The presentation has been prepared according to the new addition of Bethesda system

1. THE BETHESDA SYSTEM
FOR REPORTING
THYROID
CYTOPATHOLOGY
PRESENTER-DR.MUTAKANI AMANI(JR1,PATHOLOGY,GMC,GONDIA)
GUIDE-DR.POOJA BAMBORDE(SR,PATHOLOGY,GMC,GONDIA)

2. INTRODUCTION
 Located in the neck, anterior to the
trachea.
 Consists of two conical lobes connected
by the isthmus.
 The lobes are divided by fibrous septa into
lobules, each containing 30 to 40 follicles.
 Weight : 15-40gms

3. PROCEDURE OF THYROID
FNAC
 TO KNOW IF IT IS A THYROID
MASS : Palpate the mass while the
patient swallows. If it moves with
swallowing, it is in the thyroid.
 The aspiration is best performed with
the patient supine and neck
hyperextended using a 22 or 25
gauge needle.

4. UPDATES(2023)
 Unification of Diagnostic categories under a single name.
 Data informing use of TBSRTC in Pediatric population is now included. The ROM is
higher in children when compared to adult.
 The ROM has been further refined.
 More formalized sub categorization of AUS based on ROM.
 Terminology used has been harmonized with latest WHO 2022 classification.
 Updates in images.

5. ISSUES ADDRESSED BY BETHESDA
SYSTEM
 Indications of thyroid FNA
 Reporting of FNA based on standard terminology and morphologic criteria
 Post FNA management guidelines for clinicians.
 Risk of malignancy associated with each category.

8. Nondiagnostic
 A specimen is considered “nondiagnostic” if it fails to meet
the following adequacy criteria.
Criteria for Adequacy
 Minimum of six groups of well-visualized (i.e., well
stained, undistorted, and unobstructed) follicular cells,
with at least ten cells per group.
 They could be either on one slide/distributed among
several for adequacy determination.

9. Exceptions to this adequacy criteria
 1. Aspirates with cytologic atypia : It is mandatory to report any significant
atypia; a minimum number of follicular cells is not required.
 2. Solid nodules with inflammation. Nodules in patients with lymphocytic
(Hashimoto) thyroiditis, thyroid abscess, or granulomatous thyroiditis may contain only
numerous inflammatory cells.
 3. Colloid nodules. Specimens that consist of abundant colloid are considered benign
and satisfactory for evaluation.

10. The following scenarios describe cases
considered nondiagnostic
 Fewer than six groups of well-preserved, well-stained follicular cell groups
with ten cells each (see exceptions above)
 Poorly prepared, poorly stained, or significantly obscured follicular cells
 Cyst fluid, with or without histiocytes, and fewer than six groups of ten
benign follicular cells
 No cellular material present
 Blood only
 Ultrasound gel precipitates only
 Lack of collection of cells from targeted lesion

12. BENIGN

13. Benign
 Follicular nodular Disease
 Graves disease
 Lymphocytic (Hashimotos) thyroiditis
 Granulomatous (sub-acute , de Quervain) thyroiditis
 Acute thyroiditis
 Riedels thyroiditis / disease

14. Follicular Nodule Disease
 Definition
The designation “follicular nodular disease” applies to a cytologic sample that is
adequate for evaluation and consists of colloid and benign-appearing follicular cells in
varying proportions.

15. CRITERIA FOR FOLLICULAR NODULAR
DISEASE
 Specimens are sparsely to moderately cellular.
 Colloid is viscous, shiny, and light yellow or gold
in color (resembling honey or varnish) on gross
examination.
 Thick (dense, “hard”) colloid has a hyaline
quality and often shows cracks

16.  Thin, watery colloid often forms a “thin
membrane/cellophane” coating or film with
frequent folds that impart a “crazy pavement,”
“chicken wire,” or mosaic appearance.

