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An Official Publication of the Indian Association of Oral and Maxillofacial Pathologists

ORIGINAL RESEARCH Table of Contents   
Year : 2007  |  Volume : 11  |  Issue : 1  |  Page : 18-22

Mast cells are increased in leukoplakia, oral submucous fibrosis, oral lichen planus and oral squamous cell carcinoma

1 Department of Oral Pathology and Microbiology, KLESís Institute of Dental Sciences, Nehru Nagar, Belgaum - 590 010, India
2 Department of Oral Pathology and Microbiology, Maratha Mandalís Dental College, Hospital and Research Center, Near KSRP Ground, RS No 47A / 2, Bauxite Road, Belgaum - 590 010, India

Correspondence Address:
Madhuri R Ankle
H.No. 1116, Anantshayan Galli, Near Tilak Chowk, Belgaum - 590 002
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-029X.33959

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Introduction: Oral leukoplakia, submucous fibrosis (OSMF), oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC) are the commonly occurring oral diseases, with characteristic clinical and histological features. These diseases at some stage are associated with chronic inflammation in adjacent connective tissue. Mast cells are the local residents of the connective tissue, and are said to be pro-inflammatory, immunoamplifying in action and producing mitogenic cytokines. These functions of mast cells may play a significant role in the pathogenesis of other oral diseases.
Aims: This study was done to histologically evaluate the number of mast cells in tissue sections of oral leukoplakia, submucous fibrosis, lichen planus and squamous cell carcinoma.
Materials and Methods: Five cases each of normal oral mucosa, oral leukoplakia, oral submucous fibrosis, lichen planus and squamous cell carcinoma were studied for mast cell number using 1% Toluidine blue.
Results: Increase in mast cell number were seen in all the four above mentioned oral diseases, with the highest mast cell count obtained in oral lichen planus. The mast cell number/sq.mm in oral leukoplakia, submucous fibrosis, lichen planus, squamous cell carcinoma were; 59.50, 48.25, 59.75 and 56.75 respectively.
Conclusion: As compared to normal oral mucosa, increase in the mast cell number was noted in all the four conditions. Mast cell hyperplasia in oral leukoplakia, OSMF, OLP, OSCC suggests their probable role in the pathogenesis of these diseases.

Keywords: Mast cells, oral leukoplakia, oral submucous fibrosis, oral lichen planus, oral squamous cell carcinoma

How to cite this article:
Ankle MR, Kale AD, Nayak R. Mast cells are increased in leukoplakia, oral submucous fibrosis, oral lichen planus and oral squamous cell carcinoma. J Oral Maxillofac Pathol 2007;11:18-22

How to cite this URL:
Ankle MR, Kale AD, Nayak R. Mast cells are increased in leukoplakia, oral submucous fibrosis, oral lichen planus and oral squamous cell carcinoma. J Oral Maxillofac Pathol [serial online] 2007 [cited 2022 Dec 9];11:18-22. Available from: https://www.jomfp.in/text.asp?2007/11/1/18/33959

   Introduction Top

Paul Ehrlich in 1877 discovered a granular cell of loose connective tissue and named it as "Mastzellan"- a well fed cell. [1] Studies on mast cells in normal and various pathologic conditions have shown them to be complex, well-engineered, multifunctional cell playing a central role in acquired and innate immunity.

Mast cells have a diameter of about 12 microns; they are heterogeneous in shape; round, oval or spindle-shaped and are packed with 50-100 granules. They have a life span of weeks to months. [2],[3] Mast cells release preformed secretory mediators like histamine, heparin, tryptase; lipid derived mediators like leukotrienes B4 (LTB4), LTC4, LTD4 and LTE4; pro-inflammatory cytokines like TNF-alpha, IL-1; mitogenic cytokines: IL-3, IL-5 and immunomodulatory cytokines like IL-4, IL-10. [4] Therefore mast cells have been studied in various conditions like wound healing, chronic inflammation, keloid, pulmonary fibrosis and angiogenesis. [1],[5]

The commonly occurring oral diseases like oral leukoplakia, submucous fibrosis, lichen planus, squamous cell carcinoma have chronic inflammation in common. In addition, autoimmunity is strongly associated with OLP and angiogenesis is associated with the proliferation of carcinoma. Therefore the role of mast cells was evaluated in these four diseases.

0The present study was carried out to estimate and compare mast cell number in oral leukoplakia, OSMF, OLP and OSCC.

