jugulotympanic paragangliomas

SKULL BASE TUMOR SURGERY 00304665/01 $16.00 + .OO

JUGULOTYMPANIC PARAGANGLIOMAS

Peter C. Weber, MD, MBA, FACS, and Sunil Patel, MD

Paragangliomas of the jugular foramen were first described in the mid- ~ ~ O O S . ~ , ~ The first attem t at surgery for a paraganglioma of the ear was in 1889 by Waggenhauser?, 7,8, 1;B33,

It was not until 1941 that the causes for paragangliomas of the ear were elucidated. It was in 1941 that Guild” described naturally occurring glomus bodies along the course of the tympanic branch of the glossopharyngeal nerve (Jacobson’s nerve) from the jugular fossa foramen to the promentory of the middle. They also were found along the auricular branch of the vagus nerve (Arnold’s nerve), which passes from the jugular foramen to the descending portion of the facial nerve, and in the adventitia of the dome of the jugular bulb. Furthermore, Guild, a pathologist, described these tiny bodies as small masses that could be as large as 1.5 mm in diameter and consist of capillary and precapillary blood vessels interspersed with epithelial cells.”

It was not until 1945, however, that Rosenwasser and OtaniZ7 identified the paraganglioma of the jugular foramen, which was the same tumor type as the well-known carotid body tumor. These types of tumors were treated before Rosenwasser’s description, but they probably were labeled as other diseases such as hemangioma, fibromyoendothelioma, or some type of hemorrhagic gran- uloma. Although many names have been given to these tumors, such as carotid body-like tumor, nonchromaffin paragangliomas, chemodectomas, jugulari resec- tomas, or glomus jugulari tumors, the correct term is purugungliornu of the jugular forurnen or jugolotyrnpunic purugungliornu (JTP).

PATHOLOGY

Although known to many investigators as glomus jugulari tumors, the term really does not apply to these tumors because the chief cell is not derived from

From the Department of Otolaryngology, The Cleveland Clinic, Cleveland, Ohio (PCW); Department of Neurosurgery, Medical University of South Carolina, Charleston, South Carolina (SP)

OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA

VOLUME 34 NUMBER 6 DECEMBER 2001 1231

1232 WEBER & PATEL

specialized periocytes in the glomus complexes as once believed?, 36 Rather, the chief cells are of paraganglionic tissue, which is derived from the neural crest.l2

Tumors of the paraganglia, or what are now called paragangliomas, are di- vided into two groups: (1) tumors that are associated with the adrenal gland and (2) tumors that are extra-adrenal.'O The extra-adrenal paragangliomas are not pheochromocytomas and they can be located just about anywhere in the body. In the head and neck, however, they usually are limited to the carotid body, jugular tympanic region, vagal region, and laryngeal, nasal, or orbital region. The most common of these sites is the carotid body.35

Histologically, the paragangliomas demonstrate the clusters of chief cells commonly called zellballen cells close to a multitude of small blood vessels and unmyelinated nerve fiber^.','^,^^ When examined more closely under elec- tron microscopy, secretory granules that contain catecholemines also have been identified.I6 These granules are located in the cytoplasm of chief cells, and thus these tumors can be of the catecholemine-secreting variety. These paragangliomas belong to the amine precursor uptake decarboxylase (APUD) system7 and are associated with other paragangliomas and even pheochromocytomas, thyroid medullary carcinoma, or Reckling hausen's disease.

In looking at the common locations of JTPs, the most common sites are located on the jugular dome, which accounts for about 55% of all JTPs. Another 20% of sites are identified along Jacobson's nerve, 25% are on the promentory, and a few percent are associated with Arnold's

The three main types of jugular foramen paragangliomas are: (1) tympanic, which mainly originate in the middle ear; (2) jugular, which originate in the jugular foramen; and (3) vagal, which are located below the skull base. In large tumors, however, it is almost impossible to detect the actual origin of the tumors.

