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Chief cells have the capability of synthesizing catecholamines. Infrequently paragangliomas secrete catecholamines in significant amounts and can produce symptoms (HTN, arrhythmias, excessive perspiration, headaches, nausea, pallor, etc.). The predominant catecholamine product is norepinephrine because of a lack of the enzyme (phenylethanolamine-N-methyltransferase) needed to convert norepinephrine to epinephrine. Elevated levels of epinephrine should alert to the possibility of a concurrent pheochromocytoma.
Synchronous glomus tumors are not the only associated neoplasms. Several authors have reported an association with other neoplasms (benign and malignant). Spector et. al. reported a 7% incidence in his series of 95 patients. Those most commonly associated include thyroid C-cell carcinoma, parathyroid adenomas, pheochromocytomas, the MEN syndromes, and visceral neoplasms of neural crest origin.
In the head and neck, two anatomic groups of paragangliomas can be differentiated: cervical paragangliomas and temporal bone (aka jugulotympanic) paragangliomas. The cervical group includes primarily carotid body tumors and glomus vagale or intravagale tumors, while the jugulotympanic refers to glomus jugulare and glomus tympanicum tumors. Jugulotympanic glomus tumors are the second most common temporal bone tumors (after acoustic neurinomas). The remainder of this discussion will focus on the temporal bone lesions.
Once these tumors were recognized and reports of their occurrence increased, attempts were made to classify them. In the 1960's, Guilford and Alford coined the term glomus tympanicum to describe those paragangliomas limited to the middle ear. Their classification system was limited by the diagnostic armamentarium available at the time of its derivation and was based on symptomology. As diagnostic imaging and surgical techniques advanced, more extensive classification systems were devised. In 1969, McCabe and Fletcher offered an updated classification methodology. This was followed in 1978, by Fisch's classification system, and subsequently, in 1981, by Glasscock and Jackson's proposed scheme. The latter two are used currently.
In the 1940's and 1950's, surgical approaches to the temporal bone were limited and recurrence after resection of glomus tumors was common, as were injuries to the facial nerve. Radiation therapy for glomus tumors became popular largely for these reasons. Since the 1970's, the advances in skull base neurotologic surgery have allowed a resurgence in the surgical management of temporal bone glomus tumors. Acoustic neuroma surgery approaches paved the way for these developments. In 1974, Fisch described the infratemporal fossa approach to the lateral skull base, which probably has had the biggest impact on surgical management of these tumors. Despite surgical advances, arguments over the relative merits of radiation therapy vs surgery as treatment modalities for glomus tumors continue today.
The main blood supply to the glomus tumors is the ascending pharyngeal artery, usually via inferior tympanic and neuromeningeal branches. Numerous other arteries can contribute, or occasionally be found to be the primary supply, particularly when the tumor is large or has intracranial or intradural extension. Angiography shows that 85% of cases demonstrate non-communicating multiple vascular compartments with small feeding vessels.
A key characteristic of glomus tumors is their slow growth rate. The typical patient goes undiagnosed for 3 to 6 years after the initial onset of symptoms because of slow insidious progression. Some patients have remained asymptomatic or with stable deficits for up to 40 years after detection of glomus tumors.
The most striking bit of epidemiology is the predominant incidence in females. The female:male incidence ratio is at least 4:1.
The incidence of malignancy in glomus tumors is believed to be low (<5%). There is no histologic distinction between the benign and malignant versions, and malignancy can only be proven by the presence of metastasis.
Patient age averages 50 to 60 years at presentation, but this is highly variable.
Catecholamine secreting (aka "functional") tumors occur in 1% - 3% of cases.
There is no racial or ethnic predilection.
There are familial patterns of occurrence, although the genetic model of inheritance is not agreed upon. The familial form is associated with a high incidence (25% - 50%) of multicentric paragangliomas. Multicentricity is found in about 5-15% of non-familial form patients. Interestingly, tumors are not typically found above and below the clavicles simultaneously.
