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Year : 2010  |  Volume : 21  |  Issue : 4  |  Page : 518-522
Morphology of collagen fibers and elastic system fibers in actinic cheilitis

Department of Bioscience and Oral Diagnosis, School of Dentistry of São José dos Campos, UNESP - São Paulo State University, São José dos Campos, SP, Brazil

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Date of Submission20-Jun-2009
Date of Decision03-Dec-2009
Date of Acceptance16-Jun-2010
Date of Web Publication24-Dec-2010


Background: Actinic cheilitis (AC) is a premalignant condition intimately related to exposure of the lips to sun rays.
Aim: The objective of this study was to evaluate the elastic and collagen fibers in the lamina propria of AC. The degree of epithelial atypia was correlated with the quantity of elastic and collagen fibers.
Materials and Methods: Fifty-one cases were investigated. One slide was stained with hematoxylin-eosin for the evaluation of atypia, the second was stained with Weigert's resorcin-fuchsin for the assessment of elastic fibers, and the third slide was stained with Mallory's trichrome for the analysis of collagen fibers.
Results: Ordinal logistic regression analysis revealed a significant correlation between the presence of atypia and collagen fibers (P<0.05).
Conclusions: It was concluded that there seems to be a reduction in the quantity of collagen fibers in cases of moderate and severe atypia. No correlation was observed between the degradation of elastic system fibers and the grade of dysplasia.

Keywords: Cheilitis, collagen, sunlight, tissue elastic

How to cite this article:
Sgarbi FC, Bertini F, Tera TM, Cavalcante AR. Morphology of collagen fibers and elastic system fibers in actinic cheilitis. Indian J Dent Res 2010;21:518-22

How to cite this URL:
Sgarbi FC, Bertini F, Tera TM, Cavalcante AR. Morphology of collagen fibers and elastic system fibers in actinic cheilitis. Indian J Dent Res [serial online] 2010 [cited 2022 Nov 26];21:518-22. Available from:
Actinic cheilitis (AC) is a potentially malignant disorder of the lip, [1] intimately related to chronic sun exposure, that can progress to carcinoma. [2],[3] AC is clinically characterized by multifocal lesions that might present with dryness, desquamation, ulceration, pallor, white spots and/or plaques, areas of erythema, and blurred demarcation between the vermilion border and the skin. [2],[4] Due to the possibility of dysplasia, patients with AC should not receive treatment until a histopathologic diagnosis is established. [5],[6],[7]

The histopathologic features of AC include parakeratosis, hyperparakeratosis, orthokeratosis, hyperorthokeratosis, an increase in the granular layer of the epidermis, areas of atrophy and/or hyperplasia, acanthosis, and a variable degree of epithelial dysplasia. Inflammatory infiltrate ranges from mild to severe and is seen amid cellular connective tissue and/or acellular connective tissue of amorphous appearance, identified as solar elastosis or basophilic degeneration of collagen. [8],[9],[10]

Histopathologic analysis should be performed in cases of potentially malignant disorders due to the divergence between clinical and histologic features. [8],[11] Early clinical and histopathologic diagnosis and immediate treatment of lesions suspected of malignancy contribute to a favorable prognosis.

Ultraviolet radiation (UVR) causes damage to the epithelium and lamina propria of the lips, especially the lower lip. It remains unclear how changes in the extracellular matrix (ECM) occur after intermittent or continuous exposure to solar radiation. In an attempt to gain a deeper understanding of this process, the present study aimed to investigate the collagen fibers and elastic system fibers in AC, as well as the relationship between the degree of epithelial dysplasia and the number of fibers in the lamina propria.

   Materials and Methods Top

The study sample comprised 50 patients clinically and histopathologically diagnosed with AC and 18 controls with lower lip mucocele. Patients were submitted to biopsy at the outpatient clinic of the Department of Stomatology, and the samples were sent to the Department of Oral Pathology of the Sγo Josι dos Campos School of Dentistry, Sγo Paulo State University, Sγo Josι dos Campos, Brazil, for histopathologic analysis.

The samples were embedded in paraffin, cut into 5-μm sections and mounted on slides. Hematoxylin and eosin (H and E) staining was used to grade dysplasia, Weigert's resorcin-fuchsin staining was used to quantify elastic system fibers, and Mallory's trichrome stain was used to quantify collagen fibers.

