01 salivary gland tumors

1. Benign and malignant diseases of
salivary glands
1

2. • Embryology
• Surgical Anatomy
• Non neoplastic conditions
• Benign tumors
• Malignant tumors
• Management
2

3. Introduction
3

4. Embryology
• The parotid anlagen first to develop.
• Parenchymal tissue - proliferation of oral epithelium.
• The stroma (capsule and septae)-from mesenchyme-mesodermal or
neural crest in origin.
• PG first to develop, encapsulate AFTER SMG and SLG.
• The lymphatic system develops after the encapsulation of the SMG
and SLG but BEFORE encapsulation of the parotid
• At around the 7-8th
month in utero, secretory cells (acini) begin to
develop around the ductal system.
• Parotid 4th
wk, SMG 6th
wk, SLG 8th
wk
4

5. SURGICAL ANATOMY• Parotid Gland
Shape
Extent
Capsule
Parotid duct
5

6. Parotid gland
• Pars Accessoria
• Surfaces of the gland
• Parotid lymph nodes
Clinical importance
• Tough & inelastic nature
Stylomandibular ligament
6

7. Structures coursing within the parotid
gland
• Facial nerve
• Retromandibular vein
• External carotid artery
• Auriculotemporal nerve (from V3)
Superficial
Deep
7

8. Surgical Anatomy (Contd)
• SUBMANDIBULAR GLAND
Location
Shape
Capsule
Surfaces : Medial
Lateral
Inferior
Wharton’s duct
8

9. Surgical Anatomy (Contd)
• SUBLINGUAL GLAND
Smallest, paired.
Shape/ Wt.
Location
9

10. Vascular and nerve supply
• Blood supply-External carotid .
-Retromandibular Vein:
• Lymphatic drainage superficial and deep cervical nodes
• Para sympathetic---Inf salivary nucleus– CN IX– Lesser petrosal N—
Otic ganglion—auriculo temporal N– Parotid
• Sympathetic—Sympathetic trunk—superior cervical ganglion– Ext
carotid A plexus—Parotid gland
• Blood supply-facial and lingual .A. Drainage to corresponding veins.
• Lymphatic drainage ;deep cervical nodes (jugulo omohyoid)
• Autonomic---corda tympani, lingual N and symp trunk–SM ganglion
• Blood supply-sub lingual and sub mental vessels
•Nerve supply-similar to SMG
10

11. Obstructive
Salivary Gland Disorders
• Sialolithiasis
• Mucous retention/extravasation
(common in minor salivary glands)
11

12. Obstructive SG Disorders:
Sialolithiasis
• Sialolithiasis - mechanical obstuction of the
salivary duct
• major cause of unilateral diffuse parotid swelling
• Incidence
• Etiology
• Stone composition and characterstics
• Clinical presentation
• Diagnosis and treatment
12

13. Mucocele
• Mucus is the exclusive secretory product of
the accessory minor salivary glands and the
most prominent product of the sublingual
gland.
• The mechanism for mucus cavity
development is extravasation or retention
• Excision with strict removal of any
projecting peripheral salivary glands
13

14. Ranula
• term used for mucoceles that
occur in the floor of the mouth.
• Source, usually the
sublingual gland
– also arise from the
submandibular duct
– Or minor salivary glands
• Marsupialization fallen into
disfavour due to the excessive
recurrence rate of 60-90%
• Sublingual gland removal via
intraoral approach 14

15. Salivary Gland Infections
• Acute bacterial sialdenitis
• Chronic bacterial sialdenitis
• Viral infections
15

16. Sialadenitis
Etiology
CF
Risk factors
Investigations
Treatment—medical and
surgical
Complications
16

17. Acute viral infection (AVI)
• Mumps classically designates a viral
parotitis caused by the paramyxovirus
• However, a broad range of viral pathogens
have been identified as causes of Viral
Infection of the salivary glands.
– HIV associated salivary gland disease
– HCV
– HTLV-I
– EBV/CMV 17

