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Cholesteatoma

  • Salah Mansour
  • Jacques Magnan
  • Karen Nicolas
  • Hassan Haidar
Chapter
First Online:

Abstract

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.

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8.1 Introduction

Cholesteatoma (synonym: keratoma) is a chronic otitis of the middle ear cleft characterized by “a wrong skin in the wrong place” (Fig. 8.1). It derives from an abnormal proliferation of a keratinizing squamous epithelium.
Fig. 8.1

Right ear large cholesteatoma filling the mastoid antrum. Notice that the cholesteatoma is a cystic lesion that consists of an envelope (matrix) and whitish content (keratin)

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.

8.2 Epidemiology

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 [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 [2].

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 [3].

Association of cholesteatoma in one ear and chronic inflammatory pathology in the contralateral ear is about 50% of cases [4, 5].

8.3 Types of Cholesteatoma

There are two main types of cholesteatoma based on the disease pathogenesis: congenital and acquired [6].

8.3.1 Congenital Cholesteatoma

Congenital cholesteatoma is a benign tumoral process of the middle ear that manifests as a pearly white mass with keratinized stratified squamous epithelium, arising in the middle ear cleft behind an intact tympanic membrane, usually in young ages (Fig. 8.2). Congenital middle ear cholesteatoma is a relatively rare disease representing approximately 2% of the entire cholesteatoma cases [7]. Recently, with the increase of interest in this disease, its detection rate is increased, and thus the ratio of congenital cholesteatoma to the entire cholesteatoma has increased to more than 4% [7, 8].
Fig. 8.2

(a) Right ear congenital cholesteatoma of the anterosuperior quadrant and (b) intraoperative endoscopic removal

First Derlacki in the sixties and then Levenson in 1989 established a set of criteria for the diagnosis of congenital cholesteatoma in the middle ear (Fig. 8.3). These criteria included:

  • A white mass behind a normal tympanic membrane (Figs. 8.2 and 8.4),

  • A normal pars flaccida and pars tensa,

  • No prior history of otorrhea or perforations, and

  • No prior otologic procedures.

Fig. 8.3

Congenital cholesteatoma diagnostic criteria

Fig. 8.4

(a) Small congenital cholesteatoma in the anterosuperior quadrant of a right ear, (b) congenital cholesteatoma of the posterosuperior quadrant of a left ear and (c) congenital cholesteatoma of both quadrants: post-sup and ant-sup

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).

8.3.2.1 Primary Acquired cholesteatoma

The primary acquired cholesteatoma is the most frequent type of acquired cholesteatoma and develops by the progression of an initial retraction pocket into a cholesteatoma. Primary acquired cholesteatomas are named relative to the site of the pocket origin: (1) attic cholesteatoma consecutive to a pars flaccida pocket, (2) mesotympanic cholesteatoma due to a pars tensa pocket, and (3) combined forms, due to double pockets (Fig. 8.5).
Fig. 8.5

(a) Left attical cholesteatoma, (b) left ear meso and retrotympanic cholesteatoma and (c) left ear double cholesteatomas, attical and mesotympanic

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).

8.3.2.2 Secondary Acquired Cholesteatoma

Secondary acquired cholesteatoma develops by an epithelial migration from the bottom of the ear canal into the middle ear through a marginal tympanic membrane perforation (Fig. 8.6), which could be due to infection (acute necrotizing otitis media). It could also be due to a trapped skin inside the middle ear following trauma or surgery.
Fig. 8.6

Left ear, cholesteatoma by skin migration through a marginal perforation of right ear

8.4 Histopathology of Cholesteatoma

8.4.1 Macroscopy

In 1829, Cruveilhier [9] described cholesteatoma as a “pearly tumor”, due to its whitish pearly appearance (Fig. 8.1). In 1838 Muller [10] gave it the name of “cholesteatoma” due to the greasy aspect of the mass (Fig. 8.7).
Fig. 8.7

(a) Large cholesteatoma with its whitish pearly aspect and (b) after removal the cholesteatoma was opened to show its center full with keratin (k) with its greasy aspect, misnamed cholesteatoma

8.4.2 Light Microscopy

Light microscopy shows a cyst with three components (Figs. 8.8 and 8.9):
  1. 1.

    The “amorphic center”, formed of accumulated desquamated epithelium, enveloped by “the matrix”.

     
  2. 2.

    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.

     
  3. 3.

    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.

     
Fig. 8.8

Light microscopy of a cholesteatoma capsule showing the amorphic center made up of squamous keratin debris and matrix made up keratinizing squamous epithelium and perimatrix made up of granulation tissue infiltrated by inflammatory cells and surrounded in this special case by cholesterol granuloma and hemosiderin

Fig. 8.9

Light microscope: Cholesteatoma with Keratin debris (K), surrounded by keratinizing squamous epithelium; the matrix (M) shows hyperplasia of the basal cell layer

8.4.3 Electron Microscopy

Electron microscopy studies on cholesteatoma helped to better understand the etiopathogenesis of cholesteatoma. Cholesteatoma consists of an amorphous center containing keratin (made of desquamated keratinocytes of the epidermal layer), the matrix (epidermal layer) and the perimatrix (inflammatory layer) surrounding the matrix (Fig. 8.10). Cholesteatoma matrix has the same histological and cellular structure as the epidermis that is lining the bottom of the external auditory canal. All the maturation stages of the keratinocytes are clearly similar in both structures and demonstrated by electron microscopy of cholesteatoma matrix as the following layers (Fig. 8.11):

  • 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).

Fig. 8.10

Electron microscope of cholesteatoma with an amorphous center containing Keratin, a squamous stratified epithelium (Matrix) with subepithelial connective tissue containing inflammatory cells (Perimatrix)

Fig. 8.11

The ultrastructural characteristics of cholesteatomas matrix cell layers are similar to those found in the epidermis; the basal stratum is formed by an unicellular layer. The stratum spinosum (or spinous layer) is the layer found between the stratum granulosum and stratum basale . Their spiny (Latin, spinosum) appearance is due to shrinking of the microfilaments between desmosomes, this layer is composed of polyhedral keratinocytes that are active in synthesizing fibrillar proteins, known as cytokeratin, which build up within the cells aggregating together forming tonofilaments. The stratum granulosum is characterized by keratohyalin grains. The stratum corneum contains dead keratinocytes that became shells filled with electron dense keratin

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.

