Cancer-associated Venous Thromboembolism (VTE) is a critical complication in patients with cancer. However the pathological findings of VTE are limited. Here are investigated the histopathological features of cancer-associated VTE in human autopsy cases.
1. CONCLUSION
Vascular wall invasion or cancer cell clusters in thrombi
might influence thrombogenesis of tumor-associated
venous thromboembolism (TA-VTE). Tissue Factor (TF)
and Podoplanin (PDPN) in cancer cells and in
monocyte/macrophages may induce coagulation reactions
and platelet aggregation. Neutrophil Extracellular Traps
(NETs) may play a role in the early stages of VTE,
regardless of cancer status.
PURPOSE
The aim of this article was to demonstrate the frequency of
expression of TF and PDPN in both macrophages and
cancer cells related to the risk of venous thromboembolism
(TE).
Fig.1) Expression of prothrombotic factors of cancer cells in venous
thromboembolism tissue. A-B) TF expression in pancreatic
adenocarcinoma with TF+/PDPN- and TF+ (C,
immunohistochemistry) in gastric adenocarcinoma cells.
Histopathological Features of Cancer-Associated Venous Thromboembolism
Daniele Amato, Toshihiro Gi, Atsushi Yamashita – University of Miyazaki, Japan
FUTURE PERSPECTIVES: The use of the
Neutrophils as a positive predictive
biomarker for the risk of Cancer
Associated TE in «in vivo» Patients.
Daniele Amato, Radiology I Universitetet I Oslo – Universitetet i Bergen – Karolinska Institutet
daniele.amato@stud.ki.se +39 3935236763
BACKGROUND
Cancer-associated VTE is a critical complication in patients
with cancer. However the pathological findings of VTE are
limited. Here are investigated the histopathological features
of cancer-associated VTE in human autopsy cases.
1-A 1-B 1-C
2-A 2-B 2-C
Fig.2) Expression of prothrombotic factors of cancer cells in
pulmonary thrombus. A-B) PDPN expression with TF-/PDPN+
pattern and PDPN+ (C, immunohistochemistry) in cutaneous
squamous cell carcinoma.
Fig.3) Analysis of NETs (Neutrophils extracellular traps) in VTE. A)
Hematoxylin-Eosin staining shows lysis and fragmentation of
neutrophil cromatin corresponding to citrullinated histone H3 (Cit-
H3, arrows) expression; C) A corresponding diffuse lytic pattern
(Cit-H3+ and CD66b+) of NETs in VTE tissue on
immunohistochemical micrographs.
METHODS
The study starts from the clinical retrospective analysis of
autopsy cases of VTE with (n=114) and without cancer
(n=66) and the expression of prothrombotic factors in
intrathrombus cancer cells.
3-A 3-B 3-C
RESULTS
Vascular wall invasion or small cluster of cancer cells in
thrombi frequently showed the immunohistochemical
expression of Tissue Factor (TF, Fig.1) or podoplanin
(PDPN, Fig2) and necrosis with platelet aggregation and
fibrin formation.
The frequency of Tissue Factor-positive monocyte /
macrophages in thrombi was higher in cancer-associated
venous TE than in venous TE without cancer.
Neutrophil Extracellular Traps (NETs, Fig.3) in the thrombi
were related to the early phase of the thrombus-organizing
process, regardless of whether patients were in a cancer-
bearing state.