Lethal Complications of Meningiomas: A Case Series

Abstract

Background:

Meningiomas are the most prevalent type of primary intracranial tumor in adults, comprising nearly one-third of all intracranial tumors. They are typically benign, slow-growing, and asymptomatic but may cause neurological symptoms as they expand due to mass effect. Classification is determined by World Health Organization (WHO) grades 1 to 3 following pathological examination corresponding to benign, atypical, and anaplastic (malignant), respectively, reflecting their rate of growth and risk of recurrence. The vast majority are WHO grade 1 and their slow growth permits timely presentation for elective resection; however, meningiomas in vulnerable locations and coexisting morbidities can result in sudden death.

Objectives:

We present a series of four adult patients with meningiomas which resulted in death, including a case of fatal seizure, midline hemorrhagic meningioma, postresection meningitis, and compression of the cerebellum.

Research design:

Retrospective review of the authors’ cases was conducted. Available pathology, medical, and autopsy records including gross images were reviewed in each case. The inclusion criteria were adult patients (>18 years old) and that the cause of death had to include meningioma.

Subjects:

The four patients included a 61-year-old male, an 84-year-old female, a 62-year-old male, and a 37-year-old female.

Measures:

Qualitative; autopsy reports describing cause of death and pathology report findings including gross and microscopic analysis.

Conclusions:

Meningiomas are often benign in nature but can rarely result in death. Size and location of the tumor and risk factors are contributory. Autopsy examination can be instrumental in identifying the cause and mechanism of deaths associated with meningiomas.

Introduction

Meningiomas are the most common type of primary intracranial tumor in adults and arise from meningothelial cells of the arachnoid mater, consisting of approximately one third of all intracranial tumors (1,2). Typically benign and slow-growing meningiomas can present either with or without symptoms. Asymptomatic meningiomas can be discovered incidentally on head imaging for evaluation of unrelated diagnoses or at autopsy, and patients with symptomatic meningiomas usually experience progressively worsening symptoms that allow enough time for medical evaluation and elective treatment with surgical resection or radiosurgery (3). Unlike ruptured aneurysms, intracranial hemorrhages, traumatic head injuries, or other neurologic emergencies, meningiomas rarely lead to sudden death. Current literature of meningiomas directly contributing to rapid death consists mostly of case reports or series (4), which often cite mass effect (5) as the underlying cause. We present a series of meningiomas that resulted in death. Our cases represent a greater variety of complications involving these lethal meningiomas.

Methods

The cases were selected from the cases of the authors (JLD, EAD, AOFH, JAP). Available pathology, medical, and autopsy records including gross images were reviewed in each case. The inclusion criteria were adult patients (>18 years old) and that the cause of death had to include meningioma. Four cases were identified. The first case involved a fatal seizure precipitated by meningioma. The second death was related to a midline hemorrhagic meningioma. The third case involved postresection meningitis. The fourth death was due to mass effect on the cerebellum.

Results

Case 1: Fatal Seizure Precipitated by Meningioma

A 61-year-old male with a history of coronary artery disease, a seizure disorder related to a large right frontal meningioma, and recent colectomy for recurrent colon adenocarcinoma presented with a seizure. He had undergone a major colon resection surgery to treat his colon cancer approximately 2 weeks prior. Emergency medical services (EMS) was called and, during his postictal state while talking to EMS, he had a fatal cardiac arrest. At autopsy a 5 cm well-circumscribed meningioma was noted to compress the frontal lobe ( Figure 1 ). Medical record review revealed that his seizures were considered by his physicians to be related to the meningioma; a resection was scheduled but had not yet taken place. Autopsy revealed that the patient had deep vein thrombosis (DVT) and acute pulmonary thromboembolism, whose histologic appearance was consistent with the postoperative timeframe; the deep venous thrombosis showed early organization, as did the emboli; however, they were not adherent to or organizing within the pulmonary arterial intima, indicating that the embolic event was acute. The meningioma was consistent with a World Health Organization (WHO) grade 1 tumor. The cause of death was deep venous thromboses with bilateral pulmonary emboli, due to stasis and immobility precipitated by his postoperative hypercoagulable state for colonic adenocarcinoma, with a contributing factor of immobility due to his postictal state which was related to a meningioma-initiated seizure.

Figure 1:

Case 1 - Coronal section of the 5-cm tumor compressing the right frontal lobe.

