The document provides information on the classification of salivary gland tumors. It begins with an introduction and then discusses the etiology, histogenesis, theories of histogenesis, morphogenesis, genetics, WHO classification from 1972-2017, general features of benign and malignant tumors, problems in clinical diagnosis, investigations including imaging techniques and histopathological investigation. It also provides examples of common tumors like pleomorphic adenoma and adenoid cystic carcinoma. Finally, it briefly outlines the TNM staging system for salivary gland tumors.

1. CLASSIFICATION OF SALIVARY GLAND
TUMORS
Presented by
Dr Preeti Sharma
Dept. Of Oral and Maxillofacial Surgery

2. INTRODUCTION

3. INTRODUCTION

4. INTRODUCTION
Rule
of 80’s
parotid tumors are benign
parotid tumors are
Pleomorphic adenomas
Pleomorphic adenomas
occur in the superficial lobe
of parotid
Out of all salivary gland
Pleomorphic adenomas
occur in the parotid
Untreated Pleomorphic
adenomas remain benign

5. Roma Nirmalkumar et al Clinicopathological study of salivary gland tumors: An
observation in tertiary hospital of central India, International Journal of Research in Medical Sciences .
2015 Jul;3(7):1691-1696 www.msjonline.org
INTRODUCTION

6. ETIOLOGY
• Viruses – EBV(Epstein-barr virus),CMV(Cytomegalovirus)
• Radiation exposure to head and neck region for another medical reason
• Environmental /occupational risks - asbestos, nickel compounds or silica
dust,pesticides
• Lifestyle - Warthin’s tumors showed a strong association with cigarette
smoking.
• Genetic predisposition

7. HISTOGENESIS
• Histogenesis is the formation or development of tissues from the
undifferentiated cells of the germ layers of the embryo.

8. THEORIES OF SALIVARY GLAND TUMOR HISTOGENESIS
1.Multicellular stem
cell theory: Assumes
that each tumor type is
associated with a
specific differentiated
cell of origin within the
salivary gland unit.
Most accepted

9. MORPHOGENESIS
The morphology of salivary gland tumor reflects
the cellular make up of basic ductoacinar unit of
normal salivary gland
DUCTO-ACINAR CONCEPT
A.Tumor composed of both luminal and
myoepithelial cells.
B. Tumor composed of only luminal cells.
C. Tumor composed of only myoepithelial cells/
basal cells.

10. GENETICS IN SALIVARY GLAND NEOPLASMS
• Pleomorphic adenomas – Rearrangement of Chromosomes 3p21, 8q12 and
12q13-15 and presence of PLAG-1 and HMGI-C genes
• Warthin tumour and mucoepidermoid carcinoma - Translocations of
chromosomes 11q21 and 19p13
• Mucoepidermoid carcinoma-Elevated HER-2 gene expression and gene
amplification

11. ONCOGENE SALIVARY GLAND TUMOR
Maml2 MEC,Warthin’s tumor
C-kit/CD117 ACC,lymphoepithelioma-like
carcinoma,myoepithelial carcinoma
HER2/new SDC,ACC,MEC,CXPA
H-ras PA,CXPA,Adenocarcinomas,MEC
PLAGH PA,CXPA
WNT1 PA,CXPA,ACC,MEC,Epithelial
myoepithelial carcinoma
HMGIC/HMGA2 PA
Mdm2 PA,Myoepithelial carcinoma,ACC,CXPA

12. CLASSIFICATION

13. WHO CLASSIFICATION(1972)
EPITHELIAL TUMORS
A.Adenomas C.Acinic cell tumor
Pleomorphic adenomas(mixed tumor) D.Carcinomas
Monomorphic adenomas 1.Adenoid cystic carcinoma
a.Adenolymhoma 2.Adenocarcinoma
b.Oxyphilic adenomas 3.Epidermoid carcinoma
c.Other types 4.Undifferentiated carcinoma
B.Mucoepidermoid tumor 5.Carcinoma in pleomorphic adenoma(malignant mixed
tumor)
NON
EPITHELIAL
TUMORS
UNCLASSIFIED
TUMORS
ALLIED CONDITIONS
A.Benign Lymphoepithelial Lesion
B.Sealosis
C.Oncocytosis

