Chordoma combined with Trousseau syndrome: a case report and literature review

Abstract

Background: Trousseau syndrome (TS) refers to spontaneous, recurrent, and wandering arterial and venous thromboembolic events in patients with tumors. It results from abnormalities in coagulation and fibrinolytic mechanisms of varying degrees throughout the course of the disease. It has a high fatality rate, and it is commonly seen in patients with highly invasive tumors, such as lung, pancreatic, gastrointestinal, and breast cancers; however, to date, there has been no report of TS combined with chordoma.

Case description: A 56-year-old male with a diagnosis of chordoma underwent surgery, immunotherapy, immunotherapy combined with antiangiogenic therapy, chemotherapy combined with immunotherapy, and proton therapy for localized metastases. Subsequent to the worsening of chest tightness, a repeat chest computed tomography angiography (CTA) scan suggested pulmonary artery embolisms; eventually, a diagnosis of TS was made. After anticoagulation and synchronized antitumor therapy, the patient's condition remained recurrent, eventually leading to death.

Conclusions: TS is a frequent but easily overlooked clinical complication that can occur in a variety of tumors, including chordoma, and is currently diagnosed clinically. Thus, further exploration of its sensitive markers is needed. We have reported a case of chordoma combined with TS and conducted a literature review on TS to increase clinicians' awareness of tumor-related thromboembolism and explore strategies to optimize the diagnosis, treatment, and prevention of TS.

Keywords: Trousseau syndrome (TS); case report; chordoma; pulmonary embolism (PE); venous thrombosis.

Figure 1

List of prior treatments. SD, stable disease; PR, partial response; PFS, progression-free survival; PD, progressive disease.

Figure 2

CTA pulmonary angiography of patient. (A) CTA shows a nodular filling defect in the main trunk of the left pulmonary artery. (B,C) The filling defect is still visible in the main trunk of the left pulmonary artery, which has progressed from the previous one. (D) The filling defect shadow in the trunk of the left pulmonary aorta has narrowed and improved from the previous one. The left pulmonary aortic trunk has a better filling defect shadow than the previous one. Red arrows indicate the location of the thrombus. CTA, computed tomography angiography.

Figure 3

01/2024 pulmonary artery CTA. (A) Coronal view shows filling defects in both the right and left pulmonary arteries. (B) Axial view shows filling defects in the right pulmonary trunk and its branches. Red arrows indicate the location of the thrombus. CTA, computed tomography angiography.

Figure 4

Mechanisms associated with Trousseau syndrome. Mechanisms of tumor-associated thrombosis include activation of coagulation, dysregulation of the fibrinolytic system, inflammation, and cytokine production. TF is a procoagulant protein that initiates the extrinsic pathway of the coagulation cascade by forming a complex with coagulation factor VII, which promotes the activation of coagulation factor X and the formation of coagulation factor Xa. Tumor cells release platelet-activating factors such as ADP, TxA2, and CD40L, which activate vascular endothelial cells. Activated neutrophils form NETs, while circulating G-CSF in tumor patients increases the number of neutrophils and induces their activation, which promotes NET formation. Additionally, soluble mediators released from tumor cells, including TNF-α, IL-1β, IL-6, IL-8, and bFGF, can stimulate vascular endothelial cells to generate NETs. Histones in NETs activate platelets to generate thrombin, which promotes thrombosis. TNF-α and IL-1β can upregulate TF and downregulate TM, stimulating endothelial cells to produce the fibrinolytic inhibitor PAI-1, which promotes fibrin deposition and thrombosis. P-selectin, an important cell adhesion molecule expressed by stimulated endothelial cells and activated platelets, mediates the aggregation of activated platelets with cancer cells, as well as the adhesion of cancer cells to stimulated endothelial cells and the intercellular transfer of activated platelets with procoagulant MPs, promoting fibrin deposition and microthrombosis. TNF-α, tumor necrosis factor α; IL-1β, interleukin-1β; IL-6, interleukin-6; IL-8, interleukin-8; bFGF, basic fibroblast growth factor; VEGF, vascular endothelial growth factor; ADP, adenosine diphosphate; TxA2, thromboxane A2; CD40L, platelet-derived CD40 ligand; G-CSF, granulocyte colony-stimulating factor; TF, tissue factor; FVII, factor VII; FX, coagulation factor X; FXa, coagulation factor Xa; NETs, neutrophil extracellular traps; TM, thrombomodulin; PAI-1, plasminogen activator inhibitor-1.