Objective. To improve the clinical guidelines for lung cancer. Methods. By focusing on the discussion topics at a symposium held in the annual meeting of the Japan Lung Cancer Society 2020 and the results of two independent external evaluations of the guidelines, the history, advantages and limitations of the guidelines were reviewed with respect to problems to be solved. Results. The guidelines were established in 2003 and have been updated annually since 2011. Their contemporary and scientific validity are highly evaluated by external evaluations, whereas the constitutive framework has found to be lacking in many aspects. Rapid advancement in molecular target therapy and therapy with immune checkpoint inhibitors has forced changes in the methodology of clinical trials and in statistical interpretation, resulting in multiple recommendations for a certain specific disease condition. It is important to address the wide diversity of values used for the evaluation of therapeutic outcomes. Conclusion. Problems include heterogeneity in clinical trials, the methodology of interpretation and individual values. Although various medical staff, biostatisticians and patients were already involved in the process of preparing the guidelines, much wider discussion among various stakeholders should be undertaken to solve these problems and improvements that reflect external evaluation should be implemented.

Background. Cavernous hemangioma in the mediastinum is relatively rare, accounting for ≤0.5% of all mediastinal tumors. Case 1. A 72-year-old woman was found to have an abnormal shadow at a medical examination. Chest computed tomography showed a 27-mm lobulated nodule in the left anterior mediastinum. Paraganglioma and carcinoid were suspected. Paraganglioma was excluded through a careful examination. The intraoperative findings showed the tumor to be hemorrhagic, and the surface was red in tone. The tumor was thus suspected of being hemangioma. The phrenic nerve went through surface of the tumor, but we considered it benign, so the phrenic nerve was preserved, and the tumor was resected. Case 2. A 64-year-old man was found to have an enlarged left mediastinal shadow at a medical examination. Chest computed tomography showed a 60-mm nodule in the left anterior mediastinum and poor contrast effect. Thymoma was suspected, and extended thymomectomy was performed. Combined resection of the left phrenic nerve was performed because the nerve was involved with the tumor. The transmanubrial approach was required due to adhesion between the left brachiocephalic vein and the tumor. Conclusion. Mediastinal cavernous hemangioma presents with a variety of image findings, and a precise preoperative diagnosis can be quite difficult. However, cavernous hemangioma is an important differential diagnosis of mediastinal tumor.

Background. Granulocyte colony-stimulating factor (G-CSF)-producing tumor is associated with leukocytosis and a poor prognosis. Case. The comprehensive evaluation of a 55-year-old woman revealed a right upper lobe mass with chest wall infiltration and leukocytosis. A histological examination following right upper lobectomy with chest wall resection revealed G-CSF-producing pulmonary pleomorphic carcinoma. Her disease was judged to be pathological stage IIB (T3bN0M0). Leukocytosis persisted after the surgery for two months. A further examination revealed wall thickening limited to the small intestine, so enterectomy was performed, which revealed a metastatic lesion. Leukocytosis was subsequently normalized. We administered four courses of systemic chemotherapy consisting of carboplatin, paclitaxel, and bevacizumab. In addition, we administered bevacizumab-based maintenance chemotherapy for 50 cycles. Although G-CSF-producing lung carcinomas are associated with poor prognoses, she remained free of recurrence for five years after surgery. Conclusion. In the present case, surgery and bevacizumab-based systemic and maintenance chemotherapy may have been effective against G-CSF-producing pulmonary pleomorphic carcinoma.

Background. Therapeutic effects of chemotherapy and radiotherapy have been reported for thymic carcinoma, but the evidence is scarce. We herein report a case of postoperative intrathoracic recurrence in which a long-term progression-free survival was achieved by radiotherapy and sequential chemotherapy. Case. A 55-year-old man underwent extended thymectomy and a lymph node biopsy for anterior mediastinal tumor. Six months after the operation, recurrence was observed in the right anterior chest. Radiation therapy was performed, chemotherapy with carboplatin and paclitaxel was performed, and a complete response was obtained. Sixty months have passed since successive radiochemotherapy was performed for recurrence, and no recurrence had been observed, with the patient still alive. Conclusion. We herein report a valuable case in which a five-year progression-free survival was obtained by sequential radiochemotherapy for a recurrent case of thymic carcinoma.

