In recent years, the conditions in routine mesothelioma practice have changed dramatically. These changes include (1) the aging of patients, (2) the introduction of a combination of immune checkpoint inhibitors (nivolumab plus ipilimumab) that is superior to conventional chemotherapy, and (3) advances in the pathological diagnosis of cytology specimens, small biopsy tissue, and early-stage lesions. This review article outlines (i) the WHO 2021 classification, which for the first time introduced the category of "benign and preinvasive mesothelial tumors" including mesothelioma in situ, (ii) the morphological ancillary assays based on genetic alterations of mesotheliomas that enabled the diagnosis of the new disease category, and (iii) its application to cytology, followed by (iv) an overview of the genetic alterations in mesothelial tumors and mesothelioma subtypes. Given that over 80% of pleural mesotheliomas initially present with pleural effusions, the role of cytology is expected to become more important. However, there are caveats and pitfalls associated with the application of ancillary assays, and the careful management and evaluation are desirable. Furthermore, diagnosing mesothelioma is challenging for pathologists alone, so it is essential that the results of histology and ancillary assays always be assessed and interpreted together with clinical and imaging findings.

Among adjuvant therapies for completely resected non-small cell lung cancer (NSCLC), postoperative platinum-based adjuvant chemotherapy has been a standard of care. While postoperative radiotherapy (PORT), as an important option for treating local lesions, has been expected to be able to reduce local recurrence and further improve both the disease-free survival (DFS) and overall survival (OS) for a long period, benefit of PORT for the DFS or OS has not been verified yet, despite promoting locoregional control. In particular, a detrimental effect of PORT was observed in patients with pathological N0-1 stage I-II NSCLC. In contrast, several retrospective studies have demonstrated that PORT improved the survival of patients with pathological N2 (pN2) stage III NSCLC, proving to be a promising therapy for those patients. Regarding surgery, about 20% of patients with pN2 stage III NSCLC develop recurrence inside the systematic nodal dissection area. Accordingly, locoregional control by surgery alone seems to be insufficient. In 2021, two randomized, phase III clinical trials (Lung ART and PORT-C) revealed that PORT improved locoregional control, although this did not translate to a significant gain in the survival. Therefore, PORT still cannot be recommended as a standard treatment in patients with pN2 stage III NSCLC. A randomized phase III trial (JCOG1916: J-PORT) involving PORT for pN2 NSCLC patients with adjuvant chemotherapy is currently underway in Japan and might bring further insight in the future. At present, molecular-targeted therapies and immunotherapies are being studied in the adjuvant setting, and immune checkpoint inhibitors have been adopted as an adjuvant therapy for patients with completely resected stage II-IIIA NSCLC. In this setting, the role of PORT merits further exploration. Given that radiotherapy and immunotherapy can synergistically activate anti-tumor immunity, PORT concomitantly or sequentially combined with immunotherapy might be a promising potential treatment modality.

The emergence of effective systemic therapies, such as immune checkpoint inhibitors and molecular-targeted therapies, and the introduction of precision medicine have improved survival outcomes in advanced non-small-cell lung cancer. However, only a fraction of cases can avoid recurrence or progression. Under such circumstance, awareness of the disease state known as "oligometastases" has increased, and a multidisciplinary treatment strategy combining systemic and local ablative therapies has been explored for certain patients potentially aiming for a cure. The primary local treatment for oligometastatic lung cancer is obviously radiation therapy, with high-precision radiation therapy being at the core of local ablative therapy in several ongoing randomized phase III trials. However, studies exclusively on surgical treatment for oligometastatic lung cancer have been limited so far, although there are situations where surgical treatment is prioritized for local lesions in daily clinical practice. When considering the surgical indications for oligometastatic lung cancer, it is important to evaluate the "status of the primary lesion and metastatic lesions" and "safety of local treatment. " Surgical treatment for oligometastatic lung cancer is considered an exploratory intervention, and strict preoperative risk assessment is required due to the extreme importance of the management of postoperative complications. It is essential to clarify the criteria for surgical treatment in order to systematically develop an oligometastatic lung cancer treatment strategy in the future.

Objective. Mesothelioma patients can use the Industrial Accident Compensation Insurance Act or Asbestos Health Damage Relief System. However, the resolution of economic problems varies from person to person, and the factors that contribute to such differences have not yet been clarified. In this paper, we examine the factors and issues that cause patients to become aware of financial difficulties based on changes in their employment status. Study Design. A questionnaire survey was administered to patients, and a multiple regression analysis using a stepwise method was conducted with economic deprivation as the dependent variable and 5 items related to the status of certification and application to the system and 7 items related to the status of employment as independent variables. We also compared the number of occurrences of perceived economic deprivation at around 60 years of age. Results. When the number of patients who indicated "Asbestos Health Damage Relief System certification" and "Temporary retirement" increased, the number of patients who indicated that they were "aware of economic hardship" also increased. When the employment status was compared at around 60 years of age, "continuous employment" and "leave of absence" were significantly more common among respondents younger than 60 years of age, while "unemployed/pensioner" was significantly more common among respondents older than 60 years of age. Conclusion. It was found that perceived financial distress was more likely be reported by patients who had taken a leave of absence after the onset of mesothelioma and patients who had been certified under the Asbestos Health Damage Relief System, especially patients younger 60 years of age who were more likely to lose income from employment and to have an unstable financial base. Therefore, it is necessary to review the design of the system and expand counseling support for young and middle-aged people who used to be employed.

