Our patient was a 62-year-old Japanese man with a 4-week history of dyspnea on exertion. Key findings included hypoxemia, severe pulmonary hypertension, and negative pulmonary angiogram. Recurrence of gastric cancer was confirmed from the results of a bone marrow biopsy; PTTM was considered. He was treated with conservative management, following partial alleviation of respiratory failure, and died 6 weeks after admission. Most patients with PTTM die within a week of dyspnea onset; however, our patient survived for 10 weeks from the day of presentation.
PTTM, a special type of tumor thromboembolism, is found in 3.3% of postmortem cases of carcinoma; of all PTTM cases, 52% are attributable to gastric cancer (especially mucinous or signet ring adenocarcinoma) [
1]. Clinical manifestations include progressive dyspnea, cough, hypoxia, and pulmonary hypertension. Chest radiography is typically normal; reported chest CT findings include beading of peripheral subsegmental arteries, interlobular septal thickening [
2], and tree-in-bud pattern [
3]. Almost all patients with PTTM die within 1 week of the onset of dyspnea [
4], and establishing an antemortem diagnosis is a challenge. The rapid progression usually prevents treatment targeting the primary tumor. The prognosis in this case was better than that in the previous reports. In PTTM, tumor emboli in pulmonary vessels may not only damage the endothelium but also activate the coagulation systems and release inflammatory mediators and growth factors, including tissue factor, vascular endothelial growth factor (VEGF) [
5], platelet-derived growth factor (PDGF) [
6], and osteopontin [
7], which induce fibrocellular intimal proliferation. PDGF induces macrophage recruitment and VEGF upregulation in cancer cells [
8], which leads to inflammation through angiogenesis and enhanced vascular permeability [
9]. Osteopontin not only regulates macrophage recruitment but also modulates the production of pro-inflammatory cytokines by macrophages [
10]. Several reports have demonstrated that the cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, released by activated macrophages, play an important role in the pathogenesis of pulmonary arterial hypertension (PAH) [
11]. Moreover, inflammatory stimuli including that from IL-1β have been shown to exacerbate hypoxic vasoconstriction in a mouse model of PAH [
12]. In PTTM, corticosteroid therapy may help control local inflammation in the pulmonary microvasculature and improve hemodynamics by alleviation of pulmonary vasoconstriction [
13]. Our experience with this case suggests that the control of local inflammation with corticosteroid therapy may have helped improve the prognosis, although the time from the onset of pulmonary symptoms to death ranged from 1 day to 12 weeks in one series [
14].