Abstract
Neoplastic cerebral aneurysms (NCAs) are rare. This study reported a case of an NCA secondary to a poorly differentiated carcinoma of the parotid gland. An 84-year-old Japanese woman undergoing treatment for parotid gland cancer was admitted to our hospital with headache and progressive loss of consciousness. Based on computed tomography (CT) and CT angiography (CTA), a diagnosis of subarachnoid hemorrhage due to rupture of a left posterior inferior cerebellar artery aneurysm was made, and emergency aneurysmectomy was performed. Pathological examination of the resected aneurysm showed an NCA secondary to parotid carcinoma. After the aneurysmectomy, her condition stabilized; however, 33 days later, the patient developed an intracerebral hemorrhage, and a new aneurysm was confirmed in the right middle cerebral artery.
To the best of our knowledge, there have been no previous reports on cases of NCAs secondary to parotid carcinoma. The pathology and clinical course strongly suggest that NCAs derived from malignant tumors may have an aggressive course.
Introduction
Neoplastic cerebral aneurysms (NCAs) are cerebral aneurysms arising from tumors. A 2015 review found that fewer than 100 cases had been previously reported, and of these, most were of myxoma origin, with NCA from malignancy being even rarer.1) NCAs from malignancy are known to have much worse bleeding rates and outcomes than NCAs from myxoma,1,2) but their clinical features and pathogenesis remain unclear.
This study presented an NCA secondary to a poorly differentiated carcinoma of the parotid gland. To the best of our knowledge, this study is the first to report an NCA secondary to parotid gland carcinoma.
Case Report
An 84-year-old Japanese woman presented to the emergency department with sudden onset of severe headache in the early morning. Her severe headache continued when she arrived at the hospital, but her consciousness was clear (E4V5M6 on the Glasgow Coma Scale), and there were no abnormal neurological findings. Head computed tomography (CT) showed diffuse subarachnoid hemorrhage (SAH) (Fig. 1A). The source image of CT angiography showed an aneurysm on the surface of the left cerebellum (Fig. 1B), and angiography showed a fusiform aneurysm at the distal segment of the left posterior inferior cerebellar artery (PICA) (Fig. 1C, D).
She had been diagnosed at another hospital with poorly differentiated carcinoma of the parotid gland with confirmed metastases in the liver, pancreas, and lung. Treatment with chemotherapy was being considered. Blood samples taken at the time of the visit showed no inflammatory findings or abnormalities of the coagulation system.
Shortly after arriving at the hospital, the patient's level of consciousness decreased to E1V1M4 on the Glasgow Coma Scale. There was no evidence of rebleeding, and it was determined that the patient's loss of consciousness was exacerbated by increased intracranial pressure in the posterior fossa. Although the cause of the aneurysm was unknown, the decision was made to perform an emergency aneurysmectomy and external decompression with placement of ventricular drainage. The operation was performed with the patient in the prone position through a median suboccipital craniotomy. The dura was incised, and a hard, black hematoma was found on the surface of the cerebellum, with presumably an aneurysm within it. The PICA proximal and distal to the aneurysm was cut, and the aneurysm was removed together with the hematoma (Fig. 2A).
Hematoxylin-eosin staining of the surgical specimen showed blood vessels within the hematoma, some of which were dilated and appeared to form an aneurysm (Fig. 2B). Tumor cells adhered to and formed a layer on the intima (Fig. 2C). The tumor cells were pale with vacuoles and rich in nuclear atypia (Fig. 2D), similar to tumor cells of known parotid carcinoma (Fig. 2E); thus, they were considered to be metastases of parotid carcinoma.
Elastica van Gieson staining showed that the internal elastic lamina, smooth muscle, and adventitia of the vessel wall were preserved in non-aneurysmal areas (Fig. 3A), whereas the internal elastic lamina disappeared in aneurysmal areas, and the smooth muscle layer and adventitia were very thin (Fig. 3B). The adjacent small branch was completely embolized by the tumor (Fig. 3B, arrowhead). Masson's trichrome staining showed partial disruption of adventitia continuity and spread of tumor cells into the hematoma outside the aneurysm (Fig. 3C). Cerebrospinal fluid cytology was negative, and dissemination was considered unlikely. Based on the above, it was thought that the tumor plug derived from the parotid carcinoma destroyed the normal structure of the vessel wall and the weakened vessel formed an aneurysm and ruptured.
