Peripheral paralysis of the facial nerve as a manifestation of neuroendocrine tumor of the middle ear – Case report

Introduction: Acute idiopathic peripheral facial nerve paralysis is often linked to viral infections such as Herpes simplex virus type 1 reactivation. Neuroendocrine tumors (NETs) of the middle ear (MEANT) are rare and present with non-specific symptoms, including hearing loss, otalgia, and neuropathy, complicating early diagnosis.

Case report: Report the case of a 47-year-old patient treated for chronic otitis since 2020. In 2024, the onset of peripheral facial nerve paralysis prompted advanced diagnostics, including MRI, CT, biopsy, and immunohistochemical analyses, confirming MEANT. Treatment included surgical excision, gamma knife therapy, and regular tumor marker monitoring. A delayed diagnosis of the tumor highlighted the need for heightened clinical suspicion in cases of chronic ear pathology with atypical progression.

Conclusion: Neuroendocrine tumors of the middle ear are diagnostic and therapeutic challenges due to their rarity and non-specific presentation. Early recognition of peripheral facial nerve paralysis as a potential indicator of an underlying malignancy is critical. Multidisciplinary management, integrating advanced imaging, histopathological confirmation, surgical intervention, and adjuvant therapies, improves outcomes and minimizes relapse risks. General practitioners play a pivotal role in identifying early symptoms to reduce diagnostic delays.

INTRODUCTION

Peripheral facial nerve paralysis is often of unknown origin. It is considered an idiopathic condition, although increasing evidence links it to viral infections, such as the reactivation of Herpes simplex virus type 1 [1]. The characteristic clinical presentation includes sudden weakness or paralysis of the muscles on one side of the face, which may be accompanied by pain behind the ear, diminished sense of taste, and increased sensitivity to sound.

Diagnosing peripheral facial nerve paralysis is clinical but requires ruling out other possible causes [2]. The differential diagnosis may suggest a range of different diseases and conditions. Stroke, for instance, unlike peripheral facial nerve paralysis, often affects only the lower part of the face and is associated with other neurological deficits [3]. Lyme disease can mimic peripheral facial nerve paralysis but usually occurs in endemic areas and is accompanied by a Borrelia-related erythema [4]. Skull base tumors are also a rare cause but can produce similar symptoms, highlighting the importance of magnetic resonance imaging [5],[6]. Infections such as otitis media and Herpes zoster oticus (Ramsay Hunt syndrome) may cause similar symptoms but are usually accompanied by pain or rash, which helps guide us to the correct cause. The differential diagnosis should also consider autoimmune conditions like Guillain-Barré syndrome and sarcoidosis [5].

Neuroendocrine tumors (NETs) represent a diverse group of tumors arising from neuroendocrine cells. These cells, which share characteristics of the nervous and endocrine systems, can be found in various organs and tissues throughout the body. NETs are relatively rare but can be localized in the lungs, gastrointestinal tract, pancreas, and even the middle ear, representing a distinct and under-researched subgroup. Neuroendocrine tumors of the middle ear, also known as middle ear adenomatous neuroendocrine tumors (MEANTs), are sporadic and account for less than 2% of all middle and inner ear tumors. To date, fewer than 150 cases have been reported in the English literature, under various names, including carcinoid tumors, middle ear adenomas, middle ear adenomatous tumors, adenocarcinoid tumors, and amphicrine tumors. The first documented primary adenomatous tumor confined to the middle ear cavity was described in 1976. NETs are classified as well-differentiated (typically benign or of low malignant potential) and poorly differentiated (highly malignant). Histologically, these tumors secrete specific markers such as synaptophysin and chromogranin, which aid diagnosis via immunohistochemistry [7],[8],[9]. The clinical presentation depends on the tumor’s location and secretory activity [8]. These tumors are often referred to as adenomatous neuroendocrine tumors (NAME) or tympanic adenomas. They commonly present with symptoms such as hearing loss, tinnitus, or a sensation of fullness in the ear [9]. Histopathologically, middle ear NETs may exhibit a mixed neuroendocrine and non-neuroendocrine component [7]. It is believed that MEANTs originate from the epithelium lining the middle ear mucosa, which is a continuation and modification of respiratory epithelium [8]. Diagnostic methods include imaging such as computed tomography (CT) of the temporal bone and magnetic resonance imaging (MRI), while definitive confirmation is only possible through biopsy and immunohistochemical examination. Although middle ear NETs are extremely rare, their prevalence is slightly higher in middle-aged men [8],[10]. Clinical symptoms depend on the size and local spread of the tumor. Most patients present with unilateral hearing loss, while a smaller portion may develop otorrhea or pain [11].

