The document describes the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), which was introduced in 2007 to standardize the reporting of thyroid fine needle aspiration (FNA) results. The BSRTC recommends diagnostic categories with implied cancer risks and clinical management guidelines. It provides criteria for adequate samples and defines each diagnostic category, including non-diagnostic, benign, atypia of undetermined significance, follicular neoplasm, suspicious for malignancy, and malignant. The BSRTC aims to improve communication between cytopathologists and clinicians regarding thyroid FNA interpretations and patient management.

1. THE BETHESDA SYSTEM FOR
REPORTING THYROID
CYTOPATHOLOGY
( BSRTC)
Dr.Indira shastry.k
Kasturba medical college
Manipal university, Manipal.

2. History
• Introduced and formed in 2007 , “NCI- thyroid FNA state of science
conference “ Bethesda , Maryland, by various cytopathologists and
summarised by Baloch et al.
• Why ?
critical for cytopathologist to communicate thyroid FNA
interpretation to referring physician in terms that are succinct,
unambiguous and helpful clinically .
Uniform reporting.

3. Format of reporting
• Clarity of communication, the BSRTC recommends that each
thyroid FNA report begin with general diagnostic category .
• For each categories some degree of sub categorization can be
informative and often appropriate.
• Each category has an implied cancer risk association – linked to
evidence based clinical management guidelines.

4. The BSRTC recommended diagnostic categories
I. Non diagnostic or unsatisfactory
cyst fluid only
virtually a cellular smear
other ( obscuring blood, clotting artefact , etc ,.)
II. Benign
Consistent with a benign follicular nodule ( adenomatoid nodule , colloid nodule, etc)
Consistent with lymphocytic (Hashiomoto’s) thyroiditis ; in proper clinical context
Consistent with granulomatous ( subacute ) thyroiditis
other
III. Atypia of Undetermined significance or Follicular Lesion of Undetermined significance
VI. Follicular neoplasm or Suspicious of follicular neoplasm
Specify if Hurthle cell ( oncocytic ) type
V. Suspicious for malignancy
Suspicious for papillary carcinoma
suspicious for medullary carcinoma
suspicious for metastatic carcinoma
suspicious for lymphoma
other

5. The BSRTC recommended diagnostic categories
VI. Malignant
Papillary carcinoma of thyroid
Poorly differentiated carcinoma
Medullary carcinoma of thyroid
Undifferentiated ( Anaplastic ) carcinoma
Squamous cell carcinoma
Carcinoma with mixed features ( specify)
Metastatic carcinoma
Non-Hodgkin’s Lymphoma
Other

6. BSRTC implied risk of malignancy and recommended
clinical management
Diagnostic category Risk of malignancy Usual Management a
Non diagnostic or
Unsatisfactory
Depends on type of lesion in
USG
Repeat FNA under
Ultrasound guidance
Benign 0 - 3 % Clinical follow-up
Atypia of Undetermined
significance or Follicular
Lesion of Undetermined
significance
Approx 5 -15 % Repeat FNA
Follicular neoplasm or
Suspicious for a follicular
neoplasm
15 - 30 % Surgical lobectomy
Suspicious for malignancy 60 - 75 % Near total thyroidectomy or
Surgical lobectomyb
Malignant 97 - 99 % Near total thyroidectomyb
a) Actual management depends on other factors ( clinical , USG etc ,.) besides FNA interpretation
b) In case of “ suspicious of metastatic tumour “ or a “ malignant “ interpretation indicating metastatic
tumour rather than primary malignancy , surgery may not be indicated .

7. Criteria for adequacy
• Minimum of six groups of well visualised ( i.e., Well stained,
undistorted and un obstructed ) follicular cells with at least ten cells
per group ( preferably on a single slide )
• Exceptions : minimum no of follicles not required.
• Solid nodules with significant cytologic atypia - comment on cellularity
as a limiting factor .
• Solid nodules in patients with lymphocytic ( Hashimoto’s) thyroiditis,
thyroid abscess or granulomatous thyroiditis may contain only numerous
inflammatory cells .
• Colloid nodules: abundant thick colloid considered benign and
satisfactory.

8. Non diagnostic or Unsatisfactory
• Cellularity / adequacy is dependent not only on technique of
aspirator but also on type of lesion ( solid or cystic ).
Example :
1. NONDIAGNOSTIC : due to insufficient cellularity
2. NONDIAGNOSTIC : cyst fluid only
3. UNSATISFACTORY : due to poor fixation and preservation
NOTE : A repeat aspiration should be considered if clinically indicated /
Recommended correlation with cyst size and complexity on
ultrasound to assist with further management of lesion.

