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ORIGINAL ARTICLE
Year : 2007  |  Volume : 52  |  Issue : 4  |  Page : 184-187
Study of mast cell count in skin tags


1 Department of Dermatology, Faculty of Medicine, Cairo University, Cairo, Egypt
2 Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt

Correspondence Address:
Omar Soliman El Safoury
Department of Dermatology, Faculty of Medicine, Cairo University, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.37722

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   Abstract 

Background: Skin tags or acrochordons are common tumors of middle-aged and elderly subjects. They consist of loose fibrous tissue and occur mainly on the neck and major flexures as small, soft, pedunculated protrusions. Objectives: The aim was to compare the mast cells count in skin tags to adjacent normal skin in diabetic and nondiabetic participants in an attempt to elucidate the possible role of mast cells in the pathogenesis of skin tags. Participants and Methods: Thirty participants with skin tags were divided into group I (15 nondiabetic participants) and group II (15 diabetic participants). Three biopsies were obtained from each participant: a large skin tag, a small skin tag and adjacent normal skin. Mast cell count from all the obtained sections was carried out, and the mast cell density was expressed as the average mast cell count/high power field (HPF). Results: A statistically significant increase in mast cells count in skin tags in comparison to normal skin was detected in group I and group II. There was no statistically significant difference between mast cell counts in skin tags of both the groups. Conclusion: Both the mast cell mediators and hyperinsulinemia are capable of inducing fibroblast proliferation and epidermal hyperplasia that are the main pathologic abnormalities seen in all types of skin tags. However, the presence of mast cells in all examined skin tags regardless of diabetes and obesity may point to the possible crucial role of mast cells in the etiogenesis of skin tags through its interaction with fibroblasts and keratinocytes.


Keywords: Acrochordon, hyperinsulinemia, mast cell, non-insulin-dependent diabetes mellitus, obesity, skin tag, soft fibroma


How to cite this article:
Zaher H, El Safoury OS, El Komy MM, Mahmoud SB, El Hameed HA. Study of mast cell count in skin tags. Indian J Dermatol 2007;52:184-7

How to cite this URL:
Zaher H, El Safoury OS, El Komy MM, Mahmoud SB, El Hameed HA. Study of mast cell count in skin tags. Indian J Dermatol [serial online] 2007 [cited 2019 Jul 21];52:184-7. Available from: http://www.e-ijd.org/text.asp?2007/52/4/184/37722



   Introduction Top


Skin tags or acrochordons are common tumors of middle-aged and elderly subjects. They consist of loose fibrous tissue and occur mainly on the neck and major flexures as small, soft, pedunculated protrusions. Multiple skin tags are frequently associated with non-insulin-dependent diabetes mellitus (NIDDM) and obesity. Insulin resistance is the underlying abnormality in both the conditions.

Mast cells are increased in number in many skin diseases, including many tumors - benign or malignant. It has been noticed that human mast cells stimulate fibroblast proliferation after cell-cell contact in vitro , probably through interleukin-4 (IL-4). IL-4 acts as a second signal for fibroblasts since it amplifies the action of low doses of obligatory fibroblast growth factors such as fibroblast growth factor or platelet-derived growth factor. Several chemochines and growth factors may alter fibroblast proliferation under the control of mast cells.

The aim of this study was to compare mast cells count in skin tags to adjacent normal skin in diabetic and nondiabetic patients in an attempt to elucidate the possible role of mast cells in the pathogenesis of skin tags.


   Participants and Methods Top


For this study, 30 participants (15 nondiabetic and 15 diabetic patients) presented to dermatology outpatient clinic seeking advice for their skin tags. Patients were divided into two groups, as shown in [Table - 1].

All participants were subjected to the following:

1. The weight and height for each participant were measured and body mass index (BMI) [1] was calculated:

BMI = (Weight in kilograms) χ (Height in meters) 2

2. Investigations: Fasting blood sugar estimation for nondiabetic participants was performed

3. Skin snip: From each participant, a large skin tag (length >4 mm), a small skin tag (length <2 mm) and a normal skin snip (as a control) were obtained

In each participant, the three skin specimens were taken from the same area.

Biopsy procedure, fixation and staining: For local anesthesia, 1% xylocaine was injected around the area to be biopsied. Biopsies were fixed in 10% formalin solution for 24 h. All biopsies were processed by routine paraffin technique. Microtome sections were perpendicular to the skin surface, at the middle of the biopsy and were 4 mm in thickness.

The sections were stained with the following:

Hematoxylin and eosin: Toluidine blue-uranyl nitrate metachromatic method for mast cells. [2]

The two groups were examined by one author blindly to avoid intra-observer variation. In fact, normal skin cannot be counted in a blinded fashion.

Mast cell counts: The mast cell count was carried out with a microscope equipped with an 40 objective lens and an 10 ocular; the ocular had an eye-piece graticule in order to ensure that overlap and double counting did not occur.

All mast cell profiles in the whole section were counted. Sections from each biopsy were counted. Each section was counted twice and a mean of the two counts was used in all the calculations.

The mast cell density was expressed as the average mast cell count/high power field (HPF).