The histologic findings of epithelial atypia were identified in accordance with the classification proposed by van der Waal et al. [12] Epithelial dysplasia was graded in accordance with the classification proposed by Bαnσczy and Csiba, [13] as follows:

  • no dysplasia: fewer than two atypical findings;
  • mild dysplasia: two atypical findings;
  • moderate dysplasia: three to five atypical findings;
  • severe dysplasia: more than five atypical findings.
The images acquired by a digital microscope camera were transferred to a computer and processed using the accompanying software (AxioCam MRc5; Carl Zeiss Gφttiingen MicroImaging GmbH, Germany). The histomorphometric analysis of the changes in elastic system fibers and in collagen fibers was performed using the AxioVision software, version 4.3 (Carl Zeiss MicroImaging GmbH, Gφttiingen). All data collected were statistically analyzed through ordinal logistic regression. The significance level was set at P<0.05.

   Results Top

Normal elastic fibers, elastic fibers of blood vessels and fibers damaged by solar radiation had the same affinity for Weigert's resorcin-fuchsin and were stained with the same intensity [Figure 1]. The elastosis revealed by H and E staining corresponded to the same areas stained with Weigert's resorcin-fuchsin [Figure 2] and [Figure 3]; these regions showed little affinity for Mallory's trichrome [Figure 4] and [Figure 5].
Figure 1: Lamina propria stained by Weigert resorcin-fuchsin: (a) elastic fiber of the blood vessel; (b) elastic fiber damaged by UV radiation and (c) elastic fiber with normal look (200×)

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Figure 2: Field of the lamina propria stained by H and E; the arrow (←) corresponds to elastosis (200×)

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Figure 3: Field of the lamina propria stained by Weigert resorcin-fuchsin; the arrow (←) corresponds to elastosis (200×)

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Figure 4: Field of the lamina propria stained by H and E; the arrow (←) corresponds to elastosis (200×)

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Figure 5: Field of the lamina propria stained by Mallory's trichrome; the arrow (←) corresponds to elastosis (200×)

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Of the 51 patients under study, 16 (31.38%) had no dysplasia and 35 (68.62%) had some degree of dysplasia. Of those who had dysplasia, 7 (13.73%) presented mild dysplasia, 24 (47.06%) presented moderate dysplasia, and 4 (7.84%) presented severe dysplasia.

The analysis of collagen fibers revealed some degree of dysplasia, and ordinal logistic regression showed a statistically significant relationship between the degradation of collagen fibers and the degree of dysplasia (P=0.006). In addition, more severe dysplasia translated to a lower percentage of collagen fibers [Figure 6].The correlation between the degradation of elastic system fibers and the degree of dysplasia was weak and not statistically significant (P=0.231) [Figure 6].
Figure 6: Average values of (a) collagen fibers and (b) elastic fibers, according to atypia degrees

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Statistical tests were performed to determine whether the model used was appropriate to analyze the results. The chi-square test showed that the behavior predicted by the linear regression model correlated well with the results obtained for the samples under study (P=0.617±1.00). This showed that ordinal logistic regression was appropriate to represent our data.

   Discussion Top

Cases of AC present some degree of epithelial dysplasia. The potential of AC to develop into epidermal carcinoma is directly correlated with the grade of dysplasia. However, it should be taken into consideration that the inflammatory response found in processes of epithelial regeneration might mask the degree of dysplasia resulting from potentially malignant disorders such as AC. [8],[14]

The interpretation of epithelial atypia is subjective and, in the case of AC, might vary from rater to rater. [15] In 2005, the World Health Organization [16] recommended that architectural and cytologic changes be investigated in cases of dysplasia. However, Kujan et al, [17] recommended the use of a binary system, i.e., lesions should be classified as "high-risk" or "low-risk" lesions.

The present study adopted the grading of dysplasia as proposed by Bαnσczy and Csiba. [13] The results obtained showed that epithelial dysplasia was present in 68.62% of the patients. In other studies, [4],[6],[7] the authors reported that all the patients investigated presented some degree of dysplasia. The histopathologic interpretation of epithelial dysplasia remains controversial. [15] A literature review of potentially malignant disorders has shown that the number of AC cases that develop into carcinoma is low (recent estimates suggest a proportion of less than 2% per year). [18]

Basophilic degeneration of the lamina propria is observed in AC. [4],[6],[7],[9],[19],[20],[21] However, few studies have investigated basophilic degeneration at the vermilion border. UVR damage to the skin is diagnosed as elastosis when the dermis is affected. [22],[23],[24],[25],[26]

Various components are involved in the process of elastosis, among which are included elastin, metalloproteases and lysozymes. [26] Although the exact components of the elastotic material are unknown, it is known that they have strong affinity for stains that highlight elastic system fibers. [25],[26]

