Cholesteatoma of the middle ear is one of the most complex topics in otology; it is a chronic otitis media with the proliferation of “a wrong skin in the wrong place”.
In this chapter a comprehensive overview of this pathology with the most recent advances relative to its pathogenesis is discussed. Pertinent light- and electron microscopic histopathology along with its related molecular biology and the potential genetic factors are reported. Bone resorption mechanisms in cholesteatoma are explained. Cholesteatoma is described according to its site of origin and its growth pathways. The accurate clinical assessment is detailed.
The staging system of cholesteatoma is represented according to the recent EAONO/JOS Classification. The major contribution of imaging with CT scan is illustrated; especially to demonstrate cholesteatoma extension to the sites of difficult access (S1: anterior epitympanum, S2: sinus tympani). Also the MRI input in cholesteatoma is considered.
Cholesteatoma management being until now exclusively surgical, the main procedures are presented in detail with their correspondent advantages and disadvantages. Although the canal wall up technic responds best to the main objectives of nowadays strategies, special attention is reserved to pediatric cholesteatoma.
Follow up of cholesteatoma is a life time responsibility, so relative algorithms are proposed. Follow up by advanced MRI technics becoming more and more reliable, CWU is nowadays the procedure of choice for cholesteatoma surgery.
Cholesteatoma of the middle ear is one of the most complex topics in otology; it has stimulated much research and debates worldwide but still suffers of a lack of consensus regarding most of its aspects.
In this chapter we provide a comprehensive overview of this pathology and the contemporary advances regarding its histopathology, molecular biology, its best evaluation and most adequate management.
The annual incidence of cholesteatoma is reported to be 9.2 per 100,000 in adults and 3 per 100,000 in children with an overall male predominance of 1.4/1 . The incidence of cholesteatoma varies worldwide. The main factors that contribute to the development and frequency of cholesteatomas are: geography, genetics, sex, age, the environment, and the socio-economic status.
There is a high prevalence in Caucasian populations and it is rare in the Afro-descendants .
The incidence of middle ear cholesteatoma peaks in the second and third decade of life.
The mean age in children with cholesteatomatous otitis media is 10 years; the mean age of children with congenital cholesteatoma is 6 years .
8.3 Types of Cholesteatoma
There are two main types of cholesteatoma based on the disease pathogenesis: congenital and acquired .
8.3.1 Congenital Cholesteatoma
Prior bouts of otitis media do not exclude the congenital nature of the disease. Levenson found that the mean age at presentation was 4.5 years with a male preponderance of 3:1.
Two typical sites of origin are described: The most frequent site (two-third of cases) is in the anterosuperior quadrant in the proximity of the Eustachian tube opening, and the second most frequent in the posterosuperior quadrant close to the incudostapedial joint. In advanced cases, congenital cholesteatoma may involve more than one quadrant of the middle ear (Fig. 8.4).
8.3.2 Acquired Cholesteatoma
Acquired cholesteatoma is a special form of chronic otitis media in which keratinizing squamous epithelium grows from the tympanic membrane or/and the auditory canal skin into the middle ear mucosa. Acquired cholesteatomas of the middle ear are further divided into primary acquired and secondary acquired forms (Shambaugh).
126.96.36.199 Primary Acquired cholesteatoma
The predominant form of acquired cholesteatoma in children develops in 80% from retraction pockets of the pars tensa (especially the posterior sub-ligamentary pars tensa) whereas in adults, this form develops mainly in the pars flaccida (or Shrapnell’s membrane).
188.8.131.52 Secondary Acquired Cholesteatoma
8.4 Histopathology of Cholesteatoma
8.4.2 Light Microscopy
The “amorphic center”, formed of accumulated desquamated epithelium, enveloped by “the matrix”.
The matrix is a stimulated proliferative skin with hyperkeratosis desquamation at the surface, hyperplasia of the basal cell layer and deep papillary growing into the subepithelial tissue.
The perimatrix is formed of granulation tissue that is the site of an important inflammatory process. The thickness of the perimatrix and the intensity of its inflammatory process determine the aggressiveness of the cholesteatoma.
8.4.3 Electron Microscopy
The stratum corneum where the cells become dead shells filled with keratin fibers that are electron dense.
The stratum granulosum characterized by keratohyalin grains aligned parallel to the surface.
The stratum spinosum (due to desmosomes attachments) where maturation of the keratinocytes is accompanied by two characteristics phenomena: flattening of the cells and grouping of tonofilaments;
The basal stratum : formed by a unicellular layer, each cell tightly united to the others by desmosomes (tight junctions).
In contrast to normal epidermis, inflammatory cells, Langerhans’ cells, and Merkel cells are identified in the stratum spinosum layer of the cholesteatoma matrix in a higher amount compared to the normal epidermis where they never exceed more than 3%. Electron microscopy appearance of Langerhans cells (discovered by Michael Birbeck in 1961) in the cholesteatoma matrix showed characteristic multilobulated nuclei and long cytoplasmic extensions with dendritic expansions.
8.5 Pathogenesis of Cholesteatoma
8.5.1 Congenital Cholesteatoma
- 1.Epidermal rest theory: This theory is based on a finding of cell rests of nonkeratinizing squamous epithelial cells, localized in the lateral wall of the Eustachian tube, close to the tympanic ring. These rests have the potential to become a congenital cholesteatoma. This assumption is supported by reports on an increasing number of mesotympanic cholesteatomas originating from the anterosuperior quadrant of the middle ear (Teed-Michael’s) . Several arguments and findings published in the literature indicate that the primary origin of the congenital cholesteatoma is from foetal epidermal rests inside the tympanic cavity:
Histological documentation of congenital cholesteatoma with a squamous epithelial rest in neonatal temporal bone .
