The outer ear includes the visible part commonly known as the auricle or pinna and a slightly curved short external auditory canal that extends inward from the floor of the deepest depression of the auricle, called the concha, and ends at the tympanic membrane. The auricle consists of a thin plate of cartilage and overlying skin that forms an irregular, shallow funnel that is continuous medially with the external auditory meatus. The external auditory meatus is an S-shaped canal that extends about 1.25 inches. The outer third wall of the external auditory canal is composed of cartilage, while the inner two-thirds are formed mostly by the tympanic portion of the temporal bone. The isthmus is the narrowest point of the external auditory canal and is situated just medial to the bony-cartilaginous junction. The inferior wall of the external auditory meatus is about 5 mm longer than the superior wall, conferring obliquity to the tympanic membrane. The entire length of the passage is lined with skin, which also covers the outer surface of the tympanic membrane. The outer cartilaginous portion is covered by thicker skin with fine hairs directed outward and lined with secretory glands that produce cerumen. The ear canal is bound superiorly by the middle cranial fossa, anteriorly by the temporomandibular joint and parotid, medially by the tympanic membrane, posteriorly by the mastoid (a confluence of the squamous and petrous portions of the temporal bone), and inferiorly by the skull base and soft tissues of the neck. The tympanic membrane is a thin, semitransparent oval, and obliquely placed membrane that separates the external and middle ear. The long process of the malleus is attached to the tympanic membrane, resulting in concavity toward the external auditory meatus (Fig. 2).

The middle ear is an air-filled cavity in the petrous portion of the temporal bone located directly internal to the tympanic membrane. It is connected anteriorly to the nasopharynx via the eustachian tube and posteriorly with mastoid air cells via the mastoid antrum. The labyrinth of the inner ear forms much of the internal surface of the middle ear, with the basal turn of the cochlea representing the bulk of the surface directly medial to the tympanic membrane (a.k.a., the mesotympanum). The carotid artery passes through the medial face of the junction of the middle ear and eustachian tube (a.k.a., the protympanum). A complex air-cell system surrounds the labyrinth, connecting the middle ear to the petrous apex. The middle ear is lined by respiratory mucosa and contains three bones (malleus, incus, and stapes) and two muscles (tensor tympani and stapedius). The facial nerve passes from the internal auditory canal, over the cochlea, around the stapes, and caudal to the lateral semicircular canal en route to the stylomastoid foramen at the skull base. In the process, it emanates branches, most importantly, the greater superficial petrosal and chorda tympani nerves. Primary sensory innervations to the middle ear travel by way of Jacobsen’s nerve, or the tympanic plexus, a branch of the glossopharyngeal nerve, as it exits the jugular foramen just caudal to the cochlea (a.k.a., the hypotympanum). A branch of the vagus nerve (Arnold’s) similarly passes across the middle ear to contribute sensory fibers to the external auditory canal and pinna.

The inner ear is located in the petrous portion of the temporal bone. This is grossly divided into the cochlea, the vestibule, and the semicircular canals. Within the vestibule are the otolithic organs, the utricle, and the saccule. The inner ear consists of a bony capsule that is filled with perilymph. Within the bony labyrinth is the membranous labyrinth that is filled with endolymph. The membranous labyrinths contain the hair cells that are responsible for the detection of sound, movement, and gravity. A detailed description of the microanatomy of the inner ear is beyond the scope of this text. The internal auditory canal passes from the petrous apex to the labyrinth, just medial to the vestibule. This contains the cochlear, facial, superior vestibular, and inferior vestibular nerves. The petrous apex may contain air cells contiguous with the middle ear or bone marrow.

The early effects of radiation on the ear are typical of any inflammatory reaction. This includes vascular dilation with pyknotic changes in the endothelium and necrosis of damaged cells (Klemm 1967), swelling of endothelial cells, extravasation of blood cells, stasis, perivascular edema, sticking of platelets, and leukocyte migration leading to subendothelial proliferation (Berg and Lindergren 1961). Fibrosis and other related changes in the middle ear mucosa in rabbits exposed to 3,000–10,500 Roentgen have been reported (Berg and Lindergren 1961). In mild cases, the mucosa was thickened and fibrotic. The epithelium subsequently showed atrophy with some inflammatory cells and hemorrhagic exudates in a few cases. More severe cases exhibited destruction of the epithelium, involvement of the ossicles, evidence of lacunar absorption in the bony walls, and often purulent exudates with both plasma cells and lymphocytes. An example of middle ear fibrosis is shown in Fig. 5.

