1. Salivary gland neoplasms are relatively rare, accounting for 6% of head and neck tumors, with parotid gland tumors making up 80% of cases. 2. Clinical presentation depends on whether the tumor is benign or malignant. Benign tumors usually present as asymptomatic swellings while malignant tumors can present with pain, nerve palsies, or nodal metastases. 3. Diagnosis involves investigations like ultrasound, CT, MRI and biopsy to determine the nature and extent of the tumor. However, differentiating between benign and malignant, and identifying the exact histology can still be challenging.

1. Diagnosis & Treatment of salivary
gland tumors
Dr. Anushan Madushanka..BDS, MD/OMFS, MFDRCSI
Senior Registrar in OMF surgery
North Colombo Teaching Hospital, Sri Lanka

2. Overview
• Introduction
• Classification
• Aetiopathogenesis
• Behavior & clinical presentation
• Diagnosis & problems in clinical diagnosis
• Investigations & their limitations
• Staging of malignant tumors
• Treatment options & selection criteria
• Assessment of prognostic indicators & prognosis

3. Introduction
• salivary gland neoplasms - relatively rare
• 6% of all H & N tumors
• Incidence- approximately 1.5 cases per 100,000
in United States.
• An estimated 700 deaths annually in USA
• most commonly appear in the sixth decade of life
• malignant lesions typically present after age 60
years & distributed equally between the sexes
• benign lesions usually present when older than
40 years & common in women than men

4. Sri Lanka cancer registry
Cancer incidence by the reporting year, sex and
sub-site 2001-2005
2001 2002 2003 2004 2005
M FM Tot M FM Tot M FM Tot M FM Tot M FM Tot
Parotid 38 25 63 29 26 55 26 15 41 29 28 57 37 23 60
Submandibular
gland
12 6 18 7 7 14 1 7 08 6 2 08 8 5 13

5. Distribution of Salivary Gland Tumors
• Among salivary gland neoplasms 80% arise in the
parotid gland
• 10-15% in the submandibular gland
• Remainder in sublingual and minor salivary glands
• 75-80% of parotid neoplasms are benign
• 50% of submandibular gland neoplasms are benign
• 25% of minor salivary glands neoplasms are benign
• 100% of sublingual gland tumors are malignant
• Rule of thumb is the 25/50/75 rule
• As the size of the gland decreases, the incidence of
malignancy increases.

6. W.M.Tilakaratne et al

10. Aetiopathogenesis
• No identifiable cause. But studies suggest links with,
• Biological: Viruses- EBV- lymphoepithelial carcinoma
Hormones- Oestrogen & progesterone receptors
(MEC, Acinic cell Ca)
• Physical: Nuclear bomb radiation-Japan (MEC, Warthin’s tumor)
H & N therapeutic radiation, Dental radiography
UV exposure
• Chemicals: Rubber manufacturing, Plumbing industry
Wood work, Asbestos
Nickel, Chromium compounds
• Lifestyle: Smoking – Warthin’s tumor

11. Pathogenesis
Two theories,
1.Multicellular stem cell theory:
Assumes that each tumor type is associated
with a specific differentiated cell of origin
within the salivary gland unit.
• Excretory duct cells - Squamous cell carcinoma
• Intercalated duct cells - pleomorphic adenoma
• Striated duct cells - oncocytoma
• Acinar cells - acinic cell carcinoma

12. Pathogenesis cont… Multicellular stem cell theory

13. Pathogenesis cont…
2.Bicellular stem cell theory:
Postulates that tumor arise from one of the two undifferentiated
stem cells
• Excretory stem cells - Squamous cell and
Mucoepidermoid carcinomas
• Intercalated stem cells - Pleomorphic adenoma
Oncocytoma
Adenoid cystic carcinoma
Odenocarcinoma
Acinic cell carcinoma
Currently accepted - Bicellular theory.

