Small-Cell Lung Cancer Comorbid with Pulmonary Mycobacterium avium Infection: A Case Report.

BACKGROUND: Small-cell lung cancer (SCLC) rarely coexists with pulmonary Mycobacterium avium intracellular complex (MAC) infection. The key drug for SCLC treatment is etoposide, which is metabolized by cytochrome P-450 (CYP) 3A4. Meanwhile, the key drugs for pulmonary MAC infection are clarithromycin (CAM) and rifampicin (RFP), and their metabolism influences CYP3A4. Therefore, treatment of concurrent SCLC and pulmonary MAC infection is difficult, and to the best of our knowledge, no report of treatments for concurrent SCLC and pulmonary MAC infection has been published. Patient Concerns and Diagnoses: A 65-year-old man presented to our hospital with abnormal findings of chest computed tomography: (1) a hilar region nodule in the left lung and mediastinal lymphadenopathy and (2) a thick-walled cavity lesion in the right upper lobe of the lung. After further examinations, the former lesions were diagnosed as SCLC, cT4N3M0, stage IIIC and the latter as pulmonary MAC infection, fibrocavitary disease. INTERVENTIONS AND OUTCOMES: Concurrent treatment was conducted with discontinuation of CAM and RFP before and after etoposide administration. Specifically, intravenous cisplatin and etoposide were administered on day 1 and days 1-3, respectively, and CAM, RFP, and ethambutol (EB) were administered orally on days 6-22 every 4 weeks. Concurrent radiotherapy was added to the drug administration on days 1-27 of the first cycle. The chemotherapy was continued for 4 cycles, followed by continuation of CAM and RFP administration. EB was discontinued because of optic nerve disorder. The treatments were conducted completely and safely, and both of the SCLC lesions and the MAC lesion were improved. CONCLUSIONS: Treatments for concurrent SCLC and pulmonary MAC infection may be successfully conducted with discontinuation of CAM and RFP before and after etoposide administration.

Gene expression profiling of idiopathic interstitial pneumonias (IIPs): identification of potential diagnostic markers and therapeutic targets.

BACKGROUND: Chronic fibrosing idiopathic interstitial pneumonia (IIP) is characterized by alveolar epithelial damage, activation of fibroblast proliferation, and loss of normal pulmonary architecture and function. This study aims to investigate the genetic backgrounds of IIP through gene expression profiling and pathway analysis, and to identify potential biomarkers that can aid in diagnosis and serve as novel therapeutic targets. METHODS: RNA extracted from lung specimens of 12 patients with chronic fibrosing IIP was profiled using Illumina Human WG-6 v3 BeadChips, and Ingenuity Pathway Analysis was performed to identify altered functional and canonical signaling pathways. For validating the results from gene expression analysis, immunohistochemical staining of 10 patients with chronic fibrosing IIP was performed. RESULTS: Ninety-eight genes were upregulated in IIP patients relative to control subjects. Some of the upregulated genes, namely desmoglein 3 (DSG3), protocadherin gamma-A9 (PCDHGA9) and discoidin domain-containing receptor 1 (DDR1) are implicated in cell-cell interaction and/or adhesion; some, namely collagen type VII, alpha 1 (COL7A1), contactin-associated protein-like 3B (CNTNAP3B) and mucin-1 (MUC1) are encoding the extracellular matrix molecule or the molecules involved in cell-matrix interactions; and the others, namely CDC25C and growth factor independent protein 1B (GFI1B) are known to affect cell proliferation by affecting the progression of cell cycle or regulating transcription. According to pathway analysis, alternated pathways in IIP were related to cell death and survival and cellular growth and proliferation, which are more similar to cancer than to inflammatory response and immunological diseases. Using immunohistochemistry, we further validate that DSG3, the most highly upregulated gene, shows higher expression in chronic fibrosing IIP lung as compared to control lung. CONCLUSION: We identified several genes upregulated in chronic fibrosing IIP patients as compared to control, and found genes and pathways implicated in cancer, rather than in inflammatory or immunological disease to play important roles in the pathogenesis of IIPs. Moreover, DSG3 is a novel potential biomarker for chronic fibrosing IIP with its significantly high expression in IIP lung.

