松井 由紀子

To demonstrate the importance of preoperative diagnosis of pulmonary cancers presenting as peripheral small-sized solitary shadows we evaluated the results of morphologic definitive diagnosis together with various clinical factors in 91 tumors with less than 15-mm diameter resected surgically between 1983 and 1999. Histologically, these tumors consisted of 73 adenocarcinomas, nine squamous cell carcinomas, and nine other types. Regarding the pathologic stage, 57 tumors were classified in stage IA, three in IB, six in IIA, seven in IIIA, 14 in IIIB, and four in IV. Comparing various biopsy techniques, the sensitivity of preoperative cytodiagnosis was 43.7% for transbronchial brushing (n = 48), 52.9% for transbronchial forceps biopsy-stamp cytology (n = 51), 66.6% for transbronchial fine needle aspiration (n = 78), and 85.0% for percutaneous fine needle aspiration (n = 20). The overall sensitivity of preoperative cytodiagnosis was 79.0% for transbronchial biopsy (n = 81), and 87.3% for transbronchial and percutaneous biopsy (n = 87). Of 73 clinical N0 cases in which lobectomy was performed, 10 cases (13.6%) were diagnosed as between pathological degrees N1, N2 and N3. However, lung cancer cases with less than 10-mm diameter did not have lymph node metastasis. Our study of histologic differentiation showed that all cases of well-differentiated adenocarcinomas (n = 20) were pathological degree N0. The overall sensitivity of preoperative diagnosis increased to 89.1% in cases (n = 74) of tumors with 11-15-mm diameter. The sensitivity of cytodiagnosis for peripheral small-sized primary lung cancers is high, and we can estimate histological differentiation based on the cytological findings. Therefore, cytodiagnosis is an effective and indispensable diagnostic method for determination of the optimal treatment approach, including approaches such as intentionally limited resection.

BACKGROUND: The relative incidence of adenocarcinoma of the lung is increasing and some patients with lung carcinoma, detected at an early stage, still develop recurrent disease despite complete resection of the tumor. Recently, neuroendocrine differentiation in large cell carcinoma of the lung has been reported to be of prognostic significance. Therefore, we have evaluated the prognostic significance of neuroendocrine differentiation in adenocarcinoma of the lung. METHODS: A total of 90 resected specimens of adenocarcinoma of the lung measuring 3 cm or less (T1 N0 M0 or T2 N0 M0) were reviewed histologically and immunohistochemical staining was performed to determine the degree of neuroendocrine differentiation. RESULTS: Seven adenocarcinomas exhibited neuroendocrine differentiation in 10% or more of tumor cells. The disease-free survival rate for these patients was significantly lower than that of patients with tumors exhibiting neuroendocrine differentiation in less than 10% of tumor cells or with absent neuroendocrine differentiation (p < 0.0005). Other conventional pathologic factors such as vascular invasion (p < 0.0005), lymphatic invasion (p < 0.05), and pleural involvement (p < 0.05) were also of prognostic significance. In multivariate analysis, the presence of 10% or more neuroendocrine marker-positive tumor cells, vascular invasion, and lymphatic invasion were found to be significantly adverse prognostic factors (p = 0.0162, p = 0.0111, and p = 0.0173, respectively). CONCLUSIONS: Neuroendocrine differentiation of tumor cells is a prognostic factor in lung adenocarcinoma. It is suggested that the identification of neuroendocrine differentiation as well as vascular invasion by tumor in small peripheral adenocarcinoma of the lung may predict the prognosis of these patients.

Our aim was to assess natural history of bronchial squamous dysplasia detected by fluorescence bronchoscopy, that is, which dysplasia has potential to progress to invasive cancer. We could periodically follow up dysplasias detected by fluorescence bronchoscopy, and were subjects of this study. We assessed the correlation among histological outcome and smoking status during the follow-up period, and telomerase activity, Ki-67 labeling index, and p53 immunoreactivity of initial biopsy specimens. Some of dysplasias developed to squamous cell carcinoma, some maintained dysplasias, and another regressed to normal bronchial epithelium. Dysplasia with high telomerase activity, increased Ki-67 labeling index, and p53 positive immunoreactivity tends to remain dysplasia, and have potential to progress to invasive cancer.

Three cases of alpha-fetoprotein (AFP)-producing lung carcinoma were studied histologically and immunohistochemically. Samples were obtained from two men and one woman who ranged in age from 64 to 71 years. Serum AFP levels for the three samples were 9826, 74.4 and 24.3 ng/mL. One case was classified as stage IIIA and two as stage IIIB. Two cases were diagnosed as large cell neuroendocrine carcinoma, and AFP expression was detected immunohistochemically. One of these samples showed differentiation to a hepatoid carcinoma, while the other was combined with a squamous cell carcinoma. The remaining case was a squamous cell carcinoma, and AFP was detected in only some of the tumor cells. All patients died within 2 years. The Ki-67 labeling indices of the AFP-producing pulmonary carcinomas (30.2 +/- 4.6%) were significantly higher than those of AFP-negative pulmonary carcinomas (P < 0.05). The high proliferative activity, advanced stage at presentation, vascular endothelial growth factor expression and vascular invasion observed in these tumors may explain the poor prognosis of AFP-producing lung carcinomas.

BACKGROUND. In 1999, the World Health Organization categorized large cell neuroendocrine carcinoma, large cell carcinoma with neuroendocrine differentiation, and large cell carcinoma with neuroendocrine morphology as a variant of large cell carcinoma. Patients with large cell carcinoma with neuroendocrine features have poor prognoses, comparable to those for small cell lung carcinoma. Small cell lung carcinoma is sensitive to chemotherapy however, it is still unclear whether large cell carcinoma with neuroendocrine features is responsive to adjuvant chemotherapy. METHODS. The authors analyzed 73 patients with large cell carcinoma with neuroendocrine features who underwent resection of the tumor and studied the effect of adjuvant chemotherapy for large cell carcinoma with neuroendocrine features. RESULTS. In patients with Stage I disease, the overall survival for patients with adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide, which were used as standard chemotherapy for small cell lung carcinoma, were significantly higher than the overall survival for patients without adjuvant chemotherapy. In patients with Stage II, III, and IV disease, there was no significant difference between patients with adjuvant chemotherapy and without adjuvant chemotherapy. CONCLUSIONS. Adjuvant chemotherapy based on cisplatin, carboplatin, or cyclophosphamide prolongs survival of patients with large cell carcinoma with neuroendocrine features in early stage. © 2001 American Cancer Society.

Our aim was to evaluate whether the use of fluorescence bronchoscopy following conventional white-light bronchoscopy examination is useful in the early diagnosis of preinvasive bronchial lesions of the tracheobronchial tree. Patients with abnormal sputum cytology were referred to our institute and examined with both white-light and fluorescence bronchoscopy. All abnormal areas discovered by white-light or fluorescence bronchoscopy examination or both, had biopsy specimens taken for pathological examination. Forty-five lesions were revealed to be preinvasive bronchial lesions. Multicentric lesions were observed in 17 patients in this study. Examination using a fluorescence bronchoscopy, in addition to conventional white-light examination, was found to enhance the detection and localization of preinvasive bronchial lesions.