Focal leptomeningeal vascular anomalies on brain MRI: A mimic of leptomeningeal metastatic disease

Abstract

Background

The diagnosis of leptomeningeal metastatic disease has major prognostic and therapeutic implications. We report 13 patients with a radiologically distinct kind of focal, enhancing leptomeningeal lesion on brain MRI that mimics leptomeningeal metastatic disease.

Methods

These patients were assessed at University Health Network (Toronto, Canada) between January 2001 and December 2023.

Results

Median age was 68 years (range, 55–78 years) and 10 patients were women. All patients had brain magnetic resonance imaging (MRI) including contrast-enhanced T2-weighted fluid attenuation inversion recovery (FLAIR) and T1-weighted spin echo sequences. MRI in all 13 patients showed a focal enhancing lesion located along the leptomeningeal surface of the brain. The MRI exams were reported as possible or likely leptomeningeal metastatic disease for the majority (9/13) of patients. Each lesion was curvilinear rather than sheet-like, and some lesions consisted of multiple connected/branching curvilinear structures with the appearance of abnormal vessels. The lesions were distinct from normal blood vessels. Some lesions had a visible connection with a nearby cortical vein. Follow-up contrast-enhanced brain MRI for 8/13 (62%) patients at a median of 3.9 years (IQR 2.4–6.6 years) showed all lesions were unchanged over time. Another 2/13 (15%) patients had clinical and CT brain follow-up after one year with no evidence of metastatic disease.

Conclusions

We describe a distinct kind of focal, enhancing leptomeningeal lesion on brain MRI that mimics metastatic disease. These lesions are likely a type of low-flow vascular anomaly. Their curvilinear/branching shape and intense enhancement particularly on T2-weighted FLAIR images distinguish these lesions from tumors.

Malignant tumor disseminates to the leptomeninges (the pial and arachnoid layers covering the brain and spinal cord) in 5%–10% of solid cancer patients during the course of their disease.¹ Leptomeningeal metastatic disease has major prognostic and therapeutic implications. Median survival of these patients is poor, only 1 to 1.5 months without treatment, and 2 to 4 months with current therapies.² The subset of patients who have radiosensitive tumors or options for systemic therapy may have better outcomes.³

Leptomeningeal metastatic disease is diagnosed using a combination of clinical findings, neuroimaging, and cerebrospinal fluid analysis. Brain magnetic resonance imaging (MRI) findings include nodular or linear contrast enhancement along the leptomeningeal surface of the brain.⁴ There are known mimics of leptomeningeal tumors on MRI such as granulomatous infection and inflammatory disease, but the primary diagnostic consideration for focal leptomeningeal enhancement on brain MRI in a patient with malignancy is metastatic tumor.⁵

We report the clinical and radiological findings of a previously undescribed kind of focal leptomeningeal vascular anomaly on brain MRI that mimics leptomeningeal metastatic tumor.

Materials and Methods

This is a retrospective study approved by the Institutional Review Board of the University Health Network, Toronto (Study ID #22-5940). We describe 13 patients who were identified in our neuroradiology practice and assessed clinically and radiologically at the University Health Network between 2001 and 2023. All patients had brain MRI (3-Tesla or 1.5 Tesla) including at minimum: T1-, T2*, and diffusion-weighted sequences, and contrast-enhanced two-dimensional T2-weighted fluid-attenuated inversion recovery (FLAIR), two-dimensional T1-weighted spin echo, and three-dimensional T1-weighted gradient echo sequences (for T1 and T2 FLAIR parameters, see Table S1). For each patient, we extracted the first MRI showing focal abnormal signal and most recently performed scan. All MRI exams were reported by subspecialist neuroradiologists and subsequently reviewed by our study team. We extracted demographics and medical history for each patient from the electronic patient records.

To assess the spatial distribution of focal, enhancing leptomeningeal lesions, we manually segmented all lesions on contrast-enhanced T2-weighted FLAIR images, performed linear registration of these images to the higher spatial resolution 3D T1-weighted images, then performed non-linear registration to standard space (MNI152), and then sequentially applied both of these transformations to all segments so that all lesions were co-registered in standard space.^6,7 We overlaid the segmented lesions in standard space onto the Harvard-Oxford Cortical Structure Atlas to show the size and spatial distribution of the lesions.^8–11

Results

The clinical characteristics of the 13 patients are detailed in Table 1. Median age was 68 years (range, 55–78 years) and 10 patients were women. Clinical indications for brain MRI were “rule out brain metastases” (7/13 patients), “intracranial tumor follow-up” (4/13), “progressive unilateral numbness and weakness of the face and lower extremity” (1/13), and “memory decline” (1/13). Of the 7 patients receiving MRI to rule out brain metastases, there were no associated clinical symptoms and they were performed as screening tests. For the 4 patients with previous intracranial tumors, the initial MRI showed focal enhancing lesions and patients 6, 9, and 11 had received surgical and radiation therapy (Table 1). Previous examinations were done with the same institutional acquisition parameters. Only 1 patient had clinical findings suspicious of brain metastasis. Most patients had a history of extracranial malignancy or intracranial tumor. Of the patients with extracranial malignancy, 5/7 had systemic disease.