[Effectiveness of Nivolumab in Large-Cell Neuroendocrine Carcinoma of the Lung - A Report of Two Cases].

BACKGROUND: The anti-programmed death-1 antibody nivolumab is an important treatment option for non-small-cell lung carcinoma.However, its effectiveness for large-cell neuroendocrine carcinomas(LCNEC)is still controversial.Here, we report 2 cases of LCNECs that responded to nivolumab.Case 1: A 62-year-old man received chemotherapy and radiotherapy for stage III A lung adenocarcinoma.One year later, another lung lesion was observed and diagnosed as LCNEC using surgical lung biopsy.Although he subsequently received some chemotherapy regimens, the patient developed new brain metastasis, expanded mediastinal lesion, and increased levels of the tumor marker pro-gastrin releasing peptide(ProGRP).We started nivolumab as the sixth-line treatment.In response, ProGRP levels significantly decreased and the mediastinal lesion became smaller.Case 2: A 55-year-old man was diagnosed with stage III A LCNEC and received chemotherapy and radiotherapy.The primary lesion was controlled; however, lung metastases developed and chemotherapy was unable to control them.We provided treatment with nivolumab as the third-line therapy.The tumor marker ProGRP decreased and the lung metastases became smaller. CONCLUSION: Nivolumab can be a valuable treatment option for LCNEC.

Atezolizumab-induced Sclerosing Cholangitis in a patient with lung cancer: A case report.

Atezolizumab is an immune checkpoint inhibitor that is a key drug in non-small-cell lung cancer treatment. However, it can cause immune-related adverse events, including liver injury. Several patterns of liver injury associated with immune checkpoint inhibitor therapy have been reported; however, not much is known about sclerosing cholangitis. We present here a case of lung adenocarcinoma with atezolizumab-induced secondary sclerosing cholangitis diagnosed using needle biopsy of the liver. A 77-year-old woman with lung adenocarcinoma, cT3N2M0, stage IIIA, was treated with concurrent chemoradiotherapy involving carboplatin and paclitaxel, which markedly reduced the tumor diameter. However, 5 months later, the lesion regrew, and she underwent 39 cycles of pemetrexed monotherapy. As pulmonary metastasis progressed, she was treated with atezolizumab. After 13 cycles of atezolizumab therapy, she complained of nausea. Laboratory tests showed elevated levels of the biliary tract and hepatic enzymes. Nevertheless, abdominal computed tomography and ultrasonography revealed no underlying related cause. Ultrasound-guided needle biopsy of the liver was performed, and histopathological analysis of biopsy samples showed features of sclerosing cholangitis. Further examinations were performed, and a diagnosis of atezolizumab-induced secondary sclerosing cholangitis without strictures and dilatations of the large bile ducts was established. Prednisolone was administered orally, after which the biliary tract and hepatic enzyme levels improved immediately. In patients presenting with a hepatic injury during immune checkpoint inhibitor therapy, clinicians should be aware of the possibility of immune checkpoint inhibitor-induced sclerosing cholangitis, even if the large bile ducts have no strictures and dilatations.

Smoldering adult T-cell leukemia complicated with pneumocystis pneumonia: A case report.

