All the WHO update in thyroid neoplasm 2022 has been covered in this ppt

1. Presenter: Dr DIVYA JYOTI
Moderator : Dr SHILPl AGARWAL

2. New WHO 2022 classification of thyroid neoplasms
Several new
categories:
for clearer
understanding
Cell of origin
Pathologic
features
Molecular
classification
Biological
behaviour
WHO 2017 classification of thyroid neoplasms
 Architecture
 Morphology
 Nuclear feature

3. WHO classification of tumors of thyroid gland
(2017)
WHO classification of tumors of thyroid gland
(2022)
Not included Developmental abnormalities
Thyroglossal duct cyst
Other congenital thyroid anomalies
Follicular adenoma
Variant of Follicular adenoma
Included under Hürthle( Oncocytic) cell tumors
Follicular cell-derived neoplasm
Benign tumors
Thyroid follicular nodular disease
Follicular adenoma
Follicular adenoma with papillary architecture
Oncocytic adenoma of the thyroid
Hyalinizing trabecular tumor Low-risk neoplasm
Hyalinizing trabecular tumor

4. Other encapsulated follicular-patterned thyroid
tumors
Follicular tumor of uncertain malignant potential
Well-differentiated tumor of uncertain malignant
potential
Non-invasive follicular thyroid neoplasm with
papillary-like nuclear features (NIFTP)
Low-risk neoplasm
Thyroid tumor of Uncertain malignant potential
Follicular tumor of uncertain malignant
potential
Well-differentiated tumor of uncertain
malignant potential
Non-invasive follicular thyroid neoplasm with
papillary-like nuclear features (NIFTP)
WHO classification of tumors of thyroid gland
(2017)
WHO classification of tumors of thyroid gland
(2022)

5. 2017 WHO…………… 2022 WHO………
Follicular thyroid carcinoma (FTC), NOS
_________________________________________________
Papillary thyroid carcinoma
_________________________________________________
Variant of PTC
_________________________________________________
Hurthle (oncocytic) cell carcinoma
_________________________________________________
Poorly differentiated thyroid carcinoma
_________________________________________________
Anaplastic thyroid carcinoma
Malignant neoplasm
Follicular thyroid carcinoma
Papillary thyroid carcinoma
Invasive encapsulated follicular variant of papillary
carcinoma
Oncocytic carcinoma of thyroid
Follicular derived carcinoma high grade
A. Differentiated high grade carcinoma
B. Poorly differentiated thyroid carcinoma
Anaplastic follicular cell-derived thyroid carcinoma
Squamous cell carcinoma Included under Anaplastic follicular cell derived thyroid
carcinoma
Medullary thyroid carcinoma
_________________________________________________
Mixed medullary and follicular thyroid carcinoma
Thyroid C cell-derived carcinoma
Medullary thyroid carcinoma
________________________________________________
Mixed medullary and follicular cell-derived thyroid
carcinoma

6. 2017 WHO…………… 2022 WHO………
Mucoepidermoid carcinoma
______________________________________________
Mucinous carcinoma
______________________________________________
Not included
Salivary gland type carcinoma of thyroid
Mucoepidermoid carcinoma
Subtype of Mucoepidermoid carcinoma
Secretory carcinoma of salivary gland type
Sclerosing mucoepidermoid carcinoma with
eosinophilia
______________________________________________
Variant of PTC
Thyroid tumor of uncertain histogenesis
Sclerosing mucoepidermoid carcinoma with eosinophilia
Cribriform morular thyroid carcinoma
Ectopic thymoma
______________________________________________
Spindle epithelial tumor with thymus like differentiation
______________________________________________
Intrathyroid thymic carcinoma
______________________________________________
Malignant Teratoma – Germ cell tumor
Thymic tumors within the thyroid
Thymoma family
Spindle epithelial tumor with thymus like elements
Thymic carcinoma family
______________________________________________
Embryonal thyroid neoplasm- Thyroblastoma