Conversion of viable squamous epithelial cells of amniotic fluid debris into cholesteatoma .
Congenital cholesteatoma is due to a failure of the inhibitory function of the tympanic ring: ectodermal tissue from the external acoustic meatus may migrate into the middle ear cleft during embryogenesis .
- 2.Inclusion Theory: Other authors favor even a way of migration from cells coming initially from the external ear through non evident injuries of the tympanic membrane .
Inflammatory injury to an intact tympanic membrane results in microperforations in the basal layer that enable the invasion of the squamous epithelium by proliferating epithelial cones through a macroscopically intact but microscopically injured tympanic membrane.
“Acquired” inclusion theory, where small residual tears in the tympanic membrane lead to the formation of an inclusion cholesteatoma after healing (Toss) .
8.5.2 Acquired Cholesteatoma
Cholesteatoma is a proliferative epithelium with hyperkeratosis, desquamation at the surface, hyperplasia of the basal keratinocytes and deep papillary process growing beneath the neighboring intact mucosa (Fig. 8.21). Between the squamous pluri- stratified epithelium of the cholesteatoma and the pseudostratified epithelium of the neighboring mucosa, no interjonction is found; there is rather a confrontation line defining a zone of conflicting tissues (Fig. 8.21). This conflict favors a continuous growth and expanding of the epidermal tissue coming from the external auditory canal into the middle ear cavity.
Thus the pathogenic epidermal theory of cholesteatoma origin as from an epidermal layer of the auditory canal bottom into the middle ear—already mentioned in 1888 by Habermann )—is definitively confirmed in the 1970s.
Whatever the epidermal proliferation mode would be - tympanic retraction [26, 27], lateral epithelial migration , papillary budding —the cholesteatoma corresponds always to Gray’s definition : cholesteatoma is “skin in the wrong place”.
The common factor for all theories of acquired cholesteatomas is that the keratinizing squamous epithelium has grown beyond its normal limits.
Invagination theory (retraction pocket theory),
Basal cell hyperplasia (papillary ingrowth theory).
184.108.40.206 The Invagination Theory
Recently, the hypothesis of mucosal coupling, thought to be behind the invagination phenomenon in a retraction pocket, is presumed to be one of the main factors behind the arrest of clearance of normal mucosa secretions; consequently it enhances the progress of the retraction mechanism as a pulling effect generated by the mucosal coupling .
220.127.116.11 The Migration Theory
Thus the migration of squamous epithelium of the external ear through a tympanic membrane perforation into the middle ear and the excessive production of keratin lead to a cholesteatoma formation.
18.104.22.168 The Squamous Metaplasia Theory
22.214.171.124 The Basal Cell Hyperplasia (Papillary) Theory
The basal cell hyperplasia theory postulates that keratin-filled microcysts, buds, or pseudopods formed in the basal layer of the pars flaccida epithelium, invade the sub-epithelial tissue, fuse together, resulting in the formation of cholesteatoma of Prussak’s space [36, 37, 38].
126.96.36.199 Recent Advances in the Pathogenesis of Cholesteatoma
Current concepts in the pathogenesis of cholesteatoma postulate that cholesteatoma may be the result of a “defective wound healing process” where the inflammatory and proliferative stages predominate, but the maturation end stage of the wound healing process would never be achieved  (see below). In addition, the pathogenesis of cholesteatoma does not depend only on the middle ear pathological conditions but, also very probably, on the immunological status of the external auditory bottom skin cells with its specific immune cell potential leading to persistent inflammation process via continuous overproduction of cytokine mediators.
Actually the pathogenesis of the acquired cholesteatoma is a “complex and hybrid process” involving multiple concepts and different findings thanks to the molecular biology studies (see below); thus no single theory alone can fully explain the uncoordinated hyper proliferation, invasion, migration, altered differentiation, aggressiveness, and recidivism of this pathology .
8.6 Molecular Biology of Cholesteatoma
The induction of a cholesteatoma formation process seems to be related to both internal molecular dysregulation and some external stimuli in the form of pro-inflammatory cytokines, growth factors and/or bacterial toxins. There is an imbalance and a vicious circle of epithelial proliferation, keratinocytes differentiation and maturation, prolonged apoptosis, and disturbance of self-cleaning mechanisms. Whatever the exact molecular mechanism may be, cholesteatoma remains a chronic otitis involving both middle ear and external ear canal skin layers.
Histochemical studies lead to understand the more dynamic dimensions of the anatomopathological study of cholesteatoma, especially in regard to Langerhans’cells.
Langerhans cells seem to play a key role in the proliferative activity of the cholesteatoma, due to their positive tropism towards the keratinized squamous epithelium with its capacity for keratinization. Langerhans’ cells maintain this role because of the surrounding inflammatory reaction (induced by lymphocytic activation) and the secretion of osteolytic chemical mediators (chemical process) .
8.6.1 Immunohistochemistry of Cholesteatoma
Recent advances in immunohistochemical analysis have revealed an association between the progression of cholesteatoma and excessive host immune response to persisting inflammation in the form of paracrine and autocrine secretions [36, 39, 43, 44, 45, 46, 47, 48, 49].