Adult T-cell leukemia (ATL) is a tumor of CD4-positive T cells that accompanies an infection by human T-cell lymphotropic virus (HTLV-I). ATL is classified into four types-acute, lymphomatous, chronic, and smoldering. Opportunistic infections are known to occur in patients with acute or lymphomatous type ATL; however, whether patients with chronic or smoldering ATL also have a high risk of opportunistic infections is not yet known. Herein, we report a case of pneumocystis pneumonia in a patient with smoldering ATL. He was a 64-year-old man with primary complaints of cough and dyspnea on exertion. A chest radiograph showed infiltration shadows in the left lung field. He was prescribed antibiotics for pneumonia; however, his symptoms worsened, and he developed hypoxemia. White-blood cell count was 13000/µL, and 7% of atypical lymphocytes were found in the smears of peripheral blood cells. His serum ß-D glucan concentration was increased to 85.9 pg/mL, and his serum tested positive for anti-HTLV-1 antibody. Chest-computed tomography revealed diffuse ground-glass opacities in the bilateral lung fields. Pneumocystis-polymerase chain reaction performed on bronchoalveolar lavage fluid confirmed pneumocystis, but atypical lymphocytes were not detected via transbronchial lung biopsy. Therefore, he was diagnosed with pneumocystis pneumonia associated with smoldering ATL. Sulfamethoxazole-trimethoprim and corticosteroid therapies were administered to treat the pneumocystis pneumonia, and his symptoms and lung shadows improved rapidly. Thus, opportunistic infections, including pneumocystis pneumonia, may be caused by smoldering ATL. In the case of atypical lymphocyte detection in peripheral-blood smears, clinicians should consider the possibility of ATL.

Efficacy of erlotinib and its effects on the quality of life of older patients with epidermal growth factor receptor-mutant non-small cell lung cancer: A prospective, multicenter, dose-modification study.

AIM: Gefitinib and erlotinib are efficacious and safe for older patients with epidermal growth factor receptor-mutant non-small cell lung cancer. However, prolonged use of epidermal growth factor receptor-tyrosine kinase inhibitors in older patients is difficult, owing to potential adverse events. Hence, dose reduction or treatment discontinuation is often required. We investigated the efficacy of low-dose first-line erlotinib and its effects on the quality of life of older patients with lung cancer. METHODS: A prospective, multicenter, phase II clinical trial was carried out in patients aged ≥75 years with epidermal growth factor receptor-mutant non-small cell lung cancer. Initially, 100 mg/day erlotinib was administered orally; if well tolerated, it was increased to 150 mg/day. The primary end-point was progression-free survival, and secondary end-points were the response rate, overall survival and change in quality of life ("Care Notebook" questionnaire). RESULTS: The median progression-free survival was 17.8 months, response rate was 63.6% and median overall survival was 27.8 months. The change in the quality of life after 6 weeks was assessed in 72.7% of the patients. Fatigue, pain, anxiety and deterioration in daily activities were found in at least 40% of the patients. Despite the therapeutic effect of 100 mg/day erlotinib, many patients required dose reduction, and in some, the quality of life could not be maintained. CONCLUSIONS: Many older patients with epidermal growth factor receptor-mutant non-small cell lung cancer might require treatment dose reduction. Further studies are required to develop individualized treatments for older patients with lung cancer. Geriatr Gerontol Int 2021; 21: 881-886.

Organizing pneumonia in a carrier of human T-cell lymphotropic virus type-1.

Human T-cell lymphotropic virus type-1 (HTLV-1)-associated bronchioloalveolar disorders (HABAs) are pulmonary disorders with various interstitial lung disease patterns that often occur in HTLV-1 carriers. Among HABAs, organizing pneumonia (OP) is extremely rare. We present a case of an 82-year-old woman with OP as a HABA. This patient responded to corticosteroid therapy; however, the patient required the continuation of oral corticosteroid therapy to avoid OP relapse. In cases of OP as a HABA that are not stabilized by treatment with corticosteroids, continuation of oral corticosteroid therapy might be considered.

Multiple patchy pulmonary consolidation in granulomatosis with polyangiitis.

Multiple patchy pulmonary consolidations that are unresponsive to antibiotics and/or exist at peri-bronchial sites and bloody bronchoalveolar lavage may effectively help clinicians diagnose granulomatosis with polyangiitis.

