Salivary gland tumors

easily understandable

1. Tumors of salivary glands Dr.Madhusudhan reddy

2. Anatomy and histology 3 pairs of major salivary glands. Other locations include lateral margins of tongue, palate, lips, buccal mucosa. Seromucous glands of nasal cavity, larynx and bronchi histologically similar to minor salivary glands

3. The fundamental structure of all salivary glands is the acinar-ductal unit . Acini are variably composed of serous or mucous cells or both. Ductal unit include Striated duct Intercalated duct Excretory duct Acini and intercalated ducts are surrounded by myoepithelial cells . Preservation of the lobular architecture is an important feature favoring a diagnosis of a non- neoplastic process over a tumor.

4. Myoepithelial cells: Physiologically and functionally modified epithelial cells . Possess a duel epithelial and smooth muscle phenotype. Produce extracellular matrix . Anti-invasive effect in neoplasms by promoting epithelial differentiation, secreting protinase inhibitors and supressing angiogenesis. Basal cells: Maintain multidirectional differentiation and play a role in the process of regeneration and metaplastic changes.

5. Introduction Tumors of the salivary glands are: Most heterogeneous group of tumors . Greatest diversity of morphologic features. Relatively uncommon. The majority of these neoplasms are benign 80% and only 20% are malignant . The various types of salivary gland tumors are best distinguished by their histologic patterns.

6. Epidemiology Uncommon neoplasms 2%-6.5% of all head and neck neoplasms . Global annual incidence varies from 0.4-13.5 cases per 100000 people. Most salivary gland tumors originate in the parotid glands (64%-80%) , malignancy (15%- 32%). 7-11% occur in the submandibular glands , malignancy (37%- 45%). less than 1% in the sublingual glands , malignancy (70% 90%)

7. 9%-23% in the minor glands. Benign tumors account for 63% to 78% of all salivary gland neoplasms . Most common benign tumor : Pleomorphic adenoma -53%-77% of all cases occurs in parotid glands. Warthin’s tumor - 6%-14% of all cases Most common malignancy- Mucoepidermoid carcinoma .

8. Most common minor salivary gland tumor site: Palate, (42%- 54%). The proportion of malignant tumors varies significantly by site and is the greatest in the sublingual glands, tongue, floor of the mouth, and retromolar area. Most common among children: Mucoepidermoid carcinoma .

9. RULE OF 80S 80% of parotid tumors are benign 80% of parotid tumors are Pleomorphic adenomas 80% of salivary gland Pleomorphic adenomas occur in the parotid 80% of parotid Pleomorphic adenomas occur in the superficial lobe 80% of untreated Pleomorphic adenomas remain benign

10. Etiology Viruses- EBV, CMV, Polyoma virus , Ionizing radiation . Increased occupational risks- asbestos, nickel compounds or silica dust. Employment in the woodworking, rubber industries and beauty saloons. Lifestyle- Warthin’s tumors showed a strong association with cigarette smoking . Endogenous hormones .

11. Histogenesis

12. Cell differentiation results in three basic models of benign or malignant salivary gland neoplasms . 1) In one form of differentiation, tumor cell population results in a dual population that combines recognizable luminal and/or acinar cells with myoepithelial and/or basal cells 2) A second pattern results primarily in luminal/glandular cells that resemble to some extent normal duct epithelial and/or acinar cells 3) The third process produces tumor cells resembling normal myoepithelial and/or basal cells .

13. Classification WHO classification (2005) Malignant epithelial tumors Acinic cell carcinoma Mucoepidermoid carcinoma Adenoid cystic carcinoma Polymorphous low-grade adenocarcinoma Epithelial- myoepithelial carcinoma Clear cell carcinoma not otherwise specified Basal cell adenocarcinoma Sebaceous carcinoma Sebaceous lymphadenocarcinoma Cystadenocarcinoma Low-grade cribriform cystadenocarcinoma Mucinous adenocarcinoma Oncocytic carcinoma Salivary duct carcinoma Adenocarcinoma , not otherwise specified Myoepithelial carcinoma Carcinoma ex pleomorphic adenoma Carcinosarcoma Metastasizing pleomorphic adenoma Squamous cell carcinoma Small cell carcinoma Large cell carcinoma Lymphoepithelial carcinoma Sialoblastoma