8.6.2 Biochemistry of Cholesteatoma
The cholesteatoma develops beyond its normal anatomical site for a “skin”. The middle ear environment is not adequate to induce the habitual cell contact inhibition to stop the growth, therefore proliferation continues.
The inflammatory process produces a self-maintained immunological cycle through connective tissue — epithelial reactions in response to the conflict at the level of tissues and cells.
However, this theory of a wound healing defect cannot explain why many cases of persistent inflammation with granulation tissue formation do not end up with cholesteatoma formation.
8.6.3 Apoptosis and Apoptotic Activity in Cholesteatoma
The loss of balance between apoptotic and antiapoptotic markers (cell death/proliferation) - with the favorable antiapoptotic activity in cholesteatoma - favors its continuous expansion. It was found that cellular FLICE-like inhibitory protein, an antiapoptotic protein, was upregulated in cholesteatoma epithelium as compared to normal skin without significant changes in p53, (a well-known apoptotic protein) Also, the levels of galectin-3 were found to be significantly correlated with the level of apoptosis and had a protective role against apoptosis activity in recurrent cholesteatoma. Apoptosis was found in the suprabasal layers of cholesteatoma epithelium but not found in the basal layers [53, 54, 55].
A recent study showed that “let 7a microRNA” had a vital role in the inhibition of growth and invasion of cholesteatoma keratinocytes via downregulation of miR 21 expression, resulting in a double action: the suppression of proliferation and the induction of apoptotic activity . These results might pave the way for exploring non-surgical options for cholesteatoma management.
8.6.4 Biofilms and Cholesteatoma
The keratin layer of cholesteatoma is an ideal environment for biofilm development. The presence of bacterial biofilms in cholesteatoma mediates the host response in a form of chronic inflammation, proliferation, and bone resorption . The presence of antibiotic-resistant bacterial biofilms in cholesteatomas may also explain their aggressiveness.
Bacteria involving the retraction pocket produce some antigens, which will activate different cytokines and lytic enzymes. These cytokines lead to the activation and maturation of osteoclasts with the consequence of degradation of extracellular bone matrix and hyperproliferation, bone erosion and finally progression of the disease . Bacterial biofilms within cholesteatomas may elaborate lipopolysaccharide (LPS) and other bacterial endotoxins that stimulate osteoclastogenesis.
Endotoxin, a component of the bacterial wall, is considered responsible for the initiation of inflammation in the middle ear. It stimulates local macrophages to produce the tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β). Keratinocytes respond to this injury by producing many soluble mediators, including: TNF-α, IL-1β, IL-6, and IL-8, independently from the immune cells (T cells and B cells, macrophages,…) .
8.7 Genetics of Cholesteatoma
Recent studies have demonstrated a link between pathogenesis and potential genomic alterations in cholesteatoma. The upregulation and activation of epidermal growth factor receptor (EGFR) and its ligand and of transforming growth factor alpha (TGF-α) have been observed in cholesteatoma and in several tumor types [60, 61, 62]. Overexpression of EGFR and TGF-α is detected in cholesteatoma indicating that the dysregulation of these genes may be associated with the initiation and progression of cholesteatomas [63, 64]. Finally, alterations in the expression of proto-oncogenes (e.g., c-myc and c-jun) [65, 66, 67, 68, 69], upregulation of gap junction beta-2 (GJB2, also known as connexin 26) [70, 71, 72], and the downregulation of several tumor suppressor genes (e.g., p53, p27, CDH18, 19 and ID4, PAX3, LAMC2, and TRAF2B) [36, 39, 70, 73, 74] have been shown to contribute to the multifactorial pathogenesis of cholesteatoma.
8.8 Bone Resorption in Cholesteatoma
In vitro studies revealed that osteoclastic bone resorption could occur in the sites where adequate pressure was induced directly or transmitted to the tympanic cavity with or without the presence of cholesteatoma [75, 76, 77, 78].
Despite being the most rigid bone of the human body, the labyrinth can be affected by a variety of factors of bone erosion. Several factors stimulate bone resorption, such as inflammation, local pressure, and specific enzymes .
High TNF-α levels stimulate osteoclasts that induce bone resorption; also stimulate fibroblasts to secrete collagenase and prostaglandin E which are responsible of necrosis of soft tissues in the middle ear .
8.8.1 Matrix Metalloproteinases
Recent studies showed that variations in cellular production of matrix metalloproteinases (MMPs) and their specific inhibitors (TIMPs) contribute to the pathophysiology of cholesteatoma, especially in the development of bone erosion. Normally, their activity is tightly controlled, as an increase in their activation would cause a denudement of the extracellular matrix and increased invasiveness by the epithelium. In cholesteatoma, studies have indicated a clear imbalance in the regulation of MMPs, with an overall up-regulation of MMP expression and a decrease in MMP inhibitors resulting in degradation of the extracellular matrix [63, 64, 86, 87].
Collagenase is also involved in the local invasion process by aural cholesteatoma, stimulating the osteoclastic resorption by degrading the osteoid surface of the bone and thus facilitating osteoclastic activity .
In conclusion, TNF-alpha [, IL-1α, MMP 9 and tenascin, amphiregulin, MIB1, BMPs and RANKL/OPG ratio are considered to be a reliable index for bone erosion in cholesteatoma [47, 82, 88, 89, 90, 91, 92, 93].