Platinum-doublet chemotherapy followed by pembrolizumab therapy for lung cancer with lymphangitis carcinomatosa mimicking interstitial pneumonitis: A case report.

RATIONALE: Pembrolizumab, an immune-checkpoint inhibitor (ICI), has been shown to be effective for treatment-naive patients with non-small cell lung cancer (NSCLC) and high expression of programmed death-ligand 1 (PD-L1). Therefore, treatment regimens containing pembrolizumab have become a standard therapy for these patients. However, the use of pembrolizumab is limited owing to the side effects of ICIs. PATIENT CONCERNS AND DIAGNOSES: The patient was a 65-year-old man with a left lung mass surrounded by interstitial shadow. The tumor was diagnosed as adenocarcinoma, cT4N3M0, stage IIIC, and the tumor cells showed high PD-L1 expression. It was unclear whether the interstitial shadow was interstitial lung disease (ILD) or lymphangitis carcinomatosa. INTERVENTIONS AND OUTCOMES: The patient received carboplatin and nab-paclitaxel, a less risky regimen for ILD, as the first-line therapy. Administration of 2 cycles of this regimen markedly improved both the tumor diameter and interstitial shadow. The interstitial shadow was clinically diagnosed as lymphangitis carcinomatosa and not ILD. Subsequently, the patient was treated with pembrolizumab, and the tumor showed much further shrinkage with no deterioration of the interstitial shadow. To date, the patient is alive with no complaints and no disease progression, and has continued pembrolizumab treatment for a total of 12 months. LESSONS: In patients at a high risk of ICI-related side effects, platinum-doublet chemotherapy may be permitted as the first-line therapy for NSCLC with high PD-L1 expression. However, if the risk associated with ICIs is resolved, early switching from chemotherapy to pembrolizumab might be desirable, even if the chemotherapy is effective.

Pericardial Effusion With Tamponade in Lung Cancer Patients During Treatment With Nivolumab: A Report of Two Cases.

Background: Nivolumab is an immune checkpoint inhibitor (ICI) that has shown efficacy for treating non-small cell lung cancer and has become a standard therapy for previously treated non-small cell lung cancer. Moreover, immune-related adverse events of ICI therapy are well-known. Malignant pericardial effusions occasionally arise in patients with lung cancer. There have been a few reports of pericardial effusion in non-small cell lung cancer after nivolumab administration. However, the cause of this condition is controversial; the possibilities include serositis as an immune-related adverse event or pseudo-progression. Case Presentation: This report presents two cases of pericardial effusion with tamponade in lung cancer during treatment with nivolumab. Both patients experienced temporal increases in pericardial effusions followed by effusion regression. In one case, nivolumab administration was continued after performance of pericardiocentesis, without an increase in pericardial effusion. In the other case, temporal simultaneous increases in both the pericardial effusion and the primary tumor were detected, followed by simultaneous regression in both the effusion and the tumor. These findings support the fact that the pericardial effusions were caused by pseudo-progression. Conclusions: Pericardial effusion with tamponade can occur in lung cancer patients being treated with nivolumab; moreover, some of these effusions might be caused by pseudo-progression. In the case of putative pseudo-progression, continuation of nivolumab administration might be allowable with strict follow up.

Activation of KIF4A as a prognostic biomarker and therapeutic target for lung cancer.