14. Benign epithelial tumors Pleomorphic adenoma Myoepithelioma Basal cell adenoma Warthin tumour Oncocytoma Canalicular adenoma Sebaceous adenoma Lymphadenoma Sebaceous Nonsebaceous Ductal papillomas Inverted ductal papilloma Intraductal papilloma Sialadenoma papilliferum Cystadenoma Soft-tissue tumors Hematolymphoid tumors Secondary tumors

15. Pleomorphic adenoma/ mixed tumor Name suggested by Willis. Most common neoplasm of salivary gland tumor . Benign neoplasm- consisting of cells exhibiting the ability to differentiate to epithelial ( ductal and nonductal ) cells and mesenchymal ( chondroid , myxoid , osseous) cells. Other names: Branchioma, enclavoma, teratoma, cyindroma , myxochondrocarcinoma . Salivary gland tumor origin: EPITHELIAL Shows cytogenic abnormalities in chomosomes - 12q13-15. Putative pleomorphic adenoma gene(PLAG1) has been mapped to chromosomes 8q12.

16. HISTOGENESIS Numerous theories have been proposed The tumor is centered around myoepithelial cells and reserve cells Ultrastructural studies have confirmed the presence of ductal and myoepithelial cell. According to Hubner and associates cell responsible for morphological diversity is myoepithelial cell which produces fibrous, mucinous , chondroid , and osseous areas

17. According to Regezi and Batsakis Intercalated duct reserve cell can differentiate into ductal and myoepithelial cells. This cell in turn can undergo mesenchymal metaplasia . According to Dardick and his associates Neoplastically altered epithelial cells with the potential for multidirectional differentiation might be histogenetically responsible for pleomorphic adenoma.

18. CLINICAL FEATURES Most common tumor . Rate of occurance : 60-70%- parotid glands 40-60%- submandibular glands 40-70%- minor salivary glands seldomly - sublingual glands Age: 30-50 years Sex: female> male – 3:1 – 4:1 In parotid- presents in the lower lobe of the superior lobe as a mass over the angle of the mandible, below and infront of the ear.

19. CLINICAL PRESENTATION: painless, slow growing, firm mass, initially small in size and begins to increase in size. Initially movable but with continued growth become more nodular and less movable. Recurrent tumor - multinodular , fixed on palpation. Palate – intraorally common site. Seldom ulcerated- unless secondarily traumatized.

20. INVESTIGATION MRI CT SCAN

21. GROSS PATHOLOGY Benign tumor showing well encapsulated mass Cut surface of the tumor is tan coloured and glossy in appearance

22. HISTOPATHOLOGIC APPEARANCE HALLMARK: Morphologic Diversity. Charecterized by- Variable, Diverse, Structural & histologic patterns. It demonstrate glandular epithelium and mesenchyme like tissue and the proportion of each component varies widely. Typically a well-circumscribed encapsulated tumor The epithelium often forms ducts and cystic structures or may occur as islands or sheets of cells , anastomosing cords and foci of Keratinizing squamous cells and spindle cells .

23. Foote and Frazell (1954) categorized PA into: a) Primarilly myxoid (36%) b) Myxoid and cellular component in equal proportions (30%) c) Predominantly cellular (22%) d) Extremely cellular (12%)

24. Myoepithelial cells are major component of PA. Have variable morphology- sometimes appearing as angular or spindled , some with eccentric nucleus resembling plasma cells are responsible for characteristic mesenchyme like changes. Vacuolar degeneration of myoepithelial cells can produce a chondroid appearance . the stroma exhibits areas of an eosinophilic hyalinized change, fat or osteoid also is seen.

25. Prominent cartilagenous differentiation and surrounding ducts and myoepithelial cells Plasmacytoid myoepithelial cells

26. Many ducts and myoepithelial cells are surrounded by hyalinization

27. Focal areas of squamous differentiation with keratinization seen Focal areas of mucous metaplasia

28. DIFFERENTIAL DIAGNOSIS Polymorphous low grade adenocarcinoma , PLGA Adenoid cystic carcinoma, AdCC Epithelial myoepithelial carcinoma, EMC Squamous cell carcinoma, SCC Mucoepidermoid carcinoma, MEC

29. TREATMENT AND PROGNOSIS Surgical excision Superficial parotidectomy with preservation of the facial nerve Local enucleation should be avoided - resulting in seeding of the tumor bed. Deep lobe of the parotid- total parotidectomy is usually necessary also with preservation of the facial nerve.