8.9 Cholesteatoma Origin and Growth Pathways
“Pars flaccida (attic) cholesteatomas” (Fig. 8.35a) are located at the upper one-third portion of the tympanic membrane, filling the Prussak space. Initially, pars flaccida cholesteatomas are usually located lateral to the ossicles. On the basis of their extension, they are classified into posterior epitympanic cholesteatoma and anterior epitympanic cholesteatoma.
“Pars tensa (sinus) cholesteatomas ” develop most from the postero-superior part of the pars tensa and most often are localized in the facial recess and sinus tympani of the tympanic cavity and in the mastoid region (Fig. 8.35b). Pars tensa cholesteatomas are mostly located medial to the ossicular chain.
It is not possible to define the origin of an advanced lesion; hence neither of these classification subgroups is applicable.
Cholesteatoma origin and growth pathways
Site in the tympanum
(a) Attic/posterior epitympanum (40%)
More frequent in adults
(b) Pars tensa/posterior mesotympanum (30%)
Postero-sup. quadrant of pars tensa
More frequent in children
(c) Anterior epitympanum (the least frequent)
Cranially and anteriorly to the malleus head
Mostly in children
(d) Unclassified (about 30%)
Not clearly defined
Includes also two routes cholesteatoma
The growth pattern of the acquired cholesteatoma is oriented by two main factors: the site of origin of the cholesteatoma and the anatomical compartments in the middle ear cleft.
The ligaments, mucosal folds, ossicles, and walls of the middle ear separating the different compartments do not play the role of barriers but guide the growth of cholesteatoma into distinct pathways throughout the middle ear cleft.
8.9.1 Posterior Epitympanic Cholesteatoma
8.9.2 Mesotympanic Cholesteatoma
8.9.3 Anterior Epitympanic Cholesteatoma
8.9.4 Unclassified Cholesteatomas
8.10 Clinical Manifestations
Cholesteatomas often progress insidiously, until they become invasive and symptomatic. Occasionally, cholesteatoma manifests by a sudden intratemporal or intracranial complications.
A detailed otologic history should be obtained in order to elicit the early symptoms of cholesteatoma including hearing loss, otorrhea, tinnitus and vertigo. A chronic foul smelling otorrhea and a progressive hearing loss are quasi pathognomonic.
A persistent foul-smelling painless otorrhea is the hallmark of cholesteatoma patients. Unlike simple suppurative otitis media, the otorrhea is not abundant. When the cholesteatoma is infected, it is not responsive to systemic antibiotics. Topical antibiotics may help temporarily. If otorrhea persists for a long duration, polyp formation may occur.
188.8.131.52 Hearing Loss
A conductive hearing loss is a common finding in cholesteatoma, as ossicular chain erosion is common (70%) ; however, a relatively good hearing could be present even the ossicular chain is eroded, this is the result of the conductive mass effect of the cholesteatoma itself; patients should be counseled that there is a possibility of a hearing degradation following the removal of the pathology.
Evidence of sensorineural hearing loss may indicate an involvement of the labyrinth.
A destruction of the bone which overlies the otic capsule, especially the lateral semicircular canal, can trigger vertigo or a balance dysfunction.
184.108.40.206 Facial Nerve Palsy
Facial palsy may be the first sign of a cholesteatoma localized in the anterior epitympanic recess. Violation of the facial nerve bony canal by cholesteatoma rarely manifests by a facial paralysis. Facial nerve palsy with intact tympanic membrane and conductive hearing loss must orient the investigations to a cholesteatoma of the anterior epitympanic recess ethology (See Chap. 10).
Otalgia, headache, vomiting, and fever are not typical presentations of cholesteatoma; however, their occurrence indicates the possibility of impending intratemporal or intracranial complications.
Extreme caution should be taken with any polyp removal as it may be adherent to important underlying structures such as the ossicles or facial nerve.
It is of utmost importance to examine the contralateral ear and report the findings.
8.10.3 Audiological Evaluation
Pure tone audiometry with air and bone conduction, speech reception thresholds, and word recognition are the basic mandatory audiological assesments for ears with cholesteatoam and they usually reveal a conductive hearing loss with good speech discrimination in the affected ear. The degree of conductive hearing loss will vary considerably depending on the extent of the disease. A conductive deficit more than 40 dB indicates ossicular discontinuity. A drop in bone conduction (BC) level indicates sensorineural hearing loss which could be a sign of labyrinth involvement.
Audiometry results should always be correlated with the 512 Hz tuning fork exam.
8.11 CT-Imaging in Cholesteatoma
Cholesteatoma represents the main cause of typical bony erosions and/or ossicular lysis.
8.11.1 Erosion of the Scutum
8.11.2 Erosion of the Ossicles
In cases of a pars flaccida cholesteatoma, the lytic effect concerns initially the lateral border of the incudomalleolar chain (Fig. 8.46a); the incus being more vulnerable than the malleus, the malleus head is particularly resistant, but it becomes affected by the progress of the cholesteatoma along the anterior malleal ligament which is inserted on the anterior part of the malleus head (Fig. 8.46b).
In cases of a pars tensa cholesteatoma, the lytic effect involves initially the mesotympanic part of the ossicular chain, first the long process of the incus, then the head of the stapes and more rarely the handle of the malleus (Fig. 8.47).
