The natural history of jugular foramen tumors depends on the histological diagnosis of the lesion. Paragangliomas present in the most cases a very slow growth rate. Within a mean follow-up period of 4.2 years Jansen et al. [1] observed in 60 % of head and neck paragangliomas an average increase of > 20 %, and in 60 % a median growth rate of 1.0 mm/year with a median tumor doubling time of 4.2 years. Radiologic progression in the overwhelming majority of tumors was in average less than 1 mm/year [2]. These findings would support the strategy of “wait and scan ” as first treatment option in asymptomatic patients. Some studies found in patients with long follow-up a trend toward higher rates of tumor progression [2, 3].

Paragangliomas are in the majority of cases benign, slow-growing tumors and surgical removal is easier to be indicated if the patient presents progressive neurological deficits. Untreated patients, especially the young ones, may in the long term develop cranial nerve palsies due to tumor progression. In these cases, the “wait and scan” policy may lead to tumor infiltration of the lower cranial nerves making surgical removal more difficult or even impossible. Resection of small asymptomatic paragangliomas before they cause nerve paralysis seems advisable. Some paragangliomas present a more aggressive behavior and rarely possible malignancy. Malignant jugular foramen paragangliomas can metastasize to cervical lymph nodes, lungs, liver, spleen, and bone. Patient’s age, clinical condition, natural history, and neurological status should be considered into any clinical decision concerning management. Paragangliomas may be part of an inherited autosomal-dominant tumor predisposition syndrome in about 10 % of cases. The affected individual has greatly increased risk (30–50 %) of developing tumors at any or several sites in the autonomic nervous system [4]. Conservative approach with close observation in asymptomatic patients may be a management strategy in those patients with a tumor detected through genetic counseling and screening for carriers in families with paragangliomas [5]. Rarely the tumor secretes catecholamines causing hypertensive crises. In these cases care has to be taken during any manipulation such as anesthesia, embolization, and surgery. Treatment of jugular foramen paragangliomas includes surgical removal, radiotherapy, and radiosurgery. Preservation of cranial nerves following radiotherapy and radiosurgery are comparable to observation, and both are superior to gross total tumor resection [1, 2].

Patients with sporadic schwannomas present tumors that are in most cases, benign, slow-growing, and encapsulated lesions. No study on the natural history of jugular foramen schwannomas could be found in the literature. These tumors arise from different cranial nerves (hypoglossal, accessory, vagal, glossopharyngeal, and sympathetic chain) and may produce different clinical symptoms. Several studies evaluating the natural history and growth rates of vestibular schwannomas have been published with different results. The natural history of vestibular schwannomas regarding tumor growth and biological behavior may be compared with schwannomas arising in the jugular foramen. Approximately 40–60 % of vestibular schwannomas do not enlarge during the period of observation [6–10], and those that do enlarge 75–80 % grow at a rate of 0.9–2 mm/year [9]. Growth rate is slower in elderly patients and in 4–12 % spontaneously involution may occur [11]. Malignant schwannomas are very rare and have poor prognosis [12, 13]. Higher grade tumors were more likely to have distant metastases. In 1981, Sordillo et al. published a series of 165 patients with malignant schwannomas of various sites [14]. Forty percent had evidence of neurofibromatosis type 1 and 58 % of patients of this group presented local recurrence and 52 % developed distant metastases to lungs, liver, and bones.

Most studies of natural history of incidental meningiomas have showed that the majority of patients presented minimal growth remaining asymptomatic during the follow-up period. In addition to knowing the natural history, identifying the risk factors for tumor growth is important to plan management of these tumors. Oya et al. [15], in a series of 244 patients with 273 meningiomas managed conservatively, regarded linear tumor growth (2-mm or larger increase in the maximum diameter), and volume increase greater than 8.2 % as significant. Linear growth was observed in 44.0 % with a mean follow-up of 3.8 years. Factors related to tumor growth were: age of 60 years or younger, absence of calcification, T2 signal hyperintensity in MRI, and edema. Volumetric growth was seen in 74.0 % of the cases. Factors associated with a higher annual growth rate were: male sex, initial tumor diameter greater than 25 mm, MR imaging T2 signal hyperintensity, presence of symptoms, and edema. The natural history of skull base meningiomas is not well known and few studies have addressed this matter [16]. Van Havenbergh et al. [17] evaluated 21 patients with petroclival meningiomas treated conservatively. In a mean follow-up period of 82 months radiological growth was observed in 76 % of the patients and functional deterioration in 63 %. Although the natural history of jugular foramen meningiomas is unknown, it might extrapolate the biological behavior of petroclival meningiomas to jugular foramen meningiomas. In 2006, we reported on a series of 10 primary jugular foramen meningiomas . A high incidence (6 cases) of malignant or aggressive tumor was found in this series [18]. Four patients presented meningotheliomatous meningiomas, three papillary, two anaplastic, and one microcystic.

The natural history of skull base chordomas shows that untreated patients will live in average 18 months [19, 20]. Even with treatment these dysembryogenetic tumors present a tendency to recur and the 5-year survival rate ranges from 50 % to 80 % and the 10-year survival rate ranges from 35 % to 70 % [21–26]. Tumor biological factors and clinical variables may affect the recurrence rates. In a recent report Boari et al. found that patient’s age, rhinopharynx invasion, extent of tumor removal, and postoperative irradiation are factors that influence the prognosis [21]. Loss of heterozygosity of 1p36 chromosomal region was not an independent predictor of clinical outcome. Genetic and molecular studies may identify molecular markers for targeted therapy and improve the prognosis. Yakkioui et al. [27] studied the impact of cyclin-dependent kinase 4 (CDK4) expression and its relation to prognosis and other cell-cycle markers in chordomas, and found that expression of CDK4 (p = 0.02) and p53 (p < 0.01) were both significantly correlated with poor overall survival. Elevated Ki-67 proliferation index or deletion at 9p21 may be associated with a more aggressive clinical course and shorter survival [28].

Chondrosarcomas are slowly growing neoplasms arising from endochondrous cartilaginous remnants that in spite of presenting symptoms and signs similar to chordomas have better prognosis. They are usually classified as conventional type I–III, mesenchymal and dedifferentiated, and are graded based on cellularity, nuclear pleomorphism, and mitotic activity [29]. Mesenchymal chondrosarcomas occur more frequently in the younger age group (10–30 years). Dedifferentiated chondrosarcomas present a more aggressive behavior and poor prognosis. Tumor markers such as cytokeratin, vimentin, and S100 can differentiate chondrosarcomas from chordomas. Chordomas lack vimentin immunoreactivity and chondrosarcomas fail to express cytokeratin. S-100 protein expression is present in both [30]. Metastases from the skull base chondrosarcomas were reported in 10 % of 50 patients [31]. Skull base chondrosarcomas may be associated with Maffucci’s and Ollier’s syndrome [32]. Rosenberg et al. performed a clinicopathologic analysis of 200 patients with conventional chondrosarcomas of the skull base [33]. Grade 1 was found in 50.5 % of the tumors, 28.5 % had areas of grades 1 and 2, and 21 % were pure grade 2 neoplasms. Immunohistochemically, 96 of 97 (98.9 %) studied tumors stained for S-100 protein, 0 of 97 (0 %) stained for keratin. High-dose postoperative fractionated precision conformal radiation therapy was given to all patients with a dose that ranged from 64.2 to 79.6 Cobalt-Gray-equivalents . The 5- and 10-year local control rates were 99 % and 98 %, respectively, and the 5- and 10-year disease-specific survival rates were both 99 %.

Clinical presentation depends on the location and extension of the tumor. The most frequent presenting clinical symptom in patients with paragangliomas in our series was pulsatile tinnitus (80 %). Pulsatile tinnitus may have different etiologies. Vascular etiologies include: internal carotid atherosclerosis, arteriovenous malformation, dural arteriovenous fistula, aneurysms, tortuous internal carotid artery, venous abnormalities such as high jugular bulb idiopathic, jugular bulb dehiscence, jugular diverticula, and abnormal veins (condylar and mastoid emissary). Nonvascular etiologies include: sensorineural hearing loss, superior semicircular canal dehiscence, and myoclonic muscle contractions (tensor veli palatini, levator veli palatini, and superior constrictor). The patient may inform decreased pulsations with compression of the ipsilateral carotid (Aquino’s sign). Audible bruit may be auscultated over the mastoid region. At otoscopy a reddish tumor protruding behind the tympanic membrane may be identified (Fig. 4.1). Other frequent symptoms are conductive hearing loss (75 %), hoarseness (35 %), and lower cranial nerves palsy (30 %); the most frequent deficit of caudal cranial nerves is in order: 10th nerve, followed by 9th nerve, 12th nerve and 11th nerve, middle ear mass (25 %), dysphagia (15 %), facial nerve paresis (5 %) (Fig. 4.2), neck mass (5 %) (Fig. 4.3), and tongue atrophy (5 %).

Hydrocephalus and cerebellar symptoms were present in two patients in our series. Tumors secreting catecholamines are rare. These tumors may produce symptoms similar to pheochromocytomas : perioperative hemodynamic instability, flushing, palpitations, and diaphoresis. In these cases serum catecholamines, urinary vanillylmandelic acid, and metanephrine should preoperatively be evaluated.

Patients with jugular foramen schwannomas present clinical symptoms mostly related to tumor location. Predominantly, intracranial tumors manifest most commonly with hearing loss, tinnitus and if the lesion is large, cerebellar dysfunction and hydrocephalus. Facial nerve palsy is usually rare and was observed in 20 % of the cases in a large series [34]. Predominately extracranial and jugular foramen tumors present slowly progressive lower cranial nerves deficits with common symptoms dysphasia, tongue atrophy (hypoglossal nerve schwannomas), hoarse voice, palpable neck mass, hearing loss and tinnitus if the tumor extends into the middle ear, hydrocephalus and cerebellar symptoms if the tumor is large. Hearing loss is the most frequent symptom in patients harboring a jugular foramen schwannoma. It was observed in 60–75 % of patients [35].

In our series of patients with jugular foramen meningiomas the clinical symptoms developed sooner than in patients with paragangliomas [18]. From 13 patients 10 presented with swallowing difficulties caused by paralysis of lower cranial nerves. Hearing loss, tinnitus, and headaches were the other complains of the patients. In a recent review of the literature Bakar (2010) found 96 published cases [36]. The most common presenting symptoms were: hearing loss in 45 patients (52 %), middle ear mass in 20 (23.2 %), dysphasia in 20 (23.2 %), tinnitus in 15 (17.4 %), dizziness in 15 (17.4 %), hoarseness in 12 (13.9 %), neck mass in 10 (11.6 %), ataxia in 10 (11.6 %), lower cranial nerve palsy in 5 (5.8 %), shoulder weakness in 5 (5.8 %), headache in 5 (5.8 %), glossal atrophy in 4 (4.6 %), facial nerve palsy in 3 (3.5 %), otalgia in 2 (2.3 %), hydrocephalus in 1 (1.1 %), and hemiparesis in 1 (1.1 %). The low incidence of lower cranial nerves paralysis contrasts with our series. It is possible that some series include patients with meningiomas arising in other regions presenting extensions into the jugular foramen.

Chordomas and chondrosarcomas usually manifest with headaches and diplopia. Clinical manifestations are mainly related to their location in the jugular foramen. Most common presenting symptoms are diplopia because of paralysis of VI cranial nerve in 50 % of cases [37], trigeminal numbness, lower cranial nerve dysfunction including dysphagia, hoarseness, aspiration, tongue paralysis, shoulder drop, and voice weakness, headaches, hearing loss, and tinnitus. The median period between presentation and diagnosis is 15 months [38]. Multiple cranial nerves deficits are more common with chondrosarcomas than chordomas [37].

Endolymphatic sac tumors can be locally destructive and the most common reported presenting symptom clinical presentation is hearing loss with tinnitus. The most commonly involved nerve is the facial nerve facial nerve. Multiple cranial neuropathies (vagal, glossopharyngeal, and trigeminal nerves) can develop in patients with large lesions. These tumors can be lethal [39, 40].

The Glasscock-Jackson [41] and Fisch [42] classifications of glomus tumors are the most commonly used. The Glasscock-Jackson (Table 4.1) classification differentiates glomus tympanicum vs jugular. Fisch’s classification (Table 4.2) describes four stages of tumor development and is based on extension of the tumor to surrounding anatomic structures and is related to morbidity. De la Cruz [43] presented a classification (Table 4.3) based on surgical approach.