Endovascular aspiration to treat acute ischemic stroke caused by embolic carcinoma

Abstract

Although cardiac myxomas have been known to cause acute ischemic stroke and other cerebrovascular complications, intracranial embolization of metastatic tumor fragments is rare. This is likely because venous emboli generally cause pulmonary embolism. Pulmonary vein metastases and patent foramen ovales have previously shown to propagate intracranial embolic carcinomas, but these events are very uncommon, and are not well characterized. We report a rare case of large-cell, high-grade neuroendocrine lung cancer embolus occluding the basilar artery, which likely detached into the bloodstream from the lung after intruding into a pulmonary vein. The embolus was treated with endovascular aspiration, and achieved modified Thrombolysis In Cerebral Infarction 2c revascularization. After initial neurological recovery, the patient suffered respiratory arrest and support was withdrawn 48 h later. We discuss the tumor characteristics and implications for treatment of acute ischemic stroke in patients with cancer diagnoses.

Introduction

Although venous thromboembolism is a common complication of many cancer types,¹ and the risk of stroke is increased by coagulation disorders related to both cancer and cancer therapy,² acute ischemic stroke (AIS) caused by embolic carcinomas is an exceedingly rare occurrence.³ Cardiac myxomas are known to cause cerebrovascular complications,⁴ including AIS, as they can embolize directly into the arterial circulation.⁵ However, metastatic cancers rarely cause intracranial arterial embolization, with only one case of melanoma,⁶ breast cancer,³ and sarcoma,⁷ previously described. We report the successful endovascular aspiration of an embolic carcinoma, suggest possible mechanisms of intracerebral tumor emboli, and discuss treatment choices for cancer patients presenting with AIS.

Case report

In March 2017, after our patient noted a large inguinal node, two adjacent lung lesions located in the upper lobe of the left lung, as well as an adrenal mass, were discovered by computed tomography (Figure 1). The primary tumor was 1.7 cm in length and biopsy resulted in diagnosis of large-cell, high-grade neuroendocrine lung cancer. Treatment with multiple rounds of carboplatin and paclitaxel resulted in excellent response on imaging. The patient was an 80-year-old male with a history of hypertension, insulin-dependent diabetes mellitus, sleep apnea, coronary artery disease previously treated with multiple cardiac stents, right internal carotid artery occlusion, previous right hemispheric cerebral infarction, a left carotid stent, and recent transcatheter aortic valve replacement for aortic stenosis in 2017. Additionally, he had a history of vascular dementia, chronic obstructive pulmonary disease, and a 120 pack/y history of cigarette use.

Figure 1.

Chest computed tomography revealing two abnormal masses in the upper lobe of the left lung (black oval).

In January 2018, the patient developed aphasia in the waiting room of a family practice clinic. He was sent to the emergency room and arrived 45 min later. His vitals revealed a blood pressure of 84/96 mmHg, pulse of 92 beats/min, and respiratory rate of 21 respirations/min. The patient was re-evaluated via Telestroke with a National Institutes of Health Stroke Scale score of 19 and emergently intubated after losing consciousness. We performed angiography, and computed tomography angiography, and a basilar artery occlusion was suspected (Figure 2(a) to (c)).

Figure 2.

(a) Presentation non-contrast head computed tomography showing no acute abnormality; basilar artery is not hyperdense. (b) Angiogram confirms embolus occluding the basilar apex (arrow), as well as occlusions of the posterior cerebral arteries and the right superior cerebellar artery and partial occlusion of the left superior cerebellar artery. (c) Pre-treatment computed tomography angiography 3D coronal reconstruction showing filling defect within the basilar apex. (d) Lateral view of head; arrow shows tip of the 4MAX reperfusion catheter within the distal basilar artery. (e) Post-treatment magnetic resonance diffusion image shows scattered small patches of ischemia within the left cerebellum, posterior left temporal lobe, and the occipital lobes (arrow heads). (f) Post-treatment angiogram showing reperfusion of the basilar trunk and its dominant branches.

The patient received intravenous (IV) tissue plasminogen activator (tPA) followed by mechanical thrombectomy. During thrombectomy, a guide catheter was first advanced into the left vertebral artery and exchanged for a 6Fr Neuron MAX guide sheath (Penumbra Inc., Alameda, California, USA). Using fluoroscopic roadmap guidance, a 4MAX reperfusion catheter (Penumbra Inc.) was advanced to the occlusion site. Two aspiration embolectomy passes were made; the second yielded a 1.5-cm-long string of lobulated, soft, yellow embolic material. Based on the modified Thrombolysis In Cerebral Ischemia (mTICI) scale, angiogram revealed mTICI 2c recanalization status (>90% branches open, but not identical to normal angiogram) (Figure 2(d)).