14. REVISED WHO CLASSIFICATION
1991
ADENOMAS
Pleomorphic adenoma Ductal papilloma:a.Inverted ductal papilloma
Myoepithelioma(myoepithelial adenoma) b.Intraductal papilloma
Basal cell adenoma c.Sialadenoma Papilliferum
Warthin tumor Cystadenoma:a.Papillary cystadenoma
Oncocytoma(oncocytic adenoma) b.Mucinous cystadenoma
Canalicular adenoma
Sebaceous adenoma

15. CARCINOMAS
Acinic cell carcinoma Papillary cystadenocarcinoma Small cell carcinoma
Mucoepidermoid carcinoma Mucinous adenocarcinoma Undifferentiated carcinoma
Adenoid cystic carcinoma Oncocystic carcinoma Other carcinomas
Polymorphous low grade
adenocarcinoma(terminal duct
adenocarcinoma)
Salivary duct carcinoma
Epithelial myoepithelial carcinoma Adenocarcinoma
Basal cell adenocarcinoma Malignant
myoepithelioma(myoepithelial
carcinoma)
Sebaceous carcinoma Squamous cell carcinoma
NON-
EPITHELIAL
TUMOURS
MALIGNANT
LYMPHOMAS
SECONDARY
TUMOURS
UNCLASSIFIED
TUMOURS

16. TUMOUR LIKE LESIONS
Sialadenosis
Oncocytosis
Necrotizing sialometaplasia(Salivary gland infraction)
Benign lymphoepithelial lesion
Salivary gland cysts
Chronic sclerosing sialadenitis of submandibular gland (Kuttner tumour)
Cystic lymphoid hyperplasia in AIDS

17. WHO CLASSIFICATION 2005
MALIGNANT EPITHELIAL
TUMOURS
Acinic cell carcinoma Malignant sebaceous tumours Myoepithelial carcinoma
Mucoepidermoid carcinoma Sebaceous lymphadenocarcinoma Carcinoma ex pleomorphic adenoma
Adenoid cystic carcinoma Cystadenocarcinoma Carcinosarcoma
Polymorphous low grade adenocarcinoma Mucinous adenocarcinoma Metastasizing pleomorphic adenoma
Epithelial myoepithelial carcinoma Oncocytic carcinoma Squamous cell carcinoma
Clear cell carcinoma(not otherwise
specified)
Salivary duct carcinoma Small and large cell undifferentiated
carcinoma
Basal cell adenocarcinoma Adenocarcinoma(not otherwise
specified)
Lymphoepithelial carcinoma
Sialoblastoma

18. BENIGN
EPITHELIAL
TUMOURS
BENIGN
SEBACEOUS
NEOPLASMS
DUCTAL
PAPILLOMAS
SOFT TISSUE
TUMOURS
HAEMOTOLY
MPHOID
TUMOURS
SECONDARY
TUMOURS
Pleomorphic
adenoma
Sebaceous
adenoma
Inverted ductal
papilloma
Haemangioma Hodgkin
lymphoma
Myoepithelioma Sebaceous
lymphadenoma
Intraductal
papilloma
Diffuse large B
cell lymphoma
Basal cell
adenoma
Sialadenoma
papilliferum
Extranodal
marginal zone B
cell lymphoma
Warthin tumour
Oncocytoma
Canalicular
adenoma
Cystadenoma

19. WHO CLASSIFICATION OF SALIVARY GLAND
TUMORS 2017
MALIGNANT EPITHELIAL
TUMOURS
Acinic cell carcinoma Sebaceous adenocarcinoma Myoepithelial carcinoma
Secretory carcinoma Intraductal carcinoma Squamous cell carcinoma
Mucoepidermoid carcinoma Cystadenocarcinoma Poorly differentiated carcinoma
Adenoid cystic carcinoma Oncocytic carcinoma Neuroendocrine and non-
neuroendocrine
Polymorphous adenocarcinoma Salivary duct carcinoma Undifferentiated carcinoma
Epithelial myoepithelial carcinoma Adenocarcinoma(not otherwise specified) Large cell undifferentiated
carcinoma
Clear cell carcinoma Carcinoma ex pleomorphic adenoma Small cell undifferentiated
carcinoma
Basal cell adenocarcinoma Carcinosarcoma Lymphoepithelial carcinoma

