See Table 24-1.

Glomus Tumor (Paraganglioma)

1. 
   

   Most common neoplasm of the middle ear and second most common neoplasm of the temporal bone/cerebellopontine angle (CPA)

   
   
   
   
   1. 
      

      Glomus tympanicum (GT)

      
      
   2. 
      

      Glomus jugulare (GJ)

      
      
   3. 
      

      Glomus vagale (GV)

   
   
2. 
   

   Caucasians more commonly affected

   
   
3. 
   

   Also known as chemodectoma

   
   
4. 
   

   M:F—1:5

   
   
5. 
   

   May be multicentric (10%)

   
   
6. 
   

   Majority are sporadic; up to 30% are familial

   
   
7. 
   

   Rarely malignant—(2%-4%) with highest risk in vagal paragangliomas

   
   
   
   
   1. 
      

      Diagnosis requires metastasis to non-neuroendocrine tissue

      
      
   2. 
      

      Most common sites are nodal, bone, lung, liver, and spleen

   
   
8. 
   

   Rarely functional—5% or less secrete neuroactive peptides (palpitations, sweating, flushing, syncope, hypertension, headaches)

   
   
   
   
   1. 
      

      May result in catastrophic hypertension upon induction of anesthesia if not identified and treated preoperatively.

      
      
   2. 
      

      If secretory treat with phentolamine (nonselective reversible alpha-adrenergic agent).

      
      
   3. 
      

      Functional tumors are rare in extra-adrenal locations.

   
   
9. 
   

   Biology

   
   
   
   
   1. 
      

      Arise from chemoreceptor cells of the neuroendocrine system

      
      
      
      
      1. 
         

         Derived from parasympathetic paraganglia in the head and neck

         
         

         Found in the jugular dome, tympanic promontory, along Jacobson and Arnold nerves

         
         
      2. 
         

         Type I chief cells, and type II sustentacular cells

      
      
   2. 
      

      Genetics

      
      
      
      
      1. 
         

         Familial tumors are caused by genetic defect in mitochondrial DNA encoding for succinyl dehydrogenase subunits B, C, or D (SDHB, SDHC, SDHD) of mitochondrial complex II; involved in mitochondrial electron transport chain (Table 24-2).

         
         
         
         
         1. 
            

            Thought to be the mutation in sporadic tumors as well

         
         
      2. 
         

         SDH mutations result in pseudohypoxia and upregulation of hypoxia inducing factor 1-alpha.

         
         
      3. 
         

         SDHD and SDHC have the highest risk of developing head and neck paragangliomas.

         
         
      4. 
         

         Phenotype is maternally imprinted (ie, passed on via male carrier).

         
         
         
         
         1. 
            

            Explains why phenotype can skip a generation

            
            
         2. 
            

            Autosomal dominant

   
   
10. 
    

    Classification schemes (Table 24-3)

    
    
    
    
    1. 
       

       Fisch

       
       
    2. 
       

       Glasscock-Jackson

       
       
       
       
       1. 
          

          Glomus tympanicum

          
          
       2. 
          

          Glomus jugulare

    
    
11. 
    

    Diagnosis

    
    
    
    
    1. 
       

       Symptoms

       
       
       
       
       1. 
          

          Pulsatile tinnitus (80%) (GT and GJ)

          
          
       2. 
          

          Hearing loss, conductive or mixed (60%) (GT and GJ)

          
          
       3. 
          

          Otalgia (13%) (GT and GJ)

          
          
       4. 
          

          Aural fullness (32%) (GT and GJ)

          
          
       5. 
          

          Hoarseness/dysphagia (15%) (GJ)

          
          
       6. 
          

          Facial weakness (15%) (GT and GJ)

          
          
       7. 
          

          Functional tumors will present with palpitations, unexplained weight loss, poorly controlled hypertension

       
       
    2. 
       

       Physical examination

       
       
       
       
       1. 
          

          Middle ear mass

          
          
          
          
          1. 
             

             For diagnosis GT must be able to see 360 degrees around mass, otherwise adjunctive imaging required for diagnosis

             
             
          2. 
             

             Brown sign—blanching of middle ear mass with pneumatic otoscopy

          
          
       2. 
          

