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The International Federation
          of Head and Neck Oncologic Societies
Current Concepts in Head and Neck Surgery and Oncology 2012




     Management of
 Salivary Gland Tumors

               Ashok R. Shaha
Salivary Glands
                    Major:

                    Parotid
                Submandibular
                  Sublingual

            Minor salivary glands:
600 - 800 all over the upper aerodigestive tract

2012
            Majority on the palate
Salivary Literature
                     1985 to 2005

            Subject                 # Papers

       Salivary gland diseases      19,754
       Salivary neoplasms            7,914
       Needle biopsies              14,713
       Salivary – needle biopsies      397



2012
Salivary Gland Neoplasms
        Management Issues


       Evaluation (FNAB, CT, MRI)
       Stage v. Grade
       Imaging
       Facial nerve
       Adjunctive radiotherapy
2012   Definitive radiotherapy
Salivary Tumors
                     Sites of Origin
Sites                    # Pts         %
Parotid                  1,965         70.0
Submandibular             235           8.4
Palate                     228          8.0
Lips/Cheek                  73          2.6
Antrum                      72          2.6
Tongue                      63          2.2
Nasal cavity                60          2.1
Gingiva                     34          1.2
Floor of mouth              22          0.8
Larynx                      21          0.8
Tonsil                      13          0.5
Ethmoid                       9         0.3
Nasopharynx                   9         0.3
Pharyngeal wall               3         0.1

2012

           TOTAL          2,807        100.0
Salivary Gland Neoplasms*
                 PROPORTION MALIGNANT
          # Pts
              2500                            Benign
                                              Malignant
              2000
                           25%
              1500

              1000
                                                      82%
                500                      57%
                  0
                         Parotid Submandibular     Minor
                      n=1965       n=235           n=607
2012   *MSKCC 1939-73 (Head Neck Surg 1986)
Salivary Tumors - Histologic
   Distribution
                         Parotid




                                   Sub - Max



       Mucoepidermoid
       Adenoid cystic
                                           Minor
       Adenocarcinoma
       Malignant mixed
       Acinic cell
2012
       Squamous
       Other
Palate

        Tongue

    Cheek/Lip

        Antrum

 Nasal Cavity
          Gum

          Larynx             Tumors of Minor
           FOM              Salivary Glands.
          Tonsil
                             Site Distribution
Nasopharynx
         Ethmoid
        Pyriform
           Other
 2012

                   0   10        20   30     40
                             %
Parotid Tumors
  Pathology – Memorial Hospital, 1939-1973
                    (N=1973)

Benign (n=1342)           Malignant (n=631)
Pleomorphic adenoma
                   1133   Mucoepidermoid                 272
Warthin’s           183   Adenocarcinoma                  62
Oncocytoma           20   Acinic cell                     75
Monomorphic           6   Adenoid cystic                  62
                          Ca ex pleomorphic              107
                          Undiff                           8
                          Epidermoid                      45
 2012



                                   Spiro, 1986, Head and Neck Surg
Modification of WHO and AFIP Classifications to
   Denote Grade of Salivary Gland Tumor
                                      Low-grade   High-grade
       Acinic cell carcinoma             
       Polymorphous low grade            
       adenocarcinoma                    
       Basal cell adenocarcinoma         
       Sebaceous carcinoma               
       Papillary cystadenocarcinoma      
       Mucinous adenocarcinoma           
       Basal cell adenocarcinoma         
       Sebaceous carcinoma               
       Papillary cystadenocarcinoma
                                         
       Mucinous adenocarcinoma
       Malignant myoepithelialioma
                                         
                                         
2012
       Watkinson, 2001
Modification of WHO and AFIP Classifications to
   Denote Grade of Salivary Gland Tumor

                                            Low-grade   High-
                                                        grade
       Mucoepidermoid carcinoma                         
       Adenoid cystic carcinoma                         
       Adenocarcinoma, NOS                              
       Epithelial-myoepithelial carcinoma                
       Oncocytic carcinoma                               
       Salivary duct carcinoma                           
       Carcinoma in pleomorphic adenoma                  
       Squamous cell carcinoma                           
       Small cell carcinoma                              
       Undifferentiated carcinoma
                                                         