20. BORDERLINE
TUMOUR
BENIGN
TUMOURS
OTHER
EPITHELIAL
LESIONS
SOFT TISSUE
LESIONS
HAEMATO
LYMPHOID
TUMOURS
Sialoblastoma
Pleomorphic
adenoma
Sebaceous
adenoma
Sclerosing
polycystic adenosis
Hemangioma Extra nodal
marginal zone
lymphoma of
MALT
Myoepithelioma Ductal
papillomas
Nodular oncocytic
hyperplasia
Lipoma/
sialolipoma
Basal cell
adenoma
Lymphadenoma Lymphoepithelial
lesions
Nodular fascitis
Warthin tumour Intercalated duct
hyperplasia
Oncocytoma
Canalicular
adenoma and
other ductal
adenomas
Cystadenoma

21. GENERAL FEATURE OF SALIVARY GLAND TUMORS
BENING
Grow slowly
Usually of long duration
Do not fluctuate in size
Asymptomatic
No ulceration to skin or mucous membrane
Not fixed to overlying skin or mucous
membrane (except palate)
Present a single nodule, Recurrent lesion
may be multi- nodular
No facial nerve palsy, push or compress
adjacent structure rather then invading
Pleomorphic Adenoma. Firm mass
of the hard palate lateral to the
midline.

22. PLEOMORPHIC ADENOMA –PAROTID
GLAND
WARTHINS TUMOR-TAIL OF THE
PAROTID GLAND

23. MALIGNANT
Grow rapidly or history of slow growth
with sudden rapid activity
Regional lymph nodes may be enlarged
Shorter duration than benign Palate and retromolar gland tumors
infiltrate bone,produce radiolucencies and
loosening of teeth
Overlying skin or mucous membrane may
be ulcerated or inflamed
Surface telangiectasia
Fixed to surrounding tissues
Parotid gland tumors associated with facial
nerve paralysis or neurological symptoms

24. Mucoepidermoid Carcinoma. Blue-pigmented
mass of the posterior lateral hard palate
Carcinoma Ex Pleomorphic Adenoma.
Granular exophytic and ulcerated mass
filling the vault of the palate

25. PROBLEMIN CLINICAL DIAGNOSIS
• Tumor arising from salivary gland or adjacent structure:
Angle of mandible lesion(ameloblastoma),chondrosarcoma of atlas vertebrae, enlagement
of parotid lymph node,enlagement of jugulodiagastric lymph node may mimic parotid
tumor.
• Tumor is bening or malignant:
eg: Low grade mucoepidermoid carcinoma shows benign behavior like slow growing ,no
nodal metastasis
Benign metastasizing pleomorphic adenoma shows nodal metastasis.
• If benign then does it have malignant component: eg: Carcinoma ex Pleomorphic
adenoma
• Histologic type

26. INVESTIGATIONS
• Plain radiographs
• Ultrasound scanning
• CT and MRI Scanning
• PET and PET-CT
• Histopathological investigations

27. PLAIN RADIOGRAPH
• Less informative for the diagnosis of
malignancy
• Useful to rule any sailolithiasis
• Gives an idea of bone invasion
• Sialography
-useful to exclude obstructive disease
-should not be done if suspecting malignancy
Ball in hand appearance

28. ULTRASOUND SCANNING
• Modern clinical practice, high-resolution US
examination is commonly used.
• US with color Doppler allows the identification of
even small pathologies within the parotid gland tissue
with the assessment of perfusion pattern as well.
• Able to differentiate malignancy from benign tumors
• Cost effective
• Can be used to guide FNA or core biopsy
• Distinction of fluid-filled versus solid masses

29. • Limitation-
-Resolution of soft tissues is poorer than in CT or MRI
-Cant assess deep lobe of parotid and other deep structures.
• Criteria of description -
Echogenicity (slightly hypoechoic, highly hypoechoic)
Homogeneity (slightly heterogenous, highly heterogenous)
Vascularization
Shape and Margins

30. Mucoepidermoid carcinoma with regular, oval shape,
well-defined margins, highly hypoechogenic, highly
heterogenic, and high vascularization
Adenoid cystic carcinoma with irregular shape, well-defined
margins, highly hypoechogenic, highly heterogenic, and
poor vascularization
Anna Rzepakowska et al 2017,The differential diagnosis of parotid gland tumors with high resolution
ultrasound in otolaryngological practice, Eur Arch Otorhinolaryngol DOI 10.1007/s00405-017-4636-2

