2. Salivary gland
• Major salivary glands:- a. Parotid gland b. Submandibular
gland c. Sublingual gland
• Minor salivary gland 600 – 1,000 minor salivary gland
distributed throughout the mucosa of the upper
aerodigestive tract (most common in the soft and hard
palate).
• Malignant neoplasms of constitutes large collection of highly
heterogeneous tumors that exhibit a wide spectrum of
biologic behaviour, ranging from slow growth & indolence to
highly aggressive behaviour & rapid fatality.
• Malignant tumors of the salivary gland are relatively
infrequent.
• Cure rates are very poor for most histological types.
3. Surgical Pathology
• Salivary gland tumors are relatively rare 2.5-3/100,000/yr.
• Account for 5% of HNF malignancies.
• 70-90% salivary tumors in parotid gland.
• Malignant parotid tumors: Mucoepidermoid Ca. > Ca ex
pleomorphic adenoma > Acinic cell Ca > Adenoid cystic Ca.
• Malignant submandibular gland tumors: Adenoidcystic Ca. >
Mucoepidermoid Ca. Nerve involvementHypoglossal N >
Trigeminal Nerve > Facial Nerve.
• Intraoral salivary tumors are mostly benign Comman
malignant tumors are Mucoepidermoid Ca. > Adenoid cystic
Ca. > PLGA Palate is the MC site.
• Minor salivary tumors F>M Except adenoidcystic Ca.
( M=F)
• Sublingual gland tumors Rare MC adenoidcystic Ca.
4. General features of salivary gland tumors in adults &
children
ETIOLOGY
1) Smoking, 2) Alcohol consumption,
3) Ionizing radiations 4) Aflatoxins (mainly Aflatoxin B1),
4) Diet 5) Race mainly Eskimos
7) EBV infection. 8) Altered humoral immunity.
Polyunsaturated fatty acids (PUFA) seem to exert a beneficial
effect.
Adults Childrens
Occurs primarily in older adults. Rare in general. (only 1.7-3%)
F>M except Warthin tumor & high grade Ca. InfantsHaemangioma & Lymphangioma
MC
Older children Epithelial tumors MC
Epithelial (80%) tumors predominates. Malignant tumors are comman (60%) among
the epithelial tumors.
Benign tumor are more comman (75%)
epithelial tumors.
Most malignant tumors are low grade.
Smaller the salivary gland, higher the
proportion of malignant tumors
Tumor mortality & morbidity are low.
5. THE CELL & MOLECULAR BIOLOGY
•PCNA (proliferating cell nuclear antigen)
immunoreactivity is high in malignancy.
•ki67 antibodies Provides a useful diagnostic tool.
•Ki67 Has prognostic significance in Adenoid Cystic Ca.
•Bcl2 & apoptotic index Good prognostic markers.
•Bax is proapoptotic, decreased Bcl2 & increased Bax
leading to increased apoptosis.
•Cytokeratin14 is over expressed
•Fibroblast growth factor (FGF) 1 and 2 over expressed.
•NO has tumour promoting activity Inducible nitric
oxide synthase plays important role in tumourogenesis.
6. Increased VEGF may be associated.
METALLOTHIONEIN May be a marker of
differentiation in malignant salivary tumours.
Increased Estrogen & progesterone receptors.
Mucoepidermoid Carcinoma Positive for a variety of
Cytokeratin & also Vimentin, α1 Antichymotrypsin, S100,
Leu N1.
Adenoid Cystic Ca Ki67 antibody, p53
Mdm2 raised
Viruses implicated include HHV8, HPV, CMV
7. Cellular origin for salivary gland tumour
• Clear understanding
• Two major theories of histogenesis
1) The bicellular reserve cell theory
2) The multicellular theory
The Bicellular reserve cell theory
• Basal cells of the excretory or intercalated duct can acts as a
reserve cell with the potential for differentiation into a variety
of intercalated cells.
• Excretrory duct cell:-
1) Squamous cell carcinoma 2) Mucoepidermoid carcinoma
• Intercalated duct cell:-
1) Mixed tumours, 2) Warthin tumour
3) Oncocytoma, 4) Adenoid cystic carcinoma
5) Oncocytic carcinoma
8. The multicellular theory
• Salivary neoplasm arise from already differentiated cells along the
salivary gland unit.
