A 68-year-old-man was a former smoker of 1 pack of cigarettes per day for 27 years and had a history of type II diabetes. In early November 2017, dry cough occurred and worsened gradually. He visited his primary care doctor and underwent chest computed tomography (CT), which revealed some abnormalities. His serum tests also showed elevated levels of C-reactive protein (CRP). He was prescribed levofloxacin, but his symptoms persisted. Thereafter, he was referred to our hospital for further examinations and treatments in mid-December, 2017.
There were no abnormalities on physical findings. A serum test showed no abnormalities except for the elevated level of CRP (0.9 mg/dL) (Table 1). Chest radiography showed mild heart enlargement and enhancement in pulmonary vascular shadow (Fig. 1). High-resolution computed tomography (HRCT) of the chest showed bronchial vascular bundle thickening, centrilobular nodules, and interlobular septal thickening on both sides. Uneven ground-glass opacity was present mainly on the right side; in addition, there was pleural effusion on both sides as well as pericardial effusion (Fig. 2). No abnormalities were noted on an electrocardiogram. Echocardiography showed a normal ejection fraction (66%) and mild elevation of the tricuspid regurgitation pressure gradient (TRPG; 36 mmHg). Based on these results, we did not strongly assume the possibility of the exacerbation of chronic heart failure.
For a further inspection, we conducted a TBLB of the right upper lobe, where HRCT showed centrilobular nodules and interlobular septal thickening more strongly. In a pathological image of the TBLB specimen, phloem-like or clumping adenocarcinoma cells were noted in the thick interstitial vessels and vessels of the alveolar wall but not in the lymphatic vessels (Fig. 3). Because a tumor embolism consisting of fibrin and tumor cells was noted, a pathologist in our hospital confirmed the diagnosis of PTTM. Immunostaining showed carbohydrate antigen 19-9(+), Mac5-AC(+), D2-40(-), and thyroid transcription factor-1(-) (Fig. 4). Based on these results, we suspected that the primary tumor might be a gastric or pancreatobiliary cancer.
While we planned further inspections, he was referred to the emergency room of our hospital because of worsening dyspnea in early January 2018. HRCT showed increased pleural effusion and worse interlobular separation wall thickening on both sides than had been noted in the HRCT findings acquired previously (Fig. 5). Emergency hospitalization was implemented, and chest drain placement was conducted. Once hospitalized, he underwent upper gastrointestinal endoscopy for scrutiny. Ulcerative lesions were noted in the posterior wall of the stomach (Fig. 6). The biopsy result indicated moderately to poorly differentiated adenocarcinoma and signet-ring cell carcinoma, which was in agreement with the finding of adenocarcinoma cells on the TBLB (Fig. 7). Contrast-enhanced CT was performed to rule out pulmonary thromboembolism, but no thrombi were observed in the pulmonary artery (Fig. 8). Since the D-dimer level was also in the normal range, pulmonary thromboembolism was considered negative. Therefore, a definitive diagnosis of PTTM due to gastric cancer was made.
In late January, 2018, S-1 (120 mg/m2) and oxaliplatin (100 mg/m2) were administered to eradicate the gastric cancer. However, the gastric cancer worsened, so the regimen of chemotherapy was changed to S-1 (80 mg/m2), docetaxel (50 mg/m2), and oxaliplatin (100 mg/m2). After starting S-1, docetaxel, and oxaliplatin, his dyspnea disappeared gradually. This was because his pulmonary hypertension had improved, and the TRPG measured by echocardiography actually decreased from 36 mmHg to 23 mmHg. However, after four courses of S-1, docetaxel, and oxaliplatin, the progression of gastric cancer was confirmed, and his dyspnea worsened again. Echocardiography showed that the TRPG had increased from 23 to 41 mmHg. In late May, 2018, nab-paclitaxel (PTX) (100 mg/m2) and ramucirumab (8 mg/kg) were initiated. There were no marked changes in dyspnea during the administration of nab-PTX and ramucirumab, and the TRPG decreased from 41 to 35 mmHg. We were able to stop the worsening of dyspnea and improve the pulmonary hypertension a little, but the development of gastric cancer was confirmed after two courses.
Therefore, irinotecan (70 mg/m2) was initiated in mid-July, 2018. Soon after initiating irinotecan, his dyspnea worsened. Steroids and narcotics were prescribed to alleviate his symptoms. At the end of July 2018, his performance status was 4 owing to fatigue, anorexia, and dyspnea, so we decided to discontinue the chemotherapy and provide best supportive care. In late August, 2018, he passed away.
High-resolution chest tomography at the initial visit. The lung window showed bronchial vascular bundle thickening, centrilobular nodules, and interlobular septal thickening on both sides.