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103

J Gandhara Med Dent Sci

October - December 2026

ORIGINAL ARTICLE

How to cite this article

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DIAGNOSTIC PERFORMANCE AND RADIOCYTOLOGICAL CORRELATION OF ACR TI-RADS IN

THYROID NODULES USING BETHESDA-REPORTED FNAC AS THE REFERENCE STANDARD

Shanza Khan

1

, Maimoona Afsar

2

, Ashfa Ameer Khan

2

, Wajeeha Rahman

2

, Hasina Gohar

1

,

Asad Rehman

1

Khan S, Afar M, Khan AA, Rahman

W, Gohar H, Rehman A.

Diagnostic Performance and

Radiocytological Correlation of Acr

Ti-Rads in Thyroid Nodules Using

Bethesda-Reported Fnac as the

Reference Standard. J Gandhara Med

Dent Sci. 2026;13(4):103-107.

Date of Submission:

02-03-2026

Date Revised:

11-03-2026

Date Acceptance:

14-03-2026

1

Trainee medical Ofﬁcer, Department

of Frontier Corps Teaching Hospital,

Peshawar

Correspondence

2

Maimoona Afsar, Consultant

Radiologist, Department of Frontier

Corps Teaching Hospital, Peshawar

+92-332-9808373

Maimoonaafsar86@gmail.com

ABSTRACT

OBJECTIVES

This

study

aimed

to

evaluate

the

diagnostic

performance

and

radiocytological

concordance

of

American

College

of

Radiology

Thyroid

Imaging Reporting and Data System (ACR TI-RADS) categories for thyroid

nodules, using ﬁne-needle aspiration cytology (FNAC) reported according to

the Bethesda System as the reference standard.

METHODOLOGY

This cross-sectional study included 134 adults aged 18–80 years presenting

with clinically suspected thyroid nodules to the Department of Radiology, FC

Teaching

Hospital,

Peshawar.

High-resolution

ultrasound

was

performed

with

a

high-frequency

linear

transducer,

and

nodules

were

scored

for

composition,

echogenicity,

shape,

margins,

and

echogenic

foci.

Two

radiologists

independently

reviewed

ultrasound

ﬁndings

while

blinded

to

cytology.

Ultrasound-guided

FNAC

was

subsequently

performed

and

categorised by the Bethesda System. For the submitted analysis, Bethesda IV–

VI

constituted

the

cytologically

high-risk

reference

category

and

ACR

TI-

RADS TR4–TR5 constituted a positive ultrasound test. Sensitivity, speciﬁcity,

positive

predictive

value,

negative

predictive

value,

and

overall

accuracy

were calculated.

RESULTS

Mean participant age was 44.8 ± 12.6 years, and 102 (76.1%) were female.

Thirty-eight

nodules

(28.4%)

were

classiﬁed

as

Bethesda

IV–VI.

ACR

TI-

RADS

demonstrated

89.5%

sensitivity,

85.4%

speciﬁcity,

70.8%

positive

predictive

value,

95.3%

negative

predictive

value,

and

86.6%

overall

accuracy.

Higher

TI-RADS

categories

were

signiﬁcantly

associated

with

higher-risk Bethesda cytology (p<0.001).

CONCLUSION

ACR

TI-RADS

showed

strong

diagnostic

discrimination

and

a

particularly

high negative predictive value against Bethesda-reported FNAC. Structured

ultrasound

risk

stratiﬁcation

may

support

biopsy

selection

and

reduce

avoidable

procedures,

although

indeterminate

Bethesda

categories

should

not be interpreted as histologically proven malignancy in this clinical cohort.

KEYWORDS:

Thyroid

Nodule;

Ultrasonography;

ACR

TI-RADS;

Fine-

Needle

Aspiration

Cytology;

Bethesda

System;

Diagnostic

Accuracy;

Risk

Stratiﬁcation

INTRODUCTION

Thyroid

nodules

are

among

the

most

frequent

abnormalities

detected

during

neck

imaging,

and

their

apparent prevalence has increased with widespread use

of

high-resolution

ultrasonography.