CASE REPORT

A 47-year-old female patient was initially treated conservatively and with paracentesis for chronic nonsuppurative otitis and a noted mass in the mastoid cavity observed on MRI. In August 2024, she presented as an emergency case due to peripheral facial nerve paralysis, which prompted further investigation.

A surgical procedure was performed, including tympanoplasty with mastoidectomy and ossicular chain reconstruction on the left side. The initial histopathological finding suggested adenoid cystic carcinoma. However, a subsequent review of the pathology confirmed a middle ear neuroendocrine tumor (MEANT), classified as a G1 neuroendocrine adenoma with low proliferative potential (Ki-67 < 1%). The immunohistochemical profile showed positive markers (INSM1, synaptophysin, p63) and negative markers (chromogranin A, CD117, CK7, SOX-10).

Radiological findings, including MRI and CT scans, indicated postoperative changes and the presence of residual tumor with infiltration at the skull base, exhibiting both extracranial and temporobasal extension, but without signs of cerebral edema or intracranial hemorrhage. CT scans of the neck and upper abdomen showed no significant lymphadenopathy, while a 9 mm cystic liver lesion was classified as benign.

A multidisciplinary therapeutic approach was proposed, including surgical excision, postoperative gamma knife therapy, and monitoring neuroendocrine tumor markers (CgA and NSE). Consultations with an ENT surgeon, neurosurgeon, and oncologist were recommended for further evaluation and follow-up.

DISCUSSION

This case report of a middle ear neuroendocrine tumor (MEANT) highlights the crucial role of early symptom recognition by general practitioners, particularly in patients with persistent or recurrent symptoms. Since 2020, the patient had been treated for chronic otitis with evident effusion in the mastoid process, which already indicated the need for more thorough evaluation and a multidisciplinary approach. In this case, it was not until the development of peripheral facial nerve palsy in 2024 that further diagnostic steps were initiated, pointing to a potential time gap between symptom onset and accurate diagnosis. Middle ear neuroendocrine tumors are rare and often present with non-specific symptoms such as chronic otalgia, otorrhea, or hearing loss, which complicates early recognition [1],[2],[3],[5]. Clinical suspicion from the general practitioner can expedite the diagnostic process. Primary care physicians could improve outcomes by early recognition of symptoms such as persistent otalgia, hearing loss, and peripheral neuropathy by enabling earlier diagnostic procedures like MRI and CT scans [12].

Diagnostic challenges also include the specificity of histopathological findings, where the immunohistochemical profile of the tumor is essential for differentiating MEANT from other carcinomas. For instance, positive markers such as INSM1 and synaptophysin, combined with a low Ki-67 index (<1%), indicate a low proliferative potential of this tumor [7],[13],[14]. Ki-67 is a proliferation-associated antigen that plays a key role in cell division and tumor cell proliferation. A high Ki-67 index indicates active cell proliferation, potentially signaling the risk of malignancy [8],[9]. However, without earlier recognition, these findings often appear late in the clinical course of the disease, when aggressive therapeutic interventions are already necessary. A multidisciplinary treatment approach, including surgical excision and postoperative gamma knife therapy, has proven effective in managing such cases [13]. Additionally, monitoring markers such as chromogranin A (CgA) and neuron-specific enolase (NSE) is essential for evaluating treatment response and detecting recurrence [10],[13],[14].

This case emphasizes the need for continuous education of general practitioners regarding the importance of recognizing early symptoms of malignant middle ear diseases. Implementing diagnostic algorithms and close collaboration with specialists can improve the quality of care and significantly enhance the prognosis for patients with similar conditions.

CONCLUSION

Although rare, middle ear neuroendocrine tumors can pose significant diagnostic and therapeutic challenges. The manifestation of peripheral facial nerve paralysis as an initial symptom in such tumors necessitates prompt and accurate diagnosis to ensure timely treatment and reduce the risk of permanent consequences. The role of the general practitioner as the first point of contact, along with a multidisciplinary approach involving clinical evaluation, radiological methods, and histopathological analysis, is essential for establishing a diagnosis and determining the optimal treatment. While tumors with low proliferative potential tend to have a more favorable prognosis, continuous monitoring for possible recurrences and metastases remains critically important.