|Year : 2022 | Volume
| Issue : 3 | Page : 141-144
Cerebral venous sinus thrombosis masquerading as tumor bleed in a patient of carcinoma cervix
Vishal Mangal1, Rajagopal Srinath1, VK Lekshmi1, Shweta Pandey2
1 Department of Internal Medicine, Armed Forces Medical College, Pune, Maharashtra, India
2 Department of Radiology, Armed Forces Medical College, Pune, Maharashtra, India
|Date of Submission||12-Jan-2021|
|Date of Decision||28-Apr-2021|
|Date of Acceptance||20-May-2021|
|Date of Web Publication||14-Jul-2021|
Department of Internal Medicine, Armed Forces Medical College, Pune - 411 040, Maharashtra
Source of Support: None, Conflict of Interest: None
Cerebral venous sinus thrombosis (CVT) is an uncommon subtype of stroke. In general, patients with CVT have one or more risk factors for venous thrombosis. Malignancy is an established risk factor for venous thromboembolism, and is seen in 8.9% of the patients. However, the occurrence of CVT in the case of solid organ malignancy is a rare phenomenon. Cervical cancer is a malignancy that has rarely been associated with CVT, with only one case reported in the literature, and in that also diagnosis of CVT was incidental. We present a case of a young lady with recently diagnosed locally advanced cervical cancer who presented with headache, monoparesis, and focal onset motor seizures with preserved awareness. The initial neuroimaging showed intracerebral hemorrhage. However, subsequently, she was diagnosed with CVT with hemorrhagic infarction, which was initially masqueraded as a tumor bleed.
Keywords: Cerebral venous sinus, thrombosis, carcinoma cervix, case report
|How to cite this article:|
Mangal V, Srinath R, Lekshmi V K, Pandey S. Cerebral venous sinus thrombosis masquerading as tumor bleed in a patient of carcinoma cervix. J Med Sci 2022;42:141-4
|How to cite this URL:|
Mangal V, Srinath R, Lekshmi V K, Pandey S. Cerebral venous sinus thrombosis masquerading as tumor bleed in a patient of carcinoma cervix. J Med Sci [serial online] 2022 [cited 2022 Jun 29];42:141-4. Available from: https://www.jmedscindmc.com/text.asp?2022/42/3/141/321460
| Introduction|| |
Cerebral venous sinus thrombosis (CVT) is a rare type of venous thrombosis and is responsible for 0.5% of all strokes. The annual incidence of CVT is 0.5–1 cases per million, with wide variation globally., In contrast to other types of strokes, CVT occurs predominantly in young adults and is more common in females with a male-to-female ratio of 1:2.2. There is a partial overlap between the risk factors for deep-vein thrombosis (DVT), pulmonary thromboembolism (PTE), and CVT with head-and-neck infections and head trauma specific to CVT. Malignancy is a well-established risk factor for venous thrombosis, including CVT. The most common malignancies associated with CVT are hematological, followed by solid cancers. Cervical cancer is the fourth most common cancer in women worldwide, and the second most common cancer in Indian women. Cervical cancer is the most common gynecological malignancy associated with venous thrombosis. To the best of our knowledge CVT has never been reported in a case of nonmetastatic cervical cancer. We report the first case of symptomatic CVT in a patient of cervical cancer.
| Case Report|| |
A 41-year-old lady, recently diagnosed as a case of Carcinima cervix at a different center and had received six cycles of dual-agent neoadjuvant chemotherapy, now presented with a headache for the last 4 days and weakness of left upper limb of 1-day duration. The onset was acute, and the course was improving. She denied any history of loss of consciousness, trauma, difficulty speaking, visual disturbances, fever, or vomiting. On general physical examination, the patient was conscious and oriented, and her vital parameters were within normal limits. On examination of the nervous system, pupils were bilaterally 3 mm reacting to light; left-sided upper motor neuron-type palsy of the seventh cranial nerve was present. The power was medical research council (MRC) grade 2/5 in the left upper limb and 4/5 in the left lower limb. Deep tendon reflexes were brisk on the left side, and the left plantar was extensor. A clinical diagnosis of acute stroke was established, and an urgent noncontrast computed tomography (NCCT) of the brain was done [Figure 1].
