The Japanese Joint Committee of Lung Cancer Registry (JJCLCR) has regularly conducted nationwide registry studies of lung cancer patients. This is a report of the 7th JJCLCR registry study for lung cancer patients surgically treated in 2010. The principal results of the study were published in English. The clinicopathologic profiles, staging, and prognosis of patients who underwent surgery for primary lung cancer in 2010 at teaching hospitals certified by the Japanese Board of General Thoracic Surgery were retrospectively collected in 2016. With a recent trend in surgical treatment for lung cancer, this study focused on the following issues in addition to the basic clinicopathological information; i) early lung cancer presenting ground-glass opacity, ii) multiple lung cancers, iii) comorbid diseases and past history of patients, iv) 30/90-day mortality and postoperative complications, v) the new adenocarcinoma classification published in 2011, vi) genetic mutation of lung cancer, and vii) postoperative recurrence and treatment for recurrent disease. The cohort consisted of 18,973 cases from 296 hospitals, which was the largest in the JJCLCR history. The most recent database of lung cancer surgery in Japan was successfully presented. Especially, as for long-term outcomes, overall survivals and disease-free survivals after surgery according to the TNM staging were shown. The database obtained in this study will greatly contribute to the promotion of research and the improvement of medical care in this field.

Morphological evaluations by radiologists are essential for the diagnosis of lung cancer. Evaluations of the nodule margin, internal characteristics, and the relationship with the pre-existing lung enable the imaging diagnosis of lung cancer. However, in the field of imaging diagnoses, quantification has long been emphasized. At the 2007 meeting of the Radiological Society of North America, the Quantitative Imaging Biomarkers Alliance (QIBA) was established as a cooperative standardizing organization for biomarkers in quantitative images. The QIBA aims to create standardized guidelines that can be used to objectively measure and evaluate images or parameters in clinical trials and daily clinical practice. In a clinical setting, we not only measure the dimension of nodules but also perform various quantifications, such as volumetry. While the usefulness of many quantitative indicators has been reported, one- and two-dimensional analyses are highly versatile but subjective in their utility. Three-dimensional analyses are indispensable for more objective and reproducible analyses. In recent years, studies using artificial intelligence have been performed increasingly frequently. In this paper, focusing on the malignancy and prognosis of lung cancer, we review some analyses using quantitative methods and artificial intelligence in lung cancer.

Neuroendocrine tumors (NETs) of the lung and mediastinum are very rare, with annual incidences of only 1.49 and 0.02 per 100,000, respectively, according to Surveillance, Epidemiology, and End Results (SEER) data. According to the 4th edition of the WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart, published in 2015, NETs of the lung and mediastinum include small cell carcinoma, large cell neuroendocrine carcinoma (LCNEC), and atypical and typical carcinoid tumor. Small cell carcinoma and large cell neuroendocrine carcinoma are considered high-grade lesions, atypical carcinoid as intermediate-grade lesions, and typical carcinoid as low-grade lesions. Of note, in the 4th edition WHO classification, NETs were introduced as a single major category, despite having been grouped into different categories in the previous (3rd) edition. The pathological diagnosis of LCNEC requires not only morphological characteristics but also the differentiation phenotype; this is a drastic change of mode. It is expected to help improve our understanding of a lesion's biological characteristics and facilitate the suitable selection of treatment options. The first-line treatment for pulmonary or mediastinal neuroendocrine tumors is surgical resection, but for unresectable cases, drug therapy is performed. For high-grade tumors, platinum-based chemotherapy is used, and for carcinoids, a wide range of treatment options, such as a somatostatin analogue and the mammalian target of rapamycin (mTOR) inhibitor everolimus, which is a molecular-targeted drug, are available. This review article outlines the epidemiology, pathological diagnosis, and treatment of pulmonary and mediastinal neuroendocrine tumors, including the latest findings. We hope this article will serve as a guide in routine clinical practice for rare tumors.

