Keloids are formed by the excessive production of scar tissue, which extends beyond the margins
of the original injury, often resulting in lesions of grotesque dimensions.
Keloids present a major dilemma to surgeons because of the high recurrence rate with recurrent
growth often larger than the original keloid. The high recurrence rate and the poor response of
keloids to therapy present a great challenge to surgeons. The numerous therapeutic regimens
demonstrate that to date there is no single therapy that is absolutely successful. Therefore, it is
necessary to comprehensively establish the pathology of keloids and to determine the
aetiopathogenesis of the lesion in order to eventually provide unfailing specific effective treatment
and to better understand the mechanisms regulating fibrosis in various fibroproliferative diseases.
To evaluate the pathology and aetiopathogenesis of keloid formation.
The research protocol for the study was approved by the Nelson R Mandela Faculty of Medicine
Ethics Committee. Informed consent was obtained before the biopsies were taken. Keloid and
non-lesional skin biopsies were obtained from thirty two patients who had multiple lesions in
various locations, bringing the total number of keloids and apparently normal skin biopsies
processed and examined to fifty eight. The biopsied specimens were processed for paraffin wax
embedment and routine haematoxylin and eosin, differential and immunocytochemical staining.
Sections were scrupulously examined using the Olympus BH-2 microscope; features pertinent to
the study were photographed with the Olympus DP 10 microscope digital camera system. The
stored images were studied, using the Camedia graphics processing programme.
The results of the study showed that keloids comprise many distinct regions categorized as: the
zone of hyalinising collagen bundles, fine fibrous areas, areas of inflammation, zone of dense
regular connective tissue, nodular fibrous area and area of angiogenesis. Fibroblastic phenotypes
present ranged from spindle, fibrohistiocytic, epitheloid, elongated flattened condensed
fibroblastic cells to few wavy, fuzzy, polygonal and atrophic cell types. Immunocytochemically
these cells were vimentin-positive and actin- and desmin-negative. Few myofibroblastic
phenotypes were also identified and these were vimentin- and alpha smooth muscle actin-positive
and desmin-negative. The fibroblastic and myofibroblastic phenotypes were in proliferative or
degenerative stages and pathological features exhibited were the presence of vesicular, degenerate
or calcified nuclei; nuclear and plasma membrane damage; cytoplasmic and nucleoplasmic
clearing; atrophy, pyknosis and swelling.
Severe, moderate to mild paravascular inflammation was observed around the microvessels of the
sub-papillary plexus and within the keloid. There was compression and occlusion of small blood
vessels, coagulation necrosis and dissolution of mural cells of small blood vessels and small
peripheral nerves. Also present in keloids were oedematous areas, disorganised and hyalinised
connective tissue fibres and increased numbers of degranulated and degranulating mast cells.
Elastic fibres in keloids were minimal or absent whereas at the border of keloids there was an
Degenerate, occluded and compressed microvessels were a widespread pathological feature in
keloids. This resulted in impaired vascular supply to each of the keloid regions which impacted
directly on the pathology of keloids where degeneration and necrosis, manifesting the lack of
nutrients and oxygen to tissue, were found throughout the keloid. The vascular supply was
impaired because of the chronic inflammatory destruction of the microvessels and the elevated
stress within keloids. Factors contributing to increased intrinsic stress were: 1) the lack of elastic
fibres in keloids which decreased the elastic limit, leading to effects of excessive deformational
force which were compression and stiffening of tissue; 2) the high tension skin covering keloid
prone areas had low stretch and a low elastic modulus; 3). protruding hard connective tissue such
as bony prominences or cartilage into the dermis of keloid prone skin; 4) contractile forces exerted
by wound healing fibroblastic cells; and 5) external forces. Compression and occlusion of blood
vessels induced ischaemic and reperfusion tissue injury. During the reperfusion phase blood rich
in growth factors returned to tissue stimulating tissue growth. Tissue growth was also promoted
by elevated internal stress which stimulated increasing levels of gene expression, collagen
synthesis and mitotic activity. All these growth promoting effects resulted in keloid formation.||en