Table 1.

Clinical Features Among Cohort.

Patient	Sex	Age [years]	Extracranial malignancy	Intracranial diagnosis	Brain radiation or craniotomy or systemic treatment	Brain imaging follow-up [years]
1	F	75	No	Tentorial meningioma	No	1.0
2	M	63	Papillary thyroid carcinoma	No	No	0.9
3	F	58	Breast malignancy	No	No	0
4	F	55	Papillary thyroid carcinoma	Cerebellar metastatic disease	No	1.7
5	M	78	Anaplastic thymic carcinoma; Perianal squamous cell carcinoma	No	No	4.3
6	F	53	No	Temporal lobe astrocytoma (grade 2)	Craniotomy	8.5
7	M	66	Papillary thyroid carcinoma	Brain metastases	Craniotomy	3.4
8	F	77	Invasive ductal cell breast carcinoma	No	Anastrozole	0.4
9	F	77	No	Pterional meningioma	Craniotomy and gamma knife radiation therapy	9.3
10	F	76	No	Frontal lobe meningioma	No	0
11	F	61	No	Cerebellopontine angle meningioma	Gamma knife radiation therapy	6.6
12	F	68	Lung malignancy	Brain metastases	Whole brain radiation, talazoparib, carboplatin, etoposide, durvalumab	0
13	F	71	No	Brainstem glioma	No	2.4

Demographics, oncology history, and duration of brain imaging follow-up for the patient cohort prior to first sighting of focal leptomeningeal enhancement. F, female; M, male. Brain imaging follow-up was contrast-enhanced MRI except for patient 1 who had a contrast-enhanced CT and patient 2 who had a non-enhanced CT.

Each patient had a focal enhancing lesion located along the leptomeningeal surface of the brain (Figure 1). These lesions were all curvilinear rather than sheet-like, and some lesions consisted of multiple connected/branching curvilinear structures suggestive of abnormal vessels (Figures 2 and 3). Some lesions had a visible connection with a nearby cortical vein (Figure 3B). There were no abnormal flow voids or enlarged arteries in the vicinity of the lesions to suggest arteriovenous shunting lesions. All lesions were visible on both contrast-enhanced T1-weighted spin-echo images and T2-weighted FLAIR images. Some lesions had particularly intense contrast enhancement on the T2-weighted FLAIR images. Lesions were less conspicuous on contrast-enhanced T1-weighted gradient-echo images. Five patients also had a non-enhanced T2-weighted FLAIR sequence and none of the lesions were visible on these images. The focal enhancing lesions were all distinct from normal-appearing blood vessels elsewhere in the cerebri sulci.

Figure 1.

Imaging features of benign focal leptomeningeal enhanceming lesions. Contrast-enhanced, axial T2-weighted FLAIR images show MRI axial T1 weighted post-contrast and axial T2-weighted FLAIR images show the lesions. Benign course was defined as stable MRI scans on follow-up, no evidence of progression on follow-up CT, or no evidence of clinical progression.

Figure 2.

Representative lesion from patient 9. Sagittal contrast-enhanced T1-weighted image (A) shows a curvilinear region of enhancement (arrows) along the leptomeningeal surface of a right parietal gyrus. Magnified contrast-enhanced T1-weighted image reformatted into an oblique plane (B) shows that the lesion (short arrow) drains into a cortical vein (long arrows). Axial contrast-enhanced T2-weighted fluid attenuation inversion recovery (FLAIR) image (C), shows corresponding intense contrast enhancement which did not have corresponding T1 intrinsic hyperintensity (see inset in C). The same sequence 9 years later (D) shows no interval change. Magnified contrast-enhanced T1-weighted images (E-H) show that the lesion has a branching morphology along the surface of the brain.

Figure 3.

Representative lesion from patient 8. Axial (A) and reformatted oblique (B) contrast-enhanced T1-weighted images show an enhancing lesion along the leptomeningeal surface of the left parietal lobe. The lesion consists of several small linear parts (best seen in A and the leftmost image in B), which did not have corresponding T1 intrinsic hyperintensity (see inset in B). Axial contrast-enhanced T2-weighted FLAIR images (C) show a corresponding enhancing lesion and follow-up images 5 months later (inset in C) show no interval change.