Population-based

evidence

indicates

that

sonography

identiﬁes

substantially more nodules than palpation, while only a

minority

ultimately

represent

clinically

important

malignancy.

This

imbalance

creates

a

practical

diagnostic

problem:

clinicians

must

identify

nodules

that require tissue sampling without exposing the much

larger

group

of

low-risk

patients

to

unnecessary

invasive

procedures.

Contemporary

epidemiological

syntheses

conﬁrm

marked

geographic

variation

in

nodule prevalence, inﬂuenced by age, sex, iodine status,

imaging

intensity,

and

population

characteristics.

1

Ultrasound is the principal imaging modality for thyroid

nodule

characterisation

because

it

is

widely

available,

inexpensive,

non-ionising,

and

capable

of

depicting

morphological features linked to malignancy. Features

such as marked hypoechogenicity, irregular or lobulated

margins, punctate echogenic foci, and a taller-than-wide

configuration

increase

suspicion,

whereas

spongiform

or

predominantly

cystic

morphology

is

generally

associated with lower risk. The clinical value of these

features

depends

on

consistent

terminology

and

reproducible

interpretation.

The

American

College

of

http://doi.org/10.37762/jgmds.13-4.889

104

J Gandhara Med Dent Sci

October - December 2026

Radiology introduced ACR TI-RADS to standardise the

description,

scoring,

and

management

of

thyroid

nodules by assigning weighted points for composition,

echogenicity, shape, margin, and echogenic foci.

2

ACR

TI-RADS is designed not merely to predict risk but also

to guide decisions regarding ﬁne-needle aspiration and

imaging follow-up according to both risk category and

nodule

size.

This

is

especially

relevant

in

resource-

constrained

settings,

where

unnecessary

procedures

increase workload, cost, patient anxiety, and pathology

demand. Major thyroid guidelines similarly emphasise

selective biopsy based on sonographic risk and clinical

context rather than routine aspiration of every detected

nodule.

3

FNAC

remains

the

standard

preoperative

cytological investigation for suspicious thyroid nodules.

The

Bethesda

System

for

Reporting

Thyroid

Cytopathology provides a six-category framework that

standardises

cytological

interpretation

and

communicates

an

implied

risk

of

malignancy

and

a

corresponding

management

pathway.

4,5

Several

comparative

studies

have

shown

that

structured

TI-

RADS

systems

can

preserve

clinically

acceptable

sensitivity

while

reducing

avoidable

FNAC,

although

their

thresholds

and

trade-oﬀs

diﬀer.

6,7,8,9

The

2023

Bethesda

revision

harmonised

terminology

with

the

current

World

Health

Organisation

classiﬁcation

and

updated risk estimates.

4

Importantly, Bethesda category

IV

represents

follicular

neoplasm

rather

than

cytologically

proven

malignancy,

and

category

V

is

suspicious

for

malignancy.

Deﬁnitive

diagnosis

of

follicular carcinoma requires demonstration of capsular

or

vascular

invasion

on

histopathology.

Consequently,

when FNAC is used as the reference

standard, results

should be described as cytological risk or concordance

rather

than

histological

truth.

Radio-cytological

correlation can nevertheless be clinically useful. Higher

ultrasound

risk

categories

should

correspond,

in

aggregate,

to

higher-risk

cytology.

Studies

from

diﬀerent

populations

have

reported

meaningful

concordance

between

TI-RADS

and

Bethesda

categories, supporting the role of ultrasound as a triage

tool

before

aspiration.

9,10

However,

performance

estimates

are

inﬂuenced

by

referral

patterns,

disease

prevalence, biopsy thresholds, operator experience, and

the

way

indeterminate

cytology

is

handled.