14. Histological classification (WHO 2005)
Malignant epithelial tumours Benign epithelial tumours
•Acinic cell carcinoma 8550/3
•Mucoepidermoid carcinoma 8430/3
•Adenoid cystic carcinoma 8200/3
•Polymorphous low-grade adenocarcinoma 8525/3
•Epithelial-myoepithelial carcinoma 8562/3
•Clear cell carcinoma, not otherwise specified 8310/3
•Basal cell adenocarcinoma 8147/3
•Sebaceous carcinoma 8410/3
•Sebaceous lymphadenocarcinoma 8410/3
•Cystadenocarcinoma 8440/3
•Low-grade cribriform cystadenocarcinoma
•Mucinous adenocarcinoma 8480/3
•Oncocytic carcinoma 8290/3
•Salivary duct carcinoma 8500/3
•Adenocarcinoma, not otherwise specified 8140/3
•Myoepithelial carcinoma 8982/3
•Carcinoma ex pleomorphic adenoma 8941/3
•Carcinosarcoma 8980/3
•Metastasizing pleomorphic adenoma 8940/1
•Squamous cell carcinoma 8070/3
•Small cell carcinoma 8041/3
•Large cell carcinoma 8012/3
•Lymphoepithelial carcinoma 8082/3
•Pleomorphic adenoma 8940/0
•Myoepithelioma 8982/0
•Basal cell adenoma 8147/0
•Warthin tumour 8561/0
•Oncocytoma 8290/0
•Canalicular adenoma 8149/0
•Sebaceous adenoma 8410/0
•Lymphadenoma
•Sebaceous 8410/0
•Non-sebaceous 8410/0
•Ductal papillomas
•Inverted ductal papilloma 8503/0
•Intraductal papilloma 8503/0
•Sialadenoma papilliferum 8406/0
•Cystadenoma 8440/0
Soft tissue tumours
Haemangioma
Haematolymphoid tumours
Hodekin’s lymphoma
Diffuse large B- cell lymphoma
Extranodal marginal zone B- cell lymphoma

15. Behavior of common tumors-Benign
1. Benign pleomorphic adenoma or benign mixed tumor
• Most common parotid neoplasm (80%)
• Proliferation of epithelial and myoepithelial cells of the ducts and an increase
in stromal components
• Slow growing, lobular, and not well encapsulated
• Recurrence rate of 1-5% with appropriate excision (parotidectomy)
• Recurrence possibly secondary to capsular disruption during surgery***
• Malignant transformation occurs in 2-10% of adenomas
Long standing tumours
Carcinoma in pleomorphic adenoma- common
(Carcinosarcoma also occurs)
• PA in younger patient- higher chance of tumor recurrence
• Increased growth during pregnancy
• Benign metastasizing pleomorphic adenoma - metastasis

16. Behaviors of common tumors
(Benign tumors) cont..
2. Warthin’s tumour
• Exclusively in the parotid.
• Mostly in men & more common in smokers.
• Derived from salivary duct cells that are entrapped in
lymph nodes during embryonic development.
• Very slow growing
• Consists of large cystic spaces
• May be multiple in one parotid gland or bilateral

17. Behaviors of common tumors - Malignant
1.Mucoepidermoid carcinoma
• Common neoplasm in both adults and children
• The most common cancer in parotid and minor salivary glands
• Two grades- Low grade & High grade
• Low grade very slow growing
non-metastasizing
generally behave like a benign tumor**
• High grade - aggressive growth and invasion
widespread metastasis and death
metastasize to cervical lymph nodes
spread haematogenously to the lung, liver, bone.

18. Behaviors of common tumors
(Malignant tumours) Cont..
2. Adenoid cystic carcinoma
• Most common malignancy of the submandibular gland
• Second most common salivary gland cancer overall.
• Very slow growing over years
• Common recurrence
• Metastasis via the blood stream
• Three histologic types- tubular, cribriform, solid
• Solid type has worse prognosis
• Characteristic perineural invasion
• Perineural spread is an adverse prognostic sign
causes recurrence and distant metastasis
• Follow-up of 15 to 20 years is required as late recurrences occur.

19. Behaviors of common tumors
(Malignant tumours) Cont..
3. Polymorphous low grade adenocarcinoma
• Occurs almost exclusively in the minor salivary glands
• Second only to mucoepidermoid carcinoma at these sites.
• Behaves in a very low grade manner
• Local recurrence will occur with inadequate excision
• 03 histological patterns (Glandular ,Cribriform ,Tubular)
• Probability of misdiagnosis as - Adenoid cystic carcinoma
Pleomorphic adenoma
• Characteristically - perineural involvement are seen
• Does not lead to a worse prognosis

20. Clinical presentation & Problems in Diagnosis
Clinical Presentation:Benign
Malignant
Diagnosis: Detailed history
Thorough examination**
Clinical features of benign tumors
• A soft/firm lump over salivary gland area
• Slow growing over years
• Asymptomatic
• Well circumscribed
• Push & compress adjacent structures rather than invading
• No nodal or distant metastsis. ?

