Congenital Cholesteatoma

Definition

• Scott-Brown's Otorhinolaryngology, Vol 2, p. 4511
• Cummings Otolaryngology, p. 728

Pathogenesis / Embryology

• The Developing Human - Clinically Oriented Embryology, p. 2580
• Scott-Brown's Otorhinolaryngology, Vol 2, p. 4517

Anatomic Classification

• Cummings Otolaryngology, p. 728

Clinical Features

• White, opalescent mass behind an intact tympanic membrane (the classic "keratin pearl")
• Conductive hearing loss (usually the presenting complaint)
• ~50% of patients present with recurrent otitis media
• May fistulize through the tympanic membrane if untreated

• Facial nerve paralysis (insidious, progressive)
• Sensorineural hearing loss or vestibular dysfunction from labyrinthine/IAC erosion
• May expand dramatically before producing symptoms

• Cummings Otolaryngology, p. 733-735

Staging (Potsic System)

• Scott-Brown's Otorhinolaryngology, Vol 2, p. 4542-4557

Diagnostic Evaluation

• Otoscopy: White, pearly mass behind an intact tympanic membrane
• High-resolution CT (temporal bone): Demonstrates soft tissue density in the middle ear; identifies ossicular erosion and bony destruction
• MRI: CC shows slightly higher signal than CSF on T1, and moderately high signal on T2-weighted images. Diffusion-weighted imaging (DWI) shows restricted diffusion (bright on DWI, low on ADC map) -- key for differentiating from cholesterol granuloma (which is bright on both T1 and T2) or arachnoid cysts
• Cummings Otolaryngology, p. 740

Surgical Management

• Goal: Complete removal of the cholesteatoma matrix or permanent exteriorization
• Isolated middle ear CC: Can be removed transtympanically with full visualization of the extent of the lesion, especially on the medial aspect of the eardrum
• Ossicular erosion: Standard middle ear reconstructive techniques (ossiculoplasty, TORP/PORP)
• Perigeniculate / Petrous apex CC: Approaches include middle cranial fossa, transotic, or transsphenoidal, depending on hearing status and location
• Cummings Otolaryngology, p. 745

Key Distinguishing Features (vs. Acquired Cholesteatoma)

Why Labyrinthitis and SNHL Occur in COM

1. Labyrinthine Fistula (Most Common Mechanism)

• It is the most prominent structure in the aditus ad antrum
• It lies directly in the path of an enlarging posterior-superior cholesteatoma
• The cholesteatoma matrix produces pro-inflammatory cytokines that activate osteoclasts, causing progressive demineralization and bone resorption

1. Cholesteatoma matrix contacts the endochondral bone of the labyrinth
2. Osteoclast-mediated bone erosion -- the bone first demineralizes, then disappears
3. Intraoperatively, a thin residual bone layer appears as a "blue line" parallel to the canal lumen
4. Eventually, only the endosteum (and sometimes just perilymph) separates the middle ear from the inner ear

"Labyrinthine fistula represents an erosive loss of the endochondral bone that overlies the semicircular canals without loss of perilymph... This loss of the overlying protective bone allows pressure or mass-induced motion of the underlying endosteum, perilymph, and, by contiguity, the endolymphatic compartment, which evokes vestibular and sometimes auditory symptoms."

• Cummings Otolaryngology, p. 2307

2. Spread of Infection: Serous vs. Suppurative Labyrinthitis

• Shambaugh Surgery of the Ear, p. 5672-5675
• Scott-Brown's Otorhinolaryngology, Vol 2, p. 915-940

3. Diffusion of Ototoxic Substances Through the Round Window Membrane

• Chole and Chiu demonstrated loss of cochlear hair cell stereocilia in animals with experimental cholesteatomas, with or without infection
• McGinn and Chole showed hair cell loss in areas of the cochlea subjacent to areas of bone erosion, suggesting ototoxic substances may traverse the bony cochlear wall directly
• Meyerhoff et al. found that 17.9% of temporal bones with COM showed histologic evidence of labyrinthitis
• Vartiainen and Karjalainen compared 874 chronically infected ears to 609 controls and found significantly worse bone conduction (cochlear function surrogate) in infected ears -- ears with cholesteatoma were worse than those without

"The destructive effects of an expanding cholesteatoma within the middle ear or mastoid and concomitant chronic infection are not limited to the bony structures of the temporal bone."