Case 2: Hemorrhage of Midline Meningioma

An 84-year-old female presented with a headache where a midline anterior fossa meningioma was noted on computerized tomography. Surgery was not performed during this admission, citing lack of neurological deficits. On subsequent admission, neurologic deficits were noted with the presence of subarachnoid hemorrhage, which led to her death. At autopsy a 2 cm midline hemorrhagic meningioma was identified as the cause of the hemorrhage and of death. The mass, bilobed in appearance and measuring 4 cm at its greatest dimension, had a heterogeneous consistency ( Figure 2 ). The anterior portion, measuring 2 cm, had a mostly red-pink color and a fleshy, friable consistency, whereas the posterior portion that filled the sella turcica had a white-tan color with a more firm, neural-like consistency. In addition, numerous cerebral infarcts were also seen, though they were believed to have been a consequence of the hemorrhagic tumor and subarachnoid hemorrhage. Of note, there was no evidence of significant cerebrovascular disease. The microscopic appearance of the tumor was consistent with WHO grade 1 ( Figure 3 ).

Figure 2:

Case 2 - Left: A coronal section of the brain exposes the midline meningioma, seen as the round mass in the most inferior aspect of the image. Signs of focal acute hemorrhage are seen in addition to numerous areas of cerebral infarct. Right: Inferior view of the brain, prior to sectioning, where the meningioma is partially visualized.

Figure 3:

Case 2 - Whorled architecture, hemosiderin, psammoma bodies, and red blood cells present in histology is consistent with the patient’s age, evidence of prior bleeding, and meningioma presentation. H&E stain.

Case 3: Postresection Meningitis

A 62-year-old male who had a frontoparietal WHO grade 1 meningioma resection three weeks previously and a history of multiple myeloma treated with chemotherapy (lenalidomide) and dexamethasone complained of intractable headaches and photophobia for approximately a week before being found dead in his residence. During the several days prior to his death, the patient reported three days of severe headaches with photophobia. Gross examination at autopsy revealed a 5.5 × 5.5 cm region of cloudy, yellow discoloration the leptomeninges of the right frontoparietal lobe ( Figure 4 ). Hyperemia extending 1.5 cm deep into the subcortical white matter around this area was also noted. There was no evidence of residual tumor, hemorrhages, or malformations. Microscopic examination of the right frontoparietal subarachnoid space and the dura mater at autopsy showed abundant neutrophils, necrotic debris, fibrin, and congested vasculature near the resection site which also contained surgical hemostatic material ( Figure 5 ). Microbiologic cultures results were unavailable. The cause of death was acute meningitis following meningioma resection surgery.

Figure 4:

Case 3 - Left: Cloudy, discolored leptomeninges are seen over the right frontoparietal region near the resection site. Right: Dura mater surrounding the craniotomy site.

Figure 5:

Case 3 - Surgical hemostatic material from resection is admixed with inflammatory cells, consistent with meningitis. H&E stain.

Case 4: Mass Effect on Cerebellum

A 37-year-old female who had experienced months of worsening ataxic symptoms resulting in multiple falls was found deceased in her residence. The patient had a history of balance issues for at least 8 months and had persistent neck pain. At autopsy a previously unknown 5.7 centimeter right inferior cerebellar tumor was noted ( Figure 6 ). Mass effect from the tumor, which was noted to have caused gyral effacement of the cerebral convexities and herniation of the vermal nodulus and cerebellar tonsils, compressed her brainstem which likely led to her death. Dilated lateral and third ventricles were also noted. Histologic examination confirmed the tumor as a WHO grade 1 meningioma. The cause of death was right cerebellar meningioma.

Figure 6:

Case 4 - Left: The meningioma is seen attached to the posterior fossa calvarial dura mater effacing the right inferior cerebellar hemisphere. Right: Meningioma cross-section demonstrates mostly a homogeneous appearance, consistent with WHO grade 1.

Discussion

Deaths from meningiomas are rare but may result from mass effect-related seizure activity or lethal compression of vital structures, postoperative complications, such as meningitis and hemorrhage.

Size and Location Influence Lethality of Meningioma

Because meningiomas have variable presentation with nonspecific symptoms including headaches, seizures, vision changes, balance issues, or decreased memory and cognition, medical attention may be delayed. The risk of these complications underscores the importance of thorough evaluation and plan for urgent neurosurgical intervention and close postoperative follow-up in patients who present with acute or worsening neurological symptoms. As our cases demonstrate, the location, size, and comorbidities relevant to the presentation of the meningioma are important factors to determine the holistic risks and complications that may lead to death. Small (<2 cm), well-marginated meningiomas that otherwise attached to the dura mater abutting the superficial cortex far away from deep and speech-related structures are less likely to cause neurologic deficits than that those in more sensitive regions as in Case 2 and Case 4. The midline location of the meningioma described in Case 2 borders the confluence of the major vessels of the skull base, including the Circle of Willis and the branches of the internal carotid arteries, and growth or disruption of these vessels, including by way of tumor growth, hemorrhage, or necrosis, can lead to devastating intracranial bleeds as they did for the patient. In Case 4, both size and location of the meningioma contributed directly to the patient’s death. The large size of the meningioma (5.7 cm) compressed against the inferior aspect of cerebellar hemisphere, a vital structure important in not only regulating motor and coordination but also bordering the medulla which regulates core autonomic functions.

