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.

Pulmonary Tumor Thrombotic Microangiopathy with Circulatory Failure Treated with Imatinib

“…Imatinib down-regulates the expression of both PDGF and the PDGF receptor in tumor cells, thus resulting in increased apoptotic cell death and the inhibition of tumor angiogenesis, which even further decreases the production of PDGF by the tumor cells. In PTTM, PDGF and PDGF receptors are reportedly expressed in both carcinoma cells and endothelial cells (7). In the present case, PDGF was not detected in lung biopsy specimens of either the tumor cells or the initimal cells.…”

Platelet-Derived Growth Factor Receptor-Tyrosine Kinase Inhibitor, Imatinib, Is Effective for Treating Pulmonary Hypertension Induced by Pulmonary Tumor Thrombotic Microangiopathy

“…8) The authors of several pathological studies suggest that PDGF secreted from tumor cells is associated with vascular remodeling in PTTM-PH, [2][3][4]11,12) and that PDGF is secreted because of the endothelial damage induced by attachment of tumor thrombi.…”

“…PTTM-PH is directly caused by multiple microthrombi of cancer cells surrounded by fibrotic intimal cell proliferation 1) and/or indirectly due to vascular remodeling mediated by growth factors such as platelet-derived growth factor (PDGF), [2][3][4] vascular endothelial growth factor, 5,6) and osteopontin 7) that are released by cancer cells. Because PTTM-PH progresses rapidly, it is rarely diagnosed before autopsy.…”

Running From Her Past

“…These tumor emboli engender an obliterative fibrointimal hyperplasia and in situ thrombosis of the pulmonary vasculature, thus further diminishing the aggregate patent pulmonary vascular bed and worsening the PH. 5,6 This process of embolization and hyperplasia also disrupts the retrograde transmission of reflected left atrial pressure to the pulmonary arterial catheter in the wedged position resulting in discordant PCWP and LVEDP measurements, one of the harbingers of the diagnosis in our case. Interestingly, in the cardiac catheterization laboratory, it was noted that the V wave of the PCWP tracing might have arisen early relative to the standard electrocardiographic landmarks.…”