2012   Watkinson, 2001
Presentation
       Lump
       Pain
       Facial weakness
       Neck metastases
       Parapharyngeal mass – deep lobe
        tumors
2012
2012
2012
2012
2012
Salivary Gland Tumors

         • Dumb bell tumor
         • Deep lobe tumor
         • Parapharyngeal space
         • Extraparotid salivary tissue


2012
Parotid Carcinoma:
         Obvious Signs

       •  Facial nerve palsy

       •  Cervical metastasis

       •  Skin involvement

2012
2012
2012
Investigations

       •  Clinical evaluation

       •  Sialogram
       •  CT scan

       •  CT sialogram
       •  Needle biopsy
2012

       •  Sialendoscopy
2012
Parotid Tumors Indications for
           CT Scan

       •  Clinical uncertainty of findings

       •  Deep lobe presentation

       •  Extraglandular extension

       •  Cervical nodal involvement

2012
       •  Facial palsy or fixed mass
2012
2012
Indications for
            Anatomical Imaging
       •    To make the diagnosis
       •    Uncertain extent
       •    Size
       •    Fixation
       •    Recurrent
       •    Parapharyngeal
2012
       •    Clinically malignant
Role of Imaging

       1. CT scanning is superior to MRI for osseous and
          skull base involvement but MRI is superior for
          intracranial extension of tumour

       2. MRI is superior to CT for assessment of primary
          disease and regional recurrence, as well as
          characterising extra parotid extension.
          Perineural invasion is best characterised with
          MRI

2012
       3. Minor salivary gland tumours are best imaged
          with MRI, with irregular margins being a feature
                                                    Robson, 2002
Role of Needle Biopsy in
            Salivary Tumors
•  To suspect malignancy
•  To distinguish from metastatic carcinoma
•  To suspect lymphoma
•  To distinguish salivary from non-salivary tumors
       •  In poor risk pt - if suspect Warthin’s tumor
       •  To confirm pre-op suspicion of malignancy in
       pts with facial palsy

       •  In bilateral tumors
2012
       •  Minimum risks
                                              Shaha AR. Am J Surg
Mass in Parotid Region
            History/Head & Neck Exam
                        FNA
       Salivary                            Non-Salivary

 Benign            Malignant                Lipoma
                                            Seb. Cyst
Mixed tumor       Primary     Metastatic
                                            Lymph Nodes
Warthin’s         Ad-Cystic   Sq Ca.
                                             Benign
                  Adeno Ca. Melanoma         Melanoma
                                             Met Ca.
2012

                                             Lymphoma
2012
Salivary Gland Tumors
General Principles of Treatment

       •  Tumor factors

       •  Patient factors

       •  Physician factors

2012
Parotid Tumor
       Surgical Principles
 Every attempt should be made
 to remove all gross tumor. Radiation
 therapy does not compensate for
 inadequate surgery.

2012
Parotid Tumor
       Surgical Principles
  The extent of parotidectomy depends
  more upon the extent of the tumor
  than the histology of the tumor.



2012
Salivary Gland Carcinoma
  Treatment Principles
   The anatomic relationship of the
   tumor to the nerve dictates the
   extent of surgery, not the histologic
   classification of the neoplasm.

2012
Malignant Tumors


                         Surgical treatment of the primary tumour
                                      - Parotid Gland:
       •    Size and location determine extent of resection
       •    Most T1/T2 lesions lateral to the nerve are suitable for a superficial
            parotidectomy
       •    Larger and deep lobe tumours usually require a total conservative
            parotidectomy with preservation of the facial nerve
       •    Patients with high grade extensive disease (i.e. skin involvement or
            facial palsy) may require extended radical parotidectomy
       •    In one series, facial nerve dysfunction was apparent initially in 14% of
            patients and complete nerve sacrifice was required in about 30% of
2012
            parotidectomies
Indications of Facial Nerve Resection

•  Pre-op facial palsy

•  Large tumor adherent to the nerve

•  Direct tumor involvement into the
nerve

•  Recurrent malignant tumor
2012
2012
Resection of Facial Nerve
         •  Nerve graft
         •  Great auricular nerve
         •  Ansa Cervicalis
         •  Sural nerve
         •  Nerve transfer-hypoglossal transfer
         •  Tarsorrhaphy
         •  Facial reanimation - facial slings
2012
2012
2012
Problem Areas in Salivary Tumors:
          Parotid Gland

        •  Deep lobe parotid tumors
        •  Accessory parotid tumors
        •  Regional node metastases
        •  Local recurrences
        •  Facial nerve?

