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Case Studies

Multiple Thrombi in the Heart in Trousseau Syndrome Caused
by Pancreatic Carcinoma
Sho Takeshita, MD,* Toshiyasu Ogata, MD, PhD,* Hidekazu Mera, MD,*
Jun Tsugawa, MD,* Mikiko Aoki, PhD,† Morishige Takeshita, MD, PhD,† and
Yoshio Tsuboi, MD, PhD*

A 65-year-old woman presented to our emergency room because of sudden onset
of right hemiparesis with severe fatigue. Neurological examination revealed right
hemiparesis with right facial numbness and an extensor planter response on the
right side.Magnetic resonance imaging with diffusion-weighted imaging revealed multiple highintensity areas in both cerebral hemispheres and the right
cerebellum. A diagnosis of acute stage of multiple brain infarctions caused by emboli
was made. An abdominal computed tomography showed a pancreatic tumor with
multiple liver metastases. High D-dimer and serum carbohydrate antigen 19-9 concentration strongly suggested Trousseau syndrome associated with pancreatic cancer.
The patient had another large embolic stroke and died on day 47. Autopsy was
performed. There were large thrombi in the left ventricular apex and in the left
atrial appendage There was also a papillary-shaped vegetation on the aortic valve
that consisted mainly of fibrin without any inflammatory cells or destruction of
the valve, these findings being characteristic of NBTE. This case is remarkable in
that the patient had 3 different types of cardiac thrombi in her heart associated
with Trousseau syndrome. Key Words: Nonbacterial thrombotic endocarditis—
pancreatic cancer—Trousseau syndrome—cerebral infarction.
© 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Trousseau syndrome, which is characterized by a hyperactive coagulation state resulting in various types of
thromboembolism, may be associated with concomitantly diagnosed malignancy, often in the form of mucinFrom the *Department of Neurology, Fukuoka University School
of Medicine, Fukuoka, Japan; and †Department of Pathology, Fukuoka
University School of Medicine, Fukuoka, Japan.
Received August 23, 2017; revision received November 21, 2017;
accepted December 3, 2017.
Address correspondence to Yoshio Tsuboi, MD, PhD, Department
of Neurology, Faculty of Medicine, Fukuoka University, 7-45-1,
Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. E-mail: tsuboi@
cis.fukuoka-u.ac.jp.
1052-3057/$ - see front matter
© 2017 National Stroke Association. Published by Elsevier Inc. All
rights reserved.
https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.12.005

positive carcinomas. However, this type of coagulopathy
can occur in association with any type of malignancy. Although thrombi originating in the heart may cause ischemic
stroke in patients with Trousseau syndrome, appropriate investigations do not always reveal intracardiac thrombi.
It has been reported that around a quarter of patients
with malignancy-related coagulation disorder have coexisting nonbacterial thrombotic endocarditis (NBTE),1
which is characterized by nonbacterial vegetation without
valvular destruction.2 Because NBTE is rarely diagnosed in living patients, autopsy studies report a higher
than expected frequency of NBTE in patients with
malignancy.3 Here, we report a patient with cardioembolic
stroke who was eventually diagnosed as having Trousseau syndrome. An autopsy revealed 3 different types
of thrombus in the heart.

Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2017: pp ■■–■■

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S. TAKESHITA ET AL.

Figure 1. (A) Large thrombus in the left atrial appendage that is organized and mainly composed of fibrin. (B) Papillary-shaped fragile vegetations with
no associated inflammation on the aortic valve.