21. Clinical presentation of benign parotid
tumours

22. Clinical features of malignant tumors
• Asymptomatic lump or swelling**** -80% of parotid malignancies
• Pain - 30% Parotid CA (often indicates perineural invasion) ***
• Cranial nerve palsy: 7-20% malignant parotid tumours
indicate poor prognosis***
• Poorly defined margins
• Moderate or rapid growth- depend on tumor grade
• Surface ulceration- in advance stage
• Trismus – involvement of masticatory space
• Dysphagia
• Pus/blood discharge from the excretory duct
• Nodal metastasis 80% of cases with facial nerve palsy in parotid CA
Average survival of 2.7 years
10-year survival of 14-26%
• Distant metastasis

23. Clinical presentation of malignant
parotid tumours

24. Problems in clinical diagnosis.
1. Tumor arising from salivary gland or adjacent structures ?
Eg- Angle of the mandible lesion (Ameloblastoma)
Chondrosarcoma of atlas vertebra
Enlargement of parotid lymphnode
Enlargement of jugulodigastric node – may mimic parotid tumor
2. Whether the tumor is benign or malignant ? – major question
Eg- Low grade mucoepidermoid Ca shows benign behavior like slow growing,
No nodal mets
Benign metastasizing pleomorphic adenoma shows nodal metastasis
3. If clinically benign then does it have a malignant component ?
Eg- Carcinoma in pleomorphic adenoma.
4. If malignant, then is it a primary or secondary deposit ?
5. What is the histologic type?
6. Unusual presentation - Central mucoepidermoid CA.

25. Investigations & their limitations
• Can investigations answer the above questions?
• Investigations are important
narrow down the differential diagnosis
confirm the diagnosis
assess the lesion
stage the malignancy
• Following investigations are used to diagnose & assess the salivary gland tumour.
1. Plain radiographs
2. USS
3. CT & MRI
4. PET & PET CT
5. Histopathological investigations
FNAC – For superficial palpable tumor
USS guided FNAC/ CT guided FNAC- For non palpable deep lobe tumours
Large core needle biopsy
Incision biopsy ?
Surgical exploration & Frozen sections

26. Plain radiographs
• Less informative for diagnosis of malignancy
• Useful to rule out any sialolithiasis
• Gives an idea of presence of bone invasion
• Sialography – useful to exclude obstructive disease
not indicate presence of malignancy
Should not do if suspect malignancy

27. Ultra sound scanning
• First line investigation
• Shows anatomical structure of origin
• Excludes - Vascular lesions, Cystic lesions & other inflammatory &
benign conditions
• Able to differentiate malignancy from benign tumors
• Increased tumoural resistance on colour Doppler ultrasound usually
indicate malignancy
• Can be used to guide FNA or core biopsy
• Small, well-differentiated primary salivary gland malignancies may
appear benign – low grade MEC Vs. PSA
• Can’t assess deep lobe of parotid & other deep structures

28. Histopathological investigations
Fine needle aspiration
• Sensitivity : More than 95% in experienced hands
Positive result should only be accepted
Negative results need further attempts
• False positive rate & false negative rate range - 1-14%
• Correct diagnosis as benign or malignant range from - 81-98%
• Specific diagnosis can only be made in approximately - 60-75%
• Helps to decide - inflammatory or neoplastic
- lymphoma or an epithelial malignancy
- metastasis or a primary tumour
Therefore helps to avoid unnecessary surgery & assist in preoperative planning &
patient counselling

29. Histopathological investigations cont…
large core needle biopsies
Less popular because of potential facial nerve injury and the possibility of seeding
Incisional biopsy
Should not be performed
(high rate of local recurrence and possible risk for facial nerve injury)
*** But can be done for minor salivary gland tumour if FNAC fails.( Surgery should
be done as soon as possible)
Operative exploration & Frozen section
• Done when all attempts at obtaining a histologic diagnosis fails
• operative exploration is done & gives conclusive proof
• Overall accuracy rate for a benign / malignant diagnosis is 96%
• But if the salivary gland tumour divided into benign and malignant groups :
- accuracy rate in benign lesions group (98.7%) is excellent
- but accuracy rate in malignant tumour group(85.9%) is suboptimal

30. CT & MRI scanning
• Each modality has special benefits and limitations.
• CT scanning provides better detail of the surrounding tissues
• MRI demonstrates the mass in greater contrast than CT
• MRI superior to CT - demonstrating tumour margins
differentiate benign from malignant mass
Benign - usually margins smooth, with distinct capsule
low-grade malignancies - can appear benign due to pseudocapsule
High-grade malignancies - have ill-defined infiltrating margins
• CT & MRI may help identify - L/N involvement
- Extension into deep lobe
CT criteria for L/N metastasis :
- any L/N > 1-1.5 cm in greatest diameter
- multiple enlarged nodes
- nodes displaying central necrosis
- may appear round (than normal kidney bean shape)
- extracapsular extension may be identified
- perinodal rim enhancement

