Pulmonary tumor thrombotic microangiopathy in patients with gastric carcinoma: an analysis of 6 autopsy cases and review of the literature

Abstract

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare clinicopathological entity causing severe pulmonary hypertension (PH). Its histological features include widespread tumor emboli of the small arteries and arterioles of the lung, associated with thrombus formation and fibrocellular and fibromuscular intimal proliferation. Although PTTM has drawn increased attention as a fatal complication of gastric carcinoma (GC), comprehensive studies are still lacking. In order to clarify clinical and pathological features of GC-induced PTTM, recent autopsy cases were analyzed with a review of the literature. Of 36 autopsy cases with GC, 6 (16.7%) were affected by PTTM. Four were male and 2 female, with a mean age of 72.7 years. Three patients presented with PTTM-related clinical manifestations and died of PTTM. They showed clear morphological evidence of PH. The other 3 patients had PTTM as an incidental finding irrespective of clinical manifestations or PH. No patient was diagnosed antemortem as PTTM. All PTTM cases were associated with advanced GC, with a histology of adenocarcinoma of poorly differentiated type (n=4) or signet-ring cell type (n=2). Expression of tissue factor and vascular endothelial growth factor was confirmed immunohistochemically in tumor cells in all cases. The results were all in line with previous studies. In addition, the current study revealed vascular lesions characteristic of PTTM morphology to be present exclusively in the lung. In conclusion, our study shows a 16.7% incidence of PTTM in GC patients, with half of them developing PH and dying of PTTM, confirming a clinical significance as a non-negligible lethal complication of GC. In addition to many known clinicopathological characteristics of PTTM, the current study pointed to some PTTM issues requiring clarification, including the pathogenesis of the exclusive pulmonary distribution of vascular lesions of PTTM. Since details remain to be elucidated, interdisciplinary research is a high priority with a close collaboration between pathologists and clinicians in order to overcome this lethal condition.