Middle ear adenoma with neuroendocrine differentiation: Report of a rare case

Middle ear adenoma with neuroendocrine differentiation: Report of a rare case:



Shakti Kumar Yadav, Roshina Naeem, Amitabh Sharma, Sompal Singh, Namrata Sarin, Sonam Kumar Pruthi



Indian Journal of Cancer 2020 57(1):98-101



Middle ear adenoma with neuroendocrine differentiation (MEA-ND) is also called as neuroendocrine adenoma. Neuroendocrine tumors are rarely seen in the head and neck region and are even more rare in the middle ear. Clinical and radiological findings are non-specific and seldom suggest this diagnosis. Nomenclature and behavior of this tumor has been historically controversial. Both epithelial as well as neuroendocrine origin have been suggested. They comprise <2% of all ear tumors and commonly present with unilateral hearing loss, aural fullness, and tinnitus. We present a case report of MEA-ND in a 24-year-old woman who presented with heaviness and tinnitus in the right ear.

» Introduction

Middle ear adenoma with neuroendocrine differentiation (MEA-ND) is a rare middle ear tumor, which appears to originate from middle ear mucosal lining. It was first described by Derlacki and Barney^[1] in 1976 as “adenomatous tumor” of middle ear. In 1980, Murphy et al.^[2] reported first case of middle ear adenoma showing neuroendocrine differentiation and they called it as “middle ear carcinoid”. Although, considered benign, it can show metastasis as described by Mooney et al.^[3] MEA-ND comprise <2% of ear tumors and commonly presents with unilateral hearing loss, aural fullness, tinnitus, otorrhea, otalgia, and facial nerve palsy.^[4],[5] We present a case of MEA-ND which to the best of our knowledge, is the first one from the Indian subcontinent. Its biological behavior and relationship with carcinoid and middle ear adenomas are also discussed briefly.

» Case Report

A 24-year-old woman presented to otorhinolaryngology department with complaints of heaviness in the right ear for 9 months and tinnitus in the right ear for 4 months. The heaviness was insidious, nonprogressive, and was not associated with hearing loss. There was no history of trauma, ear-discharge, or pain. On otoscopic examination a reddish bulge was noted in the retrotympanic region.

Computed tomography (CT) scan showed a contrast enhancing soft tissue lesion measuring 5.8 × 3.7 mm near the right tympanic membrane [Figure 1] and a radiological diagnosis of glomus tympanicum was made. The mass was excised and sent for histopathology.

Figure 1: Computed tomography scan showing a soft tissue mass in the middle ear Click here to view

Grossly, the biopsy was a single gray-white soft tissue piece of size 6 × 6 × 3 mm. Microscopic examination revealed mucosal tissue lined by stratified squamous epithelium with subepithelium showing infiltration by tumor cells which were arranged in nests, sheets, glandular, and trabecular pattern. The individual tumor cells were small-to-medium sized, round-to-oval, with scant eosinophilic cytoplasm and small round hyperchromatic nucleus. The mucosal lining was devoid of dysplastic changes [Figure 2]a and [Figure 2]b.

Figure 2: (a) Stratified squamous lined tissue with subepithelium showing nests and sheets of tumor cells (H and E, ×100). (b) Individual tumor cells are round to oval with scant eosinophilic cytoplasm and hyperchromatic nuclei (H and E, ×400) Click here to view

Immunohistochemical staining revealed cytokeratin positivity of tumor cells which also showed focal chromogranin-A positivity [Figure 3] and [Figure 4]. Tumor cells were also positive for S-100 and vimentin but were negative for smooth muscle actin. Based on these features, a final diagnosis of MEA-ND was made.

Figure 3: Epithelial lining and tumor cells show cytokeratin positivity (DAB, ×100) Click here to view

Figure 4: Tumor cells show focal positivity for chromogranin-A (DAB, ×400) Click here to view

» Discussion

MEA-ND most commonly occurs in the age group of 20–30 years.^[6],[7] However, in different case series, age range of 16–80 years has been described.^[4],[5],[8] The most common presenting symptom is unilateral conductive hearing loss, although sensorineural hearing loss may also be present.^[4] A few authors have reported cases with mixed or no loss of hearing.^[9],[10] Other symptoms include aural fullness, tinnitus, otalgia, otorrhea, and facial nerve paralysis.^[4] However, classical symptoms of carcinoid syndrome are rarely identified. Otoscopic examination usually show bulged tympanic membrane due to a reddish to whitish mass.^[11] Our patient presented with complaints of fullness and tinnitus in the right ear. However, there was no associated hearing loss.

