Cholesteatoma morphed into temporal bone squamous cell carcinoma

Abstract Cholesteatoma and the ensuing chronic inflammation may promote temporal bone tumorigenesis. Our patient is an 80-year-old female who had undergone left ear surgery 72 years prior. She presented with a 3-month history of left facial asymmetry associated with otalgia. Patient had been having intermittent discharge from the left ear since her first ear surgery but worsened in the recent 3 months. The patient underwent mastoid exploration. Histopathological study showed no evidence of dysplasia or malignancy. At one-year post surgery, the patient was noted to have soft tissue swelling in the mastoid region which was reported as squamous cell carcinoma. Scans showed extensive disease with possible extradural involvement. Therefore, she was given radical radiotherapy. Chronic ear infection, especially cholesteatoma, may progress to temporal bone malignancy. If the tumour is advanced or the patient’s condition is unfavourable for the surgery, radiotherapy can be a useful modality of treatment.


Introduction
Temporal bone malignancy is an infrequent disorder with an estimated global annual incidence of 1.3 cases per million [1].It constitutes 0.2% of head and neck region malignancies [1,2].Among the malignant temporal bone histologic variants, squamous cell carcinoma accounts for 39% [1].Chronic external ear canal or middle ear inflammation is associated with the development of squamous cell carcinoma (SCC) [1,3].Inflammation is a predisposing factor of cancer and affects all the stages of oncogenesis [4].Cholesteatoma and the ensuing chronic inflammation may promote temporal bone tumorigenesis.However, at the early stages of temporal bone squamous cell carcinoma, the symptoms are similar to the chronic suppurative otitis media [5].The direct association between cholesteatoma and malignant transformation is yet to be proven.A handful of reports are available in English literature to strengthen the postulation of cholesteatoma as the causative factor of temporal bone squamous cell carcinoma (TBSCC) [6,7].