8. Chan Kwon Jung et al.Update from the 2022 WHO classification of thyroid tumor

9. Developmental abnormalities
Thyroglossal Duct cyst (TGDC):
• Essential diagnostic criteria: Perihyoidal
(at or just below hyoid)
• Desirable diagnostic criteria: midline
lesion; respiratory or squamous lined cyst
with associated thyroid follicular
epithelium.
Other congenital thyroid abnormalities
• Agenesis/hemigenesis/ectopic
thyroid/hypoplasia Thyroid dysgenesis
• Dyshormogenetic goiter: due to inborn
defects in any of proteins indispensable
for thyroid hormone synthesis
https://tumourclassification.iarc.who.int/chapters/53

10. 2017 WHO 4th edition  Single Benign Lesion – Follicular Adenoma
Follicular cell-derived neoplasms
1.Benign tumors
a. Thyroid follicular nodular disease
b. Follicular adenoma
c. Follicular adenoma with papillary architecture
d. Oncocytic adenoma of the thyroid

11. Thyroid Follicular nodular disease (FND)
• Different thyroid lesions included in this entity:
Multinodular goitre
Hyperplastic nodule
Nodular hyperplasia
Adenomatous nodule
Adenomatous hyperplasia
Colloid nodules
Colloid goitre
Diffuse goitre
Adenomatoid hyperplasia
These nodules are FREQUENTLY BUT NOT ALWAYS CLONAL
Foci of malignant transformation can occur within the
nodules

12. FND- Gross- Thyroid gland enlarged with variable size multiple nodules
Zubair W. Baloch et al. Overview of the 2022 WHO classification of Thyroid neoplasm

13. Colloid rich macrofollicular nodule
Colloid nodule with Sanderson’s
pollsters
Nodule with microfollicular pattern
Multiple nodules with variable
delineation and encapsulation
Calcification

14. Follicular thyroid adenoma with papillary architecture
• In Previous Edition this entity was classified as variant of follicular adenoma.
• Genetic alterations :
70% cases  Activating TSHR mutation
30% cases  GNAS/EZH1 mutation
Molecular alteration  activation of adenyl cyclase  increase cAMP 
stimulation and proliferation of thyroid follicle
• 15-60% of patients present with symptoms of hyperthyroidism
V/S FA  RAS Mutation

15. FA with papillary architecture
Encapsulated
Non invasive
Centripetal
intrafollicular
papillary
architecture
Lack nuclear
feature of PTC
Zubair W. Baloch et al. Overview of the 2022 WHO classification of Thyroid neoplasm

16. Oncocytic adenoma of the thyroid
Term ‘Hürthle cell”  misnomer and
is discouraged (Karl Hürthle
described C cells)
• 4th ed- Separate category Oncocytic
cell tumors
• Genomics different from FA
Alterations in the mitochondrial
genome
Copy number variations
Benign, non-invasive, encapsulated,
follicular-cell-derived neoplasm
composed of >75% oncocytic cells

17. LOW RISK NEOPLASM
• Borderline tumor morphologically and clinically intermediate between benign and
malignant tumors.
• Side effect of complete thyroidectomy
• Side effect of RAI
• Healthcare cost
Histologically classified 
a. Non-invasive follicular thyroid neoplasm with papillary-like nuclear features
b. Thyroid tumor of uncertain malignant potential
c. Hyalinizing trabecular tumor
The term TUMOR is used to reduce the risk of overtreatment.
2017 WHO  HTT was described as seperate entity.
2022 WHO  HTT combined together with NIFTP and UMP to form one category.

