title: Quantitative Imaging In Vivo of Functioning Lymphatic Vessels Around Human Melanoma and Benign Nevi.
abstract: OBJECTIVE
  The density of functioning human lymphatics in vivo and of immunohistochemically defined lymphatics was quantified around melanomas, benign nevi, and matched normal skin, to assess the current lymphangiogenesis paradigm. We investigated whether histological and functioning density increased around melanomas compared with benign nevi or matched skin; whether functioning and histological density increased similarly; and whether larger increases occurred around metastatic melanomas.
  
  
  METHODS
  Functioning density was quantified in vivo as the total amount of human dermal microlymphatics taking up fluorescent marker injected at the lesion margin. After tissue excision, perilesion histological density was quantified using podoplanin marker D2-40.
  
  
  RESULTS
  Histological density was raised similarly around metastasising and non-metastasising melanomas compared with normal skin (+71%, p < 0.0001, n = 32); but was also raised significantly around benign nevi (+17%, p = 0.03, n = 20). In contrast, functioning lymphatic density was substantially reduced around the margins of melanomas (both metastasising and non-metastasising) compared with benign nevi (by 65%, p = 0.02) or normal skin (by 53%, p = 0.0014).
  
  
  CONCLUSIONS
  Raised perilesion histological lymphatic density is not unique to melanoma but occurs also around benign nevi. The findings indicated that the number of functioning lateral lymphatics around human melanomas in vivo but not benign nevi is reduced, despite histologically increased numbers of lymphatics.
authors.affiliation: Cardiovascular and Cell Sciences (Dermatology), St George's Hospital, University of London, London, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Akhras
authors.affiliation: Histopathology Department, St George's Hospital, London, UK.
authors.forename: Rathi
authors.initials: R
authors.lastname: Ramakrishnan
authors.affiliation: Cardiovascular and Cell Sciences (Dermatology), St George's Hospital, University of London, London, UK.
authors.forename: Anthony W B
authors.initials: AW
authors.lastname: Stanton
authors.affiliation: Basic Medical Sciences (Physiology), St George's Hospital, University of London, London, UK.
authors.forename: John R
authors.initials: JR
authors.lastname: Levick
authors.affiliation: Histopathology Department, Royal Surrey County Hospital and Division of Clinical Medicine, University of Surrey, Guildford, UK.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Cook
authors.affiliation: Histopathology Department, St George's Hospital, London, UK.
authors.forename: Heung
authors.initials: H
authors.lastname: Chong
authors.affiliation: Cardiovascular and Cell Sciences (Dermatology), St George's Hospital, University of London, London, UK.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Mortimer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000000981:diagnostic imaging*; D008220:Lymphography; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009506:Nevus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D012878:Skin Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology
keywords: lymphangiogenesis; lymphangiography; lymphatic density; melanoma; metastasis