Case presentation
We present a case of TBSCC in an 80-year-old female who had undergone left ear surgery 72 years prior.She presented with a 3-month history of left facial asymmetry associated with otalgia.The patient had been having intermittent discharge from the left ear since her first ear surgery but worsened in the recent 3 months.Besides, she had been suffering from left-side hearing loss since the surgery and worsening.She denied having vertigo, tinnitus, headache, or neck stiffness.There is no history of radiotherapy and family history of malignancy.Physical examination showed left facial nerve paresis, House-Brackmann grade II.The left ear examination revealed a post-auricular scar and a cutaneous fistula at the superior part of the mastoid.There was an exophytic mass arising from the posterior wall of the left external auditory canal.Accumulation of keratin debris medial to the mass was obstructing the view of the tympanic membrane.The right ear and neck examinations were unremarkable.
A high-resolution computed tomography (HRCT) of the temporal bone performed showed the presence of well-circumscribed lobulated soft tissue lesion in the left middle ear and mastoid air cells with local mass effect.Left ossicles and tegmen tympani could not be appreciated in the scan which might have been eroded by the disease (Figure 1).The mass was abutting the dura of the left middle cranial fossa but there was no evidence of intracranial extension.In addition, the mass was extending into the lateral semi-circular canal and the osseous part of the external auditory canal.The features seen in HRCT favoured cholesteatoma.Subsequently, Magnetic Resonance Imaging (MRI) of the brain was performed to further evaluate the extent of the disease.On MRI, the central part of the soft tissue lesion demonstrated an isointense signal on T1W and the periphery of the lesion showed high signal intensity on T2/FLAIR (Figure 2) and restricted diffusion on DWI map.The tegmen tympani was not visualised and the mass was abutting dura of the left middle cranial fossa without intracranial extension.An initial biopsy of the external ear canal mass was reported as abnormal squamous proliferation with a suspicious area of stromal invasion but no malignant cells were seen.Her hearing assessment showed profound hearing loss in the left ear.
After the assessment, the patient underwent mastoid exploration.Intraoperatively, a huge cholesteatoma sac with a finger-like projection into the mastoid cavity was seen causing auto-mastoidectomy.The tympanic and mastoid segment of the facial nerve was exposed and all ossicles were eroded.The lateral semicircular canal was eroded.There was tegmen mastoideum erosion but the dura was intact.The posterior fossa dura was also exposed after the sac was removed.Temporalis fascia was harvested and placed on the middle ear and facial nerve.The Temporalis muscle pedicle flap was deployed to cover the defects in the mastoid cavity and posterior cranial fossa.In addition, specimens sent for cryosection during the surgery did not display dysplasia or malignant cells.Histopathological study of both the external auditory canal and mastoid mass showed no evidence of dysplasia or malignancy.She had an uneventful surgery and was discharged well.She was reviewed regularly at our clinic with the continuation of eye care and facial physiotherapy.
During the follow-up, the mastoid cavity was healing with debris that was easily removed but she defaulted to follow-up due to the COVID-19 pandemic.At one-year post-surgery, the patient presented  again and was noted to have soft tissue swelling in the mastoid region surrounded by an exposed mastoid cavity filled with keratin debris (Figure 3).The neck examination was unremarkable.A biopsy was taken immediately and was later reported as well-differentiated squamous cell carcinoma (SCC).Her facial nerve function did not worsen but remained at House and Brackmann grade II.
MRI of the brain and temporal was performed while waiting for histological diagnosis.It showed multilobulated soft tissue lesions occupying the left mastoid bowl and middle ear cavity.Based on the intermediate signal on T1W and mixed with hypointense signal on T2W sequences (Figure 4), it was suggested to be granulation tissue but unable to rule out malignancy.MRI did not show evidence of intracranial involvement.Subsequently, staging CT was performed after the biopsy result of SCC was obtained.Multilobulated lesions with peripheral enhancement measuring 3.5 cm × 4.5 cm × 5.7 cm were seen occupying the residual mastoid cavity (Figure 5).The tumour also extended into the middle ear cavity.In addition, the lateral and superior semicircular canal, and oval window were partially eroded as expected after the surgery.The posterior semicircular canal, cochlea, internal auditory canal, left temporomandibular joint and left carotid canal were intact.The left petrous apex and squamous part of the left temporal bone demonstrated sclerosis and cortical thickening.In the neck region, a sub-centimetre intra-parotid lymph node was visualised within the left parotid gland.However, there were no   enlarged cervical lymph nodes and distant metastasis.Based on the Modified Pittsburgh staging system, our patient was stage IV(T4N0).
There was an option of radical surgery and postoperative adjuvant treatment.However, the skin would not be able to be closed primarily and scans showed extensive disease with possible extradural involvement.Therefore, the oncologist proposed radiotherapy with or without chemotherapy.Upon consideration of the patient's age, chemotherapy was not advised.The patient and the family opted for definitive radiotherapy.She was given radical radiotherapy, 20 cycles of 50 Gy dose, to the left temporal region.The tumour responded to the radiotherapy and gradually the wound became smaller and cleaner.Two years after the completion of the radiotherapy, there was no clinical evidence of tumour recurrence.The mastoid cavity contracted and was well epithelized (Figure 6).Post auricular fistula gradually contracted with communication into the mastoid cavity was still seen.The neo-tympanic membrane was intact.

