Rare Presentation of Middle Ear Neuroendocrine Tumor: A Case Report

Introduction

Neuroendocrine tumors (NETs) of the middle ear are exceedingly rare neoplasms that arise from neuroendocrine cells within the middle ear cavity. These tumors belong to a broader category of neuroendocrine neoplasms that can occur throughout the body, but their occurrence in the middle ear is particularly uncommon. Middle ear neuroendocrine tumors represent <2% of primary ear tumors in the adult population.

Anatomically, the middle ear is a small, air-filled cavity within the temporal bone, housing the ossicles (malleus, incus, and stapes), which are crucial for sound transmission. The presence of neuroendocrine cells in this region is unusual, and the pathogenesis of middle ear NETs remains poorly understood. These tumors can manifest in various forms, ranging from well-differentiated carcinoid tumors to poorly-differentiated neuroendocrine carcinomas, each with distinct histological features. Histologically, NETs are characterized by the expression of neuroendocrine markers such as chromogranin A (CgA), synaptophysin (Syn), and cytokeratin (CK) [1].

Epidemiologically, middle ear NETs have been reported across a wide age range, from 16 to 80 years, with no significant sex predilection. The etiology of these tumors remains unclear, but potential factors include genetic predisposition, chronic inflammation, and aberrant differentiation of neuroendocrine cells. Clinically, patients often present with non-specific symptoms such as hearing loss, tinnitus, ear fullness, and, occasionally, pain, making early diagnosis challenging. Advanced imaging techniques, including CT and MRI, are essential for detecting these tumors and planning surgical intervention.

Early recognition and accurate diagnosis are critical for timely intervention and improved outcomes. Continued reporting of cases and further research are essential to enhance understanding, establish diagnostic criteria, and refine treatment strategies for this rare entity. In this paper, we present a rare case of middle ear neuroendocrine tumor and review the cases reported in the literature.

Case Report

A 27-year-old man presented with a 2-month history of left-sided hearing loss accompanied by tinnitus and a sensation of ear fullness, without vertigo, facial paralysis, or otorrhea. Examination revealed an intact left tympanic membrane with a pale pink mass within the posterior two-thirds of the left tympanic membrane with otoendoscopy (Figure 1). Pure tone hearing threshold measurement revealed a mild, low-frequency conductive hearing loss on the left side. CT of the temporal bone revealed an irregular soft tissue mass surrounding the ossicles within the left tympanic cavity and mastoid sinus, with an intact ossicular chain and increased density in the mastoid air cells. MRI provided further diagnostic clarity, showing a patchy T2WI hypointense signal in the left tympanic cavity, a low T1WI signal, and no diffusion restriction on DWI. There were multiple patchy and nodular T2WI hyperintense signals in the left middle ear mastoid, with high ADC values (Figure 2).

After completing the physical examination, we ruled out the diagnoses of cholesteatoma (no white cholesteatoma epithelium), chronic suppurative otitis media (no perforated eardrum), and secretory otitis media (no effusion within the tympanic cavity). Upon further review of the temporal bone CT and middle ear MRI, we ruled out the possibility of congenital cholesteatoma (CT: well-defined, expansile, non-enhancing mass; erosion of ossicles and bony structures; MRI: hyperintense on T2WI, variable intensity on T1WI), and paraganglioma (CT: well-defined, vascular mass with bony remodeling or erosion; MRI: intense enhancement with gadolinium, “salt-and-pepper” appearance on T2WI due to flow voids from high vascularity).

After thorough communication with the patient, we proceeded with an exploratory tympanotomy. The surgery was performed via an ear endoscope through the ear canal. After lifting the intact tympanic membrane, we discovered a smooth-surfaced neoplasm in the tympanic cavity, which was enveloping the ossicular chain and the chorda tympani nerve. Anterior to the tumor, there was “comma”-shaped new bone formation. A small piece of the neoplasm was excised and sent for intraoperative frozen section pathology. Using a micro hook, the neoplasm was slowly dissected. The tumor extended superiorly into the epitympanum, anteriorly to the level of the tensor tympani tendon, inferiorly to the lower margin of the round window niche, and posteriorly to the posterior tympanic isthmus. Due to obstruction by the ossicular chain, we were initially unable to remove the entire tumor, so we had to excise the incus to completely remove the tumor. The chorda tympani nerve and the stapes were preserved intact (Figure 3). Intraoperative pathology preliminarily suggested a malignant tumor. We informed the patient’s family of the pathological results and decided not to use an ossicular prosthesis for hearing reconstruction at this stage. To prevent further hearing loss and tympanic membrane retraction, we harvested and trimmed the tragal cartilage to an appropriate size, placing it above the head of the stapes for autologous hearing reconstruction. The postoperative immunohistochemical results indicated CK (+), Syn (+++), CK18 (+), EMA (++), CD56 (−), CgA (+), and Ki67 (2%+) (Figure 4). These findings, combined with the immunohistochemistry results, were consistent with a neuroendocrine tumor, histological grade G1. Postoperatively, the patient did not experience any complications such as facial paralysis or vertigo.