 2012
2012
2012
2012
2012
2012
2012
2012
2012
2012
2012
2012
2012
Warthin’s Tumor

   •  Papillary cystadenoma lymphomatosum
   •  Oncocytoma
   •  Branchiogenic adenoma
   •  Epitheliolymphoid
   •  Branchioma
   •  Cylindrocellular branchiogenic adenoma
   •  Orbital inclusion adenoma
2012
2012
Prognostic Factors


       •  Clinical Stage (TNM)
       •  Histological grade
       •  Age
       •  Gender
       •  Anatomical site
       •  Experience of the surgeon
2012
Ca of the Parotid, MSKCC 1939-1968
     Factors Influencing “Cure”

                       Pts Eligible     NED        %
Cervical node metastasis:
 Never documented           213         157       74
 Present on admission       57          5         9
 Appeared later             18          3         17

Local recurrence*:
 No                         194         153       79
 Yes                        71          15        21


 2012
              *No data or palliation only in 23
Ca of the Parotid, MSKCC 1939-1968
        Factors Influencing “Cure”

                                Pts Eligible               NED    %
   Stage of primary:
       I                               104                 88    85 (92)
   *
       II                              83                  57    67 (75)
       III                             99                  19    19 (20)


   Facial nerve status:
       Function intact                 212                 139   66
       Partial/complete palsy          43                  6     14
       Not recorded                    31                  18    58
       Unrelated dysfunction           2                   2     100
2012

                                 *Determinate cases only
Major Salivary Ca 1939-1982
         Node Metastasis (26%)
                             # Pts*    Nodes +
        Anaplastic           6         5 (83%)
        Squamous             26        15 (58%)
        Mucoep grades 2,3    123       54 (44%)
        Adenocarcinoma       46        18 (39%)
        Malig mixed          62        12 (19%)
        Adenoidcystic        50        4 (8%)
        Acinic cell          56        4 (7%)
2012
        Mucoep grade 1       68         2 (3%)
                         *439 determinate pts
Cancer of the Major Salivary Glands:
   Nodal Status & 5 Yr Survival

       80
       70                             N0
       60                             N+
       50
       40
       30
       20
       10
       0
            Parotid   Submandibular

2012
Elective Neck Treatment in
    Salivary Gland Cancers
•  High grade tumors
•  T3 (?) & T4 tumors
                             Elective
•  Tumors >3 cm                neck
•  Facial paralysis         treatment
•  Age >54
•  Extraparotid extension
•  Perilymphatic invasion
2012
1966 – 1998 Neck Dissection for
         Parotid Ca - MSKCC

   •  Therapeutic neck dissection with post-op RT
      yielded better results

   •  Reserve elective neck dissection for selected pts

   •  Indications for elective neck dissection

       •  High risk of metastasis based on T stage & grade

       •  Selected pts with large primary tumors in the
          tail of parotid
2012
Management of the Neck
          in Parotid Cancer
       Elective neck dissection should be
       reserved for those histologic
       diagnoses having the highest risk
       of nodal metastases plus selected
       patients whose primary tumor
       resection may be facilitated by
2012
       Lymphadenectomy.

                            Kelley and Spiro. Am J Surg 1996; 172:695-697.
Indications for Postoperative
  Irradiation-Parotid Cancer
       •  Aggressive, highly malignant tumors
       •  Invasion of adjacent tissues outside parotid capsule

       •  Regional lymph node metastases

       •  Deep lobe cancers

       •  Gross residual tumor following resection

       •  After resection recurrent tumor
2012
       •  Tumor invasion of facial nerve
Salivary Ca. - Impact of Post-op R.T. on Survival

        100

        75

        50
 %
        25

         0
              0                    5                    10
                              Time (years)
    Stage I, II   Stage I, II w/    Stage III, IV   Stage III,
 2012             RT                w/ RT           IV
Adjuvant Radiotherapy:
            Impact on Prognosis
       Survival            Surg Alone           Surg+RT
       Stage I/II                96                         82
       Stage III/IV              10                         51
       Lymph node mets           19                         49
       High-grade tumors         28                         57
       Overall                   55                         69