30. Submandibular tumors - Total removal of the gland with the tumor . Malignant degeneration is a potential complication, resulting in a carcinoma ex pleomorphic adenoma . The risk of malignant transformation is probably small, but it may occur in as many as 5% of all cases.

31. Warthims tumor Papillary Cystadenoma Lymphomatosum or Adenolymphoma 5-14% of parotid neoplasms , 2 nd most common benign tumor.. Pathogenesis is uncertain.. Believed to arise from heterotrophic salivary gland tissue found within the parotid lymph nodes .. OR.. Proliferation of salivary gland ductal epithelium that is associated with secondary formation of lymohoid tissue… Risk factor - Smokers have 8 fold greater risk .. - EBV

32. CLINICAL FEATURES Almost exclusively restricted to the parotid glands Appears as painless, slow growing, nodular mass .. Firm or fluctuant on palpation Tail of parotid is the common site Unique characteristic = occurs bilaterally (5-14%) Rare in sub- mandibular /lingual glands.. Older, Caucasian, males… 6 th – 7 th decade.. M:F = 10:1..

33. GROSS PATHOLOGY Encapsulated Smooth/ lobulated surface Cystic spaces of variable size, with turbid fluid, caseous debris, & tenaceous mucoid material with shaggy epithelium… Solid areas with white nodules representing lymphoid follicles…

34. HISTOPATHOLOGIC APPEARANCE Epithelium: mixed ductal with lymphoid stroma .. Double cell layer.. oncocytic in nature.. Luminal cells= tall columnar , centrally placed, palisaded … Basal cells= cuboidal , with more vescicular nuclei.. Lining epithelium demonstrates papillary projections into cystic spaces surrounded by lymphoid stroma … Stroma : mature lymphoid follicles with germinal centers Focal areas of metaplsia may be seen..

35. Warthin’s tumor showing papillary cystic tumor with dense lymphoid stroma

36. DIFFERENTIAL DIAGNOSIS Oncocytic papilary cystadenoma . Lymphoepithelial cystic lesions such as simple benign lymphoepithelial cyst (unrelated to AIDS), AIDS-related parotid cyst, lymphoepithelial sialadenitis , MALT (mucosa-associated lymphoid tissue)

37. TREATMENT AND PROGNOSIS Surgical excision… Malignant transformation potential – RARE Seifert showed a study results of squamous metaplsia of 7.5%.. Synodeman , & Johnson.. demonstarted 12% recurrence rates.. Though superficial parotidectomy is treatment of choice.

38. Malignant changes in warthins tumor Incidence – 1% Epithelial component – squamous cell carcinoma, oncocytic carcinoma. Adenocarcinoma , undifferentiated carcinoma, mucoepidermoid carcinoma. Lymphoid stroma - various types of non- Hodgkings lymphoma and Hodgkins lymphoma .

39. Malignant epithelial tumors of salivary glands Mucoepidermoid carcinoma Adenoid cystic carcinoma Polymorphous low grade adenocarcinoma

40. Mucoepidermoid carcinoma 5% of all salivary gland tumors Commonest malignant tumor in adult and childhood. 1 st to 9 th decade peaking in 4-5 th decade Females Parotid gland (45%) And palate (21%) Malignant glandular epithelial neoplasm characterized by mucous cells, intermediate cells, and epidermoid cells .

41. Etiology : Therapeutic Radiation Lipoidal installation Presence of other foreign material Origin: Cells of the salivary gland excretory and intercalated duct

42. CLINICAL FEATURES: Age: 3rd – 5th decade Sex: females> male Site: parotid is most commonly affected. Intraorally : palate Most common salivary gland neoplasm in children

43. CLINICAL FEATURES: Low grade: slowly enlarging, painless mass , seldom exceeds 5cm in diameter in low grade. not completely encapsulated, often contains cysts - filled with viscoid , mucoid material. may be mistaken as mucocele . High grade: grows rapidly, facial nerve paralysis ulceration, trismus , draining from the ear, dysphagia . metastasis to regional lymph node, lung, bone, brain, suncutaneous tissue.