18. Granulomatous Disease
• Tuberculosis
• Non tubercular mycobacteria-M.kansasii,
scrofulaceum, avium intracellulare
• Cat Scratch Disease
• Actinomycosis
• Toxoplasmosis
18

19. Immunologic Disease
Sjögren’s Syndrome
• Most common immunologic disorder
• lymphocyte-mediated destruction of exocrine glands
leading to xerostomia and kerato conjunctivitis sicca
Two forms:
• Primary: involves the exocrine glands only
• Secondary: associated with a definable autoimmune
disease, usually rheumatoid arthritis.
– 80% of primary and 30-40% of secondary involves
unilateral or bilateral salivary glands swelling
19

20. Sjögren’s Treatment
• Avoid xerostomic meds if possible
• Avoid alcohol, tobacco (accentuates xerostomia)
• Sialogogue (eg:pilocarpine) use is limited by other
cholinergic effects like bradycardia & lacrimation
• Sugar free gum or diabetic confectionary
• Salivary substitutes/sprays
20

21. Radiation Injury
• Low dose radiation (1000cGy) to a salivary gland
causes an acute tender and painful swelling within
24hrs.
• Serous cells are especially sensitive and exhibit
marked degranulation and disruption.
• Continued irradiation leads to complete
destruction of the serous acini and subsequent
atrophy of the gland.
• Similar to the thyroid, salivary neoplasm are
increased in incidence after radiation exposure. 21

22. Other: Pneumoparotitis
• In the absence of gas-producing bacterial parotitis,
gas in the parotid duct or gland is assumed to be
due to the reflux of pressurized air from the mouth
into Stensen’s duct.
• May occur with episodes of increased intrabuccal
pressure
– Glass blowers, trumpet players
• Aka: pneumosialadenitis, wind parotitis,
pneumatocele glandulae parotis
22

23. Salivary Gland Neoplasms –
WHO Classification - 1991
• Adenomas
• Carcinomas
• Non epithelial tumors
• Malignant lymphomas
• Secondary tumors
• Unclassified tumors
• Tumor like disorders
23

24. Salivary Gland Neoplasms – WHO
Classification - 1991
Adenomas
Pleomorphic adenoma
Warthin’s tumor
Oncocytoma
Myoepithelioma
Basal cell adenoma
Canalicular adenoma
Sebaceous adenoma
Ductal papilloma
Cystadenoma
Carcinoma
Mucoepidermoid carcinoma
Adenoid cystic carcinoma
Acinic cell carcinoma
Polymorphous low grade adenocarcinoma
Epithelial – myoepithelial carcinoma
Basal cell adenocarcinoma
Sebaceous carcinoma
Adenocarcinoma
Oncocytic carcinoma
Salivary duct carcinoma
Malignant myoepithelioma
Ca in pleomorphic adenoma
SCC
Small cell Carcinoma
Undifferentiated Carcinoma 24

25. Salivary Gland Neoplasms
• There is little to distinguish a benign tumor
from its malignant counterpart
• Pre operative diagnosis by FNAC is
difficult & often inconclusive
• Surgery is challenging and worrying owing
to the relationship with facial nerve
• Recurrence are common
• Malignant transformation of some
recurrent benign tumors is well recognised
& almost impossible to cure.
25

26. Salivary Gland Neoplasms
• Diverse histopathology
• Relatively uncommon
– 3% of head and neck neoplasms : 75% benign
• Distribution
– Parotid: 80% overall; 80% benign;80% pleomorphic
– Submandibular: 15% overall;50% benign;95%
pleomorphic
– Sublingual/Minor: 5% overall; 40% benign
26