PURPOSE AND EXPERIMENTAL DESIGN: To identify molecules that might be useful as diagnostic/prognostic biomarkers and as targets for the development of new molecular therapies, we screened genes that were highly transactivated in a large proportion of 101 lung cancers by means of a cDNA microarray representing 27,648 genes. We found a gene encoding KIF4A, a kinesin family member 4A, as one of such candidates. Tumor tissue microarray was applied to examine the expression of KIF4A protein and its clinicopathologic significance in archival non-small cell lung cancer (NSCLC) samples from 357 patients. A role of KIF4A in cancer cell growth and/or survival was examined by small interfering RNA experiments. Cellular invasive activity of KIF4A on mammalian cells was examined using Matrigel assays. RESULTS: Immunohistochemical staining detected positive KIF4A staining in 127 (36%) of 357 NSCLCs and 19 (66%) of 29 small-cell lung cancers examined. Positive immunostaining of KIF4A protein was associated with male gender (P = 0.0287), nonadenocarcinoma histology (P = 0.0097), and shorter survival for patients with NSCLC (P = 0.0005), and multivariate analysis confirmed its independent prognostic value (P = 0.0012). Treatment of lung cancer cells with small interfering RNAs for KIF4A suppressed growth of the cancer cells. Furthermore, we found that induction of exogenous expression of KIF4A conferred cellular invasive activity on mammalian cells. CONCLUSIONS: These data strongly implied that targeting the KIF4A molecule might hold a promise for the development of anticancer drugs and cancer vaccines as well as a prognostic biomarker in clinic.

Nivolumab therapy for lung cancer with tracheo-parenchymal fistula: A case report.

RATIONALE: Tracheobronchial fistulas are rare complications in lung cancer patients. These lesions are associated with a high rate of mortality caused by infection and bleeding, and there is no consensus on a definitive optimal therapy. PATIENT CONCERNS AND DIAGNOSES: The patient was a 59-year-old man with a right lung mass showing mediastinal invasion and tracheal compression, diagnosed with adenocarcinoma, cT4N0M0, stage IIIA. He was treated with concurrent chemoradiotherapy with carboplatin and paclitaxel, and the lesion markedly shrunk. Eleven months later, the lesion showed regrowth, and he underwent repeated chemotherapy for stabilization of the lesion. Thirty-six months after the first regrowth, the tumor showed regrowth again. The patient was then administered docetaxel and bevacizumab as fifth-line therapy. After 11 cycles of docetaxel and bevacizumab therapy, a tracheo-parenchymal fistula appeared. INTERVENTIONS AND OUTCOMES: Docetaxel and bevacizumab therapy was stopped, and nivolumab therapy was initiated. Subsequently, the fistula and cavity became stable with slight shrinkage. To date, the patient is alive with no complaints and no disease progression and has continued nivolumab for a total of 28 months. LESSONS: Immune-checkpoint inhibitor therapy involving nivolumab therapy might be a useful alternative for the treatment of lung cancer involving a tracheobronchial fistula.

A Rare Combination of Dermatomyositis, Interstitial Pneumonia, and Lung Cancer in a Patient Treated with Immunosuppressive Therapy and Chemotherapy.

We herein report the rare case of co-occurring dermatomyositis (DM), interstitial pneumonia (IP), and lung cancer in a 59-year-old man. Computed tomography (CT) and positron emission tomography-CT showed the presence of a left lung tumor with IP, which was diagnosed as lung adenocarcinoma by a CT-guided tumor biopsy. We diagnosed DM based on the presence of myalgia, Gottron's papules, and anti-aminoacyl-tRNA synthetase antibody positivity in the patient. Co-occurrence of the above-mentioned three diseases is rare, and acute exacerbation of IP is a major cause of death in such cases. These patients can be treated with immunosuppressive therapy followed by chemotherapy.

ROS1-rearranged putative lung adenocarcinoma presenting as carcinoma of unknown primary site: a case report.

