Dissertation on

ASSESSMENT OF MALIGNANT RISK POTENTIAL OF THYROID

NODULES USING ULTRASOUND THYROID IMAGING REPORTING

AND DATA SYSTEM (TIRADS) CRITERIA WITH CORRELATION

BY FINE NEEDLE ASPIRATION CYTOLOGY (FNAC) / EXCISION

BIOPSY

Submitted in partial fulfillment for

M.D. DEGREE EXAMINATION

BRANCH - VIII, RADIO DIAGNOSIS

COIMBATORE MEDICAL COLLEGE AND HOSPITAL

COIMBATORE – 14

Dissertation submitted to

THE TAMILNADU Dr.M.G.R. MEDICAL UNIVERSITY

CHENNAI – 600 032

TAMILNADU

APRIL 2016

CERTIFICATE

This dissertation titled “ASSESSMENT OF MALIGNANT RISK

POTENTIAL OF THYROID NODULES USING ULTRASOUND

THYROID IMAGING REPORTING AND DATA SYSTEM (TIRADS)

CRITERIA WITH CORRELATION BY FINE NEEDLE ASPIRATION

CYTOLOGY (FNAC) / EXCISION BIOPSY” is submitted to The

Tamilnadu Dr.M.G.R Medical University, Chennai, in partial fulfillment

of regulations for the award of M.D. Degree in Radio Diagnosis in the

examinations to be held during April 2016.

This dissertation is a record of fresh work done by the candidate

Dr. S. THAIYALNAYAKI, during the course of the study (2013 - 2016).

This work was carried out by the candidate herself under my

supervision.

GUIDE:

Dr.N.MURALI, M.D.RD,

Professor,

Department of Radio Diagnosis,

Coimbatore Medical College,

Coimbatore – 14

HEAD OF THE DEPARTMENT:

Dr.N.SUNDARI, M.D.RD,

Professor & HOD

Department of Radio Diagnosis,

Coimbatore Medical College,

Coimbatore – 14

DEAN:

Dr. A. EDWIN JOE, M.D, BL.,

Dean,

Coimbatore Medical College and Hospital,

Coimbatore – 14.

Submission author:Assignment t it le:Submission tit le:

File name:File size:

Page count:Word count:

Character count:Submission date:

Submission ID:

Digital ReceiptThis receipt acknowledges that Turnit in received your paper. Below you will f ind the receiptinf ormation regarding your submission.

The f irst page of your submissions is displayed below.

201318152.md Radio- Diagnosis S…TNMGRMU EXAMINATIONSASSESSMENT OF MALIGNANT RIS…f ull_thesis.docx3.01M8812,72974,55515-Sep-2015 10:49PM568077667

Copyright 2015 Turnitin. All rights reserved.

DECLARATION

I, Dr. S. Thaiyalnayaki solemnly declare that the dissertation titled

“ASSESSMENT OF MALIGNANT RISK POTENTIAL OF THYROID

NODULES USING ULTRASOUND THYROID IMAGING REPORTING

AND DATA SYSTEM (TIRADS) CRITERIA WITH CORRELATION

BY FINE NEEDLE ASPIRATION CYTOLOGY (FNAC) / EXCISION

BIOPSY” was done by me at Coimbatore Medical College, during the period

from June 2014 to July 2015 under the guidance and supervision of Dr. N.

Murali, M.D.RD, Professor, Department of Radio Diagnosis, Coimbatore

Medical College, Coimbatore. This dissertation is submitted to the Tamilnadu

Dr.M.G.R. Medical University towards the partial fulfillment of the

requirement for the award of M.D. Degree (Branch - ) in Radio Diagnosis.

I have not submitted this dissertation on any previous occasion to

any University for the award of any degree.

Place:

Date: Dr. S.THAIYALNAYAKI

ACKNOWLEDGEMENT

I express my sincere thanks to our respected Dean, Dr.A.EDWIN

JOE,MD., BL., Coimbatore Medical College and Hospital, Coimbatore for

permitting me to conduct this study.

I thank Dr.R.MANI,M.D, Vice Principal, Coimbatore Medical College,

Coimbatore for his encouragement and suggestions in completing this study.

I am greatly indebted to the Head of the Department of Radio Diagnosis,

Professor Dr.N.SUNDARI, M.D (RD), who has always guided me, by

example and valuable words of advice. She has always given me her moral

support and encouragement throughout the conduct of the study and also

during my entire post graduate course. I owe my sincere thanks to her.

I will ever remain in gratitude to Dr.N.MURALI, M.D (RD), Professor,

Department of Radio Diagnosis for his valuable support and guidance

throughout my study.

I thank Dr.C.SUBHASHREE, M.D, DNB (RD), Associate Professor,

Department of Radio Diagnosis for her valuable suggestions.

I thank Dr.R. KANNADHASAN, DMRD, M.D (RD)., Assistant

Professor, Department of Radio Diagnosis for his support throughout this

study.

I would like to thank my all other beloved teachers, Department of

Radio Diagnosis for their valuable opinion and help to complete this study.

I would grossly fail in my duty, if I do not mention my gratitude to my

subjects who have volunteered to undergo the investigations for the study.

My sincere thanks to all my fellow postgraduates for their involvement

in helping me in this work.

I’m grateful to my husband, Dr. M. KAPIL DEV, MD, my son K.T.

DEV PRASATH and my parents and parents- in-law, brothers and sisters

who helped me making this study a reality.

Above all I thank the Lord Almighty for His kindness.

LIST OF ABBREVIATIONS USED

FNAC – Fine Needle Aspiration Cytology

BIRADS – Breast Imaging Reporting Ana Data System

TIRADS – Thyroid Imaging Reporting And Data System

MRI – Magnetic Resonance Imaging

DNA – Deoxy-ribo Nucleic Acid

CSF – Cerebro Spinal Fluid

MEN – Multiple Endocrine Neoplasia

LIRADS – Liver Imaging Reporting And Data System

USG – Ultrasonogram

AV Shunt – Arterio Venous Shunt

CI – Confidence Interval

PPV – Positive Predictive Value

NPV – Negative Predictive Value

OR – Odds Ratio

MH – Marked Hypoechogenicity

ML Margin – Micro-Lobulated Margin

IR Margin – Irregular Margin

MIC CAL – Micro Calcification

TTW – Taller-Than-Wider Shape

CONTENTS

S.No

TOPIC

Page No

1.

INTRODUCTION

1

2.

OBJECTIVES

3

3.

METHODOLOGY

4

4.

REVIEW OF LITERATURE

9

5.

OBSERVATION

61

6.

REPRESENTATIVE CASES

70

7.

DISCUSSION

75

8.

CONCLUSION

85

9.

SUMMARY

87

10.

ANNEXURE – I CONSENT FORM

88

11.

BIBLIOGRAPHY

91

12.

ANNEXURE – II MASTER CHART

95

LIST OF FIGURES

S.No

FIGURES

Page

No

1.

ISOPROPYL ALCOHOL AND COPLIN JAR

7

2.

FINE NEEDLE ASPIRATION TRAY

8

3.

ANATOMY OF THYROID GLAND

11

4.

SONOGRAPHIC ANATOMY OF THYROID GLAND

(AXIAL IMAGE)

12

5.

SONOGRAPHIC ANATOMY OF THYROID GLAND

(LONGITUDINAL IMAGE)

13

6.

ARTERIAL SUPPLY TO THYROID GLAND

16

7.

THYROID COLOR DOPPLER, PULSE WAVE DOPPLER

16

8.

VENOUS DRAINAGE OF THYROID GLAND

17

9.

MICROSCOPIC ANATOMY OF THYROID GLAND

18

10.

DEVELOPMENT OF THYROID GLAND WITH

BRANCHIAL POUCHES

19

11.

DEVELOPMENT OF THYROID GLAND SHOWING

TRACT OF THYROGLOSSAL DUCT

20

12.

MECHANISM OF ACTION OF THYROID HORMONE

21

13.

SONOGRAPHIC IMAGE OF SUPPURATIVE

THYROIDITIS

25

14.

HASHIMOTO’S THYROIDITIS SHOWING COARSE

PARENCHYMAL ECHOTEXTURE AND INCREASED

VASCULARITY

26

15.

SONOGRAPHIC IMAGE RIEDEL’S THYROIDITIS

27

16.

SONOGRAPHIC IMAGE OF ADENOMAS OF THYROID

GLAND

28

17.

MICROSCOPIC PICTURE OF PAPILLARY THYROID

CARCINOMA SHOWING ORPHAN ANNIE EYE

NUCLEI WITH PSAMMOMA BODIES

30

18.

SONOGRAPHIC IMAGE OF PAPILLARY CARCINOMA

SHOWING

MULTIPLE MICROCALCIFICATION

32

19.

FOLLICULAR THYROID CARCINOMA SHOWING

CAPILLARY INVASION

33

20.

SONOGRAPHIC IMAGE OF FOLLICULAR THYROID

CARCINOMA

34

21.

MICROSCOPIC PICTURE OF ANAPLASTIC

CARCINOMA OF THYROID GLAND

35

22.

SONOGRAPHIC IMAGE OF ANAPLASTIC

CARCINOMA OF THYROID

GLAND

35

23.

MICROSCOPIC PICTURE OF MEDULLARY THYROID

CARCINOMA SHOWING AMYLOID BODIES

36

24.

SONOGRAPHIC IMAGE OF MEDULLARY THYROID

CARCINOMA

37

25.

SONOGRAPHIC IMAGE OF LYMPHOMA

37

26.

CHART SHOWING THE PERCENTAGE OF THYROID

NODULES DEPENDING UPON THE SHAPE

62

27.

CHART SHOWING THE PERCENTAGE OF THYROID

NODULES DEPENDING UPON THE ECHOGENICITY

64

28.

CHART SHOWING THE PERCENTAGE OF THYROID

NODULES DEPENDING UPON THE CONTENT

65

29.

CHART SHOWING THE PERCENTAGE OF THYROID

NODULES DEPENDING UPON THE CALCIFICATION

66

30.

CHART SHOWING THE PERCENTAGE OF THYROID

NODULES DEPENDING UPON THE MARGIN

67

31.

CHART SHOWING THE PERCENTAGE OF THYROID

NODULES DEPENDING UPON TIRADS CATEGORY

69

32.

ULTRASOUND IMAGE OF COLLOID GOITER

70

33.

ULTRASOUND IMAGE OF NODULAR GOITRE WITH

CYSTIC DEGENERATION

71

34.

ULTRASOUND IMAGE OF PAPILLARY THYROID

CARCINOMA

72

35.

ULTRASOUND IMAGE OF FOLLICULAR THYROID

CARCINOMA

73

36.

ULTRASOUND IMAGE OF LYMPHOMA OF THYROID

GLAND

74

37.

CHART SHOWING COMPARISON OF TIRADS

CATEGORY BETWEEN TWO STUDIES

76

38.

CHART SHOWING COMPARISON OF TWO STUDIES

FOR IRREGULAR MARGIN

77

39.

CHART SHOWING COMPARISON OF TWO STUDIES

FOR TALLER-THAN-WIDER SHAPE

79

40.

CHART SHOWING COMPARISON OF TWO STUDIES

FOR MICROCALCIFICATION

80

41.

CHART SHOWING COMPARISON OF TWO STUDIES

FOR MARKED HYPOECHOGENICITY

82

42.

CHART SHOWING COMPARISON OF ODDS RATIO

FOR SUSPICIOUS ULTRASOUND FEATURES

82

LIST OF TABLES

S.NO

TABLES

PAGE

NO

1.

RELIABILITY OF ULTRASOUND FEATURES TO

DIFFERENTIATE BENIGN AND MALIGNANT

THYROID NODULES

41

2.

NUMBER OF THYROID NODULES DEPENDING

UPON THE SHAPE

62

3.

NUMBER OF THYROID NODULES DEPENDING

UPON ECHOGENICITY

63

4.

NUMBER OF THYROID NODULES DEPENDING

UPON CONTENT

64

5.

NUMBER OF THYROID NODULES DEPENDING

UPON CALCIFICATION

66

6.

NUMBER OF THYROID NODULES DEPENDING

UPON THE MARGIN

67

7.

NUMBER OF THYROID NODULES DEPENDING

UPON TIRADS CATEGORY

68

8.

PERCENTAGE OF THYROID NODULES

DEPENDING UPON TIRADS CATEGORY

69

9.

COMPARISON OF TIRADS CATEGORY BETWEEN

TWO STUDIES

75

10.

COMPARISON OF TWO STUDIES FOR IRREGULAR

MARGIN

77

11.

COMPARISON OF TWO STUDIES FOR TALLER-

THAN-WIDER SHAPE

78

12.

COMPARISON OF TWO STUDIES FOR

MICROCALCIFICATION

80

13.

COMPARISON OF TWO STUDIES FOR MARKED

HYPOECHOGENICITY

81

14.

COMPARISON OF ODDS RATIO FOR SUSPICIOUS

ULTRASOUND FEATURES

83

INTRODUCTION

1

INTRODUCTION

High resolution ultrasonography is very well suited for imaging superficial

structures such as the thyroid gland in exquisite detail. The improved resolution

available with modern day high frequency transducers allows for appreciation of

disease process much before clinical detection. Also in established disease, the

characterization by ultrasound is extremely useful.

Thyroid gland is one of the major endocrine gland which can be affected by

various congenital anomalies, inflammatory disease processes and various kinds of

tumors which can present clinically as thyroid nodules. The nodules of the thyroid

gland include both benign and malignant nodules. Currently, ultrasonography is one

of the investigating procedures used for the evaluation of thyroid nodules. But it is not

the confirmatory method to differentiate the benign and malignant thyroid nodules.

The investigating procedure which is used for the differentiation of benign from

malignant tumors is fine needle aspiration cytology.

Another disadvantage of fine needle aspiration cytology is that it is an invasive

and painful procedure. Rarely it can also cause life threatening fatal haemorrhage by

causing damage to the adjacent major blood vessels and also it carries the risk of

introducing infective agents into the body. It is also difficult to decide which thyroid

nodule needs Fine Needle Aspiration Cytology and which does not need. In order to

avoid these problems the thyroid nodules were classified into TIRADS (Thyroid

Imaging Reporting AndData System) category based on suspicious ultrasound

2

features. This enables objectivity of reporting, risk stratification and guidance for the

clinician towards the next step.

OBJECTIVES

3

OBJECTIVES

1. To classify the thyroid nodules into Thyroid Imaging Reporting AndData

System (TIRADS) category based on suspicious ultrasound features.

2. To compare the suspicious ultrasound features with the pathological

findings and to analyse the risk of malignancy of suspicious ultrasound

features.

METHODOLOGY

4

METHODOLOGY

This study has been undertaken on the patients admitted in Coimbatore

Medical College and Hospital, Coimbatore during the study period (July 2014 – June

2015).

STEP: 1 Thepatients referred to radiology department for the ultrasonogram of

thyroid gland for the evaluation of thyroid nodules were analysed by their primary

thyroid complaints, the relevant positive and negative histories and proper clinical

examination of thyroid gland. Appropriate cases have been selected after evaluation of

clinical case details and diligently applying the inclusion and exclusion criteria.

INCLUSION CRITERIA:

Patients (of any age group, and both sex) came to the hospital with primary

thyroid related complaints and referred to the radiology department for

ultrasonography of thyroid gland for the evaluation of thyroid nodules were included

in this study.

EXCLUSION CRITERIA:

1. Patientswith secondary thyroid related disorders like drug / radiation induced

hypo / hyper thyroidism.

2. Systemic or central nervous system related secondary thyroid involvement.

3. Pregnant women.

4. Patients not capable of giving consent (psychiatric patients)

5. Patients not willing to participate in the study (who refused to give the consent)

5

6. Patients willing for ultrasonography of thyroid but not willing for ultrasound

guided fine needle aspiration cytology.

