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ORIGINAL ARTICLE
Year : 2015  |  Volume : 28  |  Issue : 2  |  Page : 355-359

The role of mast cells and mast cell tryptase in skin tags: an immunohistochemical study


1 Department of Dermatology and Andrology, Shebin El-Kom Teaching Hospital, Menoufia University, Menoufia, Egypt
2 Department of Pathology, Faculty of Medicine, Shebin El-Kom Teaching Hospital, Menoufia University, Menoufia, Egypt

Date of Submission05-May-2013
Date of Acceptance31-Oct-2013
Date of Web Publication31-Aug-2015

Correspondence Address:
Shimaa F Seif El Naser
Department of Dermatology and Andrology, Shebin El-Kom Teaching Hospital, Menoufia University, Sabry Abo Alm Street, Shebin El-Kom, Menoufia, 32511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.163884

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  Abstract 

Objective
The aim of this study was to assess mast cell tryptase (MCT) expression in skin tags (STs) in comparison with normal skin.
Background
STs or acrochordons are common benign connective tissue of the dermis that are composed of loose fibrous tissue, in middle-aged and elderly individuals, located predominantly in intertriginous skin and neck, which consists of a bit of skin projecting from the surrounding skin.
Patients and methods
This study was carried out on 30 patients and 10 control participants. One biopsy was obtained from each patient. Mast cell count and mast cell density were assessed by immunohistochemical staining for MCT and expressed as mean, median, and range (the average mast cell count/high-power field).
Results
The results of the present study showed a statistically significant increase in the mast cells count in STs in comparison with normal skin.
Conclusion
Higher expression of MCT in ST compared with normal skin and this enzyme mediator may be responsible for induction of fibrosis in ST.

Keywords: mast cell, mast cell tryptase, skin tags


How to cite this article:
Maraee AH, Abdou AG, Seif El Naser SF. The role of mast cells and mast cell tryptase in skin tags: an immunohistochemical study. Menoufia Med J 2015;28:355-9

How to cite this URL:
Maraee AH, Abdou AG, Seif El Naser SF. The role of mast cells and mast cell tryptase in skin tags: an immunohistochemical study. Menoufia Med J [serial online] 2015 [cited 2020 Feb 17];28:355-9. Available from: http://www.mmj.eg.net/text.asp?2015/28/2/355/163884


  Introduction Top


Skin tags (STs) or acrochordons are common benign connective tissue of the dermis that are composed of loose fibrous tissue, in middle-aged and elderly individuals, located predominantly in intertriginous skin and head and neck, which consists of a bit of skin projecting from the surrounding skin [1] .

Histologically, STs are polypoid lesions with overlying mildly acanthotic epidermis with papillomatosis and hyperkeratosis. There is a loose, edematous fibrovascular core with mild chronic inflammation [2] . The etiology of STs is not well understood. STs have a relation to diabetes mellitus, obesity, friction, acromegaly, colonic polyps, and human papilloma virus (HPV) [2] . The mast cell, tumor necrosis factor-related apoptosis-inducing ligand, and tumor necrosis factor-a may play a role in the pathogenesis of STs, following trauma to the skin, in the form of friction [3] .

Various studies have supported the notion that mast cells are profibrotic. Mast cells accumulate in fibrotic conditions including wound healing, liver cirrhosis, STs, and scleroderma [4] . Mast cell mediators can also induce epidermal hyperplasia, thus contributing toward the main pathologic abnormalities observed in all types of STs [5].

Mast cell tryptase (MCT) is involved in allergic response and is suspected to act as a mitogen for fibroblast line fluids [6]. MCT stimulates fibroblast chemotaxis and also stimulates collagen mRNA synthesis fluids [7]. MCT activates protease-activated receptors. Protease-activated receptor has by far generated the maximum interest. It targets the proliferation of fibroblasts, smooth muscle cells, and epithelial cells, causing fibrosis, tissue remodeling, and recruitment of eosinophils, neutrophils, and mast cells [8] .


  Aim Top


The aim of this study was to evaluate the possible role of mast cells and the mediator tryptase released in the pathogenesis of STs through an immunohistochemical study.