31. CT & MRI SCANNING
• CT scanning provides better detail of the surrounding tissues
• MRI superior to CT – MRI demonstrates the mass in greater contrast than CT
Benign - usually margins smooth, with distinct capsule
Low-grade malignancies- can appear benign due to pseudocapsule
High-grade malignancies - have ill-defined infiltrating margins
• MRI – Occasionally to visualize the facial nerve & parotid duct needs
gadolinium enhanced contrast
• Can combined with PET scan to get PET/CT

32. PLEOMORPHIC
ADENOMA
typically solitary, non-
infiltrating and well
demarcated

33. Axial T2-weighted magnetic
resonance image showing a
normal facial nerve (small
arrows) which is seen as a
linear low signal structure.
The retromandibular vein (V)
and external carotid artery (A)
deep (D) and superficial (S)
lobes of the parotid and
mandible (M)

35. PET-CT
• Positron emission tomography (PET) with 2-[fluorine-
18] fluoro-2-deoxy-d-glucose (FDG): used to diagnose,
stage, and restage head and neck cancer .
• FDG PET is more sensitive and specific than CT ,MRI
in the detection of recurrent neoplasm.
• FDG uptake in normal structures may confuse
interpretation and lead to false-positive results .
• FDG uptake in primary neoplasms is usually greater
than metabolically active normal structures

36. • The parotid and submandibular glands normally demonstrate mild to
moderate symmetric physiologic uptake in some cases they may
demonstrate little or no uptake.
• Asymmetric uptake can be seen in patients who have undergone surgical
removal of one of the glands or in patients with primary or metastatic
lesions to the glands.
• Benign and malignant parotid tumors cannot be distinguished with PET-CT
alone because of high false-positive rates .

37. David Hadiprodjo et al 2011,Parotid Gland Tumors: Preliminary Data for the Value of FDG PET/CT
Diagnostic Parameters, DOI:10.2214/AJR.11.7172

38. HISTOPATHOLOGICAL INVESTIGATION
• Ultimately biopsy and excision is needed for the definitive diagnosis
FINE NEEDLE ASPIRATION
• Sensitivity : More than 95%
• 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
- metastasis or a primary tumor

39. 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 tumor if FNAC
fails.

40. Adenoid cystic carcinoma
with cribriform pattern in
cystic spaces (Swiss
cheese pattern)
Warthin’s tumor with double layered oncocytic
epithelium

41. FNAB of pleomorphic adenoma (PA). (A) A typical FNAB case of PA with
fibrillar myxoid matrix and numerous myoepithelial cells. (C) The tumor
cells in PA show moderate to strong nuclear immunostaining for PLAG-1,

42. • TNM STAGING OF SALIVARY GLAND
Primary tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor ≤2 cm in without extraparenchymal extension*
T2 Tumor >2 cm but not more than 4 cm without extraparenchymal extension*
T3 Tumor >4 cm and/or tumor having extraparenchymal extension*
T4 Moderately advanced or very advanced disease
T4a Moderately advanced disease : Tumor invades the skin, mandible, ear canal, and/or facial nerve
T4b Very advanced disease:Tumor invades skull base and/or pterygoid plates and/or encases carotid artery
*Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues. Microscopic evidence alone does not constitute extraparenchymal extension for
classification purposes.

43. Regional lymph nodes (N) : Clinical N (cN)
NX Regional nodes cannot be assessed
N0 No regional lymph node metastasis
N1
Metastasis in a single ipsilateral lymph node ≤ 3 cm
in greatest dimension and ENE (-)
N2a
Metastasis in a single ipsilateral lymph node > 3 cm
but not more than 6 cm and ENE (-)
N2b
Metastasis in multiple ipsilateral lymph nodes, none
> 6 cm and ENE (-)
N2c
Metastasis in bilateral or contralateral lymph nodes,
none > 6 cm in greatest dimension and ENE (-)
N3
Metastasis in a lymph node > 6 cm and ENE (-); or
metastasis in any node(s) with clinically overt ENE
(+)
N3a Metastasis in a lymph node > 6 cm and ENE (-)
N3b
Metastasis in any node(s) with clinically overt ENE
(+)
Pathological N (pN)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node ≤ 3 cm and ENE (-)
N2a
Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest
dimension and ENE (+);
or a single ipsilateral lymph node > 3 cm but not more than 6 cm in greatest
dimension and ENE (-)
N2b Metastasis in multiple ipsilateral lymph nodes, none > 6 cm and ENE (-)
N2c
Metastasis in bilateral or contralateral lymph node(s), none > 6 cm and ENE
(-)
N3 N3a,N3b
N3a Metastasis in a lymph node > 6 cm in and ENE (-)
N3b
Metastasis in a single ipsilateral node > 3 cm and ENE (+);
or multiple ipsilateral, contralateral, or bilateral nodes, any with ENE (+);
or a single contralateral node of any size and ENE (+)

