title: Giant angiofibromas in tuberous sclerosis complex: a possible role for localized lymphedema in their pathogenesis.
abstract: BACKGROUND
  Giant angiofibromas in patients with tuberous sclerosis complex (TSC) are rare.
  
  
  OBJECTIVE
  We sought to report two patients who had TSC with unusually large and disfiguring facial angiofibromas and to identify underlying histopathologic changes that may possibly explain the clinical features.
  
  
  METHODS
  We performed a clinicopathologic, immunohistochemical, and molecular biologic study using 42 lesional specimens and peripheral blood from one of the two patients. The immunohistochemical investigations were mainly focused on the vascular moiety of the lesions. TSC1 and TSC2 alterations were studied using multiplex ligation-dependent probe amplification for large deletion/duplication mutations, whereas screening for small mutations was performed using polymerase chain reaction amplification of individual coding exons and exon-intron junctions of both genes followed by an analysis on denaturation gradient gel electrophoresis.
  
  
  RESULTS
  Histopathologic examination revealed, in addition to findings typical of angiofibroma, several unusual features including multinucleated giant cells containing multiple intracytoplasmic vacuoles, Touton-like cells, emperipolesis, pagetoid dyskeratosis, vacuolar alteration at the dermoepidermal junction, Civatte bodies, and melanophages in the subjacent dermis. Numerous dilated lymphatic vessels were detected indicating localized lymphostasis, probably caused by secondary lymphedema. The lymphatic nature of the vessels was confirmed by immunohistochemical study. Genetic testing for TSC1 and TSC2 gene mutations revealed a substitution on position c.2251C>T resulting in a nonsense mutation R751X in fragment 20.2.
  
  
  CONCLUSIONS
  Histopathologic specimens and peripheral blood were available from only one patient.
  
  
  CONCLUSIONS
  Localized lymphedema may contribute to the formation of large disfiguring angiofibromas in patients with TSC.
authors.affiliation: Sikl's Department of Pathology, Charles University in Prague, Faculty of Medicine in Pilsen, Pilsen, Czech Republic.
authors.forename: Denisa
authors.initials: D
authors.lastname: Kacerovska
authors.forename: Katrin
authors.initials: K
authors.lastname: Kerl
authors.forename: Michal
authors.initials: M
authors.lastname: Michal
authors.forename: Hana
authors.initials: H
authors.lastname: Filipova
authors.forename: Radek
authors.initials: R
authors.lastname: Vrtel
authors.forename: Tomas
authors.initials: T
authors.lastname: Vanecek
authors.forename: Hana
authors.initials: H
authors.lastname: Zelenakova
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Kraus
authors.forename: Roman
authors.initials: R
authors.lastname: Kodet
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Kazakov
mesh_terms: D000328:Adult; D018322:Angiofibroma / Q000209:etiology* / Q000473:pathology; D002648:Child; D005153:Facial Neoplasms / Q000209:etiology* / Q000473:pathology; D005260:Female; D006801:Humans; D008209:Lymphedema / Q000209:etiology*; D014402:Tuberous Sclerosis / Q000150:complications*