The radiation-induced changes (i.e., ciliary, vascular, and stromal) in the middle ear mucosa of patients treated with RT for head-and-neck tumors have been observed under transmission and scanning electron microscopes (Elwany 1985) (Table 2). The epithelial changes have included diminution of the cytoplasmic mass, variable degrees of ciliary loss, widening of the intercellular spaces, and reduction in the number of goblet cells in some cases while increases in others. Middle ear mucosa usually only has a few goblet cells (Tos 1979). The density of goblet cells typically increases significantly with chronic tubal occlusion, OME, and active chronic suppurative otitis media. Few tubular seromucous glands may be present in the anterior part of the normal mesotympanic mucosa (Gristwood and Beaumont 1979). The new-gland formation may occur through the invagination of surface epithelium or the division of basal cells. The number and activity of the newly formed glands depends on the nature of the pathologic process in the middle ear, as the glands are highly active in secretory otitis. Normal cilia should beat in the same direction and in a synchronized fashion (metachronal beating). The abnormal ciliary motility is indicative of early ciliary damage. Ciliary loss represents the end stage (Dudley et al. 1982). The reduced cytoplasmic mass could be directly due to cell damage from RT, or it could be secondary to the obliterative vascular changes. The changes in lamina propria include decreased activity of the seromucous glands, depleted secretory granules in acinar cells, and moderate swelling of mitochondria.

Similar to radiation-induced vascular changes in the other parts of the body (Rubin and Cassarett 1968), the capillaries of the middle ear mucosa show endothelial swelling, duplicated basement membrane, and fibrosis and thickening of the vessel walls with replacement by a cord of fibrous tissue, thereby altogether occluding the lumen. The vascular changes are representative of successive stages in the obliterative disease process and are also related to the amount of radiation received by the vessel. Another important factor contributing to vessel damage is injury to surrounding soft tissue with the release of different breakdown products, such as free radicals and peroxides (Baker et al. 1978).

The post-RT connective tissue stroma shows increased production of collagenous fibrous tissue and an increase in synthetically active fibroblasts in the tunica propria. These fibroblasts are characterized by abundant, irregular cytoplasmic processes, numerous mitochondria, and a well-developed granular endoplasmic reticulum.

Morbidity associated with the tympanic membrane involves thickening, sclerosis and perforation without, or after removal or extrusion of tympanostomy tubes (Bhandare et al. 2007). Fibrovascular granulation tissue formation may lead to the growth of inflammatory polyps through a tympanic membrane perforation and persistent otorrhea (Jereczek-Fossa et al. 2003). However, thickening of the tympanic membrane may persist several months after RT and permanent changes are uncommon (van Hasselt and Gibb 1999). Tympanic membrane perforations have been reported to develop long after RT (Carls et al. 2002).

Chronic otitis media (COM) and OME are frequently encountered in patients with head-and-neck cancers (particularly nasopharyngeal cancer) after RT. The development of COM and OME in post-RT patients is attributed to both impaired tubal function and middle ear inflammation (Sato et al. 1988; Young and Hsieh 1992; Young et al. 1995; Ho et al. 2002). Radiation-induced OME occurs in patients with no pre-RT tubal pathology and may have no bearing to the patency of the eustachian tube (Anteunis et al. 1994). The likelihood of an ear with pre-RT OME to have long-term post-RT OME was observed to be much higher compared to an ear without pre-RT OME (Low and Fong 1998).

The effects of radiation on middle ear mucosa in the acute phase include mucositis, sloughing, and edema (Borsanyi and Blanchard 1962), Moss (1959) coined the term “radiation otitis media” for this process. In the chronic phase, it includes epithelial atrophy and fibrosis (Berg and Lindergren 1961).