On physical examination, the hallmark of a jugulotympanic glomus tumor is a red or reddish-blue mass seen behind the tympanic membrane. The diagnosis of glomus tympanicum can only be entertained if the examiner can see a full 360 degrees around the perimeter of the lesion, otherwise the presumptive diagnosis must be a glomus jugulare. The finding of a middle ear mass is fairly reliable, with 94 - 100% of untreated cases demonstrating this in reviews of large series of patients. Brown's sign (blanching of the mass with positive pressure pneumotoscopy) is often mentioned, but the frequency of this finding is not clear. Rarely, a friable or bleeding mass in the EAC may be the presenting sign with larger tumors. HTN, tachycardia, tremor, or complaints of vascular headaches should alert for the possibility of a functional tumor.
Cranial nerve deficits are seen primarily with larger tumors. Reports cite compression or invasion of CN's IX, and X most commonly, with CN's VII, VIII, XI, and XII affected less often. The presence of lower cranial nerve deficits rules out an isolated middle ear glomus tympanicum. Isolated deficits of CN's VII and VIII are more likely to be secondary to a tympanicum.
Patients who present with "idiopathic" lower cranial nerve deficits should have their lateral skull bases evaluated with CT or MRI if no cause can be found for their neuropathy.
Sensorineural hearing loss on the side of a glomus tumor is the hallmark of labyrinthine invasion.
Glomus tumors are much more common than almost any other middle ear neoplasm, and second only to acoustic tumors in the temporal bone overall, but other lesions should be considered. Although the list of differential diagnoses includes neural lesions (neurolemmoma, neurofibroma, chordoma), osteoblastoma, adenomas, adenocarcinomas, inflammatory polyps, cholesterol granulomas, and a host of rare lesions such as histiocytosis, fibromyxoma, melanoma, rhabdomyosarcoma, lipoma, plasmacytoma, or metastatic lesions (lung, breast, prostate), almost all of these can be excluded with the appropriate physical examination and radiological studies.
After diagnosis, the workup must include a search for other tumors (multicentricity). Screens for urine catecholamine metabolites (VMA, normetanephrine and metanephrine), or serum levels of catecholamines need only be done if there is reason to suspect a secreting tumor. It has been recommended that this be done before any angiography because of possible need for selective renal vein sampling if elevated levels of epinephrine are detected, but MRI screening of the abdomen in these cases may negate the need for this. Although there is a reported increased incidence of associated non-paraganglioma tumors, a search for them is not performed unless clinically indicated.
If surgery is planned, and its suspected that the carotid artery may be at high risk, angiography with balloon test occlusion is strongly advised, although 15-25 % of people who tolerate temporary balloon occlusion will have neurologic sequelae after ligation of the tested carotid artery. Those who have neurologic changes with test occlusion should not be operated on unless there are plans for interposition graft or other recollateralization. The predictability of ICA occlusion effects is the most controversial topic in skull base surgery. Our faculty feels that if carotid resection is likely to be required to remove the tumor, strong consideration should be given to radiation treatment.
Preoperative embolization of feeding vessels is a little controversial. Proponents argue that if embolization can be performed within 48 hours of planned surgery, the blood loss is significantly reduced. Some experts, most notably The Otology Group (Glasscock, Jackson, et. al.) disagree, claiming benefits of embolization are outweighed by the risks. In the absence of planned embolization there may be no need for angiography at all.
Glomus tympanicums appear on CT as a soft tissue mass abutting the promontory of the middle ear. There may be displacement of ossicles or bony erosion of the tympanic cavity. The finding of air or bone between the tumor and the jugular bulb virtually assures the diagnosis of a tympanicum and no further imaging is required.
Glomus jugulare tumors can expand in any direction, but they tend to erode the bony plate between the jugular bulb and the internal carotid artery. An intact petrous carotid canal is helpful in ruling out an aberrant carotid artery, along with intravenous contrast imaging. Contrast CT scans and/or angiography are usually adequate to detect this.