STEP: 2 The patients were then evaluated by high resolution ultrasonography of

thyroid gland for the presence of thyroid nodules and also various sonographic

findings of the thyroid nodules were analysed. The key ultrasound features that were

analysed include the shape of the nodules (wider-than-taller / taller-than-wider),

echogenicity (iso/hyper echogenicity, hypoechogenicity, marked hypoechogenicity),

content (solid, cystic or mixed), calcification (no calcification, micro calcification,

macro calcification), margins (smooth, irregular, microlobulated). Based on the

ultrasound features the thyroid nodules were stratified into appropriate Thyroid

Imaging Reporting And Data System category.

STEP: 3. After ultrasound evaluation, these patients underwent ultrasound guided fine

needle aspiration cytology. In case of multiple nodules the nodules which had most

suspicious sonographic findings for malignancy or the dominant thyroid nodule were

selected for fine needle aspiration. The procedure and the complications of FNAC

were explained to the patient before getting the consent. Patients were positioned in

neck extension with pillow under the shoulder. Under strict aseptic precautions, 23

gauge needle was introduced into the suspicious thyroid nodule with ultrasound

guidance. The needle is moved back and forth, varying the angle. Then the needle is

withdrawn andattached to the syringe and the sample is blown onto the microscopic

slides. Then the slides are kept in the coplin jar containing the fixative isopropyl

alcohol. After fixation the slides along with coplin jar were sent to pathology

department for cytological analysis.

6

STEP: 4. The confirmatory diagnosis from fine needle aspiration material has been

obtained from pathology department. Then these FNAC reports were compared with

ultrasound findings (TIRADS category) of the corresponding nodules and analysed for

the association of these ultrasound findings with the benign and malignant thyroid

tumors. The ultrasound findings were correlated with histopathological reports of the

specimen of thyroid surgery if FNAC reports were indeterminate or of inadequate

sample volume.

DURATION OF THE STUDY: 1 year (June 2014 – July 2015)

TYPE OF THE STUDY: short term prospective study.

Total number of patients: 200 patients

Total number of nodules analysed and assigned as per TIRADS – 227 nodules.

Total number of nodules for which FNAC was done – 200 nodules.

Total number of lesions that underwent surgical excision: 46.

Total number for which definite diagnosis by FNAC was made: 154

SOURCE OF DATA:

Data consists of primary data collected by the principal investigator directly

from the patients who came for ultrasound thyroid to the Department of Radiology,

Coimbatore Medical College and Hospital, Coimbatore for primary thyroid related

symptoms.

7

MATERIALS USED IN THIS STUDY:

1. Ultrasound machine (sonoscape, control number 210724, software version SI

5000 ) using linear transduser (7 – 13 MHz)

2. 23 Gauge needle with 5 ml disposable plastic syringe

3. Glass slides

4. Isopropyl alcohol

5. Coplin jar

Figure: 1. Isopropyl alcohol and Coplin jar.

8

6. Antiseptic solution

7. Gauze pieces, sterile towel.

8. Software EPI INFO version7 used for statistical analysis.

Figure: 2. Fine Needle Aspiration Tray.

REVIEW OF LITERATURE

9

REVIEW OF LITERATURE

The thyroid gland is located superficially in the anterior aspect of the neck.

There are several diagnostic methods currently available for the evaluation of thyroid

disease. As the thyroid gland is located superficially in the neck, high resolution real

time gray scale and colour Doppler sonography can demonstrate normal thyroid

anatomy and pathologic conditions with remarkable clarity. So the ultrasound plays an

important role in the diagnostic evaluation of thyroid diseases. The high frequency

transducers (7.5 – 15.0 MHz) provide deep ultrasound penetration (up to 5 cm) and

high definition images, with a resolution of 0.5 to 1.0 mm. Contrast enhanced

sonography and sonoelastography are the two newer techniques used for the

sonographic evaluation of thyroid gland.

I) SALIENT ANATOMY OF THYROID GLAND WITH

SONOGRAPHIC CORRELATES:

Thyroid gland is a major endocrine gland located in the anterior aspect of the

neck (infrahyoid compartment) in front and at the sides of the trachea. It has a rich

vascular supply provided by carotid system of blood vessels. The gland has two

coverings namely inner true capsule and an outer false capsule. The false capsule is

derived from the pretracheal fascia which is attached above to the hyoid bone and

oblique line of thyroid cartilage and below it blends with the apex of the fibrous

pericardium. The false capsule is thickened to form the ligament of Berry which

connects the lateral lobe of the gland to the cricoid cartilage. Because of these

attachments the thyroid gland is able to move up and down with deglutition.1

10

PRESENTING PARTS:

The thyroid gland consists of two lateral lobes which are connected together by

an isthmus across the median line. Each lobe measures about 5 cm, 3 cm, 2 cm in

length, breath and thickness respectively. But the size and shape of each lobe varies

widely in different individuals. In tall individuals the sagittal scan shows

longitudinally elongated lateral lobes; in shorter individuals the gland is more oval. In

newborn the gland measures about 18 – 20 mm long with antero-posterior diameter

measures about 8 – 9 mm. At about 1 year of age the mean length is 25 mm and the

antero-posterior diameter is 12 – 15 mm.In adults the mean length is about 40 – 60

mm with antero-posterior diameter measures 13 – 18 mm. The isthmus measures

about 4 – 6 mm in mean thickness2.

The volume of the thyroid gland can be calculated with linear parameters or

with mathematical formulas. The antero-posterior diameter is considered to be most

precise in calculating thyroid volume because it is relatively independent of possible

dimensional asymmetry between the two lobes. Thyroid volume can be calculated

accurately by using sonography. The thyroid gland is considered to be enlarged,

when the antero-posterior diameter measures more than 2 cm2.

The mathematical formula to calculate the thyroid volume is length X width X

thickness X 0.529. This formula is based on the ellipsoid formula. The volume of the

thyroid gland can also be calculated by using three – dimensional ultrasound

technology either automatically or manually2.

11

The thyroid volume in neonates measures about 0.40 – 1.40 ml, in adults it

ranges from 10 – 11 ± 3 ml. The thyroid volume varies in different patients with

different diseases. The volume is more in patients living in iodine deficiency areas and

in patients with acute hepatitis or chronic renal failure. The thyroid volume is

decreased in patients with chronic hepatitis or in patients treated with thyroxine or

radioactive iodine2.

Each lateral lobe of thyroid gland consists of an apex, base, three surfaces and

two borders.

Figure: 3. Anatomy of thyroid gland

12

The apex of the lateral lobe is sandwiched between inferior constrictor and

sternothyroid, so that the thyroid swelling cannot extent above the oblique line of

thyroid cartilage. The superior thyroid artery and external laryngeal nerve diverge

from each other close to the apex of the gland.

The base is related to the inferior thyroid artery and external laryngeal nerve

and it extends up to 5th

or 6th

tracheal ring.

In 10 – 40 % of normal subjects a small thyroid lobe called as pyramidal lobe

arising superiorly from the isthmus. The pyramidal lobe can be routinely visualized in

younger patients but in adults it undergoes progressive atrophy and it becomes

invisible.Sonographically the normal thyroid parenchyma has a homogenous,

medium to high level echogenicity. The capsule of the thyroid gland is represented by

Figure: 4. Sonographic anatomy of thyroid gland (axial image)

13

a thin hyperechoic line around the thyroid lobes. The capsule becomes calcified in

patients with uremia or in disorders of calcium metabolism2.

On computed topography the normal thyroid tissue is identified by its higher

density compared to the adjacent structures. The thyroid tissue has high density due to

its high iodine content. Computed topography is mainly used for the identification of

ectopic thyroid tissue3.

Figure: 5. Sonographic anatomy of thyroid gland (longitudinal image)

On T 1 weighted images of MRI the intensity of the normal thyroid gland is

lower compared to the surrounding fat. It shows medium intensity on T 1 weighted

images whereas on T 2 weighted images the intensity is slightly increased. On T 2

images these intensity is more than the overlying strap muscles4.

14

RELATIONS:

The antero-lateral surface is related to sternothyroid, sternohyoid and superior

belly of omohyoid muscles. The medial surface is related to larynx and trachea,

pharynx and oesophagus. The poster-lateral surface is related to carotid sheath and its

content.

The parathyroid gland is located along the posterior borders of the lateral lobe

of the gland.

The isthmus measures about 1.25 cm in both vertical and transverse diameter

lies in front of 2nd

, 3rd

, 4th

tracheal ring.Occasionally a pyramidal lobe extends

upwards from the upper border of isthmus.

Levatorglandulithyroidae is a fibro-muscular band, extends from the hyoid

bone to the isthmus or to the pyramidal lobe1.

Sonographically the sternohyoid and the strap muscles appear as thin,

hypoechoic bands anterior to the thyroid gland. Sternocleidomastoid muscle seen in

the lateral aspect of thyroid gland as large oval band.The longuscolli muscle located

posterior to each thyroid lobe serves as important anatomical landmark. On

longitudinal thyroid scans inferior thyroid artery and recurrent laryngeal nerve are

seen between the thyroid lobe and oesophagus on the left side whereas on the right

side these structures are seen between the thyroid lobe and longuscolli muscle. The

oesophagus can be identified in the transverse plane by the target appearance of

bowel2.

15

BLOOD SUPPLY:

ARTERIAL SUPPLY:

Thyroid gland is mainly supplied by superior and inferior thyroid arteries

which are branches from external carotid artery and thyrocervical trunk respectively.

The superior thyroid artery accompanied by the external laryngeal nerve runs

downwards forwards and in the upper pole of the lateral lobe it divides into anterior

and posterior branches. The anterior branch runs along the anterior aspect of the

lateral lobe and the upper border of the isthmus where it anastomoses with the

corresponding artery of the opposite side. The posterior branch runs downwards along

the posterior aspect of the lateral and near the base of the gland it anastomoses with

the ascending branch of the inferior thyroid artery. The inferior thyroid artery ascends

in front of the medial border of the scalenus anterior and on reaching the lower pole of

the gland it divides into ascending and descending glandular branches which supply

the posterior and inferior parts of the gland. The thyroid gland is also supplied by

accessory thyroid arteries which are derived from oesophageal and tracheal branches.

Arteriathyroideaima is an occasional branch from arch of aorta also supplies the

gland1.

Sonographically the superior thyroid artery and vein are found at the upper

pole of each lateral lobe. The inferior thyroid artery is situated posterior to the lower

third of each lateral lobe, whereas the inferior thyroid vein is located at the lower pole.

The peak systolic velocity in the major thyroid arteries varies between 20 – 40 cm /

16

Figure: 6. Arterial supply to thyroid gland

sec and in the intraparenchymal arteries it is about 15 – 30 cm / sec. The

meandiameter of the arteries is about 1 -2 mm whereas for the lower veins it can be up

to 8 mm2.

Figure: 7. Thyroid color Doppler, Pulse wave Doppler

17

VENOUS DRAINAGE:

The venous blood is drained by superior and middle thyroid veins which drains

into the internal jugular vein and by the inferior thyroid vein which drains into the left

brachiocephalic vein. Occasionally a fourth thyroid vein (kocher’s vein) emerges from

the lower pole and drains into the internal jugular vein1.

Figure: 8. venous drainage of thyroid gland

BRIEF REVIEW OF HISTOLOGY OF THYROID GLAND:

The fibrous capsule covering the gland sends septa and divides the gland into

lobules. Each lobule is made up of an aggregation of follicles. The follicles are filled

by a homogenous material called colloid. The spaces between the follicles are filled

by delicate connective tissue. The follicles are lined by follicular cells which rest over

the basement membrane. The parafollicular cells are present between the follicular

cells and the basement membrane. They may also lie in the interval between the

follicular cells5.

18

Figure: 9. Microscopic anatomy of thyroid gland

BRIEF REVIEW OF DEVELOPMENT OF THYROID GLAND:

Thyroid gland develops from the endodermal cells dorsal to the

tuberculamimpar. These cells evaginate caudally through the substance of the tongue

and form the thyroglossal duct which grows in the median plane ventral to the hyoid

bone. Ventral to the proximal part of trachea, thyroglossal duct divides into a bilobed

mass which forms the primodium of the isthmus and the lateral lobes of the thyroid

gland. Later the thyroglossal duct disappears, but sometimes the caudal end of the

duct persist as pyramidal lobe. The cephalic end of the thyroglossal duct persists as

foramen caecum of the tongue. Later the bi-lobed mass subdivides into a series of

double cellular plates. Then the colloid materials accumulate within the bilaminar

plates and forms primary thyroid follicles. Subsequent budding from these follicles

forms the definitive follicles.

19

Figure: 10. Development of thyroid gland with branchial pouches

The lateral thyroid rudiments, derived from the caudal pharyngeal complex of

fourth pouch, fuse with the bilobed mass and prevent the further caudal migration of

the mass. The parafollicular cells are derived from the ultimobranchial body of the

caudal pharyngeal complex6.

Congenital anomalies of thyroid gland include aplasia of one lobe or the whole

gland, hypoplasia of part of thyroid gland and ectopic thyroid tissue. These anomalies

can be demonstrated by using ultrasonography. The hypoplasia of thyroid gland can

be diagnosed sonographically by demonstrating the diminished size of the gland.

Ectopic thyroid tissue can be demonstrated by using radionuclide scans2.

20

Figure: 11. Development of thyroid gland showing tract of thyroglossal duct

II) BRIEF REVIEW OF PHYSIOLOGY OF THYROID GLAND:

The thyroid gland secretes the hormone named as thyroxin through which it

regulates the various metabolic activities of the human body including lipid and

carbohydrate metabolism. It also increases the O2 consumption by the cells present in

the body.

The thyroid hormone acts by binding to the thyroid hormone receptor which is

present in the nuclei of the cell. This hormone - receptor complex after binding with

DNA via zinc fingers, increases or decreases the expression of variety of

differentgenes that code for proteins that regulate cell function. There are two thyroid

hormone

21

Figure: 12. Mechanism of action of thyroid hormone

receptor genes named as α and β receptor genes located on chromosome 17 and

chromosome 3 respectively7.

ACTIONS OF THYROID HORMONE:

1. The thyroid hormone increases the oxygen consumption of most of the

metabolically active cells.

2. Thyroid hormone increases the force of contraction and cardiac output and

it decreases the circulation time.

22

3. Thyroid hormone has marked effect on the developing brain. In

hypothyroidism the mentation becomes slow and the CSF protein level is

increased.

4. The thyroid hormone increases the protein catabolism that leads to muscle

weakness.

5. It also increases the rate of carbohydrate absorption from the GIT and

decreases the circulating cholesterol level.

6. The thyroid hormone is also essential for normal growth and skeletal

maturation.

7. The parafollicularcells of the thyroid gland secrete another hormone called

as calcitonin which also regulates the circulating calcium levels7.

III) REVIEW OF DISEASES AFFECTING THYROID GLAND AND

THEIR SONOGRAPHIC FEATURES:

Diseases of the thyroid gland are associated with either excessive release or deficiency

of thyroid hormones. Excessive release of thyroid hormone causes hyperthyroidism.

The hyperthyroidism is manifested by palpitation, rapid pulse, muscle weakness,

nervousness, fatigability, heat intolerance, weight loss with good appetite, excessive

perspiration, fine tremor of the hand and variable enlargement of thyroid gland.

Diffuse hyperplasia of thyroid gland associated with graves disease (accounts for 85%

of cases), exogenous thyroid hormone administration,

hyperfunctionalmultinodulargoiter, hyperfunctional adenomas and thyroiditis are the

causes of hyperthyroidism.

