A Role for Mast Cell-Mediated Antibodies in the Formation of Cholesteatoma and Cholesteatoma-Induced Bone Erosion

Abstract

The study aimed to evaluate the effects and relationships between mast cells in the matrix, mast cell enzymes tryptase and chymase, epithelial proliferation, microvascular density, and bone destruction in cholesteatoma. Thirty-five biopsies diagnosed with cholesteatoma and seven healthy skin tissues taken from the retro-auricular region for control were evaluated. Immunohistochemical studies were performed with CD117, CD34, Ki-67, chymase, and tryptase antibodies, in a single session for all cases and the control group. The relationship between erosion size and antibody load was determined. The mean cholesteatoma epithelium Ki-67 was higher than the control group (p < 0.001). CD117-positive mast cells, chymase-positive mast cells, tryptase-positive mast cells, and microvessel density were significantly higher in the cholesteatoma matrix compared to the control group (p < 0.002, p < 0.001, p < 0.005). In the group with bone erosion scores of two and above, immunohistochemical markers tended to be higher. A positive correlation was found between CD117 and chymase, tryptase, and microvessel density; between tryptase, chymase, and microvessel density; and between chymase and microvessel density. CD117-positive mast cells and chymase-positive mast cells stimulate angiogenesis, increase the epithelium's proliferative capacity in the cholesteatoma matrix, and form cholesteatoma. The increased proliferation of cholesteatoma epithelium and increased vascular density in the matrix exacerbate bone erosion.

Keywords: CD117; CD34; Ki67; bone erosion; cholesteatoma; chymase; tryptase.

Figure 1

Kİ-67, CD117, tryptase, chymase, and CD34 distribution graph of the patient and control groups.

Figure 2

Compared to control tissue and cholesteatoma, there is an increased order in the cholesteatoma epithelium (black arrow), increased inflammatory cells in the stroma (red arrow), increased vascularity (yellow arrow), and a significant increase in connective tissue ((a): control tissue, (b): cholesteatoma tissue) (HEX200).

Figure 3

There are rare positive nuclear reactions observed only in the epithelium of the control tissue only at the basal layer when Ki-67 (black arrow) is immunohistochemically stained. In contrast, the cholesteatoma epithelium exhibits an intense nuclear reaction both at the basal layer and at the epithelium’s higher levels (red arrows) ((a): control tissues, (b): cholesteatoma tissues) (×200).

Figure 4

In CD117 immunohistochemical staining, a minimal number of positive mast cells are found in the stroma in the control tissue ((a), black arrows), whereas, in the cholesteatoma matrix ((b), red arrows), there is an increase in easy-to-identify positive mast cells (×200).

Figure 5

An increase in the number of small-diameter microvessels in the matrix of the cholesteatoma ((b), red arrows), when compared to the control tissue ((a), black arrow) (×200).

Figure 6

In chymase immunohistochemical staining, chymase-positive mast cells are sparsely positive in control tissue ((a), black arrow) and tend to aggregate in the cholesteatoma matrix ((b), red arrows) (×200).

Figure 7

As seen in immunohistochemical staining with tryptase, mast cells are less prominent in the control tissue ((a), black arrow) and more prominent in the cholesteatoma matrix ((b), red arrows) (×200).