Radiographically, glomus tumors appear isodense to cerebellum on unenhanced CT scans, and enhancing masses with contrast. On post gadolinium T1 weighted MRI scans, there are hypodense areas as well as isodense areas, referred to as a"salt and pepper" appearance. The hypodense areas correspond to flow voids, or blood flow in vascular spaces. The isodense areas represent the solid portions of the tumor. On T2 scans, the flow voids remain, and the solid areas are slightly hyperintense.
CT scans are best for evaluating bony destruction and erosion, which is a hallmark of jugulotympanic glomus tumors. The CT may lead to the incorrect diagnosis of a malignancy because of the irregular edges of the bone destruction.
MRI in usually better than CT for delineating tumor edges and extent, especially intracranially. It is also better for evaluating the relationship of the tumor to adjacent jugular vein, carotid artery, membranous labyrinth, and cranial nerves.
Glomus Jugulare Glomus jugulare tumors can be treated with surgical excision, radiation therapy, surgery and radiation, or observation. The argument over the relative merits of surgery vs radiation center on their complications and efficacy. With advances in skull base techniques, surgery is generally efficacious, so the decision on treatment mode often centers on the potential morbidity of the surgery, and other patient factors.
Tumor size, extent, and location dictate the surgical approach to be used as well as the potential for post operative problems. The larger the tumor the higher the morbidity, with rates of cranial nerve sacrifice directly related to tumor stage. However the larger the tumor, the more likely the lower cranial nerves will be affected even before surgery. Obviously there is little consequence to surgical sacrifice of a nonfunctioning nerves, so preoperative deficits must be weighed against the likelihood of postoperative deficit. Additionally, the patient's age and overall health influence the treatment plan. Elderly (>65 years old) patients are not ideal candidates for skull base surgery. On the other hand, the unproven efficacy of XRT over the long term and otherwise long life expectancies bias the decision toward an attempt at complete excision in younger patients. Young patients also adapt to loss of cranial nerve functions better than older patients. Most often primary radiation therapy is used in cases where the patient is a poor surgical candidate, the tumor is "unresectable" without carotid sacrifice and the patient fails balloon occlusion testing, or the patient refuses surgery.
In the event of multicentricity, careful consideration of post-operative morbidity must be given. If the skull base is involved bilaterally, there is significant risk of laryngeal and pharyngeal denervation with bilateral surgical intervention. In this circumstance the most life threatening lesion is addressed first, and the subordinate lesion(s) palliated until outcome is clear.
The presence of intracranial extension or symptomatic catecholamine excretion negate the drawbacks of surgery. These tumors must be operated on to prevent dire consequences.
Glasscock & Jackson Class I & II and Fisch C1 & C2 glomus jugulare tumors can be resected with an extended facial recess approach. The canal wall can be preserved or removed as needed for exposure. Some exposure of the area anterior to the internal carotid can be exposed with this approach.
Glasscock & Jackson Class III lesions extend medially and anteriorly to involve the petrous apex, and usually the horizontal carotid canal. Class IV lesions extend beyond the petrous apex, into the clivus or into the infratemporal fossa. These are similar to the Fisch C3 & C4 classes, Both of these are most commonly treated by the infratemporal fossa approach or a variation of it. The infratemporal fossa approach has become the predominant one used for glomus jugulare resection. Extension of the dissection into the neck allows proximal and distal control of the jugular and carotid systems, which is considered essential for success in resection of larger anteromedial tumors. The exposure is adequate for removal of tumor up to and including cavernous sinus involvement, but it does require relocation of the facial nerve. It has the reputation of a significant percentage of residual lower cranial nerve deficits. However, it allows the resection of tumors that are not accessible with more conservative approaches.