17.  Follicular cells are arranged
predominantly in monolayered sheets
and are evenly spaced (“honeycomb-
like”) within the sheets or occasionally
in 3 dimentional balls / spheres
 Follicular cell nuclei are round to oval,
approximately the size of a red blood
cell (7–10 μ in diameter), and show a
uniformly granular chromatin pattern

18. Graves’ Disease
 Abundant colloid
 Cellular smear
 Follicular cells are arranged in flat sheets
and loosely cohesive groups, with abundant
delicate, foamy cytoplasm
 Nuclei are often enlarged ,vesicular , and
show prominent nuclei
 Distinctive “flame cells” may be prominent

19. Lymphocytic Thyroiditis
 Usually hypercellular
 Oncocytic cells (Hürthle cells)
 Anisonucleosis of Hürthle cells
(oncocytes) may be prominent.
 The lymphoid cells may be in the
background or infiltrating epithelial cell
groups

20. Granulomatous (de Quervain) Thyroiditis
 The cellularity is variable and depends on the
stage of disease
 Early stage demonstrates many neutrophils and
eosinophils
 Later stages : preparations are hypocellular.
 In the involutional stage, giant cells and
inflammatory cells may be absent
 Granulomas (clusters of epithelioid histiocytes)

21. Acute Suppurative Thyroiditis
 Numerous neutrophils are associated with
necrosis, fibrin, macrophages, and blood
 There are scant reactive follicular cells
and limited to absent colloid.
 Bacterial or fungal organisms are
occasionally seen in the background,
especially in immunocompromised
patients

22. Riedel Thyroiditis/Disease
 The preparations are often acellular.
 Collagen strands and bland spindle cells
may be present .
 There are rare chronic inflammatory cells.
 Colloid and follicular cells are usually
absent

23. Atypia of Undetermined
Significance

24. Criteria
AUS WITH NUCLEAR
ATYPIA
 (a) Focal Nuclear Atypia :
Most of the aspirate appears benign, but
rare cells have nuclear enlargement, pale
chromatin, and irregular nuclear contours.
Nuclear pseudoinclusions
are typically absent.

25.  (b)Extensive but mild nuclear atypia :
Many cells have mildly enlarged nuclei with
slightly pale chromatin and only limited nuclear
contour irregularity
Nuclear pseudoinclusions
are typically absent.

26.  (c) Atypical cyst-lining cells :
some cells have abundant cytoplasm,
enlarged nuclei, and prominent nucleoli.
Such changes may represent atypical but
benign cyst-lining cells, but a papillary
carcinoma cannot be entirely excluded.

27.  (D) “Histiocytoid cells” :
The histiocytoid cells are larger than
histiocytes, typically isolated but sometimes
in microfollicular arrangements or clusters.
They often have rounder nuclei, a higher
nuclear-to-cytoplasmic ratio, and “harder”
(glassier) cytoplasm, larger, discrete vacuoles
are present.

28.  (E)NUCLEAR AND ARCHITECTURAL ATYPIA:
Mild cytologic atypia coexist with architectural alterations.

29. AUS-Others
(A)ARCHITECTURAL ATYPIA:
 (a) A scantly cellular specimen with rare
clusters of follicular cells, almost entirely
in microfollicles or crowded three-
dimensional groups and with scant colloid
 (b) Focally prominent microfollicles with
minimal nuclear atypia

30. (B). Oncocytic /oncocyte atypia
 A sparsely cellular aspirate comprised
exclusively (or almost exclusively) of
oncocytic cells (Hürthle cells) with minimal
colloid
 (b) A moderately or markedly cellular
sample composed exclusively (or almost
exclusively) of oncocytic cells

31. (C). Atypia, not otherwise specified (NOS)
 (a) A minor population of follicular cells shows nuclear
enlargement, often accompanied by prominent
nucleoli
 (b) Psammomatous calcifications in the absence of
nuclear features of papillary carcinoma

32. (D). Atypical lymphoid cells, rule out
lymphoma

33. Follicular Neoplasm

34. Criteria
 Moderately or markedly cellular
 Significant alteration in follicular cell architecture,
characterized by cell crowding, microfollicles, and
dispersed isolated cells
 scant or moderate amounts of cytoplasm
 Nuclei : round and slightly hyperchromatic, with
inconspicuous nucleoli
 Colloid is scant or absent.

