Salivary gland- milan system of reporting.pptx

Anatomy of salivary gland , Normal salivary cells on FNA , Milan system

1. Salivary Gland : Milan System Of Reporting Moderator : Dr Nandini N.M Presenter : Dr Akansha Adhikari

2. Introduction Neoplasms of salivary glands accounts for about 2% - 6.5% of all head and neck tumors and 80% of these originate in the parotid gland. Majority of them are benign but to rule out malignancy fine needle aspiration (FNA) is a: 1. Well-established 2. Safe 3. Inexpensive 4. Rapid 5. Easy to perform

3. FNA helps dividing lesions into- Neoplastic vs non-neoplastic High grade vs Low grade neoplastic lesions. With this information the treatment plan for the lesions can be decided.

4. Pre FNA History Physical examination Identification of nodule essential for successful palpation and guided fna Deep lesion >1cm under guided us/ ct

5. Cytology of normal salivary gland Tissue fragment of uniform, well-formed acini along a small duct

6. Basic approach to salivary gland FNA Cellularity Architecture of epithelial-like cells Background Cell Type

7. Components of Salivary Gland FNA

8. Complications of Salivary Gland FNA Transient discomfort on salivation Local haemorrhage Infection Syncope Potential damage to 7 th cranial nerve

9. Challenges and Limitations of FNA Challenges faced are: Diversity of benign and malignant salivary gland tumors, with 34 distinct epithelial tumor subtypes recognized by the WHO in 2017.

10. 2. The morphologic overlap between many benign and low-grade malignant salivary gland tumors. 3. The wide spectrum and morphological heterogeneity of cellular elements within the same salivary gland tumors. 4. The rarity of many salivary gland tumors making it difficult for the practicing cyto-pathologist to become familiar with their cytologic features.

11. Milan System In 2015, an international group of cyto-pathologists initiated the development of a reporting system for salivary gland FNA specimens using a framework consisting of 6 diagnostic categories. The system took into account : a. Morphological spectrum b. Overlapping features of non- neoplastic, benign neoplastic and malignant entities. c. And all the features on which other systems were based on.

12. The reporting system was named “ The Milan System For Reporting Salivary Gland Cytopathology” (MSRSGC) This system was evidence based system , which correlated each diagnostic category with a risk of malignancy and clinical management strategy Its main objective was to Improve communication among clinicians and institutions. Improve patient care by providing a practical and uniform reporting system that is user friendly and internationally accepted.

13. The categories are: Non diagnostic Non neoplastic Atypia of undefined significance (AUS) Neoplasm- 4a- Benign 4b- Salivary gland of uncertain malignant potential Suspicious for malignancy Malignancy

14. Diagnostic Categories of MSRSGC 1. Non – Diagnostic: Aspirates that quantitatively and qualitatively insufficient diagnostic material to provide an informative interpretation were included.

15. Specimens can be non- diagnostic because of following reasons: Rare or absent interpretable lesion cells (<60). Poor fixation Crush artifact Necrotic debris Excessive blood Other elements obscuring cellular details Poor FNA technique

16. In MSRSGC this category also includes: 1) Benign salivary gland tissue and 2) Non mucinous cyst fluid without an epithelial component. In the report, why the sample is in- adequate it should be mentioned to rule out potential risk of malignancy. Nonmucinous cyst contents, revealing histiocytes, debris, and a few inflammatory cells

17. In Wei et al studies follow up was done on non diagnostic cases: 1) 31% was non neoplastic lesions. 2) 44% benign salivary gland. 3) 25% malignant salivary gland. It is recommended to keep non diagnostic category under <10% of the total FNA reported.

18. Non-Diagnostic. A. Showing blood , debris and rare inflammatory cells are present but insufficient for diagnosis. B. Hypocellular aspirate

19. Normal salivary gland. A, Normal acinar cells are aggregated in grapelike bunches (arrow) with admixed adipose tissue and an occasional flat sheet of ductal cells B, Acinar cells have uniform, round nuclei and abundant vacuolated cytoplasm.

20. Sample report of Non diagnostic

21. 2. Non Neoplastic Category Lacks the cytomorphologic evidence of neoplastic process, consisting of: Benign acinar and/or ductal epithelium with an inflammatory component Metaplastic changes Reactive changes

22. It also includes specimens showing reactive lymphoid tissue as, enlarged intra-parotid and peri-parotid lymph nodes are a common non neoplastic cause of salivary gland mass. Flow cytometry is needed for further investigation. Clinico -radiological correlation is essential to ensure tht the specimen is representative of the lesion

23. Estimated risk of malignancy : 10% Management : Clinical follow up and radiological correlation The most common malignant tumors found in this category are lymphomas, mucoepidermoid carcinoma and squamous cell carcinoma.

