Over Expression of Psoriasin in Middle Ear Cholesteatoma Increases Inflammation, Bone Destruction, and Severity of Disease: Ultrastructural and Molecular Findings

Introduction Cholesteatoma remains a mystery as its trigger is still not known. How insidiously tympanic membrane starts to accumulate keratin and start to invade surrounding structure is still unknown. No treatment of this disease is available to stop progression except surgery.

Aim The study was performed to evaluate the role of psoriasin and proinflammatory cytokines in progression of middle ear cholesteatoma.

Methodology Study was conducted in AIIMS, New Delhi, after ethical approval. Eighteen (12 cases of cholesteatoma tissue as study group and six cases of PSRP as control taken after tympanomastoidectomy) patients were included in the study after taking written consent. Clinical aggressiveness was evaluated on table under operative microscope by evaluation of erosion of ossicles, invasion of surrounding structures, complications, if any, associated in preoperative period. Cholesteatoma cases were divided into two groups based on severity of the disease (moderate and severe). The cases of PSRP (… please add one line about and extended form of it …), describe a condition in which a part of the eardrum lies deeper within the ear than its normal position, were taken as control. The middle ear cholesteatoma tissues were processed for histopathological, ultrastructural, and immunohistochemical analyses.

Results Hematoxylin and eosin-stained tissue sections showed stratified squamous epithelium, keratinous contents, ghost squamous cells, and inflammatory cells. The psoriasin expression in cholesteatoma tissues was significantly higher as compared with posterior superior retraction pocket (PSRP). A Psoriasin expression increases with the severity of the disease. The proinflammatory cytokines (IL-6 and IL-1β) were also upregulated along with VEGF and MMP-9 in cholesteatoma cases compared with control and the expression increased with disease severity. TEM images of ultra-thin sections of the tissues showed strips of stratified squamous epithelium layer along with inflammatory and apoptotic cells. A very unique ultrastructural feature of bacterial localization within the membrane pocket was seen, which gave direct evidence of bacterial infection in the middle ear cholesteatoma.

Acknowledgment Authors are thankful to the Electron Microscope Facility for providing an opportunity to conduct ultrastructural analysis, and AIIMS, New Delhi for providing financial (Intramural Research Funding) and all other supports.