Glomus tympanicum (GT) tumors are benign arising from paraganglion cells of the tympanic plexus in the middle ear. Although surgical resection remains the best option for definitive treatment of these tumors, the diagnostic and management algorithms have evolved considerably with the introduction of high-resolution computed tomography, MRI, and genetic testing.
Key points
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Glomus tympanicum (GT) arise from paraganglion cells of the middle ear and are distinguished from glomus jugulare by a lack of bony erosion around the jugular bulb.
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At a minimum, all patients with a suspected GT should have a high-resolution computed tomography of the temporal bone and neck for diagnostic purposes.
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Genetic testing and evaluation for tumor neurosecretory function should be considered based on a patient’s history and demographic information.
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Surgical resection is the best option for definitive treatment of GT tumors.
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During surgical resection, avoid unnecessary morbidity by leaving adherent disease on vital structures when necessary.
| CSF | Cerebrospinal fluid |
| CT | Computed tomography |
| EAC | External auditory canal |
| GT | Glomus tympanicum |
| MRI | Magnetic resonance imaging |
Introduction
Glomus tympanicum (GT) tumors, or tympanic paraganglioma, are the most common benign tumors of the middle ear. Paragangliomas are embryologically derived from the neural crest and represent a proliferation of paraganglion cells within a highly vascular environment. These cells are normally associated with structures of the autonomic nervous system throughout the body and are most abundant in the adrenal glands. Neoplastic proliferations of paraganglion cells arising from the adrenal glands are called pheochromocytomas , whereas extra-adrenal paragangliomas are most frequently found in the head and neck and have been referred to as chemodectomas and glomus tumors .
Paragangliomas of the head and neck are most commonly found at the carotid body and represent less than 1% of tumors in this region. Within the temporal bone, paraganglioma tumors arise along the tympanic plexus of the Arnold and Jacobson nerves or the adventitia of the jugular bulb. The former are called tympanic paraganglioma , and the latter are called jugular paraganglioma . These tumors are also referred to as glomus tympanicum and glomus jugulare , respectively.
Although surgical resection of tympanic paragangliomas continues to be the best option for definitive treatment, the diagnostic and management algorithms for these lesions have evolved over time. Tumor diagnosis begins clinically with the visualization of a red mass behind an intact eardrum, but computed tomography (CT) and MRI have become essential for identifying the tumor origin and defining the extent of disease. Screening for tumors with neuroendocrine secretory function remains of critical importance in select cases, and with the increasing sophistication and availability of genetic testing, the implications of patient specific tumor biology are an emerging consideration. From a surgical perspective, the generally benign nature of these tumors juxtaposed with their close proximity to the facial nerve, cochleovestibular system, jugular vein, and internal carotid artery have led to recommendations for less aggressive resection to avoid unnecessary morbidity in the setting of adherent disease. This article provides an in depth discussion of GT pathophysiology and a review of historical and contemporary trends in tumor diagnosis and management.
Introduction
Glomus tympanicum (GT) tumors, or tympanic paraganglioma, are the most common benign tumors of the middle ear. Paragangliomas are embryologically derived from the neural crest and represent a proliferation of paraganglion cells within a highly vascular environment. These cells are normally associated with structures of the autonomic nervous system throughout the body and are most abundant in the adrenal glands. Neoplastic proliferations of paraganglion cells arising from the adrenal glands are called pheochromocytomas , whereas extra-adrenal paragangliomas are most frequently found in the head and neck and have been referred to as chemodectomas and glomus tumors .
Paragangliomas of the head and neck are most commonly found at the carotid body and represent less than 1% of tumors in this region. Within the temporal bone, paraganglioma tumors arise along the tympanic plexus of the Arnold and Jacobson nerves or the adventitia of the jugular bulb. The former are called tympanic paraganglioma , and the latter are called jugular paraganglioma . These tumors are also referred to as glomus tympanicum and glomus jugulare , respectively.
Although surgical resection of tympanic paragangliomas continues to be the best option for definitive treatment, the diagnostic and management algorithms for these lesions have evolved over time. Tumor diagnosis begins clinically with the visualization of a red mass behind an intact eardrum, but computed tomography (CT) and MRI have become essential for identifying the tumor origin and defining the extent of disease. Screening for tumors with neuroendocrine secretory function remains of critical importance in select cases, and with the increasing sophistication and availability of genetic testing, the implications of patient specific tumor biology are an emerging consideration. From a surgical perspective, the generally benign nature of these tumors juxtaposed with their close proximity to the facial nerve, cochleovestibular system, jugular vein, and internal carotid artery have led to recommendations for less aggressive resection to avoid unnecessary morbidity in the setting of adherent disease. This article provides an in depth discussion of GT pathophysiology and a review of historical and contemporary trends in tumor diagnosis and management.
History
Paraganglioma of the temporal bone emerged as a distinct pathologic entity during the 20th century. Stacy R. Guild first described the existence of naturally occurring glomus formations along the Jacobson and Arnold nerves in the 1940s. Rosenwasser subsequently explained paraganglioma growth as a neoplastic proliferation of these structures, and Simpson and Dallachy reviewed reported cases of vascular middle ear tumors dating as far back as 1889, concluding that many were likely to have been paragangliomas. Using this work, Guild was able to perform a general analysis of tumor anatomy in which he noted that the vascular pedicle for most tumors was the ascending pharyngeal artery. However, many subsequent tumor characterizations were hindered by difficulty distinguishing GT from jugulare. In a 1962 meta-analysis of 316 tumors, Alford and Guilford noted that a “multiplicity of location from which these tumors may arise” complicates a description of “definite symptoms or symptom complexes that will satisfy all these tumors and/or be pathognomonic of all of them.” However, this confusion did not prevent the identification of important demographic and symptom trends associated with temporal bone paragangliomas. Alford and Guilford found that affected patients were more commonly women (66%) and middle-aged (mean, 49 years; range, 17–85 years). Patients were most likely to present with hearing loss, tinnitus, and a red, bulging tympanic membrane or a polypoid mass in the external auditory canal (EAC). Less than 5% of patients had multifocal tumors, with even fewer experiencing metastatic or secretory disease.