18. NIFTP
2022 WHO  Subtypes
• Subcentimeter NIFTP: ≤ 1 cm in size
( In <2mm size it is difficult to access capsular invasion and papillary architure)
• Oncocytic NIFTP: NIFTP with at least 75% oncocytic cells

19. Non-invasive follicular thyroid neoplasm with papillary-like
nuclear features- Diagnostic criteria (Remains same)
BRAF V600E  Negative

20. Available from: https://www.researchgate.net/figure/Typical-nuclear-features-of-papillary-carcinoma-including-nuclear-inclusions-

21. Thyroid tumors of uncertain malignant potential
• The definition of UMP is same
 Well-differentiated thyroid tumours with follicular architecture
 Encapsulated/unencapsulated
 Well circumscribed
 Invasion remains questionable after thorough sampling and exhaustive examination
• Subtypes:
Follicular tumour of uncertain malignant potential (FT-UMP): Lack nuclear feature of PTC.
Well-differentiated tumour of uncertain malignant potential (WDT-UMP) : Nuclear feature of PTC
present.

22. https://tumourclassification.iarc.who.int/chapters/53

23. Capsular or vascular invasion
Present Questionable Absent
Nuclear
Features of
PTC
Present Invasive encapsulated
follicular variant of PTC
Well differentiated
tumor of uncertain
malignant potential
(WT-UMP)
Non-invasive
follicular thyroid
neoplasm with
papillary-like
nuclear features
(NIFTP)
Questionable Well differentiated
carcinoma, NOS
Absent Follicular carcinoma Follicular tumor of
uncertain malignant
potential (FT-UMP)
Follicular adenoma

24. Zubair W. Baloch et al. Overview of the 2022 WHO classification of Thyroid neoplasm

25. Hyalinizing trabecular tumor
• 4 edition – Separate entity
• 5 edition - Follicular cell-derived Low risk neoplasm. (Rare distant metastasis and rare lymph
node metastasis)
• Architecture  Trabeculae of enlongated/polygonal cells with intrabecular hyaline material
• Hyaline material  PAS + , Diastase resistant, congo red – negative and immunoreactive for
collagen IV
• PTC like nuclear feature
• Specific genetic alteration- Not identified in other thyroid tumor
PAX::GLIS3  M/C
PAX8::GLIS1
These fusion leads to overexpression of GLIS gene  Causes upregulation of extracellular matrix
related gene including collagen gene
• HTT diagnosis confirmation MIB1 (characteristic membranous statining)+ Follicular marker
(thyroglobulin, PAX8 and TTF1)

26. Hyalinizing trabecular tumor
PAS
KI-67
Zubair W. Baloch et al. Overview of the 2022 WHO classification of Thyroid neoplasm

27. Follicular cell-derived neoplasms
3. Malignant neoplasms
a. Follicular thyroid carcinoma
b. Invasive encapsulated follicular variant papillary carcinoma
c. Papillary thyroid carcinoma
d. Oncocytic carcinoma of the thyroid
e. Follicular-derived carcinoma, high grade
f. Anaplastic follicular cell-derived thyroid carcinoma

28. Invasive encapsulated follicular variant papillary carcinoma
(IEFVPC)
• Separate entity and not part of other subtypes of PTC.
• Because -
• 1} Different biological behaviour (rare nodal spread)
• 2} Different molecular profile (RAS-like mutation)
RAS like mutation ( v/s Infiltrative follicular carcinoma can show BRAFV600E
mutation)
• Subtype(s)
Minimally invasive encapsulated FVPTC  capsular invasion only
Encapsulated angioinvasive FVPTC Invasion of vessels.
1. Within the tumour capsule or beyond
2. Intravascular tumour attached to the vessel wall, or admixed with fibrin or covered
by endothelium
Widely invasive FVPTC Grossly apparent invasive growth & extensive vascular
invasion

29. IEFVPTC
• Prognosis:
1. Indolent course
Minimally invasive EFVPTC
 Encapsulated tumours with only focal (<4 foci) vascular invasion
2. Aggressive clinical course
Widely invasive FVPTC
EFVPTC with extensive vascular invasion

30. Papillary thyroid carcinoma
• Term “variant” has been replaced by “subtype”:
Consistency with other WHO tumor classification schemes
Avoid confusion with the molecular diagnostic term “genetic
variant(s)