9. Management:
Re-aspirated but not sooner than 3 months . ( to prevent false
positive interpretation due to reactive or reparative changes)
Poor cell preservation

10. Benign
• Subclassification :
• Benign follicular nodule
• Thyroiditis
• Others
BENIGN FOLLICULAR NODULE (BFN) :
• Nodular goiter(NG)
• Hyperplastic (Adenomatoid ) nodule
• Colloid nodules
• Nodules in grave’s
• Subset of follicular adenoma ( macrofollicular type )

11. • Distinction among these different histological entities are not
possible by FNA but of little importance bec all are benign and
managed in similar conservative manner.
DEFINITION :
“ benign follicular nodule “ applies to cytologic sample that is
adequate for evaluation and consists predominantly of colloid and
benign appearing follicular cells in varying proportion.

12. CRITERIA:
• Adequate with moderate to sparse cellularity.
• Colloid : thick / thin
• Follicular cells : monolayered sheets or follicles (microfollicles +/-)
• No nuclear atypia / pleomorphism
• Minimal/no nuclear overlapping and crowding .
• Cytoplasmic granules (+/-)
• Hurthal cells (+/-)
• Macrophages and may contain haemosiderin pigment.

13. Adenomatous nodule
( macro-follicular type )

14. Graves’ disease (GD)
• Cytological features is non specific, and clinical correlation is required
for definitive diagnosis.
• Aspirates - cellular and show similar features of non graves’ BFN
(abundant collloid and variable no of follicular cells ) .
• Follicular cells : loose cohesive sheets, with abundant delicate foamy
cytoplasm with frayed edges (+/-). Nuclei are often enlarged,
vesicular and prominent nucleoli, mild pleomorphism may be present.
• Lymphocytes and oncocytes may be seen.
NOTE : focal chromatin nuclear clearing and rare nuclear grooves if not
diffuse should not be confused with papillary ca thyroid .

15. Lymphocytic ( Hashimoto’s ) thyroiditis
DEFINITION :
many polymorphic lymphoid cells associated with Hurthle cells
CRITERIA :
• Hypercellular to adequate cellularity ( does not require minimum
cellularity )
• Polymorphic lymphoid population, occasional plasma cells and
may infiltrate epithelial cell groups.
• Intact lymphoid follicles and lympho-histiocytic aggregates (+/-)
• Hurthle cells +( may have prominent anisonucleosis)

17. Granulomatous ( subacute, de quervain’s)
thyroiditis
CRITERIA :
• variable cellularity
• Clusters of epitheliod histiocytes , i.e., granulomas present along with
many multinucleated giant cells
• Early stages : demonstrates many neutrophils and eosinophils
• Late stage : smears are hypocellular. Show giant cells engulfing
colloid, epitheliod cells, lymphocytes, macrophages and scant
degenerated follicular cells.

18. Subacute thyroiditis

19. Acute thyroiditis
CRITERIA :
• Numerous neutrophils associated with necrosis, fibrin,
macrophages and blood.
• Bacterial or fungal organisms are occasionally seen.

20. Riedel’s thyroiditis / disease
• Progressive fibrosis of thyroid gland with extension in to neck soft
tissue.
• CRITERIA :
• Often acellular.
• Colloid and follicular cells are usually absent.
• Collagen strands and bland spindle shaped cells.
• Chronic inflammatory cells may be +

21. Atypia of undetermined significance
( AUS/FLUS )
• Used when FNAs are not easily classified in to Benign, suspicious or
malignant categories.
• AUS result has been reported in 3 – 18 % of thyroid FNA
• Used as a last resort
• CRITERIA : mc sinerios
• Prominent populations of microfollices that does not fulfil the
criteria for “ follicular neoplasm/ suspicious for follicular
neoplasm” - scant cellularity
• Predominance of Hurthle cells with scant cellularity

22. • Interpretation of follicular neoplasm hindered by sample preparation
artefact ( air drying and clotting )
• Clinical setting suggestive of benign nodule ( predominant Hurthle cells
) ; Hashimoto’s / MNG .
• Focal appearance of malignancy ( papillary ca ) in an otherwise
predominantly benign appearing sample .

23. • Cyst lining cells which appear atypical due to presence of nuclear
grooves, prominent nucleoli, elongated nuclei and cytoplasm and /
or intra cytoplasmic inclusions in an otherwise benign appearing
sample.
• A minor population of cells showing atypia in patients with :
• H/O radioactive iodine , carbimazole, and other pharmaceutical agents
ingestion.
• Repair due to involution changes - cystic degeneration &/ haemorrhage
• Atypical lymphoid infiltrate but the degree of atypia is insufficient .