44. Blue-pigmented mass of the posterior lateral hard palate. Mucoepidermoid carcinoma. Mass of the tongue

45. GROSS PATHOLOGY Low-grade mucoepidermoid carcinomas may have a distinctly cystic gross appearance. -Cystic spaces- viscid, mucoid material -Areas of hemorrhage seen. Cut surface of the tumor shows gray white, solid mass accompanied by multiple small cystic structures and infiltrative borders.

46. HISTOPATHOLOGICAL FEATURES: Characterized by: variety of cell types and growth patterns Composed of- a)mucous secreting cells b) epidermoid cells c)intermediate cells d)columnar or clear cells Grades: a) low grade b) intermediate grade c) high grade

47. Mucous cells- vary in shape, abundant pale foamy cytoplasm that stains positive for mucin stains . relatively large, may assume round, cuboidal , ovoid, columnar or goblet shapes. stains positive for mucicarmine and PAS stain . Epidermoid cells- squamous features, polygonal shape. Intermediate cells- larger than basal cell , smaller than squamous cell. Proginitor of epidermoid and squamous cells. Clear cells- larger, polygonal and defined cytoplasmic borders.

48. Histopathological Grades are based on- Amount of cyst formation Degree of cytoplasmic atypia Relative number of mucous, epidermoid & intermediate cells .

49. Low grade : Hallmark- prominent cystic structures accompanied by the presence of numerous mature cellular element including mucous cells and extracellular matrix. Mucous cell predominate squamous cell lining the cystic spaces seen. Size, shape & staining characteristics of cells are uniform Intermediate grade : intermediate cells predominate with scattered mucous cells and zones of epidermoid cells forming large, solid islands of tumor . Mitotic figures- rare .

50. Low-grade mucoepidermoid carcinoma: with a prominent cystic component

51. Mucus cells - mucicarmine stain, Clear cells - PAS

52. Intermediate-grade mucoepidermoid carcinoma with few mucus cells and prominent population of intermediate and epidermoid cells

53. High grade : nearly solid cellular proliferation of epidermoid & intermediate cells Noticiable degree of cellular atypia N:C ratio altered nucleoli prominent, mitosis- numerous 2 differentiation pattern: a)Resemble a MDSCC b) variety of cell types that are most often dominated by intermediate cells.

54. High-grade mucoepidermoid carcinoma with poorly differentiated, irregular nests of tumor cells and very focal mucinous differentiation.

55. varients 1) Sclerosing MEC : Extremely rare , characterized by intense central sclerosis that occupies the entirety of an otherwise typical tumor , frequently with an infiltrate of plasma cells, eosinophils , and/or lymphocytes at its peripheral region. 2 mechanism: Tumor infarction and extravasation of mucins resulting in reactive fibrosis.

56. 2) Intraosseous MEC : Primary intraosseous mucoepidermoid carcinoma (PIOC) of the jaw bones is an extremely rare malignant salivary gland tumor , comprising 2–3% of all mucoepidermoid carcinomas reported. commonly seen in the posterior part of the mandible Histologically low-grade cancers Radiographically seen as uniocular or multiocular lesions.

57. DIFFERENTIAL DIAGNOSIS: Necrotizing sialomataplasia Pleomorphic adenoma Inverted ductal papilloma Cystadenoma Matastatic SCC Sebaceous carcinoma Clear cell tumors Adenosquamous carcinoma

58. TREATMENT AND PROGNOSIS: Conservative excision with preservation of facial nerve Submandibular gland- removal of the gland Minor salivary gland- surgical Matastatis - 12% of cases Prognosis- fairly good.

59. Adenoid cystic carcinoma Cylindroma , adenocystic carcinoma, adenocystic basal cell carcinoma, psuedo adenomatous basal cell carcinoma, basaloid mixed tumor. The adenoid cystic carcinoma is one of the more common and best- recognized salivary malignancies. Slow growing but aggressive neoplasm with a remarkable capacity of recurrence. Marked propensity for perineural invasion . Adenoid cystic carcinoma is a “ basaloid tumour consisting of epithelial and myoepithelial cells in variable morphologic configurations, including tubular, cribriform , cystic and solid patterns

