(from the AHNS Cutaneous Cancer Section)
by Kush Panara, MD¹ & Robert Brody, MD¹
Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, PA

Intro
Malignancies of the external auditory canal (EAC) are relatively rare with an estimated yearly incidence of 1-6 cases per million population.¹ This review will focus on the most common pathology, squamos cell carcinoma (SCC), which accounts for >90% of cases. However other pathologies include basal cell carcinoma, malignant melanoma, merkel cell carcinoma, adenoid cystic carcinoma, and lymphoma.²

Anatomy
The EAC is a part of the outer ear anatomy. It extends from the auditory meatus laterally and connects to the tympanic membrane medially, which separates the outer and middle ear. The canal is lined circumferentially with skin. The outer two-thirds of the canal is cartilaginous and the medial one-third is bony and arises from the tympanic portion of the temporal bone.

In the cartilaginous EAC, the Fissures of Santorini allow for cancer spread through dehiscences in the cartilage directly to the soft tissue inferiorly. In the bony EAC, tumors can spread sub-dermally along periosteum and through the foramen of Huschke, which is a dehiscence along the bone allowing extension into the TMJ and parotid.^3,4

Diagnosis
Given the aggressive nature of neoplasms of the EAC, prompt diagnosis is paramount. Mortality rates for stage 1 and stage 2 disease are <10%. However, five-year survival drops dramatically to <50% for more advanced disease.⁵ Unfortunately, due to the difficult nature of diagnosing EAC malignancies, the mean time to diagnosis from onset of symptoms is over 2 years⁶ and 65% are diagnosed with T3 or T4 tumors.⁷

Neoplasms are very frequently misdiagnosed or missed (up to 40%) due to the overlap of symptoms with those of a chronically infected ear.⁸ The most common symptoms include including chronic drainage, otalgia, and hearing loss. A mass tends to be visible on otoscopy only in more advanced stages.⁹ Up to 80% of patients with EAC carcinoma have a history of otitis media.¹⁰

As opposed to the majority of malignancies arising from the outer ear, such as the pinna, sun exposure is not a risk factor for SCC of the EAC. However, clinicians should have a lower threshold for suspicion for malignancy in patients with history of radiation, chronic irritation, and exposure to inflammation.¹¹ Atypical signs include non-responsiveness to typical anti-inflammatory and anti-infectious treatments, bloody otorrhea, or facial nerve weakness, which should prompt clinicians to biopsy suspecting lesions or perform an exam under anesthesia in the operating room.

Work up
There is no universally accepted staging system for EAC carcinoma, but the Pittsburg system is often the most cited.¹² Work up for malignancy includes both CT scan to evaluate extent of bony erosion and MRI for the soft tissue and possible intracranial extension, however underestimation of extent of spread based on imaging as compared to histopathologic specimens has been reported.¹³ Importantly, work up should include evaluation of peri-parotid and cervical neck nodes. The role of PET/CT is not well established but may be helpful in identifying small nodal metastasis. While distant metastases to the lung, liver, and spine have been reported, they are overall quite rare.¹⁴

Treatment
The mainstay for treatment revolves around surgery, however the exact surgical plan is dictated by pathology and extent of invasion. Given the rarity of EAC carcinomas, most evaluations of surgical outcomes are based on small single-institution retrospective reviews. Obtaining negative margins is the most important factor in determining local recurrence and overall survival^5,15,16, thus decision for surgical approach should be primarily driven by best chance of obtaining clear margins with lowest morbidity.

Generally speaking, tumors lateral to the bony cartilaginous junction can be managed with local or sleeve resection, tumors medial to this junction but lateral to the tympanic membrane can be treated with a lateral temporal bone resection, and tumors extending into the middle ear may require subtotal temporal bone resection. A parotidectomy needs to be considered for disease eroding the anterior canal wall and or if there is frank parotid extension.¹⁰ Advanced disease, including temporomandibular joint, facial nerve or dural involvement, warrant multidisciplinary discussion. Joint surgical approaches with neurotology and neurosurgery are required with consultation to the appropriate reconstructive service.

If there are involved neck nodes those should be removed at the time of primary resection. Management of the node negative neck is controversial given the limited data available. Some authors propose elective neck dissection¹⁷ while others perform a limited peri-parotid and upper neck nodal dissection that is accessible during the resection and flap reconstruction.¹⁸

Definitive radiotherapy is associated with worse outcomes than adjuvant radiation¹⁹ and is associated with high risk of canal stenosis, osteoradionecrosis of the temporal bone, and chronic otitis externa.^20,21 Therefore definitive radiation remains reserved for patients who are not surgical candidates. Indications for adjuvant radiation follow those of SCC in the head and neck: advanced stage (T3/T4), perineural invasion, nodal metastasis, positive margins, or extracapsular spread.²² Indications for chemotherapy are not well established, but may play a role as a radiosensitizer or as primary treatment in non-surgical patients in conjunction with radiation.²³

Reconstruction is often needed depending on the surgical approach. For small tumors contained to the EAC without significant bony erosion, reconstruction of the EAC can include a skin graft. Tumors requiring temporal bone resection often require soft tissue reconstruction most commonly with rotational flaps (e.g.  sternocleidomastoid or temporalis flap) or free tissue transfer. Dural or skull base defects should be repaired with vascularized tissue to minimize the risk of a post-operative cerebrospinal fluid leak. If facial nerve sacrifice is required, interposition nerve graft can be considered, and facial reanimation procedures can be performed concurrently or in subsequent procedures. Lastly, surgical technique and closure must ensure no trapped epithelia to prevent formation of a cholesteatoma.

Immunotherapy represents the newest line of treatments. While no studies have looked at the role of immunotherapy specifically in EAC malignancies, the use of immunotherapy is extrapolated from pathologies in the head and neck. For stage 3 and greater melanoma, immunotherapy has been shown to provide benefit in disease-free survival and overall survival in the adjuvant setting.^24,25 In 2019, the FDA approved pembrolizumab as first line treatment for recurrent and non-resectable SCC in the head and neck. KEYNOTE-048²⁶ demonstrated improved overall survival with the addition of immunotherapy to chemotherapy. However, overall response rates to immunotherapy are low and its role as primary treatment remains under investigation.

Conclusion
Malignancy of the EAC is a rare entity with poor survival. Delays in diagnosis are quite common due to the overlap of symptoms with chronically infected ears. Clinicians should have a high index of suspicion in at risk populations and those who don’t respond to conventional anti-inflammatory/infectious therapy. Survival is dictated by stage and ability to obtain clear margins, making prompt diagnosis of upmost importance.

References:

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Kush Panara, MD – Kush Panara is a PGY-4 Otolaryngology resident at the University of Pennsylvania. He went to the University of Miami for undergraduate and gradated Magna cum Laude with honors. He then went on to the University of Miami Miller School of Medicine. Here he received grant funding from the American Urologic Association and the American Cancer Society for his work on studying castrate resistant prostate cancer. He is applying to Rhinology and Skull Base surgery fellowship and plans to continue in his path as a clinician-scientist.

Robert Brody, MD – Assistant Professor of Otorhinolaryngology: Head and Neck Surgery at the Hospital of the University of Pennsylvania and the Veteran’s Administration Medical Center. Dr. Brody has multiple research publications.