Acute otitis media most commonly occurs during or within a few weeks after completing RT. Swelling, puffiness, and transient edema of middle ear mucosa caused by the acute inflammatory reaction lead to functional impairment of the tube. Mucosal sloughing exposes binding sites for pathogens and impairs the normal mucociliary clearance mechanism.

OME may develop as a result of dilated capillaries and fluid transduction resulting in edema from further reduction in middle ear pressure. If the eustachian tube is impaired, the subsequent resorption of middle ear gas may create a negative pressure, which promotes further transudation (i.e., “hydrops ex vacuuo”). Inflammatory components of the middle ear effusion may then perpetuate the inflammation, creating a “vicious cycle”. Subsequent to high doses of radiation to the middle ear, two types of chronic otitis media may be observed. The presence of post-RT middle ear effusion without signs of acute inflammation indicates chronic OME (COME), whereas persistence of the suppurative process through a perforation or a tympanostomy tube indicates chronic suppurative otitis media (CSOM).

The eustachian tube connects the middle ear cavity and the nasopharynx. The eustachian tube framework is cartilage. It is lined with respiratory mucosa. Between the cartilage and mucosa is Ostmann’s fat pad, which generally occludes the tube lumen at rest (Aoki et al. 1994). The tensor veli palatini and levator veli palatini muscles arise from the tubal cleft before inserting on the palate. In its resting state, the eustachian tube is closed. Movements of the palate lead to a transient tubal opening.

Differences between pre- and post-RT eustachian tube dysfunction have been reported and are usually observed in nasopharyngeal carcinoma. Pre-RT eustachian tube dysfunction in nasopharyngeal carcinoma patients is caused by tumor invasion of the tensor veli palatini muscle, extrinsic compression, or inflammation (Young and Hsieh 1992; Young and Sheen 1998. Post-RT eustachian tube dysfunction in nasopharyngeal carcinoma patients is caused by both tumor obstruction and functional impairment of the tube (Young et al. 1994; Bhide et al. 2007. The tubal patency and clearance function are affected by radiation, but dynamic function is preserved after radiation (Young and Hsieh 1992).

Post-RT COME has been attributed to obstruction of the eustachian tube opening and fibrosis of the fascial space around the levator veli and tensor palatini muscle (Lederman 1962). Edema and fibrosis resulting from RT can interfere with muscle function and lead to eustachian tube dysfunction (Dias 1966). Abnormalities of the mucosa of middle ear affect the production of mucous and its transportation down the eustachian tube (Fischer et al. 1978). RT has been shown to affect the mucosal cells in the middle ear (Gyorkey and Pollock 1960). The altered nature of mucous production both in quality and quantity after RT can contribute to serous otitis media in these patients.

The blockage of the pharyngeal orifice of the eustachian tube due to radiation-induced inflammatory reactions and the resorption of gas from the middle ear results in negative pressure, retraction of the tympanic membrane, and decreased mobility of the ossicular chain. The end result is pressure, pain, and hearing loss.

The supporting structures surrounding the eustachian tube were seen to be replaced by fibrous tissue in one study on the histopathology of the human eustachian tube (Takasaki et al. 2000). In some cases, the recovery of its functional impairment during the 5-year period post-RT has been observed and attributed to a subsiding inflammatory reaction (Young et al. 1994). Further delayed fibrosis and atrophy of the pharyngeal orifice of the eustachian tube, its mucosal lining, and Ostmann’s fat pad may contribute to the development of a pathologically patent, “patulous,” tube 5–10 years after RT (Takasaki et al. 2000). This may lead to a constant sensation of aural fullness and the patient hearing his or her own breathing or voice (known as autophony).