Langerhans’ cells have electron-microscopically a clear appearance in contrast to the darker keratinocytes [11, 12, 13, 14] (Fig. 8.12). The key features for the identification of Langherans cells are the presence of Birbeck granules in their cytoplasm, they show 200–400 nm in size vesicles, rodlike and tennis racket-shaped structures called Birbeck granules. The nucleus is irregular and the cytoplasm has no tonofilaments. Langerhans’ cells are macrophages of the skin with complex biological and metabolic properties due to their relationship with the mononuclear phagocytic system and their immunological response [15, 16] (Fig. 8.13). The function of Birbeck granules could be that they migrate to the periphery of the Langerhans cells and release their contents into the extracellular matrix to enhance their immunologic reaction (Fig. 8.14).
Fig. 8.12

Electron microscope. Between the dark keratinocytes that are linked between themselves by tight junctions, the desmosomes, clear cells are interposed: the Langerhans’ cells (arrows)

Fig. 8.13

Electron microscopy study of a Langerhans Cell. It exhibits a cleaved or folded nucleus and no tonofilaments or desmosomes. The Birbeck granules are characteristically present in their cytoplasm. These granules are most specific marker for Langerhans Cells. Birbeck granules show a vesicle at one end and sometimes at both ends. In cross sections, the granule with vesicle at one end shows a characteristic appearance, which is termed as ‘tennis racket’ appearance

Fig. 8.14

High Magnification of intra- cytoplasm area of Langerhans’cell to identify Birbeck’s granules, columnar aspect (yellow arrows) and vesicles (blue arrow)

8.5 Pathogenesis of Cholesteatoma

8.5.1 Congenital Cholesteatoma

Several theories emerged in the explanation of congenital cholesteatomas that can be defined as “epithelial inclusions behind an intact tympanic membrane.”
  1. 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) [21]. 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 [17].

    • Epidermoid tumor arising from ectodermal implants in the fusion plates of the first and second branchial arches [18, 19].

    • Conversion of viable squamous epithelial cells of amniotic fluid debris into cholesteatoma [20].

    • 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 [22].

     
  2. 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 [23].

    • 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) [24].

     

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 [25])—is definitively confirmed in the 1970s.

Whatever the epidermal proliferation mode would be - tympanic retraction [26, 27], lateral epithelial migration [28], papillary budding [29]—the cholesteatoma corresponds always to Gray’s definition [30]: 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.

Historically, four theories have been proposed to explain the pathogenesis of acquired cholesteatoma: none is satisfactory by itself for all encountered clinical cases!
  1. 1.

    Invagination theory (retraction pocket theory),

     
  2. 2.

    Immigration theory,

     
  3. 3.

    Squamous metaplasia,

     
  4. 4.

    Basal cell hyperplasia (papillary ingrowth theory).

     

8.5.2.1 The Invagination Theory

The invagination theory is based on the assumption that the precursors to cholesteatoma are tympanic membrane retraction pockets which are caused by a dysventilation syndrome of the middle ear compartments (Figs. 8.15 and 8.16).
Fig. 8.15

Left ear mesotympanic retraction pocket that evolved into cholesteatoma after 5 years

Fig. 8.16

Retraction pocket and its skin (S) invaginating towards the middle ear (small red arrows) with desquamated keratin (K) filling the lumen of the pocket and mucous secretions in the middle ear. The mucosal epithelium medial to pocket retraction is still preserved (M)

Although the development of a retraction pocket is a passive process, the transformation of a retraction pocket into a pre-cholesteatoma and then into cholesteatoma is a dynamic biologic process along with a dysfunction of the external auditory canal bottom skin immune system (Fig. 8.17).
Fig. 8.17

From retraction pocket into cholesteatoma

Two major histological features are present in cholesteatoma and not in retraction pocket: Epithelial hyperplasia and defective skin migration. Epithelial hyper-proliferation in the fundus of a retraction pocket and loss of self-cleaning function due to defective skin migration lead to an accumulation of desquamated keratin with subsequent deepening of the retraction pocket resulting in formation of cholesteatoma (Figs. 8.17 and 8.18).
Fig. 8.18

Epithelial hyperplasia (H) with resultant increased production of keratin (K) is an essential step in the development of cholesteatoma. “Courtesy of Pr Moriyama”

Both, the loss of self-cleaning mechanism and the epithelial proliferation are not a passive phenomenon but enhanced by several immunological factors released through a persistent middle ear inflammatory process. Also an intrinsic dysfunction of the external auditory canal bottom skin immune system intervenes in these phenomena. So the retraction pocket becomes an active invaginating process, leading to a primary acquired cholesteatoma (Fig. 8.19). In Retraction pockets with a narrow neck, there will be inversion of keratin migration and accumulation of keratin inside the pocket with cholesteatoma formation. Two things are present in cholesteatoma and not present in safe retraction pocket: epithelial hyperproliferation and abnormal skin (Fig. 8.19).
Fig. 8.19

Left ear that progressed from retraction pocket (a, b) into pre-cholesteatoma (c, d) and then into cholesteatoma (e, f). In safe retraction pockets there is active self-cleaning mechanism by lateral migration of the skin without keratin accumulation (a, b). In precholesteatoma (c, d) there is hyperplasia of the epithelium of the retraction pocket fundus (d), Epithelial hyperplasia (H) with resultant increased production of keratin (K), Courtesy of Pr Moriyama) but the lateral migratory potential of skin is preserved (blue arrow). In cholesteatoma (e, f), there is both epithelial hyperplasia with defective skin migration (red arrows)

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 [31].

8.5.2.2 The Migration Theory

The migration theory assumes that the perforation of the eardrum, traumatic or iatrogenic, gives access to the squamous epithelium of the eardrum or of the outer ear canal skin, to invade or migrate into the middle ear leading to the formation of a Secondary acquired cholesteatoma (Fig. 8.20).
Fig. 8.20

Left ear with marginal perforation with secondary acquired cholesteatoma due to a migration of the skin epidermis on the edge of the perforation inside the middle ear cavity (red arrows)

In marginal perforations, there is a sharp front line between the skin of the ear canal and the mucosa of the middle ear which is usually respected by the canal skin: so it migrates laterally. However, recurrent ear infections will alter the behavior of the ear canal skin: the stimulated squamous epithelium will invert its migration direction medially into the middle ear cavity. The basal cells of the germinal layer of the skin will proliferate excessively and a keratinizing squamous epithelium will progress into the middle ear cavity through the pre-existing perforation (Fig. 8.21).
Fig. 8.21

(a) Light microscopic examination of the frontier line in a marginal perforation (white arrow) between the skin of the ear canal and the mucosa of the middle ear: the stimulated squamous epithelium of the ear canal skin (S) is very thick (*), excessively proliferative and has inverted its migration direction medially into the middle ear cavity over the middle ear mucosa (M) (red arrows), (b) at higher magnification, excessive keratin formation (K) is seen, due to the inflammatory process (I) present under the epithelium which is responsible for stimulating the ear canal epithelium

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.

