Discussion

We report a case of middle-ear carcinoid tumour metastasising to the parapharyngeal space and parotid gland. Approximately 55 cases of middle-ear carcinoid tumour have been reported.^{Reference Liu, Chen, Li and Liu4} Based on both clinical aspects of an indolent course and historical aspects of the lack of necrosis and significant mitotic activity, middle-ear carcinoid was previously considered to be benign; however, regional and distant metastases have been reported in eight cases, suggesting that the carcinoids should be classified as having a low-grade malignancy.^{Reference Fundakowski, Chapman and Thomas2} The mean duration between initial diagnosis and metastasis was 14.1 years.^{Reference Liu, Chen, Li and Liu4}

To the best of our knowledge, this is the first report of metastasis to the parapharyngeal space, based on the search results for the key words ‘carcinoid tumour’ and ‘metastasis’ in the PubMed database. According to a systematic review by Riffat et al.,^{Reference Riffat, Dwivedi, Palme, Fish and Jani5} approximately 80 per cent of tumours in the parapharyngeal space are benign and 20 per cent are malignant. These lesions commonly originate from the parotid gland and neurons.^{Reference López, Suárez, Vander Poorten, Mäkitie, Nixon and Strojan6} Although metastasis to the parapharyngeal space is rare, the spread of cancer of the pharynx and the thyroid has occasionally been reported.^{Reference Teshima, Otsuki, Shinomiya, Morita, Furukawa and Morimoto7,Reference Otsuki, Nishikawa, Iwae, Saito, Mohri and Nibu8} As the parapharyngeal space contains numerous lymphatics, including drainage of the middle-ear mucosa, this can be a site of metastasis from a middle-ear tumour.^{Reference Batsakis and Sneige9} Physicians should be aware that solitary lesions emerging in the parapharyngeal space could be mistaken for benign tumours such as neurinoma.

During surgery, the approach to the parapharyngeal space is also important, and should be determined depending on the age and condition of the patient, and on the size and location of the tumour.^{Reference Prasad, Piccirillo, Chovanec, La Melia, De Donato and Sanna10} In this case, the cervico-parotid approach was selected because the patient was a younger woman with a 17 mm tumour in the pre-styloid compartment of the parapharyngeal space, and subtotal parotidectomy was necessary.

Surgical management of parapharyngeal space tumours is subject to residual or metastatic relapse. In our case, at first, residual recurrence could be suspected in terms of carcinoid tumour extending close to the carotid canal at the last local relapse; however, the likelihood appeared to be low based on the imaging findings of a well-circumscribed tumour apart from the carotid canal, and with no previous bone invasion. Therefore, the parapharyngeal space tumour was considered metastatic and was removed to reduce complications. Neck dissection was planned for levels II–V of the malignant parotid tumour if the intra-operative rapid pathological diagnosis of level III lymph nodes had revealed malignancy. The examination showed no malignancy, leading to the decision to perform neck dissection only for levels II and III.

According to a previous report, regional metastasis of a middle-ear carcinoid tumour is likely to occur in patients with local recurrence after a long period following tumour resection.^{Reference Salzman, Stárek, Tichá, Skálová and Kučera3} Thus, careful, complete tumour removal is important to prevent metastasis. Nevertheless, the middle ear has a complicated small space containing blind spots (such as the facial recess and tympanic sinus) and has important organs (such as the inner ear and facial nerve), suggesting that tumour resection with adequate surgical margins is difficult.^{Reference Sato, Saito, Fujita, Seo and Doi11} Indeed, the surgical recurrence rate is 18–22 per cent.^{Reference Torske and Thompson12,Reference Pellini, Ruggieri, Pichi, Covello, Danesi and Spriano13} If the ossicular chain is involved and not removed, recurrence is much more likely.^{Reference Knerer, Matula, Youssefzadeh, Ulrich and Swoboda14} Therefore, radical mastoidectomy should have been selected during the second surgery. Conversely, recurrence has been reported even after radical tympanomastoidectomy, and a patient in one case finally underwent extended subtotal petrosectomy for complete removal of the lesions.^{Reference Knerer, Matula, Youssefzadeh, Ulrich and Swoboda14} A better way to prevent recurrence may be radical mastoidectomy with endoscopy, securing adequate vision. The resulting hearing loss can be improved using bone-anchored hearing aids or middle-ear implants.

Although the period between primary surgery and local recurrence is reported to range from 15 to 33 years, some cases recur within a year,^{Reference Liu, Chen, Li and Liu4,Reference Ramsey, Nadol, Pilch and McKenna15} as in our case. A planned second-stage tympanoplasty that narrows the interval may be required to lower the possibility of residual recurrence. Staged surgery after six months was effective for local control of the carcinoid in our case, whereas long-term observation was required in preparation for metastasis. Staged surgery performed within at least a year may be recommended to properly manage a middle-ear carcinoid tumour.

An indicator of metastasis has not been reported to date. In the pathological examination of Ki-67 immunoreactivity, an indicator of the ability of tumour proliferation, the majority of small-cell carcinomas show higher than 25 per cent immunoreactivity;^{Reference Aslan, Gulbahce, Pambuccian, Manivel and Jessurun16} however, Ki-67 immunoreactivity of middle-ear carcinoid tumours is generally very low, as in the case of our patient (0.6 per cent).^{Reference Aoki, Mizuta, Ueda, Yamada, Ito and Kato17} Further studies on the genetic analysis of metastatic factors should be conducted in the future.^{Reference Warth, Herpel, Krysa, Hoffmann, Schnabel and Schirmacher18,Reference Kim, Yi, Jun, Ahn, Ahn and Lee19}