       Local control       Surg Alone           Surg+RT
       Stage I/II                79                         91
       Stage III/IV              17                         51
       Lymph node mets           40                         69
       High-grade tumors         44                         63
2012
       Overall                   66                         73
                                        Armstrong, et al. Arch Oto HN Surg 1990.
Salivary Carcinoma - Survival by
       100
                   HISTOLOGY

        80

%       60

        40

        20

         0
             0     6        12        18       24         30        36
                               Time (years)

   Acinic cell     Muco ep. Gr II -     MMT              Squamous or
2012               III                                    Anaplastic ca
   Muco ep. Gr I    Adeno Ca.           Adenoid cystic
Salivary Carcinoma - Survival by SITE
        100                              Parotid
                                         Sub-max
        80
                                         Minor
        60
%
        40

        20

         0
 2012        0   5       10         15       20
                     Time (years)
Salivary Carcinoma - Survival by GRADE

  100                              Low

       75
                                 Intermediate

%50
                                    High
       25
                p< 0.0001

       0
            0               5        10        15   20
2012
                                Time (years)
Salivary Carcinoma - Survival by STAGE

       100                             Stage I


       75                               Stage II


%      50

                                          Stage III
       25
                 P< 0.0001

        0
2012
             0               5            10          15   20
                                 Time (years)
2012
Important Prognostic Factors
           in Salivary Tumors
           •  Age at diagnosis
           •  Pain at presentation
           •  T stage
           •  N stage
           •  Skin invasion
           •  Facial nerve dysfunction
           •  Perineural growth
           •  Positive surgical margins
           •  Soft tissue invasion
2012
           •  Treatment type

                                          Vander Poorten, 2002.
Radiation Therapy:
       Fast Neutron Radiation
       •  Available in few centers

       •  High LET radiation

       •  RBE especially high for adenoid cystic ca

       •  Uncertain benefit in completely resected vs
         conventional photon RT

       •  Definite advantage residual, recurrent
2012   unresectable disease
Fast Neutrons as Treatment for
         Salivary Gland Carcinoma*
 •  53 pts (24 gross resid p.o.; 13 inop; 16 rec
 p.o.)
 •  Locoreg control in Rx field in 48 (>90%)

 •  ACC = 14 pts (42 mos med f/u – min 1 yr)
 •  Actuarial 5 yr survival 33% (42% No)

 •  17% serious acute complic (Incl 1 death)
2012




                                   *Buchholz et al. Cancer 1992
Post-Op Complications


        •  Hematoma
        •  Infection
        •  Numbness of the skin
        •  Seroma      salivary fistula
        •  Frey’s syndrome
        •  Facial weakness
2012
Frey’s Syndrome
   Treatment:
       •  Anticholinergic cream
       •  Resection of auriculo-temporal nerve
       •  X-ray treatment

       •  Intracranial sectioning of IX nerve
       •  Excision of involved skin
       •  Jacobsen’s neurectomy
       •  Alcohol injection in otic ganglion
2012
       •  Elevation of skin flap and dermis or fascia lata
             graft
2012
2012
Submandibular Gland Tumors



 •  Known or suspected tumour requires
       extracapsular excision


 •  Invasive tumours require wide local
       resection

2012
2012
Minor Salivary Gland Tumors

       •  Histological type influenced the development
         of nodal disease, being more common in
         mucoepidermoid and high grade tumours.
       •  Perineural invasion reduced 5-year survival
         from approx 95% to 35%, and increased the
         likelihood of nodal disease and distant
         metastases. Involvement of named nerves led
         to a particularly unfavourable prognosis.

2012
       •  Adenoid cystic primaries require more
         generous margins due to perineural spread
                                                 Robson, 2002
Salivary Tumors Molecular Biology
 •  Loci on chromosome 8q may harbor a tumor
 suppressor gene or genes associated with
 development or progression of salivary tumors

 •  Alterations on the short arm of chromosome 17 may
 represent an event related to tumor progression


 •  Tumors with LOH at multiple loci have
        aggressive biologic characteristics
 2012
Salivary Tumors Molecular Biology
•  Warthin’s tumor showed low SPF+G2M and
   low Ki67

•  Pleomorphic adenoma showed low SPF+G2M
and high Ki67
•  Malignant tumor showed high SPF+G2M and
high Ki67

