Functional histopathology of keloid disease

N. Jumper, R. Paus, A. Bayat

Research output: Contribution to journalReview articlepeer-review

71 Scopus citations


Keloid disease is a benign, yet locally aggressive and recurrent cutaneous fibroproliferative condition characterised by excessive scarring. Unique to humans, keloids represent the end-point of a spectrum of abnormal wound healing, are aesthetically disfiguring and can cause major functional impairment. Its heterogeneous phenotype can confound clinical diagnosis leading to mismanagement. This review examines the histological morphology of keloid disease relative to the underlying pathobiology, places it in the context of other cutaneous fibroses and highlights gaps within the literature that hinder differential diagnosis. The pathological similarity to hypertrophic scarring, dermatofibrosarcoma protuberans, dermatofibroma and scleroderma emphasise the importance of detailing the architectural and cellular components of this unique entity. In the papillary dermis keloid tumours show a tongue-like advancing edge that resembles invasive tumour growth. A thickened but flattened epidermis, hyalinised haphazardly arranged collagen bundles that dominate the dermis with subsequent obliteration of the papillary-reticular boundary along with displacement and eventually destruction of skin appendages, exemplify additional hallmark findings associated with keloid disease. Compared to healthy skin, keloid scars show an increased type I/III collagen ratio, decreased fibrillin-1 and decorin expression, increased dermal cellularity and increased expression of fibronectin, versican, elastin and tenascin in the reticular dermis and hyaluronan and osteopontin in the epidermis. We illustrate these “pathognomonic” features of keloid disease by representative micrographs and discuss them in the context of inflammation, hypoxia and tension – as key elements of keloid disease. Finally, we highlight deficits within the keloid research literature as well as discuss important areas for future research in keloid histology.

Original languageEnglish (US)
Pages (from-to)1033-1057
Number of pages25
JournalHistology and Histopathology
Issue number9
StatePublished - Sep 1 2015
Externally publishedYes


  • Cutaneous fibroses
  • ECM
  • Histopathology
  • Keloid

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology


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