23

Decreased synthesis of thyroid hormone causes hypothyroidism. Clinically the

hypothyroidism manifests as cretinism (in infancy and early childhood) and

myxedema (in older children or adult). Clinical manifestations of cretinism include

severe mental retardation, short stature, coarse facial features, protruding tongue and

umbilical hernia. Myxedema manifest as slowing of physical and mental activity. The

causes of hypothyroidism include insufficient thyroid parenchyma (developmental,

radiation injury, surgical ablation, hashimato thyroiditis), decreased thyroid hormone

synthesis (iodine deficiency, drugs, hashimoto thyroiditis), pituitary lesions leads to

reduced TSH secretion and hypothalamic lesions associated with decreased

thyrotropin–releasing hormone synthesis.

The following pathological conditions can occur in the thyroid gland8.

CONGENITAL ANOMALIES:

1. Aplasia of thyroid gland

2. Hypoplasia of thyroid gland

3. Ectopic thyroid tissue

4. Lateral aberrant thyroid.

5. Thyroglossal duct anomalies.

INFLAMMATORY:

1. Acute suppurative thyroiditis

2. Subacute thyroiditis

24

3. Chronic thyroiditis including chronic granulomatous thyroiditis,

Riedels thyroiditis, autoimmune thyroiditis (hashimoto’s

thyroiditis)

ADENOMAS:

1. Follicular adenoma

2. Hyalinising trabecular tumor.

CARCINOMAS:

1. Papillary thyroid carcinoma.

2. Follicular thyroid carcinoma

3. Poorly differentiated carcinoma

4. Anaplastic carcinoma.

5. Sclerosingmucoepidermoid carcinoma with eosinophilia

6. Medullary carcinoma

7. Mucinous carcinoma

8. Mucoepidermoid carcinoma

9. Squamous cell carcinoma

10. Mixed medullary and follicular cell carcinoma.

Other thyroid tumors include teratoma, plasmacytoma, primary lymphoma,

angiosarcoma etc…

25

THYROIDITIS:

Thyroiditis is a group of disorder characterised by inflammation of thyroid

gland. The diseases included in this category are infectious thyroiditis, subacute

granulomatous thyroiditis (associated with acute illness with severe thyroid pain),

subacute lymphocytic thyroiditis (painless thyroiditis) and fibrous thyroiditis (reidel’s

thyroiditis).

Acute suppurative thyroiditis is caused by bacterial infection and mostly it

affects children. Sonographically it demonstrates an abscess with internal debris with

or without septa and also adjacent inflammatory nodes. Subacute granulomatous

thyroiditis is caused by viral infection. Sonographically it demonstrates enlarged

thyroid gland with focal hypoechoic regions2.

Figure: 13. Sonographic image of suppurative thyroiditis

Hashimoto’s thyroiditis is an autoimmune thyroiditis caused by autoantibodies to their

own thyroglobulin and thyroid peroxidase. Sonographically it typically demonstrates

26

Figure:14. Hashimoto’s thyroiditis showing coarse parenchymal echotexture and

increased vascularity.

diffuse, coarsened, parenchymal echotexture with micronodulation and multiple

fibrous septations. The color Doppler imaging shows normal or decreased vascularity

in majority of cases. The gland shows hypervascularity when hypothyroidism occurs

due to increased thyroid stimulating hormone. It also demonstrates cervical

lymphadenopathy mostly near the lower part of the gland2.

The riedel’s thyroiditis is associated with mediastinal fibrosis, retroperitoneal

fibrosis or with sclerosing cholangitis. In riedel’s thyroiditis the thyroid gland is

diffusely enlarged and it also demonstrates inhomogenous parenchymal echotexture

sonographically2.

Graves disease is an autoimmune disorder of thyroid gland produced by

autoantibodies against TSH receptors, thyroid stimulating immunoglobulin

(TSI),thyroid growth stimulating immunoglobulins, TSH binding

inhibitorimmunoglobulins. It is the most common cause of endogenous

hyperthyroidism.

27

Figure: 15. Sonographic image Riedel’s thyroiditis

Diseases of thyroid gland can present clinically with one or more thyroid

nodules. Clinically it is the challenge for the surgeons to differentiate between benign

and malignant nodules. Most of the thyroid nodules are benign in nature. Less than

one per cent of the thyroid nodules are malignant in nature.

Approximately 80 % of thyroid nodules are caused by hyperplasia of the gland.

The causes of thyroid nodular diseases include iodine deficiency, hormonal imbalance

and medications which lead to poor utilization of iodine. When the hyperplasia causes

overall increase in size or volume of the gland, it is called as goiter. Pathologically the

nodules are often referred to as hyperplastic, adenomatous or colloid nodules. Most of

the hyperplastic nodules undergo liquefactive degeneration and becomes colloid

nodules.

Sonographically these nodules are isoechoic compared to normal thyroid tissue.

Some nodules are hyperechoic because of numerous interfaces between cells and

colloid substance. The perinodular blood vessels and mild edema or compression of

28

the adjacent normal parenchyma will appear as thin peripheral hypoechoic halo

around the nodule. The serous or colloid fluid present in the nodules are anechoic in

nature. Echogenic fluid or moving fluid-fluid levels correspond to haemorrhage.

Microcrystals or aggregates of colloid substance cause bright echogenic foci with

comet tail artifacts. Calcifications of the thyroid nodules appears as either thin,

peripheral shells (eggshell) or coarse, highly reflective foci with associated shadows.

The attenuated strands of thyroid tissue appear as thin intracysticseptation.The

vascularity of the thyroid nodules are detected by color Doppler sonography and with

high sensitivity Doppler technology2.

ADENOMAS:

5 – 10 % of thyroid nodules are adenomas. Most adenomas result in no thyroid

dysfunction; less than 10 % adenomas hyperfunction and cause thyrotoxicosis. The

Figure: 16 Sonographic image of adenomas of thyroid gland

benign follicular adenomas are distinguished according to the type of cell proliferation

into fetal adenoma, hurthle cell adenoma and embryonal adenoma. Sonographically,

29

adenomas are solid masses that may be hyperechoic, isoechoic, or hypoechoic. They

often have thick, smooth peripheral hypoechoic halo due to fibrous capsule and blood

vessels2.

CARCINOMAS:

Carcinoma of the thyroid gland arising from the follicular epithelium except for

the medullary thyroid carcinoma. The most common type of thyroid carcinoma is

papillary thyroid carcinoma. 85% of thyroid carcinomas are papillary thyroid

carcinoma, 5 - 15% of carcinomas are follicular carcinoma, 5 % of cases belong to

medullary thyroid carcinoma and less than 5% thyroid carcinomas are anaplastic

carcinomas.

The incidence of solitary papillary nodules in adult in united states various

between 1 – 10%. This incidence is even higher in endemic goiterous areas. Out of

these solitary papillary nodules less than 1% of solitary thyroid nodules are malignant.

The ratio between the benign neoplasm and the thyroid carcinoma is 10: 1. The

solitary nodules present in younger patients, and the nodules in male are more likely

to be neoplastic. The nodules which show hot spot in imaging studies are benign in

nature. The nodules present in patients with the history of radiation treatment to the

head and neck region are more likely to be malignant9.

PAPILLARY THYROID CARCINOMA:

Papillary thyroid carcinoma is the most common thyroid carcinoma commonly

seen between 25 – 50 years age group. Papillary thyroid carcinoma is associated with

the history of ionizing radiation. Microscopically the cells which give rise to papillary

30

thyroid carcinoma shows characteristic appearance of the nuclei called as Orphan

Annie eye nuclei. Papillary thyroid carcinoma can contain branching papillae having

fibrovascular stalk. This fibrovascular stalk is covered by single to multiple layers of

cuboidal epithelial cells9.

Figure: 17. Microscopic picture of papillary thyroid carcinoma showing

orphan annie eye nuclei with psammoma bodies.

In cross sections of papillary thyroid carcinoma cytoplasmic invaginations give

the appearance of intranuclear inclusions called as pseudo – inclusions also called as

intranuclear grooves. Microscopically the papillary thyroid carcinoma often

demonstratesPsammoma bodies which are representing concentrically calcified

structures9.

Papillary thyroid carcinoma shows other variants like follicular variant which

has characteristic nuclei of papillary thyroid carcinoma but has an almost totally

follicular architecture.

31

It also shows tall cell variant which is marked by tall columnar cells. These tall

columnar cells are lining the papillary structures with intensely eosinophilic

cytoplasm.

Diffuse sclerosing variant of papillary thyroid carcinoma shows prominent

papillary pattern intermixed with solid areas containing nests of squamous metaplasia.

It also shows diffuse fibrosis throughout the gland.

There is another variant called as papillary microcarcinoma which shows all

the features of papillary thyroid carcinoma and the size is less than 1 cm.

Clinically the papillary carcinoma manifest as asymptomatic thyroid nodule

and mass in the cervical lymph node. It shows cold masses on scintiscan. The 10 year

survival rate for papillary carcinoma is 98%9.

Sonographically 90% of papillary carcinoma cases show hypoechogenicity due

to closely packed cell content with minimal colloid substance. It also shows

microcalcification appearing as tiny, punctate hyperechoic foci with or without

acoustic shadows. In aggressive cases microcalcification may be the only sonographic

sign.

90% of papillary carcinomas also demonstrate hypervascularity in

ultrasonography, and also cervical lymph node metastasis which may contain tiny,

punctate echogenic foci caused by microcalcification.

Papillary microcarcinoma on high frequency ultrasound shows small,

hyperechoic patch under the capsule with thickening and retraction of the capsule or

32

as a minute hypoechoic nodule with blurred irregular outline with no visible

microcalcification2.

Figure: 18. Sonographic image of papillary thyroid carcinoma showing multiple

microcalcification

FOLLICULAR THYROID CARCINOMA:

10 – 20 % of thyroid cancers are follicular carcinomas. It is commonly seen in

women with the peak incidence at 40 – 50 years of age. Dietary iodine deficiency is

associated with increased incidence of follicular carcinoma.

33

Figure: 19. Follicular thyroid carcinoma showing capillary invasion

follicular cells donot show the typical features of papillary arcinoma9.Microscopically

the follicular thyroid carcinoma composed of fairly uniform cells forming small

follicular cells containing colloid. And also the nuclei present in the

There is no sonographicfeature which differentiate follicular carcinoma from

follicular adenoma. But the features that suggest follicular carcinoma include irregular

tumor margins, thick irregular halo and a tortuous or chaotic arrangement of internal

blood vessels on color Doppler imaging2.

Clinically it presents as slowly enlarging painless nodules. Through vascular

invasion it spread to bones, lungs, liver and elsewhere with little propensity for

lymphatic spread. Usually it shows cold nodules but in rare cases it shows warm

nodules on scintiscan. The ten year survival rate for follicular carcinoma is 92%9.

34

Figure: 20. Sonographic image of Follicular thyroid carcinoma

ANAPLASTIC CARCINOMA:

Anaplastic carcinoma is also called as undifferentiated carcinoma. The

anaplastic carcinoma composed of highly anaplastic cells with variable morphology.

The cells present in the anaplastic carcinoma can be

1. Large pleomorphic giant cells with occasional osteoclast like multinucleate

giant cells.

2. Spindle cells with a sarcomatous appearance or

3. Mixed spindle and giant cells.

Anaplastic carcinoma is commonly seen in older people with mean age of 65

years. Anaplastic carcinoma develops from more differentiated tumors due to genetic

changes possibly the loss of p53 tumor suppressor gene. Clinically it presents as

rapidly enlarging bulky neck mass with the compression of adjacent vital structures

present in the neck. The disease is uniformly fatal with 100% mortality9.

35

Figure: 21. Microscopic picture of Anaplastic carcinoma of thyroid gland

Sonographically the anaplastic carcinoma demonstrates large, hypoechoic mass

often encase or invade blood vessels and neck muscles2.

Figure: 22. Sonographic image of Anaplastic carcinoma of thyroid gland

MEDULLARY THYROID CARCINOMA:

The medullary thyroid carcinoma presents as solitary nodule. These are

neuroendocrine neoplasms derived from parafollicularcells which are also called as C

cells or clear cells and it secretes calcitonin.

36

Microscopically the medullary thyroid carcinoma shows polygonal to spindle

shaped cells which may form nests, trabeculae and even follicles. The adjacent stroma

also demonstrateacellular amyloid deposits derived from altered calcitonin

polypeptides9.

Figure: 23. Microscopic picture of Medullary thyroid carcinoma showing

Amyloid bodies

Sonography of medullary carcinoma is similar to that of papillary carcinoma

and is seen most often as hypoechoic solid mass. Calcification is often seen but ismore

coarse than the calcifications seen in typical papillary carcinoma2.

Familial cases of medullary thyroid carcinoma showbilaterality and

multicentricity. Microscopically it shows multicentric C cell hyperplasia in the

surrounding thyroid parenchyma. 80% of medullary carcinomas are sporadic and the

remaining cases are associated with MEN syndrome. Medullary carcinoma in

37

association with MEN syndrome occurs in younger patients whereas sporadic cases

presents with peak incidence at 40 – 50 years of age9.

Figure: 24. Sonographic image of Medullary thyroid carcinoma

Lymphoma of thyroid gland is mostly non-Hodgkin’s lymphoma accounts for

4% of thyroid malignancies. Sonographically the lymphoma appears as an extremely

hypoechoic and lobulated mass. Large areas of cystic necrosis may occur in the

Figure: 25. Sonographic image of lymphoma

38

lymphoma. Lymphomas are mostly hypovascular on color Doppler or may show

blood vessels with chaotic distribution and AV shunts2.

Metastasis of thyroid gland usually occurs from melanoma (39%), breast (21%)

and renal cell carcinoma (10%). Sonographically metastasis of thyroid gland appears

as solid, homogenously hypoechoic masses without calcifications2.

IV) DIFFERENTIATION OF BENIGN AND MALIGNANT THYROID

NODULES:

i) ANALYSIS OF KEY ULTRASOUND FEATURES:

Ultrasonography is commonly used for evaluation of thyroid nodules. But no

single sonographic criterion can be used to distinguish between benign and malignant

thyroid nodules. The following characteristic features of thyroid nodules can be used

to differentiate benign from malignant thyroid nodules.

1. Internal contents: The thyroid nodule which has significant cystic

component is usually benign adenomatous nodule. Spongiform appearance

of thyroid nodules associated with well-defined margins and

isoechogenecity is suggestive of benign thyroid nodule. The nodules which

contain comet tail artifacts are benign in nature. Detection of solid

elements or projections of more than 1 cm into the cystic lumen with or

without microcalcification can lead to suspicion of malignancy especially in

cystic papillary carcinoma.

39

2. Shape: the malignant nodules have the tendency to grow across the normal

tissue planes. So the malignant nodules are taller than wider in shape. The

benign nodules have the tendency to grow parallel to normal tissue planes.

3. Echogenicity: the malignant thyroid nodules are usually hypoechoic in

nature, but most of the benign thyroid nodules are also hypoechoic in

nature. So the marked hypoechogenicity is suggestive of malignant nodules

whereas the benign lesions have less marked hypoechogenicity.

Hyperechoic nodules are more likely to be benign in nature. Isoechogenic

nodules carry intermediate to low risk of malignancy. Isoechogenicity has

high specificity and positive predictive value for the diagnosis of the

thyroid nodules.

4. Halo: sonographically a thin peripheral halo seen around 60 – 80 % of

benign thyroid nodules and 15 % of thyroid cancers. The thin, complete

peripheral halo which can be demonstrated by color Doppler imaging

represents blood vessels around the periphery of the lesion, strongly

suggestive of benign nodules. Rapidly growing thyroid cancers often have

thick, irregular and incomplete halos.

5. Margin: sharp, well defined margins are representing benign thyroid

nodules, whereas irregular, speculated or poorly defined margins are

representing malignant lesion.