Introduction. Osimertinib, a 3rd-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has good efficacy in the treatment of lung adenocarcinoma harboring EGFR T790M mutation in patients who have previously received TKI treatment. Some cases present severe neutropenia and require dose reduction or discontinuation. Cases. We experienced two cases of advanced lung adenocarcinoma harboring EGFR T790M mutations in patients who had received several chemotherapies and EGFR-TKIs. Case 1 was a 72-year-old man who was a former smoker. Case 2 was an 82-year-old woman who was a non-smoker. The two patients received osimertinib treatment at the standard initial dose as 6th line and 7th line treatments, respectively. In both cases, severe neutropenia occurred as an adverse drug reaction. After several periods of short-term cessation, good clinical efficacy and sustained disease control with reduced-dose osimertinib treatment, without a recurrence of neutropenia. Conclusion. This report indicates that the neutropenia caused by osimertinib may be dose-dependent and that a reduced dose of osimertinib may be clinically effective and show good tolerability, while avoiding the recurrence of severe neutropenia.

Background. Nivolumab, an immune checkpoint inhibitor, is effective for previously treated advanced non-small cell lung cancer. However, drug-induced interstitial pneumonia in nivolumab has been reported in some cases, requiring immediate management. Case. A 67-year-old woman received adjuvant chemotherapy for adenosquamous carcinoma of the lung. After six months, computed tomography (CT) revealed multiple metastases involving the bilateral lung, right kidney, and accessory nerve lymph node. Nivolumab was started and achieved a partial response. After seven cycles of treatment, CT showed multiple patchy infiltrative shadows in the bilateral subpleural areas. According to the clinical course and imaging findings, drug-induced organizing pneumonia due to nivolumab was suspected, and 30 mg/day of prednisolone was administered after discontinuing nivolumab, which promptly improved the pneumonia. Conclusion. The immediate administration of steroids is important for cases that develop drug-induced organizing pneumonia during treatment with nivolumab.

Background. Immune-checkpoint inhibitors are an effective treatment option for non-small cell lung cancer. However, in contrast to observations with cytotoxic anticancer agents, pseudoprogression-wherein tumors reduce in size after an apparent increase-is occasionally noted with immune-checkpoint inhibitors. Case. A 57-year-old man was diagnosed with postoperative recurrence of lung adenocarcinoma. Nivolumab was administered as third-line treatment. He developed an infusion reaction just after the first course. After four courses, the inside part of the tumor appeared to be of low density on computed tomography (CT). Given that the tumor had increased in size, progressive disease (PD) was considered. However, we continued administering nivolumab, as his tumor marker levels had decreased. After eight courses, the tumor diameter increased further; however, the low-density area in the tumor had also increased, with a further decrease in the tumor marker level. The patient's whole-body state showed a trend towards improvement; we therefore judged the treatment to be effective. After 12 courses, the tumor finally reduced in size and showed a partial response (PR). Conclusion. Distinguishing true progress from pseudoprogression is important when immune-checkpoint inhibitors are used for treatment. Even if imaging findings suggest PD, parameters such as a decrease in the tumor marker levels, the appearance of a low-density area in the tumor, and the occurrence of immune-related adverse events (irAEs) should be considered. The possibility of pseudoprogression should be considered when deciding whether or not to continue treatment with immune-checkpoint inhibitors.

Background. Pleomorphic carcinoma (PMC) and mucoepidermoid carcinoma (MEC) of the lung are rare histological types of tumor. We herein describe a case of PMC and MEC occurring as synchronous multiple primary lung cancers. Case. A 74-year-old man was referred to our department because of a double mass in the left lower lobe. The examination of a transbronchial lung biopsy specimen confirmed the presence of non-small cell lung carcinoma (NSCLC). Both lesions were localized in the left lower lobe, and we performed thoracoscopic left lower lobectomy with lymph node dissection (2a-1). The pathological diagnoses were PMC (S⁶, pT3N0M0, Stage IIB) and MEC (S⁹, pT4N0M0, Stage IIIA). The postoperative course was uneventful. He left our hospital 2 weeks after surgery. Conclusion. We described a rare case of simultaneous PMC and MEC. This shows that multiple lung nodules can be synchronous multiple primary lung cancers as well as primary lung cancer and pulmonary metastases.

Background. Peritoneal carcinomatosis (PC) is a rare complication of lung cancer. Although several case reports have noted that epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor treatment was effective in the treatment of PC in patients with EGFR-positive lung cancer, few case reports have documented the successful treatment of driver mutation-negative lung cancer. Case. A 76-year-old man presented with dyspnea on exertion. He was diagnosed with stage IVB driver mutation-negative lung adenocarcinoma and received chemotherapy with cisplatin, pemetrexed, and bevacizumab as a first-line treatment followed by maintenance therapy with pemetrexed and bevacizumab. At one year and four months after the initiation of chemotherapy, abdominal computed tomography showed ascites and peritoneal thickening. A relapse of lung adenocarcinoma was diagnosed based on the presence of abdominal paracentesis. He was treated with pembrolizumab as a second-line therapy; however, his ascites increased. He received treatment with docetaxel as a third-line therapy and achieved stable disease. Conclusion. If a patient's performance status is good, docetaxel might be effective for the treatment of PC as a complication of relapsed lung cancer.

