Keywords
Neuroendocrine Tumors - Hearing Loss - Adenoma
Introduction
Neuroendocrine cells are generally present in the respiratory epithelium as well as
in the bronchial and intestinal mucosa. A few of these cells are also associated with
epithelial structures found throughout the body, including the head and neck. Adenomas
with neuroendocrine differentiation are defined as neuroendocrine neoplasms, and they
are rarely found in the head and neck. When they occur in this region, they are more
commonly found in the larynx[1]. They usually grow in the lungs or gastrointestinal tract[1]
[2].
Case reports
Patient 1 was a 41-year-old woman who presented with a 3-year history of left aural
fullness associated with ipsilateral “hammer beating” tinnitus. Over the following
8 months, the patient developed left-side otalgia and was treated with systemic antibiotics
but without any improvement.
The patient consulted a colleague who raised the possibility of a tympanic paraganglioma.
Computed tomography (CT) of the temporal bones revealed a material with a soft tissue
density that diffusely obliterated the left mastoid cells, but with no signs of ossicular
chain erosion ([Figure 1]). Angiography of the temporal bone showed a lobulated solid lesion with defined
limits and contrast uptake within the left middle ear and the epitympanic recess.
Figure 1. Computed tomography of the temporal bones revealed a material with a soft tissue
density that diffusely obliterated the left mastoid cells, but with no signs of ossicular
chain erosion.A. Coronal B. Axial C. Transverse
The patient consulted our institution when her symptoms persisted. She had no complaints
of hearing loss or otorrhea. On examination, the patient was found to be in good general
condition and without neurological deficits. Otoscopy of the right ear was normal,
but a retrotympanic, non-pulsatile mass was detected in the left ear ([Figure 2]). [Figure 3] demonstrates her puretone audiometry, with a 10dB-gap in the left ear. She subsequently
underwent a left radical mastoidectomy with total resection of the lesion. Intraoperatively,
the tumor had a fibrous aspect and filled the antrum and the entire tympanic cavity,
involving the ossicular chain. The histopathological study was compatible with middle
ear adenoma with neuroendocrine differentiation.
Figure 2. Otoscopy of the left ear demonstrating a retrotympanic non-pulsatile mass.
Figure 3. Pure tone audiometry showing a gap in the left ear.
Patient 2 was a 41-year-old man who presented with unilateral conductive hearing loss.
CT scan showed a middle ear mass in the promontory mimicking a tympanic paraganglioma
([Figure 4]). Magnetic ressonance imaging (MRI) of the temporal bones revealed a small mass
in the left tympanic cavity with isosignal in T1 and post-contrast enhancement on
T2 sequences([Figure 5]). The patient underwent surgical intervention through a supra-meatal approach that
completely removed the mass. The tumor was brownish and elastic, involved the ossicles
and extended to the promontory. Histology and immunohistochemical reactions were also
compatible with middle ear adenoma with neuroendocrine differentiation ([Figure 6]).
Figure 4. Computed tomography of the temporal bones revealing a small soft tissue density material
in the left tympanic cavity. A. Coronal B. Axial
Figure 5. A: MRI of the temporal bones revealing a small mass in the left tympanic cavity with
isosignal in T1 (A) and post-contrast enhancement on T2.
Figure 6. A: Well-differentiated papillary/trabecular/solid epithelial neoplasm composed of medium-sized
cells. Central nuclei presented salt-and-pepper – like chromatin, and granular eosinophilic
cytoplasm. Some neoplastic cells were seen amidst a fibrotic stroma. HE stain, original
magnification x200. B-C: Immunohistochemical identification keratins marked by the antibodies AE1 + AE3 and
most of them were reactive for neuroendocrine markers chromogranin and synaptophysin.
Original magnification x100. D: Ki-67 Ag was expressed in very low level (< 1 % of the cells). Original magnification
x400.
Review of the Literature
In 1980, Murphy et al. first reported a middle ear adenoma with neuroendocrine differentiation,
also called carcinoid tumor, as various denominations are used for these neoplasias,
reflecting the controversy between its presumed histogenesis and differentiation[3]. The lesion had adenomatous histological characteristics, but with ultrastructural
neuroendocrine differentiation[1]
[4]. Since then, approximately 40 cases have been described in the English literature[1].
The incidence of this tumor in the middle ear is difficult to establish since it may
be confused with adenomatous tumors, ceruminomas, and even with other tumors, such
as paragangliomas[1].
Clinically, it presents with conductive hearing loss and ear fullness. Less frequently,
patients may complain of tinnitus, headache, and even facial paralysis[5]. In most cases, otoscopy demonstrates an intact tympanic membrane with a retrotympanic
mass, as occurred in this case. Carcinoid syndrome (flushing, sweating, and diarrhea)
is not found in these patients because of the small production of vasoactive peptides.
Distant metastases are rare events[1]
[5]. Imaging studies consistently show a locally infiltrative mass and may show invasion
of the ossicles[4].
Middle ear adenoma with neuroendocrine differentiation can be distinguished from adenomatous
tumors (adenomas, adenocarcinomas, and adenoid cystic carcinomas), ceruminomas, and
paragangliomas by their light microscopic appearance, argyrophilic granules, and ultrastructural
evidence of neurosecretory granules, as well as by immunohistochemical detection of
various neuroendocrine markers. These include neuron-specific enolase, chromogranin,
synaptophysin, serotonin, glucagon, insulin, gastrin, vasoactive intestinal polypeptide,
pancreatic polypeptide, and calcitonin[4].
Discussion
We reported two cases of middle ear adenoma with neuroendocrine differentiation wich
presented with unspecific clinical manifestations. In both cases, the radiological
features were very similar to tympanic paraganglioma, wich is the most frequent tumoral
lesion of the middle ear. The final diagnosis was provided by histological and immunohistochemical
analysis of the tumor.
The recommended treatment is complete surgical excision of the lesion and the technique
used is determined by the size and involvement of adjacent structures[1]. Radiotherapy is not indicated since the tumor has poor radiosensitivity[1]. The prognosis is good, however, a rigorous postoperative follow-up is indicated
for all patients[3].
Our patients underwent surgical treatment and clinical follow-up in conjunction with
the Oncology department. One of the patients (patient 1) had imaging studies performed
18 months after surgery, wich confirmed that there were no signs of disease recurrence.
Final comments
Middle ear adenoma with neuroendocrine differentiation is a rare entity, but it should
be considered as a possible diagnosis in patients with hearing loss, tinnitus, aural
fullness, and a retrotympanic mass.