31. CT & MRI Scanning cont..
• CT & MRI : are the choice for salivary gland neoplasms
• Both have sensitivities that approach 100%
• Both - show the entire gland and contralateral gland
• CT excludes recurrent, tender inflammatory masses.
• CT demonstrate invasion the earliest.
• CT - Facial nerve usually not visualized (but course of nerve can be
traced from stylomastoid foramen).
• MRI - Preferred to evaluate asymptomatic mass
Provides good soft tissue contrast
• MRI – Occasionally visualize the facial nerve & Parotid duct
Need gadolinium enhanced contrast MRI to see facial Nv
• Can combined with PET scan to get PET/CT

32. IV contrast CT of Parotid tumour

33. MRI scanning

34. Limitations of MRI & CT
• On CT or MRI, many malignant tumors are
indistinguishable from benign tumors
eg- Acinic cell carcinoma
Low-grade mucoepidermoid carcinoma
• Not available in every centres
• Expensive
• CT- high dose radiation

35. Use of Contrast Enhanced MRI for
Perineural Invasion
• MRI provides better clues about perineural invasion
• MRI features - Enlargement or bony erosions of
-skull base neural foramina
- Obliteration of peri-neural fat planes
- Nerve enlargement
• Contrast enhanced CT –
Better detail about perineral invasion
If abnormal enhancement at facial nerve area
96% probability of perineural invasion

36. Contrast Enhanced MRI for Perineural
Invasion

37. PET Scanning
• High rate of sensitivity & specificity
• Detects Primary malignancy, regional & distant
metastasis
• Can combined with CT to produce PET/CT
• Gives exact location of tumor & extent of lesion
• Useful to diagnose - Subclinical lesions
Unknown primary
• Very expensive
• Not freely available

38. PET scannig cont..CT/PET

39. TNM Staging of Tumor
N2b Metastasis in multiple ipsilateral lymph nodes, none more than 6
cm in greatest dimension
N2c Metastasis in bilateral or contralateral lymph nodes, none more
than 6 cm in greatest dimension
N3 Metastasis in a lymph node more than 6 cm in greatest dimension
Note: Midline nodes are considered ipsilateral nodes.
M – Distant metastasis
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
T – Primary tumour
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
T1 Tumour 2 cm or less in greatest dimension without
extraparenchymal extension*
T2 Tumour more than 2 cm but not more than 4 cm in greatest
dimension without extraparenchymal extension*
T3 Tumour more than 4 cm and/or tumour with
extraparenchymal extension*
T4a Tumour invades skin, mandible, ear canal, or facial nerve
T4b Tumour invades base of skull, pterygoid plates, or encases
carotid artery
Note: *Extraparenchymal extension is clinical or
macroscopic evidence of invasion of soft tissues
or nerve, except those listed under T4a and 4b.
Microscopic evidence alone does not constitute
extraparenchymal extension for classification
purposes.
N – Regional lymph nodes
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node,
3 cm or less in greatest dimension
N2 Metastasis as specified in N2a, 2b, 2c below
N2a Metastasis in a single ipsilateral lymph node, more
than 3 cm but not more than 6 cm in greatest dimension
Stage Grouping
Stage I T1 N0 M0
Stage II T2 N0 M0 Unremarkable
Stage III T3 N0 M0
T1, T2, T3 N1 M0
Stage IV A T1, T2, T3 N2 M0
T4a N0, N1, N2 M0 Clinically malignant
Stage IV B T4b Any N M0
Any T N3 M0
Stage IV C Any T Any N M1

40. Treatment Options for Salivary Gland
Neoplasia
• Surgery
• Radiotherapy
• Chemo therapy
• Targeted therapy
• Immunotherapy
• Any of combinations

41. Factors to consider in selecting a treatment
option
• Pt date line - Too young / Late stage of life
Disease date line - early Ca/ Late Ca/ end stage
Clinical behaviour of the tumour – Locally aggressive or not
Site of tumor – Parotid/ Submandibular/ Palate / Lip /Cheek
• TNM stage of the tumour -Stage 1 & 2 – can cure with surgery alone
-Stage 3 & 4 – Need surgery & adjuvant RT
• Histopathologic factors- Type of malignancy
Grade of malignancy
Invasive front, Host response
Angio trophism & Neuro trophism
Excision margin
• Pt. factors: Medical aspect, Psychosocial aspect
Pt. occupation & Pt. preference
• Oncologist opinion
• Facilities available