   Materials and Methods Top

Five cases each of oral leukoplakia, OSMF, OLP and OSCC were retrieved from the archives of the Department of Oral Pathology and Microbiology, K.L.E.S's Institute of Dental Sciences, Belgaum. Biopsies of normal oral mucosa were obtained from five adult patients undergoing extraction for orthodontic treatment. Two sections of five microns thickness each were cut; one section was stained with Hematoxylin and Eosin; the other was stained with 1% toluidine blue for mast cells. Toluidine blue stains the mast cell granules metachromatically due to its reaction with sulphated mucopolysaccharides. [6]

Mast cells were counted using an oculometer grid in 30 grid fields under a magnification of x400 in a stepladder fashion. Mast cell count was expressed as the number of mast cells per grid field and the number of mast cells per square millimeter.

Criteria to identify the mast cells

Mast cells are spindle to oval-shaped and have the same staining characteristics as the fibroblasts with hematoxylin and eosin staining. Therefore, they are difficult to differentiate from fibroblasts. Selective stain of 1% toluidine blue is used for mast cells. Mast cell granules are purplish red and the nuclei of mast cells appear sky blue in colour.

   Results Top

The results of the study showed a maximum mast cell count in oral lichen planus of 59.75/sq.mm, in leukoplakia of 59.50/sq.mm. In OSMF and OSCC the mast cell count were 48.25/sq.mm and 56.75/sq.mm respectively as compared to 25.50/sq.mm of mast cell count in normal oral mucosa [Table - 1].

   Discussion Top

Mast cells are the local residents of the connective tissue. The role played by the mast cell mediators and their interaction with other inflammatory cells has been intriguing.

Mast cells have been studied in normal gingiva, chronic inflammatory gingivitis, desquamative gingivitis, lichen planus, OSMF and oral cancer. [5],[7],[8],[9] Mast cells exhibit phenotypic plasticity. [10] There is variation in the mast cell mediators with the change in the microenvironment, which makes the study of this cell in various diseases interesting.

Therefore, the present study was done to evaluate the mast cell number in five cases each of normal oral mucosa, oral leukoplakia, submucous fibrosis, lichen planus and squamous cell carcinoma. 1% toluidine blue was used as a selective stain for mast cells. Mast cell count was done using an oculometer grid in 30 grid fields.

The results obtained showed an increased mast cell number in oral leukoplakia. The observations by Biviji et al .[7] showed a mean increase in the number of mast cells /unit microscopic field in oral leukoplakia compared to normal oral mucosa. The authors concluded that the biologically and pharmacologically active agents in the mast cells might contribute to inflammatory reaction seen in leukoplakia. These stimulated mast cells may release interleukin-1, which causes increased epithelial proliferation [11] that is seen in leukoplakia. Histamine may cause increased mucosal permeability, which could facilitate increased access for the antigen to the connective tissue [4] [Table - 2], [Figure - 1].

Five cases of oral submucous fibrosis were considered based on the clinical and histopathological features. [12],[13] Mast cell count of 48.25/sq.mm was noted. Studies on mast cells in OSMF were done by Bhatt and Dholakia. [9] They noted abundant mast cells in Grade I and Grade II of OSMF i.e., 4.5 and 4.9 respectively as compared to 1.02 in normal buccal mucosa. The authors attributed vesicle formation and symptoms of itching sensation to histamine released from the mast cells and suggested the concept of mast cell histamine chain. The mast cell hyperplasia could probably attribute to some of the signs and symptoms of OSMF. Mast cell mediators like prostaglandins and leukotrienes are potent secretogouge for the serous and mucous cells. This could attribute to the increased salivation seen in OSMF. [4]

The effect of chemical mediators can explain the histopathological changes seen in OSMF. Histamine could probably attribute to submucosal edema seen in early stages of oral submucous fibrosis. Due to increased vasopermeability eosinophilic chemotactic factor (ECF) is released from the mast cells. [4] This could probably attribute to the eosinophils that are sometimes a part of inflammatory cell infiltrate seen in the early stages of oral submucous fibrosis. Interleukin-5 causes increased proliferation and differentiation of eosinophils. [4] Interleukin-1 from the mast cells could cause increased fibroblastic response and mast cell derived tryptase causes increased production of type-I collagen and fibronectin [14] thereby attributing to the increased fibrosis [Table - 3], [Figure - 2].

Maximum numbers of mast cells were seen in oral lichen planus (59.75/sq.mm) as compared to 25.50/sq.mm seen in normal oral mucosa. These results are similar to the studies carried out by Xijing et al .[8] who observed a mast cell count of 151.5/sq.mm in lichen planus. They considered mast cells as the offenders in basement membrane destruction. TNF-alpha released from the mast cells causes increased synthesis of matrix metalloproteinases like collagenase, which cause the basement membrane destruction. TNF-alpha also causes increased expression of adhesion molecules like E-selectin, ICAM. This could probably cause increased leukocytic migration. Histamine causes vasopermeability leading to submucosal edema and antigen induced T-cell proliferation. This could attribute for the characteristic trafficking of lymphocytes. The cytotoxic lymphocytes thus recruited by the mast cells cause the basal cell degeneration, keratinocyte apoptosis and thus the characteristic Civette bodies seen in oral lichen planus [8] [Table - 4],[Figure - 3].

