Paragangliomas are neuroendocrine tumors that arise from paraganglia outside the adrenal gland. In the head and neck region, the most common locations are the carotid body, jugular foramen (jugulotympanic tumors), and vagus nerve (vagal paraganglioma). Carotid body tumors typically present as asymptomatic neck masses while jugulotympanic tumors can cause pulsatile tinnitus and hearing loss. Complete surgical resection remains the primary treatment for head and neck paragangliomas when possible due to the risk of cranial nerve deficits and malignant transformation with incomplete removal or observation alone.

1. PARAGANGLIOMAS
IN HEAD AND NECK

2. Content
◦ Introduction
◦ Anatomy and physiology
◦ Aetiology and pathology
◦ Classification
◦ Carotid body tumor
◦ Temporal paragangliomas
◦ Vagal paraganglioma
◦ Summary

3. Introduction
◦ Neuroendocrine neoplasm in the Autonomic Nervous System
◦ Neural crest cell tumor outside of the adrenal medulla
◦ NC cells function as chemoreceptors
◦ Majority of paragangliomas (PGL) found in body are from the
sympathetic nervous system (e.g. pheochromocytoma)
◦ Those found in head and neck are from the Parasympathetic
Nervous system
◦ Head and neck locations: vagus, middle ear, carotid body, nose,
orbit, thyroid and larynx (rare)

4. Anatomy
◦ Paraganglia- extra-adrenal chromaffin cells which are derived from
neuroectoderm.
◦ Vital as a source of catecholamines in fetal development
◦ Normal paraganglia contain two types of cells:
◦ Type 1 cells-Chief cells/ Granular cells
◦ Type 2 cells- Supporting cells, sustenacular cells

7. Carotid body
◦ Described by Von Haller 1743
◦ Located in the adventitia of the posteromedial aspect of the bifurcation
of the common carotid artery (Mayer’s ligament).
◦ 3 to 5 mm in diameter- weighs 1 to 47 mg.
◦ Sensory innervation is from the Hering nerve, a branch of the CN 9
◦ Carotid body acts as a chemoreceptor

8. Sensory afferent to medulla

9. Carotid body-function
◦ Modulates respiratory and cardiovascular function in response to
fluctuations in arterial pH, oxygen, and carbon dioxide tension
Acidemia
Hypoxia
Hypercapnia
Stimulates
Carotid body
Autonomic
reflex
Respiratory rate
Depth of respiration
Heart rate
Blood pressure
Cerebral cortical
activity

10. Jugular Foramen
◦ Located in the petrooccipital region and contains several vital
structures
◦ Sigmoid sinus and jugular bulb
◦ Superior and inferior petrosal sinuses
◦ Meningeal branches from the ascending pharyngeal and occipital
arteries
◦ CN IX, X, XI and their ganglia
◦ Opening of the cochlear aqueduct

11. Jugular foramen
◦ 3 compartments
◦ Sigmoid sinus compartment
(posterior compartment)
◦ Petrosal compartment
(anterior compartment)
◦ Neural interjugular
compartment

12. Epidemiology of PGL
◦ Prevalence – 0.5% of all head and neck neoplasm
◦ 0.3% of PGL found in the head and neck
◦ Tends to occur in middle age adults
◦ More common in females

13. Etiology
◦ Multifactorial causation
◦ Often solitary (60%), when multifocal often found with familial
inheritance/ syndromic association
◦ Chronic hypoxia is a risk factor for PGL including those who lived
at high altitude
◦ Recent association with genetic alterations which are responsible
for pseudohypoxia found

14. Genetics
◦ Succinate dehydrogenase (SDH) enzyme
◦ Multiprotein complex composed of SDHA, SDHB, SDHC, and
SDHD proteins in addition to SDHAF2 (a flavination/assembly
factor)
Kreb cycle
Electron
transport chain
in Mitchondria
SDH
Glycolysis

16. Other syndromic association
◦ Multiple endocrinal neoplasia 2A, 2B
◦ Neurofibromatosis type 1
◦ Von Hippel- Lindau syndrome
◦ Carney triad- PGL with SDH deficient GIST and pulmonary
chondroma without any gentic inheritance.
◦ Non syndromic- TEMEM127

17. PGL in head and neck
◦ Carotid body tumors (60%)
◦ Jugulotympanic tumors (2nd most common)
◦ Glomus vagale (only 5% -nodose ganglion))
◦ Malignancy
◦ 6-16% of carotid body tumors
◦ 4% of jugulotympanic tumors
◦ Other locations
◦ Larynx, sinonasal, orbit