          External auditory canal (EAC) mass

          
          
       3. 
          

          Neck mass or pharyngeal fullness

          
          
       4. 
          

          Cranial nerve deficits including lower cranial nerve examination

          
          
          
          
          1. 
             

             Audiogram (GT and GJ)

             
             
          2. 
             

             Laryngoscopy (GJ)

       
       
    3. 
       

       Diagnostic workup

       
       
       
       
       1. 
          

          Urine for vanillylmandelic acid (VMA), metanephrines

          
          
          
          
          1. 
             

             Must be five times higher than normal to be symptomatic

             
             
          2. 
             

             Used to exclude a functional component

          
          
       2. 
          

          Radiography

          
          
          
          
          1. 
             

             Computed tomography (CT) IAC—imaging modality of choice

             
             
             
             
             • 
               

               Used to evaluate extent of lesion

               
               
             • 
               

               GT—used to classify tumor as GT or GJ if diagnosis is unclear from physical examination

               
               
             • 
               

               Evaluate extent of carotid canal involvement for GJ

               
               
             • 
               

               Differentiate mass from high-riding jugular bulb or aberrant carotid

               
               
             • 
               

               Infiltrative and erosive into the bone

             
             
          2. 
             

             Magnetic resonance imaging (MRI) with contrast

             
             
             
             
             • 
               

               Identify the extent of the lesion and assess intracranial extension

               
               
             • 
               

               Classic “salt and pepper” appearance due to flow voids within the tumor

             
             
          3. 
             

             CT and MRI are complementary in the skull base

             
             
          4. 
             

             Angiography

             
             
             
             
             • 
               

               Four-vessel angiography to identify feeding vessels

               
               
             • 
               

               Embolization of the feeding vessels should be performed 24 to 48 hours prior to surgical resection

               
               
             • 
               

               Significantly improves intraoperative blood loss

               
               
             • 
               

               Preoperative balloon occlusion testing using ^99TmTc-HMPAO SPECT scanning or Xenon CT of the ipsilateral carotid should be performed if imaging suggests arterial invasion

    
    
12. 
    

    Treatment

    
    
    
    
    1. 
       

       Surgical

       
       
       
       
       1. 
          

          Glomus tumors are a surgical disease unless patient’s comorbidities prevent operation

          
          
       2. 
          

          GT

          
          
          
          
          1. 
             

             Small tumors limited to the promontory can be removed via a transcanal or anterior tympanotomy approach

             
             
          2. 
             

             Larger tumors require wider exposure via mastoidectomy and posterior tympanotomy

          
          
       3. 
          

          GJ

          
          
          
          
          1. 
             

             Requires proximal control of the great vessels in the neck and the sigmoid sinus

             
             
          2. 
             

             Large tumors may require transposition of the facial nerve to expose the tumor anteriorly

             
             
          3. 
             

             Infratemporal fossa approach (Fisch type A) is a method of choice for removal

             
             
          4. 
             

             Considerable care is required to preserve the lower cranial nerves (CN IX-XII)

             
             
          5. 
             

             For very large tumors—may need to stage the procedure if blood loss more than 3 L during removal of tumor from the neck and temporal bone; intracranial resection can proceed at a later date

       
       
    2. 
       

       Radiation

       
       
       
       
       1. 
          

          Can be used as primary modality, or for residual or recurrent disease

          
          
       2. 
          

          Used to prevent further tumor growth

          
          
       3. 
          

          Mechanism of action—obliterative endarteritis

          
          
       4. 
          

          Lower doses are used for single fraction (15 Gy) and external beam (40-45 Gy)

          
          
       5. 
          

          Stereotactic radiosurgery (SRS) has reported 90% to 94% rate of tumor control

          
          
          
          
          1. 
             

             Risks of SRS: radiation-induced malignancy, osteoradionecrosis of the skull base, temporal lobe necrosis, cranial nerve injury

Endolymphatic Sac Tumor

1. 
   

   Locally aggressive, slow-growing neoplasm originating from the endolymphatic sac or duct.

   
   
2. 
   

   Histologically described as a destructive papillary cystic adenomatous tumor of the temporal bone.