Hospital-

based cohorts therefore require local validation before

published

sensitivity

or

speciﬁcity

estimates

are

generalised to routine practice. Data from Pakistan and

neighbouring

South

Asian

populations

remain

comparatively limited, despite a high clinical volume of

thyroid disease. Local evaluation is important because

referral

patterns

and

access

to

specialist

imaging

or

cytopathology may diﬀer from settings in which ACR

TI-RADS

was

originally

validated.

A

reliable

risk-

stratiﬁcation

approach

could

improve

selection

for

FNAC, reduce unnecessary biopsy of low-risk nodules,

and

prioritise

patients

whose

sonographic

appearances

warrant prompt tissue assessment. The objective of this

study

was

therefore

to

evaluate

the

diagnostic

performance and radio-cytological concordance of ACR

TI-RADS in adult patients with thyroid nodules, using

Bethesda-reported FNAC as the reference standard.

Diagnostic Performance and Radiocytological Correlation

METHODOLOGY

A cross-sectional validation study was conducted in the

Department

of

Radiology,

FC

Teaching

Hospital,

Peshawar. The submitted manuscript speciﬁes a three-

month recruitment period. Institutional ethical approval

(Ref

No.

CPSP/REU/RAD-2021-492-3419)

was

obtained

before

data

collection.

Adults

aged

18-80

years

presenting

with

clinically

suspected

thyroid

nodules

were

eligible.

Both

male

and

female

patients

were

included.

Patients

were

required

to

undergo

thyroid ultrasound and ultrasound-guided FNAC within

a

maximum

interval

of

two

months

to

minimise

the

possibility

that

interval

change

could

compromise

radiocytological

comparison.

Cases

were

excluded

if

the ultrasound and FNAC targeted diﬀerent nodules or

if cytology remained nondiagnostic after two attempts.

The ﬁnal analytic

sample comprised 134 patients. The

submitted

manuscript

did

not

provide

an

a

priori

sample-size

calculation;

therefore,

the

present

report

transparently

describes

the

analysed

consecutive

clinical

cohort rather

than introducing

an

unsupported

calculation.

High-resolution

thyroid

ultrasonography

was performed with a high-frequency linear transducer

of at least 9 MHz. Each target nodule was evaluated for

the

ﬁve

ACR

TI-RADS

domains:

composition,

echogenicity, shape, margin, and echogenic foci. Points

were

assigned

according

to

the

ACR

TI-RADS

framework,

and

the

total

score

was

used

to

classify

nodules

as

TR1

to

TR5.

The

submitted

dataset

contained

TR2-TR5

categories.

Two

radiologists

reviewed

the

ultrasound

ﬁndings

independently

and

were blinded to cytology results, reducing review bias.

The

source

manuscript

did

not

state

the

ultrasound

equipment

manufacturer/model

or

reader

experience;

these

details

should

be

added

from

departmental

records

if

available

because

they

improve

reproducibility.

Ultrasound-guided

FNAC

was

performed

using

a

22-27-gauge

needle.

Smears

were

prepared and stained according to routine departmental

cytology

practice

and

interpreted

using

the

Bethesda

System

for

Reporting

Thyroid

Cytopathology.

The

submitted

analysis

grouped

Bethesda

II-III

as

the

105

J Gandhara Med Dent Sci

October - December 2026

lower-risk

reference

category

and

Bethesda

IV-VI

as

the

cytologically

high-risk

reference

category.

This

grouping

has

been

retained

to

preserve

the

authors'

reported

calculations.

It

should

not

be

interpreted

as

proof

that

all

Bethesda

IV

lesions

are

malignant,

because

follicular

neoplasm

requires

histological

assessment

of

capsular

or

vascular

invasion.

4,5

For

diagnostic-performance analysis, ACR TI-RADS TR4-

TR5 was considered a positive ultrasound test and TR2-

TR3 a negative ultrasound test. The principal outcomes

were

sensitivity,

speciﬁcity,

positive

predictive

value

(PPV),

negative

predictive

value

(NPV),

and

overall

diagnostic accuracy relative to the submitted Bethesda

grouping. The association between increasing TI-RADS

category

and

higher-risk

cytology

was

assessed

and

reported as statistically signiﬁcant in the source dataset.