• Cummings Otolaryngology, p. 1191

• Cochlear hair cells (outer > inner)
• Spiral ganglion cells
• Stria vascularis -- type I fibrocytes in the spiral ligament express NF-κB, which alters ion channel function and impairs endocochlear potential
• Scott-Brown's Otorhinolaryngology, Vol 2, p. 918-923

Summary of Mechanisms

COM (cholesteatoma/infection)
        |
        ├── Bone erosion → Labyrinthine fistula (lateral SCC most common)
        │           ├── Pressure on endosteum → Vestibular symptoms
        │           └── Bacterial invasion → Suppurative labyrinthitis → Dead labyrinth
        │
        ├── Toxin/mediator diffusion → Round window membrane
        │           └── Serous labyrinthitis → Cochlear hair cell damage → SNHL
        │
        └── Direct bony cochlear wall traversal by ototoxic substances
                    └── Hair cell loss → SNHL

Clinical Note on Surgical Management of Labyrinthine Fistula

• Removing the matrix risks perilymph loss and SNHL (~10% risk of SNHL in reported series)
• Leaving the matrix intact at first surgery (canal wall up or canal wall down) and removing it at a second stage -- when the matrix has walled off into a small cyst -- results in SNHL avoidance in >96% of cases
• Shambaugh Surgery of the Ear, p. 5651-5663

How Cholesteatoma Spreads and Destroys - The Full Picture

Part 1: Structure of the Lesion (What Is Spreading)

• Cummings Otolaryngology, p. 1186

Part 2: Routes and Direction of Spread

Pars Flaccida (Attic/Epitympanic) Cholesteatoma - Most Common

1. Retraction pocket forms in the pars flaccida → invaginates into the Prussak space (lateral epitympanic recess)
2. Keratin accumulates → sac expands medially
3. Scutum (lateral attic wall) is eroded first
4. Ossicles are displaced medially and eroded - the long process of the incus is the most frequently destroyed ossicle
5. Spreads posteriorly into the aditus ad antrum → mastoid antrum → mastoid air cells (automastoidectomy)
6. Can track medially to the tegmen (roof), causing tegmen dehiscence and dural exposure
7. Can erode the lateral semicircular canal (labyrinthine fistula)
8. Can track along the fallopian canal → facial nerve involvement

Pars Tensa (Posterosuperior) Cholesteatoma

1. Arises from posterior or posterosuperior marginal perforation
2. Grows medial to the ossicular chain (unlike pars flaccida type which is lateral to ossicles)
3. Erodes the posterior lateral attic wall and posterosuperior EAC wall
4. Tends to erode the stapes superstructure and long process of incus early
5. Higher tendency for inner ear erosion compared to pars flaccida type

• Shambaugh Surgery of the Ear, p. 2069-2083
• Scott-Brown's Otorhinolaryngology, Vol 2, p. 767-793

Part 3: The Physiology of Bone Destruction

Step 1: The Old (Wrong) Theory - Pressure Necrosis

• Cummings Otolaryngology, p. 1133

Step 2: Osteoclast-Mediated Bone Resorption (The Core Mechanism)

• Osteoclasts form a tight sealing zone against bone
• They create a ruffled border -- a highly folded membrane that dramatically increases surface area
• The space beneath the ruffled border is acidified (pH 4.0)
• Acid phosphatase dissolves the mineral (hydroxyapatite) phase of bone
• Acid proteases (cathepsin-like enzymes) and collagenase dissolve the organic collagen matrix
• The resulting resorption lacunae progressively deepen, eating through bone

Step 3: The RANK/RANKL Signaling Cascade

• The cholesteatoma matrix and surrounding bacterial products (LPS from biofilm) trigger inflammation
• This activates T cells, macrophages, and stromal cells in the perimatrix
• These cells express RANKL (Receptor Activator of NF-κB Ligand) on their surface
• RANKL binds to RANK receptors on osteoclast precursors (bone marrow-derived monocytes)
• This drives osteoclastogenesis -- differentiation of precursors into active multinucleated osteoclasts
• M-CSF (macrophage colony-stimulating factor) potentiates this process
• Osteoprotegerin (OPG) is the natural decoy receptor that would normally inhibit RANKL -- in cholesteatoma, OPG is overwhelmed by the pro-inflammatory state
• Pro-inflammatory cytokines TNF-α, IL-1, IL-6 further amplify osteoclast activation

Step 4: Matrix Metalloproteinases (MMPs)

• MMPs 1, 2, 3, and 9 -- expressed in basal and suprabasal cell layers of the matrix
• Neutrophil collagenase -- found throughout the epithelium and granulation tissue
• TIMP-1 (tissue inhibitor of MMPs) is present only in tiny amounts in granulation tissue -- meaning the inhibitory check is essentially absent

• MMPs degrade the extracellular matrix around bone (collagen, fibronectin, gelatin)
• Neutral collagenase specifically degrades the osteoid (unmineralized collagen) surface of bone, stripping away the organic layer and directly exposing mineralized bone to osteoclastic attack
• This "primes" the bone surface for osteoclast binding and resorption
• Cummings Otolaryngology, p. 1147-1150