24. MANAGEMENT :
• For initial diagnosis – clinical correlation and repeat FNA at
appropriate interval .
• 20 – 25 % of the nodule repeated as AUS
• In resected thyroid only 20 – 25 % found to have malignancy
• Overall risk of malignancy for all AUS nodule is 5 – 15 %

25. Follicular neoplasm / suspicious for
follicular neoplasm
• To identify nodule that might be FC and triage it to surgical lobectomy
• Does not differentiate between FA and FC ; FN or suspicious of FN
used instead -> lobectomy -> definitive diagnosis.
• Some prefer suspicious of FN bec significant proportion of cases (35%
) are due to hyperplasic proliferation in MNG.
• Rate of malignancy is 12 – 32 %. Most of them are follicular variant of
papillary ca thyroid.
• Parathyroid adenomas are often misinterpreted as FN / SFN

26. CRITERIA :
• Cytomorphology : high cellularity, scant to absent colloid , micro
follicles to trabacular arrangement with cellular crowding and
overlapping ( altered architectural pattern )
• Nuclear atypia ( mild ) / mitosis: uncommon
• If majority of follicles are arranged in macrofollicle fragments (
variably sized with out overlapping or crowding ) considered benign.
• Conspicuous cellularity alone does not qualify for FN/SFN
• Sparsely cellular fragments with cytomorphology of FN/SFN
reasonable to interpret as AUS / FLUS .

27. Microfollicle - <15 cells in a circle that is at least
2/3 rd complete

28. FN Hurthle cell type / SFN , Hurthle
cell type
• Defn : Refers to cellular aspirate that consists exclusively of ( or almost
exclusively ) of hurthle cells. (>75%)
• Criteria :
• Highly cellular aspirate , abundant finely granular cytoplasm
• Enlarged centrally or eccentrically located nucleus with prominent
nucleolus.
• Small cell dysplasia : small cells with high N:C ratio
• Large cell atypia : large cells with at least 2X variability in nuclear
size
• Crowded or syncytial arrangement with or with out colloid

29. moderate to markedly cellular aspirates
Colloid
Small / large cell
dysplasia
Benign
Note : although predominance of
hurthle cells arises the possibility of
hurthle cell neoplasm, the absence
of atypia suggest it is benign
Benign lesion
( with out atypia )
+ -
+ -
FNHCT/SFNHCT

31. Mimickers :
• MNG with focal hurthe cell change : mixture of elements , flat
cohesive sheets of hurthle cells admixed with normal follicular
cells, colloid + and clinico-cytologic correlation.
• LT nodules : hurthle cells are atypical in stereotypical way i e.,
they form small cohesive clusters of 3-10 cells, large nuclei,
smudgy sometimes glassy chromatin . Can mimic cells in Pap
ca . Clinical correlation is of importance.

32. Hurthle cell metaplasia in MNG

33. • Oncocytic variant of papillary carcinoma thyroid :
attention to nuclear details. If not diagnosed as suspicious
for malignancy. ( diagnosed at the time of frozen )
• Medullary carcinoma of thyroid : MGG - cytoplasm of
hurthle cells are blue . Medullary carcinoma thyroid are
red.
• Parathyroid adenomas : radiological correlation, serology
or frozen .
Medullary carcinoma of thyroid Hurthle cell neoplasm

34. Suspicious for malignancy ( SFM )
• SFM interpritation indicates the less than definitive nature of the
diagnosis and allows alternative management options ( frozen /
lobectomy ) before definitive surgery ( total thyroidectomy )
• The target PPV of this cat is 55-85 %.
Definition :
Strong suspicion for malignancy, but findings are not sufficient
for a conclusive diagnosis.

35. Suspicious of papillary carcinoma of thyroid :
• Pattern A (“ patchy nuclear changes “ )
• Benign follicular cells ( macrofollicles ) admixed with cells that
have nuclear enlargement, nuclear pallor, nuclear grooves, NM
irregularities, &/ nuclear moldings.
• Intranuclear cytoplasmicinclusions ( INCIs )are rare / absent
• Pattern B ( “ incomplete nuclear changes “)
• Generalised mild to moderate nuclear enlargement with mild
nuclear pallor .
• Evident nuclear grooves, NM irregularities and nuclear
moulding are minimal or absent.
• INCIs are rare / absent

36. • Pattern C ( “ sparsely cellular specimen “)
• Cellular features of PTC present but very sparsely cellular
• Pattern D (“ cystic degeneration “)
• Haemosiderin laden macrophages +
• Scattered groups and sheets of follicular cells , enlarged , pale
nuclei, some have nuclear grooves .
• INCIs rare / absent
• Occ atypical histiocytoid cells + , calcification +

37. Mimickers :
• Lymphocytic thyroiditis
• Cystic degenerative changes with reactive atypia
• Radioiodine and carbimazole treatment.
no definitive / reliable cytological features can differentiate these
from pap ca
• Hyalinising trabecular tumor ( HTT ) : definitive features are difficult to
appreciate in FNAC .