After surgery, the patient's consciousness improved and stabilized, and there was no obvious evidence of rebleeding, such as intracranial or trunk. Follow-up MRI on day 30 showed no obvious metastatic findings in the brain parenchyma; however, there was a punctate high-intensity signal on diffusion-weighted imaging in the left cerebral hemisphere, suggesting asymptomatic cerebral infarction due to tumor embolization (Fig. 4A). Furthermore, follow-up CT on day 30 showed a small SAH in the parietal region (Fig. 4B). However, CT angiography at that time did not include the parietal area and the aneurysm could not be detected (Fig. 4C). Three days later, the patient became comatose again, and head CT showed a cerebral hemorrhage in the right frontal lobe (Fig. 4D). Repeat CT angiography showed a fusiform aneurysm within the hematoma at the distal segment of the right middle cerebral artery (Fig. 4E). Since the primary disease was not under control, the family preferred conservative treatment, and respiratory failure due to impaired consciousness progressed, and the patient died 2 days after the hemorrhage.
Written informed consent for publication of the patient's information and images was obtained from her family.
Discussion
This study described a case in which a poorly differentiated salivary gland carcinoma derived from the parotid gland metastasized to the vascular wall of the brain and formed multiple cerebral aneurysms in a short period of time, resulting in SAH and cerebral hemorrhage.
A 2015 review reported that NCA is a rare disease with less than 100 cases.1) Benign cardiac myxoma accounts for 60.4% of primary lesions, followed by choriocarcinoma (26.1%) and other tumors (13.5%). In a review limited to non-myxoma, choriocarcinoma was followed in frequency by lung cancer and lymphoma.2) There have also been several recent reports of NCAs due to breast cancer.3,4) However, to the best of our knowledge, there have been no previous reports of NCAs due to poorly differentiated carcinoma of salivary gland origin.
The prognosis and rupture rates of NCAs greatly differ between myxoma and non-myxoma. For NCAs derived from myxoma, the intracranial hemorrhage rate is 19.6%, whereas NCAs derived from non-myxoma, the rate is 100% and 84.6% for choriocarcinoma and other tumors, respectively.1) The mortality rate is 11.4% for myxoma, compared with 60.9% for choriocarcinoma and 92.3% for other tumors, and the pathology of the primary tumor is thought to significantly correlate with the bleeding rate and prognosis. The present case had a poor prognosis, as did patients with other NCAs of non-myxoma origin. It is noteworthy that, after it was confirmed that there was no aneurysm, the patient developed an aneurysm that ruptured in a period of 33 days. Although there are other reports of multiple NCAs of non-myxoma origin,3,5) and there are several reports of cerebral hemorrhage and SAH in multiple regions over a short period of time,6) only a few reports have captured the development of de novo aneurysms in a chronological sequence. Nussbaum et al. reported a case of multiple new intracranial aneurysms 4 months after treatment for an NCA due to breast cancer,3) whereas Omofoye et al. reported a case of SAH due to a ruptured de novo left superior cerebellar aneurysm not found on magnetic resonance angiography 19 days earlier in a patient with non-small cell lung cancer.7) Moreover, the present case had a short development time of 33 days, demonstrating the possibility of aneurysm formation and rupture in a short time in NCAs associated with malignancy. In the present case, a minor leak of the SAH was observed at the routine follow-up CT on day 30, but the CTA did not include the parietal area, and the aneurysm could not be detected at that time. It has been reported that NCAs tend to form in the periphery, and it is desirable to ensure that the periphery is included in the follow-up imaging of NCAs.5)
Pathological examination of the surgical specimen showed that tumor cells had spread along the inner wall of the aneurysm and further infiltrated the wall, resulting in loss of normal membranous structure. Other reports have also described extension of tumor cells along the inner wall of blood vessels3,4) or infiltration of atypical cells into the smooth muscle layer and extension into the adventitia.8) In the present case, even the adventitia was partially disrupted, and tumor cells leaked out of the blood vessels, a finding that suggests a more aggressive nature of the disease. Although the pathogenesis and natural history of NCA remain unclear,9) the present pathological study showed that, in NCAs caused by non-myxoma, a fragile aneurysm may form in a very short time due to the invasiveness of the malignant tumor cells, resulting in a high incidence of hemorrhage. If an aneurysm is caused by tumor emboli, there is a possibility that aneurysms may occur in blood vessels throughout the body other than the cerebral blood vessels, but there are currently no reports of NCAs complicated by aneurysms or bleeding in the trunk.