|Figure 1: (a) Axial, (b) Coronal: noncontrast computed tomography head revealed multiple hyperdensities (HU 70) involving the right frontal lobe (predominantly right precentral gyrus and subjacent white matter). These areas were surrounded by hypodensities suggestive of perilesional edema. Mass effect was seen in the form of effacement of overlying sulci. However, no midline shift was seen|
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She was managed as a case of right frontal intracerebral hemorrhage, and likely tumor bleed in a known case of carcinoma cervix. Her coagulation profile including prothrombin time, international normalized ratio, and activated partial thromboplastin time were within normal limits. The patient was not on any medication which could lead to coagulopathy. She was administered injection dexamethasone 4 mg intravenous three times a day, injection phenytoin sodium bolus of 900 mg infusion followed 8 h later by a maintenance dose of 100 mg thrice a day along with other supportive measures. The patient developed multiple episodes of focal onset motor tonic-clonic seizures with preserved awareness after 6 h of admission. She was given a loading dose of injection levetiracetam 30 mg/kg, followed by tablet levetiracetam 500 mg twice a day. She underwent contrast-enhanced magnetic resonance imaging of the brain, which revealed right frontoparietal sub-acute hemorrhage [Figure 2] and cerebral venous sinus thrombosis [Figure 3]. She was started on injection low molecular-weight heparin 60 mg subcutaneous twice a day. She had marked improvement in her clinical condition and the weakness improved to MRC grade 4/5 in the left upper limb over the next 4 days. She was tested for Factor V Leiden, Prothrombin G20210A gene mutation, Protein C deficiency, antiphospholopid antibodies, and lupus anticoagulant. However she was negative for inherited and acquired thrombophilias.
|Figure 2: (a) Magnetic resonance imaging, gradient echo series showing blooming suggestive of hemorrhage. (b) Magnetic resonance imaging, fluid-attenuated inversion recovery image showing hyperintensities in the right frontoparietal region involving the precentral and postcentral gyri. It appears hyperintense on T1W1|
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|Figure 3: (a) Sagittal time of flight series (b) Coronal gadolinium-enhanced magnetic resonance imaging. Irregular and patchy filling defects are seen in the superior sagittal sinus (the red arrows), right transverse sinus (the yellow arrow), right sigmoid sinus, right internal jugular vein, and medial aspect of the left transverse sinus. These filling defects appear isointense on T1W1, hypointense on T2W1, intermediate signal intensity on fluid-attenuated inversion recovery images, and minimal signal blooming in the gradient echo sequence|
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She did not have any previous medical records of the hospital where she was diagnosed with carcinoma cervix and received six cycles of neo-adjuvant chemotherapy. She was again evaluated by a team of a gynecologist, medical oncologist, and radiation oncologist at our center to establish the diagnosis of cervical cancer and to ascertain the extent of the disease. She underwent a magnetic resonance imaging (MRI) of the pelvis, whole-body 18flouro-deoxyglucose positron-emission tomography (WB 18FFDG PET) scan, and review of the biopsy from the cervical growth for the assessment of the disease. The cervical biopsy was reported as keratinizing squamous cell carcinoma with p16 positivity on immunohistochemistry, and MRI of the pelvis and WBFDG–PET were suggestive of locally advanced carcinoma cervix with partial response. She was planned for concurrent chemoradiation therapy. Informed written consent was obtained from the patient for publication of this case report.
| Discussion|| |
Cerebral venous sinus thrombosis includes thrombosis of the cerebral veins or major dural sinuses and is an uncommon disorder in the general population and even rare among the patients with malignancy. At least one risk factor for CVT is present in 85% of the patients, and inherited thrombophilia was identified in 22% of the patients. CVT's clinical features are highly variable, and onset could be acute, subacute, or chronic. Four major syndromes have been described: (a) isolated intracranial hypertension, manifesting as headache, (b) focal neurological deficit, (c) seizure, and (d) encephalopathy. These syndromes can present in combination or isolation, depending on the extent and location of CVT. The most common focal neurological deficit is hemiparesis and is seen in 40% of the patients. Similarly, focal or generalized seizures could be present in 30%–40% of the patients. Our patient had a headache, left hemiparesis, and focal motor seizures. Hence, the clinical diagnosis of CVT was kept in consideration. However, because of intracerebral bleed on NCCT, the possibility of tumor bleed was also considered.