8.5.2.3 The Squamous Metaplasia Theory

The metaplasia theory stipulated that the epithelium of the middle ear changes into squamous epithelium under the effect of a persistent chronic inflammation. However, there is neither histological nor experimental proof [32, 33]. In fact, middle ear mucosal metaplasia exists but it never transforms into cholesteatoma. When stimulated by chronic inflammation and irritation, the pseudostratified ciliated columnar epithelium changes progressively into pluri stratified squamous (epidermoid) epithelium, but it stays at the aspect of a “non- squamous non keratinizing epithelium” [34] (Fig. 8.22). In addition, this process is reversible, whereas cholesteatoma is an irreversible squamous epidermal disorder. Moreover, the differences observed in the cytokeratin profile between cholesteatoma epithelium and middle ear epithelium are also against this theory [35]. Consequently, the metaplasia theory is not anymore accepted.
Fig. 8.22

Light microscope: progressive metaplasia of middle ear mucosa from a pseudostratified columnar epithelium (1) to a pluri-stratified squamous epithelium (2) but without keratin formation. Infl.: inflammatory process in the subepithelial layer

8.5.2.4 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].

This proliferative behavior of the basal layer is induced by subepithelial inflammatory process (Fig. 8.23) taking place following a Prussak’s space dysventilation syndrome.
Fig. 8.23

Light microscope showing a pseudopod (*) formed in the basal layer of the pars flaccida epithelium (S) and invading the sub-epithelial tissue which hosts a diffuse inflammatory process (I). K: keratin deposited by stimulated skin (keratosis)

8.5.2.5 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 [39] (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 [40].

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.

Among all cells of a normal external auditory canal bottom epidermis, the number of the Langerhans’ cells does not exceed 3%. In cholesteatoma, these cells show quantitative and qualitative modifications. Their number increases significantly and they become grouped into masses at different levels (basal, suprabasal) in the cholesteatoma matrix and perimatrix (Fig. 8.24). Moreover, Langerhans’ cells are present at the different stages of keratinocyte maturation, confirming their role as immunological sentinels.
Fig. 8.24

Immunohisto chemical study of the cholesteatoma matrix shows the extensive infiltration with Langerhans’ cells (black arrows). Their dendritic expansions create a net for a close contact with neighboring cells

Langerhans’ cells require the cooperation of activated T-lymphocytes to become functional. These activated T-lymphocytes (Fig. 8.13) represent the “vital union” of the immune process [41]. Langerhans cells emit long dendritic expansions which create a true network between the neighboring cells: keratinocytes and lymphocytes (Fig. 8.12). The close contact between these cells is essential for the immune reaction (Figs. 8.25, 8.26 and 8.27).
Fig. 8.25

Electron microscopic view showing the “vital union” between Langerhans’ cell (La), Lymphocyte-like cell (Ly) and Keratinocytes (K) by desmosomes (d)

Fig. 8.26

Electron microscopy the inflammatory and immunological process in the matrix of cholesteatoma with interactions between keratinocytes (K), Langerhans cells (La), and lymphocyte-like cells (Ly)

Fig. 8.27

Electron Microscopy: Immune cellular reactions in cholesteatoma. Keratinocyte (K), Langerhans’ cell (La), Lymphocyte (Ly), Macrophage (M)

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) [42].

This inflammatory and immunological duality of Langerhans’ cells to stimulate the proliferation of cholesteatoma has a high similarity with lichen planus of the epidermis covering some troublesome mastoid cavities. Lichen planus is characterized by a massive infiltration of the epidermal layer by an infiltrate formed of lymphocytes, macrophages and Langerhans’ cells (Fig. 8.28).
Fig. 8.28

Light microscopy transformation of the epidermic layer in Lichen planus covering a troublesome mastoid cavity. The keratinizing squamous epithelium (S) is infiltrated by lymphocyte cells (I)

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].

As shown in Fig. 8.29, there are paracrine and autocrine interactions between keratinocytes of the matrix and fibroblasts of the perimatrix that regulate homeostasis and tissue regeneration within a cholesteatoma [36]. In addition, inflammatory cell populations (e.g., lymphocytes, Langerhans cells) in the perimatrix release a variety of growth factors (e.g., IL1, TGFx, cytokeratines,…) (Fig. 8.29). The excessive inflammatory immune response and the release of growth factors in the matrix and perimatrix can lead to an uncontrolled growth and proliferation of keratinocytes and hereby to the cholesteatoma growth and its aggressiveness.
Fig. 8.29

Schematic representation of the paracrine and autocrine interactions between matrix keratinocytes and perimatrix fibroblasts. Keratinocytes release proinflammatory cytokines (e.g., IL-1α, IL-1β, IL-6, PTHrP, and IL-8), which subsequently induce fibroblasts to secrete several cytokines (e.g., KGF, GM-CSF, EGF, TNF-α, PDGF, and TGF-α). These fibroblast-derived cytokines in turn induce the differentiation, proliferation, and migration of matrix keratinocytes. In addition, the TGF-α and TGF-β are upregulated in an autocrine loop, regulating keratinocyte proliferation and differentiation. EGF: epidermal growth factor; GM-CSF: granulocyte-macrophage colony stimulating factor; IL: interleukin; KGF: keratinocyte growth factor; PDGF: platelet-derived growth factor; PTHrP: parathyroid-hormone-related protein; TGF: transforming growth factor; TNF-α: tumor necrosis factor alpha

8.6.2 Biochemistry of Cholesteatoma

Keratinocytes are the target cell’s receptive to mediator substances that lead to the development of cholesteatoma. Keratinocytes require growth factors to divide and differentiate. Growth factor polypeptides as epidermal growth factor (EGF) and transforming growth factor ((TGF-α) play an important role in wound healing, cell regulation and proliferation. Both EGF and TGF-α are upregulated in the cholesteatoma perimatrix (Fig. 8.30) and bind to the upregulated epidermal growth factor receptor (EGFR) on the matrix (Figs. 8.31 and 8.32) [50]. Keratinocytes activation is accomplished by a strong impregnation of ILI, TGF, cytokeratin expression modification and fibroblast activation [39]; also these factors are the factors encountered in the wound-healing process (Figs. 8.30, 8.31, and 8.32).
Fig. 8.30