Background. It is sometimes difficult to distinguish non-small cell lung cancer with neuroendocrine differentiation from neuroendocrine carcinoma by specimens obtained by a transbronchial biopsy. In the present case, we diagnosed small cell carcinoma by a transbronchial lung biopsy before surgery, but the lesion turned out to be basaloid squamous cell carcinoma with neuroendocrine differentiation according to an examination of a surgically resected specimen. Case. Two tumors were observed in S² and S³ of the right upper lobe of an 83-year-old man, and we diagnosed the specimen as small cell carcinoma by a transbronchial lung biopsy of the S³ tumor. The patient had chronic kidney disease, so he underwent lung resection instead of definitive chemoradiotherapy. Right upper lobectomy was performed, and the postoperative pathologic diagnosis was basaloid squamous cell carcinoma with neuroendocrine differentiation. The S² tumor was pulmonary metastasis, the #4R lymph node was positive for cancer, and the pathological stage of lung cancer was IIIA. No recurrence has been recognized in the two years since the surgery. Conclusion. In the pathological diagnosis of micro specimens, a tumor may be non-small cell lung cancer with neuroendocrine differentiation even if it has small cell carcinoma morphology and positive neuroendocrine marker staining.

Background. Solitary fibrous tumors of the pleura (SFTP) are uncommon pleural tumors derived from mesenchymal cells. The mainstay of treatment for SFTP is surgical resection. Our patient declined a detailed evaluation and treatment of a giant intrathoracic tumor. We therefore observed the natural history of the tumor until the patient's death. Case. A 69-year-old woman with dyspnea was referred to our hospital for treatment. Although computed tomography showed a giant intrathoracic tumor occupying the right hemithorax, she declined a detailed evaluation and treatment. She was lost to follow-up until she presented to the hospital again, often with dyspnea. Over time, the tumor increased in size and began to compress the right lung and heart. At 82 years of age, she suffered from severe dyspnea and presented to our hospital. She died of respiratory failure. An autopsy revealed that the tumor, which was compressing the right lung and heart, arose from the visceral pleura. A histological examination revealed that it was a uniform spindle cell tumor. In addition, immunohistochemical staining revealed that the tumor cells were positive for CD34 and STAT6. As a result, the tumor was diagnosed as SFTP. Conclusion. The clinical course of SFTP is rarely observed. Although SFTP is considered a histologically benign tumor, its growth might lead to death due to compression of the heart and lungs.

Background. Ovarian metastasis from lung cancer is rare, with tumor-to-ovarian tumor metastasis even rarer. Case. A 79-year-old woman with a 1-month history of coughing was referred to our hospital. She was diagnosed with lung cancer as well as an ovarian tumor. Positron emission tomography/computed tomography (PET/CT) did not show any accumulation in the ovarian tumor, so we judged this lesion to be benign. The patient underwent surgical resection, and the pathological diagnosis was a pulmonary large-cell neuroendocrine carcinoma (LCNEC) pT3N1M0 stage IIIA. Thirteen months after surgery, the blood level of pro-gastrin-releasing peptide was elevated. A PET/CT scan showed a high fluorodeoxyglucose (FDG) uptake in the ovarian tumor. We suspected primary or metastatic ovarian cancer. Total hysterectomy with bilateral salpingo-oophorectomy and omentectomy was performed. The ovarian tumor was composed of mixed populations of spindle- and round-shaped tumor cells. The spindle-shaped tumor cells were diagnosed as forming an ovarian fibroma. However, the round-shaped tumor cells showed a morphology similar to that of the LCNEC with regard to positive neuroendocrine tumor markers according to an immunohistochemical analysis. Therefore, we diagnosed this as metastasis to an ovarian tumor from the LCNEC. Conclusion. We encountered a patient with a pulmonary LCNEC showing a tumor-to-ovarian tumor metastasis. We should consider the possibility of tumor-to-tumor metastasis for any benign tumor showing elevated tumor marker levels.