Background. Osimertinib, which is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has shown significant efficacy in EGFR mutation-positive non-small cell lung cancer. Case. The patient was a 76-year-old man who was diagnosed with lung adenocarcinoma (T2aN3M0, stage IIIB), EGFR exon 19 deletion in December 2020. The patient received osimertinib from January 2021. He developed dyspnea from February 2021. He was diagnosed with heart failure and received azosemide in April 2021. His dyspnea worsened from July 2021, and he was admitted to the cardiology department in August 2021. Heart failure improved with the administration of vasopressor and diuretics. After his discharge from the hospital, osimertinib was changed to gefitinib. His heart failure and lung cancer have not worsened since the change. Conclusion. If signs of heart failure are observed during treatment with osimertinib, the discontinuation of treatment or drug modification should be considered immediately.

Background. There is no standard treatment for pulmonary epithelioid hemangioendothelioma (PEHE). Case. A 48-year-old woman was diagnosed with PEHE in year X-8 and followed without medical treatment. She was diagnosed with hepatic metastasis of PEHE in year X. Maintenance therapy with carboplatin (CBDCA), pemetrexed (PEM), and bevacizumab (BEV) helped prevent disease progression. Conclusion. Chemotherapy with CBDCA, PEM, and BEV may be effective for PEHE.

Background. Hypercalcemia is one of the paraneoplastic syndromes. Because most lung cancer patients with symptomatic hypercalcemia have advanced-stage lung cancer, few patients are resectable and have the chance to receive lung resection. We report the case of a patient who underwent left lower lobectomy for lung cancer after presenting with a loss of appetite and fatigue due to hypercalcemia. Case. An 82-year-old male former smoker presented with left pulmonary tumor on chest X-ray. Computed tomography showed a 7.6-cm tumor with cavities in the left lower lobe. Following a transbronchial biopsy and imaging examination, the patient was diagnosed with stage IIIA lung squamous cell carcinoma in his left lower lobe. He had a loss of appetite before surgery and a blood test indicated hypercalcemia, high parathyroid hormone-related protein (PTHrP), and low intact parathyroid hormone (PTH). The patient was diagnosed with paraneoplastic syndrome due to lung cancer of the left lower lobe. Thoracoscopic left lower lobectomy was performed. Serum calcium rapidly improved to within the normal range after surgery. Subsequently, the patient's appetite and fatigue improved. He was discharged from the hospital on postoperative day 7 with no complications. During follow-up, serology testing revealed that the serum calcium level was within the normal range, and that PTHrP decreased and was also within the normal range. Pathological testing of the resected tumor confirmed the diagnosis as a pT4N0M0 stage IIIA keratinizing squamous cell carcinoma and immunohistochemical staining showed that the specimen was partially positive for PTHrP. Conclusion. Resection should be considered for patients with PTHrP-producing lung cancer with hypercalcemia. The findings from our case indicated that hypercalcemia can be expected to rapidly improve after tumor resection.

Background. In the treatment of lung cancer, cancer immunotherapy with immune checkpoint inhibitors (ICIs) may cause or exacerbate immune-related adverse events (irAEs) in patients with pre-existing autoimmune diseases. Case. A 72-year-old man was referred to our hospital with complaints of fever and back pain. After a thorough medical examination, he was diagnosed with extensive stage small cell lung cancer (SCLC) complicated by Lambert-Eaton myasthenic syndrome (LEMS) and obstructive pneumonia. After receiving carboplatin/etoposide plus atezolizumab therapy, he is currently on maintenance therapy with atezolizumab. Conclusion. Although there are several reports of LEMS as an irAE caused by ICI therapy, we report a case of SCLC complicated by LEMS, in which the patient was treated with atezolizumab, and in which both LEMS and SCLC had an uneventful course.

Background. Malignant mesothelioma is a rare, aggressive cancer with limited treatment options and a poor prognosis. Malignant pleural mesothelioma has shown a good therapeutic response to checkpoint inhibitors. In Japan, immune checkpoint inhibitors, including nivolumab and ipilimumab and their combination, have been approved for treating malignant pleural mesothelioma but not for other types of malignant mesothelioma. Case. A 72-year-old man consulted a local general hospital because of bilateral inguinal masses. The pathological examination of biopsy samples collected from the bilaterally enlarged spermatic cords were compatible with a diagnosis of malignant mesothelioma. The patient was referred to our hospital for multidisciplinary treatment. He initially received chemotherapy with cisplatin and pemetrexed and showed a good response. However, computed tomography subsequently showed increased right pleural thickening, right pleural effusion, and an enlarged spermatic cord lesion. He was treated with ipilimumab+nivolumab combination therapy. This therapy reduced the size of his spermatic cord lesion but failed to control his pleural lesion. He was subsequently treated with vinorelbine, which was also ineffective. Conclusion. This case illustrates the potential efficacy and limitations of immune checkpoint inhibitors for malignant mesothelioma.

Background. Bronchiolar adenoma/ciliated muconodular papillary tumor (BA/CMPT) is a benign tumor with a rare histology. However, the development of BA/CMPT on computed tomography (CT) remains unclear. We herein report a case of BA/CMPT showing growth after 1.5 years of CT follow-up. Case. A 67-year-old man presented to our hospital for surgery for a ground-glass opacity nodule in the right lower lobe. He underwent wedge resection after CT-guided marking with indigo carmine and lipiodol mixture. Pathologically, the nodule was diagnosed as BA/CMPT. In addition, we examined 10 cases of BA/CMPT in our institution and summarized the clinical background, CT findings and genetic alterations. Conclusion. We experienced a case of BA/CMPT growth and examined 10 cases in our institution. BA/CMPT is a rare tumor that grows under CT observation. It is important to diagnose BA/CMPT promptly because of its favorable prognosis and the probability of malignancies with genetic alterations.