Discussion

The skin of the tympanic membrane and external auditory canal, unlike the other parts of the surface of the body, which undergo constant frictional force, does not undergo desquamation. Epithelial migration is a unique ‘modus operandi’ that functions to prevent the excessive stratum corneum from piling up within the tympanic membrane and external auditory canal. Epithelial migration is the ability of surface layers of the tympanic membrane and external auditory canal epithelium to migrate. Apart from the human tympanic membrane, myriad studies on animals have revealed that animals possess a similar unique property of epithelial migration. The distinctive characteristic of epithelial migration is attributed to the distribution of F-actin microfilament bundles in the basal layer of the tympanic membrane. Yet, the extraordinary migratory properties of the tympanic membrane and auditory canal were disregarded until skin grafting of the tympanic membrane and mastoid cavities gained popularity. The initial utilisation of non-migratory post-auricular skin led to a serious consequence: the continual accumulation of keratin and debris, causing iatrogenic cholesteatoma.

Aural epithelial migration can be characterised on the basis of the two modes of cellular mechanism: passive and active. During the passive mechanism, cells are passively displaced following the pressure elicited by the adjacent cells, which results from the generation of new cells by mitosis. The active mechanism is based on the intrinsic locomotor capability possessed by individual cells via the action of the contractile proteins. Epithelial migration of the tympanic membrane has been postulated to be secondary to the passive mechanism,^{Reference Youngs, Hawke, Ekem and Stratis19} although some authors have proposed epithelial migration to occur secondary to the active mechanism.^{Reference Youngs and Hawke20} On the other hand, epithelial migration in the external auditory canal has been associated with an active mechanism whereby migration takes place in the deeper layers of the epithelium.^{Reference Youngs, Hawke, Ekem and Stratis19}

It is noteworthy that aural epithelial migration can be affected by myriad pathological conditions, such as otitis externa, trauma, cholesteatoma and keratosis obturans, as well as the ageing process. Inflammatory processes may affect the distinct arrangement of F-actin microfilament bundles residing in the basal layer, resulting in disrupted or delayed epithelial migration. Similarly, disruption of the blood supply resulting from various pathological conditions affects the rate of epithelial migration.^{Reference Makino and Amatsu10}

The original study on epithelial migration of the tympanic membrane was pioneered in 1936 by Stinson, who undertook an incidental observation of the migration of a piece of reed, which was initially embedded in the tympanic membrane and slowly carried out from the eardrum to the posterior auditory canal and finally to the exterior.^{Reference Stinson4} Stinson, armed with this revelation, had a breakthrough by observing the migration of spots of Indian ink in various tympanic membranes. Five laws of ‘epithelial escalation’ were expounded: (1) the epidermis migrates on its natural plane from the anterior to the posterior margin of the membrane and along the canal wall to the exterior; (2) the epidermis over the pars flaccida fans out over the canal wall; (3) the epithelium over the short process proliferates in whorls to the superior part of the canal; (4) the progress is most rapid in the inferior posterior quadrant; and (5) the epithelium does not proliferate from the canal to the drumhead. Magnoni postulated that the epithelial migration movement is radial and disagreed with Stinson's finding.^{Reference Magnoni21} Similarly, Magnoni discovered that the epithelium does not migrate from the auditory canal to the tympanic membrane.^{Reference Magnoni21}

Litton estimated the rate of epithelial migration to be 0.05 mm per day and stated that a dot placed at the umbo migrates radially outward.^{Reference Litton22} Alberti, on the other hand, estimated a rate of 0.07 mm per day and observed centrifugal migration in a centrally perforated tympanic membrane.^{Reference Alberti5} In parallel to this, both Litton and Alberti found a difference in the rate of epithelial migration, and the rate was proportional to the thickness of the epithelial layer. Additionally, the rate of epithelial migration was reported to reduce with increasing distance from the umbo.^{Reference Deong, Narayanan and Raman14} Alberti discovered the umbo to be the centre of epithelial migration based on a study performed by placing ink dots on the tympanic membrane.^{Reference Alberti5} It is noteworthy that two migratory patterns were described: a radial pattern (80 per cent) and a straight pattern (20 per cent).^{Reference Alberti5}

Interestingly, Link, in 1952, found that ink dots placed on the tympanic membrane move in the same direction as the vascular channels,^{Reference Link23} and postulated that the lymph movement propelled the epithelium outward. This was followed by a study by Makino and Amatsu, who investigated epithelial migration on the tympanic membrane and found the blood vessels that supply the epidermal layer of the tympanic membrane to be responsible for its epithelial migration as well as its metabolism.^{Reference Makino and Amatsu10}

From this review, we found that the mean rate of epithelial migration in the healthy tympanic membrane is 94.51 μm per day, whereas in the pathological tympanic membrane the rate of epithelial migration reduces to 78.09 μm per day. The slower rate of epithelial migration in the pathological tympanic membrane can be explained by poor blood supply, which leads to slower metabolism and a concurrently sluggish epithelial migration rate.^{Reference Makino and Amatsu10}

As for the epithelial migration rate in the external auditory canal, a mean rate of 110.22 μm per day was observed in the healthy ear canal, and a faster rate was seen in the pathological ear canal, with a mean rate of 123.6 μm per day. Interestingly, most patients from the pathological external auditory canal group had received prior radiotherapy; high-dose radiation led to a robust differential squamous cell epithelial growth, thus increasing the rate of epithelial migration in the external auditory canal.^{Reference Santhi, Prepageran, Tang and Raman18} The rate of epithelial migration was noted to be reduced with advancing age.^{Reference Deong, Narayanan and Raman14} A faster rate of epithelial migration was observed amongst children,^{Reference O'Donoghue9} which could be secondary to the vast blood supply of the tympanic membrane.