EGF is mainly present (black arrows) in the cholesteatoma perimatrix (P) with medium intensity staining (monoclonal antibody Monosan Mon 8001), whereas the matrix (M) showed very low staining. This means that the origin of EGF is the perimatrix and then diffuse to the matrix to stimulate its proliferation

Fig. 8.31

EGF-R AB1 (extracellular epitope of the receptor) is always present in cholesteatoma matrix with a high level of staining (antibody receptor AB1 Oncogene Science)

Fig. 8.32

EGF-R AB2 (intracellular epitope of the receptor) is positive (black arrows) in children cholesteatoma matrix (M). Keratin (K)

The fundamental difference between the healing process in normal skin and in cholesteatoma, is that in cholesteatoma there is a loss of the growth inhibition by “cell to cell contact”. Two factors are involved in this loss of growth control in cholesteatoma:
  1. 1.

    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.

     
  2. 2.

    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.

     
Thus the proliferation of the cholesteatoma matrix is due to an autocrine stimulation circle at the level of the keratinocytes in the matrix and the fibroblasts of the prematrix [51, 52] (Fig. 8.33).
Fig. 8.33

Diagram of hypothetical autocrine (keratinocytes) and paracrine (fibroblasts) dysregulation loop of Keratinocyte cells in cholesteatoma

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 [56]. 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 [57]. 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 [58]. 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,…) [59].

8.7 Genetics of Cholesteatoma

Despite the fact that cholesteatoma is not a tumor, it exhibits clearly clinical features similar to those observed in neoplasms, indicating that the dysregulation of cell growth control may involve internal genomic alterations. Nevertheless, the precise underlying genomic mechanisms associated with the formation of cholesteatoma have still to be clarified (Fig. 8.34).
Fig. 8.34

The chain of multiple and complex factors involved in the pathogenesis of cholesteatoma. Most of them are genetically coded

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 [79].

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 [80].

Several upregulated cytokines in cholesteatoma, including interleukin-1, interleukin-6, interleukin-17, interferon-beta, and parathyroid-hormone-related proteins, have been shown to promote inflammatory bone resorption by promoting osteoclast activity [33, 81, 114]. IL-1 (both IL-1α and IL-1β) was found with an increased level in the epidermis of cholesteatoma compared to the normal squamous epithelium [82, 83]. Recent studies revealed that the receptor activator of nuclear factor kappa-B ligand (RANKL) and matrix-metalloproteinases (MMPs) play a pivotal role in the destruction of bony tissue by cholesteatomas [33, 73, 84].

  • Proteolytic inflammatory cytokines (metalloproteinases, MMP2, MMP9) have been shown to have an increased amount in pediatric cholesteatoma in comparison to adults [85].

  • Angiogenesis observed in the perimatrix of cholesteatoma is higher in pediatric than adult cholesteatoma [85].

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].

8.8.2 Collagenase

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 [64].

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

On the basis of their site of origin, middle ear cholesteatomas (Table 8.1) can be classified as the following:

  • “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.

Table 8.1

Cholesteatoma origin and growth pathways

Location

Site in the tympanum

Age distribution

(a) Attic/posterior epitympanum (40%)

Pars flaccida

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

Fig. 8.35

Cholesteatoma origin and spread. (a) Attical cholesteatoma usually spreads posteriorly (1) as posterior attical cholesteatoma and rarely anteriorly as anterior attical cholesteatoma (2) and (b) mesotympanic cholesteatoma growth pattern into the facial recess and sinus tympani (3); into epitympanum through posterior tympanic isthmus (4)

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

The most common spread pattern of cholesteatoma originating from the Prussak’s space is the posterior epitympanic route (Fig. 8.36) where the cholesteatoma spreads into the superior incudal space (SIS) lateral to the body of the incus and can potentially enter the mastoid through the aditus ad antrum (Fig. 8.37).
Fig. 8.36

Posterior epitympanic cholesteatoma of a left ear

Fig. 8.37

Attical cholesteatoma growth pattern. From the Prussak’s space, cholesteatoma can extend through one of the following three tracts. 1: through the posterior pouch of Von Troeltsch to the lower lateral attic (inferior incudal space, IIS). 2: through a defect in the lateral incudal fold (LIF) to the lateral malleal space and then to the superior incudal space (SIS), or 3: from the lateral malleal space through the superior malleal fold defect (SMF) to the anterior attic

8.9.2 Mesotympanic Cholesteatoma

The second most common route of cholesteatoma spread is the mesotympanic cholesteatoma through the inferior route, through the posterior pouch of von Troeltsch following the embryological course of both the saccus posticus and the saccus superior. It grows medially along the lenticular process and stapes superstructure. Then it may grow upward through the posterior tympanic isthmus toward the posterior epitympanum and then the mastoid antrum or backward directly into the sinus tympani, and may fill the entire middle ear (Figs. 8.35b and 8.38).
Fig. 8.38

Mesotympanic cholesteatoma of left ear

8.9.3 Anterior Epitympanic Cholesteatoma

The cholesteatoma reaches the anterior epitympanum through the lateral malleal space beneath the superior malleal fold (following the embryologic saccus anticus trajectory) to enter the anterior epitympanic recess (AER). It may remain in the AER, where the geniculate ganglion is at risk, or progress into the supratubal recess (STR) and the protympanum (Figs. 8.35a and 8.39).
Fig. 8.39

Left ear anterior epitympanic cholesteatoma

8.9.4 Unclassified Cholesteatomas

Cholesteatomas become unclassifiable according to the previous categories, when they grow beyond the different compartments, involving the middle ear, the epitympanum and the mastoid and their initial origin become unidentifiable or may be the result from two progressing retraction pockets (Fig. 8.40).
Fig. 8.40

Right ear showing extensive cholesteatoma that involves the attic and the mesotympanum with erosion of head of malleus and incus

8.10 Clinical Manifestations

8.10.1 Symptomatology

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.

8.10.1.1 Otorrhea

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.

8.10.1.2 Hearing Loss

A conductive hearing loss is a common finding in cholesteatoma, as ossicular chain erosion is common (70%) [94]; 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.

8.10.1.3 Vertigo/Imbalance

A destruction of the bone which overlies the otic capsule, especially the lateral semicircular canal, can trigger vertigo or a balance dysfunction.

8.10.1.4 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.