Osteoradionecrosis of the temporal bone is a well recognized, pathological entity that manifests with symptoms of refractory otitis externa, otalgia, otorrhea, and hearing loss (Leach 1965; Schuknecht and Karmody 1966; Thornley et al. 1979; Wurster et al. 1982). The basic reactions in the temporal bone to radiation involve vasculitis leading to obliterative endarteritis and aseptic necrosis of bone with compensatory reparative fibrosis enhancing the susceptibility of bone to injury, infection, and fracture. The effects of radiation have been divided into effects on soft-tissue damage and effects on bone (Leach 1965; Schuknecht and Karmody 1966; Fajardo and Berthrong 1988). The soft-tissue damage includes dermatitis of the external auditory canal, middle ear mucosal inflammation, otitis media, and aseptic labyrinthitis. The histologic observations on bone include destruction of osteoblasts from trabecular margins, loss of osteocytes (empty lacunae), progressive replacement of hematopoietic elements by loose connective tissue, thickening of vascular walls, narrowing of lumen with a concomitant decrease in the number of capillaries and sinusoids, and the absence of osteocytes followed by a lack of new osteoid deposits. The ischemic changes make the bone susceptible to infection.

Osteonecrosis of the temporal bone has been separated into two distinct patterns, localized and diffuse (Ramsden et al. 1975). The most common finding in the localized pattern was an area of exposed dead bone in the external acoustic meatus (EAM), usually in the floor of the tympanic ring, and occasionally in the anterior wall. These cases presented with mild otalgia and severe otorrhea. Although the bony dehiscence may heal when the bone sequestrum forms and gradually separates, the process may take years. In diffuse osteonecrosis of the temporal bone, there can be extensive ischemic necrosis of a large part or all of the temporal bone (van Hasselt and Gibb 1999). With diffuse osteoradionecrosis of the temporal bone, multiple bony sequestra form, and the patient may experience more serious problems such as cerebrospinal fluid leak, labyrinthine fistula, facial palsy, chronic mastoiditis, meningitis, sinus thrombosis, brain abscess, and death (van Hasselt and Gibb 1999; Leonetti et al. 1997; Sikand and Longridge 1991; Ito et al. 2000; Horan et al. 2007). Radiographs of the temporal bone may reveal a widespread moth-eaten radiolucency. The clinical manifestations in these cases often include pain, refractory otorrhea, CHL, SNHL, or mixed hearing loss. Associated diffuse white matter injury may lead to progressive cognitive neurological impairment with simultaneous vestibular or gait disorders (Jereczek-Fossa et al. 2003). A study on the incidence of radiation otomastoiditis using T2-weighted MRI reported significant increases above RT doses of 50 Gy, but decreases over time (Nishimura et al. 1997).

Delayed persistent CHL without OME is considered to be secondary to osteoradionecrosis of the ossicular chain with or without damage to the auditory end organ. Destruction of the incudostapedial joint after high-dose RT has been described in a case report (Thornley et al. 1979). Cases of osteoradionecrosis of the temporal bone along with CHL have been presented with speculation of radionecrosis of the ossicular chain (Kristensen and Jorgensen 1967). Surgical exploration in a case of CHL consistent with interruption of the ossicular chain or stapes fixation after high-dose RT revealed that the long process of the incus was replaced by a fibrous band (Kristensen and Jorgensen 1967). Another report on five patients with post-RT temporal-bone necrosis with mixed hearing loss (MHL) years after RT without symptoms of OME speculated the cause to be ossicular chain necrosis (Bhandare et al. 2007). Extensive osteonecrosis of the ossicular chain after resection of extensive osteonecrosis of the temporal bone has been documented (Gyorkey and Pollock 1960).

Table 3 lists the post-radiation noninfectious otologic histopathologic findings in human and animal studies.

Several conditions and their associated presentation include the following (some with overlap with the middle ear):

Several conditions and their associated presentation include the following:

Tinnitus, the perception of a sound without acoustic stimulation, has been associated with cochlear damage, hearing loss due to pathologically increased spontaneous firing rates, or hyperactivity of neurons in the auditory pathway. Hypoxia/ischemia may play an important role in the pathogenesis of tinnitus secondary to SNHL, although the exact pathophysiologic processes involved in post-RT tinnitus is unknown (Mazurek and Haupt 2005).