Statistical analysis: Data were summarised using mean

and

standard

deviation

for

age

and

frequency

with

percentage

for

categorical

variables.

Diagnostic

parameters

were

calculated

from

a

2×2

contingency

table.

Based

on

the

reported

totals

and

performance

estimates, the internally consistent matrix comprised 34

true-positive, 14 false-positive, 4 false-negative, and 82

true-negative

classiﬁcations,

yielding

the

published

sensitivity, specificity, PPV, NPV, and accuracy. A p

-

value

below

0.05

was

considered

statistically

significant.

The

source

ﬁle

did

not

identify

the

statistical software package; this detail should be added

if available from the original analysis record.

RESULTS

A

total

of

134

patients

were

included.

Mean

age

was

44.8 ± 12.6 years (reported range 19-78 years). Women

comprised

102

(76.1%)

participants

and

men

32

(23.9%).

The

predominance

of

female

participants

is

consistent

with

the

recognised

epidemiological

distribution

of

thyroid

nodular

disease,

although

the

study

was

not

designed

to

estimate

population

prevalence.

Table 1: Demographic Characteristics of the Study Population

(n=134)

Characteristic

Result

Age, years

44.8 ± 12.6

Age range,

years

19–78

Gender

Female

102 (76.1%)

Male

32 (23.9%)

On

ACR

TI-RADS

assessment,

TR4

was

the

most

frequent category, followed by TR3. Eighteen nodules

(13.4%) were TR2, 46 (34.3%) were TR3, 50 (37.3%)

were

TR4,

and

20

(14.9%)

were

TR5.

Thus,

70/134

nodules

(52.2%)

were

classified

as

TR4-TR5

and

treated

as

ultrasound-positive

for

the

diagnostic-

performance analysis.

RADS Categories

Table 2: Distribution of ACR TI

-

ACR TI-RADS category

n (%age)

TR2

18 (13.4)

TR3

46 (34.3)

TR4

50 (37.3)

TR5

20 (14.9)

Total

134 (100.0)

FNAC classified 96 (71.6%) nodules as Bethesda II–III

and 38 (28.4%) as Bethesda IV–VI under the authors'

prespeciﬁed grouping. Because Bethesda IV and V are

not

synonymous

with

deﬁnitive

malignancy,

this

proportion

should

be

read

as

the

frequency

of

the

study's cytologically high-risk reference category rather

than a histological cancer prevalence.

Table 3: FNAC Results Grouped for the Submitted Diagnostic

Analysis

Bethesda grouping used for analysis

n (%age)

Bethesda II–III (lower-risk reference group)

96 (71.6)

Bethesda IV–VI (cytologically high-risk

reference group)

38 (28.4)

Total

134 (100.0)

The

2×2

diagnostic

matrix

was

internally

consistent

with

the

reported

performance

estimates.

Of

38

Bethesda IV-VI nodules, 34 were categorised as TR4-

TR5

and

four

as

TR2-TR3.

Of

96

Bethesda

II–III

nodules, 82 were TR2-TR3 and 14 were TR4-TR5. This

distribution corresponds to 89.5% sensitivity and 85.4%

specificity.

Table 4: Cross-Classification of ACR TI-RADS and Bethesda-

Reported FNAC

ACR TI-RADS result

Bethesda

Total

IV–VI

II–III

TR4–TR5 (positive)

34

14

48

TR2–TR3 (negative)

4

82

86

Total

38

96

134

ACR

TI-RADS

demonstrated

sensitivity

of

89.5%,

specificity

of

85.4%,

PPV

of

70.8%,

NPV

of

95.3%,

and overall accuracy of 86.6%. The high NPV indicates

that nodules categorised as TR2-TR3 were unlikely to

fall

into

the

study's

Bethesda

IV-VI

grouping.

