Seminar on Solitary Thyroid Nodule

1. SOLITARY THYROID NODULE
MODERATED BY
DR. P. P. DAS
DR. A. SARMA
DR. M. M. ALAM
PRESENTED BY
JAYDEEP MALAKAR

2. DEFINITIONS
• OLD :
In an otherwise normal gland, a single palpable
nodule in the thyroid on clinical examination.
• NEW :
A DISCRETE lesion /nodule, WITHIN the thyroid,
that is PALPABLY and/or RADIOLOGICALLY DISTINCT
from the surrounding thyroid parenchyma.
*5-15 % of all Solitary Thyroid Nodules = Thyroid Malignancy.

3. The prevalence of thyroid nodules detected on palpation (Broken Line) or by Ultrasonography or
Post Mortem examination (Solid Line) *
*Mazzaferri EL. Management of a solitary thyroid nodule. New England Journal of Medicine. 1993 Feb 25;328(8):553-9.

5. SOLITARY THYROID
NODULE
MULTI NODULAR
GOITRE
COLLOID
GOITRE

6. EPIDEMIOLOGY
• A palpable thyroid nodule is usually > 1 cm.
• Prevalence varies considerably worldwide, depending on regional iodine
sufficiency.
– Iodine deficient areas: up to 50% of adults.
– Iodine sufficient areas: ~5% of adults (U.S.A).
• It is more common in women (6.4%) than men (1.5%).
• The prevalence is
– 4% by palpation,
– 19 to 67% by ultrasound examination,
– and 50% in autopsy series.

7. CLASSIFICATIONS
Benign 90% Cysts
Adenomas Papillary
Follicular Colloid
Fetal
Embryonic
Hurthle Cell Type
Toxic Adenoma Solitary
Hyperfunctioning
thyroid nodule
Non Toxic Adenoma Solitary
Nonfunctioning
thyroid nodule

8. CLASSIFICATIONS
Malignant 10% Primary Follicular
Epithelium –
Differentiated
Papillary 80%
Follicular 10%
Follicular
Epithelium – Poorly
Differentiated
Anaplastic 5%
Parafollicular Cells Medullary 2.5%
Lymphoid Cells Lymphoma 2.5%
Secondary Metastatic
Local infiltration
The main aim in the evaluation of STN is to differentiate benign from malignant lesions at a
reasonable cost & trauma to the patient.

9. SYMPTOMS AND SIGNS
SYMPTOMS
A. Nontoxic adenomas: Large adenomas present as a neck mass. Smaller
adenomas are typically asymptomatic.
B. Toxic adenoma: Symptoms of thyrotoxicosis.
C. Association with other Endocrinopathies (MEN) :Multifold Symptoms
SIGNS
Most palpable nodules are > 1 cm in diameter.
Ability to detect a palpable thyroid nodule on physical examination depends on :
a. Location within the gland, c. Degree of adiposity and
b. Anatomy of patient’s neck d. Experience of examiner.

10. HISTORY
The thyroid nodule is often discovered incidentally during a clinical examination
performed for another purpose.
– Size: All nodules larger than 1 cm and nonpalpable nodules with suspicious imaging
need further evaluation.
>4cm increases incidence of malignancy.
– Rate of growth:
• Over hours with pain suggests hemorrhage into an existing nodule.
• Over weeks is more strongly associated with malignancy, and
• During levothyroxine therapy is especially suggestive of cancer.
• Sudden change in the size of a pre-existing nodule may indicate malignancy.

11. HISTORY
• Age and Gender
-Around 20 to 50% of solitary nodules in patients younger than 20 years are malignant.
-Pediatric thyroid carcinoma occurs in teenage years (mean 16) and in girls 5.6 times more often
than in boys.
-Beyond 70 years of age, malignancy is not common, but prognosis is worse when present.
-Risk of malignancy in men is twice that of women.
• Diet
-Patients from iodine-sufficient areas have a higher rate of malignancy than those from iodine-
deficient areas (5.3% vs 2.7%)*.
However, follicular and anaplastic carcinomas are relatively more common in iodine-deficient areas.
*Zimmermann MB, Galetti V. Iodine intake as a risk factor for thyroid cancer: a comprehensive review of animal and human studies. Thyroid research. 2015 Dec;8(1):8.

