Salivary gland tumors classification

classification of 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. Factors which determine the histologic pattern of the tumour that is central to the categorisation of the salivary gland tumours are: The tumour cell organisation The tumour cell type or types of differentiation The materials synthesised by the cells Their placement within the tumour

11. 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

12. 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

13. CLASSIFICATION

14. 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

15. 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

16. 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

17. 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

18. 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

19. BENIGN EPITHELIAL TUMOURS BENIGN SEBACEOUS NEOPLASMS DUCTAL PAPILLOMAS SOFT TISSUE TUMOURS HAEMOTOLYMPHOID 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

20. 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

21. BORDERLINE TUMOUR BENIGN TUMOURS OTHER EPITHELIAL LESIONS SOFT TISSUE LESIONS HAEMATOLYMPHOID 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

22. 2017 WHO Classification of salivary tumors; conclusions Includes new entities, such as MASC(Mammary analog secretory carcinoma)/Secretory carcinoma Included “Other epithelial lesions” Improved the section on “undifferentiated and neuroendocrine carcinomas“ Improves the section on “low-grade SDC“ by including “ intraductal carcinoma “

23. 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 .

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

25. 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

26. 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

27. PROBLEM IN 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

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

29. 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

30. ULTRASOUND SCANNING M odern 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

31. 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

32. 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

33. Echohomogenicity and increased vascularity were proven as the most reliable features for defining the malignant character of a lesion T he diagnostic accuracy of US in distinguishing malignant from benign tumors was satisfactory 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

34. 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

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

36. 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)  

37. 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

38. 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 .

39. 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

40. 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

41. 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) b ut can be done for minor salivary gland tumor if FNAC fails .

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

43. 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,

44. 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.

45. 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 (+)

46. Distant metastasis (M) cM0 No distant metastasis cM1 Distant metastasis pM1 Distant metastasis, microscopically confirmed Stage T N M 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

47.   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

48. 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

49. 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)

50. 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

51. 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.)

52. differential diagnosis Mucocele Swelling caused by pooling of saliva at the site of severed or obstructed minor salivary duct C ommon site- lowerlip , T ypes-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

53. 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 -5 th to 6 th decade of life