However, lyses of the long process of the incus or even the stapes can be observed in non- cholesteatomatous inflammatory pathologies, as in pars tensa retraction pocket.
8.11.3 Erosion of the Cog
8.11.4 Erosion of the Semicircular Canals (Labyrinthine Fistula)
8.11.5 Erosion of the of Fallopian Canal
8.11.6 Erosion of the Tegmen
8.11.7 Extension of the Cholesteatoma into the Mastoid
CT becomes very indicative of an extension of the cholesteatomatous process to the mastoid, when the mastoid is filled by condensation images with irregular borders (Fig. 8.52c) or the antrum is entirely filled with condensations that have smooth rounded borders (Fig. 8.52d).
8.11.8 External Auditory Canal Lysis
8.11.9 Limitations of CT Imaging
Well aerated ME cleft spaces
High negative predictive value
Condensation images with rounded borders
Relative high diagnostic value
Diffuse condensations in ME or Mastoid: Granulation tissue? Effusion? Cholesteatoma?
8.12 MRI in Cholesteatoma
MRI offers a very specific diagnostic tool for the detection of postoperative recurrent or residual cholesteatoma: the diffusion weighted imaging. Initially obtained by Echo Planar Imaging (EPI) with 5 mm thickness, it suffered from fair spatial resolution and from susceptibility artefacts. Nowadays, Non-Echo-Planar Diffusion Weighted Imaging (Non EPI-DWI), using turbo spin-echo or multi shot turbo spin echo types of imaging with lesser slice thickness and lesser susceptibility-artefacts, became unanimously the state of the art in MR Imaging for cholesteatoma .
Due to the high keratin content of cholesteatoma, both the restricted molecular diffusion and the T2 shine-through effect produce a high signal intensity relative to brain tissue on DW images obtained with b values of 800 or 1000 s/mm2. The bright signal on b 1000 DW images is evaluated by a subjective qualitative analyses, that can be objectivated by a quantitative analyses of the apparent diffusion coefficient (ADC) in the lesion, that is low in cholesteatoma (values about 700 × 10−6 mm2/s) but high in non cholesteatomatous tissue that shows values around 1800 × 10−6 mm2/s. The ADC value is of special interest, when the lesion is of small size and the signal is not very bright on b 1000 mm2/s. Lingam et al.  proposed recently a threshold value of 1300 × 10−6 mm2/s, ADC values inferior to the threshold being in favor of cholesteatoma, values above of non cholesteatomatous pathologies.
Differential diagnosis by MRI
For the primary diagnosis of cholesteatoma, MRI is rarely indicated. Nevertheless, its diagnostic performance in the primary diagnosis has been confirmed with a pooled sensitivity of 92% and a pooled specificity of 97% .
However, MRI becomes a precious complementary imaging tool when the clinical presentation and the CT suspect complications and for the postoperative follow up in relation to second look indications.
8.13 Staging of Cholesteatoma
Multiple classifications have been proposed (AAO, Lien, Tos, Saleh and Mills, JOS, Telmesani et al., Belal et al.) with the primary aim of comparing results between studies. In addition to the objective of an inter-study comparison of surgical outcomes, a classification system should be able to identify patients who are at risk of cholesteatoma recidivism.
Staging of cholesteatoma according to EAONO/JOS [ 97 ] is described as follows:
Stage I: Cholesteatoma localized at the primary site: in the attic (A) for pars flaccida cholesteatoma, the tympanic cavity (T) for pars tensa cholesteatoma, cholesteatoma secondary to tympanic perforation and congenital chole
Stage II: Cholesteatoma involving two or more sites
Stage III: Cholesteatoma with intratemporal and/or extracranial complications
Stage IV: Cholesteatoma with intracranial complications
Preoperative CT-Imaging permits to classify the extension of the cholesteatoma correlated to the clinical findings, with a special attention to the anatomical areas of difficult access (S1, S2), which require a planned surgical attention and expertise with a good counseling of the patient. This methodology implies a better compliance for a long follow up.
8.13.1 Clinico-Radiologic Correlations
The scanographic analysis of cholesteatoma can be illustrated according to the schema of the EAONO/JOS Classification, with a special regard to the sites of difficult access (S1 and S2). Sagittal reconstructions along the axis of the incudomalleal chain show the middle ear cleft as seen by the otosurgeon during the surgical approach, this plane is very helpful to assess the S1 space anteriorly and the atticoantral transition posteriorly. The sinus tympani, space S2, however, is much better seen on the initial axial acquisition plane.
Two representative cases of CT-Evaluation of a cholesteatoma according to EAONO/JOS Classification of 2017.
8.14 Management of Cholesteatoma
8.14.1 Medical and Preventive Measures
Until now, no medical treatment is available for cholesteatoma. Research trials for non-surgical treatment of cholesteatoma are limited. New therapeutic approaches should focus on trial of drugs that block the activity of cytokines which are closely related to bone erosion, chiefly TNF-α, MMPs, and IL-1 and IL-6 [98, 99]. In addition, targeted molecules to suppress proliferation and induce apoptotic activity (like 7a microRNA) were proven to have a vital role in the inhibition of the growth of cholesteatoma keratinocytes via downregulation of miR 21 expression .
Antimetabolites like topical 5-Fluorouracil act by a downregulation of the keratinocyte growth factor and reduction of proliferative activity and thus curtail the production of keratin debris .