Background. Pulmonary adenoid cystic carcinoma (PACC) is a rare tumor and may be differentially diagnosed as small-cell lung carcinoma (SCLC). We herein report a case of resected PACC that was differentially diagnosed as SCLC. Case. We encountered a 62-year-old non-smoking woman in whom a small nodule on the lower left lobe of the lung was revealed during chest X-ray. Chest computed tomography revealed that a 20-mm diameter nodule had developed in the anterior basal segment of the lung. The tumor was diagnosed as SCLC using a transbronchial biopsy (cT1bN0M0, stage IA2). The patient underwent left lower lobectomy in the department of the hospital. Although a pathological examination revealed that the resected tumor had morphological characteristics similar to SCLC, the results of immunohistochemical staining led to a final diagnosis of differentiated PACC. Conclusion. Although PACC may be differentially diagnosed as SCLC, these cancers require different treatments. If SCLC is clinically unlikely, it is necessary to perform immunohistochemical staining and make a sufficient differentiation from other tumors, such as PACC.

Background. Preservation of the nerve and shoulder joint function is important in patients who undergo excision of superior sulcus tumors. Case. A 25-year-old woman diagnosed with neurofibromatosis type 1 in childhood presented with a 1-year history of left shoulder dullness. The shoulder pain worsened, and chest computed tomography revealed a tumor (51×42 mm) originating from the left superior sulcus. Magnetic resonance imaging revealed that the tumor had increased in size from 35 to 51 mm within a year. The tumor was successfully excised via a transmanubrial approach under electrophysiological monitoring without any brachial plexus injury. A histopathological evaluation indicated a malignant peripheral nerve sheath tumor. We observed no postoperative complications, including neurological injury. The patient was followed up and showed no recurrence over 2 years. Conclusion. We recommend the transmanubrial approach as a valuable operative procedure for excision of nerve sheath tumors originating from the superior sulcus. Notably, electrophysiological monitoring is important to avoid peripheral nerve injuries.

Background. Checkpoint inhibitor pneumonitis (CIP) has been reported as a common immune-related adverse event induced by immune checkpoint inhibitors (ICIs). There have been few reports on the efficacy and safety of ICI re-administration following drug withdrawal due to CIP. Case. A 70-year-old man diagnosed with pulmonary adenocarcinoma (cStage IVB) was treated with pembrolizumab. Although he achieved a partial response (PR), he developed grade 2 CIP and adrenocortical insufficiency after the 10th administration of pembrolizumab. CIP improved after pembrolizumab withdrawal and prednisolone (PSL) administration. Following pembrolizumab withdrawal, the left hilar lymph node increased in size. After explaining our intention to administer chemotherapy, the patient expressed a preference for the re-administration of an ICI. In addition, ICI therapy seemed to be promising in this patient due to his high expression of PD-L1 (75%) and favorable response to pembrolizumab. Due to concerns about pembrolizumab-associated CIP recurrence, atezolizumab was administered as a second-line therapy. Although CIP repeatedly developed after 6 cycles of atezolizumab, it was within the acceptable range of grade 1, and atezolizumab was eventually administered for 18 cycles without exacerbation of CIP. Conclusion. This case showed that the continuous administration of an ICI was possible despite repeated CIP.

Background. The administration of an immune checkpoint inhibitor (ICI) to patients with rheumatoid arthritis worsens joint symptoms. No study has focused on carcinomatous polyarthritis (CP), which develops as a paraneoplastic syndrome-like symptom of rheumatoid arthritis, recurring after the administration of an ICI. Case. A 50-year-old man had joint pain from August X and was referred to our hospital for suspected rheumatoid arthritis in October X. The patient had multiple joint pain without joint swelling or hot sensation. He was diagnosed with left upper lobe lung adenocarcinoma and underwent left upper lobectomy and lymph node dissection in December X. After surgery, the joint pain resolved without any treatment; therefore, the patient was diagnosed with paraneoplastic syndrome. Furthermore, he was diagnosed with lung cancer recurrence and received chemoradiotherapy in November X+1. After chemoradiotherapy, the patient received durvalumab in January X+2. After the administration of durvalumab twice, the joint pain recurred, being considered relapse of CP. The symptoms improved after the oral administration of a steroid, and durvalumab was able to be continued. Conclusion. Relapsed symptoms were observed in a patient with CP following durvalumab administration; however, durvalumab was able to be continued following steroid administration.