27. Etiology
• Exact cause is UNKNOWN
• Probable causes :
Exposure to radiation
Survivors of childhood malignancy
Thyroid CA pts. Treated with Radioactive iodine
Long term effects of high freq. electromagnetic
fields.
Role of PLAG I - pleomorphic adenoma
EBV- lymphoepithelial tumor
27

28. Bicellular Theory
• Intercalated Ducts
– Pleomorphic adenoma
– Warthin’s tumor
– Oncocytoma
– Acinic cell
– Adenoid cystic
• Excretory Ducts
– Squamous cell
– Mucoepidermoid
28

29. Multicellular Theory
• Each tumour type maps to different cell type
• Acinar cells—acinic cell carcinoma
• Striated duct—oncocytic tumors
• Excretory Duct—squamous cell and
mucoepidermoid carcinoma
• Intercalated duct and myoepithelial cells—
pleomorphic tumors
29

30. Pleomorphic Adenoma
• Most common of all salivary gland neoplasms
• 80% of parotid tumors
• 50% of submandibular tumors
• 45% of minor salivary gland tumors
• 6% of sublingual tumors
• 4th
-6th
decades
• F:M = 1.4:1
30

31. Pleomorphic Adenoma
• Slow growth, Benign course
• Clinical features :
Asymptomatic / Symptomatic
Clinical examination
False capsule-sub capsular clefts
• Prone to recurrence
• Associated with another salivary gland tumor
• Incidence of malignant change 6%
31

32. Pleomorphic Adenoma
• Gross pathology & Cut
surface
– Smooth
– Well-demarcated
– Solid
– Cystic changes
– Nodularity
– Greyish white
– Myxoid stroma-characterstic
– Haemorrhagic degeneration
32

33. Pleomorphic Adenoma
• Histology
Epithelial tumor of
complex morphology
– Mixture of epithelial,
myoepithelial and
stromal components
– Epithelial cells: nests,
sheets, ducts, trabeculae
– Stroma: myxoid,
chrondroid, fibroid,
osteoid
– Calcification of bone –
characterstic
Malignant change markers
33

34. Pleomorphic tumor
• Recurrence
After primary surgery 5%
Enucleation 20 – 30%
• Features
Cause
Multiple
Management difficult
Malignant change
34

35. Pleomorphic Adenoma
• Treatment: complete surgical excision
– Parotidectomy with facial nerve preservation
• Avoid enucleation and tumor spill
35

36. Warthin’s Tumor
• Papillary cystadenoma lymphomatosum / Adenolymphoma
• 14% of salivary gland neoplasms
• Second most common tumor.
• Exclusively a tumor of Parotid gland.
• Seventh decade; M:F::1.5:1
• Heavily built or obese individuals
• Etiology
• Clinical presentation 10% bilateral
36

37. Warthin’s Tumor
• Most common site
Tail of parotid
• Gross pathology
– Encapsulated
– Smooth/lobulated surface
– Soft, fluctuant, compressible
– Cystic spaces of variable size,
with viscous fluid, shaggy
epithelium
– Solid areas with white nodules
representing lymphoid follicles
37

38. Warthin’s Tumor
• “WHALE”
Warthins Has Abundant Lymphoid and Epithelial
components
• Histology
– Papillary projections into cystic
spaces surrounded by lymphoid
stroma
– Epithelium: double cell layer
• Luminal cells
• Basal cells
– Stroma: mature lymphoid follicles
with germinal centers
38

39. Warthin’s Tumor
• Second tumor, most commonly
pleomorphic adenoma.
• Almost Never Malignant
• Recurrences very rare
39

40. Oncocytoma
• Oxiphilic Adenoma- Outer part of parotid gland
• Rare: 2% of benign salivary tumors
• 7th
– 8th
decade
• M:F = 1:1
• Parotid: 78%
• Submandibular gland: 9%
• Minor salivary glands: palate, buccal mucosa,
tongue
• Arises from striated duct cells
• Benign; excision curative 40