•  MIB 1 and PCNA immunohistochemistry may
help distinguish benign/low grade/ACC
 2012
Salivary Diseases
       •  Outpatient parotidectomy
       •  Needle biopsy
       •  Sialoendoscopy
       •  Sialocholithotomy
       •  Molecular markers
2012
       •  Radiation therapy
Salivary Gland Carcinoma Rx
             Principles
       •  Adequate local excision of tumor based on extent
       of the primary

       •  Preserve the nerve, if possible

       •  Elective neck dissection reserved for selected
       patients
       •  Post-operative radiotherapy when indicated
       (appropriate fields)
2012   •  Most important prognostic factors: stage &
       grade
“In seventh nerve paralysis, joy,
   happiness, sorrow, shock, surprise,
   all the emotions have for their common
   expression the same blank stare.”


                    Sterling Burnell, 1927
2012

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Salivary gland tumors by J. Shaha

  • 1. The International Federation of Head and Neck Oncologic Societies Current Concepts in Head and Neck Surgery and Oncology 2012 Management of Salivary Gland Tumors Ashok R. Shaha
  • 2. Salivary Glands Major: Parotid Submandibular Sublingual Minor salivary glands: 600 - 800 all over the upper aerodigestive tract 2012 Majority on the palate
  • 3. Salivary Literature 1985 to 2005 Subject # Papers Salivary gland diseases 19,754 Salivary neoplasms 7,914 Needle biopsies 14,713 Salivary – needle biopsies 397 2012
  • 4. Salivary Gland Neoplasms Management Issues Evaluation (FNAB, CT, MRI) Stage v. Grade Imaging Facial nerve Adjunctive radiotherapy 2012 Definitive radiotherapy
  • 5. Salivary Tumors Sites of Origin Sites # Pts % Parotid 1,965 70.0 Submandibular 235 8.4 Palate 228 8.0 Lips/Cheek 73 2.6 Antrum 72 2.6 Tongue 63 2.2 Nasal cavity 60 2.1 Gingiva 34 1.2 Floor of mouth 22 0.8 Larynx 21 0.8 Tonsil 13 0.5 Ethmoid 9 0.3 Nasopharynx 9 0.3 Pharyngeal wall 3 0.1 2012 TOTAL 2,807 100.0
  • 6. Salivary Gland Neoplasms* PROPORTION MALIGNANT # Pts 2500 Benign Malignant 2000 25% 1500 1000 82% 500 57% 0 Parotid Submandibular Minor n=1965 n=235 n=607 2012 *MSKCC 1939-73 (Head Neck Surg 1986)
  • 7. Salivary Tumors - Histologic Distribution Parotid Sub - Max Mucoepidermoid Adenoid cystic Minor Adenocarcinoma Malignant mixed Acinic cell 2012 Squamous Other
  • 8. Palate Tongue Cheek/Lip Antrum Nasal Cavity Gum Larynx Tumors of Minor FOM Salivary Glands. Tonsil Site Distribution Nasopharynx Ethmoid Pyriform Other 2012 0 10 20 30 40 %
  • 9. Parotid Tumors Pathology – Memorial Hospital, 1939-1973 (N=1973) Benign (n=1342) Malignant (n=631) Pleomorphic adenoma 1133 Mucoepidermoid 272 Warthin’s 183 Adenocarcinoma 62 Oncocytoma 20 Acinic cell 75 Monomorphic 6 Adenoid cystic 62 Ca ex pleomorphic 107 Undiff 8 Epidermoid 45 2012 Spiro, 1986, Head and Neck Surg
  • 10. Modification of WHO and AFIP Classifications to Denote Grade of Salivary Gland Tumor Low-grade High-grade Acinic cell carcinoma  Polymorphous low grade  adenocarcinoma  Basal cell adenocarcinoma  Sebaceous carcinoma  Papillary cystadenocarcinoma  Mucinous adenocarcinoma  Basal cell adenocarcinoma  Sebaceous carcinoma  Papillary cystadenocarcinoma  Mucinous adenocarcinoma Malignant myoepithelialioma   2012 Watkinson, 2001
  • 11. Modification of WHO and AFIP Classifications to Denote Grade of Salivary Gland Tumor Low-grade High- grade Mucoepidermoid carcinoma   Adenoid cystic carcinoma   Adenocarcinoma, NOS   Epithelial-myoepithelial carcinoma  Oncocytic carcinoma  Salivary duct carcinoma  Carcinoma in pleomorphic adenoma  Squamous cell carcinoma  Small cell carcinoma  Undifferentiated carcinoma  2012 Watkinson, 2001