Aeration disorders of the middle ear and inflammation are the main predisposing factors for the development of a retraction pocket and cholesteatoma; therefore every mean to improve and optimize the Eustachian tube function must be taken. Special attention must be addressed to the underlying atopy and mucosal disease manifestations which are frequently associated with a dysventilation syndrome, recurrent ME effusions and retraction pocket recidivism.
Retraction pockets have to be identified according to clinico-radiological correlations, that permit their division into stable and unstable pockets, in order to avoid any delay for their surgical therapy and prevent their progress to cholesteatoma (see Chap. 7).
8.15 Surgical Treatment of Cholesteatoma
8.15.1 Patient Counseling
The nature of the pathology and its great potential of recurrence.
The actual conditions of hearing, the stage of the disease, its functional and vital impacts.
Why it is a surgical pathology and the impact of an adequate surgery to insure a safe ear.
The selection of the surgical techniques will depend on the per-operative findings.
The possible complications of the disease and the possible complications of the surgery.
The main objective is to insure a safe ear, hearing rehabilitation may be left to staging.
Why second looks must be considered.
Why strict care of an open cavity is a need.
The great importance of a long term follow up and why it could be for life.
Given the disease complexity in the pediatric population, surgeons should provide the comprehensive informations about various surgical strategies to both parents and children in order to avoid any misunderstanding and to ensure a fully informed consent.
8.15.2 Surgical Techniques
Total eradication of cholesteatoma to obtain a safe and dry ear.
Maintain the best condition for a successful wound healing process in the ear.
Restore or maintain the best functional status of hearing.
The essential objective of any surgical technique facing cholesteatoma is to insure at the end of the surgical procedure, that the otologist has done his best to perform, regardless of the applied technique, a complete removal of the disease. This is possible to be accomplished whatever the operative time would be. The surgical procedure should be designed for each individual case according to the extent of the disease and his available compliance. Having satisfied this objective, the last step of the surgical procedure is to restore the normal anatomo-physiology of the ear. Whatever the operative procedure would be, the surgery can be divided into two major groups according to the final anatomical aspect:
220.127.116.11 A Closed Technique
It is mainly centered on the respect of the ear canal anatomy or its reconstruction once the complete removal of the disease has been accomplished; this include CWU, CWD with reconstruction of the canal wall, CWD with mastoid obliteration. Each one of these techniques ends up with the absence of an open mastoid cavity.
18.104.22.168 An Open Technique
It is mainly centered on the creation of an open mastoid cavity. This technique includes the classic CWD, atticotomy without reconstruction or obliteration thus maintaining a communication between the EAC and the operative cavity.
8.15.3 Surgical Procedures
A CWD mastoidectomy involves the removal of the posterior bony canal wall.
CWU mastoidectomy implies the removal of all mastoid air cells while maintaining the integrity of the posterior ear canal wall.
- 3) Other procedures:
Reconstruction of the ear canal defect which could be partial or total to restore the normal anatomy of the ear canal with the tympanic graft.
Atticoantral mastoid obliteration can be done after CWU or CWD restoring in both cases the ear canal and thus avoiding an open mastoid cavity.
- Ossicular reconstruction must be decided in relation to the following:
The extension of the disease,
The hearing level of both ears,
The age of the patient,
The degree of confidence of the surgeon that he has accomplished a complete removal of the disease (unthoughtful residual)
22.214.171.124 Canal-Wall-Down (CWD) Procedure
Cholesteatoma of an only hearing ear,
A major erosion of the posterior bony canal wall,
A history of vertigo due to a labyrinthine fistula,
A poor Eustachian tube function,
A sclerotic mastoid with limited access to the epitympanum (Fig. 8.63).
Patient non-compliant for follow-up.
Relatively short duration of the surgery despite extensive disease.
Easy detection of the postoperative residual disease and reduced rate of recurrences; the facial recess is well exteriorized as well as the attic.
Any postoperative cholesteatoma regrowth can readily be seen and removed as an office procedure (Fig. 8.64).
Hearing reconstruction is less successful.
Open cavity: the mastoid bowl maintenance can be a lifelong problem. Unpleasant appearance of the meatoplasty.
A secondary reconstruction would be less successful.
Difficulty fitting a hearing aid because of meatoplasty.
- Wet Ear Cavity is the most common reason for revision surgery after CWD mastoidectomy (troublesome mastoid cavity) , due to the following:
Incomplete eradication of the mastoid air-cells disease or inadequate lowering of the facial ridge (85%),
Very large cavity or/and inadequate meatoplasty (10%),
Recurrent or persistent cholesteatoma (5%) (Fig. 8.65).
126.96.36.199 Canal-Wall-Up (CWU) Procedure
The CWU procedure is recommended to avoid the disadvantages of the CWD.
Nowadays a CWU technique is indicated in most cases of cholesteatoma especially for cases with a large pneumatized mastoid. In modern otosurgery, CWU must be the first choice for most cholesteatoma cases.
Only hearing ear,
A long-standing ear disease after multiple previous procedures and persistent extended pathology,
A poor Eustachian tube function.
Extensive lysis of the bony ear canal.
Advantages (Fig. 8.70)
A more rapid healing with respect of the ear anatomo-physiology.
A better quality of life for the patient and normal ear contours.
A better fit of hearing aids when needed.
Long duration of the surgical procedure in extended pathologies.
Unsatisfactory exposure and high rate of residual disease.
