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Case Studies

Histological Examination of Trousseau Syndrome-Related
Thrombus Retrieved Through Acute Endovascular
Thrombectomy: Report of 2 Cases
Naoki Matsumoto, MD,*† Hitoshi Fukuda, MD,* Akira Handa, MD,*
Toshinari Kawasaki, MD,* Yoshitaka Kurosaki, MD,* Masaki Chin, MD,* and
Sen Yamagata, MD*

The mechanism of thrombus formation in Trousseau syndrome remains unclear.
The purpose of this study was to investigate specific pathological findings of the
thrombi in Trousseau syndrome. The authors report on 2 cases of thrombi in Trousseau syndrome from large cerebral vessels removed by endovascular therapy and
compared with thrombi in atherosclerosis or cardiac embolism. The first patient,
a 67-year-old man, was transferred to our hospital for sudden onset consciousness disturbance and tetraparesis. He had been diagnosed with stage IV lung cancer.
The magnetic resonance (MR) angiography demonstrated basilar artery occlusion. An endovascular thrombectomy was performed.The second patient, an 84year-old woman, was transferred to our hospital for sudden onset motor aphasia
and right-sided motor weakness. She has a history of stage IV pancreatic body
cancer. The MR angiography demonstrated left middle cerebral artery occlusion.
An endovascular thrombectomy was performed for the floating thrombus. Macroscopic findings of retrieved thrombi were observed immediately after thrombectomy.
The thrombi in Trousseau syndrome were white in color and solid against manual
compression, whereas thrombi from other causes were red and fragile. In terms
of microscopic findings, the thrombi in Trousseau syndrome mainly contained fibrin.
On the other hand, thrombi associated with atherosclerosis or cardiac embolism
had smaller area of fibrin with a considerable amount of red and white blood
cells. The thrombi in Trousseau syndrome, which caused occlusion of large cerebral vessel, almost exclusively consisted of fibrin. Key Words: Thrombus—acute
cerebral large vessel occlusion—Trousseau syndrome—histological examination.
© 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

From the *Department of Neurosurgery, Kurashiki Central Hospital, Kyoto, Japan; and †Department of Neurosurgery, Kyoto University
Hospital, Kyoto, Japan.
Received May 10, 2016; revision received July 13, 2016; accepted
August 27, 2016.
Address correspondence to Naoki Matsumoto, MD, Department
of Neurosurgery, Kyoto University Hospital, 54 Shogoinkawahara-Cho,
Sakyo-Ku, Kyoto-Shi, Kyoto 606-8507, Japan. E-mail: naoki@
kuhp.kyoto-u.ac.jp.
1052-3057/$ - see front matter
© 2016 National Stroke Association. Published by Elsevier Inc. All
rights reserved.
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.08.041

Introduction
Trousseau syndrome is characterized as cerebral embolism due to hypercoagulation related to malignant
tumors.1 The mechanism of thrombus formation in Trousseau syndrome remains unclear, and thus there is no
evidence for secondary prevention.
We retrieved 2 thrombi in 2 cases with acute cerebral
large vessel occlusion related to Trousseau syndrome using
neuroendovascular therapy, performed histological examination, and compared the thrombi with 7 from other

Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2016: pp ■■–■■

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N. MATSUMOTO ET AL.

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Figure 1. Macroscopic findings of the retrieved
thrombi. (Left) The thrombus in Trousseau syndrome, retrieved from patient CASE 2, was white
in color and solid. (Right) The thrombus of atherosclerotic brain infarction, retrieved from patient
ATBI 3, was red in color and fragile.

causes (atherosclerotic thrombus [ATBI] = 4, cardiogenic
embolism [CE] = 2, embolic stroke of undetermined
source = 1), according to Trial of ORG 10172 in Acute Stroke
Treatment classification.2
Tissue plasminogen activator (tPA) was administered
to 4 of 9 patients. The thrombi were retrieved by stent
retrievers in 8 cases and by an aspiration catheter in 1
case.

Case Presentation
Case 1 is a 67-year-old man who was transferred to
our hospital for sudden onset consciousness disturbance and tetraparesis. He had been diagnosed with stage
IV lung cancer but had been doing well without any evidence of multiple organ failure or hemorrhagic
complications. The laboratory data included platelet of
9.3 × 104/μL, D-dimer level of more than 10.0 μg/mL,
plasma fibrinogen of 239.0 mg/dL, fibrin degradation
product of 71.7 μg/mL, and prothrombin time of 15.2
seconds, suggesting that the patient did not present with
clinically overt disseminated intravascular coagulation
(DIC), assessed using International Society on Thrombosis and Haemostasis criteria.3 The diffusion-weighted
imaging of head magnetic resonance imaging (MRI) and
MR angiography (MRA) demonstrated acute stage bilateral cerebellar infarction and basilar artery occlusion,
respectively. Cardiac vegetation was not detected by transthoracic echocardiogram. Given lack of evidence for ATBI
and CE, his embolism was categorized into Trousseau syndrome. tPA was not administered because of low platelet
count. His thrombus in the basilar artery was retrieved
by a stent retriever.
Case 2 is an 84-year-old woman who was transferred
to our hospital for sudden onset motor aphasia and rightsided motor weakness. She has a history of stage IV
pancreatic body cancer but had been doing well without
any evidence of multiple organ failure or hemorrhagic
complications. The laboratory data included platelet of
16.3 × 104/μL, D-dimer level of 19.9 μg/mL, plasma fibrinogen of 164.0 mg/dL, fibrin degradation product of
44.6 μg/mL, and prothrombin time of 15.2 seconds, sug-