  Patients and methods Top


This study was carried out on 40 individuals including 30 individuals presenting with STs and 10 healthy individuals.

All individuals were recruited from Dermatology Outpatient Clinic, Menoufia University Hospital, during the period between May 2011 and September 2012.

All individuals were subjected to the following:

  1. Complete assessment of history including family history of the same condition and history of diabetes mellitus.
  2. Clinical examination to assess the number and site of STs.
  3. Skin biopsy: excisional skin biopsies were taken from lesions of individuals presenting with STs and from the normal skin of the controls, after obtaining written consent.
Biopsies were fixed in a 10% formalin solution for 24 h. All biopsies were subjected to routine tissue processing in the Pathology Department, Faculty of Medicine, Menoufia University. After fixation in 10% neutral formalin, biopsies were subjected to dehydration in ascending grades of alcohol, followed by xylene, and then paraffin-embedded blocks were prepared. Several 5-μm-thick sections were cut from paraffin-embedded blocks and stained with the following:

(1) Hematoxylin and eosin to evaluate the degree of inflammation and collagenosis.

(2) Immunohistochemical staining with MCT: MCT Ab-2 (clone AAI, cat no. MS-1216-R7, ready-to-use for immunohistochemical staining; Thermo Fisher Scientific, Labvision, California, USA).

Immunohistochemistry

The method used for immunostaining was the streptavidin-biotin amplified system. The slides were subjected to subsequent steps of deparaffinization and rehydration. Antigen retrieval was performed by boiling in citrate buffer saline (pH 6), followed by cooling at room temperature. The primary antibody was incubated overnight at room temperature. Then, the secondary antibody was applied with diaminobenzidine (DAB) as a chromogen substrate and Mayer's hematoxylin as a counter stain. The primary antibody was MCT (mouse monoclonal antibody; Labvision, USA). It was received as 1.0 ml concentrated and diluted by PBS at a dilution of 1 : 100 according to the instructions in the pamphlet supplied. A positive control for MCT (normal human tonsil) together with a negative control (by omitting the primary antibody step) were included in each run of staining.

Interpretation of immunohistochemical staining for mast cell tryptase

Positive MCT expression was assigned when any number of mast cells showed cytoplasmic and granular staining. The percentage of immunoreactivity was evaluated as mean, median, and range.

Statistical analysis

Data were collected, tabulated, and analyzed statistically using a personal computer using the 'statistical package for the social sciences' (version 16; SPSS Inc., Chicago, Illinois, USA) program. The Mann-Whitney U-test was used for comparison between quantitative variables. Spearman's correlation coefficient (r) was used to assess the correlation between two quantitative variants. P value 0.05 or less was considered significant.


  Results Top


Mast cell density assessed by mast cell tryptase expression in normal skin and skin tag

MCT was expressed in 80% of normal skin. MCT was expressed in total ST (100%). There was a significant difference between STs and controls in mast cell density evaluated by MCT (P = 0.001); the density was higher in STs compared with normal skin [Figure 1] [Figure 2] [Figure 3] [Figure 4] and [Table 1] [Table 2] [Table 3].
Figure 1: Few mast cells were identified in the perivascular infl ammatory infiltrate (hematoxylin and eosin staining, ×400)

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Figure 2: Mast cell tryptase immunoreactivity in scattered mast cells in a case of skin tag (immunohistochemical staining, ×100)

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Figure 3: Higher power view of a skin tag showing membranous expression in mast cells (immunohistochemical staining, ×200 )

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Figure 4: Mast cell tryptase immunoreactivity in mast cells in a case of skin tag (immunohistochemical staining, ×400 )

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Table 1 Clinical and pathological data of selected patients

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Table 2 Differences between skin tag and control in mast cell density assessed by toluidine blue and mast cell tryptase expression

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Table 3 Relation between mast cell tryptase and other parameters studied

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  Discussion Top


STs are small, soft, pedunculated, flesh to dark brown colored, benign skin tumors commonly occurring on the neck and axilla. They are considered to be relatively common lesions and it has been reported that they might reflect a state of insulin resistance. Age, obesity, and atherogenic lipid profile are also associated with STs [9] .