41. Oncocytoma
• Gross
– Encapsulated
– Homogeneous, smooth
– Orange/rust color
• Histology
– Large polyhedral
eosinophilic cells with
mitochondria.
– Distinct cell membrane
– Granular, eosinophilic
cytoplasm
– Central, round, vesicular
nucleus 41

42. Malignant Salivary gland tumors
• Relatively UNCOMMON
• Slow growth pattern does not lessen their
malignant nature
• Considerable morbidity & mortality
• INCIDENCE : 1.2 PER 1,00,000 population
• Parotid 58% ; minor salivary glands 23%
• Malignancy is far more frequent in Minor
salivary glands & Sublingual glands
43

43. Malignant Salivary gland tumors
• Environmental / Nutritional
• Ionizing radiation
• Diet & nutritional habits : PUFAs
• Occupation : Workers involved with Livestock
feed processing-aflatoxin
• EBV
• Carcinogens - Benzopyrine, Dihydrodiol analogue
44

44. Cell and molecular biology
• Increased AgNOR clusters
• Immunohistochemical markers of prognostic
interest :
Ki 67 - Adenoid cystic CA
PCNA
Bcl -2
Cytokeratin 14 - SCC
FGF 1 & 2 & FGF R1
45

45. Malignant Salivary gland tumors
• Features suggestive of Malignancy
Induration
Fixed to overlying skin or mucosa
Ulceration of overlying skin or mucosa
Rapid growth; growth spurt
Pain often severe
Facial nerve palsy
Short duration 46

46. MALIGNANT NEOPLASMS
TNM
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor 2 cm or less in greatest dimension without gross
extraparenchymal extension
T2 Tumor more than 2 cm but not more than 4 cm in greatest dimension
without gross extraparenchymal extension
T3 Tumor more than 4 cm and/or tumor having gross extraparenchymal
extension
T4a Tumor invades skin, mandible, ear canal, and/or facial nerve
T4b Tumor invades skull base and/or pterygoid plates and/or encases
carotid artery
47

47. Stage Grouping
Stage I T1 N0 M0
Stage II T2 N0 M0
Stage III T3 N0 M0
T1 N1 M0
T2 N1 M0
T3 N1 M0
Stage IVA T4a N0 M0
T4a N1 M0
T1 N2 M0
T2 N2 M0
T3 N2 M0
T4a N2 M0
Stage IVB T4b Any N M0
Any T N3 M0
Stage IVC Any T Any N M1 48

48. Mucoepidermoid Carcinoma
• Most common major salivary gland malignancy
• MC salivary gland neoplasm in children
• 5-9% of salivary neoplasms
• Parotid 45-70% of cases
• Palate 41%
• 3rd-8th decades, peak in 5th decade
• M:F 1:1
49

49. Mucoepidermoid Carcinoma
• Presentation
– Benign Spectrum Aggressive
– Classified histologically :
• Low-grade: 80 %, slow growing, painless mass
• High-grade: 33%, rapidly enlarging, +/- pain
– Grows slowly & recur locally
50

50. Mucoepidermoid Carcinoma
• Gross pathology
– Well-circumscribed ,
partially encapsulated
to unencapsulated
– Solid tumor with cystic
spaces
51

51. Mucoepidermoid Carcinoma
• Histology—
Low-grade
– Mucus cell > epidermoid cells
– 10% tumour cells and 90% intracystic
spaces
– Prominent cysts
– Mature cellular elements
High-grade
– Epidermoid > mucus
– 90% tumour cells,<10% intracystic
spaces.
– Solid tumor cell proliferation
Old classification into
intermediate-dubious and no
prognostic significance 52

52. Mucoepidermoid Carcinoma
• Treatment
– Influenced by site, stage, grade
– Stage I & II
• Wide local excision
– Stage III & IV
• Radical excision
• +/- neck dissection
• +/- postoperative radiation therapy
• low grade-local resection and follow up.
• high grade –Radical resection and RT
53