The mean mast cell count in oral squamous cell carcinoma in the present study was 56.75/sq.mm. Rooney et al .[5] suggested that heparin from the mast cells cause vasoproliferation and increases the half-life of basic fibroblastic growth factor (FGF), which is a potent angiogenic substance, thereby promoting tumour angiogenesis and facilitating local tumour invasion. Interleukin-1 leads to epithelial proliferation [5] [Table - 5], [Figure - 4].

In this study, mast cell hyperplasia was observed in all the oral diseases considered. The mediators in mast cells are known to vary with the variation in microenvironment in various diseases. Thus it is probable that mast cells play a key role in mediating the cross talks between the external antigenic agent and the local immunologic factors.

The study needs to be carried out in greater number of cases. The tissue level and the type of mediators should be analysed in the various diseases considered.

   References Top

1.Riley JF: Mast Cells, (1959 Edition), E and S Livingston, Edinburgh London.  Back to cited text no. 1    
2.The origins, morphologies and functions (Including immunological functions) of the cells of loose connective tissue. In: Ham WA, Cormack HD (1979): Histology, (8 th Ed): J.B.Lippincott Company, Philadelphia. Pages: 225-59.  Back to cited text no. 2    
3.Lawrence B (2000): Haemolymphoid system. In: Lawrence B, Martin BM, Patricia C, Mary D, Juhan D, Mark F (Eds.), Gray's Anatomy (38 th Ed), Churchill Livingston Harcourt Publishers Ltd, Edinburg. Pages: 1399-451.  Back to cited text no. 3    
4.McNeil PH, Frank Austen K. (1995): Chapter 13, The biology of mast cells. In Frank MM, Austen KF, Claman HN, Unanue ER (Eds). (5 th Ed), Samter's Immunologic Diseases, Little Brown and Company, Boston. Pages: 185-204.  Back to cited text no. 4    
5.Rooney P, Kumar P, Ponting J, Kumar S (1997): Chapter 13, The role of collagen and proteoglycans. In: Bicknell R, Lewis CE, Ferrara N (Eds) (1 st Ed), Tumour Angiogenesis, Oxford University Press, New York. Pages: 141-51.  Back to cited text no. 5    
6.Cytoplasmic granules organelles and special tissues. In: Bancroft JD, Steven Alan, eds. (1996), Theory and Practice of Histological Techniques (4 th Ed), Churchill Livingston, London. Pages: 383-90.  Back to cited text no. 6    
7.Biviji AT (1973): Mast cells in normal and leukoplakia buccal mucosa, J Indian Dent Assoc, 45:189-91.  Back to cited text no. 7    
8.Zhou XJ, Sugerman PB, Svage NW, Walsh LJ, Seymour GJ (2002): Intra epithelial CD8+ T- cells and basement membrane disruption, J Oral Pathol Med, 31:23-7.  Back to cited text no. 8    
9.Bhatt AP, Dholakia HM (1977): Mast cell density in oral submucous fibrosis, J Indian Dent Assoc, 49:187-91.  Back to cited text no. 9    
10.Flier JS, Underhill LH, Galli SJ (1993): New concepts about mast cells, N Engl J Med, 328:257-65.  Back to cited text no. 10    
11.Oppenheim JJ, Francis W, Rus WF, Faltynek C (1994): Chapter 9, Cytokines. In: Stites DP, Terr AI, Parslow TG (8 th Ed), Basic and Clinical Immunology, Appleton and Lange Publication, London. Pages: 105-21.  Back to cited text no. 11    
12.Chaturvedi VN, Sharma AK, Marathe NG (1990): Intraoral injection of hydrocortisone and hyaluronidase in oral submucous fibrosis, Indian Prac, 575-80.  Back to cited text no. 12    
13.Pindborg JJ, Sirsat SM (1966): Oral Submucous Fibrosis Oral Surg Oral Med Oral Pathol, 22(6):764-79.  Back to cited text no. 13    
14.Abe M, Kurosawa M, Ishikawa O, Miyachi Y, Kido H (1998): Mast cell tryptase stimulates both human dermal fibroblast proliferation and type -I collagen production, Clin Exp Allergy, 28:1509-17.  Back to cited text no. 14    


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

  [Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5]

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