Mast cells are important effector and multifunctional tissue-dwelling cells with an important role in conditions such as inflammatory, allergic reactions, angiogenesis, and tissue remodeling. They attract other key players of the immune system by releasing cytokines [9] . The uneven distribution in the numbers of mast cells in different body sites may be a result of differences in their functional, environmental, and hemodynamic properties. The number of mast cells on the face were higher compared with other body sites. Higher numbers of mast cells were found in the forearm and lower leg (distal extremities) compared with those in the trunk, upper leg, and upper arm (center and proximal extremities) [9] .

Mast cells are increased in number in many skin diseases, including many tumors - benign or malignant. Mast cell count was found to be significantly higher in small and large ST lesions than adjacent normal skin [5] .

The aim of our study was to detect mast cell density by immunohistochemical staining for MCT in ST compared with normal skin to identify whether they play a role in ST development or not.

Our study did not find any differences between women and men in ST numbers, which is in agreement with that of Zaher et al. [5] . The male to female ratio in our investigated cases was 7 : 8, which may be related to cosmotic consideration in women compared with men.

Family history was positive in 80% of our cases, signifying an important role for familial tendency in STs, although Rasi et al. [10] reported that family history was positive in only 44% of patients with STs. Some studies have shown a genetic predisposition toward the development of STs, suggesting that STs can run in families [11] .

Although it was reported previously that STs are often found in and around the affected areas of acanthosis nigricans [12] , particularly lesions in the axillae and groin, associated acanthosis nigricans was detected in the current work in 47% of cases.

A history of diabetes was found in 50% of our patients. This figure was lower than reported in other studies, where it reached 62% in the Thappa's [13] study and 75% in the Demir and Demir's [14] study. Diabetes mellitus and obesity could still contribute toward the development of ST through hyperinsulinemia, which may favor upregulated tissue growth, leading to many disorders including STs. Hyperinsulinemia may induce both fibroblasts proliferation in STs by activation of insulin-like growth factor I receptors on their surfaces and epidermal proliferation associated with the formation of STs [5] .

The association of acanthosis nigricans, STs, diabetes mellitus because of insulin resistance, and obesity in adolescents and young adults represents a well-defined syndrome [15] .

Zaher et al. [5] suggested that areas with a high count of mast cells can only initiate ST formation. Mast cells stimulated by friction or viral infections such as HPV in the presence or absence of hyperinsulinemia can localize and initiate ST formation through its interaction with fibroblasts and keratinocytes.

We used MCT antibody to detect mast cells by immunohistochemistry and we found that MCT was expressed in all cases of ST in a percentage higher than detected in normal skin; this may suggest that the presence of mast cells and its expression of MCT may be essential for the development of ST [16] .

The antitryptase monoclonal antibody is now considered to be the gold standard for identification of mast cells. The enzyme tryptase is also present in basophilic granulocytes, but its concentration is so low that they are stained very weakly with antitryptase monoclonal antibody [17] .

MCT is involved in allergic response and is suspected to act as a mitogen for fibroblast cell lines [6] . The tryptase can activate fibroblasts by stimulating procollagen mRNA synthesis [7] .

El Safoury et al. [17] found that the mast cell count was higher in diabetic than nondiabetic participants. Mast cell count differs according to the method used; the latter study used Bismarck brown staining for detection and counting of mast cells.

We observed that the density of mast cells was higher in cases showing marked collagenosis (P = 0.052). It was reported that human mast cells produce type VIII collagen [18] . Generally, mast cells participate in the pathogenesis of fibrotic diseases; they are found to stimulate fibroblast proliferation and collagen synthesis through some fibrotic mediators such as histamine and tryptase [17] . Therefore, mast cells play a direct and potentiating role in skin remodeling and fibrosis [17] . In addition to fibroblast proliferation, mast cell mediators can also induce epidermal hyperplasia. All this could, thus, contribute toward the main pathologic abnormalities observed in all types of STs [5] .

Finally, our study found higher expression of MCT in ST compared with normal skin and this enzyme mediator may be responsible for induction of fibrosis in ST.