Higher

TI-RADS categories were signiﬁcantly associated with

higher-risk Bethesda cytology (p<0.001).

Table 5: Diagnostic Performance of ACR TI-RADS Using the

Study-Deﬁned Bethesda Reference Grouping

Diagnostic measure

Value (%age)

Sensitivity

89.5

Specificity

85.4

Positive predictive value

70.8

Negative predictive value

95.3

Overall accuracy

86.6

Diagnostic Performance and Radiocytological Correlation

106

J Gandhara Med Dent Sci

October - December 2026

DISCUSSION

The present study evaluated the diagnostic performance

of ACR TI-RADS in stratifying thyroid nodules, using

FNAC interpreted through the Bethesda system as the

reference

standard.

Our

results

show

that

ACR

TI-

RADS exhibits high sensitivity and speciﬁcity and has

a signiﬁcantly

strong negative predictive value. These

findings

support

its

clinical

usage

as

a

reliable,

non-

invasive

risk

stratiﬁcation

modality

in

patients

with

thyroid

nodules.

The

general

malignancy

rate

in

our

cohort was 28.4%, which is slightly higher than that of

global pooled estimates. However, it is consistent with

hospital-based

populations

where

symptomatic

or

clinically ambiguous nodules have

a higher likelihood

of

undergoing

evaluation.

12

Present-day

epidemiological

analyses

demonstrate

that

thyroid

cancer incidence continues to rise in the world mostly

because of increased detection through imaging instead

of

a

true

surge

in aggressive

disease.

11

This changing

pattern

highlights

the

signiﬁcance

of

balancing

early

diagnosis without unnecessary invasive procedures. Our

study

demonstrates

that

ACR

TI-RADS

shows

a

sensitivity of 89.5% and a speciﬁcity of 85.4%, which

is

approximately

consistent

with

recent

multi-centre

validations. A similar diagnostic accuracy was observed

by Granj et al., who highlighted the system's ability to

decrease

unnecessary

biopsies

while

maintaining

justifiable cancer detection rates.

13

Similarly, Middleton

and

colleagues

showed

that

TI-RADS implementation

markedly enhances risk stratiﬁcation consistency across

institutions.

14

An

important

fact

is

that

nodules

categorised as low risk can be safely monitored without

immediate

biopsy,

as

suggested

by

the

high

negative

predictive

value

(95.3%)

observed

in

our

study.

An

expanding

collection

of

studies

advocates

the

role

of

structured

ultrasound

scoring

systems

in

reducing

unnecessary

biopsy.

ACR

TI-RADS

has

achieved

a

remarkable balance between sensitivity and speciﬁcity,

as

demonstrated

by

comparative

studies

evaluating

multiple TI-RADS frameworks.

15

Tan et al. performed

a comparative study of four TI-RADS versions, which

concluded

that

ACR

TI-RADS

remarkably

reduces

unnecessary

FNAC

while

simultaneously

preserving

diagnostic

reliability.

5

Our

observations

line

up

with

these

ﬁndings

and

strengthen

its

practical

value

in

routine clinical settings. Cytopathological classiﬁcation

using the Bethesda

system remains the

foundation

for

preoperative diagnosis. The present-day updates to the

WHO classiﬁcation of thyroid tumours, as well as the

corresponding

Bethesda

revisions,

show

advancement

in the understanding of tumour biology and malignancy

risk stratiﬁcation.

9

Indeterminate categories continue to

provoke

clinicians

despite

this

structured

framework.

Radiopathological

studies

have

shown

signiﬁcant

concordance

between

higher

TI-RADS

categories

and

Bethesda IV-VI cytology, which supports the predictive

role

of

sonographic

morphology.

16

Further

reinforcement

of

the

correlation

between

higher

TI-

RADS categories and malignant cytology is observed in

our

study

with

a

statistically

signiﬁcant

association.

Local

data

are

essential

when

clarifying

diagnostic

performance.