6. Calcification: large and coarse calcifications are seen more likely in benign

nodules. Peripheral egg shell calcification is a characteristic feature of

40

benign thyroid nodule. Fine and punctate calcifications, thickened and

interrupted peripheral calcifications especially when associated with

hypoechoic halo are strongly suggestive of malignant nodules.

Microcalcfications have the highest accuracy rate (76%), specificity (93%)

and positive predictive value (70%) for malignancy as a single sign.

7. Doppler flow pattern: 80 – 95% of adenomatous nodules demonstrate

peripheral vascularity in color Doppler imaging. 70 – 90 % of malignant

thyroid nodules demonstrate internal vascularity. The intranodular vessels

has significantly higher resistive index in malignant nodules.

8. Malignant cervical lymph nodes are located in the lower third of the neck,

usually rounded and have no echogenic hilum, whereas benign cervical

lymph nodes are slender, oval shape with central echogenic band that

represents the fatty hilum2.

41

Table: 1. Reliability of ultrasound features to differentiate benign and malignant

thyroid nodules.

Features Benign Malignant

Shape:

Taller than wider

Wider than tall

+

+++

++++

++

Echogenicity:

Hyper / isoechognic

Hypoechogenic

Marked hypoechogenic

++++

+++

+

+

+++

++++

Internal contents:

Cystic

Mixed solid and cystic

++++

+++

+

++

Halos:

Thin halo

Incomplete thick halo

No halos

++++

+

+

++

+++

+++

Calcification:

Coarse calcification

Microcalcification

Eggshell calcification

+++

++

+++

+

++++

++

Margin:Smooth

Poorly defined

Spiculated

+++

++

+

++

+++

++++

42

Doppler:

Internal flow pattern

Peripheral flow pattern

++

+++

+++

++

Sonoelastography:

Pattern 1 &2

Pattern 3 & 4

++++

+

+

++++

Sonoelastography:

Sonoelastography is a new sonographic technique used to evaluate the thyroid

nodules. It is also called as elastosonography. The physical characteristics of the

tissues are altered by pathologic processes. Based on this principle the

sonoelastography provides information about the tissue elasticity. During the

ultrasound examination, sonoelastographic measurements are performed by using the

same ultrasound machine and the same transducer. The sonographic images are

obtained before and after tissue compression and track tissue displacement by

assessing the propagation of the beam, providing accurate measurement of tissue

distortion. The ultrasound elastogram is displayed over the typical B – mode gray –

scale ultrasound scan in a color scale and classified by using the elasticity score. There

are four elastographic patterns are described as follows:

Pattern 1: elasticity in the whole nodule.

Pattern 2: large part of the nodule show elasticity with inconstant appearance of

anelastic areas

43

Pattern 3: constant presence of large anelastic areas at periphery.

Pattern 4: uniformly anelastic.

78 – 100 % of benign nodules show pattern 1 to 2, whereas 88 – 96 % of

malignant nodules show pattern 3 to 4. The free hand compression applied on the neck

region is standardized by real-time measurement displayed on a numerical scale to

maintain an intermediate level optimal for elastographic evaluation. This will

minimise the intraobserver and interobserver variability2.

ii) FINE NEEDLE ASPIRATION CYTOLOGY:

Fine needle aspiration cytology is the most effective method for diagnosis of

thyroid cancer. It is an invasive procedure used for collection of tissue samples for

cytopathological examination. It provides more direct information than any other

diagnostic procedure. The following instruments are used for fine needle aspiration.

NEEDLES:

Standard disposable 27 – 22 gauge (0.4 – 07 mm) with 30- 50 mm long needles

are used for superficial palpable lesions. 27 gauge needles are used for cell-rich and

vascular tissues such as lymph nodesand thyroids and also in children and in sensitive

areas such as eyelid, orbit, genitals etc…

For deeper tissues 22 gauge, 90 mm disposable lumbar puncture needles with

trocar or 22 gauge 150 or 250 mm chiba needles are used for taking specimen from

deeper tissues.

44

SYRINGES AND SYRINGE HOLDER:

Standard disposable plastic syringes mounted in a syringe holder / pistol grip

are suitable for conventional aspiration biopsy. The holder leaves one hand free to feel

and fix the target which allows better precision in placing the needle.

CONTAINERS AND SLIDES:

Small sterile containers which contain physiological saline or a transport

media such as Hank’s balanced salt solution with tightly closed lids should be in hand.

Special culture media may be used in certain circumstances.

FIXATIVES AND STAINS:

Smears are air-dried or wet fixed. Routine wet fixatives should be available at

all the time. 70 – 90 % ethanol is the commonly used routine fixative. Glutaraldehyde

and 10% buffered formalin should be used for the fragments to be examined under

electron microscope. A set of Diff – Quik stains in suitable container should be

available at all time.

Other instruments like skin disinfectant, sterile dressings, local anesthetic

agent, electric torch, tongue depressor, sterile scaple blades all should be available on

the biopsy tray. Latex gloves and face masks should also be available.

PATIENT PREPARATION:

The procedure and the complications of the procedure should be clearly

explained to the patient before getting the consent and the cooperation from the

45

patient. Local anesthesia is often warranted to avoid the unwanted movements or jerks

by the patient during the procedure.

BIOPSY PROCEDURE:

FINE NEEDLE BIOPSY WITH ASPIRATION:

The thyroid nodules with suspicious ultrasound features are selected for biopsy.

In case of multiple thyroid nodules or in case of nodules with no suspicious ultrasound

features the largest thyroid nodule is selected for biopsy.

The needle should be placed accurately after feeling the consistency of the

tissue through the needle. The plunger is pulled to apply the negative pressure inside

the tissue. The needle should be passed through the tissue in a near vertical pathway

which is less painful and allow better appreciation of depth. The ultrasonographic

guidance also can be used for this purpose. Then the needle is moved back and forth

inside the target tissue to aspirate the sample. After aspirating the tissue the negative

pressure is released while the needle remains in the target tissue. Then the needle is

withdrawn from the tissue and air drawn into the syringe after detaching the needle.

Then the sample had blown onto the microscopy slide.

FINE NEEDLE SAMPLING WITHOUT ASPIRATION:

In this the needle is inserted into the target tissue and then the needle is moved

back and forth, varying the angle. Then the needle is withdrawn and the needle is

attached to the syringe and then the sample is blown onto the microscopy slide.

46

After placing the tissue onto the microscope slide tissue processing is done.

The tissue should be fixed with appropriate fixative and then stained with necessary

stain10

.

There are two types of smears can be obtained. Dry sample can be smeared by

placing the tissue on the specimen slide. Then the sample is smeared with the flat of a

second slide by exerting a little pressure as it is moved along the specimen slide. The

pressure should be adjusted to achieve a thin, even spread smear. In a wet smearing

method the smearing slide is held against the specimen slide at blunt angle near one

end of the slide, so that the fluid accumulate in the angle. Then the smearing slide is

rapidly moved along the specimen slide so that the fluid is left behind while the cells

tend to follow the smearing slide. Then the concentrated cells are smeared with the

flat of the slide as for a dry aspirate. The wet smear should be immediately fixed with

95% alcohol.

Fine needle aspiration of thyroid nodules has sensitivity of 65 – 98 %,

specificity of 72 – 100 %, false negative rate of 1 – 11 % and false positive rate of 1 –

8 %10

.

COMPLICATIONS OF FNA11

:

The fine needle aspiration is complicated by localized pain which may be

referred to ipsilateral ear. It also can be complicated by haemorrhage and localized

hematoma formation.

47

PITFALLS IN FNA12

:

1. Inadequate specimen collection can lead to failure of the procedure.

2. The accuracy of the cytopathological interpretation.

3. Accuracy of the specimen.

4. Hurtle cell lesion; follicular lesions may not be clearly demarcated.

ULTRASOUND GUIDED FINE NEEDLE BIOPSY:

The ultrasound guided fine needle biopsy has the advantage that it allows

continuous real-time monitoring of the needle. This helps in taking the biopsy of small

lesions. A 25-gauge needle is used for this purpose employing either capillary action

or minimal suction with a syringe. Sonographic guidance is recommended in the

following situations:

1. When the physical examination shows inconclusive or questionable

nodules.

2. Patients with normal thyroid gland on physical examination but has

sonographically demonstrated nodules. Patients with family history of MEN

II syndrome, previous history of head and neck irradiation are at high risk

for thyroid cancer. These patients usually have normal thyroid gland with

sonographically demonstrated nodules.

3. When the biopsy performed under direct palpation is inconclusive or

nondiagnostic.

Sonographically guided fine needle aspiration is also useful in the early diagnosis of

recurrent or metastatic disease in the neck after previous thyroid resection for

48

carcinoma. Sonography guidance is also needed in patients who underwent

hemithyroidectomy for benign nodule which shows occult malignant tumor in the

surgically resected specimen to exclude the existence of residual nodule in the

contralateral lobe2.

iii) CONCEPT OF TIRADS:

Fine needle aspiration cytology is the confirmatory procedure for the thyroid

nodules to rule out whether the nodule is benign or malignant. But the major

disadvantage of the procedure is that it is an invasive procedure. So various studies

have been undertaken in the initial assessment of thyroid nodule to standardize the

ultrasound based thyroid imaging to make the diagnosis and to help the surgeons to

plan the treatment protocol.

American college of radiology designed a classification system for breast

lesions called Breast Imaging Reporting And Data System (BI-RADS). The BI-RADS

help to standardise breast imaging reports and management of breast lesions. BI-

RADS classification categories range from 1 (negative finding) to 6 (known proved

malignancy). Categories 2-5 are distinguished according to the level of suspicion for

malignancy. According to BI-RADS definitions, category 2 has less than 2%

malignant risk. Categories 4a, 4b, 4c have a malignancy risk of 2 – 10 %, 10 – 50 %,

50 – 95 % respectively. Category 5 has more than 95% of malignancy risk. Based on

BI-RADS another imaging system called Thyroid Imaging Reporting And Data

System (TIRADS) has been developed for the assessment of thyroid nodules and to

standardise the thyroid imaging system for thyroid lesions.In addition TIRADS saves

49

the unnecessary FNACs from clearly benign lesions thus saving time and resources

besides ensuring uniformity in reporting and interpretation13

.

V) REVIEW OF EARLIER STUDIES BASED ON TIRADS OR SINGLE /

MULTIPLE ULTRASOUND FEATURES:

A study has been conducted to develop a practical TIRADS to categorize

thyroid nodules and to stratify their malignancy risk. In this study thyroid nodules

with atleast 1 cm in maximum diameter were considered. These nodules were

described sonographically according to internal component, echogenicity, margins,

calcifications and shape. Then ultrasound guided fine needle aspiration biopsy was

performed with 23 – gauge needle attached to a 2 ml disposable plastic syringe and

aspiration. The aspirated material were expelled onto glass slides and smeared. These

smears were placed immediately in 95% alcohol for papanicolaon staining. Then the

cytology reports were classified as benign, indeterminate, suspicious for carcinoma,

malignant or inadequate. Then the benign or malignant thyroid nodules were

compared according to ultrasound features by using Chi square test.

The benign nodules are larger (20.7 mm ± 11.4 mm) than malignant nodules

(15.5 ± 7.5 mm) and benign nodules are seen in older patients (51.2 ± 12.3) than the

malignant nodules(47.5 ± 13.7). Solid component, hypoechogenicity, marked

hypoechogenicity, microlobulated or irregular margins, microcalcifications, taller than

wider shape all showed significant association with malignancy. Multivariate analysis

showed the risk of malignancy increased as the number of suspicious ultrasound

features increased. The values of fitted probabilities and risk of malignancy were

50

0.02 – 0.028 and 0.017 for the nodules with no suspicious ultrasound features

respectively. The nodules with one, two, three suspicious ultrasound features had the

probability and risk of malignancy 0.036 – 0.127 and 0.033, 0.068 – 0.378 and 0.092,

0.21 – 0.771 and 0.444 respectively. The nodules with four and all five suspicious

ultrasound features had the probability and risk of malignancy 0.57 – 0.919 and 0.724,

0.887 – 0.979 and 0.875 respectively. Among the suspicious ultrasound features solid

component alone have the fitted probability of malignancy ranges from 0.036 – 0.05.

Hypoechogenicity have the 0.039 – 0.054, microlobulated margin and

microcalcifications have 0.127 and 0.109 respectively. Based on these findings

TIRADS category has been created. Category 3 has no suspicious ultrasound feature.

Category 4a, 4b, 4c and 5 has one, two, three or four and five suspicious ultrasound

features respectively. So the risk of malignancy was determined according to the

number of suspicious ultrasound features13

.

Ultrasonography is commonly used for the initial assessment of thyroid

nodules. Various kinds of features seen in ultrasonography may favour the benignity

or malignity. These features include internal component of the nodule, margins,

echogenicity, calcification and the shape. A study was conducted to access the risk of

malignancy for these features seen in ultrasonography. Then these nodules were

categorized into TIRADS category.

In this study all thyroid nodules were investigated by ultrasound scan by using

a linear array transducer (5 – 12 MHz). Then all thyroid nodules were categorized

according to the following features.

51

1. Shape – taller than wider or wider than taller.

2. Echogenicity – hyper echogenicity, iso echogenicity, hypo or marked

hypoechogenicity.

3. Internal component – solid, mixed or cystic.

4. Calcification – micro calcification (< 3 mm), macro calcification (> 3 mm)

5. Margins – circumscribed, lobulated or irregular.

After ultrasound assessment all thyroid nodules were examined by ultrasound guided

fine needle aspiration cytolgy. The procedure was performed by the same radiologist

who has done the ultrasound, using 23 gauge needle attached to 10 ml plastic syringe.

The materials were expelled onto glass slide, smeared and sent to pathology

laboratory. The cytology reports were classified as benign, indeterminate, suspicious

for carcinoma, malignant or inadequate.

The high suspicious features of malignancy in ultrasound include taller than wide

shape, microcalcifications, marked hypoechogenicity, irregular or microlobulated

margins. According to the cytology and ultrasound reports the following TIRADS

classification has been proposed.

TIRADS 1: Normal thyroid ultrasound.

TIRADS 2: Benign nodules. This category includes simple cyst, isolated

macrocalcification, subacute thyroiditis, spongiform nodules and white knight aspects.

TIRADS 3: Probably benign nodules. The nodules with no high suspicious features

and the isoechogenic and hyperechogenic nodules are included in this category.

52

TIRADS 4A: The nodules with no high suspicious features, and moderately

hypoechogenic nodules are included in this category.

TIRADS 4B: The nodules with one or two high suspicious features with no

lymphadenopathy are included in this category.

TIRADS 5: The nodules with three or more than three high suspicious features

with or without lymphadenopathy are included in this category.

After the cytological results the risk of malignancy were calculated for each

TIRADS category. Totally 430 patients were selected for the study. Out of 430

patients 23 cases were proved to be malignant cytologically. Total numbers of cases

included in TIRADS category 2, 3, 4A, 4B, 5 are 83, 226, 101, 19and 1 respectively.

The risk of malignancy for each category is 0%, 2.2%, 5.9%, 57.9% and 100%

respectively.

The odds ratio was calculated for each of the major ultrasound features. The

odds ratio for benign and malignant cytology for the nodules with irregular margins is

0.21, 22.40 respectively. Nodules with taller than wider shape shows odds ratio of

19.50 for malignant nodules. Odds ratio for benign cytology is 0.43, for malignant

cytology is 15.24 for the nodules with microcalcification. Nodules with marked

hypoechogenicity showed odds ratio for benign and malignant cytology is 0.42, 12.75

respectively.