Radiological features are non-specific and often a radiological diagnosis of cholesteatoma or paraganglioma is made. In present case, radiological diagnosis of glomus tympanicum was suggested; however, no extension into the  Eustachian tube ^{More Details}, mastoid bone, or external auditory canal was noted.^[8] Clinicoradiological diagnosis of this tumor is extremely difficult and histopathological examination is mandatory for its diagnosis.^[12]

Macroscopically the size of middle ear adenoma ranges from 2 to 30 mm (mean = 8 mm).^[8] In present case, the size of tumor was 6 mm in maximum diameter. Microscopically, different architectural patterns are described, most common being glandular pattern followed by trabecular, solid, infiltrating, and organoid patterns. However, most tumors show more than one pattern. MEA-ND is usually a moderately cellular tumor having cuboidal to columnar tumor cells with indistinct cytoplasm. The nuclei are round-to-oval with minimal nuclear pleomorphism.^[8] Present case showed tumor cells arranged in nests, sheets, trabecular, and focal glandular pattern. The individual tumor cells were small-to-medium sized, round-to-oval cells, with scant eosinophilic cytoplasm and small round hyperchromatic nucleus.

Tumor cells are characteristically positive for epithelial markers like cytokeratin (89.6%) predominantly CK7 (89.6%), CAM 5.2 (81.3%), and occasionally CK20 (6.4%). Neuroendocrine markers like chromogranin-A (87.5%), NSE (50%), synaptophysin, and serotonin may be focally or diffusely positive. S-100 (variable), vimentin, epithelial membrane antigen, and pancreatic polypeptide positivity can also be seen.^[4],[8] The present case showed cytokeratin, S-100, and focal chromogranin-A positivity.

The most important histological differential diagnosis of MEA-ND is paraganglioma. Immunohistochemical staining for cytokeratin can differentiate the two lesions. Paraganglioma is negative for cytokeratin.

Complete surgical removal of the tumor mass is treatment of choice.^[4] Although a few patients may show recurrence (12.7–18%), which can be attributed to incomplete removal of the tumor or the involved ossicular chain. However, subsequent surgery to remove the other involved structures may result in better clinical outcome.^[4],[8] Our patient is asymptomatic for 1 year 9 months.

MEA-ND has previously been described by different names including carcinoid tumor, neuroendocrine adenoma of middle ear, and adenomatous tumor of middle ear. This variable nomenclature of one entity is due to the uncertainty around the origin and biological behavior of this tumor. Neuroendocrine tumors are typically seen in the lungs and gastrointestinal tract due to the presence of neuroendocrine cells. Wassef et al.^[13] described ultrastructural similarities between the normal middle ear mucosa and tumor cells. However, native neuroendocrine cells are not described in the middle ear under normal conditions and even in serous otitis media.^[14],[15] There is a hypothesis that neuroendocrine cells are derived from the epithelial stem cells suggesting an abnormal differentiation of epithelial cell into neuroendocrine cells, possibly this differentiation occurs in early stages of middle ear development.^[16]

There are only a few case reports, which also hinders the consensus on the origin and development of this lesion. Due to dual immunostaining for epithelial and neuroendocrine markers, which reflects dual nature of this lesion, Ketabchi et al.^[17] suggested the use of terms like “adeno-carcinoid” and “amphicrine tumor of middle ear”.

Torske and Thompson^[8] claim that the adenoma and carcinoid tumor of middle ear “represents the same tumor”, in a review based on clinical, histological, immunohistochemical, and ultrastructural findings. In contrast to neuroendocrine tumors of lung, they considered this lesion as benign and suggested “neuroendocrine adenoma of middle ear” to be a more accurate nomenclature.

Ramsey et al.^[5] concluded that carcinoid tumor of middle ear should be considered a distinct entity from middle ear adenoma and it should be termed as well-differentiated neuroendocrine carcinoma like lung carcinoid tumor. However, with 22% recurrence rate and 9% incidence of metastasis, the authors classified it as a low-grade indolent malignancy.

Saliba and Evrard^[4] reported that adenoma and carcinoid of middle ear are indistinguishable from each other. Although benign, these tumors may have metastatic potential. Based on the presence or absence of neuroendocrine immunohistochemical markers and metastasis, they classified middle ear glandular tumors into three subtypes as – Type I i.e., neuroendocrine adenoma of the middle ear (NAME) which represented the most common subtype (76%) showing positive immunohistochemistry and absence of metastasis, Type II i.e., middle ear adenoma (MEA) (20%) showing negative immunostaining and absence of metastasis, and Type III i.e., carcinoid tumor of middle ear (CTME) (4%) with positive immunostaining and presence of metastasis and/or carcinoid syndrome.

» Conclusion

MEA-ND is an extremely uncommon tumor. Presently it is difficult to exactly classify these tumors as adenoma or carcinoid. We feel that MEA-ND or neuroendocrine adenoma of middle ear (NAME) is appropriate nomenclature for this tumor. However, it is necessary to differentiate these tumors from paraganglioma of the middle ear. Histological diagnosis must be supported with immunohistochemical staining in all the cases. Surgical excision of the mass is usually done after clinical and radiological diagnosis. In majority of the cases, excision of the mass is curative, although, patient must be kept in follow up as removal of involved left over ossicular chain might be needed to prevent recurrence.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 

» References

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Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]