Ischemic stroke with concomitant clear cell carcinoma of the ovary: A case report and review of literature

Abstract

BACKGROUND

Ischemic stroke is a rare event associated with an elevated risk of blood clot formation owing to an underlying malignancy. Herein, we present a case of ovarian carcinoma that led to cerebral infarction.

CASE SUMMARY

A 43-year-old woman experienced sudden onset right-sided paralysis and difficulty speaking two days after discovery of a large ovarian tumor measuring approximately 14 cm, which was suspected to be malignant. Further examination revealed left middle cerebral artery infarction. The patient had a history of hypertension and adenomyosis. Following stabilization with heparin treatment and vital signs management, the patient underwent debulking surgery, including total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and bilateral pelvic and para-aortic lymph node dissection. The final diagnosis was clear cell carcinoma of the right ovary (stage IA). Subsequently, the patient completed six rounds of adjuvant chemotherapy while simultaneously undergoing rehabilitation. Presently, the patient is able to walk independently, although she still experiences aphasia.

CONCLUSION

Prompt medical intervention and interdisciplinary care are crucial in the setting of incidental findings such as a large ovarian tumor.

Key Words: Ovarian cancer; Ischemic stroke; Coagulation; Infarction; Case report

Core Tip: We report a case of ischemic stroke associated with ovarian cancer. We have updated the information on ovarian cancer with concurrent ischemic stroke regarding its symptoms, signs, diagnosis, and treatment. Because of the rarity of combined ischemic stroke and ovarian cancer, we provide a strategy for diagnosing and treating this condition.

INTRODUCTION

Ovarian cancer is a relatively rare but severe malignancy that develops in the ovaries and female reproductive organs[1]. It ranks fifth in cancer-related deaths among women, with approximately 1000 new cases diagnosed annually in Taiwan[2]. The symptoms of ovarian cancer are often vague and nonspecific, including abdominal bloating, pelvic pain, urinary urgency, and changes in bowel habits[3]. Owing to the lack of specific symptoms, ovarian cancer is frequently diagnosed at an advanced stage, emphasizing the importance of awareness and early detection[4].

Diagnosis typically involves a combination of imaging tests, such as ultrasound and computed tomography (CT), alongside blood tests to measure tumor markers such as CA-125 levels[5]. A definitive diagnosis is made through surgical biopsy and histological examination of the ovarian tissue. Treatment strategies vary based on the disease stage, patient age, and overall health. The primary treatment typically involves surgery for tumor resection, followed by chemotherapy to target any remaining cancer cells[6].

Ischemic stroke is a leading cause of disability and mortality worldwide and occurs when a blood vessel in the brain is blocked by a clot or narrowed due to atherosclerosis[7]. Ischemic strokes account for approximately 87% of all stroke cases[7]. The symptoms of ischemic stroke typically manifest suddenly and include weakness or paralysis on one side of the body, difficulty speaking or understanding speech, sudden confusion, vision problems, and severe headache. Prompt recognition of these symptoms is critical, as early intervention can minimize brain damage and improve outcomes[7].

The diagnosis of ischemic stroke involves a thorough neurological examination, imaging studies such as CT or magnetic resonance imaging to confirm the presence of a clot and determine the extent of brain damage, and additional tests such as Doppler ultrasound or angiography to identify the underlying cause[8].

Treatment aims to restore blood flow to the affected brain areas and prevent further damage. This may involve administering clot-dissolving medications (thrombolytics) such as tissue plasminogen activator or performing mechanical thrombectomy to remove clots directly[9,10]. Supportive care, rehabilitation, and lifestyle modification to reduce stroke risk factors are crucial components of stroke management. Early recognition, rapid intervention, and comprehensive care are essential for optimizing outcomes in individuals with ischemic stroke.

Ischemic stroke is an uncommon occurrence resulting from an increased tendency for blood clot formation induced by an underlying malignancy[11]. Venous thromboembolism (VTE) is the leading secondary cause of death in patients with ovarian cancer, especially those with clear cell histology[12]. However, the incidence of arterial thrombosis in patients with ovarian carcinoma is only 2.4%, and cerebral infarction accounts for only 2.2%[12].

Herein, we describe a case of ovarian clear cell carcinoma with concurrent cerebral infarction.

CASE PRESENTATION

Chief complaints

Sudden onset of right hemiplegia and aphasia for 2 days.

History of present illness

A 43-year-old female (G0P0) experienced a sudden onset of right hemiplegia and aphasia. Two days prior, a large ovarian tumor measuring approximately 14 cm and suspected to be malignant was found incidentally. She visited our emergency room, where a brain CT scan showed a left parietal hypodensity without intracranial hemorrhage and was diagnosed with a left middle cerebral artery infarction. Abdominal CT revealed a 14 cm ovarian tumor in the right pelvis. She was admitted to the surgical intensive care unit, where heparin therapy was initiated. After one week of therapy, her vital signs were stable, heparin therapy was discontinued, and she was transferred to the gynecologic service.