60. CLINICAL FEATURES: Age: 5th- 7th decade Sex: F>M Site: 50-60% within minor salivary gland - palate> tongue, buccal mucosa. Slowly growing mass. Pain is a common and important finding Patients often complain of a constant , low-grade, dull ache , which gradually increases in intensity. Facial nerve paralysis may develop with parotid tumors . Palatal tumors can be smooth surfaced or ulcerated. Tumors arising in the palate or maxillary sinus may show radiographic evidence of bone destruction

61. Adenoid cystic carcinoma. Painful mass of the hard palate and maxillary alveolar ridge.

62. HISTOPATHOLOGIC FEATURES: The adenoid cystic carcinoma is composed of a mixture of myoepithelial cells and ductal cells that can have a varied arrangement. Three major patterns are recognized; (1) Cribriform (2) Tubular (3) Solid. Usually a combination at these is seen, and the tumor is classified based on the predominant pattern.

63. Cribriform pattern: The cribriform pattern is the most classic and best recognized appearance, characterized by islands of basalaid epithelial cells that contain multiple cylindrical, cyst like spaces resembling Swiss cheese or honeycomb pattern .

64. These spaces often contain a mildly basophilic mucoid material a hyalinized eosinophilic product , or a combined mucoid hyalinized appearance. Sometimes the hyalinized material also surrounds these cribriform islands. Adenoid cystic carcinoma. The tumor cells are surrounded by hyalinized material

65. Tubular pattern: Tubular structure that are lined by stratified cuboidal epithelium. Longitudinal section- ductal structures are viewed as ducts or tubules. Lumina contains mucinous substance- PAS positive Cribriform pattern may exist with tubular pattern.

66. Solid pattern: Solid groups of cuboidal cells with little tendency towards ducts or cyst formation. Arranged in nests or sheets of varying size and shape. Areas of necrosis seen Cellular pleomorphism , mitosis observed.

67. Adenoid cystic carcinoma. Perineural invasion.

68. DIFFERENTIAL DIAGNOSIS: Basal cell adenoma Polymorphous low grade adenocarcinoma Basaloid squamous carcinoma Basal cell adenocarcinoma

69. TREATMENT AND PROGNOSIS Surgical excision Adjunct radiation therapy may slightly improve patient survival in some cases. Prognosis- poor

70. Polymorphous low grade adenocarcinoma Lobular carcinoma, terminal duct carcinoma . Evans and Batsakis first used the term PLGA occurs almost exclusively in the minor salivary glands Characterized by: Bland, uniform nuclear feature , diverse by characteristic architecture, infiltrative growth and perineural invasion.

71. CLINICAL FEATURES: Age: 50-80 years Sex- F:M=2:1 Site: 50-60%- palate, 16%- buccal mucosa, 12%- upper lip, major SG- parotid c/p- Most often appears as a pain less mass that may have been present for a long time with slow growth. Associated with bleeding, discomfort, telangiectasia , ulceration. Tumor can erode or infiltrate the underlying bone .

72. Polymorphous low-grade adenocarcinoma . Ulcerated mass of the posterior lateral hard palate

73. GROSS PATHOLOGY: Firm, circumscribed , but non-encapsulated , yellow tan lobulated nodule, average size 2.2cms. Bony invasion may be seem in large lesion in the hard patate , may impinge upon the maxillary bone and cause bone resorption and laterally medullary invasion

74. HISTOPATHOLOGIC FEATURES : Characterized by: Infiltrative growth with diverse morphology & Uniform nuclear appearance At low power, the tumor sometimes appears well circumscribed. peripheral cells are usually infiltrative, invading the adjacent tissue in a single- file fashion . Difference growth pattern- hence the name polymorphous. Variety of growth patterns- solid, ductal , cystic, tubular or cribriform

75. Indian file pattern

76. Tumor stroma - varies from mucid to hyaline and in some areas Separated by fibrovascular stroma . In some tumors , a cribriform pattern can be produced that mimics adenoid cystic carcinoma . Mitotic figures are uncommon . Perineural invasion common

77. DIFFERENTIAL DIAGNOSIS: Pleomorphic adenoma Adenoid cystic carcinoma

78. TREATMENT AND PROGNOSIS The polymorphous low-grade adenocarcinoma is best treated by wide surgical excision , sometimes including resection of the under lying bone. Metastasis to regional lymph nodes is relatively uncommon , occurring in just under 10% of patients. Therefore, radical neck dissection seems unwanted Distant metastasis is rare.