24. Sialadenosis Acinic cells are significantly larger, with small and peripheral nuclei an showing plenty of zymogen granules

25. Sialolithiasis

26. This aspirate of acute sialadenitis shows abundant acute inflammation, but no evidence of a neoplastic process Chronic Sialadenitis : Fragments of epithelium mainly of ductal origin showing mild reactive atypia; fragments of fibrous stroma; relatively few chronic inflammatory cells.

27. Lymphoepithelial sialadenitis Non-Neoplastic. This aspirate demonstrates the lymphoepithelial lesion of lymphoepithelial sialadenitis, which consists of a bland sheet of ductal epithelial cells with admixed small lymphocytes

28. Granulomatous Sialadenitis Non-Neoplastic. (a) This aspirate of granulomatous sialadenitis shows a large group of epithelioid histiocytes; an infectious agent should be excluded. (b) Aspirates of sarcoidosis yield loose collections of epithelioid histiocytes, and usually lack background necrosis

29. Reactive Lymphadenitis These aspirates of reactive lymph node hyperplasia show (a) a cohesive group of lymphocytes and follicular dendritic cells representing a germinal center fragment. (b, c) Tingible body macrophages are present in a background of predominantly small mature lymphocytes and occasional follicular dendritic cells

30. Sample Report of Non Neoplastic

31. 3. Atypia of Undetermined significance The diagnostic category “Atypia of Undetermined Significance (AUS)” applies to a salivary gland FNA that lacks either qualitative or quantitative cytomorphologic features to be diagnosed with confidence as non-neoplastic or neoplastic. Heterogenous category <10% of salivary gland FNA

32. Common AUS conditions: Reactive and reparative atypia indefinite for a neoplasm Squamous, oncocytic , or other metaplastic changes indefinite for a neoplasm Low cellularity specimens suggestive of, but not diagnostic of a neoplasm

33. Specimens with preparation artifacts hampering distinction between a non-neoplastic and neoplastic process Mucinous cystic lesions with an absent or very scant epithelial component Non-mucinous cystic lesions with atypical epithelial cells

34. Estimated risk of malignancy : 20% Management : Repeat FNA or surgery

35. Atypia of Undetermined Significance. These two images ( a , b ) show rare atypical cells in an inflammatory background, indefinite for a neoplasm

36. Atypia of undetermined significance. This aspirate contains abundant mucin without epithelial cells. The differential diagnosis includes a benign mucinous cyst (mucocele); however, a low-grade mucoepidermoid carcinoma cannot be excluded.

37. Hypocellular aspirate contains occasional epithelioid and spindled cells that are suggestive of a neoplasm Hypocellular aspirate shows a very rare group of mildly atypical epithelial cells with associated “lymphocytic tangles,”suggestive but not diagnostic of a neoplasm

38. Sample Report of AUS

39. 4. Neoplasm It is divided into two sub-categories : Benign neoplasm Salivary gland of uncertain malignant potential.

40. A) Benign Neoplasm This subcategory is reserved for classical examples of benign neoplasms diagnosed based on established cytologic criteria. It includes cases of Pleomorphic adenoma, W arthin tumour, Oncocytoma, Haemangioma, Lipoma and S chwannoma. Estimated risk of malignancy : <5% Management : Surgery or clinical and radiological follow up

41. Neoplasm: benign. Pleomorphic adenoma. Abundant fibrillary matrix with embedded myoepithelial cells.

42. Cytological variations of Pleomorphic adenoma Cellular (matrix poor) Matrix- predominant Pleomorphic adenoma with atypia Squamous metaplasia +/- keratin pearls Mucinous metaplasia Sebaceous metaplasia Spindled with palisading Clear cell changes Oncocytic changes Cystic degeneration Specific IHC : PLAG1 (high sensitivity) HMGA2 (low sensitivity)

43. Pleomorphic adenoma variations

44. Warthins Tumor - Oncocytes, chronic inflammation, and cystic debris

45. Oncocytoma : Cohesive sheetlike clusters of oncocytes with distinct cell borders are present in a clean background .

46. Schwannoma shows a group of bland spindle cells with wispy cytoplasm. The cytoplasmic borders are indistinct. Nuclei are spindle-shaped and display bends or curves

47. B) Salivary gland of uncertain malignant potential (SUMP) It is made for specimens diagnosed as neoplasms but specific entity cannot be made and a malignant neoplasm cant be excluded. The most common pattern seen in this category is salivary gland tumour with basaloid features or basal cell neoplasm.