1) Oncocytic tumours Striated ductal cells
2) Acinous cell tumour Acinar cell
3) Sq & mucoepidermoid Excretory ductal cell
4) Mixed tumour Intercalated ductal cell & myoepithelial cells
9. WHO CLASSIFICATION BY SOBIN &
SHEIFERT
• 7 Categories: 1) Adenomas, 2) Carcinomas
3) Malignant melanoma 4) Non epithelial tumours
5) Secondary tumour 6) Undifferentiated tumours
7) Tumour like lesions
• Histologically, carcinomas are probably best classified as below
1) Acinic cell Ca. 2) Mucoepidermoid Ca.
3) Adenoid cystic Ca. 4) Adenocarcinoma
5) Polymorphous low-grade adenocarcinoma
6) Papillary cystadenoCa. 7) Squamous cell carcinoma
8) Mucinous adenocarcinoma
9) Carcinoma ex pleomorphic adenoma;
10) Malignant mixed tumour;
11) Undifferentiated carcinoma.
10. MUCOEPIDERMOID CARCINOMA
• Stewart, Foote & Becker- 1945
• Mucus secreting cells & epidermoid cells epithelial type.
• Most common malignant salivary gland tumor in adult &
childrens 29 – 34%
• Parotid gland MC involved. (80-90%), Intraorally MC Palate
Pathogenesis-: 1) Entrapment of retromolar mucous glands within
the mandible Neoplastic transformation. 2) Developmentally
Remnants of the submaxillary gland within mandible 3) Neoplastic
transformation of the mucus secreting cells
C/F:- 1) Appears as asymptomatic swelling, F>M 3rd -5th decade.
2) Aware of lession for yr or less. 3) Fluctuant & blue/red color.
11. Low grade malignancy
1) Slowly enlarging, painless, <5mm
2) Not comp. encapsulated
3) Often contain cyst with viscoid,
high ratio of mucous cells
4) Closely resembles to mucocele
5) Intraoral lessions buccal
mucosa, tongue, retromolar area
6) C/S:- solid white mass
High grade malignancy
1) Grows rapidly with pain & infiltrate
2) FN palsy Parotid tumors
3) Trismus, ear drainage, dysphagia,
ulceration & numbness of adj. area
4) Metastises to regional LN
5) Lung, bone, brain metastasis
6) C/S - mucinous fluid & high ratio of
epidermoid cells
Histologically:- Three cell type :-
1) Epidermoid cell,
2) Mucus cell
3) Intermediate cell
13. • Low-grade tumours 5 yr survival of 96% & high-grade tumours
Asso. with a death rate 10 times this.
• The extent & grade of a tumour dictate the treatment.
•TREATMENT :-
• 1) For the most favorable tumours Superficial parotidectomy
with facial nerve preservation, if possible,
• 2) Radical excision is necessary for pts with large &/or high-grade
lesions.
• 3) Asso. elective ND to include level 2 & 3 for the
No neck would also be appropriate.
• 4) With more severe neck disease RND.
• 5) High grade tumours Require post op RT.
14. ADENOID CYSTIC CARCINOMA
• Slow growing, aggressive neoplasm. 2nd MC malignant tumor.
• Slow-growing mass (tumour doubling time around an year)
• 10%- non sq Ca in H & N. , 15%- all salivary gland neoplasm
• Comman malignant tumor- submandibular, sublingual & minor
salivary , 2/3rd – occurs in minor salivary glands.
• C/F:- 1) MC seen in females 5th-6th decade. Local recurraance
comman (30-50%).
• 2) Parotid, submaxillary, acc. palate & tongue gland- MC involved.
3) Early local pain (surface ulceration), FN palsy, local invasion &
fixation to deeper structure. LN metastasis 10%-30%.
4) Tendancy to spread through perineural spaces (20%-30%)
• C/S :- Solid and well-circumscribed but unencapsulated.
15. • Perineural spread 50% Axial & circumferential pattern along
the involved nerve & furthur spread can occur- antegrade &
retrograde fashion.
• Commanly involved nerves- Facial nerve, mandibular & maxillary
nerve Pathway for invasion of the skull base
• Tumor cell may reach trigeminal..pterigopalatine ganglion &
cavernous sinus.
• Spread along Haversial canal of bone with little bone erosion.