8.10.2 Otomicroscopy

The diagnosis of cholesteatoma is clinical and requires a perfect cleaning of the outer ear canal before inspection of the drum (Fig. 8.41). Typical findings are a marginal tympanic perforation with debris extending into the middle ear (Fig. 8.20) or a retraction pocket filled with keratin. Erosion of the scutum and/or the ossicular chain can be seen. A retraction pocket may be seen, often in the attic and posterosuperior quadrant of the tympanic membrane. Granulation tissue or a polyp may arise from the diseased infected bone of the scutum or the posterior bony wall (Fig. 8.42). Through a transparent tympanic membrane a congenital cholesteatoma in the middle ear can be observed (Figs. 8.4 and 8.6).
Fig. 8.41

Right ear with attical cholesteatoma. Cholesteatoma visible after ear cleaning

Fig. 8.42

Cholesteatoma with aural polyp

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

The cardinal scanographic sign of cholesteatoma is a soft tissue image, that has characteristically a rounded appearance in early stages (Fig. 8.43).
Fig. 8.43

Axial CT image of right ears of different patients: Typical scanographic appearance of a cholesteatoma as a soft tissue mass (arrows), with rounded borders, typically with some air inclusions in an early phase. (a) In front of the malleus handle, (b) in the posterior mesotympanum (short arrow), and insinuating in the sinus tympani (long arrow)

The cholesteatoma may show initially a slight mass effect on the surrounding structures (Fig. 8.44a), that can become extensive in later stages (Fig. 8.44b).
Fig. 8.44

Axial CT-image of a right ear: (a) condensation of the lateral attic with slight mass effect on the incudomalleal chain (arrows), (b) atticoantral condensation with a prominent mass effect on the incudomalleal chain (white arrows), and advanced lysis of the incus (black arrow)

Cholesteatoma represents the main cause of typical bony erosions and/or ossicular lysis.

8.11.1 Erosion of the Scutum

The erosion of the scutum is suggestive of a pars flaccida cholesteatoma. It may be difficult to assess such bone erosion clinically in an early stage, particularly if a polyp formation is associated (Fig. 8.42). CT-Scan is helpful to detect this early sign, especially in comparing the affected side with the normal aspect of the scutum of the opposite side (Fig. 8.45a, b). Nevertheless lysis of the scutum may be secondary to a Pars Flaccida retraction pocket before its progress to a cholesteatomatous stage (Fig. 8.45c, d).
Fig. 8.45

Coronal CT view of (a) a right ear with amputation of the scutum (arrow) in contact with a rounded condensation of the lateral attic (*), protruding in the EAC, corresponding to a polype on clinical exam, (b) in comparison: the intact scutum (arrow) of the contralateral ear, (c) a right ear: amputated scutum (white arrow) due to a retraction pocket, the “virtual” pocket membrane is not individualized on the CT due to its adhesion to the bony attic wall (black arrow) and (d) endoscopic view, RP and scutum erosion without cholesteatoma formation

8.11.2 Erosion of the Ossicles

  1. 1.

    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).

     
Fig. 8.46

Right ears of two different patients. (a) Axial view of a pars flaccida cholesteatoma, that has invaded the malleus head (dotted arrow) and the incus (arrow), (b) coronal view of a pars flaccida cholesteatoma, lytic effect on the malleus head (dotted arrow), amputation of the scutum (white arrow)

  1. 2.

    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).

     
Fig. 8.47

(a) Rounded soft tissue image (between the empty arrowheads) causing lysis of the head of the stapes (arrow). The long process of the incus is still present (dashed arrow), (b) polylobulated soft tissue mass (empty arrow) of a pars tensa retraction pocket (curved arrow) with lyses of the stapedial head (arrow) and disappearance of the long process of the incus (*) and (c) cholesteatoma around the handle of the malleus, with lyses of the malleus handle (arrow)

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

Sign of a cholesteatomatous process invading the AER is the erosion of the cog; the cog is always preserved in non- cholesteatomatous inflammatory condensations of the AER (Fig. 8.48).
Fig. 8.48

Axial view of a left ear with extended cholesteatoma to the AER (*), the cog is almost completely eroded (black arrow), eroded malleus head (empty arrow)

8.11.4 Erosion of the Semicircular Canals (Labyrinthine Fistula)

CT-scan reveals the erosion of the bony wall of the semicircular canals with a sensitivity and specificity up to 100% (see Chap.  9.8) (Fig. 8.49). It may assess the size of the bony defect, that is of concern for its surgical strategy and management.
Fig. 8.49

Axial CT images of the right ear of different patients with cholesteatoma of the tympanic cavity (*): (a) advanced focal lysis of the bony cover of the lateral semicircular canal (arrow), (b) erosion of the superior semicircular canal (arrow) and (c) erosion of the posterior semicircular canal (arrow)

8.11.5 Erosion of the of Fallopian Canal

The integrity of the thin bony facial nerve canal is not always easy to confirm scanographically and to differentiate from adjacent soft tissue (Fig. 8.50). Not rarely, the bony canal is spontaneously dehiscent with a slight prominence of the facial nerve, best seen on coronal views. Role of CT Scan is to alert the otosurgeon especially about the anatomical location of the facial nerve in relation to the neighboring soft tissue pathologies.
Fig. 8.50

(a) Coronal CT on a right ear with pars flaccida cholesteatoma, intact facial nerve canal (arrow) and (b) coronal CT of a right ear with a huge cholesteatoma (*), the facial nerve canal is eroded (arrow)

8.11.6 Erosion of the Tegmen

CT-Scan is specific in confirming the tegmen integrity. The absence of a visible tegmen can be due to a lytic involvement of the tegmen or to a congenital dehiscence: the differential diagnosis is made with the clinical context, comparaison with the controlateral side or associated lytic lesions elsewhere in the middle ear cleft (Fig. 8.51).
Fig. 8.51

CT-Scan with a left ear cholesteatoma: (a) axial view of the normal right side, intact bony facial nerve canal (arrow) and intact tegmen (empty arrow), (b) axial view of the left ear: large condensation image at the site of the geniculate ganglion (thick white arrow), absence of the lateral bony canal of the facial nerve (thin arrow), disappearance of the tegmen (empty arrow), (c) coronal view of the condensation occupying the site of the geniculate ganglion (long white arrow), disappearance of the tegmen (empty arrow). Amputation of the scutum (short arrow), large opening of the tegmen (empty arrow)