EPIDEMIOLOGY

Paragangliomas of the jugular foramen are normally benign in nature. In about 3% of cases, they may be malignant.7 These malignant paragangliomas ac- tually may metastasize to distant sites such as the lung, bone, or liver. Generally, paragangliomas occur in the fifth decade of life, although they can occur in ages ranging from the very young to the elderly.32 Paragangliomas are more common in women (fema1e:male ratio, 3:l) and appear to be more common in whites.'rz1

Although paragangliomas of the jugular foramen are typically isolated, multiple or asynchronous paraganglioma tumors can occur in 4% to 10% of patient^.^,^,^' There is no typical combination pattern; however, there is one small series that describes the tympanicum tumor with the carotid body tumor.31 It seems that there is a small subset of patients who develope these tumors through autosomal dominant transmission (i.e., a hereditary pattern).I3, 22, 31 These patients more frequently exhibit (up to 30%) multiple paragangliomas, which may be associated with other tumors such as pheochromocytomas?2

SIGNS AND SYMPTOMS

Because of their slow growth, JTPs are not detected until they are quite large. Delays in diagnosis may take more than 4 years.8 The most common symptom of JTP is pulsatile tinnitus?,13 Although tympanic gangliomas are rarer than jugular foramen paragangliomas, the gangliomas change the tympanic membrane

JUGULOTYMPANIC PARAGANGLIOMAS 1233

mobility or decrease the ossicular movement, which results in conductive hearing

Overall, the signs and symptoms of JTPs can be grouped based on the site in which the tumor is located. When the tumor is located in the middle ear, hearing loss, otorrhea, or a olyp may develop. Because this is a vascular tumor, a positive Brown's sign:" such as pulsatile tinnitus and aural bleeding, may occur. With significant tumor extension, patients may develop otalgia, vertigo, sen- sorineural hearing loss, or other cranial neuropathies such as facial paralysis, hoarseness, or dysphagia.

~ o s s . ~ ~ , ~ ~

EVOLUTION

Paragangliomas, though slow to grow, destroy significant amounts of bone; over time, however, they tend to spare the otic capsule and ossicles. Paragan- gliomas ultimately follow a path of least re~istance.~ They may follow the eustachian tube to the nasopharynx. Others may go to the petrous apex by way of peritubal cells or down past the jugular bulb through the jugular foramen to the skull base. They also may follow the carotid artery, leading to the middle fossa or cavernous sinus, or may track up the inferior petrosal s i n u ~ . ~ , ~ ~ It is rare for JTPs to grow through the tympanic membrane and into the external auditory canal.14 Fortunately, intracranial extension is less than 15%.30 Depending on the path of extension, other cranial nerve abnormalities (up to 37%) may be seen, including facial paralysis (in up to 20% of patients);O cranial nerve deficits with compres- sion at the jugular foramen, or Horner's syndrome in patients in whom the middle cranial fossa has been in~aded .~ , 30

DIAGNOSIS

Visualization

Microscopic examination often reveals a mass in the hypotympanum or on the promontory (Fig. 1). In tumors that do not invade the middle ear or have questionable diagnoses, imaging studies are very useful.

Figure 1. Glomus tympanicum as seen in the middle ear.

1234 WEBER & PATEL

Imaging Studies

Regardless of whether one believes that a tumor is a small or very large glomus tympanicum, proper imaging is essential for the classification and treatment planning of the patient’s disease. This solidifies the belief that a combination of high-resolution CT scanning and MR imaging, with and without con- trast, is essential in evaluating large turn or^.*^,^^ CT scanning is all that is needed for small tympanicum pa ragang l ioma~~~ ,~~ (Fig. 2). The carotid artery may be in- volved or surrounded by paragangliomas and can be seen by CT scanning and MR imagingF6 On CT scanning, larger juguloforamen paragangliomas demonstrate the relationship of the tumor to the surrounding great vessels and whether there is any significant venous in~as ion .~ CT scans also show the amount of bony destruction of the temporal bones (Fig. 3) and help locate intracranial extension and differentiate paragangliomas from vascular anomalies or other skull base turn or^.^ T2-weighted MR images often display the characteristic salt-and-pepper appearance typical in paragangliomas (Fig. 4), whereas T1-weighted MR images display the actual vascularity of the tumor matrix.