It is established that malignancy is a risk factor for venous thrombosis (DVT and PTE). The most common malignancies associated with venous thrombosis are hematological, including acute leukemias, chronic leukemias, lymphomas, and rarely multiple myeloma. The solid-organ malignancies most commonly associated with venous thrombosis are breast cancer, gastrointestinal malignancies, lung cancer, and gynecological malignancies. CVT associated with cervical cancer is a rare phenomenon and we could search only one case reported in the literature, which had metastatic adenocarcinoma of the cervix with scalp metastasis, and CVT was an incidental finding. The risk of CVT is maximum during the 1st year after the diagnosis of malignancy. Our patient was diagnosed with cervical cancer 6 months back before she developed CVT.
The possible mechanism of CVT in this case could be tissue factor-like procoagulant or cancer procoagulant. Tissue factor is a transmembrane protein expressed by many human parenchymal cells, connective tissue cells, and their malignant counterparts. The second mechanism could be tissue factor-bearing microparticles (TFMP). TFMP is the tissue factor without the transmembrane domain and circulates in plasma. Recently the elevated level of TFMP has been associated with the VTE in cancer patients of different histologies. Thirdly cancer procoagulant, which is a cysteine protease found in malignant tissue, and can activate factor X directly and lead to thrombosis.
As per latest consensus routine testing for inherited procoagulant states is not mandatory. Thrombophilia work up is indicated in patients who have atleast one first degree relative with documented VTE before the age of 45 years, or patients age less than 45 years, with history of recurrent thrombosis, thrombosis at unusual vascular beds like hepatic vein, portal vein, mesenteric vein, or cerebral venous sinuses. Our patient was less than 45 years of age, with thrombosis at unusual site, hence we tested her for inherited thrombophilias; however she was negative. We did not test for protein S deficiency and anti-thrombin deficiency as there levels can be falsely low in the face of acute thrombosis.
The sensitivity of NCCT in picking up CVT is 30% only; however, NCCT is the first screening investigation of choice in a patient of focal neurological deficit and headache to exclude other disorders such as bleed or arterial strokes. In cases of uncertainty in a computed tomography scan's diagnostic utility, MRI of the brain with possible MR angiography or venography may help narrow down the differential diagnoses. In our patient also, the initial NCCT head was suggestive of intracerebral hemorrhage. However, the subsequent MRI brain revealed the diagnosis of CVT with hemorrhagic infarction. Not all intracerebral hemorrhages in the background of malignancy are tumor bleeds; CVT can masquerade the same.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bousser MG, Ferro JM. Cerebral venous thrombosis: An update. Lancet Neurol 2007;6:162-70.
Coutinho JM, Zuurbier SM, Aramideh M, Stam J. The incidence of cerebral venous thrombosis: A cross-sectional study. Stroke 2012;43:3375-7.
Devasagayam S, Wyatt B, Leyden J, Kleinig T. Cerebral venous sinus thrombosis incidence is higher than previously thought: A retrospective population-based study. Stroke 2016;47:2180-2.
Capecchi M, Abbattista M, Martinelli I. Cerebral venous sinus thrombosis. J Thromb Haemost 2018;16:1918-31.
Silvis SM, Hiltunen S, Lindgren E, Jood K, Zuurbier SM, Middeldorp S, et al.
Cancer and risk of cerebral venous thrombosis: A case-control study. J Thromb Haemost 2018;16:90-5.
Trugilho IA, Renni MJ, Medeiros GC, Thuler LC, Bergmann A. Incidence and factors associated with venous thromboembolism in women with gynecologic cancer. Thromb Res 2020;185:49-54.
Ferro JM, Canhão P, Stam J, Bousser MG, Barinagarrementeria F; ISCVT Investigators. Prognosis of cerebral vein and dural sinus thrombosis: Results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004;35:664-70.
Davoudi V, Keyhanian K, Saadatnia M. Risk factors for remote seizure development in patients with cerebral vein and dural sinus thrombosis. Seizure 2014;23:135-9.
Abhishek A, Ouseph MM, Sharma P, Kamal V, Sharma M. Bulky scalp metastasis and superior sagittal sinus thrombosis from a cervical adenocarcinoma: An unusual case. J Med Imaging Radiat Oncol 2008;52:91-4.
Zwicker JI, Liebman HA, Neuberg D, Lacroix R, Bauer KA, Furie BC, et al
. Tumor-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy. Clin Cancer Res 2009;15:6830.Epub 2009 Oct 27.
BaglinT,GrayE, Greaves M, Hunt BJ, Keeling D, Machin S, et al
. Clinical guidelines for testing for heritable thrombophilia. Br J Haematol 2010;149:209.
[Figure 1], [Figure 2], [Figure 3]