Step 5: Keratin Debris as a Direct Inflammatory Trigger

• Keratin itself triggers a foreign body granuloma response
• This elicits further macrophage and inflammatory cell infiltration
• Which amplifies the osteoclastic response locally

Part 4: Why Endochondral Bone Is More Resistant

• The mastoid air cells and middle ear walls are destroyed early
• The otic capsule resists erosion longer, but once breached causes labyrinthine fistula
• Cummings Otolaryngology, p. 1143

Summary Flowchart

Cholesteatoma matrix expansion
          │
          ├── Physical: Sac grows along paths of least resistance
          │     (Prussak space → aditus → antrum → mastoid → tegmen/labyrinth/skull base)
          │
          └── Biochemical bone destruction:
                │
                ├── Bacteria (LPS) + cholesteatoma products
                │       ↓
                ├── Inflammation → TNF-α, IL-1, IL-6
                │       ↓
                ├── RANKL on T-cells/stromal cells → RANK on osteoclast precursors
                │       ↓
                ├── Osteoclast activation → acid phosphatase + cathepsins
                │       → demineralize + digest bone collagen
                │
                ├── MMPs from epithelium → degrade extracellular matrix
                │   Neutral collagenase → strips osteoid → exposes bone
                │
                └── Keratin extrusion → foreign body granuloma → amplifies cycle

• Cummings Otolaryngology, p. 1131-1165
• Scott-Brown's Otorhinolaryngology, Vol 2, p. 767-793
• Shambaugh Surgery of the Ear, p. 2051-2097

Attic Reconstruction in Cholesteatoma: When and Why

First, Understand the Anatomy: What Is the "Attic"?

• A lateral wall = the scutum (the bony lateral attic wall, part of the EAC superior wall)
• A medial wall = the tegmen, facial nerve, and otic capsule structures
• Contents = the head of malleus, body and short process of incus

The Two Types and Their Position Relative to Ossicles

Pars Flaccida (Lateral to Ossicles): Attic/Scutum Reconstruction

• After complete removal of the cholesteatoma, the scutum defect must be reconstructed in almost all canal-wall-up (CWU) approaches
• The goal is to restore the lateral bony buttress so the tympanic membrane/pars flaccida cannot re-retract
• This is done at the primary surgery or at second-look surgery depending on disease extent

1. Tragal cartilage with perichondrium -- most popular; rigid, resistant to resorption, good for defects up to ~3 mm
2. Cortical bone pate (crushed mastoid bone mixed with blood)
3. Temporalis fascia alone -- less rigid, higher retraction/recurrence risk
4. Calcium phosphate ceramics / hydroxyapatite -- synthetic option

• Marchioni et al., Otolaryngol Clin N Am 2013: In 146 patients with attic cholesteatoma managed endoscopically, 52.7% had cartilage scutum reconstruction, 14.4% bone pate, and 32.9% temporalis fascia.

Pars Tensa (Medial to Ossicles): Ossiculoplasty, Not Scutum Repair

• Incus interposition -- reshaped removed incus placed between malleus and stapes head (if stapes suprastructure intact = Type III tympanoplasty equivalent)
• PORP (Partial Ossicular Replacement Prosthesis) -- from stapes head to tympanic membrane/malleus, when incus is gone but stapes suprastructure present
• TORP (Total Ossicular Replacement Prosthesis) -- from footplate to tympanic membrane, when stapes suprastructure also eroded
• Staged reconstruction -- if disease was extensive or infected, leave the middle ear with a Silastic sheet and reconstruct at a second-look operation (6-12 months later)

The Decision Framework: Lateral vs. Medial

Cholesteatoma position relative to ossicles
         │
         ├── LATERAL to ossicles (Pars flaccida / Prussak space)
         │      │
         │      ├── Scutum eroded → ATTIC (SCUTUM) RECONSTRUCTION needed
         │      │      Material: cartilage > bone pate > fascia
         │      │
         │      └── If ossicles also eroded → ossiculoplasty ALSO needed
         │
         └── MEDIAL to ossicles (Pars tensa / posterosuperior)
                │
                ├── Incus long process / stapes eroded → OSSICULOPLASTY needed
                │      (PORP or TORP depending on stapes status)
                │
                └── Scutum less commonly affected → attic repair less critical
                    (posterior attic wall may need repair if eroded posteriorly)

The Bigger Picture: Why Attic Reconstruction Matters for Recurrence

1. Eustachian tube dysfunction → negative middle ear pressure
2. Thinned, unsupported pars flaccida is sucked medially → retraction pocket
3. Keratin accumulates → cholesteatoma

"The recurrence consists in a new dangerous tympanic retraction pocket caused by inadequate reconstruction of the scutum and tympanic loss of substance, inducing persistence of the physiopathologic process of middle ear depression."

• Marchioni et al., Otolaryngol Clin N Am 2013

Summary Table