Sensitivity, specificity, positive predictive value and negative predictive value

for irregular margin are 34.78%, 99.51%, 80%, 96.43% respectively. For taller than

wide shape sensitivity, specificity, positive predictive value and negative predictive

53

value are 4.35%, 100%, 100% and 94.87% respectively. Sensitivity, specificity,

positive predictive value and negative predictive value for microcalcification are

30.4%, 98.8%, 58.3% and 96.2% respectively. For marked hypoechogenicity

sensitivity, specificity, positive predictive value and negative predictive value are

13.04%, 99.51%, 60% and 95.29% respectively14

.

In another study it was stated that the sonographic features of papillary

carcinoma of thyroid include hypoechoic texture (86%), microcalcification (42%),

well defined margins (47%), and intrinsichypervascularity (69%). This also includes

some uncommon features like irregular margins, hypovascularity, coarse or peripheral

calcifications.

Out of 29 lesions which showed calcifications, 69% (20 cases) had

microcalcifictions; 17% (5 cases) had coarse calcifications and 1 patient had

peripheral calcification.

Out of 55 patients analysed sonographically, 54% of cases had atleast one

uncommon feature. 87% of patients had solid lesions whereas the remaining patients

had either cystic elements or predominantly cystic architecture.

Colour Doppler sonography of those patients showed primarily intrinsic flow

pattern in 43 lesions, whereas the remaining 12 lesions showed perinodular flow15

.

In another study the author took antero-posterior and transverse diameter of the

nodules, microcalcification, blurred margin, hypoechogenicity into account for

predicting the malignant risk of thyroid nodules.

54

The author stated that in small nodules (≤ 0.5 cm) the most accurate

sonographic feature forpredicting papillary thyroid carcinoma is antero-posterior to

transverse diameter ratio > 1 with sensitivity 81.4%, specificity 96.8%. Whereas in

larger nodules (> 1 cm), the microcalcifications showed higher sensitivity.

Hypoechogenicity and blurred margins had the sensitivity of 95.3% and 97.7%

respectively, but has low specificity (19.4% and 29.9% respectively) in predicting

papillary thyroid carcinoma in small thyroid nodules. So the ratio between antero-

posterior and transverse diameter along with other sonographic features help in the

diagnosis of thyroid carcinoma in small nodules16

.

According to the cytology the thyroid nodules can be classified into benign

(negative for cancer), suspicious for thyroid cancer, indeterminate, malignant (positive

for cancer) or unsatisfactory (non diagnostic).

Fine needle aspiration cytology which is an invasive procedure is considered to

be unnecessary for the detection of thyroid carcinoma. Because only 4% (1 – 10%)

lesions have the probability to be malignant. The fine needle aspiration cytology also

has indeterminate results because of low cellularity, small size and cystic nature of

nodules or due to inexperience of the operator performing the fine needle aspiration

cytology.

Sonographically internal content of the nodule, echogenicity, shape,

calcifications, echotexture, margin, capsular invasion, halo are considered to classify

thyroid nodules as probably benign, suspicious for malignancy and indeterminate17

.

55

The most common clinical feature of papillary thyroid carcinoma is solitary

thyroid nodule. Hypoehoic solid lesion with microcalcification and internal

vascularity are the features suggestive of papillary thyroid carcinoma on sonography.

An unusual presentation of papillary thyroid carcinoma has been reported in which the

papillary thyroid carcinoma presented as left hip mass with predominantly cystic

nodule on sonography. Magnetic resonance imaging of the left hip mass demonstrated

destructive lesion measured 9.5 X 9.5 X 15 cm. Histopathology of the mass showed

metastatic papillary thyroid carcinoma confirmed by immunohistochemistry and

positive staining for thyroid transcription factor 1. The ultrasonographic examination

of the thyroid demonstrated unilocular thick walled cystic lesion with no hypoechoic

halos or calcifications. Color Doppler showed abnormal vascularity in the thick

irregular wall. Ultrasound guided fine needle aspiration biopsy was performed and

histopathology demonstrated papillary thyroid carcinoma. The sonographic

appearance of thyroid nodules did not suggest a malignant lesion and did not fit the

biopsy criteria18

.

In another study it was stated that the mean size of benign nodules is larger

than malignant nodules. The benign nodules are seen in elder patients than the

malignant nodules. There was no association has been demonstrated between sex and

malignancy. Thyroid nodules with no suspicious feature have the malignant rate of

7.30. Non parallel orientation and ill-defined margins has the malignant rate of 8.3.

Microloulated or speculated margin has 59.1; marked hypoechogenicity has 43.6

malignant rate. Microlobulated or spiculatedmargin, marked hypoechogenicity has

56

high odds ratio for malignancy. Non-parallel orientation, microcalcification, ill-

defined margin and hypoechogenicity have low odds ratio for malignancy19

.

A study has been conducted in 462 patients who had cytological report

suspicious for malignancy. Out of 462 patients 327 patients had suspicious follicular

or hurthle cell carcinoma, 125 patients had suspicious papillary carcinoma and 10

patients had other suspicious lesions (medullary carcinoma, lymphoma) in the

cytology. All the patients underwent surgery and the lesions were examined

histopathologically. The malignancy rate for the lesions suspicious for papillary

carcinoma was 77%, and for follicular/hurthle cell neoplasm was 15%. In this study it

was reported that the patient age, serum TSH level and the history of radiation

exposure are not associated with increased risk of malignancy. The study also stats

that multiple nodules carries more risk (41.1%) for malignancy than single nodules

(26.4%) and the smaller nodules carries more risk (2.6 ± 1.8 cm) than the larger

nodules (2.9 ± 1.6 cm). The risk of malignancy increased in patients who received

thyroid hormone therapy than those patients who did not receive thyroid hormone

therapy. The reason for this association is not known20

.

Study has been conducted to compare the quantitative sonoelastography to

conventional qualitative sonoelastography and sonography. In this study 98 thyroid

masses were examined by sonography and sonoelastography and the strain ratios were

calculated. The average strain of representative region of interest from lesion were

calculated and expressed as A. Then the average strain of corresponding region of

adjacent thyroid tissue was expressed as B. Then the strain ratio was calculated by the

following formula: strain ratio = B/A which reflected the stiffness of the lesion. The

57

strain ratio of more than 3.79 was considered as the predictor of the nodule

malignancy. This cut off point was decided by Receiver Operating Characteristic

(ROC)curve. The benign lesions showed strain ratio of 2.97 ± 4.35 (mean ± SD) and

the malignant lesion had 11.59 ± 10.32 with P value less than 0.0001. 43 out of 53

benign lesions had a score of 1 or 2, whereas 40 out of 45 malignant nodules had a

score of 3 or 4 with sensitivity of 97.8%, specificity of 85.7%, positive predictive

value 80.0%, and negative predictive value 89.5%. Sonoelastography also shows

additional information about elasticity in color on B mode images. The blue color

representing hard tissue, red and green color representing soft and medium tissue

respectively.But this method is limited by lack of standardization21

.

A study has been conducted to analyse the tumor vascularity on power Doppler

sonograms in differentiating malignant and benign solid thyroid nodules using tumor

histologic evaluation as the reference standard. In this study 86 solid thyroid

tumorswere qualitatively analysed for nodule vascularity. Increase in the level of

intranodular vascularization is associated with an increase in tumor size. Increased

intranodular vascularization has sensitivity of 65.2%, specificity of 52.5% and 58.9%

overall accuracy in differentiation between benign and malignant thyroid lesions.

Resistive index characterize the arterial waveform produced on Doppler sonography,

it also not dependent on insonation angle (the angle at which the ultrasound beam

intercepts the axis of the vessel). But for the large nodules the quantitative and

qualitative criteria of vascularity shows very low accuracy because in the benign

thyroid nodules intranodular vascularity is increased with increase in tumor size22

.

58

In another study totally 675 nodules underwent biopsy. All these nodules had

the diameter between 0.8 – 4.6 cm (mean 1.96 cm; SD – 0.877 cm). Out of these 675

nodules 36 were malignant. 31 were papillary thyroid carcinoma (86.1%), 2 were

lymphoma (5.56%), 1 were medullary thyroid carcinoma (2.78%), 1 were hurthle cell

carcinoma (2.78%) and 1 were indeterminate between hyalinising trabecular adenoma

Vs papillary thyroid carcinoma. So the prevalence of malignant thyroid nodules was

5.33%. In this study the hypoechogenicity seen in 30.6% of benign lesions Vs 47.1%

of malignant lesions. Isoechogenicity seen in 61.1%, 47.1% of benign and malignant

thyroid nodules respectively. Hypoechogenicity seen in 8.3% of benign and 5.8% of

malignant lesions respectively. None of these findings are statistically significant in

differentiating benign and malignant thyroid lesions. Solid echo texture was present in

83.3% benign and 85.3% malignant lesions and also predominantly cystic nodules

were seen in 5.6% benign and 2.9% malignant lesions. 11.1% benign and 14.7%

malignant thyroid nodules had clearly defined borders and 47.2% benign and 41.1%

malignant thyroid nodules had irregular or less defined borders. None of these

findings were statistically significant.

3 out of 36 benign thyroid nodules showed grade 4 internal vascularity in color

Doppler. No malignant nodules showed flow pattern higher than grade 3. 20.6% of

malignant and 19.4% benign thyroid nodules showed intermediate grades of internal

flow. 69.4% benign and 64.7% malignant nodules showed color Doppler grade 0 or 1.

So the internal vascularity and the nodule shape also statistically not significant in

differentiating benign and malignant nodules.

59

Calcifications were seen in 5.6% benign and 35.3% malignant lesions. So the

presence of calcifications were statistically significant (p value < 0.005)to differentiate

benign and malignant thyroid nodules. The presence of calcifications in thyroid

nodules was 94.4% specific for malignancy. It also had positive predictive value of

0.857 and negative predictive value of 0.60723

.

Based on the principles of BI-RADS and TI-RADS another imaging system

has been developed for the evaluation of hepatic nodules with magnetic resonance

imaging named Liver Imaging Reporting And Data System (LI-RADS). According to

LI-RADS hepatic nodules are divided into 5 categories. Various studies have been

conducted for the diagnosis of hepatocellular carcinoma. In one study patients with

cirrhosis with sonographically newly detected hepatic solitary nodule with less than

20 mm in size were considered. The magnetic imaging and fine needle biopsy were

used as reference standard. Then the LI-RADS category was assigned to nodules seen

at magnetic resonance imaging. Out of 133 nodules evaluated 102 lesions were

hepatocellular carcinoma, 3 lesions were intrahepatic cholangiocarcinoma, 1 were

neuroendocrine metastasis and 27 were benign lesions. None of category 1 lesions

(0%), 3 out of 12 category 2 lesions (25%), 29 out of 42 category 3 lesions (69%), 24

out of 25 category 4 lesions (96%), 44 out of 45 category 5 lesions (98%) were

hepatocellular carcinomas. Two out of four lesions categorized as other malignancies

were hepatocellular carcinomas. So the LI-RADS has the sensitivity 42.3%,

specificity 97.8%, positive predictive value 97.8%, negative predictive value 47.4%

for the diagnosis of benign hepatic nodules. It also has 65.4%, 96.4%, 97.1%, 59.6%

60

sensitivity, specificity, positive predictive value, negative predictive value

respectively for the diagnosis of malignant nodules24

.

OBSERVATION

61

OBSERVATION

The present study has been undertaken in 200 patients presented with primary

thyroid related complaints. The patients were analysed by ultrasonography and fine

needle aspiration cytology.

Total number of patients: 200 patients

Total number of nodules analysed and assigned as per TIRADS – 227 nodules.

Total number of nodules for which FNAC was done – 200 nodules.

Total number of lesions that underwent surgical excision: 46.

Total number for which definite diagnosis by FNAC was made: 154

Ultrasonographically the thyroid nodules were evaluated for shape (wider than

taller, taller than wider), echogenicity (isoechogenicity, hyperechogenicity,

hypoechogenicityand markedhypoechogenicity), content of the nodules (solid, mixed),

calcification (no calcification, microcalcification, macrocalcification) and margins

(smooth, irregular, microlobulated). The results are shown below.

1. SHAPE:

Out of 200 nodules evaluated 194 nodules were wider than taller in shape and 6

nodules were taller than wider in shape. Among the 194 nodules which were

wider than taller in shape 184 nodules showed benignity on FNAC report. The

remaining 10 nodules were malignant in nature on FNAC. All the nodules

which showed taller than wider in shape showed malignant character.

62

According to the current study the nodules which had wider than taller shape

have 94.1% chances of benignity and 5.1% chances of malignancy. The

nodules which had taller than wider shape have 100% chances of malignancy.

Table: 2. Number of thyroid nodules depending upon the Shape

S.No Shape Benign Malignant

1 Wider than taller 184 10

2 Taller than wider 0 6

Figure: 26. Chart showing the percentage of thyroid nodules depending upon the

Shape

94.84%

5.20%0%

100%

0.00%

20.00%

40.00%

60.00%

80.00%

100.00%

120.00%

Benign Malignant

1 Wider than taller

2 Taller than wider

63

2. ECHOGENICITY:

Ultrasonographically 172 thyroid nodules showed either isoechogenicity or

hyperechogenicity, 16 nodules showed hypoechogenicity and the remaining 12

nodules demonstrated marked hypoechogenicity. All the 172 nodules which

had iso or hyperechogenicity on USG have demonstrated benignity on FNAC.

Among the 16 nodules which had hypoechogenicity 12 nodules were benign

and 4 were malignant on FNAC. All the nodules which showed marked

hypoechogenicity were malignant. So the nodules with iso or

hyperechogenicity on USG are benign in 100% cases. The nodules with

hypoechogenicity have 75% chances of benignity and 25% chances of

malignancy. The nodules with marked hypoechogenicity have 100% chances of

malignancy.

Table: 3. Number of thyroid nodules depending upon Echogenicity

S. No ECHOGENICITY BENIGN MALIGNANT

1. ISO /

HYPERECHOGENICITY

172 0

2. HYPOECHOGENICITY 12 4

3. MARKED

HYPOECHOGENICITY

0 12

64

Figure: 27. Chart showing the percentage of thyroid nodules depending

upon Echogenicity

3. CONTENT:

Ultrasonographically 102 nodules were solid in nature and 98 nodules

demonstrated mixed content (solid and cystic). Out of 102 nodules which were

Table: 4. Number of thyroid nodules depending upon Content

S.No CONTENT BENIGN MALIGNANT

1. SOLID 86 16

2. MIXED (SOLID AND

CYSTIC)

98 0

100%75%

0%0% 25%

100%

0%

20%

40%

60%

80%

100%

120%

ISO / HYPERECHOGENICITY

HYPOECHOGENICITY MARKED HYPOECHOGENICITY

1 2 3

BENIGN MALIGNANT

65

solid in nature 86 nodules were benign and 16 nodules were malignant on

FNAC. So the nodules which have solid content have 84.3% chances of

benignity and 15.7% chances of malignancy and the nodules which have mixed

content have 100% chances of benignity.

Figure: 28. Chart showing the percentage of thyroid nodules depending

upon the Content

4. CALCIFICATION:

Out of the 200 nodules analysed 176 nodules had no calcification 10 had

macrocalcification and 14 had microcalcification. The nodules which had no

calcification have 97.7% chances of benignity (172 nodules were benign on

FNAC) and 2.3% chances of malignancy (4 nodules were malignant on

FNAC). The nodules which had macrocalcification have 100% probability of

benignity (all 10 nodules had benign character on FNAC). The nodules which

have microcalcification have 85.7% chances of malignancy (12 nodules were

84.31%

15.68%

100%

0%0.00%

20.00%

40.00%

60.00%

80.00%

100.00%

120.00%

BENIGN MALIGNANT

1 SOLID

2 MIXED (SOLID AND CYSTIC)

66

malignant on FNAC) and 14.3% chances of benignity (2 nodules were benign

on FNAC).