18. Pathology of PGL
GROSS APPEARANCE
• Well-circumscribed
• Firm to rubbery consistency
• Highly vascular (readily bleed in surgery)
• Color
– Jugulotympanic (deep red when viewing through tympanic
membrane)
– Carotid body (deep red to brown-grey)

19. Pathology of PGL
MICROSCOPIC APPEARANCE
Chief cells = primary cell (a.k.a Type I cells)( may contain
catecholamine bound granules)
• Type II cells are structural support (fibrovascular)
- a.k.a sustenacular cells
– Zellballen = nest of cells
• Nuclear polymorphism, neurovascular invasion, high rate of
mitosis, and necrosis often present in both benign and malignant
paragangliomas

20. Chief cells
Support
cells

21. Pathology of PGL
◦ Immunohistochemistry of PGL
◦ Chief cells (Type I)
– (+) for chromogranin, synaptophysin, neuron specific enolase,
serotonin, & neurofilament
– (-) for S100
• Sustenacular cells (Type II)
– (+) for S100

22. A. H and E stain (Nestlike pattern)
B. Neuroendocrine-type chromatin
and paleto- pink granular cytoplasm
C. (+) immunstaining for
chromogranin
D. Sustenacular (II) cells (+) for S100
stain
H stain E stain
Chromogranin
stain S100 stain

24. Investigation
◦ Radiology is the preferred diagnostic modality
◦ Combination of multiple modalities
– Ultrasound
– CT with contrast
– MRI with contrast
– Angiography
◦ Biopsy not necessary

25. Treatment consideration
◦ Wait and watch policy
◦ Surgery
◦ Radiation therapy
◦ Stereotactic radiosurgery

26. ◦ Goal = reduce intra-operative bleeding
◦ Controversial as being beneficial but commonly used
◦ Prefer surgical resection within 2 days of embolization (prevent
regrowth of vessels)
◦ May lead to scarring obscuring tissue planes
Notes: If tumor is invading the carotid wall and lots of operative bleeding expected, can work with vascular
surgery to place a balloon shunt in the internal carotid.
Preoperative embolization

27. Non surgical treatment
◦ Wait and watch policy
◦ Langerman et al. reported in their study outcome of observation on
43 cervical paraganglioma over mean time period of 5 yrs
◦ 42% remained stable
◦ 38% grew (maximum rate 2mm per year)
◦ 20% reduced in size

28. Radiotherapy (45-50Gy over 22-25 fractions)
-Primarily use when not a surgical candidate
- Elderly patients with multiple comorbidities
-Controversial
-Also in patients with multiple paraganglioma
- E.g. patient w/ carotid body and glomus vagale tumor
- Recurrent tumors
Non-surgical treatment

29. • Depends on...
Who you ask
• surgeon vs radiation oncologist
Tumor characteristics
• Size, location, multicentricity
Patient’s health status
• RT for the sicker patients
Radiation vs Surgery

30. • “fractionated RT offers high probability of tumor control with
minimal risk to patients...”- Hinerman et al. 2008
–– Recommend surgery mainly for healthier patients with smaller tumors that
have low risk for cranial nerve sacrifice
• Sheehan et al. (Laryngoscope 2010) demonstrated “Gamma Knife
Radiosurgery is an effective treatment for patients with glomus
jugulare tumors...”
– Tumor control in 12/15 patients (mean follow up of approx 4 yrs)
Role of Radiation

31. Carotid body tumor
◦Most common type of PGL in head and neck
◦Von Haller first described the carotid body in 1743
◦Von Luschka first described a tumor of the carotid body in
1862
◦1889, Albert was the first surgeon to successfully resect a
carotid body without ligating the carotid vessels

32. • Usually asymptomatic (painless swelling)
• 10% have cranial nerve symptoms
- IX, X, XI, XII, and sympathetic chain
- can result in pain, hoarseness, dysphagia, shoulder drop,
tongue paresis & Horner’s syndrome
* Vagus most commonly affected
• Could be functional (HTN, diaphoresis, palpitations)
Carotid Body Tumor- Signs and Symptoms

33. Duplex U/S
- hypervascular massnext to carotids
(also see carotidplaques)
Radiology

34. Radiology- CT with contrast
• CT description same as the US
• R arrows are two different carotids

35. ◦ Said to have a “salt and pepper” appearance on
T2
MRI (gadolinium)