38. Suspicious for medullary carcinoma thyroid :
• Thyroid FNA has higher sensitivity for detection of MTC than
PTC
• Sparse to moderatley cellular
• Monomorphic population of noncohesive small to medium
sized cells , high N:C ( ? Lymphoid / ? Medullary )
• Small amt of ? Colloid/? amyloid
• Clinico-pathologial correlation : S. Calcitonin
• Diagnostic pitfall : cellularity and preservation
Amyloid Colloid

39. Suspicious for Lymphoma
• Monomorphic small to intermediate lymphoid cells.
• Diagnostic limitation :
• DLBCL : technical ( cellularity and preservation )
• Low grade lymphoma ( MALT / follicular ) : MALT is difficult to
distinguish from LT with out Immunophenotyping .
• False positive results have been reported with LT.
• Definitive diagnosis : Flow cytometry

40. Ex:
• Suspicious for papillary carcinoma thyroid
• Suspicious for medullary thyroid carcinoma
• Note : correlation with S.calcitonin level or re-aspiration for
IHC studies might be helpful for definitive diagnosis if
clinically indicated.
• Suspicious for lymphoma
• Re- aspiration for immunophenotyping studies by flow
cytometry might be helpful for definitive diagnosis if clinically
indicated.

41. Papillary thyroid carcinoma
• Criteria :
• Follicular cells are arranged in papillae &/ syncytial monolayers.
• Characteristic nuclear features : enlarged nuclei , oval or
irregularly spaced/ moulded nuclei, longitudinal nuclear
grooves, INCI, pale nuclei with powdery chromatin ( “Orphan
Annie eye” nuclei ), marginally placed micronucleoli (solitary or
multiple ).
• Psammoma bodies +/-
• Amount of colloid is variable ( ropy / bubble gum colloid )

43. • None of nuclear features are diagnostic of PTC in isolation, only
when widespread and in combination they are diagnostic of PTC.
• crowding, overlapping, and moulding are important diagnostic
features – distinguish from benign follicular cells.
• various subtypes/ variants can be identified in FNA.
• Precise sub-typing is not possible ; prominent pattern may not
have been sampled in FNA.
• Awareness of cytological characteristics of various subtypes can
diminish the risk of misdiagnosis.

44. Variants of PTC
Follicular variant : ( Mc variant of PTC – 30% )
• Tumor composed of almost completely of small to medium sized
follicles lined by cells with nuclear features of PTC.
• Some colloid may be present : dense
• INCI, PB, papillary architecture, cystic changes are typically absent.

46. Macrofollicular variant :
• Over 50 % of the follicles are arranged as macrofollicles /
variably sized follicles.
• With convincing nuclear features of PTC often subtle.
• Abundant thick colloid may be present.
• DD: follicular nodule in nodular goiter and follicular adenoma
of macrofollicular type.

47. Cystic variant :
• PTC predominantly cystic , comprised of thin watery fluid, abundant
histiocytes and hyper-vacoulated ( histiocytoid )tumor cells.
• Neoplastic cells typically arranged in small groups with irregular
borders; sheets, papillae/ follicles +.
• Hemosidrin laden macrophages , variable amt of colloid +.
• Usually diagnosed as nondiagnostic : cyst fluid only.
• DD: cystic change in benign nodule regenerating cells arranged in
streaming sheets but can be distinguished their elongated shape,
lack of nuclear crowding and INCI.

48. Cystic change in papillary thyroid carcinoma

49. Oncocytic variant :
• Nuclear features are characteristic of PTC but composed
predominantly of oncocytic cells.
• Cyto :
• papillae, sheets or isolated cells.
• Lymphocytes are typically absent.
• DD: hurthle cell neoplasm : rounder nuclei and prominent nucleoli

50. Warthin-like variant :
• Circumscribed thyroid tumor with papillary architecture
and lymphoid follicles mimic warthin tumor of salivary
gland.
• Cyto : oncocytic cells arranged in papillae , singly
dispersed. Lymphoplasmacytic background, permeating
the fibrovascular stalk.
• DD: Hashimoto’s thyroiditis

51. Tall cell variant :
• An aggressive form of PTC, occur in elderly more in males.
• Cyto : papillae lined by single layer of elongated( tall – to
width ratio of at least 3:1 ) tumor cells with abundant
granular cytoplasm. At least 50% tumor .
• INCI tend to be more frequent imparting “soap bubble”
appearance to nucleus .