Discussion
Primary temporal bone malignancy is a rare entity comprising about 0.2% of head and neck region malignancies [1,2].Approximately 60-80% of temporal bone tumours are SCC and have 60% predilection for men.It is frequently diagnosed in the 7 th decade of life [1,6].The exact aetiology of TBSCC is still unestablished.Postulated risk factors for TBSCC are chronic otitis media and previous radiation exposure [2,8].Studies have reported a preceding history of chronic or recurrent otitis media or otitis externa among TBSCC patients between 12.6-43% [1].The risk of developing SCC post radiotherapy in the head and neck region is 0.13% which is 1000 times higher compared to the general population [1].Both could be linked to the pathway of chronic inflammation resulting in metaplasia and subsequent malignant transformation [2,4,8].Our patient is an 80-year-old female with a history of chronic otitis media for more than 60 years.She had no radiation therapy prior to this presentation.
Symptoms of TBSCC encountered during the initial presentation are otalgia, chronic otorrhea, bleeding and deafness, all of which are common complaints in benign ear diseases [3,6,7].These symptoms are nonspecific to TBSCC and may mask and delay the diagnosis.Although metastasis is rare in TBSCC, aggressive local spread of this tumour is widely reported.The temporal bone structures which facilitate tumour spread into the middle cranial fossa and infratemporal fossa are the tegmen tympani, fissure of Santorini, and foramen of Huschke.At this stage, patients may present with headache, parotid swelling and skin ulceration [2].Besides, the spread of the tumour into the inner ear and petrous bone may result in vestibulopathy and facial nerve palsy [3].The incidence of facial nerve palsy among TBSCC patients is reported to be 10% [2].TBSCC involving EAC classically presents with exophytic and ulcerative mass.The role of otoscopic examination becomes limited as the tumour grows and obstructs distal canal visualisation [1].In this instance, imaging studies provide great assistance in staging the tumour and guide further management.
HRCT Temporal is helpful in determining tumour extension and bony erosion.The drawback of CT imaging in assessing soft tissue is complemented by MRI.MRI assists in the diagnosis of cholesteatoma as it appears hypointense on T1W, hyperintense on T2W, and demonstrates diffusion restriction without any enhancement on DWI [9].Thus, both HRCT and MRI are vital for accurate staging of TBSCC [2,3].Coexisting middle ear soft tissue density with bony erosion of ossicles and mastoid are highly specific for cholesteatoma [9] but still do not rule out malignancy.Based on the initial HRCT and MRI findings, the patient's lesion was highly suggestive of cholesteatoma and supported by postoperative histological confirmation.The modified Pittsburgh staging system is widely used in TBSCC staging [1,2,8].Our patient was stage IV(T4N0).
Surgery is the preferred treatment modality for TBSCC with or without adjuvant radiotherapy [1,2,[6][7][8].In terms of surgery, three options in the literature are lateral temporal bone resection (LTBR) for tumour-sparing middle ear and mastoid, subtotal temporal bone resection (STBR) for diseases affecting facial nerve and labyrinth, and total temporal bone resection (TTBR) in the case of tumour extension into or medial to the bony labyrinth [1,3].STBR is preferred if the tumour extends beyond the tympanic membrane into the middle ear or mastoid.The incidence of cervical nodal metastasis is 10-17.7%[1,2].Therefore, elective neck dissection is not routinely performed for TBSCC patients.Apart from cervical nodal metastasis, the spread of the disease to the parotid gland needs to be considered due to the close proximity of the temporal bone and the gland.The percentage of parotid gland involvement in T1 and T2 lesions is below 50% [2].However, a retrospective review by Ngu CYV et al. showed 4 out of 6 patients with T3 lesions had parotid glands tested positive for malignancy [2].The author recommended superficial parotidectomy for T ≤ 2 lesions and total parotidectomy for lesions T ≥ 3.
Most literature advice for adjuvant radiotherapy for all T stages of the disease.However, the advantage of radiotherapy for T1 tumours with negative margins is limited.Survival outcomes of T ≥ 2 lesions can be enhanced by radiotherapy [1,2].The role of radiotherapy is significant in stage T ≥ 2 due to the challenge of achieving tumour-free margin as these stages have bony involvement.Most studies do not advocate chemotherapy due to the rare occurrence of metastasis [6].Definitive radiotherapy is a controversial modality for TBSCC and has limited studies to substantiate its role.Studies have shown improved survival rates with definitive radiotherapy in T1-2 patients [1,10].No literature review was found for T3-4 patients' survival with definitive radiotherapy alone.However, Morita et al. advocated for definitive chemoradiotherapy for T3-4 patients with unresectable tumours [10].We would like to highlight that our patient with T4 tumour who had completed radiotherapy without radical surgery had been showing no signs of recurrence after 2 years.

Conclusion
Chronic ear infections, especially cholesteatoma, may progress to temporal bone malignancy.The clinical features of both benign and malignant lesions of the temporal bone may be similar.Therefore, a high index of suspicion is vital to identify TBSCC earlier.Temporal bone resection and adjuvant radiotherapy remain the most practised and preached method.However, when the tumour is advanced or the patient's condition is unfavourable for surgery, definitive radiotherapy can be a useful modality of treatment.

Informed Consent
Informed consent has been obtained from the patient for the purpose of publication.

Figure 2 .
Figure 2. A t2 weighted Mri scan performed prior to the surgery shows high signal intensity in the periphery of the mastoid and middle ear soft tissue lesion (arrow head).

Figure 1 .
Figure 1.Hrct (bone window) of the temporal bone performed before the surgery shows erosion of the mastoid cavity and ossicles (arrow).

Figure 3 .
Figure 3.A fungating mass with crusting in the mastoid region (arrowhead) and exposed mastoid cavity with keratin debris(arrow) before radiotherapy was commenced.

Figure 4 .
Figure 4.A t2 weighted Mri image prior to the radiotherapy shows a hypointense soft tissue lesion occupying the left mastoid bowl (arrow head) and middle ear cavity.

Figure 5 .
Figure 5.An Axial view of ct temporal before the radiotherapy shows enhancing soft tissue lesions occupying the residual mastoid cavity (arrow) and extending into the middle ear cavity.

Figure 6 .
Figure 6.patient's mastoid wound one-year after completion of radiotherapy is well epithelialized and no mass is seen.