title: Intratumoral hemorrhage, vessel density, and the inflammatory reaction contribute to volume increase of sporadic vestibular schwannomas.
abstract: Vestibular schwannomas show a large variation in growth rate, making prediction and anticipation of tumor growth difficult. More accurate prediction of clinical behavior requires better understanding of tumor biological factors influencing tumor progression. Biological processes like intratumoral hemorrhage, cell proliferation, microvessel density, and inflammation were analyzed in order to determine their role in vestibular schwannoma development. Tumor specimens of 67 patients surgically treated for a histologically proven unilateral vestibular schwannoma were studied. Preoperative magnetic resonance imaging (MRI) scans were used to determine tumor size and to classify tumors as homogeneous, inhomogeneous, and cystic. Immunohistochemical studies evaluated cell proliferation (histone H3 and Ki-67), microvessel density (CD31), and inflammation (CD45 and CD68). Intratumoral hemorrhage was assessed by hemosiderin deposition. The expression patterns of these markers were compared with tumor size, tumor growth index, MRI appearance, patients' age, and duration of symptoms. No relation between cell proliferation and clinical signs of tumor volume increase or MRI appearance was found. Intratumoral hemosiderin, microvessel density, and inflammation were significantly positively correlated with tumor size and the tumor growth index. Cystic and inhomogeneous tumors showed significantly more hemosiderin deposition than homogeneous tumors. The microvessel density was significantly higher in tumors with a high number of CD68-positive cells. The volume increase of vestibular schwannomas is not based on cell proliferation alone. Factors like intratumoral bleeding, (neo)vascularization, and intensity of the inflammatory reaction also influence tumor volume.
authors.affiliation: Department of Otolaryngology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Maurits
authors.initials: M
authors.lastname: de Vries
authors.forename: Pancras C W
authors.initials: PC
authors.lastname: Hogendoorn
authors.forename: Inge
authors.initials: I
authors.lastname: Briaire-de Bruyn
authors.forename: Martijn J A
authors.initials: MJ
authors.lastname: Malessy
authors.forename: Andel G L
authors.initials: AG
authors.lastname: van der Mey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis; D005260:Female; D006485:Hemosiderin / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology; D009464:Neuroma, Acoustic / Q000098:blood supply* / Q000473:pathology* / Q000503:physiopathology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D006485:Hemosiderin; D019394:Ki-67 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule