Pheochromocytomas are the majority of paragangliomas tumors, and according to the World Health Organization these tumors are classified as neuroendocrine tumors . Ninety percent of all pheochromocytomas are adjacent to the adrenal gland and only 0.3 % of all paragangliomas are located in the head and neck. They can also be found in other areas of the body as the aortic arch, larynx, nasal cavity, and orbit. Sixty percent of the paragangliomas in the head and neck are carotid body tumors. It is the most common tumor of the middle ear and the second most common temporal bone tumor [1]. Jugulotympanic paragangliomas are the most frequent jugular foramen tumor with an estimated annual incidence of 1 case per 1.3 million people. They originate from the auricular branch of vagal nerve (Arnold’s nerve) or from the tympanic branch of glossopharyngeal nerve (Jacobson’s nerve). Paragangliomas of the vagal nerve are rare, and tumors restricted to the middle ear are called glomus tympanicum , occurring most frequently in middle aged adults, with a female to male ratio of 4:1. A small number of cases produce significant levels of catecholamines (dopamine, norepinephrine, and 5-hidroxytriptamin) resembling a pheochromocytoma [2–5].These tumors require special pre-intra and postoperative management. Alfa-blockers are usually used to avoid intraoperative hemodynamic shock.

When there is a familial inheritance they may be multicentric in almost 80 % of the cases. Transmission of paragangliomas is by an autosomal dominant gene [6]. In recent years, researchers have isolated a group of defective genes known as PGL 1, 2, and 3 (also termed the SDH gene), which arise from a familial gene mutation found at the 11q23 locus with an autosomal dominant inheritance pattern. Predisposition genetic syndromes are recognized such as MEN Type IIA and B , von Hippel–Lindau (VHL) disease, and neurofibromatosis type 1 [7, 8]. Four different paraganglioma syndromes (PGLs 1–4) have been described: PGL 1—associated with mutations of the succinate dehydrogenase (SDH) subunit D (SDHD) gene; PGL 2—gene susceptibility is unknown, PGL 3—associated with SDHC gene mutations, and PGL 4—SDHB gene mutations [9]. Malignant paragangliomas have been observed with SDHC and SDHD gene mutations, more common in SDHB mutation carriers [10, 11]. Patients with genetic syndromes have lifelong predisposition to develop paragangliomas. Genetic counseling and diagnostic testing should be offered to young patients with diagnosis of paraganglioma.

The majority of paragangliomas are benign, slow growing with mild symptoms. Malignancy is rare and most frequent with carotid body tumors. Approximately 10 % of head and neck paragangliomas and pheochromocytomas are malignant [12]. Usually they are locally invasive but may metastasize to cervical lymph nodes, mediastinum, lungs, and bones.

Jugular foramen schwannomas constitute approximately 2.9–4 % of all intracranial schwannomas [13]. They represent 10–30 % of all tumors observed around the jugular foramen [14, 15]. These tumors commonly occur between third and sixth decades of life. There is a marginal female preponderance with no tumor predilection for the left or right side [16, 17], they grow slowly and it is difficult to identify the nerve that originates the tumor. The most frequent are the vagus and glossopharyngeal nerves . In a review of the literature Bakar found 199 patients in 19 articles published between 1984 and 2007. The nerve of origin was identified in 87 cases [18]. In 47 patients the glossopharyngeal nerve was the nerve of origin of the tumor, the vagal nerve in 26 cases, and the accessory nerve in 11 patients. They may also originate from the hypoglossal nerve and from the sympathetic cervical chain. Jugular foramen schwannomas may be purely intracranial, intra-extracranial (hourglass), or purely extracranial. In the majority of the cases are benign tumors that may be predominantly cystic, solid, or both. These lesions are poorly vascularized, present slow growth causing mild symptoms at the beginning. Jugular foramen schwannomas, as other schwannomas, may be associated with genetic syndromes as neurofibromatosis and schwannomatosis . NF2 is a well-known autosomal dominant disease characterized by bilateral vestibular schwannomas. Three types of NF2 according to clinical presentation and severity are described: Wishart type occurs in childhood or late adolescence and consists of bilateral vestibular schwannomas associated with spinal tumors; Gardner type less severe, patients present bilateral vestibular schwannomas and meningiomas; and mosaic NF2 when a postzygotic mutation occurs and only a portion of the cells carry this mutation. In cases of NF2 half of patients do not have a familial history of the disease.

Several pathogenic mechanisms may explain the molecular biology of vestibular schwannomas : chromosome 22 loss (total loss varies among studies), deregulation of genes, immunogenic factors, NF2 gene mutation, NF2 gene mitotic recombination, DNA methylation, and growth factors [19–25]. Schwannomatosis is characterized by multiple schwannomas but no vestibular schwannomas. The tumor suppressor gene INI1/SMARCB1 on chromosome 22 is a schwannomatosis‐predisposing gene. The SMARCB1 gene is mutated in schwannomatosis patients [26].

Primary meningiomas of the jugular foramen are extremely rare [27]. A higher incidence of these tumors was associated with neurofibromatosis. In a review of the literature, Bakar (2008) found 96 patients treated for primary jugular foramen meningiomas between 1992 and 2007 [18]. The mean age of the patients was 39.4 years with a male/female ratio of 0.4. Most tumors were benign but in our series a high incidence of malignant or aggressive tumors was found [27]. The genetic basis of meningioma development and transformation is not fully understood. In a recent article Pham MH et al. [28] reported that the mutation of the tumor suppressor gene NF2 on chromosome 22q12 is a critical initiating event in the formation of approximately half of all meningiomas. Other genes and pathways involved in meningioma formation and progression are: low levels of TIMP1 and TIMP3 tumor suppressors (associated with invasive behavior), NDRG2 (recurrent meningiomas); loss of chromosome 9p and its CDKN2A, CDKN2B, and p14ARF tumor suppressors (rapid growth and progression), C-sis, c-myc, c-fos, Ha-ras, c-mos, TP73, bcl-2, and STAT3 (high incidence in meningiomas) [28].

Chordomas are rare malignant midline tumors arising from persistent rests of notochordal remnants with an incidence of 0.08 per 100,000. Almost one-third of chordomas have eccentrically positioned extensions [29]. The male/female ratio is 2:1 with a mean age of 46 years [30]. They may occur anywhere from the skull base to the coccyx and constitute 0.2 % of all tumors of the central nervous system. Chordomas are slowly growing, local aggressive, and in almost 80 % of the cases are located in the posterior fossa. Very rarely their origin is in the jugular foramen but jugular foramen chordomas with extracranial extension into the carotid and neck have been described in the literature [31, 32]. They present more commonly during the fourth and fifth decades and in childhood are more frequent found at the skull base. These malignant tumors constitute between 1 % and 8 % of primary malignant bone tumors [33]. Chordoma expresses the transcription factor T , and changes in the T gene have been associated with chordoma. The T gene is involved in the process of making a protein called brachyury which has roles during embryonic development. The brachyury protein is related to the development of the notochord, precursor of the spinal column. Notochord rests may remain in the base of the skull or in the spine causing the development of a chordoma.

Scientists at University College London, Royal National Orthopedic Hospital , and the Sanger Institute reported that over 95 % of caucasian chordoma patients present a variation in the DNA sequence at a particular site on T gene. People with that variation of the T gene are five times more likely to develop chordoma than the general population [34]. Familial chordoma are extremely rare and different chromosomal loci have been identified including 7q33 and isochromosome 1q [35].

Chondrosarcomas are rare malignant tumors that produce cartilage matrix, with estimated incidence of 1 in 200,000 per year [36]. Primary intracranial chondrosarcomas correspond to 0.16 % of all intracranial tumors and 6 % of all skull base lesions [37], and may develop at any age with an average of 37 years [38]. They are exceptionally rare in the Jugular foramen [39]. Derivation from undifferentiated cells from cartilaginous synchondroses has been reported by some authors as the origin of chondrosarcomas [40]. However it is not well known when occurring at this location. Dural invasion occurs in 30 % of cases [37], and distant metastases in 10 % [41].

Described chondrosarcomas subtypes are: conventional (grades I to III), myxoid, clear cell, dedifferentiated, and mesenchymal [42]. Sixty-two percent of the skull base chondrosarcomas are conventional and the overall survival rates are 90 %, 81 %, and 43 %, respectively, for grades I, II, and III [37, 38]. Mesenchymal chondrosarcomas originate from primitive multipotential mesenchymal cells, manifest usually at a younger age (below 30 years), being more common in females, and constituting 30 % of skull base chondrosarcomas [41, 43]. Dural and cerebral invasion, recurrences, and systemic metastases are not infrequent [37].

Differential diagnosis between chordomas and chondrosarcomas is sometimes difficult since the clinical, radiological, and even histological findings may overlap. Distinction between these two tumors is important due to different treatment strategies and prognosis. In a recent study Kanamori et al. [44] analyzed 7 SBCS specimens for chromosomal copy number alterations (CNAs) using comparative genomic hybridization and examined IDH1 and IDH2 mutations and brachyury expression. They detected CNAs in 6 of the 7 cases with chromosomal gains of 8q21.1, 19, 2q22-q32, 5qcen-q14, 8q21-q22, and 15qcen-q14. Mutation of IDH1 was found in 5 of 7 cases. There were no IDH2 mutations, and immunohistochemical staining for brachyury was negative in all cases. They concluded that these molecular findings are consistent and differentiate chondrosarcomas from skull base chordomas.

Endolymphatic sac tumor (ELST) is a rare, histologically benign but locally invasive and destructive, highly aggressive neuroectodermal neoplasm [45]. They originate in the posteromedial petrous portion of the temporal bone from the endolymphatic sac. ELSTs can arise sporadically or in association with VHL disease. In a literature review Diaz RC et al. found at the time of presentation patients with ages ranging from 17 to 75 years, female/male ratio of 2:1, and 24 % of the cases were associated with VHL syndrome [45, 46]. Histologically proliferation of cuboidal cells forming a papillotubular pattern is observed with occasional colloid-filled cysts. ELSTs usually stain positive for cytokeratin, vimentin, and epithelial membrane antigen [47]. Differential diagnosis includes paragangliomas, metastatic carcinomas, and other intrinsic temporal bone tumors.

Comprehension of the invasion routes of Jugular foramen paragangliomas will help the surgeons to plan the surgical approach and predict the difficulties. These tumors tend to spread around the venous sinuses related to the jugular bulb (inferior petrosal sinus, internal jugular vein, and sigmoid sinus) [48]. From the jugular bulb the tumor can extend to the protympanum, hypotympanum, mesotympanum, and intradural cavity [49, 50] (Fig. 3.1). From the protympanum the tumor may involve the Eustachian tube and the carotid canal extending to the middle cranial fossa and nasopharynx (Fig. 3.2). The antrum, epitympanum, facial nerve canal, mastoid cells, and external auditory canal through the tympanic membrane may be invaded from the mesotympanum. Medially may erode the cochlea and the internal auditory canal. Into the posterior fossa these tumors may spread directly through the dura or along the cranial nerve through the pars nervosa of the jugular foramen (Fig. 3.3).