8.11.7 Extension of the Cholesteatoma into the Mastoid

In cases where the antrum is aerated, the negative predictive value is very high that there is no extension of the cholesteatoma into the mastoid (Fig. 8.52a). If the mastoid septa are preserved despite cell condensations, a chronic non-cholesteatomatous infection is the most probable diagnosis (Fig. 8.52b).
Fig. 8.52

Axial CT-images at the attico-antral level of different patients that presented with attical cholesteatoma, but associated to the following very different aspects of antrum and mastoid: (a) a sclerotic mastoid, only the antrum (A) is pneumatized, with regular borders → no extension of the cholesteatoma to the mastoid is suspected, (b) antrum (A) and the mastoid cells (M) are completely condensated, but all trabeculations are well preserved → most probably no extension to the antrum/mastoid. Preserved Korner’s septum (arrow), (c) very thick soft tissue formations with irregular borders (arrows), extending into the antrum (A) highly suspicious for a cholesteatoma extension in a sclerotic mastoid and (d) complete disappearance of any mastoid cell with smoothed borders, evident extension of the cholesteatoma to the entire mastoid cavity: T (tympanic cavity), A (antrum), M (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

This is a significant CT-scan finding especially when a major part of the posterior bony wall is eroded. This finding is important because of its impact on the selection of the surgical procedure! (see Fig. 8.53).
Fig. 8.53

Axial CT image of a right ear with a large defect of the posterior wall of the external auditory canal (between the arrows), due to the bone necrosis by the cholesteatomatous process (*) of the mastoïd

In some occasions CT may be advantageous over the clinical exam, especially in front of a very dense tympanic membrane after tympanoplasty, with limitation of the otoscopic evaluation (Fig. 8.54).
Fig. 8.54

Left ear post tympanoplasty, CHL, behind a thick tympanic membrane on otoscopy, CT revealed (a) on the axial CT-image a thickened tympanic membrane (arrow), a retrotympanic round condensation with polylobulated borders, highly suggestive of cholesteatoma (*) and (b) on the coronal reconstruction the thickened tympanic membrane (thick arrow), the condensation image (*) in contact with the incudostapedial joint that starts to be lytic (thin arrow)

8.11.9 Limitations of CT Imaging

Condensation images in the tympanic cavity and mastoid are not specific for cholesteatoma and can be also sign of granulation tissue, fibrous tissue, mucosal oedema, effusion or other inflammatory reactions. This is why the cholesteatoma diagnosis is primarily a clinical diagnosis and CT must be read as a complement to the clinical informations. The diagnostic value of CT Imaging is resumed in Table 8.2.
Table 8.2

CT-Scan Contribution

Imaging Findings

CT-Scan Value

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?

Non-specific value

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 [95].

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. [95] 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.

Before the era of the diffusion weighted images, delayed T1 images 30–40 min after injection of Gadolinium have been used for the diagnosis by showing a thin enhancement around the cholesteatoma, that itself does not show any uptake of Gadolinium (Fig. 8.55). However, realization of these delayed sequences is time consuming and today not anymore routinely done, as the diffusion weighted sequences (Fig. 8.56) have proved high sensitivity and specificity.
Fig. 8.55

Typical MRI patterns of Cholesteatoma in the right mastoid: (a) T2 hyperintense (arrow), (b) T1 hypointense (arrow) and (c) T1 post Gd delayed images: contrast enhancement around the hypointense cholesteatoma (arrows)

Fig. 8.56

Cholesteatoma of the antrum on the right side, the different slides are taken at the same anatomic level, MCF (middle cranial fossa), the cochlea (small arrow in all slides), (a) T1 weighted: hypointense rounded lesion (arrow) surrounded by hypointense mastoid cells, (b) T2 slightly hyperintense lesion (arrow) surrounded by condensated mastoid cells, (c) Diffusion image b 1000: striking restriction (bright appearance) in this lesion, no restriction elsewhere in the mastoid cells

MRI permits to differentiate other pathologies from cholesteatoma, mainly cholesterol granuloma that has high signal intensity on both T1 and T2 sequences, but no restriction, no contrast enhancement (Fig. 8.57). Granulation tissue, inflammatory mucosa and scar tissue do not show any restriction, but early Gadolinium contrast enhancement (Fig. 8.58). The main MR findings for the different pathologies are summarized in Table 8.3.
Fig. 8.57

Cholesterol granuloma: hyper T1, hyper T2 of a left ear. (a) coronal T1 weighted image showing a round mass predominantly hyperintense (arrow), containing some central hypointense structures and (b) coronal T2 weighted image showing the same hyperintense aspect of the mass lesion (arrow)

Fig. 8.58

Inflammatory granulation tissues: T2 hyperintense, T1 hypointense, T1 post GD uptake characteristic aspects of inflammatory granulation tissues (white arrow) behind the cholesteatomatous process of Fig. 8.55: (a) hyperintense on T2 weighted images, (b) hypointense on T1 weighted images and (c) with clear contrast uptake on T1 weighted images after Gd administration

Table 8.3

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% [96].

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.

Therefore, the most recent classification proposed by EAONO/JOS in 2017 does not only describe the various localisations of cholesteatoma in the Attic (A), Tympanum (T) and Mastoid (M), but also indicate the sites where the surgery of cholesteatoma meets difficulties for a complete excision hence a high rate of recidivism (Anterior Epitympanum (AER) = S1, Sinus tympani = S2) (Fig. 8.59).
Fig. 8.59

Division of the middle ear spaces using the STAM system as proposed in the EAONO/JOS Classification in 2017

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.

Case 1:

Pars tensa retraction from the cavity into the attic, with a rounded process of tissular density extended into the AER (Fig. 8.60a, b). Reconstructions in a sagittal plane enable a superposition of the manifestations to the Schema of the EAONO/JOS Classification (Fig. 8.60c, d) and classifies the cholesteatoma as S1 AM.
Fig. 8.60

Pars Tensa Retraction Pocket Cholesteatoma: S1 AM. Axial CT- image of the right ear: (a) retraction of the tympanic membrane (blue arrow), tissue density mass anterior to the malleus handle extending into the anterior epitympanum (S1), (b) huge PT retraction pocket (blue arrow) with complete absence of the long process of the incus, soft tissue mass anterior to the malleal neck (S1). Space S2 is free (S2), (c) sagittal reconstruction: soft tissue mass in the anterior epitympanum (S1, yellow circle), condensation images of the Attic (blue circle) and the Mastoid (red cercle) and (d) Schema of sites according to EAONO/JOS 2017

Case 2:

A pars tensa retraction pocket invading the tympanic cavity adherent to the promontory (Fig. 8.61). On CT, there is a rounded soft tissue mass extended into the sinus tympani (S2) (Fig. 8.62a). Advanced lyses of the incus (Fig. 8.62b). Sagittal reconstruction along the incudomalleal axis show an aerated S1, free attic (A) and mastoid (M) (Fig. 8.62c) .Staging according to EAONO/JOS shows posterior tympanic cavity condensations (T) together with a S2 mass (S2) = stage S2 T.
Fig. 8.61

Left pars tensa RP cholesteatoma

Fig. 8.62

Pars tensa retraction pocket and cholesteatoma of the sinus tympani (S2), according to EAONO Classification S2 T. (a) Axial CT-Image of the left ear: retraction of the tympanic membrane on the promontorium (empty arrow) and on a soft tissue mass developed inside the sinus tympani (black arrows), slightly different in density to the round window recess (dotted arrow). S2 localization (orange circle), (b) axial CT image of the same ear: slightly above a): no further condensation images, but absence of the incus (empty arrow), S1 free, (c) sagittal CT-Scan reconstruction along the incudomalleolar axis (red line) showing a aerated AER (S1), free attic (A) and mastoid (M) and (d) schema EAONO/JOS 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 [56].

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 [100].

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

When the diagnosis of cholesteatoma is made, a complete adequate work up should be done and a surgical procedure be considered, a clear and detailed counseling must be undertaken and the following items should be discussed with the patient or his family:
  1. 1.

    The nature of the pathology and its great potential of recurrence.

     
  2. 2.

    The actual conditions of hearing, the stage of the disease, its functional and vital impacts.

     
  3. 3.

    Why it is a surgical pathology and the impact of an adequate surgery to insure a safe ear.

     
  4. 4.

    The selection of the surgical techniques will depend on the per-operative findings.

     
  5. 5.

    The possible complications of the disease and the possible complications of the surgery.

     
  6. 6.

    The main objective is to insure a safe ear, hearing rehabilitation may be left to staging.

     
  7. 7.

    Why second looks must be considered.

     
  8. 8.

    Why strict care of an open cavity is a need.

     
  9. 9.

    The great importance of a long term follow up and why it could be for life.

     
  10. 10.

    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

Surgery of cholesteatoma implies the following:
  1. 1.

    Total eradication of cholesteatoma to obtain a safe and dry ear.

     
  2. 2.

    Maintain the best condition for a successful wound healing process in the ear.

     
  3. 3.

    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:

8.15.2.1 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.

8.15.2.2 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

Several clinical considerations must be taken into account when choosing a surgical approach, as each technique has advantages and disadvantages. In addition, the surgeon’s expertise of surgical procedures is a major determinant to achieve the main objectives: “a safe ear and a preserved hearing”.
  1. 1)

    A CWD mastoidectomy involves the removal of the posterior bony canal wall.

     
  2. 2)

    CWU mastoidectomy implies the removal of all mastoid air cells while maintaining the integrity of the posterior ear canal wall.

     
  3. 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)

     

8.15.3.1 Canal-Wall-Down (CWD) Procedure

Indications

  • 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.

Fig. 8.63

CWD mastoidectomy of left ear

Advantages

  • 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).

Fig. 8.64

Right ear mastoid cavity of a patient who was operated two years ago for third recurrent cholesteatoma. The cavity is stable and self cleaning. Any residual disease can be easily seen and removed in the office. There are no hidden spaces for the skin to retratct inside it and thus the possibility of recurrent cholesteatoma is very low

Disadvantages

  • 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) [101], 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).

Fig. 8.65

Right troublesome mastoid cavity

8.15.3.2 Canal-Wall-Up (CWU) Procedure

The CWU procedure is recommended to avoid the disadvantages of the CWD.

CWU consists of a preservation of the posterior bony external auditory canal wall during a complete simple mastoidectomy with or without a posterior tympanotomy (Figs. 8.66, 8.67, 8.68).
Fig. 8.66

CWU mastoidectomy of left ear. Cholesteatoma originating from Prussak’s space (black arrow) and extending into the antrum (A)

Fig. 8.67

In CWU mastoidectomy, the posterior wall of the ear canal is preserved (C). (a) Anterior epitympanotomy is performed to expose the anterior epitympanum and supratubal recess and (b) posterior tympanotomy is performed to expose the retrotympanum. M: malleus; I: incus; VII: facial nerve

Fig. 8.68

Resection of middle ear cholesteatoma by CWU mastoidectomy. (a) Removal of cholesteatoma from the middle ear, at this stage the stapes and facial nerve should be identified, Incus connection to the stapes should be also verified (b) after mastoidectomy and removal of cholesteatoma from antrum, posterior tympanotomy is performed to expose the retrotympanum, (c) cholesteatoma is dissected from facial nerve and footplate and (d) the residual cholesteatoma in the retrotympanum is removed en bloc

A staged CWU procedure is often necessary with a scheduled second look operation at 6–18 months for removal of any residual cholesteatoma and for ossicular chain reconstruction, when indicated (Fig. 8.69). In younger children, second-look operations are often scheduled 6–9 months following the primary surgery. In adults, the second look operation is mostly planned after 12 months postoperatively.
Fig. 8.69

Residual cholesteatoma in a second look surgery after CWU.

Indications

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.

Contraindications
CWU procedures are relatively contraindicated in:

  • 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.

Fig. 8.70

Advantages of CWU procedure

Disadvantages

  • 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).

8.15.3.3 Other Surgical Approaches

Various surgical approaches have been developed to address the drawbacks of CWU (high residual rates) and CWD (cavity problems) mastoidectomies. Modified methods include tailor-made tympanomastoidectomy with cartilage reconstruction, transcanal endoscopic management of the cholesteatoma, and laser-assisted cholesteatoma surgery. However, only minimal data related to their outcomes are available. Long-term outcomes require more studies.
  1. (a)

    Mastoid obliteration

    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 [102]. 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.

     
  2. (b)

    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.

     
  3. (c)

    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.