Background. IgG4-related disease is a fibroinflammatory condition that is capable of affecting multiple organs. There are no previous reports of cases involving a lesion on the paravertebral body alone, and only a few cases involving complication with primary lung cancer have been reported. Case. The patient was a 67-year-old man who had been diagnosed with multiple ground glass nodules (GGNs) on chest CT 6 years previously. During follow-up, a GGN in the right upper lobe increased in size, and lung cancer was suspected. Thus, he presented to our department 2 years previously. Soft tissue tumors around the Th10 vertebral body were recognized at the initial visit to our hospital, and showed a tendency toward enlargement. Right upper lobectomy and a biopsy of the tumor on the paravertebral body revealed that the GGNs were lung adenocarcinoma. A histological examination of the paravertebral tumor revealed IgG4-positive plasma cell infiltration and an increased IgG4 concentration, leading to a diagnosis of IgG4-related disease. Conclusion. This is a valuable case of IgG4-related disease composed of only a paravertebral lesion that co-existed with multiple lung adenocarcinomas.

Background. Ciliated muconodular papillary tumor (CMPT) is a rare lesion characterized by the papillary growth of ciliated and goblet cells, making it difficult to distinguish from primary lung adenocarcinoma. Case. A man in his 60s was followed for a 1.3-cm partially solid nodule (solid component diameter: 0.9 cm) in S⁹ of the left lung, as observed on abdominal computed tomography (CT) before surgery for renal cancer. Chest CT at the three-year follow-up examination revealed an increase in the solid diameter of the tumor, while 18F-fluorodeoxyglucose-positron emission tomography showed a low maximum standardized uptake value of 1.1. Primary lung cancer with cT2a (PL1) N0M0 or a metastatic lung tumor from renal cancer was suspected, and the patient underwent surgical resection for a histopathological diagnosis and treatment. A rapid intraoperative histopathological diagnosis from the partial resection specimen revealed primary lung adenocarcinoma; therefore, thoracoscopic left lower lobectomy was performed. In the routine histopathological specimen, cuboidal and columnar epithelial cells arranged in a single layer were found to have replaced the alveolar epithelium, and cilia were observed on the airspace side of the cells. Mucus accumulation was noted in the area corresponding to air space. The final histopathological diagnosis of the nodule was CMPT. In addition, a small 3-mm nodule found in S⁶ of the resected lung showed a similar histology, resulting in a diagnosis of multiple CMPTs. Conclusion. We reported a rare case of simultaneous multiple CMPTs in the same lobe mimicking primary adenocarcinomas with lepidic growth on preoperative CT and an intraoperative histopathological diagnosis.

Background. Combined small cell lung carcinoma is a small cell cancer containing non-small cell lung cancer components, such as adenocarcinoma and/or squamous cell carcinoma. Case. A 61-year-old man with chronic hepatitis B and hepatocellular carcinoma was admitted to our hospital because of a nodule in the right lower lobe that was detected on follow-up CT. His serum carcinoembryonic antigen level was slightly elevated. High-resolution CT revealed a lobulated nodule measuring 10 mm in diameter. Fiberoptic bronchoscopy was nondiagnostic. However, lung cancer was suspected because the nodule increased in size on serial CT. Thoracoscopic right lower lobe resection with mediastinal lymph node resection was performed. A pathological examination of the resected specimen revealed a tumor composed of similar proportions of small cell carcinoma cells, adenocarcinoma cells, and squamous cell carcinoma cells. Conclusion. Most combined small cell carcinomas contain cells of one type of non-small cell carcinoma; however, in the present case, small cell carcinoma, adenocarcinoma, and squamous cell carcinoma cells were distinctively present in similar proportions.