Numerous patterns of epithelial migration have been described by various authors. Classically, the anterior-inferior direction of epithelial migration was associated with adults^{Reference Alberti5} and the posterior-superior direction with children.^{Reference O'Donoghue9} The most common pattern of epithelial migration in this review is the posterior-superior direction, found in the healthy tympanic membrane (66.7 per cent), followed by the anterior-inferior^{Reference Makino and Amatsu10} and superior patterns of epithelial migration.^{Reference Moriarty, Johnson and Patel12} As for the pattern of epithelial migration direction in the pathological tympanic membrane, the posterior-superior direction is the most common pattern (50 per cent), followed by the posterior-inferior (25 per cent)^{Reference Santhi, Prepageran, Tang and Raman18} and inferior (25 per cent) patterns.^{Reference Makino and Amatsu10} The linear pattern was the most common pattern observed in the healthy external auditory canal (66.7 per cent).^{Reference Revadi, Prepageran, Raman and Sharizal17,Reference Santhi, Prepageran, Tang and Raman18} In the pathological external auditory canal, despite the linear direction being seen in both studies,^{Reference Revadi, Prepageran, Raman and Sharizal17,Reference Santhi, Prepageran, Tang and Raman18} Santhi et al.^{Reference Santhi, Prepageran, Tang and Raman18} reported superior and whorled patterns, in addition to the linear direction, in their group of patients,^{Reference Santhi, Prepageran, Tang and Raman18} and an inferior direction was noted by Makino and Amatsu.^{Reference Makino and Amatsu10} In the post-mastoidectomy group, the patterns of epithelial migration in the cavity were inferior-lateral^{Reference Ong, Narayanan, Godbole and Raman15} and centrifugal.^{Reference Bonding and Charabi13}

The fastest epithelial migration was observed in the external auditory canal, with a mean of 144.75 μm per day amongst irradiated nasopharyngeal carcinoma patients.^{Reference Santhi, Prepageran, Tang and Raman18} A post-radiation increase in squamous cell differentiation in the external auditory canal contributed to an increased rate of epithelial migration amongst these patients. Surprisingly, the rate of epithelial migration in the tympanic membrane of the post-radiation group was found to be low, which was suggested to be secondary to poor blood supply in the post-radiated tympanic membrane.^{Reference Santhi, Prepageran, Tang and Raman18} We postulate that the varying rate of epithelial migration between external auditory canal and tympanic membrane could be caused by a variation of radiation-induced toxicity between the tympanic membrane and the external auditory canal.

In our review, the slowest epithelial migration rate was seen in the post-mastoidectomy cavity, at 20 μm per day.^{Reference Bonding and Charabi13} However, Bonding and Charabi highlighted that large inter-subject variations were found in their study.^{Reference Bonding and Charabi13} The self-cleansing property is especially pertinent in the post-mastoidectomy group. The pattern of epithelial migration in the post-mastoidectomy cavities is not uniform because of the randomly organised blood vessels of the epithelial lining. Ong et al. found an epithelial migration rate of 0.10 mm per day in their post-mastoidectomy cavities, which is faster than the average migration rate in healthy ears.^{Reference Ong, Narayanan, Godbole and Raman15} Accumulation of wax could be attributed to a varying epithelial migration rate and patterns in other parts of cavities that do not move outward. Additionally, the pattern and rate of epithelial migration in post-mastoidectomy cavities will differ between cavities obliterated with a muscle flap and those without obliteration. Bonding and Charabi concluded that the accumulation of debris is related to the surgical technique used and the contour of the cavity.^{Reference Bonding and Charabi13} Mastoidectomy cavities habitually regain their self-cleansing property once epithelial migration is re-established. As for the size of the cavity, Bonding and Charabi reported that normal epithelial migration is established regardless of the cavity size.^{Reference Bonding and Charabi13}

Failure or abnormality of epithelial migration has been associated with numerous aural pathologies, including otitis externa, keratosis obturans, cholesteatomas and retraction pockets. There are various explanations for the variation in epithelial migration rates in different conditions. In keratosis obturans, chronic inflammation within the subepithelial tissue causes hyperplasia of the epithelium, resulting in the build-up of squamous material in the auditory canal, hindering the epithelial migration.^{Reference Persaud, Hajioff, Thevasagayam, Wareing and Wright24} Parallel to that, a deficiency in the unidentified enzyme responsible for the separation of the superficial layers of keratin and damage to the migratory basal epithelial cells has been linked to a delay in the rate of epithelial migration. The ageing epithelium has been postulated to lose its ability to migrate. Additionally, hypoxic conditions resulting from the poor blood supply to meatal skin also leads to a slower epithelial migration rate.

Meanwhile, an atelectatic retraction pocket of the tympanic membrane has been regarded as unstable because of its dynamic epithelial migration characteristics.^{Reference Tang, Narayanan, Raman and Sharizhal16} Interestingly, retraction of the tympanic membrane fluctuates during sleep over weeks and months. Nonetheless, Tang et al. found no difference in epithelial migration rate between the atelectatic ear and contralateral healthy tympanic membrane in the same patient.^{Reference Tang, Narayanan, Raman and Sharizhal16}