     
Fig. 8.71

Schema demonstrating the technical concept in mastoid obliteration: Intact canal wall technique with mastoid and attic obliteration, reducing the ME cavity volume in order to adapt the middle ear mucosa gas exchange to the inadequate ET ventilation function

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

The use of endoscopy demonstrated a positive impact on the management of cholesteatoma. Otoendoscopy has the advantages of better visualization of some hidden areas such as: sinus tympani, facial recess, anterior epitympanic space, attic, hypotympanum, medial epitympanum and retrotympanum (Fig. 8.72). The disadvantages of oto-endoscopic surgery are time consuming and “one hand surgery”. However endoscope assisted-microsurgery allows the use of the most efficient tools to face difficult sites of localization of the cholesteatoma, and allow its complete removal.
Fig. 8.72

(a) Endoscopy of the attico-mastoid area showing the whole epitympanum, (b) endoscopy of the middle ear through the posterior tympanostomy showing the Eustachian tube (ET) and (c) endoscopy of the retro tympanum using angled scope from the posterior tympanotomy. R: round window; I: incus; M: malleus

Combined surgeries done with microscope, endoscope or endoscope/microscope [106] 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

Congenital cholesteatoma occupies mostly the anterior upper quadrant of the eardrum. When discovered as small as a pearl (Figs. 8.2 and 8.73), complete and in toto excision without opening the capsule of the cholesteatoma is the rule. Extension of such type of congenital cholesteatoma may follow the malleal folds, medial to the malleus neck, the manubrium and the interosseous fold to reach the incus and the anterior stapes crura. In this case, delicate dissection is required to insure complete excision without opening the capsule or dislocating the ossicles.
Fig. 8.73

Right ear with a congenital cholesteatoma, localized posterosuperiorly EAONO/JOS stage I. (a) axial CT-view and (b) coronal reconstruction: small condensation image (arrrow) in the outer attic beside an intact scutum

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.

When the diagnosis is delayed, congenital cholesteatoma may extend largely and requires the same approaches as in acquired cholesteatoma (Fig. 8.74).
Fig. 8.74

Extended congenital cholesteatoma. (a) Otoscopic view of a congenital cholesteatoma bulging behind an intact eardrum, (b) corresponding CT view in the coronal plan showing the bulging of the tympanic membrane into the EAC (arrow), (c) axial CT-view of the polylobulated bulging (arrows) of the tympanic membrane, that molds an underling polylobated process, even if its density is not specific, (d) mass effect on the ossicular chain (arrow), that is pushed laterally and partially lytic

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).

The ossicular chain can be restored in one stage surgery when the complete removal of the cholesteatoma is certain. In cases with a potential risk of residual disease, however, ossicular chain reconstruction is often deferred to a second-look operation where a potential residual is anticipated: “safe ear prevails on hearing restoration” (Fig. 8.75).
Fig. 8.75

Primary vs. secondary ossicular chain reconstruction (OCR) in cholesteatoma surgery

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.

It is admitted that the recurrence and residual lesion rates are higher in children: 30% versus 15% in adults. The following factors are incriminated:
  1. 1.

    Sinus tympani invasion and ossicular lysis at the moment of diagnosis

     
  2. 2.

    An impaired ET function with persistent impaired aeration of the ME

     
  3. 3.

    A large périmatrix with its more active inflammatory and aggressive mediators.

     

8.15.10 Follow-Up

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

8.15.11.1 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 [112], 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 [96].

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 [113].

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.

Accordingly and in order to insure a safe ear especially in children, the otologist’s attitude would be as the following:
  1. 1.

    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

     
  2. 2.

    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.

     

8.15.11.2 Postoperative Imaging Longtime After the Initial Surgery in Cases with a “Non-Adequate Follow-Up”

In cases when the clinical diagnosis of a possible residual is doubtful or the surgical procedure has been executed in a different center, CT is the first imaging method to be requested:
  1. 1.

    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. 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

     
  3. 3.

    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. 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).

     
  5. 5.

    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).

     
Fig. 8.76

Right ear with recurrence of cholesteatoma in the cavity of mastoïdectomy after CWU. (a) A normal thin tympanic membrane, normal EAC, (b) amputation of the scutum with a free attic, (arrow) (c) axial and (d) coronal CT-images show the hidden atticoantral cavity of mastoidectomy, that contains a huge recurrent cholesteatoma (*)

Fig. 8.77

ATCDs of CWD for cholesteatoma. (a) Axial CT view of the right ear: rounded tissular masses in the anterior tympanic canal wall (thin arrow) and posterior part of the open cavity (thick arrow), near to the prominent sigmoid sinus (SS in all images), AER free (S1, empty arrow), (b) axial CT image passing by the upper attic, with residual cholesteatoma (arrowheads), (c) sagittal CT reconstruction showing cholesteatoma anteriorly (thin arrow), in the posterior wall (thick arrow) and in the attic (arrowhead), the prominent sigmoid sinus is lining the whole cavities’ height (SS) and (d) axial CT image showing the tympanic cavity with a myringostapedopexy (arrow), and a well aerated sinus tympani (S2, empty arrow)

Fig. 8.78

CT follow up with a suspicious otoscopy. The whole middle ear cleft is condensated M: cavity of mastoidectomy, T: tympanic cavity

Fig. 8.79

MRI of the temporal bone in the same patient of Fig. 8.76. (a) T1 SE weighted image showing a rounded hypointense mass (thick arrow) in the middle ear cavity on the level of the basal turn of the cochlea (dashed arrow), (b) T2 TSE weighted image on the same level: the mass is hyperintense (thick arrow), good visibility of the cochlea (dashed arrow) at the same level, (c) diffusion weighted image at b = 0: the mass (arrow) is hyperintense due to its T2 effect and (d) diffusion weighted image at b = 1000: the mass shows still a high hypersignal that represents restriction and is specific for cholesteatoma at b = 1000

Fig. 8.80

(a) After cholesteatoma-surgery, a non specific mastoid opacification (*) is seen on the axial CT-view, (b) injected MRI T1 sequence: no enhancement in the corresponding hypointense lesion (*), (c) MRI T2 sequence: lesion with homogeneous hypersignal (*), (d) diffusion weighted image at b = 0 is very bright (*), and (e) diffusion weighted image at b = 1000 is dark for the lesion (*), meaning no restriction; (f) surgical exploration reveals only fluid and absence of cholesteatoma

Conclusion

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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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Salah Mansour
    • 1
  • Jacques Magnan
    • 2
  • Karen Nicolas
    • 3
    • 4
  • Hassan Haidar
    • 5
  1. 1.Lebanese University, Department of OtolaryngologyHNS Amoudi Center Boulevard MazraaBeirutLebanon
  2. 2.Aix-Marseille UniversityMarseilleFrance
  3. 3.Department of RadiologyMiddle East Institute of HealthBsalimLebanon
  4. 4.Lebanese UniversityBeirutLebanon
  5. 5.Department of OtolaryngologyHamad Medical Corporation, Weill Cornell Medical CollegeDohaQatar

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