title: Reactive retinal astrocytic tumors (so-called vasoproliferative tumors): histopathologic, immunohistochemical, and genetic studies of four cases.
abstract: OBJECTIVE
  To evaluate the cellular nature of and diagnostic terminology used in connection with acquired retinal "vasoproliferative tumors."
  
  
  METHODS
  Retrospective clinicopathologic study.
  
  
  METHODS
  Clinical records and microscopic slides of 4 enucleated globes were reviewed. Special stains and immunohistochemical probes for CD31, CD34, p53, glial fibrillary acidic protein (GFAP), CD163, and Ki67 (cell replication) were employed; ultrastructural and fluorescence in situ hybridization (FISH) analyses were performed.
  
  
  RESULTS
  Tumors were located inferotemporally in middle-aged patients. They were uniformly composed of compacted elongated, GFAP-positive spindle cells (due to intermediate filaments identified ultrastructurally) with a Ki67 index of less than 1%. Rosenthal fibers and eosinophilic granular bodies were observed. Hyalinized periodic acid-Schiff-positive vessels were widely separated. CD31 and CD34 revealed a sparse microvasculature. Tumor-associated exudate spread predominantly subretinally. The retinal pigment epithelium had undergone extensive placoid fibrous metaplasia with focal ossification. P53 upregulation, BRAF-KIAA gene rearrangement, and IDH1R132H mutation typically associated with low-grade astrocytic neoplasms were absent.
  
  
  CONCLUSIONS
  Retinal "vasoproliferative" tumors have been mischaracterized, because they actually display a paucity of microvessels. Proliferating fibrous astrocytes with a very low proliferation index predominate, without immunohistochemical or genetic evidence favoring a neoplasm. Subretinal exudate appeared capable of provoking widespread fibrous metaplasia of the pigment epithelium that was mainly responsible for secondary retinal damage. The term "reactive retinal astrocytic tumor" is proposed as more appropriate for this entity. In carefully selected progressive lesions, consideration should be given to earlier surgical intervention before extensive subretinal exudate accumulates and pigment epithelial proliferation with fibrous metaplasia ensues.
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.
authors.forename: Lynn J
authors.initials: LJ
authors.lastname: Poole Perry
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Jakobiec
authors.forename: Fouad R
authors.initials: FR
authors.lastname: Zakka
authors.forename: Elias
authors.initials: E
authors.lastname: Reichel
authors.forename: Martina C
authors.initials: MC
authors.lastname: Herwig
authors.forename: Arie
authors.initials: A
authors.lastname: Perry
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Brat
authors.forename: Hans E
authors.initials: HE
authors.lastname: Grossniklaus
mesh_terms: D000328:Adult; D000368:Aged; D001253:Astrocytes / Q000378:metabolism / Q000648:ultrastructure; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015353:Eye Enucleation; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction; D019572:Retinal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D009626:Terminology as Topic
chemical_list: C568616:BRAF-KIAA1549 fusion protein, human; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human