The most common lesion location was the parietal convexity (7/13 patients), particularly the postcentral gyri (4/13). All enhancing lesions were relatively short in length. A surface rendering of the brain (Figure 4) shows the spatial distribution and size of all lesions.

Figure 4.

Lesions from all 13 patients overlaid on a three-dimensional surface rendering of the brain. Craniocaudal (A) and lateral (B) projections show the spatial distribution of manually segmented, individual, focal leptomeningeal-enhancing lesions in standard space (Montreal Neurological Institute brain). The pixelated appearance of the lesions in B is due to technical limitations of the 3D interpolation. Most lesions were located in the parietal-occipital regions.

All MRI exams had been reported by neuroradiologists. Differential diagnoses provided for the focal leptomeningeal enhancing lesions included leptomeningeal metastatic tumor (9/13 patients), vascular abnormalities (10/13), infectious processes (2/13), ischemic injury (1/13), Sturge-Weber syndrome (1/13), sarcoidosis (1/13), and Behcet’s disease (1/13).

Following the brain MRI reporting, no additional diagnostic workup for leptomeningeal metastatic disease was done in 12/13 patients as there was no clinical suspicion (Table 2). One patient had cerebrospinal fluid sampling to assess for leptomeningeal spread and this showed no malignant cells. Eight of the 13 patients (62%) had follow-up contrast-enhanced MRI brain. For these 8 patients, the median duration of MRI follow-up was 3.9 years (interquartile range 2.4 to 6.6 years) and all of the lesions were unchanged over time. Another 2 of the 13 patients (15%) had both CT brain and clinical follow-up after 1 year with no evidence of intracranial metastatic disease. (The CT exam was contrast-enhanced in one of these patients and non-enhanced in the other.) Three of the 13 patients (24%) had no brain imaging or clinical follow-up.

Table 2.

Diagnostic Workup, Follow-up Management, and Clinical Suspicion for Leptomeningeal Metastasis Among Cohort

Patient	Intracranial tumor status	Diagnostic workup at time of finding	Management after finding	Clinical Suspicion of leptomeningeal metastasis	Length of brain imaging follow-up [years]
1	Stable	None	Brain imaging	No	1.0
2	None (worsening extracranially)	None	Extracranial imaging	No	0.9
3	None	Lumbar puncture	None	Yes	0
4	Stable (worsening extracranially)	None	Stereotactic body radiotherapy, levatinib, brain imaging, extracranial imaging	No	1.7
5	None	None	Chest wall radiation, brain imaging, extracranial imaging	No	4.3
6	Stable	None	Brain imaging, chemotherapy	No	8.5
7	Worsening intra- and extracranially		Chest wall radiation, brain imaging, extracranial imaging		3.4
8	None	None	Brain imaging	No	0.4
9	Worsening intracranially	None	Brain radiation, brain imaging	No	9.3
10	Stable	None	None	No	0
11	Stable	None	Brain imaging	No	6.6
12	Stable (worsening extracranially)	None	Palliative care, extracranial imaging	Yes	0
13	Stable	None	Brain imaging, extracranial imaging	No	2.4

Patient tumor status (where applicable), diagnostic workup at the time of diagnosis, follow-up management, and overall clinical suspicion of leptomeningeal metastasis are shown.

Discussion

We have described a kind of focal enhancing leptomeningeal lesion on brain MRI that mimics leptomeningeal metastatic disease. The first impression would be that these lesions are ESMO-EANO Type A, the linear subtype of leptomeningeal disease on MRI.¹² While these lesions enhance on contrast-enhanced T1-weighted and contrast-enhanced T2 FLAIR-weighted images, on close inspection, their curvilinear/branching shape distinguishes them from tumors. Based on their morphology and visible connection with cortical veins, the lesions are likely vascular.

The observed lesions have a radiological appearance which is distinct from other, well-known vascular mimics of intracranial tumors such as normal cerebral sulcal blood vessels, developmental venous anomalies, and capillary telangiectasias. Visibility of normal blood vessels in the cerebral sulci on contrast-enhanced MRI depends on multiple factors such as magnetic field strength (1.5 Tesla versus 3.0 Tesla), two-dimensional versus three-dimensional acquisition, slice thickness, contrast bolus timing, and use of sedation.¹³ Increased prominence of normal vessels related to these factors is a diffuse phenomenon though compared with the focal lesions we have observed. Small developmental venous anomalies and capillary telangiectasias can have the appearance of a small focus of enhancement on brain MRI that might be mistaken for a metastasis, but these lesions are intraparenchymal rather than leptomeningeal.