History of past illness

The patient’s medical history was significant for hypertension controlled on antihypertensive medications. She had adenomyosis. The patient was nulliparous.

Personal and family history

The patient’s father had a history of colon cancer, but no other family history of cancer was recorded.

Physical examination

The patient was 160 cm tall and weighed 65.4 kg. Her body mass index was 25.5, and her blood pressure upon admission was 182/97 mmHg. One week after admission, a blood pressure of 142/83 mmHg was noted on the day of surgery. On postoperative day 9 (day of discharge), the patient’s blood pressure was 132/85 mmHg. She presented with right hemiparesis, aphasia, and an ill-looking appearance. The patient’s motor power was 0 in the right upper and lower extremities and 4 in the left upper and lower extremities. The pupils were located at the midline. Babinski’s sign was positive. Clear breath sounds and regular heartbeats were also observed. Vaginal examination revealed a pinpoint cervical opening and an enlarged pelvic tumor.

Laboratory examinations

All tumor markers were elevated including carcinoembryonic antigen (18.4 ng/mL; normal limit: 3.0 ng/mL), CA125 (676.5 U/mL; normal limit: 35.0 U/mL), and CA19-9 (52.9 U/mL; normal limit: 35.0 UmL). Electrocardiogram findings were normal. Before the operation, D-Dimer was 7361 ng/mL. The D-dimer value was returned to normal (325.99 ng/mL) 2 months postoperatively.

Imaging examinations

CT revealed a left parietal hypodensity without intracranial hemorrhage (Figure 1). Transabdominal ultrasonography revealed a large pelvic tumor measuring 14 cm × 9 cm. CT revealed a 14.2 cm mixed cystic and solid component tumor in the pelvic cavity (Figure 2). We did not find thrombus in other body parts.

Figure 1  Coronary view of computer tomography of the brain. Left cerebrum infarction was noted (arrow).

Figure 2 Coronary view of computer tomography of the abdominal cavity. A 14.2 cm mixed cystic and solid components tumor was noted in the pelvic cavity (arrow).

FINAL DIAGNOSIS

The final diagnosis was clear cell carcinoma of the right ovary, stage IA. An ischemic stroke was noted at the left middle cerebral artery.

TREATMENT

After one week of heparin therapy, her stroke status was stable. The patient underwent debulking surgery with total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, and omentectomy (Figure 3). Histopathological examination revealed stage IC clear cell carcinoma of the ovary (Figure 4). After surgery, adjuvant chemotherapy with paclitaxel (175 mg/m²) and carboplatin (dose-area under the curve = 5) was administered.

Figure 3 Gross picture of the right ovarian tumor. A yellowish multi-lobulated ovarian tumor was noted.

Figure 4 Pathological picture of the tumor. Clear cell carcinoma of the ovary was noted. Clear cytoplasm and varied nuclei morphology (cubmoidal to large, polygonal nuclei) were noted. Scale bar = 100 μm.

OUTCOME AND FOLLOW-UP

The patient received six courses of adjuvant chemotherapy. The tumor markers returned to normal levels after treatment. During treatment with chemotherapy, the patient underwent simultaneous rehabilitation. Regarding subsequent therapy for stroke, she received a subcutaneous injection of 60 mg clexane for two months. The novel anticoagulation agent, dabigatran (150 mg twice daily), was given for three months. Thereafter, 100 mg of aspirin was administered daily. Antihypertensive medications were administered. After follow-up for one year and four months, she was able to walk independently, but aphasia persisted.

DISCUSSION

Ovarian clear cell carcinoma is a subtype of epithelial ovarian cancer comprising approximately 5%–10% of all ovarian malignancies[13]. While it is less common than histological subtypes such as serous carcinoma, its prevalence varies depending on geographic and ethnic factors. Clear cell carcinoma of the ovary is characterized by distinct histological features[13]. Under a microscope, the tumor cells have a clear cytoplasm owing to the accumulation of glycogen and lipids[14]. Additionally, clear cell carcinomas often present with hobnail cells and papillary structures. Dysregulation of the PI3K/AKT/mTOR pathway has also been implicated in the pathogenesis of this cancer subtype[15]. Clinically, ovarian clear-cell carcinoma tends to present at an advanced stage, and is often associated with resistance to conventional platinum-based chemotherapy[16]. Patients with clear cell carcinoma may have a poorer prognosis than those with other histological subtypes of ovarian cancer[17].