Table: 5. Number of thyroid nodules depending upon Calcification

S. No CALCIFICATIONS BENIGN MALIGNANT

1. NO CALCIFICATION 172 4

2. MACROCALCIFICATION 10 0

3. MICROCALCIFICATION 2 12

Figure: 29. Chart showing the percentage of thyroid nodules depending

upon the Calcification

97.72% 100%

14.28%2.27% 0%

85.71%

0.00%

20.00%

40.00%

60.00%

80.00%

100.00%

120.00%

NO CALCIFICATION MACROCALCIFICATION MICROCALCIFICATION

BENIGN MALIGNANT

67

5. MARGIN:

Among the 200 nodules 140 nodules had smooth margin, 52 nodules had

irregular margin and 8 nodules had microlobulated margin on USG. The

nodules which had smooth margin on USG have 98.6% chances of benignity

Table: 6. Number of thyroid nodules depending upon the Margin

S.NO MARGIN BENIGN MALIGNANT

1 SMOOTH 138 2

2 IRREGULAR 46 6

3 MICROLOBULATED 0 8

Figure: 30. Chart showing the percentage of thyroid nodules depending

upon the Margin

98.57%88.46%

0%1.42% 11.54%

100%

0.00%

20.00%

40.00%

60.00%

80.00%

100.00%

120.00%

SMOOTH IRREGULAR MICROLOBULATED

BENIGN MALIGNANT

68

(138 nodules were benign) and 1.4 chances of malignancy on FNAC (2 nodules

were malignant). The nodules which had irregular margin have 88.5% chances

of benignity and 11.5 % chances of malignancy (46 were benign and 6 were

malignant on USG). Out of 8 nodules which had microlobulated margin all was

demonstrated malignant character on FNAC. So the nodules which have

microlobulated margin on USG have 100% chances of malignancy on FNAC.

According to the ultrasound features all the thyroid nodules were categorized into

TIRADS category. Out of the 200 nodules evaluated 140 nodules were included in

TIRADS category 3, 12 nodules in category 4a and 40 nodules in category 4b. The

remaining 8 nodules were included under category 5. All the nodules in category 3

were shown benign character on histopathology. Two nodules in category 4a and six

nodules in category 4b were malignant and all the 8 nodules in category 5 had

malignant character in histopathology.

Table: 7. Number of thyroid nodules depending upon TIRADS category

S.No TIRADS category Benign Malignant Total

1. TIRADS 3 140 0 140

2 TIRADS 4a 10 2 12

3 TIRADS 4b 34 6 40

4 TIRADS 5 0 8 8

69

Table: 8. Percentage of thyroid nodules depending upon TIRADS category

S.No TIRADS category Percentage of benign

nodules

Percentage of malignant

nodules (risk of

malignancy)

1. TIRADS 3 100% 0%

2. TIRADS 4a 83.3% 16.7%

3. TIRADS 4b 85% 15%

4. TIRADS 5 0% 100%

Figure: 31. Chart showing the percentage of thyroid nodules depending upon

TIRADS category

100%83.30% 85%

0%0% 16.70% 15%

100%

0%

20%

40%

60%

80%

100%

120%

TIRADS 3 TIRADS 4a TIRADS 4b TIRADS 5

Percentage of benign nodules

Percentage of malignant nodules (risk of malignancy)

REPRESENTATIVE CASES

70

REPRESENTATIVE CASES

1. 45 years old male patient came with complaints of swelling infront of the neck for

two months. Ultrasound showed solitary thyroid nodule with following findings:

1. Wider than taller shape.

2. Iso Echogenicity

3. Solid Content

4. No Calcification

5. Smooth Margin

TIRADS Category: 3

Figure: 32. Ultrasound image of colloid goitre

FNAC report of the above mentioned nodule is Colloid goitre.

71

2. 36 years old female patient presented with complaints of swelling in front of the

neck for 3 months.Sonography of thyroid nodule showed following findings:

1. Wider than taller shape

2. IsoEcogenicity

3. Solid with Cystic changes

4. No Calcification

5. SmoothMargin

TIRADS category:3

Figure: 33 Ultrasound image of nodular goitre with cystic degeneration

FNAC report of above nodule is Nodular goitre with cystic degeneration.

72

3. 44 years old female patient presented with complaintsof neck swelling for 6

months. Ultrasonography of thyroid nodule showed the following findings:

1. Taller than wider shape

2. Solid Content

3. Marked Hypoechogenicity

4. Microcalcification

5. Smooth Margins.

TIRADS Category: 5.

Figure: 34 Ultrasound image of Papillary Thyroid Carcinoma

FNAC report of the above nodule is Papillary Thyroid Carcinoma.

73

4.55years old female patient came with the complaints of swelling infront of the neck

for 2 months. Ultrasound of solitary thyroid nodule showed following findings:

1. Wider than taller shape

2. Solid Content.

3. Marked Hypoechogeniity

4. No Calcification

5. Smooth Margin

TIRADS category: 4B

Figure: 35. Ultrasound image of Follicular Thyroid Carcinoma

Biopsy report of the above mentioned nodule is Follicular Thyroid Carcinoma.

74

5. 58 years old male patient came with the complaints of swelling infront of the neck

for 6 months.Ultrasound of thyroid nodule showed following findings:

1. Wider than taller shape

2. Solid Content

3. Marked Hypoechogenicity

4. No Calcification

5. Irregular Margin

TIRADS category: 4B

Figure: 36. Ultrasound image of Lymphoma of thyroid gland

FNAC report of the above mentioned nodule is Lymphoma of thyroid gland.

DISCUSSION

75

DISCUSSION

Malignancy of thyroid gland has the prevalence of about 5%25, 26

. In some

studies it was stated that less than 10% of thyroid nodules are malignant. In the

present study 8% of thyroid nodules were malignant on histopathology. It correlates

with the previous studies.

In a study conducted by Moifo B et al it was stated that the risk of malignancy

was increased from TIRADS category 2 to category 5. In his study he stated 0% risk

of malignancy in TIRADS category 2. TIRADS category 3, 4a, 4b had 2.2%, 5.9%,

57.9% as risk of malignancy respectively. TIRADS category 5 had 100% risk of

malignancy. In our present study no thyroid nodules were included in category 2.

Table: 9. Comparison of TIRADS category between two studies

S. No TIRADS category Risk of malignancy in

study by Moifo et al.

Risk of malignancy in

present study

1. Category 3 2.2 % 0 %

2. Category 4a 5.9 % 16.7 %

3. Category 4b 57.9 % 15 %

4. Category 5 100 % 100 %

76

Figure: 37. Chart showing the comparison of TIRADS category between two

studies

But the risk of malignancy for TIRADS category 3, 4a, 4b was 0%, 16.7%, 15%

respectively. TIRADS category 5 had 100% risk of malignancy.

Horvath et al suggested that the risk of malignancy for TIRADS category 3, 4a,

4b was less than 5%, 5 – 10%, 10 – 80% respectively. The TIRADS category 5 carries

greater than 80% risk of malignancy27

. In the present study the risk of malignancy for

TIRADS category 3, 4a, 4b, 5 was 0%, 16.7%, 15%, 100% respectively. These results

are corresponding to the previous study done by Hoverth et al expect for TIRADS

category 4a in which we had slightly increased risk for malignancy. This can be

explained by the fact that the assessment of the margins of the thyroid nodules was

subjected to inter observer variation.

There are various ultrasound features associated with increased risk of thyroid

malignancy. These features include taller-than-wider shape, irregular contour, marked

2.20% 5.90%

57.90%

100%

0%

16.70% 15%

100%

0.00%

20.00%

40.00%

60.00%

80.00%

100.00%

120.00%

Category 3 Category 4a Category 4b Category 5

Risk of malignancy in study by Moifo et al.

Risk of malignancy in present study

77

hypoechogenicity and the presence of microcalcifications. Presence of these features

is suspicious for malignancy.

Moifo et al reported that the presence of irregular contour of the thyroid

nodules had the sensitivity, specificity of 34.78%, 99.51% respectively. The positive

Table: 10. Comparison of two studies for irregular margin

S.No Study Sensitivity

(%)

Specificity

(%)

PPV (%) NPV (%) OR

1. Moifo B et al 34.78 99.51 80 96.43 22.40

2. Present study 37.5 75 11.54 93.24 1.71

Figure: 38. Chart showing comparison of two studies for irregular margin

34.78

99.51

80

96.43

22.4

37.5

75

11.54

93.24

1.710

20

40

60

80

100

120

Sensitivity (%) Specificity (%) PPV (%) NPV (%) OR

Moifo B et al Present study

78

predictivevalue and negative predictive value for the irregular contour of the nodule

are 80%, 96.43% respectively with the odds ratio 22.40 (CI – 12.47 – 40.23). In our

present study presence of irregular margin has sensitivity, specificity, positive

predictive value and negative predictive value is 37.5%, 75%, 11.54%, 93.24%

respectively with the odds ratio 1.71 (CI – 0.65 – 4.47).

In our present study we also analysed the sensitivity, specificity, positive

predictive value and the negative predictive value for the microlobulated margin.

These values are 50%, 100%, 100%, 95.83% respectively. Odds ratio for the

microlobulated margin is 24 (CI – 12.18 – 47.30) according to the current study.

Kwak el al reported that the odds ratio for microlobulated margin is 20.135 (CI –

14.038 – 28.880).

Moifo B et al reported that the thyroid nodules with taller-than-wider shape had

sensitivity, specificity, positive predictive value and negative predictive value 4.35%,

Table: 11. Comparison of two studies for taller-than-wider shape

S.No Study Sensitivity

(%)

Specificity

(%)

PPV (%) NPV (%) OR

1. Moifo B et

al

4.35 100 100 94.87 19.50

2. Present

study

37.5 100 100 94.84 19.40

79

100%, 100%, 94.81% respectively with odds ratio of 19.50. In our present study

taller-than-wider shape have sensitivity, specificity, positive predictive value and

negative predictive value 37.5%, 100%, 100%, 94.84% respectively. The odds ratio

for taller-than-wider nodule is 19.4 (CI – 10.61 – 35.48).

Figure: 39. Chart showing comparison of two studies for taller-than-wider shape

So the results of the current study corresponds to the study done by Moifo B et

al. according to both the studies nodules with taller-than-wider shape carries around

19.40 times increased risk of being malignancy than the nodules without taller-than-

wider shape.

In our current study the presence of microcalcification have sensitivity,

specificity, positive predictive value and negative predictive value 75%, 98.91%,

85.71%, 97.85% respectively. It also has the odds ratio 20.35 (CI – 10.00 – 41.45). So

according to the current study presence of microcalcification carry 20.35 times

4.35

100 10094.87

19.5

37.5

100 10094.84

19.4

0

20

40

60

80

100

120

Sensitivity (%) Specificity (%) PPV (%) NPV (%) OR

Moifo B et al Present study

80

increased risk of malignancy. Moifo B et al had sensitivity, specificity, positive

predictive value and negative predictive value 30.4%, 98.8%, 58.3%, 96.2%

Table: 12. Comparison of two studies for Microcalcification

S.No Study Sensitivity

(%)

Specificity

(%)

PPV (%) NPV (%) OR

1. Moifo B et

al

30.4 98.8 58.3 96.2 15.24

2. Present

study

75 100 100 97.87 20.35

Figure: 40. Chart showing comparison of two studies for Microcalcification

30.4

98.8

58.3

96.2

15.24

75

100 100 97.87

20.35

0

20

40

60

80

100

120

Sensitivity (%) Specificity (%) PPV (%) NPV (%) OR

Moifo B et al Present study

81

respectively. In that study the odds ratio for microcalcification is 15.24 (CI – 7.74 –

30.02). So according to both the studies presence of microcalcification carries higher

risk of malignancy than the nodules without microcalcification.

In our present study presence of marked hypoechogenicity has sensitivity,

specificity, positive predictive value and negative predictive value 75%, 100%, 100%,

97.87% respectively with the odds ratio 47 ( CI – 17.83 – 123.92). So the thyroid

nodules with marked hypoechogenicity has 47 times increased risk of malignancy

than the nodules without marked hypoechogenicity. Moifo B et al had sensitivity,

specificity, positive predictive value and negative predictive value 13.04%, 99.51%,

60%, 95.29% respectively with odds ratio 12.75 (CI – 5.54 – 29.35).

Table: 13. Comparison of two studies for marked hypoechogenicity

S.No Study Sensitivity

(%)

Specificity

(%)

PPV (%) NPV (%) OR

1. Moifo B et

al

13.04 99.51 60 95.29 12.75

2. Present

study

75 100 100 97.87 47

82

Figure: 41. Chart showing comparison of two studies for marked

hypoechogenicity

In another study done by Kwak et al the odds ratio for marked

hypoechogenicity, microlobulated margins, irregular margins, microcalcification and

Figure: 42.Chart showing comparison of odds ratio for suspicious ultrasound

features

13.04

99.51

60

95.29

12.75

75

100 100 97.87

47

0

20

40

60

80

100

120

Sensitivity (%) Specificity (%) PPV (%) NPV (%) OR

Moifo B et al Present study

0

20

40

60

80

100

120

MH ML Margin IR Margin MIC CAL TTW

1.Moifo B et al

2.Kwak et al

3.Present study

83

Table: 14. Comparison of odds ratio for suspicious ultrasound features

Marked

Hypoechogenicity

(MH)

Microlobulated

(ML) Margin

Irregular

(IR)

Margin

Micro

calcification

(MIC CAL)

Taller-than-

wider (TTW)

shape

1.Moifo

B et al

12.75 - 22.40 15.24 19.50

2.Kwak

et al

69.756 20.135 113.828 25.871 24.478

3.Present

study

47 24 1.71 20.35 19.4

taller-than-wider shape was 69.756 (CI – 37.216 – 130.747), 20.135 (CI – 14.038 –

28.880), 113.828 (CI – 60.771 – 213.205), 25.871 (CI – 17.503 – 38.240), 24.478 (CI

- 17.152 – 34.933). According to this study all the above mentioned sonographic

features are associated with increased risk of malignancy.

According to the current study taller-than-wider shape, marked

hypoechogenicity and the microlobulated margins in ultrasonography are 100%

specific for malignancy. There are certain sonographic features consistently associated

with benign nodules. These features include isoechogenicity or hyperechogeicity,

mixed (solid and cystic) content of the nodules and the presence of macrocalcification.

These sonographic features help to exclude the malignant thyroid nodules. However

84

there are rare exceptions like cystic necrosis of papillary carcinoma which was not

encountered in our study.

CONCLUSION

85

CONCLUSION

The present studyhas been undertaken to classify the thyroid nodules into

various TIRADS category and to analyse the suspicious sonographic features with the

histopathological reports to assess the risk of malignancy for the suspicious

sonographic features and to assess the risk of malignancy for each TIRADS category.

This also helps to reduce the incidence of unnecessary FNAC procedures.

According to the present study TIRADS category 3 has 0% risk of malignancy

and category 5 has 100% risk of malignancy. So the risk of malignancy increases from

TIRADS category 3 to TIRADS category 5. So the thyroid nodules which are

included in TIRADS category 3 or less than 3 do not need FNAC. They need short

term follow up every 6 months to document stability of the lesion. Since thyroid

malignancies grow slowly, follow up for atleast 2 years is warranted. Only the nodules

included in TIRADS category 4 and 5 require biopsy to differentiate the benign from

malignant thyroid nodules.

The sonographic features like irregular margins, microlobulated margins,

marked hypoechogenicity, microcalcification and taller-than-wider shape are all

associated with increased risk of malignancy. Presence of microlobulated margins,

marked hypoechogenicity and taller-than-wide shaped nodules are 100% specific for

malignancy. Sonographic features like isoechogenicity or hyperechogenicity, mixed

(solid and cystic) content of the nodule, macrocalcificationare predictive of benignity.