42. Role of Surgery
• Surgery - Primary treatment modality - Curative or Palliative
• Involves – 1. Resection & reconstruction of primary
2. Neck dissection
3. Rehabilitation – Functional rehabilitation
Aesthetic rehabilitation
Psychological rehabilitation
Social rehabilitation
4.Follwup
• Benign tumours – Sole treatment modality is surgery
• Malignant tumours – Stage 1, 2 – Surgery alone
Stage 3,4 - Surgery + Neck dissection + Adjuvant
chemoradiation
Neck dissection – N0 neck – selective neck dissection(if high risk)
N+ neck - Comprehensive neck dissection
Reconstruction - Primary closure, local flap, distant flap, free flap
• ***If pt can’t cure by surgery, then hope for survival is questionable.

43. Role of Surgery cont..
• Parotid tumours
04 Surgeries – Superficial parotidectomy benign tumours
Total conservative parotidectomy Low grade malignancy
High grade malignancy involving
Few FN branches
Radical parotidectomy Stage 3,4 malignancy involving
Extended radical parotidectomy facial nerve & surrounding tissues

44. Role of Radiotherapy
• Earlier- radioresistant now definite role as adjuvant RT
• Neoadjuvant RT- No role as a primary modality
Can be given for inoperable cases
Only 40% of cases – improvement
• Adjuvant RT – Has proven role
Better control of local disease
• Linear accelerator, Fast beam neutron therapy, accelerated
hyperfractionated photon-beam therapy- good results than
conventional RT .
• If combined with CT – Increased Radio sensitivity
• Palliative RT – Given for inoperable & advanced cases

45. Role of Radiotherapy cont..
General indications for postsurgical radiation therapy include
- tumours >4 cm in greatest diameter
- tumours of high grade
- tumour invasion of local structures
- lymphatic invasion
- neural invasion
- vascular invasion
- tumour present very close to a nerve that was spared
- tumours originating in or extending to the deep lobe
- recurrent tumours following re-resection
- positive margins on final pathology
- and regional lymph node involvement.

46. Role of chemotherapy
Adjuvant Chemotherapy
• Salivary gland cancers are definitely sensitive to chemotherapy
drugs
• Studies show proven benefits.
• Some oncologists Combine with XRT – to increase the radio
sensitivity & local control (eg- Cisplatin)
• This integration is important since 5-year survival in tumours with
high grade histology is approximately 50%
• Overall incidence of metastases is approximately 25%
• Clinical trials are being done with- gemcitabine, capecitabine, and
oxaliplatin,Cisplatin
• Studies are few due to less number of cases

47. Role of chemotherapy Cont…
• Palliative chemotherapy
• Indication- advanced stage or metastatic
carcinomas
• Few reports of cases
Cisplatin is considered the most active drug-
response rate of 16% in 25 consecutive cases
Combinations associating cisplatin +
anthracycline/vinorelbine are well tolerated
• Neoadjuvant chemotherapy –
No proven benefit
Some studies- improve prognosis.But Questionable

48. Role of advanced therapy
Targeted therapy-
carcinomas of the salivary glands express target
molecules which promote
Cell proliferation
Facilitate metastasis
Eg - C-kit
EGFR
Estrogen receptors
Progesterone receptors
Natural or synthetic target drugs inhibits this receptors &
impairs cell proliferation.
This is still in experimental level

49. Role of advanced therapy cont..
• Immunotherapy
Process of immunological destruction of cancer
cells
Can be done by-
1. Giving Ab against cancer cells
2. Promote NK cells against Ca cells
Still in experimental level

50. Assessment of prognostic indicators &
prognosis.
• The major determinants of survival: tumour type, grade & clinical stage.
• Poor prognostic factors include :
- high grade
- locally advanced disease, associated pain, neural involvement -
- regional lymph node metastases
- distant metastasis
- accumulation of p53 or c-erbB2 oncoproteins
- advanced age
• Though statements of survival are difficult, due to large variety of histologic types
- Overall 5-yr.survival for all stages & histologic types is approximately 62%
- 20% of all patients will develop distant metastases.
The presence of distant metastases heralds a poor prognosis, with a
median survival of 4.3-7.3 months.
- Overall 5-yr. survival for recurrent disease is approximately 37%
As this causes greater likelihood of distant metastasis, importance of
offering aggressive initial surgery is visible.

51. Thank You