Staging and multiple surgical looks (relative patient compliance dependance and economic burden).
188.8.131.52 Other Surgical Approaches
Partial Mastoid obliteration (Fig. 8.71) has been suggested to reduce the size of the open cavity following open technique. Mosher first introduced mastoid obliteration using a pedicle musculoperiosteal flap in 1911 to overcome problems associated with the postoperative mastoid cavity . Since that time, numerous otologists have reported success with mastoid obliteration techniques using alloplastic materials as well as various biogenic implants, such as fat, cartilage, bone paté, bone chips, ceramic powder, Ceravital, and hydroxyapatite [103, 104, 105].
The obliteration technique does not confer a great physiological value to the concept of the “mastoid reservoir theory” considered in the CWU technique. Mastoid obliteration reduces the volume of ME cleft cavity, and thereby the amount of gas exchange consumed by the mastoid mucosa; thus the smaller cavity would adapt better to the dysfunction of the Eustachian tube and the aeration deficit. In doing so it reduces a possible dysventilation and secondarily a possible retraction pocket or cholesteatoma recurrences.
Transcanal anterior atticotomy
A transcanal anterior atticotomy is indicated for a cholesteatoma with limited involvement of the middle ear, intact ossicular chain and/or a healthy epitympanum. After removal of the disease, in bloc reconstruction of the resulting cavity is done with cartilage and perichondrium. In such technique the recurrence rate and the probability of a residual tissue are low.
Bondy modified radical mastoidectomy
Although rarely used today, the Bondy procedure is indicated for attic and mastoid cholesteatoma that does not involve the middle ear space and is situated lateral to the ossicles. The Eustachian tube function should be adequate, with an intact pars tensa and well aerated free middle ear spaces.
In conclusion Facing the duty of any selected technique to secure a perfectly safe ear and exclude any possible residual, surgical expertise is a prerequisite to avoid an unhappy situation when postoperative complications become more frequent or more troublesome than the disease itself. Moreover, if repeated surgeries or multiple looks on the same ear could be the cause of increased surgical risks or patient compliance deficits, it remains that a permanent open mastoid cavity, requiring regular cleaning is not by itself a guaranteed solution for a long term safe ear.
8.15.4 Endoscopy in Cholesteatoma
Combined surgeries done with microscope, endoscope or endoscope/microscope  should prove their value by confirmed satisfying long term results.
8.15.5 Laser in Cholesteatoma
Some cholesteatoma may be more effectively removed using laser and not by mechanical dissection alone. Using Laser, reduced rates of residual cholesteatoma have been reported with level 2 evidence. This technique permits to maintain hearing when the ossicular chain is still intact. Matrix on the surface of ossicles can be vaporized with laser without the need to manipulate or remove the ossicle.
8.15.6 Surgery of Congenital Cholesteatoma
Cases of posterosuperior localization of a congenital cholesteatoma are also encountered and may imply an endoscopic removal taking care of a possible extension to the sinus tympani where a residual is feared. In the later situation, Laser surgery is helpful not to disturb a preserved ossicular chain.
8.15.7 Hearing Rehabilitation in Cholesteatoma Surgery
The second role of surgery in cholesteatoma is to either fix hearing or restore serviceable hearing whenever possible. The management of hearing impairment depends on the type of hearing loss and the possibly reachable degree of hearing recovery.
Hearing results are better with the closed technique than with the open technique, because the tympanic membrane is kept of normal size and position. BAHA offers a viable option to improve hearing outcomes, as long as the bone conduction remains intact.
Ossiculoplasty can be achieved by the placement of an autologous ossicular graft (e.g., bone or cartilage) or a prosthetic device (e.g., partial or total ossicular replacement prosthesis).
For surgical technique of ossiculoplasty please refer to Chap. 6.14.2.
8.15.8 Surgery for Cholesteatoma in an “Only Hearing Ear”
In such situation, an utmost surgical expertise must be looked for: cholesteatoma is a much greater risk for hearing loss than a good surgery. Good surgery preserves the present hearing from further deterioration by the cholesteatoma. Careful surgery is expected to insure complete removal of the disease and a satisfactory hearing result. Therefor a transfer of such cases to a tertiary care center is recommended.
8.15.9 Disease Control (Surgery Outcome)
Depending on the procedure, there is a large variation in the postoperative outcomes regarding residuals or recurrences.
Sinus tympani invasion and ossicular lysis at the moment of diagnosis
An impaired ET function with persistent impaired aeration of the ME
A large périmatrix with its more active inflammatory and aggressive mediators.
Nearly 90% of recurrent disease will appear within 5 years after surgery; however, in a recent long-term study (mean follow-up period of 15.4 years) on cholesteatoma, the mean delay until discovery of the recidivism was found to be 10.4 years. Another long-term study revealed an increase in the rate of recidivism when the follow-up period was extended [107, 108, 109, 110, 111]. Thus, it seems imperative that patients undergo periodic follow-up for as long as possible. However, the keys of success to minimize the recidivism rate is the strict and complete eradication of the disease at the initial surgery and the serious consideration of potential recurrence risk factors. Children need more frequently an office follow-up than adults because of their increased likelihood to develop residual cholesteatoma. Pediatric patients are generally followed at least annually until adulthood.
