Heterogeneous Tumor-Immune Microenvironments between Primary and Metastatic Tumors in a Patient with ALK Rearrangement-Positive Large Cell Neuroendocrine Carcinoma.

Evolution of tumor-immune microenviroments (TIMEs) occurs during tumor growth and dissemination. Understanding inter-site tumor-immune heterogeneity is essential to harness the immune system for cancer therapy. While the development of immunotherapy against lung cancer with driver mutations and neuroendocrine tumors is ongoing, little is known about the TIME of large cell neuroendocrine carcinoma (LCNEC) or anaplastic lymphoma kinase (ALK) rearrangement-positive lung cancer. We present a case study of a 32-year-old female patient with ALK-rearrangement-positive LCNEC, who had multiple distant metastases including mediastinal lymph-node, bilateral breasts, multiple bones, liver and brain. Multiple biopsy samples obtained from primary lung and three metastatic tumors were analyzed by fluorescent multiplex immunohistochemistry. Tissue localizations of tumor-infiltrating lymphocytes in the tumor nest and surrounding stroma were evaluated. T cell and B cell infiltrations were decreased with distance from primary lung lesion. Although each tumor displayed a unique TIME, all tumors exhibited concomitant regression after treatment with an ALK-inhibitor. This study provides the first evidence of the coexistence of distinct TIME within a single individual with ALK-rearrangement-positive LCNEC. The present study contributes to our understanding of heterogeneous TIMEs between primary and metastatic lesions and provides new insights into the complex interplay between host-immunity and cancer cells in primary and metastatic lesions.

Pulmonary Nocardiosis With Endobronchial Involvement Caused by Nocardiaaraoensis.

We report a rare case of pulmonary nocardiosis with endobronchial involvement caused by Nocardia araoensis. A 79-year-old man with a history of asthma and a previous right upper lobectomy for lung cancer and organizing pneumonia presented with cough and dyspnea. He presented with right bronchial stenosis associated with various mucosal lesions, including ulcerative and exophytic lesions. N araoensis was detected in sputum samples collected via bronchoscopy. The mucosal lesions improved after a 2-week course of meropenem. After a further 6 months of oral sulfamethoxazole-trimethoprim treatment, the mucosal lesions completely disappeared. Based on bronchoscopic and pathophysiologic findings, the patient was diagnosed with pulmonary nocardiosis with endobronchial involvement. Nocardiosis should be considered in the differential diagnosis of endobronchial mucosal lesions.

[A case of Epstein-Barr virus-positive diffuse large B-cell lymphoma in an elderly person with a necrotizing pulmonary bulky mass].

A 52-year-old man presented with a pulmonary bulky mass, fever and cough. Chest CT showed a necrotizing bulky mass 10 cm in diameter in the right lung lower lobe. Transbronchial biopsy and CT-guided biopsy of the tumor and endobronchial ultrasound-guided transbronchial needle aspiration of the right hilar lymph node did not yield a definitive diagnosis, but the histological findings showed necrosis. We performed CT-guided biopsy of the part of the lesion where a high uptake of FDG-PET was observed. The histological diagnosis was diffuse large B-cell lymphoma. The immunohistochemical findings were positive for Epstein-Barr virus (EBV). Because the patient was more than 50 years old and had no underlying diseases, he was given a diagnosis of EBV-positive diffuse large B-cell lymphoma of an elderly patient. The pulmonary manifestation of this disease as a bulky tumor is extremely rare. In spite of the presence of a bulky pulmonary tumor, the EBV-positive diffuse large B-cell lymphoma contained necrotizing tissue, and it was difficult to obtain tissue specimens for histological examination.

[An elderly case of anomalous systemic arterial supply to the normal basal segment of the left lower lobe and summary of reports of the disease in Japan].

A 69-year-old asymptomatic woman was admitted because of an abnormal chest shadow. Chest X-ray films showed a tumorous shadow behind the heart. Chest CT scans showed an aberrant artery branching from the thoracic aorta and supplying the left basal segment, but the bronchial tree was normal. The left lung vein was normal but wide, and the left lower pulmonary artery could not be observed. Based on these findings, we diagnosed anomalous systemic arterial supply to the normal basal segment of the left lower lobe. Because this patient had a high risk of heart failure and pulmonary hypertension, we decided to perform a left lower lobectomy, but she refused the operation. As this disease is generally found in younger patients, diagnosis in older age, as in the present case, is rare. In this report we also summarize 39 other reports of this disease in Japan.

Respiratory evaluation of the risk for postoperative pulmonary complications in patients who preoperatively consulted pulmonologists: Studying both patients who underwent and who precluded planned surgery.

BACKGROUND: Due to advances in medicine, patients with pulmonary diseases have become candidates for surgery under general anesthesia. They often consult pulmonologists to assess their tolerability for surgery. The purpose of this study was to evaluate the significant characteristics responsible for postoperative pulmonary complications (PPCs) and the preclusion of the planned surgery. METHODS: The clinical data of 462 consecutive patients who consulted at the Department of Respiratory Medicine before surgery under general anesthesia were used in this study. The relationship between the patient׳s characteristics and their outcomes were analyzed. The patients who were scheduled for lung resection were excluded. RESULTS: Of the 386 patients who underwent planned surgery, 353 had no PPCs (Group A) and 33 developed PPCs (Group B). Planned surgery under general anesthesia was precluded in 31 patients due to respiratory problems (Group C). The significant predictors for PPCs consisted of a higher age, male gender, asthma, gastrointestinal surgery, cardiovascular surgery and a lower percentage of the predicted forced expiratory volume in 1 second (% predicted FEV1). The significant factors associated with the preclusion of planned surgery included interstitial pneumonia (IP), dermatologic surgery and a lower % predicted FEV1. The predicted probability of PPCs in Group C was significantly higher than that in Group A and lower than that in Group B (all p-values < 0.05). CONCLUSION: The common clinical finding for predicting PPCs and encouraging the preclusion of the planned surgery under general anesthesia was a lower % predicted FEV1.