13. HISTORY
WELL DIFFERENTIATED THYROID CANCER
• GARDNER’S SYNDROME (AD)
– FAP.
– Osseous/Soft Tissue Tumours
– Retinal Epithelium Hypertrophy
– Supernumerary Teeth.
MEDULLARY CARCINOMA THYROID
• MEN II A&B (AD).
COWDEN’S SYNDROME (AD)
-Multiple hamartomas
-Fibrocystic Breast Disease.
-Breast Cancer (PTEN)

14. EXPOSURE TO RADIATION
• The risk is maximum 20 to 30 years after exposure.
• Papillary Thyroid Carcinoma is most common.
• Thyroid nodule + History of radiation = 40% Chance of Thyroid Cancer.
• Exposure to Radiation for Hodgkin’s Lymphoma / CA Breast
– 35 years after exposure, in 7- 10% of exposed patients.
– 100 Rads- Thyroid nodules, Thyroid carcinoma
– >2000 Rads - Prevent thyroid neoplasm (Thyroid gland destroyed)
10 mSv = 1 Rad
A chest x-ray, delivers 0.1 mSv.

15. PHYSICAL EXAMINATION
• Consists of local examination of thyroid and systemic examination for features of
hypo/hyperthyroidism and other stigmata of malignancy or other etiology.
• The thyroid gland and nodules within it move with swallowing.
• The size, site, shape consistency and presence of any other palpable nodules should be
noted.
– Nodule with firm consistency - autoimmune thyroid disease
– Stony hard consistency favors malignancy.
– Firm nodule along with fixity suggests invasion and may be a pointer toward
malignancy.

16. Positive Pemberton’s Sign
To demonstrate
the presence of
latent pressure in
the thoracic inlet.
“Cork effect”
Retrosternal
Goiter.

18. SUMMARY OF MALIGNANT
CHARACTERISTICS
• Young patients (< 20 years) or old (> 70 years),
• Male sex,
• H/O external neck radiation during childhood or adolescence,
• Recent change in voice (RLN Involvement)
• Past family history of thyroid carcinoma.
• Enlarging Nodule (Size >4 cms)
• Firm consistency of nodule,
• Irregular shape,
• Fixation to underlying or overlying tissues,
• Suspicious regional lymphadenopathy.
• Family history of PTC, MTC, or MEN2

19. DIFFERENTIAL DIAGNOSIS
• Primary thyroid cancer
• Functioning adenoma
• Nonfunctioning adenoma
• Cyst
• Thyroid lymphoma
• Cancer metastasizing to the thyroid
• Hashimoto’s Thyroiditis.
• Simple Goiter
• Development defects e.g. - ectopic tissue.

20. DIAGNOSTIC APPROACH
• Evaluation of a STN consists of 2 components.
• To determine if
– nodule is autonomously functioning and possibly causing hyperthyroidism
Or
– has high risk of malignancy.

21. WORK UP OF A THYROID NODULE

22. SEROLOGY AND BIOCHEMICAL TESTS
• Initial screening test FOR ALL PATIENTS with a thyroid nodule is serum TSH level to know
if the patient is euthyroid, hypothyroid or hyperthyroid.
• Most of the patients with a thyroid nodule are euthyroid and if they are not euthyroid,
then the underlying pathology is likely to be benign and functional.
• When hypothyroidism is confirmed, anti thyroid peroxidase antibodies should be assayed
to evaluate for Hashimoto’s thyroiditis.
• A baseline preoperative ionized calcium estimation is helpful, since a parathyroid
adenoma may mimic a thyroid nodule. This also gives a clue to MEN I or II and helps
decide further plan of management.