A complaint of pulsatile tinnitus requires imaging studies that can help de- lineate some of the other vascular diagnoses, which could include a high-riding jugular bulb and dehiscent or aberrant carotid artery, which are seen well on a CT can.^,'^

Nonimaging Tests

Besides radiographic studies, other tests need to be ordered. Complete blood counts are essential because JTPs are very vascular tumors, and blood loss is significant. The issue of using a patient’s own blood for transfusions during removal of large paraganglioma tumors should be discussed. Knowledge of PT and PTT is

Figure 2. Coronal CT scan demonstrating glomus tympanicum in the middle ear.


Figure 3. Axial CT scan demonstrating large glomus jugulare tumor with bony erosion to the carotid artery.

Figure 4. MR image demonstrating glomus jugulare with salt and pepper look.

1236 WEBER & PATEL

essential in evaluating possible bleeding disorders. Electrolytes and thyroid function studies are also important.

Although catecholamine-secreting tumors are rare, their presence must be determined. Because these tumors cannot convert norepinephrine to epinephrine, norepinephrine is secreted. A 24-hour urine sample is tested for urinary metanephrines and vanillylmandelic acid (VMA).28 Patients who test positive are treated preoperatively with a p-blocker such as phentolamine or phenoxylenza- mine, and anesthesia is consulted. Small tympanicum paragangliomas do not require routine screeningz8

CLASSIFICATION

Three systems are employed when classifying JTPs. These systems are based on tumor location and extent of disease with some surgical management features. Glasscock and Jackson‘s classification is a refinement of Alford and Guilfords classification.’ The de la Cmz system is useful in contemplating different surgical approaches depending on the extent of the tumor7 These schemes are listed as follows:

Glasscock and Jackson’s Classification Type I: small tumor involving the jugular bulb, middle ear, and mastoid Type 11: tumor extending under the internal auditory canal; may have intracra-

Type 111: tumor extending into the petrous apex; may have intracranial

Type IV. tumor extending beyond the petrous apex into the clivus or infratem-

Fisch’s Classification Type A: tumor limited to middle ear Type B: tumor limited to the tympanomastoid area with no infralabyrinthine

Type C: tumors involving the infralabyrinthine compartment of the temporal

Type D: tumors with intracranial extensions less than 2 cm Type E: tumors with intracranial extensions greater than 2 cm de la Cruz’s Classification Tympanic: transcanal Tympanomastoid: mastoid-extended facial recess Jugular bulb: mastoid neck (possible limited facial nerve rerouting) Carotid artery: infratemporal fossa Transdural: infratemporal fossa or intracranial

nial extension

extension

poral fossa; may have intracranial extension

involvement

bone and extending into the petrous apex

TREATMENT

The treatment of paragangliomas of the jugular foramen consists of either surgery or radiotherapy. Observation may be one treatment option for the patient; however, the risk of continued growth of the tumor is high and would only be a consideration in patients who are not medically suitable for surgery or radiotherapy or who may not have a very long expected life span. The authors recently presented an anecdotal case that shows the resolution of a glomus tympanicum tumor in a young girl.


Radiotherapy

Radiotherapy has no affect on the actual tumor cells. It acts by inducing a vascular thrombosis inside the tumor. The tumor cells themselves remain viable and may recur more than a decade after radiotherapy.20 Radiotherapy is still a mainstay of treatment in Europe and in parts of the United States. It is especially useful for the treatment of elderly patients who have symptomatic complaints or patients who are unwilling to undergo the risks, complications, and sequelae of surgical resection of large jugulotympanic paragangliomas. The use of radiotherapy in the treatment of glomus tumors is still controversial, and there are reports of adequate or good control rates using this therapy as a primary modality when using at least 4000 rads.'r2'

Surgery

Surgical removal of JTPs is the only effective means of achieving a complete cure. The risks of surgery are not inconsequential and must be evaluated over the natural progression of growth of this benign, slow-growing tumor. For tumors that are regulated and involve only the tympanic portion of the middle ear, a transcanal excision is the best means of removal. This type of surgery is relatively benign because the risk of significant bleeding is low. The risks of permanent hearing loss, vertigo, disequilibrium, or facial nerve paralysis are also low. The risk for removal of a tumor confined to the tympanomastoid area requires a mastoidectomy and possible extended facial recess to adequately remove the tumor. This surgery imposes slightly higher risks but is still a surgery that can effectively remove all the tumor with few complications.

The larger tumors require more detailed planning. The authors typically rec- ommend embolization of the tumor 24 to 48 hours before surgery. They feel that this significantly reduces intraoperative blood loss and lessens the total amount of operating time. Depending on the size of the tumor, balloon occlusion studies also are indicated, and the patient should be counseled and prepared for the possibility of a carotid revascularization procedure during the initial surgery. The two best perfusion studies are single photon emission CT (SPECT) scanning or xenon CT scanning studies:, 7, 25 although balloon occlusion studies are sometimes used.

The surgical technique most commonly employed is the Fisch intratemporal fossa approach in which a large C-shaped incision is made post auricularly and down into the neck. The ear canal itself is commonly transected and oversewn. This particular step may be eliminated if the tumor itself is small and confined to the jugular bulb where a mastoid neck procedure, as described by Brackman3 or Maniglia et all8 is possible, with only limited facial nerve rerouting.

Exposure of the neurovascular components in the neck is completed, and identification of the internal and external carotid arteries, internal jugular vein, and cranial nerves IX to XI1 is performed. The three vessels are controlled with vessel loops and are dissected up toward the skull base. The mastoidectomy then is performed. Exposure of the sigmoid sinus and dura, both anterior and posterior to the sinus, is completed. The facial nerve is identified and dissected to the stylomastoid foramen. In large tumors in which the facial nerve is transposed, the facial nerve is dissected from the stylomastoid foramen to the pes in the parotid. The mastoid tip is drilled down, and a cuff of tissue is left around the facial nerve at the stylomastoid foramen to help preserve function.2 The posterior canal wall is drilled down, exposing the entire middle ear, hypotympanum,

1238 WEBER & PATEL

jugular bulb, sigmoid sinus, and jugular foramen. The carotid artery is identified, and the bone may be unroofed from it into the horizontal segment and inferi- orly into the jugular foramen. The eustachian tube is plugged with muscle un- less it is filled with tumor. To facilitate more exposure, a large Perkin’s retrac- tor is placed beneath the mandibular angle, and the entire mandible is retracted anteriorly, allowing complete access to the carotid artery, sigmoid sinus, and jugular foramen.

Once exposure is accomplished, the external carotid artery and jugular vein in the neck are ligated. The sigmoid sinus is packed externally with Surgicel, or it may be ligated with silk sutures. Once this is freed and the tumor is freed from the carotid artery, an incision in the sigmoid sinus is made inferior to the ligature, and is removed through the jugular bulb with the tumor. Surgicel is used to pack the bleeding area, which includes the inferior petrosal sinus and condylar vein. Any remaining tumor is removed, and the affected bone is drilled away. It should be noted that before removal the tumor had been dissected off cranial nerves IX to XI1 and the carotid artery.

Intracranial extension is managed based on the size and location of the tumor. Small extensions may be removed with just the tumor from the jugular bulb; however, large extensions may prove more formidable. Any remaining vessels should be cauterized with bipolar cautery. The tumor usually is removed from the posterior fossa using a team approach with neurosurgery, which is used in all the authors’ cases. Neural defects are closed primarily or more commonly with fascia and fat grafts or sometimes with donated dural grafts. In cases in which a large amount of tissue has been removed, a free tissue graft or a local flap may be used for closure.

If there is any risk of a cerebrospinal fluid (CSF) leak, a lumbar drain is placed for approximately 5 to 7 days postoperatively. Typically, 10 mL of CSF per hour are drained.

Complications

The risks of complications, though high, are relatively infrequent as recorded in the literature. Complications of concern include pneumonia, CSF leak, menin- gitis, aspiration, pulmonary embolus, wound infections, and seromas. As expected, the risk of facial paralysis after surgery with facial translocation is high; however, if the nerve has been kept intact and a cuff of tissue has been kept around the facial nerve at the stylomastoid foramen, the nerve typically returns to a Grade I or I1 fun~tion.~ The patient will have a loss of taste as the chorda tympani is sacrificed. Patients typically also have significant hearing loss with large tumors because the ear canal is transected and closed off. For patients in whom a smaller.procedure was indicated and the ear itself could be maintained, the inci- dence of hearing loss is much lower.

As expected, the most common complications are speech and swallowing disorders. Dissection of the lower cranial nerves off the tumor often results in trauma to these nerves that very often can be long term. Unfortunately, though many studies document the preoperative effect of the tumors on cranial nerves IX, X, XI, and XII, few studies offer any postoperative results.1,17,23,24,30 In one large study by Woods et al,37 postoperative complication rates on the following cranial nerves were noted: IX, 68%; X, 50%; XI, 50%; and XII, 40%. This is in com- parison with the preoperative problems for cranial nerves IX (17%), X (22%) XI (13%), and XI1 (15%). Speech pathology is an integral part of the postoperative rehabilitation process for these patients. It is critical in preventing aspiration and decreasing significant coughing, which could induce a CSF leak. It seems the need


for tracheotomy or gastrostomy tube placement is low (in one report it is less than 4%).7 The use of early intervention for vocal cord augmentation for vagal paralysis is useful.

Recurrence rates at one time were as high at 40%; however, with the advent of more refined skull base surgical techniques, the rate probably is now between 15% and 20%.

In cases in which it is believed that tumor may have been left behind, the use of radiotherapy may have some merit. Another option would be to continue to follow these patients, and if a recurrence takes place, radiotherapy would be con- sidered. Because of the slow-growing nature of these tumors, CT scanning and MR imaging may be insufficient to identify small tumor remnants that only can be ascertained on angiography. The patient probably would not undergo any type of treatment until there was growth detected on CT scanning or MR imaging or if there were significant symptoms.

Thankfully, patients have low mortality rates, and because of the significant amount of blood loss that occurs during this surgery, patients should be encour- aged to donate their own blood before surgery.

SUMMARY

JTPs are the most common tumors of the middle ear and temporal bone, and though these larger tumors can prove to be formidable, the advent of microscopic surgical techniques and skull base surgery techniques has enhanced greatly the ability to treat and manage these tumors.

References

1. Alford BR, Guilford FR: A comprehensive study of tumors of the glomus jugulare. Laryngoscope 72:765,1962

2. Bra&annbE: The facial nerve in the infratemporal aproach. Otolaryngol Head Neck Surg 9715,1987

3. Brazkmann DE, Arriaga MA: Surgery for glomus tumors. In Brackman DE, Shelton C,

4. Brown, LA Glomus jugulare tumor of the middle ear, clinical aspects. Laryngoscope

5. Buck AH: A case of intratympanic vascular growth with membrane tympani intact. Am

6. deVries EJ, Sekhar LN, Horton JA, et al: A new method to predict safe resection of the internal carotid artery. Laryngoscopy 100:85,1990

7. Friedman RA, Brackmann DE: Jugulotympanic paragangliomas. In Jackler RK, Driscoll CLW (eds): Tumors of the Ear and Temporal Bone. Philadelphia, Lippincott Williams & Wilkins, 2000, pp 344-360

Arriaga MA (eds): Otologic Surgery. Philadelphia, WB Saunders, 1994, p 579

63:281,1953

J Otol1:126-127,1879

8. George B: Jugulare foramen paragangliomas. Acta Neurochirurgica 118:20-26,1992 9. Glasscock E, Dickins JRE, Jackson CG, et al: Vascular anomalies of the middle ear.

Laryngoscope 90:77,1980 10. Glenner GG, Grimley PM: Tumors of the extra-adrenal paraganglion system (includ-

ing chemoreceptors). In: Atlas of Tumor Pathology, series 2, fascicle 9. Armed Forces Institute of Pathology, Washington, DC, 1974, p 1

11. Guild SR The glomus jugulare, a nonchromaffin paraganglion in man. Ann Otol Rhino1 Laryngol62:1045,1953

12. Gulya AJ: The glomus tumor and its biology. Laryngoscope 103(suppl):3,1993 13. Horn K, Hankinson H: Tumors of the jugular foramen in neurotology. In Jackler RK,

14. House WE, Glasscock ME: Glomus tympanicum tumors. Arch Otolaryngol87550,1968 Brackmann D (eds): Neurotology. St. Louis, Mosby, 1994, pp 1054-1068

1240 WEBER & PATEL

15. Krause W: The tympanic gland of the human. Centralbl Med Wissensch 16:737,1878 16. Lawson W The neuroendocrine nature of the glomus cells: An experimental ultrastruc-

tural and histochemical tissue culture study. Laryngoscope 90120-144,1980 17. Malek M, Franklin DJ, Zhao JC, et al: Neural infiltration of glomus temporale tumors.