31. PTCs measuring ≤ 1.0 cm: “PTC-microcarcinoma”:
should NOT be considered as a distinct subtype (size does not indicate a specific histologic
subtype & can display aggressive pathological and clinical behaviour)

32. CRITERIA FOR TALL CELL VARIANT OF PTC IS REDEFINED
4 th edition – Tall cells 2 to 3 times tall as they are wide.
5 th Editon- Tall cell must have atleast 3 times height as they are wide and shows dense eosinophilic
cytoplasm

33. Follicular-derived carcinomas, high grade
2022 WHO introduced criteria to diagnose thyroid carcinoma having prognosis
intermediate between favourable outcome and poor outcome.

34. 1. Differentiated high-grade thyroid carcinoma  Retain architectural and/or
cytological properties of well differentiated histiotypes of follicular cell derivation
2. Poorly differentiated thyroid carcinoma  Histologically poorly differentiated-
solid, trabecular and insular growth pattern

38. Anaplastic follicular cell-derived thyroid carcinoma
• New: Squamous cell
carcinoma has been included
in Anaplastic carcinoma:
(ATC, squamous cell
carcinoma pattern)
Similar poor overall survival
Frequent BRAF V600E
mutations
Express PAX8 and TTF1 –
follicular origin

39. Jung C K et al. Update from the 2022 WHO classification of thyroid tumor: A standardized diagnostic approach

40. Jung C K et al. Update from the 2022 WHO classification of thyroid tumor: A standardized diagnostic approach

41. Medullary carcinoma thyroid : grading
• Histologic grading schemes have been validated -
 Impacts on overall survival, disease-specific survival, local recurrence free survival, and
distant metastasis free survival.
• The International Medullary Thyroid carcinoma grading scheme:
High-grade MTCs  Tumours with at least one of the following 3 features:
1. Mitotic count ≥5 per 2 mm2
2. Ki67 proliferation index ≥5%, and/or
3. Tumour necrosis ( Tumor necrosis can be focal  generously sample the tumor)

43. New 2022 WHO classification scheme of thyroid neoplasm
Salivary gland-type carcinomas of the thyroid
1. Mucoepidermoid carcinoma of thyroid
2. Secretory carcinoma of salivary gland type
Thyroid tumors of uncertain histogenesis
1. Sclerosing mucoepidermoid carcinoma with eosinophilia
2. Cribriform morular thyroid carcinoma
Thymic tumors within the thyroid
1. Thymoma family
2. Spindle epithelial tumor with thymus-like elements
3. Thymic carcinoma family
Embryonal thyroid neoplasms
1. Thyroblastoma

44. Mucoepidermoid carcinoma
• Histogenesis:
Squamous metaplasia
Ectopic salivary gland
tissue
• Pathogenesis: MAML2
rearrangement
• Indolent behaviour,
favourable outcome
NEW: Mucinous carcinoma of the thyroid: very rare incorporated as subtype of MEC
Indicating one extreme with glandular differentiation, signet ring features and accumulation of
extracellular mucin among neoplastic cells.

45. Secretory carcinoma of salivary gland type
• Incorporated in new WHO classification of thyroid tumor
• Morphologically and genetically similar to its mammary and salivary gland counterparts
• Does not share the histological and immunophenotypical features of differentiated
follicular cell–derived carcinomas
• Age: slightly older than at salivary sites (mean=61.5 years)
• More aggressive course than that of other locations, with locoregional recurrences and
distant metastasis in upto 30% cases

46. Secretory Carcinoma – Mammary analogue of
secretory carcinoma
• Architecturemicrocystic, tubular,
and solid
• Tumor cells  eosinophilic to
vacuolated cytoplasm with
abundant eosinophilic bubbly
luminal secretions
• Nuclei  cleared and ovoid with
prominent nucleoli
• IHC  diffuse Positive  GATA3,
mammaglobin and S100
negative  TTF1, thyroglobulin and
PAX8