36. T1: isointense to muscle
T2: hyperintense
- Avid enhancement on
- Postcontrast imaging
“Salt and pepper”
Pepper: low signal contrast flow voids
Salt: high signal foci of hemorrhage
and/or slow flow
MRI Features

37. • Used for definitive diagnosis
• Often not necessary for initial diagnosis due to use of MRI
detection
More historical
• Helps delineates feeder blood vessels and means of
embolization
• Best means to show Lyre’s sign
Angiography

38. Lyre’s Sign = splaying of external and internal carotid
arteries by tumor
Angiography

39. ◦ Carotid angiography
Angiography

40. ◦ Bilateral tumors - much higher
incidence in inherited form
Other (MRA)

41. ◦ MRA 3D reconstruction
◦ Octreotide scanning (Indium 111
Labelled somatostatin analogue)
◦ 18f DOPA PETCT
Other Imaging Modalities

42. ◦ video
Intra-op

43. • Greater nerve/arterial injury risk with increased size
- do no paralyze patient)monitor cranial nerves(
• ID of cranial nerves )IX, X, XI, XII(
- Superior laryngeal N. (X) often on posterior edge of
tumor (most commonly injured/sacrifice)
• Bilateral ) only excise one at a time(
Intra-op Considerations

44. • Purpose: Predict morbidity in highly vascular lesions
• Class I: minimally attached to vessels and easily removed
)complete resection, minimal risk(
• Class II: partially surround vessels, more adherent to
adventia) more risk(
• Class III: adherent to entire surface of carotid
bifurcation)resection impossible(
Surgical Classification- Shamblin

45. Shamblin classification
Luna Ortiz et
all

46. Arya and Rao classification
◦ MR angiography
◦ I- less or equal to 180
◦ II- 180-270
◦ III- >270 degree

48. 1. Bleeding Carotids, IJV
2. CN injury Mainly X, XI, XII
- X )aspiration, hoarseness(
- XI )shoulder pain/weakness(
- XII )speech and swallowing problems(
3. Cervical sympathetic chain
- Ipsilateral Horner’s
- First bite syndrome (parotid pain)
4. Stroke due to embolism or decreased
blood flow
Surgery complications

49. Tympanic PGL- arising over
promontory and stay confined to
middle ear, mastoid- NO JUGULAR
PLATE EROSION
Jugular PGL- arising within jugular
bulb and associated with jugular plate
erosion
Jugulotympanic PGL

50. ◦ Brown’s sign )blanching of the TM on pneumatic otoscopy(
Glomus tympanicum- deep red

51. • Confined to middle ear
– Arise along Jacobson’s nerve (inferior tympanic nerve )branch of CN
IX)
– Fisch Type A
• Most common tumor of the middle ear
• Presenting symptoms
– 80% )pulsatile tinnitus(
– 60% )unilateral hearing loss(
• Treatment )tympanotomy (smaller lesions) or mastoidectomy (larger
lesions)(
Glomus tympanicum

52. CT Temporal Bone- round mass on cochlear promontory
Glomus tympanicum

53. • Arise from paraganglia in/around jugular bulb
– Along Jacobson’s (CN IX) or Arnold’s nerve (X)
• Most common symptoms )tinnitus/hearing loss(
• CT distinguishes tympanicum from jugulare
– MRI defines extent of disease
• Tendency towards multiplicity of tumors
– 10% in non-familial and 50% in familial cases
• 30% have CN deficits
Glomus Jugulare

54. ◦ Erosion of
Caroticojugular crest
◦ PHELP sign

55. • Classified by location in temporal
bone
• Less commonly used
Glassock-Jackson Classification

56. • Based on extension of the tumor to surrounding anatomic structures and is closely
related to mortality and morbidity.
• Type A - Tumor limited to the middle ear cleft (glomus tympanicum)
• Type B - Tumor limited to the tympanomastoid area with no infralabyrinthine
compartment involvement
• Type C - Tumor involving the infralabyrinthine compartment of the temporal
bone and extending into the petrous apex including portions of carotid canal )C-
subclasses C1-3 based on involvement in carotid canal(
• Type D1 - Tumor with an intracranial extension less than 2 cm in diameter
• Type D2 - Tumor with an intracranial extension greater than 2 cm in diameter
Fisch Classification of Temporal Bone
Paraganglioma

57. Treatment options
• Total surgical removal.
• Planned subtotal removal aiming to preserve
neurovascular structures with or without
postoperative radiotherapy.
• Partial resection for symptomatic control.
• Primary radiotherapy.
• Conservative or wait and scan policy.

