Vertebral Intraosseous Vascular Malformations in a Familial Cerebral Cavernous Malformation Population: Prevalence, Histologic Features, and Associations With CNS Disease

Steven R Tandberg, Thèrése Bocklage, Mary R Bartlett, Leslie A Morrison, Jeffrey Nelson, Blaine L Hart, Steven R Tandberg, Thèrése Bocklage, Mary R Bartlett, Leslie A Morrison, Jeffrey Nelson, Blaine L Hart

Abstract

OBJECTIVE. The purpose of this study was to investigate whether MRI-typical and MRI-atypical intraosseous vascular malformations are associated with familial cerebral cavernous malformation (FCCM). MATERIALS AND METHODS. In a retrospective matched case-control study, two radiologists reviewed the spinal imaging, both CT and MRI, of 22 patients with FCCM seen between 2006 and 2017 and of age- and sex-matched control subjects for MRI-typical and MRI-atypical intraosseous vascular malformations. Quantitative analysis of lesions identified included vertebral level, size, and number of lesions. Pathologic samples from two lesions were analyzed for histologic and immunohistochemical features. Whether the presence of typical, atypical, and total intraosseous vascular malformations differed between patients and control subjects was tested. For patients with complete spinal imaging, whether intraosseous vascular malformations were associated with age, sex, brain lesion count, and spinal lesion count was also tested. RESULTS. MRI-atypical intraosseous vertebral malformations were more commonly present in patients with FCCM (p = 0.003). Sixteen lesions were found in nine patients and none in the control group. The numbers of MRI-typical intraosseous vascular malformations were similar between patients and control subjects (p = 0.480). Age was associated with typical intraosseous vascular malformations (p = 0.027), though not with atypical malformations. MRI-atypical malformations were larger (mean diameter double) than MRI-typical malformations (p = 0.023). Histologic analysis of two lesions from different patients with pathologic collapse revealed the same histologic features consistent with combined capillary-venous malformations. CONCLUSION. Vertebral capillary-venous malformations (MRI-atypical intraosseous vascular malformations) are common in patients with FCCM and may have a more aggressive clinical course than MRI-typical malformations.

Keywords: cerebral cavernous malformation; intraosseous vascular malformation; neurocutaneous disorder; spinal cavernous malformation; vertebral hemangioma.

Figures

Fig. 1—
Fig. 1—
51-year-old woman with proven familial cerebral cavernous malformation (FCCM), back pain, and neurologic signs and symptoms. Example of multiple MRI-atypical intraosseous vascular malformations in single patient with FCCM. A, T1-weighted MR image shows area of low signal intensity filling much of L3 vertebral body and well-demarcated round areas within L2 and T1. B, Sagittal CT reconstruction shows coarse, vertical trabeculations (corduroy pattern) of L3 lesion. L2 lesion is not clearly visible in this slice. C and D, Sagittal T1-weighted (C) and T2-weighted (D) MR images show T1 lesion has low T1 signal intensity and T2 prolongation. Lesions were stable at 10-year follow-up MRI.
Fig. 2—
Fig. 2—
57-year-old man with proven familial cerebral cavernous malformation and right-sided weakness. A, Sagittal STIR MR image shows high-signal-intensity lesion within marrow space of C4 vertebral body, cavernous malformation in brainstem, and small cavernous malformation (arrow) on dorsal surface of spinal cord at C4. B, Sagittal CT reconstruction shows corduroy pattern of thickened vertical trabeculation with intervening low attenuation (arrow). C, Axial T2-weighted multiecho data image combination MRI image at C4 shows high-signal-intensity lesion in vertebral body and two spinal cord cavernous malformations (arrows). D, Axial T1-weighted MR image shows low signal intensity of atypical intraosseous vascular malformation. MRI appearance of osseous lesion was stable over 2 years.
Fig. 3—
Fig. 3—
55-year-old man with familial cerebral cavernous malformations. Example of growth of MRI-atypical intraosseous vascular malformations. A, Initial sagittal T1-weighted MR image shows typical intraosseous vascular malformation within L4 as very small focus (arrow) of low signal intensity. B, Initial axial T2-weighted MR image shows typical intraosseous vascular malformation in L2 as very small focus (arrow) of high signal intensity. C and D, Sagittal (C) and axial (D) MR images 17 months after A and B show growth to 1.4 cm with coarse stippled appearance (arrow).
Fig. 4—
Fig. 4—
40-year-old woman with sudden, severe back pain due to pathologic fracture. A, Sagittal T1-weighted MR image shows replacement of normal T12 marrow and collapse with spinal cord compression. Small, typical T1-hyperintense lesion is present in T9. Patient underwent T12 corpectomy and instrumentation. B and C, Photomicrographs (B, H and E, medium magnification; C, Ki67 antibody stain, high magnification) show anastomosing blood vessels embedded in fibrous stroma replacing marrow fat. Ki67 is expressed in scattered endothelial nuclei (yellow arrow, C) and stromal cell nuclei (blue arrow, C) consistent with low proliferative capacity.
Fig. 5—
Fig. 5—
44-year-old woman with familial cerebral cavernous malformations and pathologic fracture managed surgically. A, Photomicrograph (smooth-muscle actin [SMA] antibody stain, medium magnification) shows expression of SMA even in thin-walled vascular channels. B, Axial T2-weighted gradient-recalled echo MR image shows multiple cerebral cavernous malformations in brain.

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