Thyroid

1. Bethesda Thyroid
UPDATES

2. Changes in 3rd 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
I. Non Diagnostic or Unsatisfactory
II. Benign
III. Atypia of undetermined significance (AUS) or Follicular lesion of
undetermined significance (FLUS)
IV. Follicular Neoplasm (FN) or Suspicious of Follicular Neoplasm
(SFN)
V. Suspicious of Malignancy
VI. 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. I. 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. I. 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. I. 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. II. 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. III. 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. IV. 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

19. V. Suspicious of Malignancy
• Suspicious of Papillary thyroid carcinoma
• Suspicious of Medullary thyroid carcinoma
• Suspicious of metastatic carcinoma
• Suspicious of lymphoma

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

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

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

23. VI. 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

24. 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

25. 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

26. 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

27. 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

28. Lymphoma

29. 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, I123 Scintigraphy, 99Tc-Mibi scan

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

31. 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

32. Relationship between Genomic alterations and thyroid tumor type

33. 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

34. Molecular and Other Ancillary tests
• 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