At the 3-week follow-up, the tympanic membrane was intact, and hearing was slightly decreased compared to pre-surgery levels (Figure 5). Six months postoperatively, a follow-up CT of the temporal bone and middle ear MRI showed no signs of tumor recurrence, and the patient had no symptoms of ear fullness, tinnitus, or vertigo in the left ear.

Reviewing the literature, neuroendocrine tumors are most commonly found in the gastrointestinal system. Therefore, 1-year after the surgery, we conducted a thorough examination of the patient’s gastrointestinal system and systemic lymph nodes, as well as a re-evaluation of the ear. No tumor recurrence was detected in any of these examinations. The patient was followed up for 2 years postoperatively, with no evidence of tumor recurrence or metastasis.

Discussion

HEARING REHABILITATION AND LONG-TERM AUDITORY PROGNOSIS:

The patient experienced mild hearing loss postoperatively (Figure 5), an outcome also noted in similar cases of middle ear NETs [5,6]. Hearing rehabilitation hearing aids or ossicular reconstruction could be considered for patients who experience more severe auditory impairment after surgery. Our patient had mild postoperative hearing loss and no tumor recurrence after 2 years of follow-up. He was a young man with unilateral hearing loss, refused to use hearing aids, and needed to undergo hearing reconstruction surgery after 5 years of follow-up without recurrence. Case reports in the literature show there is no clear risk of or approximate time of tumor recurrence. Therefore, in agreement with our patient, we decided to follow up for 5 years without tumor recurrence and then perform hearing reconstruction surgery.

LONG-TERM SURVEILLANCE AND RISK OF RECURRENCE:

Although our patient had no recurrence over 2 years, the optimal duration for surveillance remains uncertain due to the rarity of middle ear NETs. Evidence from similar neuroendocrine neoplasms in other anatomical sites suggests that long-term follow-up may be necessary, especially in higher-grade tumors, given the potential for delayed recurrence or metastasis. Salzman [2] reported cases of NETs with metastasis, emphasizing the need for vigilant follow-up in higher-grade cases. Middle ear NETs require biannual imaging and periodic audiological assessments, although there are no guidelines specific to this tumor type.

TUMOR GRADING AND ITS IMPLICATIONS FOR TREATMENT AND PROGNOSIS:

Histopathological grading, including differentiation levels and Ki67 index, plays a crucial role in prognosis and treatment planning. The low-grade (G1) classification of this tumor and the 2% Ki67 index suggest a low risk for recurrence, as seen in similar cases where low-grade tumors had limited aggressive behavior. Nevertheless, cases with higher Ki67 proliferation rates or G2 classification may require monitoring and consideration of adjunct therapies if aggressive features are present [7,8]. Current evidence highlights the utility of histopathological markers in stratifying patients by risk, potentially guiding the intensity and duration of follow-up.

CONSIDERATION OF ADJUNCT THERAPIES:

While surgery remains the primary treatment modality for NETs, adjunct therapies such as radiotherapy or chemotherapy could be considered in cases with incomplete resection or higher-grade tumors [9]. Although not commonly indicated for low-grade NETs, these treatments have been explored in more aggressive NETs at other anatomical sites, where they help manage residual disease and reduce recurrence. For middle ear NETs exhibiting aggressive features, such as higher Ki67 indices or extensive invasion, that provide additional therapeutic benefit, particularly if achieving clear surgical margins is challenging. For middle ear neuroendocrine tumors (NETs) that have aggressive characteristics, such as high Ki67 labeling indices or extensive invasion, additional therapeutic benefits can be particularly important when achieving clear surgical margins is challenging.

Conclusions

This case of a middle ear neuroendocrine tumor highlights both the diagnostic challenges and the surgical approaches essential for managing such rare tumors. Consistent with the literature, neuroendocrine tumors of the middle ear can present variably and require differential diagnosis that includes more common conditions like cholesteatoma and chronic otitis media. Surgical intervention via an endoscopic tympanotomy, as applied in this case, underscores the benefits of minimally invasive approaches in preserving ear structures and hearing where possible.

While recurrence remains a potential risk, as reported in other cases with malignant progression or metastasis to adjacent regions, this case had a favorable prognosis over a 2-year follow-up period. Further accumulation of cases is crucial to solidify diagnostic criteria and to explore whether alternative treatments or adjuvant therapies could be beneficial. This case adds to the limited body of evidence supporting that middle ear neuroendocrine tumors, though rare, can be managed effectively with tailored surgical approaches. Continued case reporting will be vital to enhance understanding and to refine treatment guidelines for optimal patient outcomes.