Moreover,

variations

in

iodine

intake,

genetic predisposition, and healthcare access may aﬀect

disease

patterns.

Large-scale

studies

from

Asia

have

recently

shown

remarkable

diﬀerences

in

thyroid

nodule

frequency

and

malignancy

rates

compared

to

Western populations.

17,18

Our study provides signiﬁcant

evidence speciﬁc to our population given the restricted

local

data

from

South

Asia.

Our

observations

remain

consistent

with

the

growing

consensus

that

ACR

TI-

RADS

is

a

dependable

and

clinically

signiﬁcant

modality

for

initial

thyroid

nodule

evaluation.

It

can

carefully guide decisions with regard to nodules which

warrant

biopsy

or

which

may

be

followed

conservatively, as suggested by its high sensitivity and

negative

predictive

value.

Unnecessary

interventions

may

be

reduced

in

resource-limited

environments

by

using a structured ultrasound-based risk stratiﬁcation.

LIMITATIONS

This

was

a

single-centre

cross-sectional

study

with

a

relatively

modest

sample

and

a

hospital-referred

population, so prevalence-dependent measures may not

generalise

to

community

settings.

The

submitted

manuscript did not provide an ethics approval number,

formal

sample-size

calculation,

ultrasound

equipment

model,

reader

experience,

statistical

software,

interobserver

agreement,

nodule-size

distribution,

or

full

six-category

Bethesda

counts.

FNAC

rather

than

surgical

histopathology

was

used

as

the

reference

standard, and the study grouped Bethesda IV-VI despite

the

indeterminate

nature

of

category

IV

and

the

suspicious

nature

of

category

V.

These

limitations

should

be

considered

when

interpreting

the

term

diagnostic accuracy and should be addressed in future

prospective, histology-verified studies.

CONCLUSIONS

ACR

TI-RADS

demonstrated

good

radiocytological

diagnostic

performance

in

this

cohort,

with

high

sensitivity and a particularly strong negative predictive

value

relative

to

the

study-defined

Bethesda

reference

grouping.

Structured

ultrasound

risk

stratiﬁcation

can

support rational selection of thyroid nodules for FNAC

and

may

help

reduce

avoidable

procedures.

Because

Bethesda IV and V are not equivalent to histologically

proven malignancy, deﬁnitive cancer diagnosis should

Diagnostic Performance and Radiocytological Correlation

107

J Gandhara Med Dent Sci

October - December 2026

remain

based

on

appropriate

cytological,

clinical,

and

histopathological correlation.

CONFLICT OF INTEREST:

None

FUNDING SOURCES:

None

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doi:10.3389/fonc.2022.1029926.

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Tessler FN, Middleton WD, Grant EG, Hoang JK, Berland LL,

Teefey SA, et al.

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Thyroid

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Shanza

Khan

-

Concept

&

Design;

Data

Acquisition;

Data

Analysis/interpretation;

Drafting

Manuscript;

Critical

Revision; Final; Approval

Maimoona

Afsar

-

Concept

&

Design;

Data

Acquisition;

Drafting

Manuscript;

Critical

Revision;

Supervision;

Final;

Approval

Ashfa

Ameer Khan

-

Concept & Design; Data Acquisition;

Data

Analysis/interpretation;

Drafting

Manuscript;

Critical

Revision; Final; Approval

Wajeeha

Rahman

-

Concept

&

Design;

Data

Acquisition;

Data

Analysis/interpretation;

Drafting

Manuscript;

Final;

Approval

Hasina

Gohar

-

Concept

&

Design;

Data

Acquisition;

Drafting Manuscript; Supervision; Final; Approval

Asad

Rehman

-

Concept

&

Design;

Data

Acquisition;

Drafting Manuscript; Supervision; Final; Approval

AUTHORS CONTRIBUTION

The authors accept responsibility for all aspects of the work

and will ensure that any concerns regarding the accuracy or

integrity of any part are properly investigated and resolved.

Diagnostic Performance and Radiocytological Correlation