• More frequent- advanced, recurrent & high grade tumors.
16. 3 Histological types Cribriform(40%) > Solid(25%) > Tubular (20%)
• Solid Variant Worst prognosis, rarely cured & 100% recurrence
seen at primary site at 30 yrs.
• Distant metastases, particularly to the lung is characteristic. 70
% at 5 yrs and 100 % at 10 yrs.
• IOC:- MRI of the primary site & CT scans of the lungs and liver and
an isotope bone scan.
1) Sweese cheese pattern
2) Basaloid epith. cell nests
3) Intermediate prognosis.
1) Basaloid pattern
2) Sheets of cells with few
or no luminal spaces
3) Worst prognosis
4) Least comman
1) Trabecular
2) More glandular
architecture
3) Best prognosis
17. •TREATMENT:-
1) Radical primary surgery Best survival rates at 20 yrs.
2) Postoperative irradiation Integral part of treatment.
3) No prophylactic neck dissection required (like in
mucoepidermoid ca)
4) Limited role of chemotherapy Cisplatin + Doxorubicin.
5) Skip lesions in the facial nerve Frozen section and on later
paraffin section histology, certainly take place.
6) If gross or frozen section histology involvement of a nerve is
found at operation, the nerve should be sacrificed & an
immediate nerve graft carried out in the case of the facial nerve
18. CARCINOMA EX PLEOMORPHIC ADENOMA
(Malignant mixed tumor)
• 2nd MC parotid gland tumor Malignant form of pleomorphic Ca.
• Primary malignant tumor involving both epithelial and mesenchymal
element of the mixed tumor
• Pre-exicting benign mixed tumor
• Typical history of slowly growing mass demonstrating sudden increase
in the growth,
• Tumor Patterns:- 1) Noninvasive,
2) Minimally invasive:- < 1.5 mm penetration of the malignant
component into extracapsular tissue
3) Invasive:- > 1.5 mm of invasion from the tumor capsule into
adjacent tissues.
19. • 3 type:- 1) Ca. in pleomorphic adenoma 2) Carcinosarcoma.
3) Metastasing peomorphic adenoma
• Cervical metastasis Pain
• Malignant transformation Men > 40 years , tumours of the deep
parotid lobe, solitary nodules >2 cm diameter & patients with a h/o
a previous operation.
TREATMENT:-
Aggressive Tumour
1) Total parotidectomy with facial nerve conservation is ideal
2) facial nerve is sacrified if involved.
3) Post operative radiotherapy is must.
4) Invasion of <1 cm 5 yr survival approx 100%
5) Invasion of >1 cm 5 yr survival is halved. Poor prognosis.
20. Acinic cell carcinoma
• Shows serous acinar cell differentiation characterized by
cytoplasmic zymogen secretory granules.
• 3rd most comman malignant Ca. of parotid gland.
• Low malignancy. M:F=3:2, mainly in middle ages (44yrs)
• Tumor may be multifocal or B/L.
• Clinically – Painless lump, resembles pleomorphic adenoma in
gross appearance.
• Encapsulated & lobulated. Chiefly occurs Parotid (80%)
• Most comman intraoral site Lips & buccal mucosa
• Slowly growing, mobile or fixed mass of variable duration.
21. Histological pattern:-
•Local recurrence & distal metastasis.
•Has the best survival rate of any salivary cancer
•Excision of a facial nerve is not justified unless it is
grossly involved.
•It is regarded as at the more benign end of the spectrum
of malignant salivary disease.
Microcystic follicular Papillary cystic Solid
22. Polymorphous Low-Grade
Adenocarcinoma
• Synonyms:- Terminal duct carcinoma, Lobular carcinoma.
• Characterized by cytologic uniformity, morphologic diversity, an
highly infiltrative growth locally, and low metastatic potential.
• 2ND most common malignant intraoral tumor of the salivary
glands. Palate (60-70%) > buccal mucosa (16%) > upper lip,
retromolar area, base of tongue.
• F:M = 2:1 & comman in 5th to 7th decade.
• A painless mass in the palate is the most common presentation.
• Gross - firm, circumscribed, but non-encapsulated, yellow tan
lobulated nodule, average size 2.2cms.
• Characteristic infiltrative growth.
