Hypertrophic and keloid scars fail to progress from the CD34- /α-smooth muscle actin (α-SMA)+ immature scar phenotype and show gradient differences in α-SMA and p16 expression.

BACKGROUND: Our understanding of the pathogenesis underlying keloid scar formation is still very limited, and the morphological distinction between hypertrophic and keloid scars remains difficult. OBJECTIVES: To test whether hypertrophic and keloid scars may reflect an inability to progress from immaturity to the desired mature normotrophic scar phenotype. METHODS: Using whole-biopsy imaging and an objectively quantifiable way to analyse immunoreactivity, we have compared the immunohistopathological profiles of young immature scars with mature normotrophic scars, hypertrophic scars, and keloids with their surrounding-normal-skin. RESULTS: Abnormal scars (hypertrophic scars and keloids) maintain the immature scar phenotype, characterized by a CD34- (tumour biomarker) and α-smooth muscle actin (α-SMA)+ (myofibroblast) dermal region. This is in contrast to normal skin, surrounding-normal-skin and mature normotrophic scars that were CD34+ / α-SMA- . Immature, hypertrophic and keloid scars showed abnormal epidermal differentiation (involucrin), but only hypertrophic scars and keloids showed increased epidermal thickness. Immature scars did show increased epidermal and dermal proliferation (Ki67), which was absent from abnormal scars, where mesenchymal hypercellularity (vimentin) and senescence (p16) were predominant. Keloidal collagen and α-SMA were previously considered to distinguish between hypertrophic scars and keloids. However, α-SMA staining was present in both abnormal scar types, while keloidal collagen was present mostly in keloids. There were no obvious signs of heterogeneity within keloid scars, and the surrounding-normal-skin resembled normal skin. CONCLUSIONS: Both abnormal scar types showed a unique CD34- /α-SMA+ /p16+ scar phenotype, but the differences between hypertrophic scars and keloids observed in this study were of a gradient rather than absolute nature. This suggests that scar progression to the mature normal scar phenotype is, for as yet unknown reasons, hindered in hypertrophic and keloid scars. What's already known about this topic? Hypertrophic and keloid scars both have sustained epidermal barrier dysfunction, suggesting the persistence of an immature scar phenotype. Morphological distinction between hypertrophic and keloid scars remains a topic of debate, although α-smooth muscle actin (α-SMA) and keloidal collagen have been considered distinguishing features of hypertrophic and keloid scars, respectively. It has been suggested that keloids are not simply homogeneous growths, as heterogeneity within keloid scars and possible involvement of the surrounding-normal-skin have been reported. What does this study add? An extensive whole-biopsy imaging and quantifiable immunohistochemical assessment of immature, mature normal, hypertrophic and keloid scars, including normal skin surrounding keloids. Hypertrophic and keloid scars maintain dermal characteristics of immature scars, rather than transitioning into the normal mature phenotype. Differences between hypertrophic and keloid scars were of a gradient rather than absolute nature, with keloids showing the more extreme phenotype. There was no obvious heterogeneity within keloids, and the normal skin surrounding keloids resembled normal skin. What is the translational message? Keloids remain primarily a clinical diagnosis. A raised scar with the CD34- /α-SMA+ /p16+ phenotype with strong immunoreactivity for p16 and significant amounts of keloidal collagen, together with a thickened and strongly abnormal involucrin-stained epidermis, would sway the diagnosis towards keloid scars. A hypertrophic scar seems more likely when the CD34- /α-SMA+ /p16+ phenotype shows very strong presence of α-SMA+ in large dermal nodules, with lesser p16 staining and absent or negligible keloidal collagen.

Increased epidermal thickness and abnormal epidermal differentiation in keloid scars.

BACKGROUND: The pathogenesis underlying keloid formation is still poorly understood. Research has focused mostly on dermal abnormalities, while the epidermis has not yet been studied. OBJECTIVES: To identify differences within the epidermis of mature keloid scars compared with normal skin and mature normotrophic and hypertrophic scars. METHODS: Rete ridge formation and epidermal thickness were evaluated in tissue sections. Epidermal proliferation was assessed using immunohistochemistry (Ki67, keratins 6, 16 and 17) and with an in vitro proliferation assay. Epidermal differentiation was evaluated using immunohistochemistry (keratin 10, involucrin, loricrin, filaggrin, SPRR2, SKALP), reverse-transcriptase polymerase chain reaction (involucrin) and transmission electron microscopy (stratum corneum). RESULTS: All scars showed flattening of the epidermis. A trend of increasing epidermal thickness correlating to increasing scar abnormality was observed when comparing normal skin, normotrophic scars, hypertrophic scars and keloids. No difference in epidermal proliferation was observed. Only the early differentiation marker involucrin showed abnormal expression in scars. Involucrin was restricted to the granular layer in healthy skin, but showed panepidermal expression in keloids. Normotrophic scars expressed involucrin in the granular and upper spinous layers, while hypertrophic scars resembled normotrophic scars or keloids. Abnormal differentiation was associated with ultrastructural disorganization of the stratum corneum in keloids compared with normal skin. CONCLUSIONS: Keloids showed increased epidermal thickness compared with normal skin and normotrophic and hypertrophic scars. This was not due to hyperproliferation, but possibly caused by abnormal early terminal differentiation, which affects stratum corneum formation. Our findings indicate that the epidermis is associated with keloid pathogenesis and identify involucrin as a potential diagnostic marker for abnormal scarring.

Complications of otoplasty: a literature review.

Over 200 otoplasty techniques have been described in the current literature. However, relatively few articles focus on the associated complication rates. The goal of this review is to examine the incidence of complication rates associated with otoplasty procedures. An electronic search of the Pubmed database yielded 205 articles with significant overlap in search results. Twenty articles published between 2000 and 2007 adhered to our inclusion criteria. Early complications included in this review were haematoma, bleeding, infection, skin necrosis and wound dehiscence; late complications included suture extrusion, scarring, hypersensitivity, asymmetry and inaesthetic results. The cumulative incidence of early complications was low and varied from 0% to 8.4%, with the exception of two outliers. Although cumulative late complication incidences varied greatly from 0% to 47.3%, complication rates on the higher end of the spectrum were not accompanied with revision rates of the same magnitude. Comparison of the different articles was made difficult by the lack of a uniform calculation method for complication incidence, variable follow-up length and data collection, inconsistent use of operation technique and publication bias. Recommendations for future studies include: consistent use of operative technique or at least differentiate between the used surgical techniques when presenting complication rates, inclusion of only patients with bilateral primary procedures, considering each operated ear as an independent variable when calculating complication incidence and a minimum follow-up period of 2 years, with both objective and subjective data collection.