The elastic fibers of the skin damaged by UVR undergo changes that result in the accumulation of elastotic material. [26] In solar elastosis, elastic system fibers can be detected through histochemistry and immunohistochemistry. [23] In this study, when these fibers were histochemically studied using Weigert's resorcin-fuchsin staining, we observed that the elastotic material found in AC, the normal fibers found in AC, and elastic system fibers of the control patients were stained with the same intensity. This happened because normal elastic system fibers and elastotic material have the same affinity for specific stains. [24]

Actinic elastosis might be a process of accumulation and degradation of elastic system fibers. [24] When stained with H and E, fibers with degenerative alterations (due to chronic solar exposure) bind to hematoxylin, hence the term basophilic degeneration. [22] In this study, the elastotic material observed in the sections stained with H and E was also observed in the sections stained with Weigert's resorcin-fuchsin. It is likely that elastosis in AC and elastic system fibers have the same histochemical affinity, as occurs in the skin.

In the skin, it is known that elastic system fibers undergo progressive degradation, characterized by the presence of elastotic material, which is the principal sign of continuous exposure to solar radiation. [26],[27] This condition is generally evident in individuals aged 30 or older. [22]

The effect of UVR on the epidermis and lamina propria is cumulative and can be used to estimate the amount of actinic damage. [28] Therefore, it was expected that the degree of dysplasia would be proportional to the intensity of the damage to elastic system fibers. However, no significant correlation was observed when the damage to these fibers was compared with the degree of dysplasia.

Regarding collagen fibers, the progressive effect of solar radiation on the skin increases proteolytic activation in the ECM, leading to the degradation of collagen fibers. [29] When solar radiation is absorbed by keratinocytes, metalloproteases (which play an important role in the pathogenesis of photoaging due to their ability to digest collagen) are expressed. [30]

Mast cells and their proteases (tryptase and kinase) are substantially increased in lip lesions caused by UVR, such as AC. In addition, increased and degranulated mast cells are found infiltrating or surrounding areas of elastosis, which suggests that these cells are involved in the ECM observed in AC. [21] This might indicate that these changes affect elastic system fibers and collagen fibers.

Chronic exposure to UVR causes an increase in the levels of reactive oxygen in the skin. Reactive oxygen destroys interstitial collagen and induces metalloprotease synthesis, which increases collagen degradation. [31] Collagen loss is related to the degradation caused by proteolytic enzymes secreted by the inflammatory infiltrate in sun-damaged skin. [32]

The inflammatory infiltrate in AC can be mild, moderate, or severe. [4],[7],[19] We believe that the effects of chronic UVR exposure on metalloproteases, combined with the inflammatory response and the release of chemical mediators of inflammation, can indeed contribute to a decrease in the amount of collagen fibers in the vermillion border, as occurs in the skin.

Talwar et al, [33] observed a reduction in precursors of collagen in severely sun-damaged skin. The authors reported that this was probably due to qualitative changes in the organization of collagen fibers and quantitative changes in the precursors of collagen. In addition, UVR reduces the amount of collagen and affects the biosynthesis of fibroblasts, which also contributes to the decrease in the amount of collagen in the skin. [34] MA et al. [31] have reported degradation of collagen fibers, which was also observed in this study.

In this study, statistically significant values were obtained when the amount of collagen fibers was compared with the degree of dysplasia. These data showed that in AC patients with no dysplasia, as well as in AC patients with mild dysplasia, the amount of collagen remained practically unaltered. However, in AC patients with moderate dysplasia, as well as in AC patients with severe dysplasia, the amount of collagen fibers tended to decrease.

The percentage of collagen fibers was significantly higher in patients with mucocele (control group) than in patients with AC. However, no significant differences were observed between AC patients and mucocele patients with regard to the percentage of elastic system fibers.

Various studies have reported the effects of UVR on the connective tissue of the skin; however, the only data available regarding the effects of UVR on the lamina propria of the vermillion border refer to the intensity of the inflammatory infiltrate in AC. [6],[7],[21] Further studies investigating collagen fiber degradation and elastosis in AC are needed in order to draw a parallel between the alterations found in the vermillion border and those found in the skin exposed to UVR.

In this study, the amount of collagen fibers was lower in the AC group than in the control group. In addition, increased collagen fiber degradation was observed in the AC group. No significant differences in the amount of elastic system fibers were observed between the AC group and the control group. A positive correlation was observed between the degradation of collagen fibers and the grade of dysplasia. No correlation was observed between the degradation of elastic system fibers and the grade of dysplasia.

   References Top

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Correspondence Address:
Flávia C Sgarbi
Department of Bioscience and Oral Diagnosis, School of Dentistry of São José dos Campos, UNESP - São Paulo State University, São José dos Campos, SP
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-9290.74224

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

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