PB0948 - Title: Presence of intrathrombus cancer cells as vascular wall invasion and cell cluster patterns in human cancer-associated venous thromboembolism

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Toshihiro Gi, MD (he/him/his)

Department of Pathology, Faculty of Medicine
University of Miyazaki
Miyazaki, Miyazaki, Japan

Co-Author(s)

AK

Aya Kuwahara

Department of Laboratory Center
Faculty of Medicine, University of Miyazaki
Miyazaki, Miyazaki, Japan
Atsushi Yamashita, MD, PhD

Professor, Department of Pathology, Faculty of Medicine
University of Miyazaki
Miyazaki, Miyazaki, Japan
SM

Shuntaro Matsuda

Department of Medicine and Community Health
Faculty of Medicine, University of Miyazaki, Miyazaki
Miyazaki, Miyazaki, Japan
KM

Kazunari Maekawa

Department of Pathology, Faculty of Medicine
University of Miyazaki
Miyazaki, Miyazaki, Japan
SM

Sayaka Moriguchi-Goto

Department of Diagnostic Pathology
Miyazaki University Hospital, University of Miyazaki
Miyazaki, Miyazaki, Japan
YS

Yuichiro Sato

Department of Diagnostic Pathology, Miyazaki University Hospital, Faculty of Medicine
University of Miyazaki
Miyazaki, Miyazaki, Japan
YA

Yujiro Asada

Department of Pathology
Miyazaki Medical Association Hospital
Miyazaki, Miyazaki, Japan

Background: Pathological findings of thrombi in cancer-associated venous thromboembolism (VTE) are limited.

Aims: To determine histopathological features of cancer-associated VTE in human.

Methods: We examined the thrombotic foci from autopsy cases of VTE with cancer (n=65) and without cancer (n=109). We histologically or immunohistochemically analyzed presence of cancer cells in the thrombus with cytokeratin (a marker of epithelial cell), expression of thrombotic factors in intrathrombus cancer cells, necrosis of intrathrombus cancer cells with cytokeratin and histone H3 (a marker of chromatin), the thrombus contents of erythrocytes, fibrin, platelets, citrullinated histone H3 (a marker of neutrophil extracellular trap), and degree of thrombus organization.

Results: Histological sections of cancer-associated VTE tissue revealed the presence of cancer cells in thrombi (27%). These intrathrombus cancer cells were observed as vascular wall invasion from adjacent primary or metastatic cancer lesions (52%) or as cancer cell clusters (48%). These intrathrombus cancer cells were immuno-positive for tissue factor, podoplanin, tissue type-plasminogen activator, and plasminogen activator inhibitor (76%, 44%, 36%, and 20%, respectively). Cancer cell necrosis was highlighted by fragmented immunoreactivity for cytokeratin and histone H3, and was observed in 51% of the intrathrombus cancer cells. The necrotic cells and their fragments were surrounded by predominantly fibrin (50%) or fibrin and platelets (38%). There was no significant difference in erythrocytes, fibrin, platelets, or citrullinated histone H3 contents between VTE with cancer and without cancer groups. Neutrophil extracellular traps were predominantly observed in early stages of thrombi with none or small organizing area.

Conclusion(s): Vascular wall invasion of cancer cells can initiate thrombus formation via venous wall damage and prothrombotic factor expression. The presence of cancer cell clusters in the thrombus suggests contribution of circulating tumor cells to venous thrombus formation. Expression thrombotic factors and necrosis of cancer cells may affect coagulation reaction, platelet aggregation, and fibrinolysis.