  • 12. Presentation Lump Pain Facial weakness Neck metastases Parapharyngeal mass – deep lobe tumors 2012
  • 13. 2012
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  • 17. Salivary Gland Tumors • Dumb bell tumor • Deep lobe tumor • Parapharyngeal space • Extraparotid salivary tissue 2012
  • 18. Parotid Carcinoma: Obvious Signs •  Facial nerve palsy •  Cervical metastasis •  Skin involvement 2012
  • 19. 2012
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  • 21. Investigations •  Clinical evaluation •  Sialogram •  CT scan •  CT sialogram •  Needle biopsy 2012 •  Sialendoscopy
  • 22. 2012
  • 23. Parotid Tumors Indications for CT Scan •  Clinical uncertainty of findings •  Deep lobe presentation •  Extraglandular extension •  Cervical nodal involvement 2012 •  Facial palsy or fixed mass
  • 24. 2012
  • 25. 2012
  • 26. Indications for Anatomical Imaging •  To make the diagnosis •  Uncertain extent •  Size •  Fixation •  Recurrent •  Parapharyngeal 2012 •  Clinically malignant
  • 27. Role of Imaging 1. CT scanning is superior to MRI for osseous and skull base involvement but MRI is superior for intracranial extension of tumour 2. MRI is superior to CT for assessment of primary disease and regional recurrence, as well as characterising extra parotid extension. Perineural invasion is best characterised with MRI 2012 3. Minor salivary gland tumours are best imaged with MRI, with irregular margins being a feature Robson, 2002
  • 28. Role of Needle Biopsy in Salivary Tumors •  To suspect malignancy •  To distinguish from metastatic carcinoma •  To suspect lymphoma •  To distinguish salivary from non-salivary tumors •  In poor risk pt - if suspect Warthin’s tumor •  To confirm pre-op suspicion of malignancy in pts with facial palsy •  In bilateral tumors 2012 •  Minimum risks Shaha AR. Am J Surg
  • 29. Mass in Parotid Region History/Head & Neck Exam FNA Salivary Non-Salivary Benign Malignant Lipoma Seb. Cyst Mixed tumor Primary Metastatic Lymph Nodes Warthin’s Ad-Cystic Sq Ca. Benign Adeno Ca. Melanoma Melanoma Met Ca. 2012 Lymphoma
  • 30. 2012
  • 31. Salivary Gland Tumors General Principles of Treatment •  Tumor factors •  Patient factors •  Physician factors 2012
  • 32. Parotid Tumor Surgical Principles Every attempt should be made to remove all gross tumor. Radiation therapy does not compensate for inadequate surgery. 2012
  • 33. Parotid Tumor Surgical Principles The extent of parotidectomy depends more upon the extent of the tumor than the histology of the tumor. 2012
  • 34. Salivary Gland Carcinoma Treatment Principles The anatomic relationship of the tumor to the nerve dictates the extent of surgery, not the histologic classification of the neoplasm. 2012
  • 35. Malignant Tumors Surgical treatment of the primary tumour - Parotid Gland: •  Size and location determine extent of resection •  Most T1/T2 lesions lateral to the nerve are suitable for a superficial parotidectomy •  Larger and deep lobe tumours usually require a total conservative parotidectomy with preservation of the facial nerve •  Patients with high grade extensive disease (i.e. skin involvement or facial palsy) may require extended radical parotidectomy •  In one series, facial nerve dysfunction was apparent initially in 14% of patients and complete nerve sacrifice was required in about 30% of 2012 parotidectomies
  • 36. Indications of Facial Nerve Resection •  Pre-op facial palsy •  Large tumor adherent to the nerve •  Direct tumor involvement into the nerve •  Recurrent malignant tumor 2012
  • 37. 2012
  • 38. Resection of Facial Nerve •  Nerve graft •  Great auricular nerve •  Ansa Cervicalis •  Sural nerve •  Nerve transfer-hypoglossal transfer •  Tarsorrhaphy •  Facial reanimation - facial slings 2012