23. SEROLOGY AND BIOCHEMICAL TESTS
• Routine evaluation of thyroglobulin and calcitonin levels is not
recommended since this approach is not cost effective.
• Thyroglobulin levels are useful as a surveillance test in well differentiated
thyroid carcinoma after a total thyroidectomy but it has no role in initial
evaluation of a thyroid nodule.
• Patients having positive family history of MTC, a serum calcitonin should
be included in the initial test as it is sensitive in detecting even small
MTCs.
• Patients with personal or family history of MTC, mutational screening of
the RET protooncogene should be employed.
• High levels of TPOab suggests an autoimmune etiology – Hashimoto’s
Thyroiditis .

25. FINE-NEEDLE ASPIRATION CYTOLOGY
• Fine-Needle Aspiration Cytology (FNAC) is the most important diagnostic evaluation
for a thyroid nodule.
• It is the safest, most cost-effective, and most reliable technique to differentiate
between benign and malignant diseases of the thyroid.
• FNACs reduces the number of thyroidectomies by half while doubling the surgical
confirmation of carcinoma.
• FNAC can be done with or without USG guidance. USG guided FNAC is more reliable,
rapid, accurate and safe. The specimen should be evaluated immediately on-site to
judge the adequacy of FNA specimen. For proper reporting, smear should be adequate.

26. FINE-NEEDLE ASPIRATION CYTOLOGY
• For a thyroid FNA specimen to be satisfactory for evaluation at least 6 groups of
benign follicular cells are required and each group should be composed of at least
10 cells.
• Current sensitivity and specificity generally exceed 90 and 70%, respectively.
• Since, the size of needle used is very small (21 to 24 gauge), needle-track seeding
is unlikely.
• The false negative rate varies from 1 to 5% and is associated with cysts or nodules
smaller than 1 cm or masses greater than 3 cm.

27. THE BETHESDA SYSTEM FOR REPORTING THYROID
CYTOPATHOLOGY

28. THE THY CLASSIFICATION ADOPTED BY THE ROYAL
COLLEGE OF PHYSICIANS
CLASS DESCRIPTION ACTION
Thy1 Non-diagnostic
(inadequate/ technical artefact precludes
interpretation)
FNAC should be repeated with or without
ultrasound guidance..
Thy 1 c Non-diagnostic cystic
Thy2 Non-neoplastic
(features consistent with a nodular goitre
or thyroiditis).
Two non neoplastic results 3-6 /12 months apart
advised
Thy3 (i) All follicular lesions. Lobectomy. Complete thyroidectomy will be
necessary if histology proves malignant.
Thy3 (ii) Worrying feature but cells to scanty to
qualify for Thy 4
Discuss with cytopathologist to determine
course of action.

29. THE THY CLASSIFICATION ADOPTED BY THE ROYAL
COLLEGE OF PHYSICIANS
CLASS DESCRIPTION ACTION
Thy4 Suspicious of malignancy
(but not diagnostic)
Surgical intervention indicated for differentiated
tumour. Further treatment dependent upon
pathology report. For lymphoma, metastatic
tumour or undifferentiated i.e. anaplastic thyroid
carcinoma, further investigation indicated.
Thy5 Diagnostic of malignancy Surgical intervention indicated for differentiated
thyroid cancer, depending on tumour size, clinical
stage and other risk factors such as gender and
extremes of age. Appropriate further investigation
indicated alongside radiotherapy/chemotherapy for
anaplastic carcinoma, lymphoma or metastatic
tumor.