Recommendations

  1. Screening for diabetes in ST patients may result in the diagnosis of prediabetic or diabetic patients.
  2. Mast cell mediators may predispose toward the development of STs; thus, mast cell stabilizers may play a role in the prophylaxis or the treatment of STs for further clinical trials.

  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Millington GW, Graham-Brown RA. Skin and skin disease throughout life. In: Burns A, Breathnach S, editors. Rook's textbook of dermatology. Oxford: Blackwell; 2010. 8.1-8.30.  Back to cited text no. 1
    
2.
Gupta S, Aggarwal R, Gupta S, Arora SK. Human papillomavirus and skin tags: is there any association?. Indian J Dermatol Venereol Leprol 2008; 74 :222-225.  Back to cited text no. 2
    
3.
El Safoury OS, Abdel Hay RM, Fawzy MW, Kadry D, Amin IM. Skin tags, leptin, metabolic syndrome and change of the life style. Indian J Dermatol 2011; 77 :577-581.  Back to cited text no. 3
    
4.
Navi D, Saegusa J, Liu FT. Mast cells and immunological skin diseases. Clin Rev Allergy Immunol 2007; 33 :144-155.  Back to cited text no. 4
    
5.
Zaher H, El Safoury OS, El Komy MH, Mahmoud SB, Abd El Hameed H. Study of mast cell count in skin tags. Indian J Dermatol 2007; 52 :184-187.  Back to cited text no. 5
    
6.
Selwood T, Jaffe EK. Dynamic dissociating homo-oligomers and the control of protein function. Arch Biochem Biophys 2011; 519 :131-143.  Back to cited text no. 6
    
7.
Gruber BL, Kew RR, Jelaska A, Ren S, Marchese MJ, Garlic J. Human mast cells activate fibroblasts: tryptase is a fibrogenic factor stimulating collagen ribonucleic acid synthesis and fibroblast chemotaxis. J Immunol 1997; 158 :2310-2317.  Back to cited text no. 7
    
8.
Hallgren J, Pejler G. Biology of MC tryptase. An inflammatory mediators. FEBS J 2006; 273 :1871-1895.  Back to cited text no. 8
    
9.
Janssen AS, Heide R, Tank B, Oranje AP. Mast cell distribution in normal adult skin. J Clin Pathol 2005; 58 :285-289.  Back to cited text no. 9
    
10.
Rasi A, Razieh SA, Nasim S. Skin tag as a cutaneous marker for impaired carbohydrate metabolism: a case-control study. Int J Dermatol 2007; 46 :1155-1159.  Back to cited text no. 10
    
11.
Stoppler MC, Sheil WC. Emedicine healeth. 2014. Available at http://www.emedicinehealth.com/skin_tags/article_em.htm.  Back to cited text no. 11
    
12.
Baron J, Levine N. Acanthosis nigricans. eMedicine; 2006. Available at: www.healthcaremagic.com.  Back to cited text no. 12
    
13.
Thappa DM. Skin tags as markers of diabetes mellitus: an epidemiological study in India. J Dermatol 1995; 22 :729-731.  Back to cited text no. 13
    
14.
Demir S, Demir Y. Acrochondrons and impaired carbohydrate metabolism. Acta Diabetol 2002; 39 :57-59.  Back to cited text no. 14
    
15.
Barbato MT, Cariado PR, daSilva AK, Guerine MB, desa NB. Association of acanthosis nigricans and skin tags with insulin resistance. An Bras Dermato.  Back to cited text no. 15
    
16.
Andrew FW, David BJ, Julie HW, Martin KC, Stephen H. Immunohistochemical identification of mast cells in formaldehyde-fixed tissue using monoclonal antibodies specific or tryptase. J Pathol 2005; 162 :119-126.  Back to cited text no. 16
    
17.
El Safoury OS, Fawzy MM, El Maadawa ZM, Mohamed DH. Quantitation of mast cells and collagen fibers in skin tags. Indian J Dermatol 2009; 54 :319-322.  Back to cited text no. 17
    
18.
Rüger B, Dunbar PR, Hasan Q, Sawada H, Kittelberger R, Greenhill N, Neale TJ. Human mast cells produce type VIII collagen in vivo. Int J Exp Pathol 1994; 7:397-404.  Back to cited text no. 18
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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