47. ETV6:NTRK3 translocations: hallmark of SC respond to targeted therapy with TRK
inhibitors

48. New 2022 WHO classification scheme of
thyroid neoplasm
Thyroid tumors of uncertain histogenesis
1. Sclerosing mucoepidermoid carcinoma with
eosinophilia
2. Cribriform morular thyroid carcinoma
2017 WHO classification scheme of thyroid
neoplasm
1.Separate entity
2.Variant of PTC

49. Sclerosing mucoepidermoid carcinoma with eosinophilia
(SMECE)
• 4th edition- Classified as separate entity.
• 5th edition – classified under tumor of uncertain histiogenesis.
• Mean age: 55 years
• M:F= 1:13
• Origin Ultimobranchial body/solid cell nest.
• Lack MAML2 rearrangements and BRAF mutation
• Uncertain Histogenesis

51. Cribriform-morular thyroid carcinoma (CMTC)
• Originally classified as a subtype of papillary carcinoma because of the presence of
papillae and in some instances diagnostic nuclear features
• REMOVED FROM PAPILLARY VARIANT BECAUSE-
Distinct molecular profile: no BRAF and rare RAS mutations
Genetic alteration – Wnt/beta-catenin pathway (APC mutation- M/C)
• Usually multifocal and/or bilateral in familial adenomatous polyposis (FAP), while
sporadic cases appear as a solitary nodule
• Almost exclusively occurs in young women (mean age= 28 years)

53. New 2022 WHO classification scheme of
thyroid neoplasm
Thymic tumors within the thyroid
1. Thymoma family
2. Spindle epithelial tumor with thymus-like
elements
3. Thymic carcinoma family
2017 WHO classification scheme of
thyroid neoplasm
1. Ectopic thymoma
2. Spindle epithelial tumor with thymus-like
differentiation
3. Intrathyroid thymic carcinoma

54. Thymic tumors within the thyroid
• Postulated to develop from branchial pouch remnants differentiating along the thymic
line
• No major changes in new WHO classification
• Term “Ectopic thymoma”: discouraged

55. New 2022 WHO classification scheme
of thyroid neoplasm
Embryonal thyroid neoplasms
1. Thyroblastoma
2017 WHO classification scheme of
thyroid neoplasm
Malignant teratoma

56. Thyroblastoma
• Embryonal high-grade thyroid neoplasm.
• Predilection for females (3: 1)
• Median age of 43 years (range: 17 to 65 years)
• Presents as rapidly growing mid-cervical thyroid mass diffusely infiltrating one or both
thyroid lobes and extending into perithyroid tissue
• Pathogenesis: arise due to somatic mutations in the DICER1 gene
• Highly aggressive course with >50% of patients dying at a median follow-up of 11.5
months

57. Thyroblastoma
• Three cellular components:
fetal-type primitive-appearing thyroid follicles (TTF1+/PAX8+/focal thyroglobulin+)
Primitive small round to oval cells (SALL 4 +)
Surrounded by a primitive spindle cell stroma of variable cellularity arranged into
fascicles,(usually SMA, desmin and myogenin +)
• Foci of cartilage are seen in half of cases

58. Primitive small round cells Fetal type thyroid cells Primitive stromal component
Jung C K et al. Update from the 2022 WHO classification of thyroid tumor: A standardized diagnostic approach

59. References:
1. Baloch, Zubair W et al. “Overview of the 2022 WHO Classification of Thyroid
Neoplasms.” Endocrine pathology vol. 33,1 (2022): 27-63. doi:10.1007/s12022-022-
09707-3
2. Jung CK, Bychkov A, Kakudo K. Update from the 2022 World Health
Organization Classification of Thyroid Tumors: A Standardized Diagnostic
Approach. Endocrinol Metab (Seoul). 2022 Oct;37(5):703-718. doi:
10.3803/EnM.2022.1553. Epub 2022 Oct 4. PMID: 36193717; PMCID:
PMC9633223.
3. https://tumourclassification.iarc.who.int/chapters/53

60. Thank you