30. FNAC SPECIMENS
• 70% Benign,
• 5% Malignant,
• 10% Suspicious, and
• 15% Unsatisfactory

31. USG GUIDED FNAC
Indicated if:
• Palpation-guided FNA is non diagnostic
• Complex (solid/cystic) nodule
• Palpable small nodule (<1.5 cm)
• Impalpable nodule
• Abnormal cervical nodes
• Nodule with suspicious US features

32. BENIGN (-VE) CYTOLOGY
Most common finding
Indicative of:
• Colloid nodule
• Macrofollicular adenoma
• Lymphocytic thyroiditis
• Granulomatous thyroiditis
• Benign cyst

33. MALIGNANT (+VE) CYTOLOGY
• Commonest is Papillary Thyroid Cancer:
– Increased cellularity, Tumor cells arranged in sheets
and papillary cell groups.
– Typical nuclear abnormalities, which include
intranuclear holes and grooves.
• Others include:
– MTC, anaplastic carcinoma, and high grade metastatic
cancers

34. SUSPICIOUS CYTOLOGY
Diagnosis cannot be made
Includes:
• Follicular neoplasms (Adenoma vs Carcinoma)
• Hürthle cell neoplasms.
• Reidels Thyroiditis
• Atypical PTC
• Thyroid Lymphoma.
• Patients with a family history of Thyroid Malignancy.
• Patients with history of low dose radiation exposure during
childhood.

35. INDICATIONS FOR REPEAT FNA
• Follow-up of benign nodule
• Enlarging nodule
• Recurrent cyst
• Nodule >4 cm
• Initial FNA non-diagnostic.
• No nodule shrinkage after T4 therapy

36. THYROGLOBULIN OF FNA OF CERVICAL L.N.
• Thyroglobulin (Tg) can be measured in lymph
node or nodule aspirates.
• FNA-Tg levels were markedly elevated in
metastatic lymph nodes
• FNA-Tg sensitivity is 84.0%
• The combination of cytology plus FNA-Tg
increased FNA sensitivity from 76% to 92.0%.

37. IMMUNOHISTOCHEMICAL MARKERS
• HBME-1 (Hector Battifora mesothelia-1)
– monoclonal antibody
– stains papillary cancer positively but does not stain benign follicular tumors
• Galectin-3
– acts as a cell-death suppressor
– distinguishes benign from malignant thyroid follicular tumors.
• MoAb 47 (Monoclonal Antibody 47)
– Thyroid peroxide (TPO) immunochemistry with a monoclonal antibody termed
Moab 47 increases the accuracy of FNAC in patients with follicular carcinoma.

38. Monolayered Sheets Of Follicular Cells In Goiter.

39. Papillary Carcinoma Of Thyroid
Increased cellularity, Tumor cells arranged in sheets and
papillary cell groups. Typical nuclear abnormalities,
which include intranuclear holes and grooves

40. Medullary Carcinoma—
Intracytoplasmic Granules With Plasmacytoid Cells

41. Follicular Pattern

42. IMAGING THE THYROID

43. ULTRASONOGRAPHY
• Most sensitive test to detect lesions in the thyroid.
• It is recommended that ALL patients who have a nodular thyroid, with a palpable solitary
nodule or a multinodular goiter, be evaluated by US.
• Not indicated as screening test in general population.
• Indicated in:
– Palpable nodule - History of radiation to the neck
– Age<20 & >70 - Family history of MTC, MEN2, or PTC
– Presence of cervical lymphadenopathy.

44. ULTRASONOGRAPHY FEATURES OF MALIGNANCY
• Hypoechogenicity in solid nodules,
• Presence of micro calcifications,
• Irregular shape,
• Taller than wider lesion
• Intra nodular vascular spots,
• Absence of halo and Cystic elements.
• Evidence of invasion or regional lymphadenopathy, and
• Increased blood flow in the center of the nodule seen on a Doppler study
suggests high malignancy.
*Macroscopic Capsular Breach and Nodal involvement are diagnostic of malignancy.

