Pulmonary thrombotic microangiopathy caused by gastric carcinoma

Abstract

Pulmonary tumour thrombotic microangiopathy (PTTM) is characterised by wide spread tumour emboli along with fibrocellular intimal proliferation and thrombus formation in small pulmonary arteries and arterioles. PTTM is a rare but fatal complication of carcinoma, but the pathogenesis remains to be clarified. An autopsy case of PTTM caused by gastric adenocarcinoma is described, in which tumour cells in the PTTM lesion had positive immunoreactivity for platelet-derived growth factor (PDGF) and PDGF receptor (PDGFR), and proliferating fibromuscular intimal cells also showed expression of PDGFR. In addition, the overexpression of PGDF was detected in the alveolar macrophages. These findings suggest that PDGF derived from alveolar macrophages and from tumour cells may act together in promoting fibrocellular intimal proliferation. To the best of the authors' knowledge, the possible involvement of activated alveolar macrophages in PTTM has not been previously reported.

Figure 1

(A) Stenosis and obstruction of many pulmonary arteries and arterioles are shown. Bar, 1000 μm. (B, C) A pulmonary artery showing fibrous thickening of intima and fibrin thrombus (B: H&E stain; C: elastic van Gieson stain). (D) Intimal proliferating fibromuscular cells are positive for α-smooth muscle actin. (E, F) Fibrin thrombus with (E) or without (F) adenocarcinoma cells. Immunoreactivity of pancytokeratin antibody (AE1/AE3) is indicated in the carcinoma cells (F). (E) Arrowheads indicate cancer cells in the vessel. (B–F) Bar, 100 μm.

Figure 2

(A) Carcinoma cells and endothelial cells are immunopositive for platelet-derived growth factor (PDGF)-A. (B) Alveolar macrophages show the overexpression of PDGF-A in the PTTM lesion. (C) Carcinoma cells, endothelial cells and fibromuscular cells are immunopositive for PDGF-B. (D, E) The expression of PGDF receptors (PDGFRs) (PDGFR-α (D); PDGFR-β (E)). PDGFR-α and -β were detected in tumour cells and fibromuscular cells. PDGFR-α were detected in endothelial cells. (F) Immunoreactivity of phosphorylated Src was found in the tumour cells. (A, C, D, E, F) Arrowheads indicate cancer cells in the vessel. (A–F) Bar, 100 μm.