[Chronic and acute hypersensitivity pneumonitis in a dairy farmer and his son].

We encountered a dairy farmer and his son with farmer's lung who had worked on the same farm for 25 years and 5 years, respectively. The son was admitted to our hospital because of cough, sputum, and shortness of breath. Chest computed tomography (CT) on admission revealed diffuse ground-glass opacities in both lung fields. Following admission, the clinical symptoms and radiological findings improved spontaneously without specific treatment. A provocation test (following return to work on the farm) elicited recurrence of the symptoms and radiological findings. He was diagnosed with acute hypersensitivity pneumonitis (HP) based on the clinical findings. After quitting his job, no reccurence was noted. The farther was admitted to our hospital complaining of repeated episodes of cough and high fever. He had been diagnosed with lung fibrosis 10 years previously. Chest CT on admission revealed progression of thin-walled cystic changes over ten years. Following admission, his symptoms improved without medication. However, because he has continued working on the farm, his radiological findings have gradually deteriorated. He was diagnosed with chronic HP based on his clinical features. These cases are suggestive of farmer's lung with familial occurrence, difference between acute HP and chronic HP, and long-term prognosis.

[Autopsy case of von Recklinghausen's disease associated with lung cancer, gastrointestinal stromal tumor of the stomach, and duodenal carcinoid tumor].

A 58-year-old man with von Recklinghausen's disease was admitted for further investigation of right chest pain. Chest X-ray revealed multiple emphysematous bullae in both lungs and a tumor shadow in the right upper lobe. Bronchofiberscopy was performed, but an adequate specimen was not obtained. The tumor was diagnosed as a non-small-cell lung cancer with direct invasion to the adjacent rib. Although chemotherapy and radiotherapy resulted in decrease in tumor size, the tumor subsequently increased in size and the patient died 14 months after the first admission. Autopsy revealed multiple emphysematous bullae, poorly differentiated adenosquamous cell carcinoma of the lung, gastrointestinal stromal tumor of the stomach, and duodenal carcinoid tumor. This case suggests the possibility that von Recklinghausen's disease associated with emphysematous bullae is a risk factor for lung cancer. It has also been suggested that the genetic abnormality responsible for von Recklinghausen's disease increases the risk for various types of malignancy. Although von Recklinghausen's disease is reportedly associated with various malignant tumors, it is quite rare for von Recklinghausen's disease to be associated with triple non-neurogenic tumors. Careful observation is mandatory for patients with von Recklinghausen's disease.

[A case of pulmonary MALT lymphoma with 6-year natural history].

A 58-year-old asymptomatic man was referred for investigation of an abnormal shadow on chest X-ray films. Chest computed tomography (CT) revealed an infiltrative shadow containing an air-bronchogram. Video-assisted thoracic surgery was performed for a lung biopsy of an abnormal region in the right upper lobe of the lung. Based on immunohistochemical examinations and gene analysis, the abnormal shadow was diagnosed as primary pulmonary B-cell lymphoma of mucosa-associated lymphoid tissue, t(11; 18)/API2-MALT1. Rituximab-CHOP therapy yieled a complete response. He had abnormal shadows on chest X-ray films in both lung fields since 6 years previously. Retrospective examination of chest radiographs revealed slow growth during the 6 years.

CD4+ T cells in cancer stroma, not CD8+ T cells in cancer cell nests, are associated with favorable prognosis in human non-small cell lung cancers.

We investigated intratumoral tumor-infiltrating lymphocytes (TILs), including CD4(+) and CD8(+) T cells, in non-small cell lung cancers (NSCLCs) and their relationships with clinicopathological variables and post-operative survival. Tumor specimens from 178 NSCLCs were consecutively obtained by surgery at the Hokkaido University Medical Hospital between 1976 and 1994. CD8(+) T cells, CD4(+) T cells and Ki-67/CD8(+) T cells were visualized immunohistochemically, and counted within cancer cell nests and in cancer stroma. CD8(+) T cells and CD4(+) T cells were observed at higher frequencies within cancer cell nests in moderately and poorly differentiated tumors compared with well differentiated tumors (P < 0.01), and in tumors with high Ki-67 expression compared with low Ki-67 expression (P < 0.01), that showed severe cellular atypia and a higher growth rate. Patients with higher numbers of CD8(+) T cells within cancer cell nests showed significantly shorter survival times compared to those with lower numbers of CD8(+) T cells within cancer cell nests (5-year survival rates, 47% and 60%, respectively; P = 0.03). Moreover, patients with higher labeling index of Ki-67/CD8(+) T cells showed significantly shorter survival than those with lower labeling index of Ki-67/CD8(+) T cells within cancer cell nests (5-year survival rates, 41% and 69%, respectively; P = 0.02), and the labeling index of Ki-67/CD8(+) T cells within cancer cell nests was found to be a significant and independent unfavorable prognostic factor by multivariate analysis (P = 0.01). On the other hand, higher numbers of CD4(+) T cells in cancer stroma, but not within cancer cell nests, were correlated with longer survival times in patients with NSCLC (5-year survival rates, 64% and 43%, respectively; P = 0.04). CD4(+) T cells in cancer stroma might reflect immune responses against cancer cells, while CD8(+) T cells do not appear to work as effectors in tumor tissues of NSCLC. Moreover, the higher labeling index of Ki-67/CD8(+) T cells within cancer cell nests is a strong indicator of unfavorable clinical outcome.