   Statistical Analysis Top


Data were statistically described in terms of range, mean, standard deviation (SD), median, frequencies (number of cases) and relative frequencies (percentages) when appropriate. The comparison of quantitative variables between nondiabetic and diabetic groups was performed using Mann-Whitney U test for independent samples. The comparison of mast cell count within the same group was done using Kruskal-Wallis nonparametric analyses of variance test with posthoc multiple two-group comparisons. For comparing gender, Yates corrected Chi square (χ2 ) test was performed. P values less than 0.05 were considered to be statistically significant. All statistical calculations were performed using computer programs Microsoft Excel version 7 (Microsoft Corporation, NY, USA) and SPSS (Statistical Package for the Social Science; SPSS Inc, Chicago, IL, USA) statistical program. Confidence interval (CI) was not calculated because our sample is relatively small and generalization on the population is not expected.


   Results Top


The comparison of age between group I (non-diabetic) and group II (diabetic) showed statistically significant difference ( P = 0.002), which reflects the late onset of diabetes in the second group. The comparison of gender between both groups (nondiabetic and diabetic) showed no statistically significant difference ( P = 0.699). Although the mean BMI in the nondiabetic group is <30 kg/m 2 (BMI above 30 is considered to be obese), comparison to group II (diabetic) showed statistically significant difference ( P = 0.018), which reflects the association of obesity and type II DM [Table - 1].

Mast cell count in nondiabetic group: The comparison of mast cell count between large skin tags (ST), small ST and normal skin in nondiabetic participants showed an increase in number of mast cells in ST in relation to normal skin with an overall statistically significant difference ( P = 0.0008). This was attributed to the significant difference between mast cell counts in both large and small ST in comparison to normal skin ( P < 0.0001 and P = 0.0055 respectively). No statistically significant difference was found on comparing mast cell count in large ST with small ST ( P = 0.145) [Table - 2].

Mast cell count in diabetic group: A similar comparison of mast cell count in diabetic participants showed an increase in mast cell count in ST in comparison to normal skin with an overall statistically significant difference ( P = 0.0017). This statistically difference was attributed to the significant difference of mast cell counts in both large and small ST in comparison to normal skin ( P = 0.011 and 0.0006, respectively). No statistically significant difference was found on comparing mast cell count in large ST with small ST ( P = 0.854)

The comparison between the mast cell count in large ST, small ST as well as normal skin between nondiabetics and diabetic groups showed no statistically significant difference ( P = 0.244, 0.735 and 0.569, respectively) [Figure - 1].


   Discussion Top


The etiology of skin tags is not effectively understood. A relation to diabetes mellitus, obesity, friction, acromegaly, colonic polyps and HPV has been suggested. [3],[4] As the skin tag protrudes out, there should be a proliferation of the epidermis with it is the core of dermis. Regardless of hyperinsulinemia (which is a common association with obesity and diabetes), mast cell mediators are capable of inducing epidermal hyperplasia and fibroblast proliferation, which are the main pathologic abnormalities observed in all types of skin tags or acrochordons. In the skin, mast cells are usually found in the dermis with some accentuation around the superficial vascular plexus and appendages. [5],[6] Mast cells produce a number of multifunctional cytokines. [7],[8] Such molecules are potentially important mediators in mast cell/fibroblast interactions. [9]

These cytokines include tryptase, chymase, histamine, IL-4 and basic fibroblast growth factor; all these cytokines directly or indirectly stimulate fibroblast growth, differentiation and collagen deposition [10],[11],[12],[13] (see arrow-1 in [Figure - 2]). Moreover, there is evidence that fibroblasts influence mast cell maturation/differentiation. [14] Stem cell factor, a mast cell growth factor produced by fibroblasts, plays a role in maintenance of survival and differentiation of mast cells [15] (see arrow-2 in [Figure - 2]).

Mast cells not only potently stimulate fibroblast growth and activation but also stimulate keratinocyte proliferation [16] and epidermal acanthosis, [17] although to a lesser extent (see arrow-3 in [Figure - 2]).

It was reported that hyperinsulinemia due to type II diabetes or obesity may favor unregulated tissue growth leading to many disorders including skin tags. [18] Hyperinsulinemia may induce both fibroblasts proliferation in skin tags via activation of insulin-like growth factor I receptors on their surfaces [19] (see arrow-5 in [Figure - 2]) and epidermal proliferation associated with formation of skin tags [20] (see arrow-6 in [Figure - 2]). However, our results showed that mast cells are increased in number in all examined skin tags regardless the presence of diabetes or obesity. Mast cells can probably induce skin tags through interaction with fibroblast and keratinocytes.

Therefore, the question is that if friction (regardless hyperinsulinemia) is the precipitating factor of skin tags, why the skin tags do not affect the whole axilla?

From this study, it is suggested that areas with high count of mast cells can only initiate skin tag formation. Mast cell stimulated by friction (see arrow-7 in [Figure - 2]) or viral infections as HPV (see arrow-4 in [Figure - 2]) in presence or absence of hyperinsulinemia can localize and start skin tag formation through its interaction with fibroblasts and keratinocytes. Further, the finding that skin tags are not a common association in mastocytosis indicates that mast cells without precipitating factor cannot initiate skin tags.