Intracranial and/or intradural extension is a subclass (CxD1-3) of the Fisch classification system. The same approaches are used, but the extracranial portion of the tumor is resected first. This may help reduce bleeding during the intracranial dissection by removing the primary blood supply. Single stage complete resection is fairly common now.
The incorporation of subtemporal exposure can be combined with the infratemporal approach. An attraction of this technique is that it allows adequate exposure of medial structures without transposition of the facial nerve. Patel et. al. recently reported on a series of patients treated with this and other combined approaches and their incidence of facial and lower cranial nerve injury compared favorably to those reported in larger series of traditional infratemporal fossa resections.
Retrosigmoid, or suboccipital approaches can be incorporated as needed for posterior fossa extension.
Incomplete resection is not desirable but may be necessary in some cases. If this occurs, postoperative radiation therapy is usually indicated.
Evaluating the reports of success or failure of various treatment options has been plagued by low numbers of patients, poor long term follow up, and the inability to generate data that represent results of "current state of the art" treatment for either modality. Additionally, nonuniformity in the presentation of data, frequent lack of distinction between different glomus tumor locations, combining of previously treated (ie - treatment failures) with previously untreated cases, indistinct therapeutic endpoints, and potential patient selection bias have led to difficulty making meaningful comparisons between reported surgical results and results of primary radiation therapy. Carrasco and Rosenman, in an effort to resolve some of the controversy, reviewed and analyzed 24 commonly cited treatment series published between 1964 and 1987. 582 patients were included in these studies. They point out shortcomings in the published studies, but make several pertinent observations.
Green et. al., published their results of surgical treatment of 52 glomus jugulare patients between 1981, and 1991. The follow up period was relatively brief, averaging only 3.4 years. They reported that they were able to perform complete primary excision in 85% their cases, and there were no surgical mortalities. In all 8 cases of incomplete resection, the tumor had intradural spread, and 5 of these 8 cases had to be stopped secondary to excessive blood loss. They reported 83% of their cases performed via the infratemporal fossa approach. Compared to pre-operative status, post-surgical cranial nerve deficits occurred in 26%, 13%, 25%, and 6% of patients, for CN's IX, X, XI, and XII respectively.
Wilson et. al., reviewed the results of their primary surgical treatment of 71 patients with glomus jugulare tumors between 1971 and 1991. Sixty-seven of these patients underwent total resection, with 4 subtotal resections. These four underwent post operative XRT. There were two perioperative mortalities, one due to a pulmonary embolus, another due to stroke after a carotid injury intraoperatively. Forty-one percent of their patients had pre-operative lower cranial nerve deficits. Of the patients without pre-operative deficits, post- operative CN deficits were noted in 13%, 61%, 36%, 40%, and 33% with respect to CN's VII, IX, X, XI, and XII, respectively. Overall, the rates of sacrifice of CN's VII, IX, and X were 23, 63%, and 59%.
The fact that cranial nerve preservation decreases commensurate with increasing tumor size was dramatically illustrated in Wilson et. al.'s series. No patients with Type IV tumors had preservation of CN's VIII through XII. Contrarily, preservation rates in Glasscock & Jackson Type I tumors was greater than 90% for all cranial nerves except VII (83% reserved) and IX (74% preserved).
Finally, what constitutes successful treatment? Surgery supporters insist eradication of disease is the true measure of success, whereas radiotherapy advocates generally define successful treatment as an arrest in the progression of symptoms and tumor growth. It is difficult to prove a cure because of the impossibility of proving the absence of microscopic disease in post surgical patients, and the observation that recurrences can be extremely delayed (in some cases 20 or more years post treatment). The validity of claims of curative therapy, with what we traditionally consider to be adequate follow up, may not be certain.
More data and long term follow up from this generation of skull base surgery patients will be needed before the controversy is settled (if it ever is). Included will no doubt be additional data about radiotherapeutic measures, such as the Gamma Knife, for which there is a dearth of data in regard to glomus tumor treatment.
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