23. • The main microscopic patterns are:- 1) lobular 2) papillary or
papillary–cystic 3) Cribriform areas, sometimes resembling those
in adenoid cystic carcinoma; and 4) trabecular or small, ductlike.
• Variability of growth pattern is the most consistent architectural
feature of the tumor
Low power view showing
histologic diversity within
the tumor. Mainly solid and
tubular growth patterns
with focal cribriform and
papillary areas
Papillary configurations of
columnar or cuboidal cells
Polymorphous low-grade
adenocarcinoma
‘‘Indian-file’’ growth
pattern
D/D:- 1) Pleomorphic carcinoma
2) adenoid cystic carcinoma
24. Squamous cell carcinoma
• Primary salivary gland SCC is very rare(<1%)
• The tumour must arise from the gland itself and not from lymph nodes
within the gland.
• There must be no regional or adjacent tumour especially of the skin
• Parotid (80%), submandibular gland(20%)
• Age : 60 to 65years, M:F= 2:1.
• History of previous radiotherapy.
• Risk factors for locoregional metastasis from cutaneous Sq. cell Ca
1) Tumor location in the area of the forehead, temples, eyelids,
cheek, and auricle
2) Resection of the tumor without healthy margins, with narrow
safety margins (tumor recurrence)
3) Tumor size >1.5 cm dia 4) Tumor thickness > 4mm
5) Low differentiation of tumor 6) Perineural invasion
7) Patientʼs age (> 70 years) 8) Immunosuppression
25. Salivary duct carcinoma
• An aggressive adenocarcinoma which resembles high-grade
breast ductal carcinoma”
• Consist of solid, papillary cystic, and cribriform patterns.
• M>F, after 50 years of age.
• Site- parotid(~80%).
• Present with a rapidly enlarging parotid mass associated with
facial nerve palsy , pain and cervical lymphadenopathy.
• Differential Diagnosis :
1) Metastasis : Breast
2) Oncocytic adenocarcinoma
3) High grade mucoepidermoid Ca.
4) Papillarycystic acinic cell ca
5) Cystadenocarcinoma.
26. Secondary (metastatic) tumors
• Hematogenous metastasis – lung, kidney & breast
• Parotid gland most comman site
• Lymphatic spread from cutaneous malignancy of head & neck
• <10% -Malignant parotid tumors,40%-melanomas,40% -Sq. cell ca.
• 2/3rd of metastatic sq. cell Ca to parotid occurs within 1st yr after
T/t of the primary skin cancer.
28. TNM classification of carcinomas of the major
salivary glands
• Tx = Primary tumor cannot be
assessed
• T0 = No evidence of primary tumor
• T1 = Tumor < 2 cm, no
extraparenchymal extension
• T2 = Tumor > 2 cm, < 4 cm, no extra
parenchymal extension
• T3 = Tumor > 4 cm or
extraparenchymal extension (or
both)
• T4a = Tumor invades skin,
mandible, ear canal, facial nerve, or
any of these structures
• T4b = Tumor invades skull base or
pterygoid plates, or encases
carotid artery
• N0 =No cervical nodes
metastasis
• N1 =Single I/L LN < 3 cm
• N2a =Single I/L LN >3cm & ≤ 6cm
• N2b =Multiple I/L LN metastases,
each ≤ 6 cm
• N2c = B/L or contralateral LN
metastases, each ≤ 6 cm
• N3= Single or multiple LN
metastases > 6 cm
• MX =Distant metastases cannot
be assessed
• M0 =No distant metastases
• M1 =Distant metastases present
29. Evaluation of patient
A] History:- Important points in the history:
1) Mass (duration, rate of the growth, presence of pain)
2) Facial paralysis, B/L 3) Cervical lymphadenopathies
4) Eyes and joints symptoms 5) H/O exposure to radiation
6) Ipsilateral weakness or numbness of tongue
B] Examination:-
1) Size of the mass 2) Overlying skin, Skin fixation, mobility
3) Lymphadenopathies 4) Cranial nerves essp. CN V,VII,
30. C] Investigations:-
1) Plain X ray 2) X ray chest To R/O secondaries.
3) OPG To R/O mandibular involvement.
4) Open biopsy Rarely used due to risk of recurrence & FN
damage Useful HP guidance for use of palliative CTRT,
poor surgical candidate, obvious malignancy.