86

In conclusion high resolution ultrasound is an accurate technique to assess the

morphology of thyroid nodules. Describing the findings using standard lexicon and

categorizing using TIRADS achieves the following.

i. It ensures objectivity in reporting

ii. Malignant lesions are identified with high accuracy

iii. It aids in clinical decision making

iv. It prevents unnecessary FNACs.

v. This avoids unnecessary patient discomfort, cost and wastage of resources.

SUMMARY

87

SUMMARY

Ultrasonography is commonly used for the evaluation of thyroid nodules. But

reporting of thyrosonogramis often vague, subjective and inconclusive. Taking this

problem into account this study has been undertaken to improve the sensitivity,

specificity of the ultrasonography and to classify the thyroid nodules into five major

categories based on Thyroid Imaging Reporting And Data System (TIRADS) for the

diagnosis of malignant thyroid nodules.

The patients coming to Coimbatore Medical College and Hospital, Coimbatore

with the complaint of thyroid nodules have been evaluated sonographically for the

suspicious ultrasonographic features of thyroid malignancy. Then these nodules were

subjected to fine needle aspiration cytology and the results were obtained from

pathology department.

These results were analysed and compared with the suspicious sonographic

features to assess the risk of malignancy for each TIRADS category and for each

suspicious feature. These results were also compared with the previous literature it

was concluded that the sonographic features like taller than wider shape, irregular

margin, microlobulated margin, microcalcification and marked hypoechogenicity are

all associated with increased risk of thyroid malignancy. By designating an

appropriate TIRADS category, the highly suspicious nodules (category 4 and 5)are

sampled by FNAC or dealt with surgery immediately, while category 3 lesions are

followed up. Category 2 lesions do not require any further investigations. This is

analogous to the stratification of breast lesion by BIRADS.

ANNEXURE –I CONSENT FORM

88

CONSENT FORM

You, Shri./ Smt./ Kum. _________________________, aged ____ years, S/o / D/o /

W/o ___________________________, residing at ________________

_______________________________________ are requested to be a participant in

the research study titled “Assessment of malignant risk potential of thyroid nodules

using Ultrasound Thyroid Imaging Reporting And Data System(TIRADS)criteria with

correlation by Fine Needle Aspiration Cytology (FNAC)/Excision biopsy” conducted

by Dr.THAIYAL NAYAKI.S., one of the post graduate trainees in the Dept. of

Radiodiagnosis, Govt. Coimbatore Medical College and Hospital, Coimbatore. You

are eligible for the study as per the inclusion criteria. You can ask her any question or

seek from her any clarifications about the study which you may have before agreeing

to participate in the study.

TOPIC OF THE RESEARCH

Assessment of malignant risk potential of thyroid nodules using ultrasound Thyroid

Imaging Reporting And Data System(TIRADS)criteria with correlation by Fine

Needle Aspiration Cytology (FNAB)/Excision biopsy.

PURPOSE OF RESEARCH

To develop a practical Thyroid Imaging Reporting and Data System(TIRADS)

from which to categorize the thyroid nodules and stratify their malignant risk.

89

PROCEDURES INVOLVED IN THE STUDY

Fetching baseline characteristics of the patient like age, gender etc.

Proper history pertaining to the patient’s complaints.

Collecting thyroid profile reports(if applicable)

Ultrasonography of thyroid for localising and characterisation of thyroid nodules.

Ultrasonography guided Fine Needle Aspiration Biopsy of thyroid nodules.

Continued follow-up of patient and collecting Biopsy reports for analyzing them with

sonographic findings.

Recordingall theabove variants/events into the database and analyzing them by

statistical methods to arrive at our objectives.

DECLINING FROM PARTICIPATION

You are hereby made aware that participation in this study is purely voluntary and

honorary, and that you have all the rights to decline from participating in it.

PRIVACY AND CONFIDENTIALITY

You are hereby assured that your privacy is respected. Any information about you or

provided by you during the study will be kept strictly confidential.

90

AUTHORIZATION TO PUBLISH RESULTS

Results of the study may be published for scientific purposes and/or presented to

scientific groups. In any case, neither will your identity be revealed nor will your

privacy be breached.

STATEMENT OF CONSENT

I, _____________________, do hereby volunteer and consent to participate in this

study being conducted by Dr.THAIYALNAYAKI.S. I have read and understood the

consent form (or) it has been read and explained to me thoroughly. I am fully aware of

the study details as well as aware that I may ask questions to her at any time.

Signature / Left Thumb Impression of the patient

Station: Coimbatore

Date:

Signature / Left Thumb Impression and Name of the witness

Station: Coimbatore

Date:

BIBLIOGRAPHY

91

BIBLIOGRAPHY

1. DattaA K. Essentials of Human Anatomy, Head and Neck, 5th

edn, Chapter 7;

Deep structures of neck, Current books international: Kolkata, 2009; 160-6.

2. Rumack C M, Wilson S R et al. Diagnostic Ultrasound, Volume 1, 4th

edn,

Chapter 18; The thyroid gland, ELSEVIER: Chaina, 2011; 708-46.

3. Michael M, Dean S et al., Diagnostic imaging techniques in thyroid cancer,

American journal of surgery, 1988; 155: 215-20.

4. Charles B H et al. MR imaging of thyroid, ATR, 1993; 140: 455-60.

5. Singh I B. Textbook of human Histology, 4th

edn. The Endocrine System,

JAYPEE Brothers, Medical Publishers (P) Ltd: New Delhi, 2002; 306-8.

6. DattaA K. Essentials of Human Embryology, 6th

edn, Chapter 12; The

Alimentary System, Current books international: Kolkatta, 2010; 116-7.

7. Barrett K E, Barman S M et al. Ganong’s Review of Medical Physiology,

24th

edn. The Endocrine System, Tata Mcgraw Hill education (P) Ltd: New

Delhi, 2012; 339-50.

8. Lloyd R, Delellin R et al. Pathology and genetics of tumors of endocrine

organs. USA: 2004: 45. Available from URL lhp://www.jarc.fr/who-blue books

/ index.wtml.

9. Abbas A K, Fausto N et al. Robbin’s Pathological basis of diseases, 8th

edn.

Endocrine system, Elsevier: New Delhi, 2013; 1118 – 26.

10. Orell S R, Sterrett G F et al. Fine needle aspiration cytology, 5th

edn. The

technique of FNA cytology, Churchill livingstone, Elsevier: New york, 2012; 8

– 14.

92

11. Hales M S, Hsu M Set al. Needle tract implantation of Papillary carcinoma of

the thyroid following aspiration biopsy, Actacytol 2002; 34:801.

12. SahaA et al. Controversies in the management of thyroid nodules.

Laryngoscope, 2000; 110: 183 – 93.

13. Kawk Y J, Han H K et al. Thyroid Imaging Reporting and Data System for US

features of Nodules: A step in establishing better stratification of cancer risk,

RSNA, 2011; vol 260: 892 – 99.

14. Moifo B, Takoeta et al. Reliability of Thyroid Imaging Reporting and Data

System (TIRADS) classification in Differentiation Benign from Malignant

Thyroid Nodules, Open Journal of Radiology, 2013; 3: 103 – 7.

15. Chan K B, Desser T S et al. Common and uncommon sonographic features of

Papillary Thyroid Carcinoma, Journal of Ultrasound in Medicine, 2003; vol. 22

(10): 1083 – 90.

16. RenJ, Liu B et al. A Taller-Than-Wide shape is a good predictor of Papillary

Thyroid Carcinoma in small solid nodules, J Ultrasound Med, 2015; 34: 19 –

26.

17. Acharya U R, Swapna G et al. A review on ultrasound based thyroid cancer

tissue characterization and automated classification technology in cancer

research and treatment, ISSN 1533 – 0346, 2014; vol 13 (4): 289 - 301

18. Liu Y I, Shin L K et al. An Unusual Imaging and clinical Presentation of

Papillary Thyroid Carcinoma, Journal of ultrasound in Medicine, 2008; vol 27

(8): 1241 – 44.

93

19. Kwak J Y, Jung I et al. Image Reporting and characterization system for

ultrasound features of Thyroid nodules: Multicentric Korean Retrospective

Study, Korean J Radiol, 2013; 14(1):110 -17.

20. Castro M R, Espiritu R P et al. Predictors of Malignancy in patients with

cytologically suspicious Thyroid Nodules, Irish Journal of Medical Science,

2014; vol 183: 633 – 37.

21. Xing P, Wu L et al. Differentiation of benign from malignant lesions, Journal

of Ultrasound in Medicine, 2011; vol 30: 663 – 9.

22. Lyshchik A, Moses R et al. Quantitative analysis of tumor vascularity in benign

and malignant solid thyroid nodules, Journal of ultrasound in medicine, 2007,

vol 26 (6): 837 – 46.

23. Iannuccilli J D, Cronan J J et al. Risk for malignancy of thyroid nodules as

assessed by sonographic criteria, Journal of ultrasound in medicine, 2004; vol

23(11): 1455 – 64.

24. Darnell A, Fornet A et al. Liver imaging reporting and data system with MR

imaging: Evaluation in nodules 20 mm or smaller detected in cirrhosis at

screening US, RSNA, 2015; vol 275 (3).

25. Kim K M, Park J B et al. Ultrasonographic guideline for thyroid nodules

cytology: Single institute experience, Journal of the Korean surgical society,

2013; vol 84 (2): 73-9.

26. Dean D S et al. Epidemiology of thyroid nodules, Best practice and Research:

clinical endocrinology and metabolism, Journal of radiology, 2012; vol 262(3):

901-11.

94

27. Horvath E, Majlis S et al. An ultrasonogram reporting system for thyroid

nodules stratifying cancer risk for clinical management, The journal of clinical

endocrinology and metabolism, 2009; vol 9 (5): 1748-51.