35. Micro follicle
 crowded, flat groups of less than 15
follicular cells arranged in a circle that is at
least two-thirds complete

36. Follicular Neoplasm(Oncocytic
Follicular Neoplasm)

37. Criteria
 moderately to markedly cellular.
 The sample consists exclusively (or almost
exclusively) of Oncocytes
- Abundant finely granular cytoplasm
- Enlarged, central or eccentrically
located, round nucleus
- Prominent nucleolus

38.  Small cells with high nuclear/cytoplasmic
(N/C) ratio (small-cell dysplasia)
 Large cells with at least two times variability
in nuclear size (large-cell dysplasia)
 Binucleation is fairly common.
 Little or no colloid.
 No lymphocytes

39. Suspicious for
Malignancy

40. Definition
 The term is used when some cytomorphologic features (most often those of PTC)
raise a strong suspicion of malignancy but the findings are not sufficient for a
conclusive diagnosis.
 Specimens that are suspicious for a follicular or oncocytic neoplasm are excluded
from this category

41. Criteria

42. Pattern A (Patchy Nuclear Changes Pattern
 Mostly unremarkable follicular cells (predominantly in
macrofollicles).
 Few cells : nuclear enlargement, nuclear pallor, nuclear
grooves, nuclear membrane irregularity, and/or nuclear
molding.
 Intranuclear pseudoinclusions (INCIs), Psammoma bodies
and papillary architecture : absent
Suspicious for Papillary Thyroid
Carcinoma

43. Pattern B (Incomplete Nuclear Changes Pattern
 sparsely, moderately, or highly cellular.
 Mild-to-moderate nuclear enlargement with mild
nuclear pallor. Nuclear grooves are evident.
 Intranuclear pseudoinclusions (INCIs), Psammoma
bodies or papillary architecture : absent.

44. Pattern C (Sparsely Cellular Specimen Pattern)
 Many of the features of PTC are present, but the sample is very sparsely cellular.

45. Pattern D (Cystic Degeneration
Pattern)
 There is evidence of cystic degeneration based
on the presence of hemosiderin-laden
macrophages.
 Pseudo nuclear inclusions, psammoma bodies
or papillary architecture : absent
 There are occasional large, atypical,
“histiocytoid” cells with enlarged nuclei and
abundant vacuolated cytoplasm

46. Suspicious for Medullary Thyroid
Carcinoma
 Sparsely or moderately cellular.
 Monomorphic population of noncohesive
small- or medium-sized cells with a high
nuclear/cytoplasmic (N/C) ratio.
 Nuclei are eccentrically located, with
smudged chromatin.
 There may be small fragments of
amorphous material – amyloid

47. Suspicious for Lymphoma
 monomorphic
 Sparsely cellular.
 Contains atypical lymphoid cells

48. Suspicious for Malignancy, Not Otherwise
Specified
 Undifferentiated carcinoma
 Poorly differentiated carcinoma
 metastasis

49. MALIGNANCY

50. Papillary Thyroid Carcinoma
CRITERIA
 Enlarged and crowded nuclei, often molded
 Oval or irregularly shaped nuclei
 Longitudinal nuclear grooves
 Pale nuclei with powdery chromatin
 Thick nuclear membranes
 Macronucleoli or micronucleoli, central or marginally
placed

51.  Variable amount of colloid; may be stringy,
ropy, or “bubblegum”-like Hobnail cells
 Oncocytic metaplasia
 Squamoid metaplasia

52.  Intranuclear cytoplasmic pseudoinclusions
(INCIs)

53.  Cells arranged in papillae and/or
monolayers  Cellular swirls (“onion-skin” or
“cartwheel”)

54.  Psammoma bodies
 “Histiocytoid” cells

55. Follicular Variant of PTC and NIFTP
 Hypercellular
 Dispersed microfollicular clusters, isolated
neoplastic follicles
 Nuclear changes are subtle.
 Following features are usually absent or
inconspicuous: papillary and papillary-like
fragments, multinucleated giant cells,
INCIs, psammoma bodies, and marked
cystic change.

56. Macro follicular Variant
 It is defined as a PTC in which 50% of the
follicles are arranged as macrofollicles
(follicles measuring more than 200 μm in
diameter)
 monolayered (two-dimensional) sheets of
neoplastic epithelium and/or variably sized
follicles
 nuclear features are subtle.