Trousseau syndrome, first described in 1865 by Armand Trousseau, describes the hypercoagulability associated with malignant diseases[18]. Although ovarian cancer has a high incidence of VTE, cerebral infarction or arterial embolism rarely occur in ovarian cancer[19]. In a study that included 13031 patients with ovarian cancer, 5.2% had VTE events within 24 months[20]. Compared to patients with VTE or pulmonary embolism, patients with ovarian cancer rarely develop cerebral infarction[21]. In a retrospective study consisting of 827 patients with primary epithelial ovarian cancer, 3.2% presented with cerebral infarction within one year before the commencement of treatment for malignant disease or during initial clinical treatment[18]. This study also demonstrated a statistically significant association between cerebral infarction occurrence and the histological subtype of clear cell carcinoma. Tissue factors, cancer procoagulants, and inflammatory cytokines such as interleukin (IL)-6 all play essential roles in promoting hypercoagulable states in ovarian cancer. Clear cell carcinoma is associated with excess levels of tissue factor and IL-6 and is thus more likely to lead to the development of VTE[22].

Generally, risk factors for arterial thromboembolic events in other parts of the body, including the heart and brain, are hypertension, hyperlipidemia, obesity, diabetes, and smoking[23]. In gynecology, taking combined oral contraceptive pills or hormone replacement therapy increases the arterial thromboembolic risk[24]. In a prospective cohort study documenting 893 incident stroke cases, women with endometriosis had a 34% greater risk of stroke than those without endometriosis[25]. Also, in another study of 521612 participants, endometriosis was significantly associated with increased risks of ischemic stroke[26]. Endometriosis can increase arterial stiffness; thus, patients may be at an increased cardiovascular risk[27].

We searched the literature and found one populational study and 15 case reports related to this topic (Table 1)[19,21,28-40]. The patients’ ages ranged from 35 to 76 years, and most patients had a history of hypertension. The tumor stages ranged from I to IV. The most commonly used chemotherapeutic regimens in these reports were carboplatin and paclitaxel, and five of the 13 patients died. The populational study revealed ovarian cancer patients faced a heightened likelihood of experiencing ischemic stroke, with age, hypertension, diabetes, and chemotherapy treatment emerging as distinct risk factors[39].

Table 1 Literature review of the previous studies from 2010 to 2024.

Ref.	Year	Age	BMI (kg/m2)	Parity	History of hypertension	Stage	Thrombosis site	Adjuvant therapy	Status
Blustein et al[19]	2023	35	No record	1	Yes	IIB	Right MCA	Carboplatin, dose-dense paclitaxel for 6 courses	Survive
You et al[30]	2022	41	No record	No record	No record	No record	Left parietal, temporal lob	Neoadjuvant therapy × 3	Died
Tandi et al[33]	2022	76	No record	No record	No	IIA	posterior cortical artery	No record	No record
Farooqui et al[34]	2021	52	No record	No record	No	IV	Right MCA and ACA	No record	No record
Chen et al[21]	2020	46	21.8	No record	Yes	IIIC	Deep vein thrombosis and pulmonary embolism	Carboplatin, paclitaxel for 3 courses	Survive
Sakuta et al[35]	2019	55	No record	No record	No	IV	Left MCA	Not yet started	Survive
Potugari et al[36]	2019	52	No record	No record	Yes	IIIB	Multiple acute and subacute infarcts in the brain	Neoadjuvant therapy × 6, post-op chemotherapy × 3	Survive
Ricci et al[37]	2018	57	No record	No record	No	No record	Left mesial-occipital lobe	Yes	Survive
Lin et al[31]	2015	60	Not record	Not record	Yes	IIIC, recurrent	Bilateral cerebra and cerebella	No	Died
Yagi et al[38]	2014	54	No record	No record	No	No record	Right MCA	No	Died 3 weeks after the onset of stroke
Kuan et al[39]	2014	49 (median of 8810 patients)	No record	No record	Yes (risk factor)	No record	Ischemic stroke risk: 1.38-fold	No record	No record
Tadokoro et al[40]	2013	55, 56	No record	No record	No	No record	Left MCA	No record	No record
Naoi et al[28]	2013	55, 62	No record	No record	No record, Yes	IIIC, IC	Bilateral thalamus, right frontal lobe, and left cerebellum	Carboplatin, paclitaxel for 6 courses, recurrence	Died, survive
Devulapalli et al[29]	2012	62	No record	No record	Yes	I	Occipital	Carboplatin, paclitaxel for 6 courses	Survive
Oueida et al[32]	2011	56	Not record	Not record	No	IC	Endocarditis with multi-organ embolic infarction	5 courses of adjuvant chemotherapy	Died
Current case	2024	43	25.5	0	Yes	IA	Left MCA	Carboplatin, paclitaxel for 6 courses	Survive

MCA: Middle cerebral artery; ACA: Anterior cerebral artery.

Given the known association between ovarian malignancy and thromboembolic states, it is reasonable to relate the hypercoagulable state of ovarian cancer to the cerebral infarction event in this case.

CONCLUSION

Clear ovarian cell carcinomas may be associated with thromboembolic events. Therefore, malignancy should be considered a risk factor for cerebral infarction development, particularly in patients diagnosed with ovarian cancer.