Currently, the only way to diagnose NCAs is by pathology. NCAs are relatively rare, and it is difficult to determine on imaging whether a cerebral aneurysm in a patient with cancer is an incidental dissecting aneurysm or an NCA.
The treatment strategies for NCA are also unclear. As mentioned above, it is currently difficult to make a definitive diagnosis of NCA at the stage of an unruptured mass, and treatment strategies for ruptured masses are the main focus. While 75.9% of myxoma patients are treated conservatively, 92% and 69.2% of NCAs from choriocarcinoma and other tumors, respectively, receive aggressive therapeutic intervention, including surgery.1) Although clipping or trapping of the aneurysm may be the surgical treatment of choice,2) an NCA secondary to a malignant tumor is expected to have a fragile structure due to tumor cell infiltration of the aneurysm and the parent vessel, as seen in the pathology specimen of the present case, necessitating resection of the entire parent vessel, as advocated by Suematsu et al.8)
In addition, frequent imaging for the possibility of new aneurysm formation and early radiotherapy of the primary tumor to prevent new metastases are considered important to improve prognosis.2,3) However, it is extremely difficult to make a timely diagnosis of an aneurysm that develops and ruptures in such a short period of time, and treatment after confirmation of aneurysm recurrence may miss the appropriate time for surgery. Nussbaum et al. reported a case of NCA regression after whole brain irradiation and mentioned the possibility of controlling NCAs by whole brain irradiation.3) Although whole brain irradiation is not less invasive, based on the rapid course of this case and the high mortality rate, we believe that upfront whole brain irradiation may be justified for possible recurrence of NCAs associated with malignant tumors. However, since tumor cell metastasis may occur after whole brain irradiation, and the efficacy of whole brain irradiation itself in preventing aneurysm formation is unknown, the validity of upfront irradiation needs to be evaluated based on review of future cases.
Conclusion
A case of an NCA caused by poorly differentiated adenocarcinoma of the salivary gland was reported. Aneurysms in patients with a carcinoma can be NCAs, and caution is needed due to the poor outcomes from the high rupture and recurrence rates. Whole brain irradiation may be considered for patients diagnosed with NCAs in parallel with treatment of the primary tumor.
Funding
This publication was prepared without any external source of funding.
Conflicts of Interest Disclosure
The authors declare no conflicts of interest.
References
- 1) Zheng J, Zhang J: Neoplastic cerebral aneurysm from metastatic tumor: a systematic review of clinical and treatment characteristics. Clin Neurol Neurosurg 128: 107-111, 2015
- 2) Nussbaum ES, Torok CM, Khalil ZM, Pederson JM: Non-myxoma neoplastic cerebral aneurysms: A systematic review. Journal of Clinical Neuroscience 82: 200-206, 2020
- 3) Nussbaum ES, Torok CM, Khalil ZM, Pederson JM: Neoplastic cerebral aneurysm from triple-negative breast cancer: A case report. Surgical Neurology International 3: 12, 2022
- 4) Koga M, Aoki T, Negoto T, et al.: Leptomeningeal carcinomatosis after neoplastic cerebral aneurysm rupture. World Neurosurgery 126: 281-284, 2019
- 5) In BC, Byung MC, Se HP, Dae YY, Sae MO: Metastatic choriocarcinoma with multiple neoplastic intracranial microaneurysms: case report. J Neurosurg 108: 1014-1017, 2008
- 6) Wang D, Shu H, Zhang Q, Zhang H, Qing C, Wang H: Brain metastasis of choriocarcinoma presenting as multiple intracranial hematomas: A case report. Medicine (Baltimore) 97: e12275, 2018
- 7) Omofoye OA, Barnett R, Lau W, Trembath D, Jordan JD, Sasaki-Adams DM: Neoplastic cerebral aneurysm from metastatic nonsmall cell lung carcinoma: case report and literature review. Neurosurgery 83: E221-E225, 2018
- 8) Suematsu T, Murakami T, Sudo Y, et al.: Neoplastic ruptured cerebral aneurysm caused by intimal sarcoma: a case report. NMC Case Report Journal 9: 329-335, 2022
- 9) Sedat J, Chau Y, Dunac A, Gomez N, Suissa L, Mahagne MH: Multiple cerebral aneurysms caused by cardiac myxoma: a case report and present state of knowledge. Interventional Neuroradiology 13: 179-184, 2007