48. Cases included are cellular pleomorphic adenoma, neoplasms with atypical features and low grade carcinomas( e.g.: basaloid tumours, oncocytic tumours etc) E stimated risk for this category is 35% Management : Surgery

49. Sub-categories of SUMP Cellular basaloid neoplasm Cellular oncocytic / oncocytoid neoplasm Cellular neoplasm with clear cell features

50. Neoplastic cells with dense, granular cytoplasm Neoplasm: SUMP. FNA of a cellular neoplasm with clear cell features showing sheets of epithelial cells with vacuolated cytoplasm. Nuclei are enlarged, but retain smooth nuclear membranes. The histologic follow-up of this case was acinic cell carcinoma

51. A group of basaloid cells suggestive of basal cell adenoma versus other basaloid salivary gland tumors

52. Sample report of category IVA & IVB

53. 5. Suspicious for malignancy This category is for aspirate which show features that are highly suggestive of malignancy but are unequivocal for malignancy due to Insufficient quantitative and/or Qualitative features. Most of the specimens in this category turn out to be high grade carcinomas.

54. Common Conditions Markedly atypical cells with poor preparation or obscuring factors Limited cytologic features of a specific malignancy ACC with limited cellular atypia or hyaline globules MEC with limited mucus cells or extracellular mucin Secretory carcinoma with limited cytoplasmic vacuolization or papillae

55. Suspicious cytologic features in a subset of cells but admixed with predominant features of a benign lesion (ex: CA ex PA) Monomorphic population of small lymphocytes (?low grade NHL) Scant large atypical lymphocytes (?High-grade NHL/ HL)

56. Estimated risk of malignancy :60% Management : Surgery

57. Suspicious for Malignancy. Adenoid cystic carcinoma. This FNA shows basaloid tumour cells associated with poorly formed hyaline globules. SUMP basaloid neoplasm” to “suspicious for adenoid cystic carcinoma” to frankly malignant

58. The smear shows a group of epithelial cells suggestive of acinic cell carcinoma, but hypocellularity and background blood in the absence of ancillary studies limits its diagnosis. Markedly atypical cells suspicious for high-grade carcinoma, but with obscuring blood limiting the assessment

59. Sample report for category V

60. 6. Malignancy This category is for specimens which cytomorphologically show malignancy. On the basis of cytological features an attempt should be made to sub classify into specific types and grades.

61. Other malignancies are also categorized under this category. For e.g. – Lymphomas , sarcomas and metastases. Estimated risk for malignancy : 90% Management : Surgery

62. Malignant : Acinic cell carcinoma Cellular smear with cohesive groups of acinar cells.

63. Epithelial-myoepithelial carcinoma This aspirate of epithelial-myoepithelial carcinoma has a prominent biphasic pattern of ductal cells and Abundant pale myoepithelial cells as well as focal proteinaceous material

64. Salivary Duct Carcinoma Three-dimensional groups of epithelial cells with moderate amounts of cytoplasm and hyperchromatic nuclei in a background of blood and necrosis Groups of high-grade malignant cells with abundant cytoplasm, nuclear pleomorphism, prominent nucleoli, and glandular features

65. LGMEC The aspirate contains abundant mucin in the background and loose sheets of bland epidermoid and mucinous cells This aspirate of low-grade mucoepidermoid carcinoma contains bland epidermoid cells with moderate amounts of dense cytoplasm and well-defined cell borders, while mucus cells contain abundant delicate pink mucinous cytoplasm

66. HGMEC

67. Adenoid cystic carcinoma. A, Numerous variably sized stromal spheres are evident. B, the same tumor shows cribriform architecture. The basaloid tumor cells are readily apparent, but the matrix material is transparent.

68. Ancillary studies Ancillary testing should be considered for cases in which results would alter clinical management or at least modify diagnostic category/clinical risk within the Milan system framework. Recurrent and specific chromosomal translocations or mutations are present in several salivary gland tumors.

69. Their detection by fluorescence in situ hybridization or alternative techniques such as next generation sequencing is diagnostic. Many studies have conducted emphasizing the role of ancillary studies, including newer IHC for enhancing the diagnostic accuracy of salivary gland FNA. For this to happen FNA specimens should have adequate material which can be made sure by rapid onsite cytologic evaluation.

70. Conclusion The MSRSGC was born out of the need for a standardized reporting system which reflects the everyday practice of cytopathology. It takes into account the limitations of salivary gland FNA and provides a framework for reporting, including those specimens where a definite diagnosis may not be possible.

71. It assists in communication between pathologists and treating clinicians and between different institutions by : Providing information for risk stratification Clinical decision making, and Preoperative patient counseling ultimately leading to improved patient care.

72. References Orell S, Sterrett G. Orell & Sterrett's fine needle aspiration cytology. Edinburgh: Churchill Livingstone Elsevier; 2012. Rossi, Esther & Baloch, Zubair & Pusztaszeri , Marc & Faquin , William. (2018). The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC): An ASC-IAC-sponsored system for reporting salivary gland fine-needle aspiration. Journal of the American Society of Cytopathology. 7. 10.1016/j.jasc.2018.02.002.