A 65-year-old woman presented to our emergency room
because of sudden onset of right hemiparesis with severe
fatigue. Neurological examination revealed right hemiparesis with right facial numbness and an extensor planter
response on the right side. Magnetic resonance imaging
with diffusion-weighted imaging revealed multiple highintensity areas in both cerebral hemispheres and the right
cerebellum. A diagnosis of acute stage of multiple brain
infarctions caused by emboli was made and the patient
was admitted to our stroke unit. Because the patient also
reported abdominal discomfort, an abdominal computed tomography (CT) was performed, which showed
a pancreatic tumor with multiple liver metastases. Blood
concentrations of fibrinolytic markers such as D-dimer and
fibrin degradation product were very high, as was the
patient’s serum carbohydrate antigen 19-9 concentration, strongly suggesting Trousseau syndrome associated
with pancreatic cancer.
Despite treatment with intravenous heparin (15,000 units/
day), further embolic strokes occurred. Chest and
abdominal CT showed asymptomatic thromboemboli in
the patient’s lungs and kidneys, and an ultrasound examination revealed deep venous thrombus in her right
leg. Because of the advanced stage of the pancreatic cancer,
the patient received palliative care rather than curative
treatment.
On day 23, the patient had another embolic stroke, which
resulted in disturbance of consciousness, conjugate eye
deviation to the right, and left hemiplegia. Brain CT revealed fresh infarction throughout the right middle cerebral
artery territory. The patient died on day 47 and autopsy
was performed 18 hours after her death.
Macroscopically, there was extensive neuromalacia in
the right hemisphere. On microscopic examination, multiple small infarcts were found throughout the cerebral
hemispheres, brain stem, and cerebellum. Ischemic lesions

were also seen in both lungs, the spleen, and kidneys,
indicating general thromboembolism. The patient’s heart
weighed 465 g. There were large thrombi in the left
ventricular apex (Supplemental Fig S1) and in the left
atrial appendage (Fig 1, A) accompanied by rich
neovascularization, suggesting that the thrombi were not
fresh ones. There was also a papillary-shaped vegetation on the aortic valve (Fig 1, B) that consisted mainly
of fibrin without any inflammatory cells or destruction
of the valve, these findings being characteristic of NBTE.
A 4-cm tumor was found in the tail of pancreas; this was
thought to be a primary cancer. Histological examination showed proliferation of atypical epithelial cells forming
irregular ducts, accompanied by abundant fibrous stroma
(Supplemental Fig S2). These findings are consistent with
invasive pancreatic carcinoma. Additionally, multiple cancerous lesions in the liver had similar pathological features
on microscopic examination, indicating they were metastases from the pancreatic cancer. Hence, the patient
had Trousseau syndrome with the characteristic thromboembolism in multiple organs.
NBTE may result in paradoxical cerebral embolism,
tumor embolism, and sinus thrombosis.1 NBTE can induce
both cerebral infarction and asymptomatic systemic emboli
causing, for example, splenic and renal infarction. Cerebral infarction may also result from the hypercoagulable
state associated with malignancy known as Trousseau syndrome. Our patient developed multiple cerebral infarctions
and had pancreatic cancer with liver metastases, consistent with a diagnosis of Trousseau syndrome.3
This case is remarkable in that the patient had 3 different types of cardiac thrombi in her heart associated
with Trousseau syndrome. The thrombus on her aortic
valve was likely responsible for her initial stroke because
it was granular and fragile and thus likely to produce
emboli, whereas the other thrombi in her left appendage

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MULTIPLE THROMBI IN THE HEART IN TROUSSEAU SYNDROME

and apex were relatively large and had smooth surfaces,
so these thrombi were less likely to have induced multiple small embolic strokes. The patient developed
neurological symptoms resulting from multiple small cerebral infarctions, which is characteristic of Trousseau
syndrome. The patient’s hypercoagulable state with malignancy played important roles in this case. Thus, when
a patient with small, multiple cerebral infarctions is encountered, the whole body should be carefully checked
for any evidence of malignancy to enable establishment
of an early diagnosis.
Acknowledgment: We thank Dr. Trish Reynolds, MBBS,
FRACP, from the Edanz Group (www.edanzediting.com/
ac) for editing the draft of this article.

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Appendix: Supplementary Material
Supplementary data to this article can be found online
at doi:10.1016/j.jstrokecerebrovasdis.2017.12.005.

References
1. Graus F, Roqers LR, Posner JB. Cerebrovascular
complications in cancer patients. Medicine (Baltimore)
1985;64:16-35.
2. Asopa S, Patel A, Khan OA, et al. Nonbacterial thrombotic
endocarditis. Eur J Cardiothorac Surg 2007;32:696701.
3. El-Shami K, Griffiths E, Streiff M. Nonbacterial thrombotic
endocarditis in cancer patients: pathogenesis, diagnosis
and treatment. Oncologist 2007;12:518-523.