5) Sialography:-
a) C/I:-Acute infection, Iodine allergy, Multiple myeloma.
b) Limitation:- Mass < 2mm, Deep lobe pathology.
6) Radiosialography Tc99 To detect mass lession &
parenchyma function No use in ductal system study.
7) Color doppler sonography Noninvasive Evaluates
vascular anatomy.
8) PET Differentiate benign from malignant lessions.
31. Main investigations
9] FNAC:-
1) Accuracy95-98%
2) Diff benign from malignant dis.
2) The key to successful FNAC is
immediate evaluation of the
specimen for adequacy.
10] Ultrasound:- 1) Ideal tool for the initial assessment of
superficially located tumors of the parotid and submandibular
gland Distinguish intrinsic from extrinsic neoplasm
2) USG f/o malignant tumors include
ill-defined margins,
heterogeneous architecture,
subcutaneous invasion,
& the presence of LN metastases.
32. 11] C.T. & MRI:- 1) Effective modalities for imaging the size, the
local, and the regional extension of the primary tumor and the neck
metastasis & to differentiate intra from extra glandular mass.
2) CT IOC for subtle cortical involvement & bone destruction.
3) MRI IOC for bone marrow invasion.
3) MRIIOC for detecting perineural spread.
4) Contrast-enhanced MRI IOC for intracranial invasion.
T1-weighted MRI shows enlargement & enhancement
of the rt mandibular nerve (thick arrows), extending
into the foramen ovale. Histology confirmed
perineural spread. The normal lf mandibular nerve
(short arrows) noted forcomparison.
MRI of adenoid cystic carcinoma
arising in the deep lobe
of the right parotid gland.
Disadvantage Of MRI :- 1) Less sensitive in cystic lessions.
2) Inability to detect calcification.
33. • C.T. saliography
• Quantitative DCE-MRI, DW-MRI, and MRS New & evolving
techniques for differentiating between benign and malignant
salivary gland neoplasms.
• FDG-PET/CT For local extent of the tumor and to detect
locoregional & distant metastases.
• Stage T N M
• I T1 N0 M0
• II T2 N0 M0
• III T3 N0 M0
• T1-3 N1 M0
• IVa T1-3 N2 M0
• T4a N0-2 M0
• IVb T4b Any N M0
• Any T N3 M0
• IVc Any T Any N M1
Prognostic factors
1) Histopathological daignosis
2) Facial nerve paralysis
3) Skin involvement
4) Stage
5) Location
6) Incedence of recurrence
7) Distant metastasis
8) Radiotherapeutic sensitivity
9) Chemotherapeutic sensitivity
36. UNTREATED
RESECTABLE
Clinically benign <4cm
(T1, T2)
Clinically suspicious of
cancer >4cm or deep lobe
Complete surgical excision
Benign
Low grade
mucoepidermoid
Intermediate
or high grade
Follow up RT
CT/MRI
Base of the skull
or clavicle
Consider FNA
Surgical
resection
Benign
Cancer Follow up
Superficial lobe Deep lobe
N0 N+ N0 N+
Parotidectomy
Parotidectomy +
comprehensive
neck dissection
Total
Parotidectomy
Total Parotidectomy
+ comprehensive
neck dissection
37. INCOMPLETELY
RESECTED
H & P
CT/MRI
Pathology
Review
Negative Physical
Exam + imaging
Gross residual disease on physical
examination or imaging
Adjuvant RT
Follow up
Surgical Resection
if possible
Non Surgical
resection possible
Adjuvant RT Definitive RT
Follow up
38. CANCER
SUPERFICIAL LOBE
DEEP LOBE
Completely excised Pariotidectomy
No adverse
characteristics
Adverse characteristics
Incompletely excised
gross residual disease
No further surgical
resection possible
Adjuvant RT Definitive RT
Surgery ± adjuvant RT
RT if feasible or clinical
trial or single agent
chemotherapy or best
supportive care
Rescetable
Not
Rescetable
Chest X-ray
annually TSH
annually if thyroid
irradiated
Physical examination
year 1 (every 1-3 mon)
year 2 (every 2-4 mon)
yr 3-5 (every 4-6 mon)
≥5 (every 6-12 mon)
39. SURGICAL MANAGEMENT OF PARAPHARYNGEAL
SPACE SALIVARY GLAND NEOPLASMS
PARAPHARYNGEAL SPACE
Primary salivary gland
neoplasm
Parotid neoplasm that extend
from the deep lobe
Transcervical submandibular
approach
Superficial parotidectomy with facial
nerve identification resection of deep
lobe and paraharyngeal tumor
a) Massive or recurrent benign neoplasms and invasive malignant
neoplasm – Anterior mandibulotomy and mandibular swing.
b) Complete tumor excision – Transcervical transoral approach
41. T/t modality depending upon grading
• Excision of the tumor with cuff
of a normal tissue.