57. Cystic Variant
 Arranged in small groups with irregular
borders; sheets, papillae, or follicles may
also be present.
 Tumor cells look “histiocytoid”
(hypervacuolated).
 Macrophages containing hemosiderin
 Variable amount of thin or watery colloid
 Convincing nuclear changes of PTC must be
present

58. Oncocytic Variant
 predominantly of oncocytic cells (polygonal
cells with abundant granular cytoplasm),
arranged in papillae, sheets, microfollicles, or
as isolated cells.
 nuclear changes of PTC
 Lymphocytes are absent or few in number.

59. Warthin-Like Variant
 Oncocytic cells arranged in papillae and
as dispersed cells.
 Lymphoplasmacytic background.
 Convincing nuclear changes of PTC

60. Tall Cell Variant
 Polygonal cells with centrally located
nuclei but can be elongated and
cylindrical with an eccentrically placed
nucleus (“tail-like cells” or “tadpole
cells”).
 Convincing nuclear changes of PTC

61. Columnar Cell Variant
 Papillae, clusters, and flat sheets,
sometimes with small tubular structures.
 The nuclei are elongated and
pseudostratified.
 Focal cytoplasmic vacuolisation.
 Convincing nuclear changes of PTC

62. FEW OTHER VARIANTS OF PTC
 SOLID VARIANT
 DIFFUSE SCLEROSING VARIANT
 CRIBRIFORM – MORULAR VARIANT
 HOB NAIL VARIANT
 HYALINIZING TRABECULAR TUMOR / HYALINIZING TRABECULAR
ADENOMA

63. Medullary Thyroid Carcinoma
 Moderate to marked cellularity.
 Cells are plasmacytoid, polygonal, round, and/or
spindle-shaped.
 mild to moderate pleomorphism
 Nuclei are round, oval, or elongated and often
eccentrically placed, with finely or coarsely
granular (“salt and pepper”) chromatin.
 Binucleation is common.
 Nucleoli are usually inconspicuous.
 Cytoplasm is granular and variable in quantity.
 AMYLOID

64. High-grade Follicular cell-Derived Non-
Anaplastic Thyroid carcinomas
 Insular, solid, or trabecular cytoarchitecture
 uniform population of malignant follicular cells
with scant cytoplasm (sometimes plasmacytoid)
or with oncocytic features.
 The cells have a high nuclear/cytoplasmic (N/C)
ratio with variable nuclear atypia
 Colloid is scant.

65. • Apoptosis and mitotic activity .
• Necrosis is often present.

67. Undifferentiated (Anaplastic) Carcinoma
 Cells are epithelioid and/or spindle-shaped.
“Plasmacytoid” and “rhabdoid” cell shapes are
seen.
 Nuclei show enlargement, irregularity, extreme
pleomorphism, clumping of chromatin with
parachromatin clearing, prominent irregular
nucleoli, intranuclear pseudoinclusions,
eccentric nuclear placement, and
multinucleation.
 Necrosis, extensive inflammation
 Mitotic figures are often numerous and
abnormal.
 Osteoclast-like giant cells (nonneoplastic) are
conspicuous

68. METASTATIC TUMORS
 Metastases from distant organs and direct extension from tumors in adjacent organs are
uncommon but important to recognize in fine needle aspiration (FNA) samples of thyroid
nodules.
 Metastatic carcinomas characteristically present in one of three patterns:
(1) multiple small discrete nodules less than 2 mm in diameter,
(2) solitary large nodules, and
(3) diffuse involvement.
 Common tumors that present clinically as metastases to the thyroid are cancers of the
lung, breast, skin (especially melanoma), colon, and kidney

71. LYMPHOMA OF THYROID
 Markedly cellular.
 Composed of noncohesive round to slightly oval cells.
 Lymphoglandular BODIES
 Marginal zone lymphoma are about twice the size of a small mature lymphocyte.
 Nuclei have vesicular (“open”) chromatin
 Diffuse large B-cell lymphomas contain cells with moderate to abundant basophilic
 cytoplasm. Nuclei have coarse chromatin with one or more prominent nucleoli

73. THANK YOU