52. EXAMPLE
• MALIGNANT ;
• Papillary thyroid carcinoma
• MALIGNANT :
• Papillary thyroid carcinoma , favour tall cell variant

53. Medullary thyroid carcinoma
• MTC comprises of approximately 7 % of thyroid neoplasm's.
• Derived from and morphologically recapitulate the parafollicular
cells.
• The diagnosis of MTC can be suggested by cytomorphology, but
confirmed by IHC .
• DD : Hurthle cell neoplasm
• Papillary carcinoma
• Anaplastic carcinoma
• plasmacytoma

54.  Syncitia like clusters
alternate with numerous
islands of cells.
 Plasmacytoid, polygonal,
round and / or spindle shaped.
 Mild to moderate
pleomorphism.
 Nuclei : round , eccentrically
placed ,“ salt pepper “
chromatin.
 Cytoplasm : granular , MGG
stain : pink granules ( 80% )
 Amyloid often present.
 Bizarre giant cells may be
seen : giant cell variant.
IHC calcitonin

55. Poorly differentiated carcinoma
• Rare malignancy – 4 – 7 %
• Criteria :
• Cellular aspirates : Insular, solid, or trabecular cytoarchitecture.
• Un-uniform population of follicular cells , scant cytoplasm ( sometimes
plasmacytoid)
• High N:C ratio ; marked nuclear atypia
• Apoptosis & mitotic activity + , necrosis +.
• Insular form : ch endothelial cell wrapping
• Pitfall : less specificity.
• WHO( endocrine ): “definitive diagnosis of poorly differentiated
carcinoma can be made only at histological level”

56. DD :
follicular neoplasm ( SFN- 42 % ),
Papillary carcinoma ( 15 % ),
carcinoma NOS ( 10 % ),
Medullary carcinoma,
lymphoma.

57. Undifferentiated ( Anaplastic )carcinoma
• K/S “ giant and spindle cell carcinoma “ - < 5%
• High grade pleomorphic, epithelial derived malignancy with
epitheloid and / spindle cell features.
• Plasmacytoid / Rhabdoid cell features may be seen.
• Nucleus : pleomorphic, irregular, clumping of chromatin with
parachromatin clearing.
• Necrosis – extensive ; abscess like , neutrophilic infiltration of
tumor cells.
• Osteoclast like giant cells +/-

59. Squamous cell carcinoma
• 1 % of primary thyroid malignancy
• Poorly differentiated : large, pleomorphic, keratinised cells
• Morphologically and immunohistochemically
Indistinguishable from mets from other organs .
• EX :
malignant :
consistent with SCC of thyroid
Note : the distinction B/W primary / mets from other
organs not possible. Correlation with clinical and imaging
is advised.

60. Metastatic tumors
• Metastasis to thyroid from other organs is rare: lung, breast,
skin ( melanoma ), colon, and kidney.
• Malignant lymphomas: can arise in thyroid as primary but
secondary involvement is MC .
• Lymphomas represent 5 % of thyroid malignancy, usually
associated with Hashimoto’s thyroiditis.
• Criteria :
• Cellular mostly lymphocytes.
• Lymphocytes : 2 X small mature lymphocyte
• Background of numerous lymphoglandular bodies
• Vesicular nuclei / coarse chromatin with prominent nucleoli

61. Patterns of lymphoma on FNA
Monomorphous
population of small
lymphocytes
Monotonous
population of large
lymphocytes
Mixture of small and
large lymphocytes
Absence of oncocytes,
follicular cells, and
plasma cells favour
lymphoma
DD : Hashimoto’s
Morphologically
diagnostic
DD: inactive
thyroiditis
Definitive diagnosis : flow cytometry / IHC on HP

62. • Secondary involvement by MALT / DLBCL is 20% in disseminated
lymphoma.
• MALT : monocytoid / plasmacytoid B cells in isolation / in
clusters.
• DLBCL : monotonous large lymphocytes in non cohesive clusters.
MALT DLBCL

63. References
• Syed ali. Edmund S. Cibas : The Behtesda system for
reporting thyroid cytopathology.
• Orell & sterrett’s FNAC . 5th ed
• Gray . Diagnostic cytopathology . 3rd ed