Prognostic Significance of Extranodal Cancer Invasion of Mediastinal Lymph Nodes in Lung Cancer

Transcription

1 Jpn. J. Clin. Oncol. 198, 1 (), 7-1 Prognostic Significance of Extranodal Cancer Invasion of Mediastinal Lymph Nodes in Lung Cancer KEIICHI SUEMASU, M.D. AND TSUGUO NARUKE, M.D. Department of Surgery, National Cancer Center Hospital, Tokyo Abstract The presence of perinodal cancer invasion in specimens obtained from the mediastinum during curative surgery on 49 patients with metastasis-bearing mediastinal nodes was determined and evaluated with special reference to its prognostic significance. When an en-bloc dissection technique for the mediastinal lymph nodes and fatty tissue surrounding the nodes during surgery was used, lymphatic vessel invasion in fatty tissue other than a breach in the capsule of a lymph node by cancer could be seen. A breach in the node capsule and lymphatic vessel invasion are designated as "extranodal invasion" in this paper. A breach in the capsule was seen in 16 cases, lymphatic vessel invasion in 1 and both a breach in the capsule and lymphatic vessel invasion in 4. In 17 cases there was only intranodal cancer metastasis. The 5-yr survival rate was 7.5% and 17.7% for patients with and without extranodal invasion, respectively. However, extranodal invasion did not seem to be a distinctive prognostic factor. Introduction There is a controversy over the indications for surgery for lung cancer with metastasis in the mediastinal lymph nodes (N lung cancer, which I will describe later). Paulson et al. (1971), Gibbons (197), Asharf et al. (198) and Pearson et al. (198) stated that N lung cancer is contraindicative to lung resection. On the other hand Kirsh et al. (1971), Naruke et al. (1976), Abbey Smith (1978) and Martini et al. (1981) reported a relatively high Received June 5, 198. Reprint requests: Keiichi Suemasu, M.D., Department of Surgery, National Cancer Center Hospital, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 14, Japan. This work was supported by a Grant-in- Aid for Cancer Research from the Ministry of Health and Welfare (56S-I) Japan. survival rate for patients who had curative resection for N lung cancer. We stand by the opinion that patients with N lung cancer should be operated upon when there is a high expectation of complete eradication of the cancer tissue by lung resection associated with so-called complete lymphadenectomy. The 5-yr survival rate for our N lung cancer patients who received curative resection is 18.%. Bergh and Scherstein (1965) stated that a breach in the capsule of a lymph node indicates a poor prognosis in patients with resected lung cancer. The results of the microscopic examination of metastasis-positive nodes dissected from the mediastinum of patients with N lung cancer are presented in this paper, with special reference to features of "extranodal cancer invasion" a breach in the node capsule and lymphatic vessel invasion and their prognostic significance. Downloaded from at Pennsylvania State University on September 19, 16