45. ULTRASONOGRAPHIC FEATURES OF BENIGN AND MALIGNANT NODULE

46. THYROID IMAGING REPORTING AND DATA SYSTEM
• TIRADS was first used by Horvath et al to standardize the reporting of
results of thyroid USG.
• Helpful in the stratification of nodules in benign and malignant.
• 10 ultrasound patterns were described. He related the rate of malignancy
according to the pattern.
• Six categories, ranging from a normal thyroid gland to a malignant nodule.

47. TIRADS system of classification

48. The
TIRADS
classification
algorithm

49. • Should be limited to patients with a low TSH level to identify autonomously
functioning nodules (~5%).
• Nodules with increased uptake (hot) are toxic adenomas and almost never
malignant. (1- 4% chances only).
• Nodules that accumulate radionuclide equal to surrounding tissue (warm), or
nodules with low uptake (cold), are most often benign (~80%) but may be
malignant in upto 25% of the cases and therefore require FNA biopsy.
THYROID SCINTIGRAPHY
(123IODINE OR 99MTECHNETIUM)

50. CT SCAN / MRI
• CT Scanning & MRI role is limited, except to see the spread and compression of
neighboring structures.
• Both can accurately determine substernal extension and invasion of surrounding
structures, such as esophagus, larynx, or trachea, and should be used only if
invasion or substernal extension is suspected.
• The use of contrast dyes delivers an iodine load that can delay postoperative
thyroid scanning for 4 to 8 weeks and can also cause a subclinically hyperthyroid
patient to enter thyroid storm.

51. PET- SCAN
• Indicated in follow up to detect recurrence.
• The phenomenon of the PET identified thyroid incidentallomas is becoming more
prevalent.

52. ELASTOGRAPHY
• Noninvasive ultrasound procedure which gives information about tissue stiffness.
• Stiffness depends upon the composition and structural organization of the lesion.
• When pressure is exerted on thyroid tissue with ultrasound probe, strain values of the thyroid
nodule and the parenchyma can be obtained. This pressure can be applied by using a probe from
outside or using the in vivo compression caused by carotid artery pulsation.
• Quantitative elastography provides a time elasticity graph, plotted on the region of interest, in
compression and relaxation cycle. Thus, two images of thyroid are acquired, before and after
compression with the probe. The tissue displacement is noted by analyzing the imaging beam.
• A software is used for accurate measurement of tissue distortion

54. INCIDENTALLOMAS
• Clinically non-palpable incidental thyroid swelling < 1 cm are called “incidentallomas”.
• These are not uncommonly noted during surgery or imaging performed for another
purpose. In patients with low risk characteristics these nodules are less cancerous.
• Also, there is no evidence to show that treatment of such sub centimetric micro
carcinomas improves outcome.
• The exception to the above is an incidentalloma identified by FDG-PET scan, which
carries a 50% chance of malignancy and therefore should be operated.

55. THYROID SURGERIES
TOTAL THYROIDECTOMY
HEMI
THYROIDECTOMY
SUBTOTAL
THYROIDECTOMY
HARTLEY
DUNHILL
PROCEDURE
Near Total Thyroidectomy = Small Amount of thyroid tissue left in the Trache Oesophageal Groove

56. THYROID SURGERIES
• Total thyroidectomy = 2 total lobectomy + isthmusectomy
• Subtotal thyroidectomy = 2 subtotal lobectomy +
isthmusectomy (4-6 grams in both lobes are preserved)
• Near-total thyroidectomy = Total lobectomy + subtotal
lobectomy + Isthemusectomy.
• Lobectomy = Total Lobectomy + Isthmusectomy

57. SURGICAL MANAGEMENT
• Cyst : Aspirate. Maximum 3 times and if it still recurrs, Hemithyroidectomy.
• Papillary : Total Thyroidectomy + Removal of Enlarged Central Lymph Nodes.
If any LN is positive then MRND on that side.
• Follicular : Total Thyroidectomy. Lymph Nodes preserved.
• Medullary : Total Thyroidectomy
+ Routine Central Lymph Node Dissection
+ Ipsilateral MRND if size of tumour is >1cm
and Bilateral MRND if any LN is positive.
• Anaplastic : Total Thyroidectomy only in early phases; Tracheostomy.
• Lymphoma (Intermediate NHL) : CHOP; Radiation.