After 24 h, magnetic resonance imaging showed multiple areas of subacute infarction in the cerebellum, left thalamus, midbrain, right occipital lobe, and a larger infarction in the left temporo-occipital region (Figure 2(e)). Angiogram confirmed reperfusion of the basilar trunk and its dominant branches (Figure 2(f)). He was extubated approximately 48 h post-operatively. The patient was alert and interactive with only mild visual deficits. However, he developed respiratory failure and expired one day after extubation.

The retrieved embolus was fixed in formalin and histology processing revealed hyperchromatic neoplastic cells amid fibrin on hematoxylin and eosin staining; neoplastic cells displayed mitoses and apoptotic debris, and the mass was classed as a Grade IV tumor (Figure 3(a) to (c)). Staining with anti-CD45 and cytokeratin AE1/AE3 were both negative. Synaptophysin staining showed positive for immunoreactivity (Figure 3(d)), indicating that the embolus was neuroendocrine carcinoma. Because the patient’s lung lesions were also high-grade neuroendocrine carcinomas, it is likely that the embolus detached into the bloodstream from the lung after intruding into a pulmonary vein.

Figure 3.

(a) Vessel-shaped embolus with eosinophilic fibrin on the left and hyperchromatic neoplastic cells on the right; original magnification 100×, hematoxylin and eosin. (b) Round-contoured embolus with hyperchromatic admixed neoplastic cells; original magnification 200×, hematoxylin and eosin. (c) High-power photomicrograph showing hyperchromatic, irregular cells with mitoses and apoptotic debris; original magnification 400×, hematoxylin and eosin. (d) Immunohistochemical stain for synaptophysin showing immunoreactivity within neoplastic cells; original magnification 200×.

Discussion

Our case demonstrates that embolic carcinoma is a possible complication of large-cell, high-grade neuroendocrine lung cancer. Given that most previously reported tumor emboli were autopsy findings,³ our case gives insight into treatments for patients at risk of AIS caused by embolic carcinomas.² Embolic carcinoma represents a rare event that may account for ineffective recanalization with IV tPA. Although embolic carcinoma has not been associated with worse outcomes for cancer patients in large, retrospective studies,⁸ embolic carcinomas are unlikely to respond to IV tPA. Our case serves as a novel example of the possible origin of intracerebral emboli in patients with lung cancer and demonstrates that mechanical thrombectomy can be used to achieve revascularization.

Embolic carcinoma–induced AIS is rare. Tumor emboli from the venous circulation generally embolize to the lungs as they pass through the right side of the heart and subsequently occlude pulmonary arteries and capillaries. To embolize intracranially, tumors must traverse the capillary beds, pass through a patent foramen ovale, or, as is likely in the present case, embolize directly from the pulmonary veins to the left atrium.^3,9 Intracranial emboli can also result from cardiac metastases.¹⁰ Emboli from cardiac myxomas and other heart tumors provide guidance on management of rarer metastatic emboli,^5,10 as there have been mixed results for the efficacy of IV tPA, but promising outcomes in patients treated with mechanical thrombectomy. An earlier case of successful endovascular retrieval of a breast cancer embolus suggests that the presence of metastases in the pulmonary veins should be considered a risk factor for intracranial emboli.³ Successful recanalization using the Penumbra System was also achieved following a metastatic melanoma embolus.⁶ Histology in another case of a sarcomatoid carcinoma embolus had peripheral endothelialization similar to that seen in our case, serving as a marker of tumor emboli in addition to neoplastic cells.⁷ This case shows that mechanical embolectomy of metastatic cancer emboli can achieve recanalization, and that embolic carcinomas are a rare but important risk to consider for patients diagnosed with metastatic cancers.

Conclusions

Although carcinomas rarely embolize intracranially, circumstances allowing entry to the left atrium can lead to AIS, due to tumor intrusion into a pulmonary vein or other extraordinary circumstance. Treatment with IV tPA may be contraindicated for embolic carcinomas, because these emboli are not thrombotic in nature. Treatment with endovascular aspiration achieved revascularization and reasonable neurological recovery, but the patient died of respiratory arrest.

Declaration of conflicting interests

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: KMK works for and holds equity in Superior Medical Experts.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: grant from the United Hospital Foundation.