Brain Arteriovenous Malformation Hemorrhage and Pituitary Adenoma in a COVID-19-Positive Patient

Abstract

Brain arteriovenous malformations (AVMs) are usually asymptomatic. They can cause intense pain or bleeding or lead to other serious medical problems. We present a rare case of a woman who presented with a severe headache and was brought to the emergency service for an intracerebral hemorrhage due to a ruptured AVM. During the surgery, a sellar mass was identified that was also resected. AVM showed vasculitis, endarteritis, endothelial damage, leukocyte plug, and damage to the vessel wall with fragmentation of the collagen and actin filaments. The sellar mass showed a non-functioning pituitary adenoma with hemorrhagic foci and necrosis as well as a proteinaceous vs. lipid material deposition with minimal vascular changes such as endothelial hyperplasia with minimal vasculitis and hyperplasia of reticular stellate cells, with positive glial fibrillary acidic protein (GFAP), which expressed low expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), IL6, IL10, IL17, tumor necrosis factor-alpha (TNFa), HIF1a, factor VIII (FVIII), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and VEGF receptor 2 (VEGFR2). The patient's polymerase chain reaction COVID-19 test was positive, and she died three days after the surgery procedure. In our knowledge of COVID-19 brain lesions and in the literature review, this was a rare case of a double pathology associated with COVID-19 infection characterized by rupture of the AVM with hemorrhages and brain infarcts associated with endarteritis, vessel wall injuries, and pituitary apoplexy.

Keywords: brain arteriovenous malformation; cerebrovascular disease; covid-19; pituitary adenoma; pituitary apoplexy.

Figure 1. Preoperative imaging studies.

(A) An axial non-contrast CT image of the head shows an intracerebral hemorrhage (yellow arrow). (B) Cerebral angiography reveals an arteriovenous malformation, Spetzler-Martin grade III (yellow arrow). (C) A coronal MRI image demonstrates the presence of a pituitary macroadenoma (yellow arrow) and a left frontal arteriovenous malformation (red arrow). (D) An axial non-contrast CT image of the head shows a heterogeneous component in the sellar region (yellow arrow).

Figure 2. Computed tomography images.

(A) Axial computed tomography (CT) image of the lung taken preoperatively. (B) Axial CT image of the lung taken postoperatively during respiratory deterioration in the patient, showing bilateral ground-glass opacity with peripheral predominance (yellow arrows) and foci of consolidation (red arrows). (C) Axial and coronal (D) CT images of the postoperative head show expected surgical changes (yellow arrows).

Figure 3. Histological features and electron microscopy of the arteriovenous malformation.

(A) Abnormal vascular dilatation was observed. Some vessels displayed a single layer of endothelium with a thin collagenous wall. Necrosis and bleeding were noted, as well as malformed capillaries, arteries, and venules with abrupt changes in the thickness of the medial and elastic layers of vessels (hematoxylin & eosin (H&E), x5). (B) Some hyalinized thin-walled vessels have atypical endothelial cells and necrosis (H&E, x20). (C) Loss of endothelial cells with the presence of inflammatory cells (H&E, x40) is observed in some vessels. (D) Periodic acid-Schiff (PAS) staining and fragmentation of large vessels (PAS, x20) are better observed. (E) Masson stain was observed in blue vessels with necrosis, fibrin, and inflammation (H&E, x20). (F) Reticulin stain showed fragmentation of the fibers and loss of them (x5). (G) A semithin section stained with toluidine blue stain showed hyperplastic endothelial cells, nuclei with apoptotic morphology, and retrograde migration changes (x100). Transmission electron microscopy (H) revealed granular material at the luminal border (*) (500 nm, 15K).

Figure 4. Immunohistochemistry of the arteriovenous malformation.

(A) CD34-positive immunoreaction in endothelial cells (x40). (B) CD31 showed overexpression in endothelial cells (x40). (C) Platelet-derived growth factor (PDGF)-positive immunoreaction in endothelial cells (x40). (D) Interleukin 6 was also positive in endothelial cells and endothelial cell migration (x40). (E) Galectin 3 was positive both in endothelial cells, inflammatory cells, and the extravasated fluid in the lumen of the vessels (x40). (F) Collagen IV shows a thick, fragmented subendothelial layer (x40). (G) Smooth muscle actin fragmentation is observed (x40), and muscle fibers (H) were also positive for PDGF (x40).

Figure 5. Histopathological and immunohistochemical features of pituitary adenoma.

(A) A classic pituitary adenoma is identified. However, foci of hemorrhage, necrosis, and a liquid eosinophilic material were observed (hematoxylin & eosin (H&E), x10). (B) Foci of foamy material with a lipid appearance arranged diffusely with edema (H&E, x400), and in (C), we observed some blood vessels that showed endarteritis (H&E, x40). (D) By immunohistochemistry, it was positive for follicle-stimulating hormone (FSH) (x400). (E) Glial fibrillary acidic protein (GFAP) was intensely positive, showing thick fibers between epithelial cells (black arrows) (x400). (F) Vessel endothelial cells had a CD31-positive immunoreaction (black arrows) (x400). (G) Stellate cells and endothelial cells show positive expression for platelet-derived growth factor (PDGF) (black arrows) (x400) and for COVID-19 spike proteins in (H) (black arrows) (x400).

Figure 6. Electron microscopy of the arteriovenous malformation.

(A) Endothelial cells with apparently preserved structures were found (arrow; bar scale: 5 μm; x3000). (B) Loss of intercellular junctions (arrows) were observed among endothelial cells (bar scale: 2 μm; x5000). (C) The cells showed deformed nuclei (N) and alteration of the cell membrane (curved arrow; bar scale: 500 nm; x15k). (D) Cells with signs of apoptosis were found with chromatin (Ch) condensed toward the nuclear membrane (bar scale: 1 μm; x8000). Uranyl acetate-lead citrate stain.