The observed lesions share some imaging features with the enhancing leptomeningeal vascular malformation (pial angiomatosis) seen in patients with Sturge-Weber syndrome. Pial angiomatosis of Sturge-Weber syndrome is usually more spatially extensive and there are associated findings on MRI including cortical atrophy, calcification, and dilated medullary veins in the adjacent white matter. However, it is possible that our observed lesions reflect small, isolated pial angiomatoses. In the context of Sturge-Weber syndrome, leptomeningeal enhancement may reflect slow turbulent flow through abnormal, tortuous pial vasculature or contrast leakage into the interstitium between abnormal leptomeningeal vessels.¹⁴

The observed lesions are also somewhat similar to the abnormal leptomeningeal vessels associated with meningioangiomatosis, but this entity also has parenchymal abnormality including calcification.

The observed lesions were all visible on both contrast-enhanced T1-weighted spin echo and contrast-enhanced T2-weighted FLAIR sequences. T2-weighted FLAIR images are predominantly T2-weighted, but there is a degree of T1-weighting (due to the long inversion time) which enables contrast enhancement.¹⁵ Some of the observed lesions had particularly intense enhancement on the T2-weighted FLAIR images relative to the T1-weighted images, a phenomenon also seen with the pial angiomatosis of Sturge-Weber syndrome.¹⁵

We have deduced that the observed lesions are benign based on long-term imaging follow-up confirming stability, and we believe the lesions are vascular based on their curvilinear/branching morphology (and some lesions visibly connecting with a cortical vein). A limitation of the study is lack of histological correlation as none of these patients had brain biopsy or autopsy.

The etiology of the observed lesions is unclear. All patients in our study had either an extracranial malignancy or intracranial tumor, but that could reflect patient selection bias as a high proportion of contrast-enhanced MRI brain exams are performed for tumor workup. Only a minority of patients had a history of brain radiation therapy, so there is no evidence to suggest these are radiation-induced vascular lesions. The youngest patient in our cohort is 58 years old which suggests these lesions might be acquired rather than developmental, but selection bias could be a factor.

The clinical significance of these lesions is that they mimic leptomeningeal metastatic disease. It is important to recognize their curvilinear/branching morphology to avoid misdiagnosis. A few other imaging features we find helpful are: The lesions are usually solitary whereas leptomeningeal tumor is often multifocal at the time of diagnosis, the lesions sometimes show particularly intense contrast-enhancement on T2-weighted FLAIR images compared to metastatic disease, and it is sometimes possible to visualize a connection of these lesions with a cortical vein. In weighing the likelihood of leptomeningeal disease, it is important to consider the clinical presentation and the propensity of the primary tumor to metastasize to the leptomeninges. In our cohort, only one patient had clinical findings suggestive of leptomeningeal metastatic disease, and most patients had breast or thyroid primaries which are not among the more common causes of leptomeningeal tumor. Regular collaboration between neuroradiology, neurology, neurosurgery, medical oncology, and radiation oncology teams, for example, multidisciplinary rounds, emphasizes the integration of both the clinical and imaging data which is essential in ruling out differential diagnoses of leptomeningeal metastases. For an imaging lesion with the typical characteristics we have described, and no clinical reason to suspect leptomeningeal metastatic disease, further workup is likely not warranted. For an imaging lesion with the typical characteristics we have described, and clinical reason to suspect leptomeningeal metastatic disease, cerebrospinal fluid sampling and short-interval follow-up MRI would be reasonable, but we still suggest caution in interpreting this kind of lesion as evidence of leptomeningeal metastatic disease without confirmatory CSF findings or evidence of lesion growth on serial imaging.

There are several major limitations to this study. First, this is a single-center study performed at a single academic center which limits generalizability of our findings. Second, it is a retrospective case series which limits statistical analysis. Replication by other centers and histopathological evaluation will further elucidate the nature of the lesions we have described.

We have described a kind of focal leptomeningeal anomaly on brain MRI that mimics leptomeningeal metastatic disease. This anomaly is likely a low-flow leptomeningeal vascular lesion. It is radiologically distinct from other, well-known vascular mimics of intracranial tumors. Further investigation (ideally histopathological correlation) is warranted, but in the meantime, it is important for physicians to recognize this entity and distinguish it from metastatic tumors.

Supplementary material

Supplementary material is available at Neuro-Oncology Practice (https://academic.oup.com/nop).

Funding

None.

Conflict of interest statement

None declared.

Authorship statement

Ethical approval and study design: A.B. and D.M.M.. Identifying and selecting cases: D.M.M.. Data collection: A.B. and M.M.. Image segmentation and interpolation: A.B., M.M., J.G., and A.Y.. Writing draft manuscript: A.B. and M.M.. Writing revised manuscript: A.B., M.M., D.M.M., A.Y., J.G., S.H., H.S., A.V., and V.P.. Figure and table creation: A.B., M.M., and D.M.M..

Data availability

Any study data will be made available upon request.

Disclosure

None. Sources of financial and material support: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.