• Facial nerve is preserved.
• Regional lymph node evaluated
at the time of surgery.
• No post-op radio therapy
unless the resection margin is
not clear
• Total parotidectomy with
excision of the first node
(digastric & submandibular
nodes).
• Facial nerve involvement:
A) Patient with facial paralysis
pre-op. Resection of the facial
nerve with primary grafting.
B) Patient with normal facial
function pre-op. Resect the
tumor of the facial and post-
operative wide field radiation.
Group 1: T1 and T2NO low-grade
malignancy Low grade
epidermoid tumour, acinic cell ca.
Group 2: T1 and T2NO high-
grade malignancy
42. • Radiacal parotidectomy
(sacrifice Of CN VII with
immediate reconstruction)
• Modified radical neck
dissection
• Wide field PORT.
• Radical parotidectomy with
MRND and resection of masseter
muscle, part of the mandible or
mastoid or ear canal as required.
• Resection of the facial nerve with
the tumor and primary grafting.
• Followed by wide field PORT.
Group 3: T3NO or any N+ high-
grade or recurrent cancer
Group 4: Include all T4 tumor
T1 & T2
LOW GRADE
T1 & T2
HIGH GRADE
STAGE T3 STAGE T4
Submandibular gland
excision
1) Wide excision
2) Preserve nerve
unless involved
2) PORT
1) Wide excision
with neck
dissection
2) PORT
1) Surgery to fit
extent of disease
2) PORT
43. Indications of PORT
1) High-grade tumor 2) Deep lobe cancers
3) All T3 and T4 cancers
4) Recurrent disease 5) Documented LN metastasis
6) Extraparotid extension 7)Gross/microscopic residual disease
8) Tumor involving or close to the facial nerve
Indications of neck dissection
1) Clinically cervical Lympadenopathies (15%).
2) Parotid tumor bigger than 4cm Occult metastasis risk >20%.
3) High grade malignancy Occult metastasis risk >25%.
44. Chemotherapy Treatment
• Useful in pallation & in inoperable cases.
Combination regimen have not proven better results
AdenoCa. like tumors i.e.
Adenoid cystic Ca.,
Acinic cell Ca.,
Ca. ex polymorphic Ca
Epidermoid like tumor
i.e.
Sq. cell CA
Mucoepidermoid Ca.
Adriamycine
Cisplatinum
5-flurouracil
Methotrexate
Cisplatin
2 groups
45. Points to remember in parotid surgery
A] Pre-op evaluation: Patient general condition, all routine
investigation
B] Consenting patients for possible facial weakness.
C] Operating in bloodless field by:
1) Hypotensive technique 2) Head end elevation
3) Delicate tissue handling 4) Proper hemostasis
D] Using facial nerve monitoring during operation and at the end of
operation.
E] Exposure of the eye and the operative side of the face.
F] Modified Blair’s incision. G] Landmark for the facial nerve
Acute Late
Facial nerve palsy Sensory deficit
Bleeding or hematoma Cosmetic deformity
Seroma Frey’s syndrome
Salivary fistula
COMPLICATIONS
OF PAROTID
SURGERY
46. Facial nerve marker
during surgery
• .
2) Posterior belly of digastric muscle:-
The facial nerve is superior to the upper
border of the belly of the digastric muscle
1) Tragal cartilage (pointer):- always
point to the facial nerve. The facial nerve is 1
cm. inferior &1cm. medial to the pointer
47. 4)Retrograde inferior approach to the
facial nerve:- The lower branch of the facial
nerve invariably can be found immediately
ext to the post. facial vein as it exits the
lower pole of the parotid gland.
3)Tympanomastoid fissure – FN is
4 mm inferior to the
tympanomastoid fissure as it exit
from the stylomastoid foramen.