Complete surgical resection has historically been the preferred treatment for GT. House and Glasscock described the importance of preoperative polytomography and retrograde jugulography for accurate diagnosis, and standardized surgical approaches as either transcanal or postauricular depending on the presumed tumor extent. For cases in which the tumor was locally advanced, a postauricular incision allowed for a mastoidectomy, posterior tympanotomy, extended facial recess, and fallopian bridge. The importance of functional preservation was also reinforced with the recommendation that “the posterior canal wall, the tympanic membrane, ossicles, and facial nerve should remain intact”. The collective experience of these authors set the general standards for GT surgery that persist into the current era of operative management.
Tumor histology and pathophysiology
A histologic analysis of GT tumors reveals many similarities to paragangliomas that occur elsewhere in the body. Grossly, tumors are solid and encapsulated, although they can often have an invasive appearance in the temporal bone because of growth within haversian canals and air cells. Microscopically, tumors are conglomerations of chief cells surrounded by sustentacular cells (“zellballen”) and an extensive capillary network that creates a reticular appearance ( Fig. 1 ). Chief cells are characterized by a polyhedral shape, round nuclei, and eosinophilic cytoplasm that can contain granular structures ( Fig. 2 ). Immunohistochemical staining generally reveals chromogranin, serotonin, neuron-specific enolase, and somatostatin expression in chief cells and S-100 expression in sustentacular cells.
Neurosecretory function in GT tumors is rare, but screening for functional tumors remains an important part of tumor management. Pheochromocytomas of the adrenal medulla are not uncommonly secretory and are able to produce dopamine, norepinephrine, and epinephrine. However, functional head and neck tumors are only seen in 1% to 3% of cases and, because of a lack of the enzyme phenylethanolamine- N -methyltransferase, which is not commonly found in extramedullary paragangliomas, norepinephrine secretion predominates. Although the incidence of neurosecretory function in GT tumors is low, the autonomic instability provoked by catecholamine release during surgical manipulation necessitates careful screening during tumor workup. Historically, preoperative venous sampling was encouraged in all cases to avoid a rare intraoperative crisis. Presently, the identification of functional tumors relies on a preoperative workup that includes a detailed medical history and laboratory testing designed to identify an excess of catecholamines or their byproducts in the systemic circulation or urine. The details of this workup are discussed in more detail later.
Despite being prone to locally aggressive behavior, GT tumors are generally benign histologically. According to multiple sources, malignancy is ultimately identified in approximately 5% of temporal bone paragangliomas. Although some have suggested that microscopic evidence of increased mitotic activity, necrosis, and local invasion can be indicators of malignancy, a histopathologic basis currently does not exist for distinguishing between benign and malignant disease. Rather, the presence of regional or distant metastasis serves as the most widely accepted trait of malignancy.
The genetic basis of paraganglioma development is an emerging topic. Ten percent of head and neck paraganglioma are believed to be familial in nature, and previous work has identified multiple potential loci on chromosome 11, termed paraganglioma loci (PGL), that seem to play a role in tumor pathogenesis. Inheritance via an autosomal dominant pattern influenced by genomic imprinting has been described. Subsequent studies have revealed mutations in succinate dehydrogenase (SDH) complexes at these locations that are believed to be responsible for familial tumor pathogenesis. Because the phenotypes associated with distinct mutations may differ, the genetic origin of a glomus tumor may also have implications on its malignant potential, particularly in the case of SDHB mutations.
Presentation: demographics and clinical evaluation
GT tumors are more commonly seen in specific patient populations. A strong female predilection was reported previously, and this trend was verified by a recent review of the authors’ experience at The Otology Group of Vanderbilt, in which 90.4% of patients were women, the mean age at presentation was 55.2 years (range, 25.9–79.1 years), and bimodal peaks were seen in patients in their 30s and 60s. The authors also observed that men with GT typically present at a younger age. In other reports, tumors have even been diagnosed in infants. A significant preponderance in tumor laterality was not seen (52.2% right-sided), which is consistent with what has been previously described.
The history and physical examination are an important part of the evaluation of a patient with a suspected GT. Patients commonly present with complaints of pulsatile tinnitus (81.4%), subjective hearing loss (77.1%), and aural fullness (70.2%), whereas otalgia is uncommon. In extensive tumors that have grown though the tympanic membrane, episodic bloody otorrhea can occur (9.6%). Rarely, growth within the eustachian tube can lead to epistaxis. Symptoms suggestive of lower cranial neuropathy, such as dysphonia, dysphagia, and weakness of the shoulder or tongue, should raise suspicion for a jugular paraganglioma. Preoperative facial paralysis was seen in only one patient in the authors’ series (0.9%), who presented 9 years after a subtotal resection at an outside center. On otoscopic examination, tumors are generally recognizable as red, pulsatile masses of the middle ear ( Fig. 3 , [CR] ). When the mass is in contact with the tympanic membrane, blanching can occasionally be seen with pneumatic pressure, which is referred to as Brown’s sign. In the authors’ series, Brown’s sign was documented in approximately half of the cases. In additional to a history and physical examination, baseline audiometry should always be performed during the initial evaluation to objectively evaluate the degree to which a tumor has affected hearing.
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