In our department, two studies are being currently done; the first is measuring mast cells - fibroblasts surface area in skin tags - and the second is measuring estrogen receptors in skin tags in comparison to the normal skin.

 
   References Top

1.Abraham S, Carrol MD, Najjar MF, Fulwood R. Overweight and obese adults in the United States. Vital Health Stat II 1983;230:1-93.  Back to cited text no. 1    
2.Hughesdon PE, Roy J. Micr Soc, 16: 1. Quoted from Drury. In : Roy C, editor. RAB: Wallington, EA; 1976 and In : Carleton's Histological Technique. 4 th ed. Oxford University Press: 1949. p. 14.  Back to cited text no. 2    
3.Vinel JP, Marcerou P, Cassigneul J, Carballido M, Cales P, Viraben R, et al . Molluscum pendulum and colorectal preneoplastic and neoplastic lesions. Gastroenterol Clin Biol 1987;11:177-8.  Back to cited text no. 3  [PUBMED]  
4.Dianzani C, Calvieri S, Pierangeli A, Imperi M, Bucci M, Degener AM. The detection of human papillomavirus DNA in skin. Br J Dermatol 1998;138:649-51.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Olafsson JH, Roupe G, Enerback L. Dermal mast cells in mastocytosis: Fixation, distribution and quantitation. Acta Derm Venereol 1986;66:16-22.  Back to cited text no. 5    
6.Leder LD. Intraepidermal mast cells and their origin. Am J Dermatopathol 1981;3:247-50.  Back to cited text no. 6  [PUBMED]  
7.Galli SJ. New concepts about the mast cell. N Engl J Med 1993;328:257-65.  Back to cited text no. 7    
8.Bradding P, Feather IH, Howarth PH, Mueller R, Roberts JA, Britten K, et al . Interleukin-4 is localized to and released by human mast cells. J Exp Med 1992;176:1381-6.  Back to cited text no. 8  [PUBMED]  
9.Trautmann A, Krohne G, Brφcker EB, Klein CE. Human mast cells augment fibroblast proliferation by heterotypic cell-cell adhesion and action of IL-4. J Immunol 1998;160:5053-7.  Back to cited text no. 9    
10.Garbuzenko E, Nagler A, Pickholtz D, Gillery P, Reich R, Maquart FX, et al . Human mast cells stimulate fibroblast proliferation, collagen synthesis and lattice contraction: A direct role for mast cells in skin fibrosis. Clin Exp Allergy 2002;32:237-46.  Back to cited text no. 10    
11.Riekki R, Harvima IT, Jukkola A, Risteli J, Oikarinen A. The production of collagen and the activity of mast cell chymase increase in human skin after irradiation therapy. Exp Dermatol 2004;13:364-71.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.QU Z, Liebler JM, Powers MR, Galey T, Ahmadi P, Huang XN, et al . Mast cells are a major source of basic fibroblast growth factor in chronic inflammation and cutaneous hemangioma. Am J Pathol 1995;147:564-73.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Reed JA, Albino AP, McNutt NS. Human cutaneous mast cells express basic fibroblast growth factor. Lab Invest 1995;72:215-22.  Back to cited text no. 13  [PUBMED]  
14.Levi-Schaffer F, Austen KF, Caulfield JP, Hein A, Bloes WF, Stevens RL. Fibroblasts maintain the phenotype and viability of the rat heparin-containing mast cell in vitro. J Immunol 1985;135:3454-6.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]
15.Welker P, Grabbe J, Gibbs B, Zuberbier T, Henz BM. Human mast cells produce and differentially express both soluble and membrane-bound stem cell factor. Scand J Immunol 1999;49:495-500.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]
16.Algermissen B, Hermes B, Feldmann-Boeddeker I, Bauer F, Henz BM. Mast cell chymase and tryptase during tissue turnover: Analysis on in vitro mitogenesis of fibroblasts and keratinocytes and alterations in cutaneous scars. Exp Dermatol 1999;8:193-8.  Back to cited text no. 16  [PUBMED]  
17.Oike Y, Yasunaga K, Ito Y, Matsumoto S, Maekawa H, Morisada T, et al . Angiopoietin related growth factor (AGF) promotes epidermal proliferation, remodelling and regeneration. Proc Natl Acad Sci USA 2003;100:9494-9.  Back to cited text no. 17  [PUBMED]  [FULLTEXT]
18.Cordain L, Eades MR, Eades MD. Hyperinsulinemic diseases of civilization: More than just syndrome X. Comp Biochem Physiol A Mol Integr Physiol 2003;136:95-112.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]
19.Mathur SK, Bhargava P. Insulin resistance and skin tags. Dermatology 1997;195:184.  Back to cited text no. 19    
20.Norris PG, McFadden J, Gale E, Griffiths WA. Skin tags are more closely related to fasting insulin than fasting glucose levels. Acta Derm Venereol 1988;68:367-8.  Back to cited text no. 20  [PUBMED]  


    Figures

  [Figure - 1], [Figure - 2]
 
 
    Tables

  [Table - 1], [Table - 2]

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