gesting that the patient did not present with clinically
overt DIC, assessed using International Society on Thrombosis and Haemostasis criteria. 3 MRI and MRA
demonstrated acute stage infarction of left corona radiata
and left middle cerebral artery occlusion, respectively.
Cardiac vegetation was not detected by transthoracic
echocardiogram. She demonstrated drastic recovery temporarily after MRI so that tPA was not administered. A
few hours later, her symptoms deteriorated again. Thrombectomy was performed by a stent retriever.
Macroscopic findings of retrieved thrombi were observed immediately after thrombectomy. The thrombi in
Trousseau syndrome were white in color and solid against
manual compression, whereas thrombi from other causes
were red and fragile (Fig 1). In terms of microscopic findings, the proportion of the area of each hematological
component in the thrombi is shown in Figure 2. The
thrombi of Trousseau syndrome contained more than 90%
fibrin. On the other hand, thrombi associated with ATBI,
CE, or embolic stroke of undetermined source had smaller
area of fibrin and a considerable amount of red and white
blood cells. No tumor cells were found in the thrombi
in Trousseau syndrome (Fig 3).

Discussion
Trousseau syndrome was reported by Armand Trousseau in 1865 and is characterized by cerebral embolism
caused by hypercoagulation due to malignant tumors. Although there are no defined criteria to differentiate
Trousseau syndrome from other infarctions, Trousseau syndrome has been reported to be associated with extremely
high level of plasma D-dimer level.4
The mechanism of thrombus formation in cerebral large
arteries in Trousseau syndrome remains unclear. However,
nonbacterial thrombotic endocarditis (NBTE) associated
with hypercoagulation is most commonly accepted as an
embolic source.5 The cardiac vegetation formed in NBTE
was reported to mainly consist of fibrin component and
sparsely include leukocytes or erythrocytes,6 which is
similar to thrombi of DIC in microvessels.7 In the present
study, thrombi associated with Trousseau syndrome con-

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THROMBI OF TROUSSEAU SYNDROME

3

100
90
80
70

%

60
50
40
30
20
10
0
CASE1

CASE2

ATBI1

ATBI2
fibrin

ATBI3
RBC

ATBI4

CE1

CE2

ESUS

WBC

Figure 2. Bar graph demonstrating the proportion of the area of each hematological component in the thrombus. Abbreviations: ATBI, atherothrombotic
brain infarction; CE, cardiogenic embolism; ESUS, embolic stroke of undetermined source; RBC, red blood cells; WBC, white blood cells.

tained extremely higher proportion (>90%) of fibrin than
thrombi from other causes. In addition, high levels of
plasma D-dimer and fibrin degradation product of
patients with Trousseau syndrome suggested
hypercoagulation, although they did not reach international DIC criteria.3 Taken together, our result supports
that Trousseau syndrome-related thrombi that occluded
cerebral large vessels were caused by emboli from NBTE
associated with cancer-related hypercoagulation. The detection rate of vegetation in NBTE was 18% by
transesophageal echocardiography,8 and the rate was lower

by transthoracic echocardiography.9 Thus, it is no wonder
that vegetation was not detected by transthoracic
echocardiography in either of our Trousseau cases.
Histological findings obtained in this study give an
insight into potential treatment of Trousseau syndrome.
Although first-line treatment for preventing recurrence
of embolism in Trousseau syndrome is anticoagulation
therapy,10 the optimal anticoagulant drug remains undetermined. Because thrombin mediates conversion of
fibrinogen into fibrin, selective thrombin inhibitor including dabigatran, or direct Xa inhibitor rivaroxaban and

Figure 3. Hematoxylin-eosin staining of the retrieved thrombi. In this staining, fibrin component is stained pink by eosin. Erythrocytes are depicted as
red, and nuclei in the leukocytes are stained purple by hematoxylin. (A) CASE 1, (B) CASE 2, (C) ATBI 1, (D) CE 1, (E) ESUS in Figure 2. In Trousseau CASE 1 (A) and CASE 2 (B), almost all the parts of thrombi consist of fibrin. In ATBI 1 (C), the rates of fibrin, red blood cells, and white blood
cells are comparable in the thrombus. In CE 1 (D), fibrin and red blood cells are almost equally included in the thrombus. In ESUS (E), the most part of
the thrombus is red blood cells, with a small amount of fibrin. Scale bar = 200 μm.

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apixaban, may be more promising than warfarin. A previous study failed to demonstrate significant superiority
of dabigatran over warfarin in preventing recurrent venous
thrombosis associated with malignant tumors.11 However,
histological findings of venous thrombi in patients with
tumor are not necessarily identical to those of arterial
thrombi in Trousseau syndrome. Investigating efficacy and
safety of selective thrombin inhibitor to prevent recurrence of Trousseau syndrome may be valuable. In addition,
several randomized trials using rivaroxaban (official title
“Efficacy and Safety of Rivaroxaban Prophylaxis Compared with Placebo in Ambulatory Cancer Patients Initiating
Systemic Cancer Therapy and at High Risk for Venous
Thromboembolism”; URL https://clinicaltrials.gov/ct2/
show/NCT02555878) or apixaban12 are ongoing. The present
study is the first report describing histological findings
of thrombi retrieved from large cerebral vessels associated with Trousseau syndrome. We hope histological
findings described here may facilitate further research of
clinical entity and treatment of Trousseau syndrome.

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