   
   
   
   
   1. 
      

      Lack of transthyretin (prealbumin) staining, which is seen in choroid plexus tumors, confirms an endolymphatic sac tumor.

      
      
   2. 
      

      Positive staining for cytokeratin, vimentin, and S-100, negative for chromogranin (paraganglioma), negative for thyroglobulin (metastatic thyroid cancer).

   
   
3. 
   

   Sporadic tumors are more common than von Hippel-Lindau (VHL)-associated disease.

   
   
   
   
   1. 
      

      Diagnosis typically occurs in the fifth and sixth decade in sporadic tumors and the third and fourth decades in VHL-associated tumor.

      
      
   2. 
      

      VHL-associated tumors are more commonly seen in females, whereas sporadic tumors have no gender predilection.

      
      
   3. 
      

      11% of VHL patients will develop endolymphatic sac tumors, of which 30% will be bilateral.

      
      
   4. 
      

      VHL caused by loss of function of tumor-suppressor gene located on chromosome 3p25.5.

      
      
   5. 
      

      Ubiquitin ligase that targets hypoxia inducing factor 1-alpha (HIFs). HIFs regulate angiogenesis and metabolism.

      
      
   6. 
      

      Screening with cranial MRI every 1 to 3 years is appropriate in VHL patients.

   
   
4. 
   

   Typically involves the sac and the endolymphatic duct.

   
   
5. 
   

   Dysfunction of the otic capsule is the most common presenting symptom.

   
   
   
   
   1. 
      

      Symptoms often mimic endolymphatic hydrops, likely due to obstruction of the normal flow and resorption patterns of endolymph.

      
      
   2. 
      

      Sensorineural hearing loss, followed by tinnitus, vertigo, and aural fullness are the most common symptoms, respectively.

      
      
   3. 
      

      Sudden hearing loss typically results from intralabyrinthine hemorrhage.

      
      
   4. 
      

      Middle ear extension can mimic Eustachian tube dysfunction and otitis media.

      
      
   5. 
      

      Late symptoms include facial paralysis, symptoms of brain stem compression, and lower cranial neuropathies.

      
      
   6. 
      

      No cases of distant metastasis have been reported, but drop metastasis into the thecal sac causing lower extremity weakness has been reported.

   
   
6. 
   

   Imaging

   
   
   
   
   1. 
      

      CT—bony destruction of the posterior fossa plate centered over the operculum with central calcifications; may extend into the mastoid as well

      
      
   2. 
      

      MRI

      
      
      
      
      1. 
         

         T1—heterogeneous, hypo, iso, or hyperintense. Hyperintensity secondary to intralesional hemorrhage (methemoglobin, hemosiderin, cholesterol crystals), hypointensity reflects residual bone or calcifications

         
         
      2. 
         

         T2—heterogeneous (suggesting its highly vascular nature)

         
         
      3. 
         

         T1 with gadolinium—heterogeneous enhancement

      
      
   3. 
      

      Angiography

      
      
      
      
      1. 
         

         Hypervascular lesion that may benefit from preoperative embolization

         
         
      2. 
         

         External carotid supply, but can also have contributions from the internal carotid or vertebral arteries

         
         
      3. 
         

         Blood supply typically from the inferior tympanic or a dural branch of the stylomastoid artery which arise from the ascending pharyngeal and postauricular artery, respectively

   
   
7. 
   

   Differential—paraganglioma, choroid plexus tumor, metastasis, eosinophilic granuloma, meningioma, arachnoid granulation, aneurysmal bone cyst, primary bone tumors

   
   
8. 
   

   Treatment

   
   
   
   
   1. 
      

      Surgery is the method of choice.

      
      
      
      
      1. 
         

         Should involve removal of both surfaces of the dura to ensure complete removal

         
         
      2. 
         

         Hearing sparing approaches for small tumors

         
         
         
         
         1. 
            

            Retrolabyrinthine—transdural

         
         
      3. 
         

         Patients with nonserviceable hearing

         
         
         
         
         1. 
            

            Translabyrinthine approach

         
         
      4. 
         

         Large tumors can be preoperatively embolized to minimize blood loss