  • 39. 2012
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  • 41. Problem Areas in Salivary Tumors: Parotid Gland •  Deep lobe parotid tumors •  Accessory parotid tumors •  Regional node metastases •  Local recurrences •  Facial nerve? 2012
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  • 54. Warthin’s Tumor •  Papillary cystadenoma lymphomatosum •  Oncocytoma •  Branchiogenic adenoma •  Epitheliolymphoid •  Branchioma •  Cylindrocellular branchiogenic adenoma •  Orbital inclusion adenoma 2012
  • 55. 2012
  • 56. Prognostic Factors •  Clinical Stage (TNM) •  Histological grade •  Age •  Gender •  Anatomical site •  Experience of the surgeon 2012
  • 57. Ca of the Parotid, MSKCC 1939-1968 Factors Influencing “Cure” Pts Eligible NED % Cervical node metastasis: Never documented 213 157 74 Present on admission 57 5 9 Appeared later 18 3 17 Local recurrence*: No 194 153 79 Yes 71 15 21 2012 *No data or palliation only in 23
  • 58. Ca of the Parotid, MSKCC 1939-1968 Factors Influencing “Cure” Pts Eligible NED % Stage of primary: I 104 88 85 (92) * II 83 57 67 (75) III 99 19 19 (20) Facial nerve status: Function intact 212 139 66 Partial/complete palsy 43 6 14 Not recorded 31 18 58 Unrelated dysfunction 2 2 100 2012 *Determinate cases only
  • 59. Major Salivary Ca 1939-1982 Node Metastasis (26%) # Pts* Nodes + Anaplastic 6 5 (83%) Squamous 26 15 (58%) Mucoep grades 2,3 123 54 (44%) Adenocarcinoma 46 18 (39%) Malig mixed 62 12 (19%) Adenoidcystic 50 4 (8%) Acinic cell 56 4 (7%) 2012 Mucoep grade 1 68 2 (3%) *439 determinate pts
  • 60. Cancer of the Major Salivary Glands: Nodal Status & 5 Yr Survival 80 70 N0 60 N+ 50 40 30 20 10 0 Parotid Submandibular 2012
  • 61. Elective Neck Treatment in Salivary Gland Cancers •  High grade tumors •  T3 (?) & T4 tumors Elective •  Tumors >3 cm neck •  Facial paralysis treatment •  Age >54 •  Extraparotid extension •  Perilymphatic invasion 2012
  • 62. 1966 – 1998 Neck Dissection for Parotid Ca - MSKCC •  Therapeutic neck dissection with post-op RT yielded better results •  Reserve elective neck dissection for selected pts •  Indications for elective neck dissection •  High risk of metastasis based on T stage & grade •  Selected pts with large primary tumors in the tail of parotid 2012
  • 63. Management of the Neck in Parotid Cancer Elective neck dissection should be reserved for those histologic diagnoses having the highest risk of nodal metastases plus selected patients whose primary tumor resection may be facilitated by 2012 Lymphadenectomy. Kelley and Spiro. Am J Surg 1996; 172:695-697.
  • 64. Indications for Postoperative Irradiation-Parotid Cancer •  Aggressive, highly malignant tumors •  Invasion of adjacent tissues outside parotid capsule •  Regional lymph node metastases •  Deep lobe cancers •  Gross residual tumor following resection •  After resection recurrent tumor 2012 •  Tumor invasion of facial nerve
  • 65. Salivary Ca. - Impact of Post-op R.T. on Survival 100 75 50 % 25 0 0 5 10 Time (years) Stage I, II Stage I, II w/ Stage III, IV Stage III, 2012 RT w/ RT IV
  • 66. Adjuvant Radiotherapy: Impact on Prognosis Survival Surg Alone Surg+RT Stage I/II 96 82 Stage III/IV 10 51 Lymph node mets 19 49 High-grade tumors 28 57 Overall 55 69 Local control Surg Alone Surg+RT Stage I/II 79 91 Stage III/IV 17 51 Lymph node mets 40 69 High-grade tumors 44 63 2012 Overall 66 73 Armstrong, et al. Arch Oto HN Surg 1990.
  • 67. Salivary Carcinoma - Survival by 100 HISTOLOGY 80 % 60 40 20 0 0 6 12 18 24 30 36 Time (years) Acinic cell Muco ep. Gr II - MMT Squamous or 2012 III Anaplastic ca Muco ep. Gr I Adeno Ca. Adenoid cystic