Am J Otoll1:1-5,1990 18. Maniglia AJ, Sprecher RC, Megerian CA, et a1 Inferior mastoidectomy-hypotympanic

approach for surgical removal of glomus jugulare tumors: An anatomical and radiologic study emphasizing distances between critical structures. Laryngoscope 102407- 414,1992

19. McElveen JT, Lo WWM, El Gabri TH, et al: Aberrant internal carotid artery: Classic findings on computed tomography. Otolaryngol Head Neck Surg 94616,1986

20. Mumber MP, Greven, KM: Control of advanced chemodectomas of the head and neck with irradiation. Am J Clin Oncol18:389-391,1995

21. OLeary MJ, Shelton C, Giddings NA, et al: Glomus tympanicum tumors: A clinical perspective. Laryngoscope 101:1038,1991

22. Parkin JL: Familial multiple glomus tumors and pheochromocytomas. AM Otol 90:60, 1981

23. Pate1 SJ, Sekhar LN, Cass SP, et al: Combined approaches for resection of extensive glomus jugulare tumors. J Neurosurg 80:102&1038,1994

24. Pensack ML, Jackler RK: Removal of jugular foramen tumors: The fallopian bride technique. Otolaryngol Head Neck Surg 117586-591,1997

25. Peterman SB, Taylor A, Hoffman JC: Improved detection of cerebral hypoperfusion with internal carotid balloon test occlusion and 99"Tc-HMPA0 cerebral perfusion SPECT imaging. AJNR Am J Neuroradiol12:1035,1991

26. Phelps PD, Stansbie JM: Glomus jugulare or tympanicum? J Laryngol Otol102:766-776, 1988

27. Rosenwasser H: Carotid body tumor of the middle ear and mastoid. Arch Otolaryngol 41:64, 1945

28. Schwaber MK, Glasscock ME, Jackson CG, et al: Diagnosis and management of catecholamine secreting glomus tumors. Laryngoscope 94:1008,1984

29. Som I'M, Reede DL, Bergeron T, et al: Computer tomography of glomus tympanicum tumors. J Comput Assist Tomogr 714,1983

30. Spector GJ, Gado M, Ciralsky R, et al: Neurologic implications of glomus tumors in the head and neck. Laryngoscope 85:1387,1975

31. Spector GJ, Giralsy R, Maisel RH, et al: Multiple glomus tumors in the head and neck. Laryngoscope 85:1066,1975

32. Spector GJ, Sobol S, Thawley SE, et al: Glomus jugular tumors of the temporal bone: Patterns of invasion in the temporal bone. Laryngoscope 89:1628,1979

33. Valentin G: Report of a tume faction of a ganglion in the Jacobson's anastomosis of the human. Arch Anat Physiol Wisseach Med 89:287,1840

34. Weir RF Two cases of intratympanic vascular tumor with a pulsating intact drum membrane. Am J Otol1:120-125,1879

35. Wenig BM: Neoplasms of the ear. In Wenig BM (ed): Atlas of Head and Neck Pathology. Philadelphia, WB Saunders, 1993, p 368

36. Winship T, Klopp CT, Jenkins W H Glomus jugularis tumors. Cancer 1:441,1948 37. Woods CI, Strasnick B, Jackson CG: Surgery for glomus tumors: The Otology Group ex-

38. Wright JW, Wright JW, Hicks GW Radiologic appearance of glomus tumors. Laryngo- perience. Laryngoscope 103(supp1):65-70,1993

scope 89:1620,1979

Address Yeprint requests to Peter Weber, MD

Department of Otolaryngology, Suite A71 The Cleveland Clinic Cleveland, OH 44195

jugulotympanic paragangliomas

Documents