The availability of a baseline evaluation is necessary for accurate diagnosis. Before beginning RT with high doses to the hearing apparatus, patients should be considered for a basic otologic evaluation including morphological evaluation by otoscopy, tympanometry, and other basic functional audiometric tests including pure-tone audiometry, speech audiometry (for speech-reception threshold and speech discrimination), and stapedial reflexes. Tympanometry objectively measures the middle ear acoustic impedance as well offers information on middle ear aeration, ossicular chain mobility, and eustachian tube function. Tympanometry may be followed by pure-tone audiometry to exclude otitis media and ossicular fixation as the cause of hearing loss (Raaijmakers and Engelen 2002). The audiologic assessment should be followed by repeated biannual evaluations for a period of at least 5 years after RT. Tuning-fork tests (e.g., Rinne and Weber) may be done with a 512 Hz tuning fork and yield relatively crude insights into the nature of the hearing loss (i.e., CHL vs. SNHL).

Pure-tone audiometry, including air and bone conduction, can subjectively assess patients’ hearing thresholds and detect sensorineural, conductive, or mixed hearing loss. Transient CHL secondary to middle ear effusion is evaluated by pure-tone audiometry (air-bone-gap measurement), tympanometry, and otoscopy.

SNHL can be detected with audiometric assessment by measuring speech understanding and pure-tone thresholds with bone conduction at 0.5, 1, 2, 4, and 6 kHz. Pure-tone stimuli are presented via a bone oscillator placed on the mastoid of the ear to be tested, thus by passing the conductive mechanism. “Masking” of the contralateral ear is often necessary to avoid inadvertent detection of sound by the contralateral ear. There remains significant variation in the criteria used for coding of post-RT SNHL in the literature in terms of frequencies and the thresholds (Bhandare et al. 2007; Pan et al. 2005; Chen et al. 1999; Kwong et al. 1996) making the comparison between the studies difficult. To standardize reporting following criteria has been suggested (Bhandare et al. 2010).

An air-bone gap, assessed by the difference in the air-bone-conduction thresholds, is consistent with CHL. Persistent CHL, without symptoms of OME, is an attenuation of signals stimulating the cochlea without damage to the auditory end organ. It is attributed to fixation and/or osteoradionecrosis of the ossicular chain. Variation in the hearing thresholds over consecutive evaluations should be used to determine if SNHL is transient or persistent. Note that bone-conduction thresholds may also, to a much lesser extent, be altered by the presence of middle ear pathology in addition to the usual test-retest variabilities (Anteunis 1996). In addition to these, in patients with age-adjusted normal values, additional tests may provide useful information. Auditory brainstem response (ABR) testing may be used to assess retrocochlear pathology, such as radiation damage to the auditory nerve. An intra-neural latency response difference of at least 0.30 ms for wave V of the auditory brainstem indicates neural involvement.

In post-RT audiometric evaluations, a recovery from a higher bone-conduction threshold to a threshold of less than 10 dB in consecutive tests may indicate transient SNHL (Kwong et al. 1996). An increase in the bone-conduction threshold exceeding 10 dB in two consecutive tests performed at least 6 months apart may be considered persistent SNHL.

Radiology studies such as CT, positron emission tomography (PET), MRI, and nuclear medicine (bone scans) studies can help reveal the development and extent of delayed radionecrosis of the brain or osteoradionecrosis of the temporal bone (Nishimura et al. 1997).

Post-RT morbidities, including hemorrhage into the inner ear, labyrinthitis, and neuronitis, can be revealed by MRI. MRI has been used to visualize the eustachian tube and to assess its anatomy and pathology in patients with nasopharyngeal carcinoma. MRI has been a powerful tool in evaluating endocochlear diseases that cause sudden SNHL (Hegarty et al. 2002). Findings of high labyrinthine signal on unenhanced T1-weighted MRI of the internal acoustic canal in patients who presented with a sudden onset of SNHL 5–20 years following head and neck RT have been reported by Poh and Tan (2007). They posited that these findings are due to labyrinthine hemorrhage as a rare, delayed complication of head-and-neck RT seen in T1-weighted signal changes in the labyrinths of patients who experienced sudden SNHL. Further patency of inner ear fluid spaces as well as occlusion of inner ear fluid spaces by a fibrotic process can be revealed by MRI along with CT (Jereczek-Fossa et al. 2003).