44. Distant metastasis (M)
cM0 No distant metastasis
cM1 Distant metastasis
pM1
Distant metastasis, microscopically
confirmed
Stage T N M
0 Tis N0 M0
I T1 N0 M0
II T2 N0 M0
III
T3 N0 M0
T0–T3 N1 M0
IVA
T4a N0–N1 M0
T0–T4a N2 M0
IVB
T Any N3 M0
T4b N Any M0
IVC T Any N Any M1

45. Extraoral view : swelling over the
left mandibular angle and
submandibular region
Intraoral view : swelling in the
oropharyngeal region causing
dysphagia
coronal scan : swelling located in
the left parapharyngeal space
displacing the tongue medially
CASE REPORT
Deep lobe parotid gland pleomorphic adenoma involving the parapharyngeal space
Yadavalli Guruprasad et al (2012)
Website: www.mjdrdypu.org DOI: 10.4103/0975-2870.97518

46. sagittal scan :swelling located in
the left parapharyngeal space
displacing the tongue medially ,
obliterating oropharynx
axial scan : extension of
swelling from deep lobe of
parotid into the left
parapharyngeal space
Cytopathology : (H&E
×100) confirmed
pleomorphic adenoma

47. Tumor grade-based management
strategy for salivary gland tumors
Jeon yeob jang et al , Treatment outcomes in
metastatic and localized high-grade salivary
gland cancer: high chance of cure with surgery
and post-operative radiation in T1–2 N0 high-
grade salivary gland cancer, BMC Cancer
volume 18, Article number: 672 (2018)

48. PROGNOSIS
• The major determinants of survival: tumor type, grade & clinical stage.
• Poor prognostic factors include : -
- high grade malignancy
- locally advanced disease, associated pain, neural involvement
- regional lymph node metastases
- distant metastasis
- advanced age

49. • Overall 5-yr.survival for all stages & histologic types is approximately 62%
• (stage I –II-93%,stage III – 67%, satge IV- 37%)
• 20% of all patients will develop distant metastases.
• The presence of distant metastases has a poor prognosis, survival rate is 4-8
months(approx.)

50. DIFFERENTIAL DIAGNOSIS
Mucocele
Swelling caused by pooling
of saliva at the site of
severed or obstructed minor
salivary duct
Common site-lowerlip,
Types-mucous extravasation
cyst-truma,Mucous
retention cyst-obstruction
Ranula
Special type of mucocele
occurs on floor of the
mouth due to trauma to
submandibular or
sublingual duct
Rsembles the belly of
frog
CT-Lymphoepithelial
cyst
pleomorphic adenomas,
mucoepidermoid
carcinomas, or
Warthin’s tumors may
appear cystic on
imaging

51. Sialoadenitis
Painfull swelling of of
salivary gland due to
bacterial,viral,allergic
reactions
Most commonly -parotid
Mumps
viral non suppurative condition
due to paramyxo virus
Fever, chills, headache, and
preauricular pain occur 1 to 2
days before unilateral or
bilateral swelling of the parotid
glands that may last between
5 and 10 days.
Necrotizing sialometaplasia:
reactive non-neoplastic
process most commonly involving
the minor salivary glands of the
palate
Non inflammatory/autoimmune
condition
Male -5th to 6th decade of life

52. REFERENCE
• Shafer’s ,Textbook of oral pathology , 8th edition.
• Peterson’s ,Principle of oral and maxillofacial surgery,3rd edition
• Naville ,Oral and maxillofacial pathology, 4th edition
• Histogenetic and Morphogenetic Concepts of Salivary Gland Neoplasms, Ajay Kumar Jagdish et
al, International Journal of Science and Research (IJSR)ISSN (Online): 2319-7064 ,Impact
Factor (2012): 3.358
• WHO classification salivary tumors: What's new? An update on Histopathology of Salivary
Gland Tumors,La Spezia, Italy, Oct 18-20, 2017
• The American Joint Committee on Cancer (AJCC) tumor/node/metastasis (TNM) classifications
for cancer of the major salivary glands.
• Internet sources