  • 68. Salivary Carcinoma - Survival by SITE 100 Parotid Sub-max 80 Minor 60 % 40 20 0 2012 0 5 10 15 20 Time (years)
  • 69. Salivary Carcinoma - Survival by GRADE 100 Low 75 Intermediate %50 High 25 p< 0.0001 0 0 5 10 15 20 2012 Time (years)
  • 70. Salivary Carcinoma - Survival by STAGE 100 Stage I 75 Stage II % 50 Stage III 25 P< 0.0001 0 2012 0 5 10 15 20 Time (years)
  • 71. 2012
  • 72. Important Prognostic Factors in Salivary Tumors •  Age at diagnosis •  Pain at presentation •  T stage •  N stage •  Skin invasion •  Facial nerve dysfunction •  Perineural growth •  Positive surgical margins •  Soft tissue invasion 2012 •  Treatment type Vander Poorten, 2002.
  • 73. Radiation Therapy: Fast Neutron Radiation •  Available in few centers •  High LET radiation •  RBE especially high for adenoid cystic ca •  Uncertain benefit in completely resected vs conventional photon RT •  Definite advantage residual, recurrent 2012 unresectable disease
  • 74. Fast Neutrons as Treatment for Salivary Gland Carcinoma* •  53 pts (24 gross resid p.o.; 13 inop; 16 rec p.o.) •  Locoreg control in Rx field in 48 (>90%) •  ACC = 14 pts (42 mos med f/u – min 1 yr) •  Actuarial 5 yr survival 33% (42% No) •  17% serious acute complic (Incl 1 death) 2012 *Buchholz et al. Cancer 1992
  • 75. Post-Op Complications •  Hematoma •  Infection •  Numbness of the skin •  Seroma salivary fistula •  Frey’s syndrome •  Facial weakness 2012
  • 76. Frey’s Syndrome Treatment: •  Anticholinergic cream •  Resection of auriculo-temporal nerve •  X-ray treatment •  Intracranial sectioning of IX nerve •  Excision of involved skin •  Jacobsen’s neurectomy •  Alcohol injection in otic ganglion 2012 •  Elevation of skin flap and dermis or fascia lata graft
  • 77. 2012
  • 78. 2012
  • 79. Submandibular Gland Tumors •  Known or suspected tumour requires extracapsular excision •  Invasive tumours require wide local resection 2012
  • 80. 2012
  • 81. Minor Salivary Gland Tumors •  Histological type influenced the development of nodal disease, being more common in mucoepidermoid and high grade tumours. •  Perineural invasion reduced 5-year survival from approx 95% to 35%, and increased the likelihood of nodal disease and distant metastases. Involvement of named nerves led to a particularly unfavourable prognosis. 2012 •  Adenoid cystic primaries require more generous margins due to perineural spread Robson, 2002
  • 82. Salivary Tumors Molecular Biology •  Loci on chromosome 8q may harbor a tumor suppressor gene or genes associated with development or progression of salivary tumors •  Alterations on the short arm of chromosome 17 may represent an event related to tumor progression •  Tumors with LOH at multiple loci have aggressive biologic characteristics 2012
  • 83. Salivary Tumors Molecular Biology •  Warthin’s tumor showed low SPF+G2M and low Ki67 •  Pleomorphic adenoma showed low SPF+G2M and high Ki67 •  Malignant tumor showed high SPF+G2M and high Ki67 •  MIB 1 and PCNA immunohistochemistry may help distinguish benign/low grade/ACC 2012
  • 84. Salivary Diseases •  Outpatient parotidectomy •  Needle biopsy •  Sialoendoscopy •  Sialocholithotomy •  Molecular markers 2012 •  Radiation therapy
  • 85. Salivary Gland Carcinoma Rx Principles •  Adequate local excision of tumor based on extent of the primary •  Preserve the nerve, if possible •  Elective neck dissection reserved for selected patients •  Post-operative radiotherapy when indicated (appropriate fields) 2012 •  Most important prognostic factors: stage & grade
  • 86. “In seventh nerve paralysis, joy, happiness, sorrow, shock, surprise, all the emotions have for their common expression the same blank stare.” Sterling Burnell, 1927 2012