2 8 SUEMASU AND NARUK.E Jpn. J. Clin. Oncol. August 198 Materials and Methods Among 1,16 lung cancer patients who were operated upon in the National Cancer Center Hospital during the period from 196 to 198, 41 had N lung cancer and 8 of the 41 received curative resection. For curative resection, lung cancer was removed and a complete lymphadenectomy as well as dissection of the fatty tissue surrounding the nodes was carried out. Among these 8 patients, 49 were analyzed in regard to the prognostic significance of the presence of extranodal cancer invasion in the mediastinum. The precise site of the dissected mediastinal nodes was determined according to the lymph node map made by Naruke et al. (1976). The dissected materials were fixed with 1% formalin solution and histological sections were prepared. To determine the extent of the primary tumor in the lung, the T variable according to the TNM classification of UICC (1978) was used. Results 1. Recognition of Lymphatic Vessel Invasion as a Feature of Extranodal Involvement When the material dissected from the mediastinum was examined for the presence of metastasis, both intranodal invasion (Fig. 1) and extranodal invasion were seen. The latter was subdivided into perinodal invasion indicating a breach in the capsule of a lymph node by metastasis (Fig. a and b), and lymphatic vessel invasion in the fatty tissue surrounding the lymph nodes or in a lymphatic vessel close to a lymph node (Fig. a and b).. 5-Yr Survival and Extranodal Invasion (Table 1) Seventeen patients whose mediastinal lymph nodes and fatty tissue revealed no extranodal invasion had a 5-yr survival rate of 17.7% and the rate in patients with extranodal invasion was 7.5%. The presence of extranodal cancer invasion was not indicative of a poor prognosis. Lymphatic vessel invasion was seen in 1 patients, a breach in the capsule of a lymph node in 16 and both a breach in the capsule and lymphatic vessel invasion in 4. Each of these three groups with extranodal invasion showed a better survival rate than the group of patients without extranodal invasion.. Other Prognostic Factors (Table ) The histological type, number of the lymph node stations involved, and the T variable in the TNM classification were reviewed and compared in patients with and without extranodal invasion. Among the patients with extranodal involvement, the lymphatic vessel invasion Table 1 Five-Year Survival in Patients with or without Extranodal Invasion Downloaded from at Pennsylvania State University on September 19, 16 Survival Survived 5 yr or more 6 Died within 5 yr 1 Extranodal Invasion Ly" B & Ly c Total 1 7.5%" Tntranodal Invasion Total %" a) indicates a breach in capsule. b) indicates lymphatic vessel invasion. c) indicates both breach in capsule and lymphatic vessel invasion in the same ca^e. d) indicates 5-year survival rate.

3 Vol. 1, No. EXTRANODAL CANCER INVASION AND LUNG CANCER 9 Fig. a: Breach in the capsule of a lymph node by metastasis of adenocarcinoma. Hematoxylin and eosin staining. X. Fig. 1: Intranodal metastasis in a dissected mediastinal lymph node of a patient with adenocarcinoma. Hematoxylin and eosin staining. X. Downloaded from at Pennsylvania State University on September 19, 16 Fig. b: Breach in the capsule of a lymph node by metastasis of squamous cell carcinoma. Hematoxylin and eosin staining. X.

4 1 SUEMASU AND NARUKE Jpn. J. Clin. Oncol. August 198 Fig. b: Lymphatic vessel invasion of squamous cell carcinoma in fatty tissue close to a lymph node. Hematoxylin and eosin staining. X. Fig. a: Lymphatic vessel invasion of adenocarcinoma in the fatty issue surrounding the mediastinal lymph nodes. Hematoxylin and eosin staining. X. Downloaded from at Pennsylvania State University on September 19, 16 Fig. 4 Mediastinal lymph nodes with surrounding fatty tissue dissected as a mass. Hematoxylin and eosin staining. 1/ X.

