and 4D
10 5
0 7
p = 0.005.
R.A. Dedivitis / International Congress Series 1240 (2003) 695–700
699
Table 2 Relation between mode of invasion and outcome of the patients Mode of invasion
Tumor-free survival
Deaths
Grades 1 and 2 Grades 3, 4C and 4D
10 7
0 5
p = 0.04.
The relationship between the mode of invasion and the outcome is shown in Table 2. We classified the patients into two groups: alive with no evidence of disease and dead before the disease. All the 10 patients classified as grades 1 and 2 were alive without disease. From the 12 patients classified as grades 3, 4C and 4D, five died at the moment of this study.
4. Discussion The more invasive the tumor tissues were, the more frequent metastasis formation was and it is indicative of a poorer prognosis. The prognosis of grades 3 and 4 was poor, while the outcome was good in the other grades. Tumor cells of most invasive types can metastasize resulting in a poorer prognosis. The more invasive the tumor cells are to the host, the more frequent metastasis formation is found [7]. Invasive cell grading is of value as a supplement to clinical staging in treatment planning [8]. The patients who belong to these groups should undergo more aggressive therapy, including prophylactic neck dissection and postoperative concomitant chemoradiation therapy. Preliminary investigations [1,2] suggest that the initial diagnostic biopsy can classify the tumor according to its mode of invasion. So the prognosis could be determined earlier. We found various types of grades of invasion in the same specimen. We consider the typical grade the most advanced in the specimen. So the initial biopsy possibly would not be able to determine the exact grade of the complete specimen.
5. Conclusions We conclude that: the more invasive the tumor (grades 3, 4C and 4D), the more frequent regional metastasis are; the more invasive tumors (grades 3, 4C and 4D) are indicative of a poorer prognosis; the mode of invasion of the deep invasive margins of SCC of the oral tongue has prognostic value.
References [1] P.A. Jakobsson, G.M. Eneroth, D. Killander, G. Moberger, B. Martensson, Histologic classification and grading of malignancy in carcinoma of the larynx, Acta Radiol. 12 (1973) 1 – 7. [2] E. Yamamoto, G. Kohama, H. Sunakawa, M. Iwai, H. Hiratsuka, Mode of invasion, bleomycin sensitivity, and clinical course in squamous cell carcinoma of the oral cavity, Cancer 51 (1983) 2175 – 2180.
700
R.A. Dedivitis / International Congress Series 1240 (2003) 695–700
[3] C. Lund, H. Sogaard, O. Elbrond, K. Jorgensen, A.P. Andersen, Epidermoid carcinoma of the tongue: histological grading in the clinical evaluation, Acta Radiol. 14 (1975) 513 – 520. [4] B. Leipzig, J.A. Hokanson, Treatment of cervical lymph nodes in carcinoma of the tongue, Head Neck Surg. 5 (1982) 3 – 9. [5] J.A. International Union Against Cancer (UICC), TNM Classification of Malignant Tumors, in: L.H. Sobin, Ch. Wittekind (Eds.), 5th ed., Wiley-Liss, Geneva, 1997. [6] R. Wille´n, A. Nathanson, G. Moeberger, G. Anneroth, Squamous cell carcinoma of the gingiva: histological classification and grading of malignancy, Acta Otolaryngol. 79 (1975) 146 – 154. [7] E. Yamamoto, A. Miyakawa, G. Kohama, Mode of invasion and lymph node metastasis in squamous cell carcinoma of the oral cavity, Head Neck Surg. 6 (1984) 938 – 947. [8] M. Bryne, H.S. Koppang, R. Lilleng, A. Kjærheim, Malignancy grading of the deep invasive margins of oral squamous cell carcinoma has high prognostic value, J. Pathol. 166 (1992) 375 – 381.