Bethesda updates with Thyroid path 2023.pptx

Thyroid

1. Bethesda Thyroid UPDATES

2. Changes in 3 rd Edition of TBSRTC Unification of diagnostic categories under single name Use of TBSRTC in paediatric population Redefined risk of malignancy (ROM) Subcategorization of AUS based on ROM – AUS with nuclear atypia, AUS-other Wherever possible terminology harmonised with latest 2022 WHO classification Incorporate High grade follicular derived carcinoma – PDTC, DHGTC New chapters on Clinical perspectives, imaging studies, molecular tests and other ancillary tests

3. Diagnostic Categories Non Diagnostic or Unsatisfactory Benign Atypia of undetermined significance (AUS) or Follicular lesion of undetermined significance (FLUS) Follicular Neoplasm (FN) or Suspicious of Follicular Neoplasm (SFN) Suspicious of Malignancy Malignant

4. Diagnostic Category Risk Of Malignancy Mean % (range) ROM in Pediatric Patients Mean % (range) Non Diagnostic 13 (5-20) (5-10) 14 (0-33) Benign 4 (2-7) (0-3) 6 (0-27) Atypia of Undetermined Significance 22 (13-30) (6-18) 28 (11-54) Follicular Neoplasm 30 (23-34) (10-40) 50 (28-100) Suspicious of Malignancy 74 (67-83) (45-60) 81 (40-100) Malignant 97 (97-100) (94-96) 98 (86-100) Redefined Risk of Malignancy

5. Non Diagnostic Cyst fluid only Virtually Acellular specimen Obscuring blood, Clotting artifact, drying artifact, etc. Exceptions Aspirate with cytological atypia (TBSRTC cat. III – VI) Aspirate from solid nodule with inflammation (TBSRTC cat. II) Colloid Nodule (TBSRTC cat. II)

6. Non Diagnostic Criteria for adequacy ≥ 6 groups of well visualized, well stained, well preserved, undistorted and unobstructed follicular epithelium cells with ≥ 10 cells per group.

7. Non Diagnostic Case scenarios for ND Not meeting criteria of Adequacy Poorly preserved, poorly stained, significant obstruction Cyst fluid with or without histiocytes and < 6 group of 10 benign follicular cells No cellular material Blood only USG gel precipitate Lack of Collection of cells from targeted lesions

8. Benign Consistent with Benign Follicular nodule nodular disease Consistent with Chronic lymphocytic (Hashimoto) thyroiditis Consistent with granulomatous (subacute) thyroiditis

9. Benign Preferred term over Negative for Malignancy Follicular Nodular Disease Benign Follicular Nodule Sparse or moderate cellularity Colloid viscous shiny and light yellow or Thin watery impart crazy pavement appearance Follicular cells monolayered sheets honeycomb like, 3-dimensional fragments Minimal nuclear overlapping and overcrowding

10. Benign Preferred term over Negative for Malignancy Lymphocytic Thyroiditis Usually Hypercellular, Oncocytic cells, Anisonucleosis, Polymorphic lymphoid cells, Occasional plasma cells, Lymphoiod cells infiltrating epithelial cell groups.

11. Atypia of Undetermined significance Specify AUS – nuclear atypia or AUS - other

12. AUS- Nuclear atypia Focal nuclear atypia, Intranuclear pseudo-inclusions absent Extensive but mild nuclear atypia, INCI absent Atypical cyst lining cells Histiocytoid cells Nuclear and architectural atypia

13. AUS- other Architectural atypia – 3-D groups of follicular cells or microfollicles Oncocytic atypia – Oncocytes in clinical setting of lymphocytic thyroiditis Atypia, NOS – Minor population of follicular cells with nuclear enlargement, atypia does not raise concern for PTC, Psammomatous calcification in absence of follicular cells with nuclear features of PTC Atypical lymphoid cells, rule out lymphoma – atypia insufficient for SFM category

14. AUS-Other

15. Follicular Neoplasm Specify if oncocytic type Diagnostic criteria Architectural patterns – microfollicles, crowded 3-D, less frequent trabecular pattern or isolated cells Cytologic finding – Round nuclei, clumpy hyperchromatic chromatin, inconspicuous nucleoli, lack nuclear clearing To avoid overdiagnosis of NIFTP as Malignant or Suspicious of Malignancy – this category include follicular patterned aspirate (FA, FTC, NIFTP, FVPTC) with mild nuclear changes if true papillae absent, INCI rare.