8.15.11 Radiological Follow Up
184.108.40.206 Planned Follow UP During the First Year Postop
Nowadays, MRI imaging can be considered as the first line follow up imaging, because of its lack of irradiation and its superiority to CT-Scan for tissue differentiation. The high negative predictive value of negative diffusion weighted images, reported with up to 100% in early publications , raised an enthusiasm among otologists and motivated numerous studies during the last 10 years on this subject. The most recent meta analysis that enrolled 26 postoperative studies over the last 10 years with a series of 1152 patients, confirmed a high pooled sensitivity of 0.93 and specificity of 0.91 for the improved technical conditions by non EPI Diffusion weighted sequences to detect residual/recurrent cholesteatoma in postoperative middle ear cleft cavities .
The PPV was 97.3%, and the NPV 85.2%. The authors found that cholesteatoma as small as 2 mm could be predictably found. The use of this imaging modality may help to prevent unnecessary surgery for patients when there is doubt about residual or recurrent cholesteatoma .
Nowadays the otologist feels more at ease to perform and promote CWU techniques for most cholesteatoma cases regardless of their location and extension, having in mind that MRI may replace second look surgery, and can even be used repetitively.
However, there is a non-negligible rate of 7.4% of false negative cases found with MRI that turned out to be most often due to the small size of the residual cholesteatoma inferior to 3 mm.
A lack of diagnosis at this stage may give enough time to the growing cholesteatoma to invade once again some challenging areas (S1, S2) before the next imaging control. This dilemma is especially of great concern in pediatric patients and can only be resolved in case by case evaluation of the potential risk of recurrence and realisation of a real second look surgery, that remains the gold standard of diagnostic fiability.
A surgical second-look procedure should be proposed always for patients when a complete removal of the disease during the primary surgery was uncertain to the surgeon and this despite a negative imaging
MRI evaluation may be appropriate to avoid a surgical second look for patients when the otologist was sure that all the disease has been completely excised by his first surgery and when an unequivocal normal microscopic examination is observed during the first 6 months of the postoperative period.
220.127.116.11 Postoperative Imaging Longtime After the Initial Surgery in Cases with a “Non-Adequate Follow-Up”
When CT-Scan demonstrates a complete aeration of the tympanic cavity and the absence of any condensation image in the middle ear cleft, CT alone confirms the absence of any residual or recurrence. In such situation CT has a negative predictive value of almost 100%
- 2.When CT shows condensation images in the cavity, a high suspicion of a cholesteatoma recurrence is retained if these condensations are:
Associated to a recurrent tympanic membrane retraction pocket
Associated to smoothed borders of the mastoid septa around the mass
Associated to additional bony erosions in comparison with previous CT-Imaging
In cases of previous CWU for cholesteatoma, CT can shows a typical aspect of recurrent cholesteatoma hidden in the atticoantral spaces (Fig. 8.76)
- 4.In cases of an open mastoid cavity, and when the otoscopy favors a cholesteatoma recurrence, CT Imaging has an added value (Fig. 8.77)
To show erosions of the bony plates: tegmen lysis, sinus plate, LSCC, which are not evident with microscopy
To predict the anatomic localization of the sigmoid sinus
To assess the sites of predilection for recurrence (S1 and S2).
If the CT shows a complete condensation of the cavity, it is impossible to distinguish an eventual focal cholesteatoma from surrounding granulation or scar tissue (Fig. 8.78). Complementary MR evaluation can provide differential diagnoses, in case of positive restriction in favour of choelesteatoma (Fig. 8.79); absence of restriction, this is in favour of a non-cholesteatomatous condition (Fig. 8.80).
Despite the impressive recent progress concerning cholesteatoma pathology, molecular biology and its immune behavior, its definite pathogenesis remains uncertain. The huge progress in the basic sciences of cholesteatoma was not accompanied by the same level of advances in its surgical therapy. A complete knowledge about the impact of the aeration pathways on the functional anatomo-physiology of the middle ear is a prerequisite to deal correctly with its management and better control of its recurrences. All procedures of reconstruction would not control cholesteatoma recurrences if an adequate aeration of the middle ear spaces is not insured and well preserved.
The early diagnosis of a cholesteatoma is the key point to avoid extensive forms and consequently decrease the dilemma of the residual. Advanced Imaging in cholesteatoma pathology enriches its assessment, helps in the clear counseling of the patient and may orient the surgical strategies. An early treatment prevents complications and preserves hearing.
Knowing that the middle ear mucosa cannot generate epidermal tissue as cholesteatoma, a recurrence behind an intact tympanic membrane after a complete removal of cholesteatoma must not exist. Therefore the duty of the otologist is to reach the needed expertise to accomplish the complete and total removal of the cholesteatoma during the first surgery; hereby he decreases greatly the necessity of a systematic second look surgery after a closed technique.
Surgical approaches must be customized to each patient depending on the extent of his disease. The most relevant aim from the surgery is to free the ear from its disease and at the same time to preserve its natural anatomo-physiology.
The otologist must be aware of the serious and potentially life-threatening complications of cholesteatomas especially when preventive medicine is not affordable to all countries.
Nowadays the true rate of recidivism tends to be underestimated or wrongly considered due to the variations in the length of the postoperative follow-up period and the great number of cases which lost compliance to the same otology center. Regarding all surgical techniques it is of utmost importance to screen the correct rate of postoperative “recurrences” in a lifetime follow up duration.
The related advances in the knowledge about its molecular biology and genetic modeling may engender hopefully possible medical therapies of cholesteatoma in the near future.
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