53. Adenoid Cystic Carcinoma
• 40% of malignant tumors of all salivary sites
• Most common in minor salivary glands
– 25% parotid, 15% submandibular gland, 1% sublingual
gland, 60% minor glands.
• 41% locally advanced, 11% distant metastasis
54

54. Adenoid Cystic Carcinoma
• F > M
• 6th
decade
• Source – intercalated ducts
• Spreads perineural –central and peripheral
• Presentation
– Asymptomatic enlarging mass
– Pain, paresthesias, facial weakness/paralysis
– Nodal spread-8% early and 7% late.
– 7th
nerve palsy – 20%
55

55. Adenoid Cystic Carcinoma
• Gross pathology
– Well-circumscribed
– Solid, rarely with
cystic spaces
– Infiltrative
– hard and fixed
56

56. Adenoid Cystic Carcinoma
• Histology— 4 types
Solid pattern 25%
Cribriform 40% (MC)
Tubular 20%
Cylindromatous Polymorphous
low grade adenocarcinoma
15%-benign outcome
• Solid pattern
-worst prognosis. Cure
never achieved
57

57. Adenoid Cystic Carcinoma
• Histology—tubular
pattern
– Layered cells forming
duct-like structures
– Basophilic mucinous
substance
• Histology—solid
pattern
– Solid nests of cells
without cystic or
tubular spaces
58

58. Adenoid Cystic Carcinoma
• Bad prognosis in the long term
• Treatment
– Radical operation-? Sacrifice facial N
– Postoperative RT
– Recurrent tumour-surgery + RT
– Role of Chemotherapy
• Prognosis
– Primary site recurrence rate : 100% within 30 yrs.
– Neck node recurrence 23% within 15 yrs.
– Distant metastasis: lung, bone, liver
– Indolent course: 5-year survival 75%, 20-year survival 13%
59

59. Acinic Cell Carcinoma
• Low grade malignancy
• 2nd
most common parotid and pediatric malignancy
• 2.5 –4% of all salivary gland tumors
• 5th
decade
• F>M
• Bilateral parotid disease in 3%
• Source-terminal tubular intercalated duct cells
• Presentation
– Solitary, slow-growing, often painless mass
60

60. Acinic Cell Carcinoma
• Gross pathology
– Encapsulated lesion
– Well-defined margins
– Most often not
homogeneous
61

61. Acinic Cell Carcinoma
• Histology
Solid microcystic, Papillary cystic
& follicular.
• Rare, pleomorphic, pleotrophic
– Solid microcystic pattern
• Most common
• Solid sheets
• Numerous small cysts
– Polyhedral cells
– Small, dark, eccentric nuclei
– Basophilic granular cytoplasm
– Constituent cells contain zymogen
granules
62

62. Acinic Cell Carcinoma
• Best survival rate
• Treatment
– Complete excision of gland
– Preservation of uninvolved nerve
– +/- postoperative RT
• Prognosis
– 5-year survival: 82%,10-year survival: 68% 25-year survival: 50%
– Late recurrence
– 10% recurrence-LN
– 15% -distant metastasis
63

63. METASTATIC TUMOURS
• 80% Skin of face, pinna, temple or scalp
• SCC or Melanoma
– Parotidectomy with neck dissection in
continuity with primary lesion
• Lung, breast and kidney.
– Dismal prognosis
64

64. MANAGEMENT
INVESTIGATION :
• Clinical History
• Examination
• Lab tests
• USG Neck
• CT Or MRI
• FNAC
• Frozen section-5-12% false negative
65

65. Imaging of Salivary glands
• USG
Distinguish intrinsic from extrinsic tumors
USG guided FNAC
Malignant tumors have low reflectivity with poorly defined borders.
Disadv
Deep lobe parotid masses
Masses with parapharyngeal extension
Bone & dental artefacts
66