-

ANNEXURE –II MASTER CHART

95

KEY TO MASTER CHART

NS – Neck Swelling

DR – Duration

CV – Change of Voice

DG – Dysphagia

DN – Dysphea

P – Pain

SN – Single Nodule

MN – Multiple Nodule

M – Month

Y – Year

S – Shape

E – Echogenicity

C – Content

CAL – Calcification

M – Margin

TTW – Taller-than-wider

WTT – Wider than taller

HR – Hyperechogenicity

IS – Isoechogenicity

HO – Hypoechogenicity

96

MHO – Marked Hypoechogenicity

SD – Solid

MX – Mixed

CY – Cystic

AB – Absent

MIC – Microcalcification

MAC – Macrocalcification

SO – Smooth

IR – Irregular margin

ML – Microlobulated margin

NCG – Nodular Colloid Goiter

CdNG – Cystic degeneration of Nodular Goiter

CdCG – Cystic degeneration of Colloid Goiter

CdNCG – Cystic degeneration of Nodular Colloid Goiter

NG – Nodular Goiter

CG – Colloid Goiter

PTC – Papillary Thyroid Carcinoma

FTC – Follicular Thyroid Carcinoma

FPTC – Follicular variant of Papillary Thyroid Carcinoma

L - Lymphoma

97

MASTER CHART

S.No NAME Age/Sex Clinical Findings USG Findings TIRADS

category

FNAC

Report NS DR CV DG CL P SN MN S E C CAL M

1. Akilandam 78 y / F + 6M - + - + + - WTT HR SD AB SO 3 NCG

2. Baby 32 y / F + 4M - + - + + - WTT HR SD AB SO 3 NCG

3. Bagyalakshmi 51 y / F + 3M - - - + + - WTT IS SD AB SO 3 NCG

4. Basha 38 y / M + 1Y - + - + + - WTT HO MX AB SO 4A CdNG

5. Essakiyammal 36 y / F + 4M - - - + + - WTT HR SD AB IR 4B CdCG

6. Eswari 45 y / F + 5M - - - + + - WTT HR SD AB SO 3 NCG

7. Eswari 55 y / F + 3M + + - + + - WTT MHO SD AB ML 4B PTC

8. Ganesh 40 y / M + 8M - - - + + - WTT HO SD AB IR 4B CdNCG

9. Kalaivani 36 y / F + 5M - - - - + - WTT HR SD AB SO 3 NG

10. Ganga 40 y / F + 2M - - - + + - WTT HR MX AB SO 3 NCG

11. Krishnaveni 42 y / F + 1Y - - - - + - WTT IS MX AB SO 3 CdCG

12. Kunaladevi 31 y / F + 5M - - - + + - WTT IS MX AB SO 3 CdCG

13. Lithy violet 50 y / F + 2Y + + + + + - TTW MHR SD MIC IR 5 PTC

14. Kavitha 27 y / F + 1M - - - - + - WTT HR SD MAC SO 3 NCG

98

15. Kondappan 53 y / M + 6M - - - - + - WTT HR MX AB SO 3 CdNCG

16. Pushpa 52 y / F + 5M + + + + + - WTT MHO SD MIC IR 5 FTC

17. Mallika 31 y / F + 3M - - - + - + WTT HO SD AB SO 4A CG

18. Mary philomina 48 y / F + 2M + + + + + - TTW MHO SD MIC IR 5 PTC

19. Marudbaul 55 y / M + 4M - + - + + - WTT MHO SD MIC ML 5 PTC

20. Rani 44 y / F + 1M - - - - + - WTT HR MX AB SO 3 NG

21. Rihana 21 y / F + 3M - - - - + - WTT HR MX AB SO 3 CdCG

22. Sampoorna 50 y / F + 2M - - - - + - WTT HR SD AB SO 3 NG

23. Sasikaladevi 33 y / F + 9M - + - + + - WTT HR MX AB SO 3 NG

24. Selvi 49 y / F + 4M - + - + + - WTT HO SD MIC IR 4B PTC

25. Shanthi 45 y / F + 3M - - - - - + WTT HO MX AB SO 4A CdNG

26. Sonia 41 y / F + 2M - - - - + - WTT HR MX AB IR 4B CdNG

27. Thilakavathi 45 y / F + 3M - - - + + - WTT HR MX AB SO 3 NG

28. Daniel 59 y / M + 2Y + - - + + - WTT MHO SD AB ML 4B FvPTC

29. Kavitha 36 y / F + 2M - - - + + - WTT HR MX AB SO 3 CdNG

30. Jothimani 40 y / F + 6M - - - + + - WTT HR SD AB SO 3 NCG

99

31. Muthulakshmi 30 y / F + 2M - - - - + - WTT HR SD AB SO 3 NCG

32. Ponmani 22 y / F + 1M - - - + + - WTT HR SD AB SO 3 CdNG

33. Ananthi 29 y / F + 1M - - - + + - WTT HR MX AB SO 3 NG

34. Anitha 30 y / F + 3M - - - + + - WTT HR MX AB SO 3 NG

35. Arokyamari 60 y / F + 2Y - - - - + - WTT HR MX AB IR 4B CdNG

36. Bharathi 68 y / F + 3M - - - - + - WTT HR MX AB SO 3 CdNG

37. Jannamuthu 50 y / M + 6M - - - + + - WTT HR SD AB IR 4B NG

38. Jeganathan 35 y / M + 2M - - - + + - WTT HR MX AB SO 3 NCG

39. Jeya 36 y / F + 2M - - - - + - WTT HR MX AB SO 3 CdNCG

40. Kannammal 49 y / F + 1M - - - + - + WTT HR MX AB SO 3 NG

41. Eashwari 38 y / F + 3M - - - + + - WTT HR SD AB SO 3 NG

42. Kavitha 36 y / F + 2M - - - + + - WTT HR MX AB SO 3 NG

43. Manimegalai 28 y / F + 5M - - - - + - WTT HR SD AB IR 4B CdNG

44. Mary 57 y / F + 9M - - - + + - WTT HR MX AB SO 3 CdNG

45. Shanthi 37 y / F + 2M - - - - + - WTT HR SD AB SO 3 NG

46. Sangeetha 27 y / F + 1M - - - + + - WTT HR MX AB SO 3 CdNG

47. Saraswaathi 42 y / F + 5M - - - + + - WTT HR SD AB SO 3 NG

100

48. Lilly 50 y / F + 1Y - - - - + - WTT HR SD AB SO 3 NG

49. Muthulakshmi 43 y / F + 2M - - - - + - WTT HR SD AB IR 4B NG

50. Nachiyammal 63 y / F + 2M - - - + + - WTT HR SD AB IR 4B NCG

51. Muthulakshmi 30 y / F + 4M - - - + + - WTT HR SD AB SO 3 NG

52. Pitchaikani 37 y / F + 5M - - - - + - WTT HR SD AB SO 3 CG

53. Thulasimani 39 y / F + 6M - - - - + - WTT HR SD AB SO 3 NG

54. Kalaimani 40 y / F + 1M - - - - + - WTT HR SD AB SO 3 NG

55. Deepa 28 y / F + 1M - - - + + - WTT HR MX AB SO 3 NG

56. Kavitha 38 y / F + 3M - - - - + - WTT HR SD AB IR 4B NG

57. Deepa 36 y / F + 5M - - - + + - WTT HR SD AB SO 3 NG

58. Jeya 43 Y / F + 6M - - - + + - WTT HR SD AB SO 3 NG

59. Veerammal 45 y / F + 2M - - - + + - WTT HR SD AB IR 4B NG

60. Shanmugam 58 y / M + 7M - + - - + - WTT MHO SD AB IR 4B L

61. Susheela 36 y / F + 2M - - - - - + WTT HR SD AB SO 3 NG

62. Subhulakshmi 35 y / F + 3M - - - + + - WTT HR MX AB SO 3 NG

63. Saraswathy 45 y / F + 6M - - - + + - WTT HR MX AB SO 3 NG

64. Subhathal 60 y / F + 1Y + - - + + - WTT HR SD MAC IR 4B NG

101

65. Nithya 36 y / F + 3M - - - + + - WTT HR MX AB SO 3 CdNG

66. Geetha 54 y / F + 2M - - - + + - WTT IS MX AB SO 3 CdNG

67. Arokkyamary 60 y / F + 1M - - - + + - WTT IS MX AB IR 4B NG

68. Pushpa 30 y / F + 4M - - - - + - WTT HR SD AB SO 3 NG

69. Jameela 60 y / F + 2M - - - + + - WTT HR SD AB SO 3 NG

70. Rukmani 40 y / F + 6M - - - + + - WTT IS MX AB SO 3 CdNG

71. Rani 34 y / F + 3M - - - + + - WTT HR SD AB SO 3 NCG

72. Mary 42 y / F + 2M - - - - + - WTT HR MX AB IR 4B NG

73. Rakkaye 53 y / F + 1M - - - - + - WTT HR MX AB IR 4B CdNCG

74. Povayee 35 y / F + 7M - - - - + - WTT HR SD AB SO 3 NG

75. Kuppusamy 29 y / M + 4M - - - - + - WTT HR MX AB SO 3 NCG

76. Veerammal 54 y / F + 3M - - - - - + WTT HR SD AB IR 4B NG

77. Rajesh 60 y / M + 9M - - - - + - WTT HR MX AB SO 3 CdNCG

78. Meena 51 y / F + 4M - - - + + - WTT HR MX AB SO 3 NCG

79. Subhulakshmi 70 y / F + 5M + + + + - + TTW MHO SD MIC ML 5 PTC

80. Kannammal 45y / F + 1M - - - + + - WTT HR SD AB SO 3 CdNG

81. Savithiri 37 y/ F + 2M - - - - + - WTT HR SD AB SO 3 NCG

102

82. Sekar 62 y / M + 7M - - - - + - WTT HR MX AB IR 4B NG

83. Guna 57 y / M + 3M - - - - + - WTT HR SD MIC IR 4B CdNCG

84. Rajesh 43 y / M + 8M - - - - + - WTT HR SD MAC SO 3 NCG

85. Kumar 63 y / M + 1M - - - - + - WTT HR MX AB IR 4B CdNG

86. Saraswathi 50 y / F + 5M - + + + + - TTW MHO SD MIC IR 5 PTC

87. Karthik 37 y / M + 3M - - - - + - WTT HR MX AB SO 3 CdNCG

88. Mekala 27 y / F + 7M - - - - + - WTT HR SD AB SO 3 NG

89. Abirami 44 y / F + 9M - - - - + - WTT HO MX AB SO 4A NCG

90. Ravisankar 53 y / M + 1M - - - + + - WTT HR MX AB SO 3 CG

91. Sundari 34 y / F + 4M - - - - + - WTT HR SD AB SO 3 CdNCG

92. Surya 63 y / M + 3M - - - - + - WTT HR MX AB IR 4B CG

93. Ponnammal 38 y / F + 6M - - - - + - WTT HR MX AB SO 3 NCG

94. Hariharan 53 y / M + 2M - - - - + - WTT HR SD AB IR 4B NG

95. Kokila 46 y / F + 7M - - - - + - WTT HR SD MAC IR 4B CdNCG

96. Kannan 38 y / M + 1M - - - - - + WTT HR SD AB SO 3 CdNG

97. Radhika 50 y / F + 5M - - - - + - WTT IS MX AB SO 3 CG

98. Veena 55 y / F + 8M - - - - + - WTT HR SD AB SO 3 NCG

103

99. Ashwini 65 y / F + 5M + + - + - + WTT HO SD MIC ML 4B PTC

100. Roopa 53 y / F + 3M - - - - + - WTT HR MX AB SO 3 NCG

101. Devi 52 y / F + 5M - - - - + - WTT HR SD AB IR 4B NG

102. Pradhap 36 y / M + 9M - - - - + - WTT HO SD MAC IR 4B NG

103. Ashok 63 y / M + 2M - - - - + - WTT IS SD AB SO 3 NG

104. Praveen 49 y / M + 3M - - - - + - WTT IS SD AB SO 3 NCG

105. Shailaja 58 y / F + 7M - - - - + - WTT IS SD AB SO 3 NG

106. Srimathi 49 y / M + 4M - - - - + - WTT HR MX AB IR 4B CG

107. Komala 60 y / F + 9M - - - - + - WTT IS MX AB SO 3 NCG

108. Kannaki 46 y / F + 2M - - - - + - WTT HR MX AB SO 3 CG

109. Sridhar 38 y / M + 5M - - - - + - WTT HR MX AB IR 4B CdNCG

110. Shankar 45 y / M + 2M - - - - + - WTT HO SD AB SO 4A NCG

111. Krishnan 50 y / M + 8M - - - - + - WTT HR MX AB IR 4B CdNCG

112. Papathi 47 y / F + 4M - - - - + - WTT IS SD AB IR 4B NCG

113. Alamelu 54 y / F + 8M - - - + + - WTT IS SD AB SO 3 NCG

114. Saroja 47 y / F + 2M - - - + + - WTT HO MX AB SO 4A CdNG

115. Vijaya 38 y / F + 9M - - - + + - WTT HR MX AB IR 4B CdNCG

104

116. Rajeswari 70 y / F + 4M + + + + - + TTW MHO SD MIC ML 5 FTC

117. Harish 28 y / M + 8M - - - - + - WTT HR MX AB SO 3 CdNCG

118. Pachiyammal 50 y / F + 3M - - - - + - WTT IS MX AB IR 4B NCG

119. Pondiyammal 50 y / F + 5M - - - - + - WTT IS MX MAC IR 4B CdNCG

120. Banumathi 48 y / F + 1Y - - - - + - WTT IS SD AB SO 3 NG

121. Shanmugam 39 y / M + 3M - - - + + - WTT HR MX AB SO 3 NCG

122. Varunkumar 27 y / M + 9M - - - - + - WTT HR MX AB IR 4B CdNCG

123. Lakshmi 46 y / F + 3M - - - + + - WTT HR SD AB IR 4B CG

124. Palaniyappan 51 y / M + 6M - - - - + - WTT HO MX AB SO 4A CdNCG

125. Radha 38 y / F + 3M - - - + + - WTT HR SD AB IR 4B NG

126. Balasubramani 39 y / M + 8M - - - - + - WTT HR MX AB SO 3 NCG

127. Mohanambal 52 y / F + 2M - - - + + - WTT HR MX AB IR 4B NCG

128. Suseela 48 y / F + 7M - - - - + - WTT HR SD AB SO 3 CdNG

129. Prabavathi 48 y / F + 3M - - - + + - WTT HR MX AB SO 3 CG

130. Murugan 38 y / M + 8M - - - - + - WTT HR SD AB SO 3 CdNCG

131. Natarajan 25 y / M + 4M - - - - + - WTT IS MX AB SO 3 NCG

132. Veeran 48 y / M + 5M - - - - + - WTT IS SD MAC SO 3 CdNCG

105

133. Sudha 39 y / F + 9M - - - - + - WTT HR MX AB SO 3 CG

134. Baby 47 y / F + 2M - - - - - + WTT IS MX AB SO 3 CdNCG

135. Revathi 61 y / F + 5M + + - - + - WTT HO SD AB SO 4A FTC

136. Dhanalakshmi 43 y / F + 3M - - - - + - WTT HR MX AB SO 3 CG

137. Mayavan 63 y / M + 7M - - - - + - WTT IS MX AB SO 3 CdNCG

138. Latha 52 y / F + 3M - - - - + - WTT HR SD AB SO 3 NG

139. Kesavan 46 y / M + 1M - - - - + - WTT HR MX AB SO 3 NCG

140. Selvi 31 y / F + 2M - - - - + - WTT HR MX AB SO 3 CdNG

141. Vijayan 52 y / M + 5M - - - - + - WTT IS MX AB SO 3 NCG

142. Sarala 50 y / F + 3M - - - - + - WTT HR SD AB SO 3 NG

143. Narayanan 48 y / M + 3M - - - - + - WTT HR MX AB SO 3 CG

144. Geethalakshmi 42 y / F + 7M - - - - - + WTT HR SD AB SO 3 CdNCG

145. Velusamy 53 y / M + 9M - - - - - + WTT IS MX AB SO 3 CG

146. Vimala 30 y / F + 2M - - - - + - WTT IS MX MAC SO 3 NG

147. Rukmani 51 y / F + 6M - - - - + - WTT HR SD AB SO 3 NCG

148. Nadesan 45 y / M + 4M - - - + + - WTT HR MX AB SO 3 CG

149. Saraswathi 37 y / F + 6M - - - + + - WTT HR MX AB SO 3 CdNCG

106

150. Ganesan 46 y / M + 3M - - - - - + WTT HR SD AB SO 3 NCG

151. Hemalatha 52 y / F + 5M - - - + + - WTT HR MX AB SO 3 CG

152. Annamalai 60 y / M + 3M - - - + + - WTT IS SD AB SO 3 NG

153. Poongothai 54 y / F + 4M - - - - - + WTT HO MX AB SO 4A CdNCG

154. Abdul kareem 48 y / M + 6M - - - - + - WTT HR SD AB SO 3 NCG

155. Stephen 52 y / M + 2M - + - + + - WTT HO SD AB SO 4A NG

156. Yasodha 58 y / F + 7M - - - + + - WTT HR SD AB SO 3 CdNCG

157. Narmatha 46 y / F + 4M - - - - + - WTT HR SD AB SO 3 NCG

158. Ganga 37 y / F + 3M - - - - + - WTT HR MX AB SO 3 CG

159. Manimegalai 40 y/ F + 7M - - - - + - WTT HR SD AB SO 3 CdNG

160. Selvi 38 y / F + 4M - - - + + - WTT HR MX AB SO 3 NCG

161. Bhuvana 47 y / F + 8M - - - - + - WTT HO MX AB SO 4A CG

162. Sathish 45 y / M + 3M - - - + + - WTT IS SD AB SO 3 CdNCG

163. Balaji 36 y / M + 6M - - - - + - WTT IS MX AB SO 3 CG

164. Palanivelraja 42 y / M + 3M - - - + - + WTT HR SD AB SO 3 NCG

165. Muthu 35 y / M + 6M - - - - - + WTT HR MX AB SO 3 CG

166. Indharani 58 y / F + 3M + + + - - + TTW MHO SD MIC ML 5 PTC

107

167. Vidhya 50 y / F + 7M - - - - + - WTT IS SD AB SO 3 CdNCG

168. Sarasawathi 60 y / F + 3M - - - - + - WTT HR MX AB SO 3 CG

169. Gayathri 48 y / F + 5M - - - + + - WTT HR SD AB SO 3 NCG

170. Kannammal 50 y / F + 2M - - - + + - WTT HR MX AB SO 3 CdNCG

171. Pache 65 y / F + 8M + + - + + - WTT MHO SD AB ML 4B PTC

172. Palaniyappan 52 y / M + 1M - - - + + - WTT HR MX MAC SO 3 NCG

173. Radha 48 y / F + 9M - - - - + - WTT IS SD AB SO 3 NG

174. Sudhakar 31 y / M + 1M - - - - + - WTT HR MX AB SO 3 CG

175. Kannaki 36 y / F + 1Y - - - - + - WTT IS SD AB SO 3 NG

176. Murugan 39 y / M + 3M - - - - + - WTT IS MX AB SO 3 NCG

177. Lakshmi 51 y / F + 6M - - - - + - WTT HR SD AB SO 3 NG

178. Subramani 48 y / M + 4M - - - - + - WTT HR MX AB SO 3 NCG

179. Kanaga 51 y / F + 7M - - - - + - WTT HR SD AB SO 3 CdNG

180. Kannan 47 y / M + 3M - - - - - + WTT HR MX AB SO 3 CG

181. Moorthy 50 y / M + 9M - - - + - + WTT HR SD AB SO 3 CdNCG

182. Kalpana 48 y / F + 2M - - - + + - WTT IS MX AB SO 3 NCG

183. Ponni 38 y / F + 4M - - - + + - WTT IS SD AB SO 3 NG

108

184. Natarajan 63 y / M + 3M + - - - - + WTT HO SD AB SO 4A FTC

185. Thangavel 47 y / M + 2M - - - - + - WTT HR MX AB SO 3 CG

186. Durairaj 40 y / M + 3M - - - - + - WTT IS MX AB SO 3 NCG

187. Mallika 46 y /F + 2M - - - + + - WTT HR SD AB SO 3 NG

188. Selvi 42 y / F + 2M - - - - - + WTT HR MX MAC SO 3 CdNG

189. Duraisamy 58 y / M + 6M - - - + - + WTT HR MX AB SO 3 CdNCG

190. Chithra 46 y / F + 7M - - - - + - WTT IS MX AB SO 3 NCG

191. Vijayanandh 45 y / M + 9M - - - + + - WTT HO SD AB SO 4A CdNCG

192. Suganya 28 y / F + 5M - - - - + - WTT HR MX AB SO 3 CG

193. Hariharan 30 y / M + 6M - - - + + - WTT IS SD AB SO 3 NCG

194. Alamelu 53 y / F + 3M - - - + + - WTT HR MX AB SO 3 CdNCG

195. Senthilkumar 48 y / M + 3M - - - + + - WTT HR MX AB SO 3 CG

196. Jothi 39 y / F + 6M - - - + - + WTT HR MX AB SO 3 CdNG

197. Sheela 50 y / F + 7M - - - + + - WTT IS SD AB SO 3 NG

198. Maheswari 45 y / F + 8M - - - - + - WTT IS MX AB SO 3 NCG

199. Pondi 61 y / M + 2M - - - - - + WTT HR SD AB SO 3 NG

200. Thangammal 35 y / F + 6M - - - - + - WTT HR MX AB SO 3 CdNCG