Carcinoma of unknown primary site (CUP) is diagnosed only in 2-9% of all cancer cases. Adenocarcinomas account for approximately 60% of CUP, and some of these are putative lung adenocarcinomas. The frequency of driver oncogene positivity in the putative lung adenocarcinomas is unknown, and the efficacy of targeting therapies for the driver oncogene is also unknown. This is the first case report of C-ros oncogene 1 (ROS1)-rearranged putative lung adenocarcinoma presenting as CUP showing a good response to ROS1 inhibitor therapy. A 55-year-old woman presented with neck lymphadenopathy. Computed tomography and [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) showed swelling of the bilateral supraclavicular, left accessory, mediastinal, and abdominal lymph nodes. The pathological analysis of the lymph node specimen biopsy indicated adenocarcinoma with cytokeratin 7 and thyroid transcription factor-1 positivity. Thus, this case was identified as ROS1- rearranged putative lung adenocarcinoma presenting as CUP. Oral crizotinib, an ROS1 inhibitor, was administered at a dose of 250 mg twice daily. Four weeks later, several swollen nodes showed marked improvement, and eight weeks later, FDG PET showed almost no uptake. In conclusion, putative lung adenocarcinoma presenting as CUP may involve ROS1 rearrangement, and ROS1 inhibitor therapy may be effective.

Putative lung adenocarcinoma with epidermal growth factor receptor mutation presenting as carcinoma of unknown primary site: A case report.

RATIONALE: Only a few cases of putative lung adenocarcinoma presenting as carcinoma of unknown primary site (CUP) with epidermal growth factor receptor (EGFR) mutation have been reported, and the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) for these cases is unclear. PATIENT CONCERNS AND DIAGNOSES: A 67-year-old man complained of paresis of the right lower extremity, dysarthria, and memory disturbance. Computed tomography and magnetic resonance imaging showed multiple brain tumors with brain edema and swelling of the left supraclavicular, mediastinal, and upper abdominal lymph nodes. Moreover, a metastatic duodenal tumor was detected via upper gastrointestinal endoscopy examination. The biopsy specimen of the lesion was examined and was diagnosed as adenocarcinoma with CK7 and TTF-1 positivity. Finally, the case was diagnosed as EGFR mutation-positive putative lung adenocarcinoma presenting as CUP. INTERVENTIONS AND OUTCOMES: Oral erlotinib, an EGFR-TKI, was administered at 150 mg daily. Five weeks later, the brain lesions and several swollen lymph nodes showed marked improvement, and the symptoms of the patient also improved. Three months later, the duodenal lesion was undetected on upper gastrointestinal endoscopy. After an 8-month follow-up, the patient was well with no disease progression. LESSONS: Putative lung adenocarcinoma presenting as CUP may have EGFR mutation, and EGFR-TKI therapy may be effective for such malignancy.

Acetylcholine receptor antibody-positive myasthenia gravis associated with small-cell lung cancer: A case report.

RATIONALE: Only few cases of myasthenia gravis (MG) associated with small-cell lung cancer (SCLC) have been reported, and cases positive for acetylcholine receptor antibody (AChR-ab) are even rarer. The efficacy of standard MG treatment, such as cholinesterase inhibitor therapy, immunosuppressive therapy using steroids and immunosuppressive drugs, plasma exchange, and intravenous immune globulin (IVIg), for these cases is unclear. PATIENT CONCERNS AND DIAGNOSES: A 71-year-old man complained of bilateral eyelid ptosis. He also presented with dysphagia and masticatory muscle fatigue after chewing. The edrophonium test was positive, and the serum AChR-ab level was increased; therefore, the patient was diagnosed with MG. Computed tomography scan showed a nodule on the left upper lobe of the lung and mediastinal lymphadenopathy. Further examination revealed the lesion as SCLC. Finally, he was diagnosed with AChR-ab-positive MG associated with SCLC. INTERVENTIONS AND OUTCOMES: Oral pyridostigmine and tacrolimus were administered to treat MG; however, his symptoms worsened. Therefore, methylprednisolone and IVIg were administrated, which temporarily improved his symptoms. However, they remained uncontrolled. Meanwhile, chemotherapy with carboplatin and etoposide was administered to treat his SCLC. The lesions shrunk, and the MG symptoms and serum AChR-ab level also improved. LESSONS: AChR-ab-positive MG may develop as a comorbidity of SCLC. In such cases, management might require treatment for SCLC in addition to the standard MG treatment to stabilize the MG symptoms.