Risk Factors

Descriptions in the literature about the benign nature of meningiomas do not account for the complications of meningioma sequelae with other comorbid conditions which may significantly increase the lethality of the tumor. In isolation, meningioma-triggered seizures, and seizures in general, are often nonfatal and spontaneously terminate. Postictal states are typically managed supportively and last up to half an hour. Of course, seizures of whatever etiology can also result in sudden death (6). In Case 1, the patient died as a result of pulmonary thromboembolism due to deep venous thrombosis related to stasis and immobility following major abdominal surgery for recurrent colonic adenocarcinoma. Certainly, the surgery and cancer were likely sufficient in and of themselves to induce the formation of DVT with subsequent embolism; however, because of the temporal association of the additional stasis and immobility imparted by the postictal state with the subsequent acute pulmonary thromboembolism, collapse, and death, the pathologist considered the meningioma-induced seizure as contributory to death.

Apart from comorbidities, risks of complications arising from craniotomies for tumor resection are exceptionally rare yet devastating. In most cases, the surgery itself is safe and predictable with proper preoperative planning; the challenge of such an invasive procedure and the least predictable course of the surgery is the postoperative recovery. In Case 3, the patient had a history of multiple myeloma and was also in an immunosuppressed state due to his chemotherapy and steroid regimen. The risk of infection is universal with any disruption of the skin, and studies have noted postcraniotomy meningitis rates of <2.5% (7), which was likely higher for the patient in Case 3. Given the hidden nature of the craniotomy wound site and the rapid progression of meningitis, vigilant monitoring with criteria specific for meningitis should be ensured.

Grading of Meningiomas and Potential Prognostic Factor

While MRI is the best noninvasive method for characterizing the size, shape, and heterogeneity of a meningioma (8), postoperative pathologic examination is crucial for grading (1). Grade 1, considered benign, is the most common type, comprising approximately 78%-81% of all meningiomas (9). Grade 2 tumors are atypical, which are of intermediate grade, and are diagnosed on the basis of increased mitotic activity (4 to 19 mitotic figures in 10 consecutive high power fields), brain invasion, subtype (chordoid or clear cell), or certain histologic features (e.g., increased cellularity, prominent nucleoli, sheeting); these account for approximately 15% to 20% of meningiomas. Grade 3 tumors are anaplastic, with features including abundant mitotic figures (20 or more mitotic figures in 10 consecutive high-power fields) or frank anaplasia and are considered malignant; these make-up 1% to 4% of meningiomas. The significance of the WHO grading system is to assess the risk of recurrence, for which adjuvant radiotherapy is much more likely to follow the surgery (10). This is especially important with WHO grade 2 to 3 tumors, which may grow significantly faster than the majority of meningiomas and may potentially contribute to sudden death if the patient does not receive periodic postoperative surveillance. None of the cases presented were grade 2 or 3 tumors.

Conclusion

Despite their mostly benign nature, meningiomas can rarely result in death. Our cases each demonstrated a different scenario in which a meningioma either resulted in or contributed to death. These include a meningioma-induced seizure in the setting of a recent gastrointestinal surgery, an insult to cerebral vessels leading to hemorrhage, inflammation/infection of the meningioma resection cavity, and compression of the brainstem. Forensic pathologists provide a crucial and unique perspective during the investigative process through systematic gross and microscopic examination of cranial tissue, vasculature, and cavities in areas that otherwise would have been impossible to visualize directly in living patients. Autopsy examination can be instrumental in identifying the cause and mechanism of deaths associated with meningiomas.

Authors

Jeffrey J. Feng, MS, Western Michigan University Homer Stryker MD School of Medicine

Roles: A, B, C, D, E, 1

Joyce L. deJong, DO, Department of Pathology, Western Michigan University Homer Stryker MD School of Medicine

Roles: A, B, C, D, E, 4, 5, 6

Elizabeth A. Douglas, MD, Department of Pathology, Western Michigan University Homer Stryker MD School of Medicine

Roles: B, C, D, E, 4

Amanda O. Fisher-Hubbard, MD, Department of Pathology, Western Michigan University Homer Stryker MD School of Medicine

Roles: A, B, C, D, E, 4, 5, 6

Joseph A. Prahlow, MD, Department of Pathology, St. Louis University School of Medicine

Roles: A, B, C, D, E, 4, 5, 6