58. COMPLICATIONS
• FNA:
– Local discomfort, Hematomas, Infection.
• THYROIDECTOMY :
– Tension Haematoma.
– Respiratory Obstruction.
– Nerve Injuries (RLN/SLN/CST- Horner’s Syndrome)
– PTH Insufficiency
– Thyroid Insufficiency.
– Thyroid Crisis.

59. FOLLOWUP
• Thyroglobulin levels checked every 6 months.
Normally undetectable after total thyroidectomy (<2
ng/mL).
• Simultaneous Cervical USG every 6-12 months.
• If TG is raised and Nodule is + on USG = Indicates
Recurrence = RAI Ablation.
• If TG is raised and Nodule is – on USG = Indication for
PET Scan = RAI Ablation.

60. PROGNOSIS
• Benign nodules; usually persist or grow slowly
& Malignant transformation is rare.
• Malignant nodules; Prognosis depends on
histology.

61. PREVENTION
• Avoid exposure to external radiation.
• Adequate iodine intake may reduce the
incidence of thyroid nodular disease.

62. CONCLUSION
• The goal of the evaluation of the solitary thyroid nodule is to identify whether the
patient will require surgical treatment and to identify a malignancy.
• A majority of the thyroid nodules present with a lump in front of the neck, common in
females, 90% of them are benign, adenoma being the commonest amongst benign
lesion.
• FNAC is a very reliable and powerful screening method in the pre- operative diagnoses
of Simple Thyroid Nodule. Jointly, FNAC, thyroid imaging, and ultrasonography can
detect them with 90% accuracy.
• Thyroid scan is indispensable for toxic nodular goitre.

64. TNM DEFINITIONS (AJCC 8E)
TX – Primary Tumor cannot be assessed.
T0 – No evidence of Primary Tumor.
T1 – Size ≤ 2 cms; Intrathyroid.
T1a - ≤ 1cm
T1b – 1-2 cms.
T2 – 2-4 cms.
T3 - > 4 cms.
T3a - > 4 cms intrathyroid.
T3b – Any Size, Extrathyroid extension
upto Strap Muscles.
T4 – Any size, gross Extrathyroid extension.
T4a – Larynx, Trachea, Esophagus, RLN.
T4b - Prevertebral Fascia, Carotids.
NX – Regional LN Cannot Be Assessed.
N0 – No evidence of regional LN
metastasis.
N0a - ≥1 Confirmed benign lymph
node.
N0b – No radiological or clinical
evidence of LN Metastasis.
N1 – Metastasis to regional Nodes.
N1a – Level VI or VII Positive,
Unilateral or Bilateral.
N1b – Levels I-V or retropharyngeal
LN Positive, Unilateral or Bilateral.
M0 - No Distant Metastasis.
M1 - Distant Metastasis Present.

71. CLINICAL APPROACH TO SOLITARY
THYROID NODULE
WITH AN AIM TO EVALUATE AND TREAT

73. FNAC
INCONCLUSIVE
REPEAT
FNAC
BENIGN
CYSTIC
ASPIRATE. MAX 3
TIMES
RECURRENCE
HEMITHYROIDECTOMY/
THYROIDECTOMY
SOLID
(COLLOID)
EARLY PHASES
THYROXINE SUPRESSION
STILL GROWING/
COMPRESSIVE FEATURES
THYROIDECTOMY
SUSPICIOUS
/FOLLICULAR
RADIOACTIVE IODINE
SCAN
HOT
(RAI UPTAKE +
1-3%)
RADIOACTIVE
IODINE ABLATION
COLD
(RAI UPTAKE –
15-20%)
THYROIDECTOMY
MALIGNANT
THYROIDECTOMY