66. Imaging of Salivary glands
• CT Scan : CECT / CT Sialography
Differentiate benign from malignant masses
Differentiate superficial from deep lobe tumors
Separate a parapharyngeal mass from deep lobe tumor
Relationship of mass to facial nerve
Considerable insight into probable histology
Malignant tumors : irregular outline
Diffuse border
Nodal metastases
67

67. Imaging of Salivary glands
• MRI :
Superior soft tissue delineation
Multiplanar capabilities
Malignancy :
Infiltration
Bony changes
Perineural enhancement
signal intensity in T2 wt.
images (improved by
gadolinum)
68

68. Fine-Needle Aspiration Biopsy
• Efficacy is well established
– Accuracy = 84-97%: Sensitivity = 54-95%
– Specificity = 86 - 100%
– Safe(controversial– tumor seeding): well tolerated
• Limitations
– offers least possibility of pre op diagnosis
– Missing critical area at tumor border
– Important to distinguish benign vs. malignant nature of
neoplasm
– Preoperative patient counseling
69

69. Sialography
• Watery or oily iodinated contrast
• Multiple radiographs
• Adv-
– Quick
– Widely available
– Depiction of extra and intra glandular ducts
• Disadvantage-
– Invasive
– Complications
– In complete obstruction, not useful
– Interference with TFT 70

70. MANAGEMENT
• TREATMENT
– Surgery
– Radiotherapy
– Chemotherapy
• Factors that influence treatment
• Age
• Metastatic spread
• Facial nerve involvement
• Mandibular / Temporal bone involvement
• Skin
• Site of tumor
• Size, Extent, Grade & stage
71

71. Management
• Parotid masses
– Superficial parotidectomy
Most benign tumors
– Total conservative parotidectomy
-deep to nerve and deep lobe of
gland
– Total Radical parotidectomy
– Extended radical parotidectomy
• Submandibular masses : Total
excision of gland
• Sublingual & Minor salivary
gland tumors : Wide local
excison 72

72. MANAGEMENT
Superficial parotidectomy:
• Fundamental Principle
• Facial nerve monitoring
• Frozen section confirmation
• Monobloc clearance
• Neck dissection
• Complications : Facial weakness
Facial anaesthesia
Frey’s syndrome
Salivary fistula
Xerostomia 73

73. MANAGEMENT
SUB MANDIBULAR GLAND:
• FNAC And Frozen section – malignancy
-complete resection +nerves in close
proximity to tumour + suprahyoid LN
dissection.
MINOR SALIVARY GLAND TUMOUR:
Hard palate –partial maxillectomy
74

74. Role of Radiotherapy
• Deep lobe parotid tumors
• Close or positive histologic surgical margins
• Undifferentiated or high-grade histology
• Recurrent malignancy
• Bone or connective tissue involvement
• Metastatic regional cervical lymph nodes
• Perineural involvement
• Intraoperative tumor spillage or capsular rupture
75

75. ROLE OF CHEMOTHERAPY
• Single or multiple regime – adenoid cystic Ca
• Inoperable disease-distant metastasis
• Cisplatin –slow i.v 50-100mg/m2 every 3-4wks
• Doxorubicin –slow i.v,60-75mg/m2 every 3wks
• 5-fluorouracil –12mg/kg/day for 4 days,6mg/kg
i.v on alternate days
76

76. PROGNOSIS
• Survival time – varies widely
• Depends on :
-age and sex
-grade and stage
-histological type of tumour
-method of diagnosis
-type of treatment administered
• 5 yr survival rate –acinic cell tumour 82%
-mucoepidermoid 70%
-adenoid cystic 62%
malignant mixed tumour 56%
77

77. Bibliography
Scott Brown Otorhinolaryngology, Head and Neck surgery, 7th
edition
Cumming’s otolaryngology, head and neck surgery 4th
edition
Gray’s Anatomy, 36th
edition
78

78. Thank you
79