58. Patient factors
• Patient’s age, general medical condition, life expectancy
• Lower cranial nerve function, mainly the vagus nerve
• Tumor size, with particular regard to intracranial
extension and carotid artery involvement
• Collateral venous drainage: significantly the patency
of the contralateral sigmoid sinus and jugular bulb
• FN function
• Hearing status

66. Surgical Approaches

67. Approaches to lateral skull base
◦ Approaches passing through the otic capsule:
◦ The translabyrinthine approach.
◦ The transcochlear approaches: these include the original
transcochlear approach of House, the transotic approach of Fisch,
and the system of the modified transcochlear approach.

68. ◦ Approaches conserving the otic capsule (extralabyrinthine
approaches):
◦ Passing above the otic capsule: the middle cranial fossa, enlarged middle
cranial fossa, and middle fossa transpetrous approaches.
◦ Passing behind the otic capsule: the retrosigmoid, the retrolabyrinthine, and
the retrolabyrinthine transtentorial approaches.
◦ Passing inferior to the otic capsule:
◦ Approaches to the jugular foramen area: infratemporal type A; petro-
occipital transsigmoid (POTS).
◦ Approach dealing mainly with the craniovertebral junction: Extreme lateral
approach.
◦ Passing anterior to the otic capsule: the preauricular infratemporal
subtemporal fossa approach and the infratemporal fossa approaches types B, C,
and D.

76. • Arise from the inferior (nodose), middle, or superior vagal ganglia
• Least common type( < 5% of head and neck paragangliomas)
• Present as asymptomatic neck mass behind angle of mandible
– Displaces internal carotid anteromedially
• Most likely of the head and neck paragangliomas to be malignant
Glomus Vagale

77. •Tend to be higher than CB tumors
•Situated between IJV and ICA
Glomus vagale

79. • Intracranial extension in 22% of cases
– Primary cause of death
• Up to 50% manifest with CN deficit
– IX(dysphagia)
– X(hoarseness, aspiration)
– XI(shoulder drop)
– XII(aspiration and hemiatrophy of tongue)
Glomus Vagale

80. Classification

81. • Technique often requires lateral cervical incision with possible
mandibulotomy for better exposure
– Neurosurgery involved for intracranial extension tumors
• Involved vagus nerve usually sacrificed with associated morbidity
– Dysphagia and aspiration expected complication
• Unilateral paralyzed cord
– Vocal medialization via silastic thyroplasty commonly used post op
– Some advocate thyroplasty at time of initial resection
• Greatest risk to aspiration found with concurrent CN X and XII injury
Vagale Surgical Treatment

83. • Offergeld et al 2012
- “only occurence of lymph node and/or distant metastases are the
ultimate criteria for malignancy”
- “ tumor invasion into adjacent structures including bone does not
indicate biologic malignancy”
• 4-15% head & neck paragangliomas believed to be malignant
– Highest rate in vagal tumors (16-19%)
Malignancy of Paragangliomas

84. • Chapman et al. (2010) studied clinical, histopathologic and
radiologic features
• 84 patients; 77 benign, 7 malignant (8%)
• Of 7 malignant, 6 were considered based on lymph node metastasis
– 1 based on very aggressive local features
– 6/7 were carotid body tumors, 1/7 was glomus vagale
Other Malignancy Predictors?

85. Factors Determining Malignancy

86. Lymph node invasion
Perineural invasion & tumor
encircling nerve

87. Found mainly clinical factors help predict malignancy
• Pain
– 5/7 (71%) malignant; 5/77 (8%) benign(p<0.0001)
• Enlarging cervical mass in past 12 months
– 100% of malignant, 33% of benign
• Younger age of presentation (p<0.02)
– Benign(54 ± 16 y.o)
– Malignant(40 ± 12 y.o)
Predictors of Malignancy

88. • Slow growing and usually benign
• Carotid body most common, then jugulotympanic, then vagal least
common
– Vagal most likely to be malignant with most cranial nerve
morbidity
• Surgery preferred in smaller masses and healthier patients
– some role for RT as alternative or adjunct
Summary of Paragangliomas