ABSTRACT
A 75-year-old man with diabetes mellitus showed elevated C-reactive protein (CRP) level at his regular visit. Computed tomography scan showed a lung tumor in his left lower lobe and systemic lymphadenopathy including abdominal lymph nodes. The patient was diagnosed as primary pulmonary squamous cell carcinoma with systemic lymph node metastasis. Thereafter, unexpected steroid pulse therapy for accidental acute exacerbation of interstitial pneumonia rapidly shrank lymphadenopathy. At this time, we also found elevated serum immunoglobulin G4 (IgG4) level (385 mg/dL). Considering these findings, we doubted the lymph nodes metastases at the initial staging, and then corrected cancer-staging (C-staging) from inferior vena cava (IVC) to inferior abdomen (IA). In addition, during the steroid tapering, sudden onset and uncontrollable left pneumothorax required surgical approach. Curative-intent left lower lobectomy with lymphadenectomy was performed for the lung cancer. Pathological findings revealed coexistence of adenosquamous carcinoma and infiltration of IgG4-positive plasma cells in the resected mediastinal lymph node. We detected 384 IgG4-positive cells per high power field. IgG4/IgG-positive cell ratio was 54%. Based on these findings, the diagnosis of IgG4-related disease with primary adenosquamous carcinoma (p-stage IIIA) was confirmed. The patient died 24 days after surgery because of another acute exacerbation of interstitial pneumonia. Our case alerts oncologists to IgG4-related disease as a possible underlying comorbidity which may confuse pretreatment clinical stage.
ABSTRACT
Osimertinib-induced cardiotoxicity is a well-known but rare disorder. An 84-year-old woman was diagnosed with recurrence of lung adenocarcinoma showing an epidermal growth factor receptor mutation of exon 19 deletion, which was initially treated by curative-intent thoracic radiotherapy 4 years prior. She started taking osimertinib (80 mg/day). She had no history of heart disease and showed no signs of cardiac problems. However, 2 months later she presented with symptoms of cardiac failure and QT prolongation on electrocardiogram. Cardiac enzyme levels were not elevated and coronary computed tomography angiography showed no significant stenosis. On admission, sudden-onset torsade de pointes required electrocardioversion. Thus, drug-induced cardiac failure was strongly suspected and we stopped osimertinib therapy. Cardiac function and the electrocardiogram abnormality improved. To our knowledge, this is the third case of coincidence of cardiac failure and QT prolongation and the second case of sudden-onset torsade de pointes associated with osimertinib treatment. In our case, osimertinib-induced cardiac failure with QT prolongation was recovered by stopping the drug treatment. The potential for cardiotoxicity should be considered with osimertinib treatment.
ABSTRACT
Durvalumab, a programmed cell death ligand 1 inhibitor, induces various immune-related adverse events (irAEs), including lung injury. However, diffuse alveolar hemorrhage (DAH) is a rare type of lung injury due to immune checkpoint inhibitors. A 76-year-old man with c-stage IIIA squamous cell carcinoma of the lung received maintenance durvalumab therapy after chemoradiotherapy. He developed dyspnea and malaise after 11 cycles of durvalumab. Chest computed tomography showed rapidly spreading bilateral ground-glass opacity in the lungs. We diagnosed DAH by hemosiderin-laden macrophages in bloody bronchoalveolar lavage fluid. Despite mechanical ventilation, steroids, and cyclophosphamide, he died of respiratory failure. The autopsy revealed that fresh and old bleeding areas coexisted, and neither pulmonary vasculitis nor diffuse alveolar damage was detected microscopically. Furthermore, CD3+ and CD8+ lymphocytes were observed in the lung interstitium, whereas CD20+ and CD4+ lymphocytes were scarcely detected. We report the first case of durvalumab-induced DAH. We should be alert to irAEs with DAH as a potential differential diagnosis of lung injury during durvalumab treatment.