5 Vol. 1, No. EXTRANODAL CANCER INVASION AND LUNG CANCER 11 Table Prognostic Factors in Patients with or without Extranodal Invasion Histology squam. cell ca. adeno ca. large cell ca. Number of lymph node stations involved 1 4 T variable 1 7 () 6 () () 9 5 (5) () 1 (5) 1 () Extranodal Invasion _. _ Ly b B & Ly 4 8 () 5 () 1 () 6 () 6 () 1 I () () Total 1 (4) 16 (6) () 17 (8) 8 I 6 () 1 (5) 18 (7) () n) indicates a breach in capsule. b) indicates lymphatic vessel invasion. c) indicates both a breach of capsule and lymphatic vessel invasion in the same case. Nummbers in parenthesis indicate number of 5-yr survivors. group seemed to contain a few more cases of adenocarcinoma, a few more patients with metastasis in only one lymph node station and more cases of Tl. There were a few more cases of adenocarcinoma among patients without extranodal invasion than among those with such invasion. In regard to the other two prognostic factors there was almost no difference between these two groups. Discussion In discussing a very controversial problem concerning the indications for surgery for N lung cancer, one of the important points is how much the presence of a breach in the capsule of a lymph node by metastasis influences the prognosis of the disease. Bergh and Scherstein (1964) made a significant distinction between intranodal and perinodal (breach in the nodal capsule) metastasis in regard to the prognostic significance after lung resection for lung cancer. Paulson et al. (1971) cited the data of Intranodal Invasion Total 7 () 1 1 () 5 () () 7 9 () 1 () Bergh and Scherstein and agreed with their conclusions. While examining the specimens by microscopy it was recognized that there were two different types of cancer invasion outside of the lymph nodes. That is, in addition to a breach in the lymph node capsule, lymphatic vessel invasion in the fatty tissue surrounding the nodes, which was not recognized in the study by Bergh and Scherstein, was frequently seen and we considered that too should be evaluated in relation to prognostic significance. It is necessary to carry out an en-bloc dissection of the fatty tissue and lymph nodes from the mediastinum in order to recognize and to evaluate lymphatic vessel invasion (Fig. 4). Picking lymph nodes up from the mediastinum as a node dissection technique is inadequate for determining true extent of the extranodal involvement in the mediastinum. In contrast to the results of Bergh and Scherstein (1965) we found no definite correlation between the presence of extranodal Downloaded from at Pennsylvania State University on September 19, 16

6 1 SUEMASU AND NARUK.E Jpn. J. Clin. Oncol. August 198 invasion including a breach in the capsule and lymphatic vessel invasion, and prognosis. There was no difference in histology, spread of lymph node involvement or T factor between patients with and without extranodal invasion. For evaluation of these three prognostic factors the number of patients was still too small for us to determine the factor that really influences the prognosis. It is quite apparent, however, that the prognosis for patients with extranodal invasion is not worse but a little better than that for patients without extranodal invasion. References Abbey Smith, R., The importance of mediastinal lymph node invasion by pulmonary carcinoma in selection of patients for resection. Ann Thorac Surg 5: 5, Asharf, M. H., P. L. Milsom and R. K. Walesby, Selection by mediastinoscopy and long-term survival in bronchogenic carcinoma. Ann Thorac Surg : 8, 198. Bergh, N. P. and T. Scherstein, Bronchogenic carcinoma: A follow-up study of a surgically treated series with special reference to the prognostic significance of lymph node metastases. Ada Chir Scand 47: 1, (suppl) Gibbons, J. R. P., The value of mediastinoscopy in assessing operability in carcinoma of the lung. Br J Dis Chest 66: 16, 197. Kirsh, M. M., D. R. Kahn, O. Gago, I. Lampe, J. V. Fayos, M. Prior, W. Y. Moores, C. Haight and H. Sloan, Treatment of bronchogenic carcinoma with mediastinal metastases. Ann Thorac Surg 1: 11, Martini, N., B. T. Flehinger, N. B. Zaman and E. J. Beattie, Jr., Prospective study of 445 lung carcinomas with mediastinal lymph node metastases. J Thorac Cardiovasc Surg 8: 9, Naruke, T., K. Suemasu and S. Ishikawa, Surgical treatment for lung cancer with metastasis to mediastinal lymph nodes. J Thorac Cardiovasc Surg 71: 79, Paulson, D. L. and H. C. Urshel, Jr. Selectivity in the surgical treatment of bronchogenic carcinoma. J Thorac Cardiovasc Surg 6: 554, Pearson, F. G., N. C. DeLarue, R. lives, T. R. J. Todd and J. D. Cooper, Significance of positive mediastinal nodes indentified at mediastinoscopy in patients with resectable cancer of the lung. J Thorac Cardiovasc Surg 8: I, 198. UICC, TNM classification of malignant tumors. nd ed. International Union against Cancer, Geneva, Downloaded from at Pennsylvania State University on September 19, 16