16. Oncocytic Follicular Neoplasm As in WHO 2022 term Hürthle cells Oncocyte is used Diagnostic criteria Cellular , Almost exclusively Oncocytes, Atypia/Dysplasia No or scant colloid Lack of background lymphocytes or plasma cells

17. If aspirate composed exclusively of oncocytes If scantly cellular specimen composed of exclusive oncocytes – AUS If cellular specimen composed of exclusive oncocytes without dysplasia , abundant colloid – Benign If cellular specimen composed of exclusive oncocytes with dysplasia or atypia , scant colloid – OFN

18. Suspicious of Malignancy Suspicious of Papillary thyroid carcinoma Suspicious of Medullary thyroid carcinoma Suspicious of metastatic carcinoma Suspicious of lymphoma

19. Suspicious of Papillary thyroid carcinoma Patchy nuclear changes pattern Incomplete nuclear changes pattern Sparsely cellular specimen pattern

20. Suspicious of Lymphoma Abundant monomorphic small to medium sized lymphocytes Scant atypical large lymphocytes, insufficient material for ancillary test

21. Suspicious for Metastatic carcinoma Scant atypical cells, insufficient material for IHC to confirm/exclude

22. Malignant Papillary thyroid carcinoma High-grade follicular cell derived non-anaplastic thyroid carcinoma Medullary thyroid carcinoma Undifferentiated (Anaplastic) carcinoma Squamous cell carcinoma Metastatic malignancy Non Hodgkin lymphoma Cribriform Morular thyroid carcinoma, subtype of PTC Tumor of Uncertain Histiogenesis

23. High grade follicular cell derived non anaplastic carcinoma Differentiated high grade thyroid carcinoma (DHGTC) – Papillary or Follicular architecture, High mitotic activity and necrosis Poorly differentiated thyroid carcinoma (PDTC) – Lack conventional nuclear features of PTC, Uniform small convoluted nuclei, High N/C ratio

24. Papillary thyroid carcinoma Flat sheets/monolayered, papillary fragment PTC nuclear features – Convoluted, INCI, Nuclear grooves, Pale chromatin, Nuclear enlargement Cytoplasm – granular, eosinophilic, squamoid, oncocytic Psammoma bodies Colloid scant In accordance with WHO Tumor Classification 2022 term, Papillary carcinoma, variants subtypes is used

25. Medullary Thyroid carcinoma Cellular, single cells and syncytial groups Heterogenous tumor cells Binucleation Diffuse pleomorphism, Mitosis, Necrosis INCI present Amyloid in one half of aspirate Intracytoplasmic vacuoles

26. Undifferentiated Anaplastic Thyroid carcinoma Variable cellular, Isolated tumor cells Predominant cytologic pattern – spindle, pleomorphic, squamous, epithelioid, rhabdoid, Osteoclast like giant cells Mitosis, Necrosis Binucleated, Multinucleated cells Neutrophil rich inflammation

27. Lymphoma

28. Clinical Perspectives and Imaging Multimodal approach for thyroid nodules – Clinical, Biological association with hormone levels, Risk stratification with Ultrasound (TI-RADS category), Cytological (TBSRTC category) All these findings are discussed before treatment plan. Additional diagnostics may be done in inderminate nodules – Needle core biopsy, Cross sectional CT, I 123 Scintigraphy, 99 Tc-Mibi scan

29. Model summarizing role of FNA based molecular testing for thyroid tumor

30. Molecular and Other Ancillary tests Molecular diagnostics for thyroid nodules with indeterminate (AUS or FN) cytology BRAF V600E - Classic Papillary Thyroid Carcinoma, Tall cell subtype of PTC ALK and NTRK fusion – specific for PTC RET mutations, Somatic RAS mutations - Medullary Thyroid Carcinoma

31. Relationship between Genomic alterations and thyroid tumor type

32. Molecular and Other Ancillary tests RAS- like alterations (HRAS, KRAS, NRAS, PTEN, DICER1) can considered molecularly indeterminate for cancer, found in broad spectrum of both benign and malignant follicular patterned neoplasms Mutations in TP53, TERT promoter, AKT1 and PIK3CA considered late events in thyroid tumorigenesis, clinically aggressive cancers Mitochondrial DNA mutations – Oncocytic neoplasms

33. Molecular and Other Ancillary te sts Traditional methods – Sanger sequencing, real time PCR, allele-specific PCR, pyrosequencing, fluorescence melting curve analysis, FISH NGS based genotyping Molecular testing platforms – TyroSeq GC Afirma GSC ThyGeNEXT

34. THANK YOU