3. 1. 52 yo woman in good health; presented with
back pain of a musculoskeletal nature.
Exam of neck: palpable right sided thyroid
nodule approx 2x3 cm; gland otherwise not
enlarged and no other nodules or
lymphadenopathy.
Ultrasound: solid nodule; uptake scan: no
excess uptake in nodule
TFTs: normal
A FNA was performed.
DX: Hurthle cell neoplasia
4. 2. 64 yo woman with hyperlipidemia;
presented for a preventive health
exam with no complaints.
Neck exam: 4x2 cm right sided
thyroid nodule, gland otherwise
normal, no lymphadenopathy.
Ultrasound-solid nodule, uptake scan
no excess uptake in nodule. TFTs
A FNA was performed.
DX: Hurthle cell neoplasia
5. 3. 28 yo woman presented after having
a thyroid nodule found incidentally on
a carotid ultrasound being performed
as a normal control for a study.
Exam: 2x2 cm right sided thyroid
nodule, gland otherwise normal, no
lymphadenopathy. TFTs normal
Dedicated ultrasound: solid nodule;
FNA performed that day because of
availability of pathology support
DX: Papillary thyroid carcinoma
6. Epidemiology
• Thyroid nodules: very common
• Clinically detectable thyroid carcinoma:
rare: <1% of all cancers
• Female to male ratio- 2.5:1
• Median age at dx: 45-50
7. • Overall incidence is rising:
• In 1935: 1.3/100,000 women, .2/100,000
men
• By 1991: 5.8/100,000 women, 2.5/100,000
men
• Incidence has continued to rise in past 10
years: most rapid rate of increase in all
tracked cancers
8. Reason for rise?
• Neck irradiation: used between 1910 and
1960
• Better diagnosis?
BUT: only rise is in papillary type; if better
diagnosis was reason, would expect rise in
all types
9. Hegedus, L. N Engl J Med 2004;351:1764-1771
Algorithm for the Cost-Effective Evaluation and Treatment of a Clinically Detectable Solitary
Thyroid Nodule
11. Benign Tumour
• Follicular adenoma :
- It is present clinically as solitary nodule.
-The differentiation between the follicular
carcinoma and adenoma can only made by
histological examination ,that in adenoma there is
no invasion of the capsule or of pericapsular
blood vessels .
-Treatment ___ wide excision ( preferably a
lobectomy ) .
13. Thyroid cancer: epithelial types
Differentiated:
Papillary: 70-75 % of all thyroid cancers
Follicular: 15-25%
Undifferentiated:
Anaplastic: 2-5%
14. Thyroid cancer: non epithelial
Medullary thyroid cancer
• Sporadic
• Familial
• MEN-2A and B
Others:
lymphoma, mets from breast, colon,
renal and melanoma
15. Clinical characteristics that suggest
Malignancy
1.Gender ___ male gender(F:M__3:1 ??)
2.Age <15,>60 years
3.Hx of head & neck radiation
4.Family hx of thyroid cancer
5.Rapidly enlarging nodule
6.Hard single nodule & nodules fixed to
surrounding structures
7.Hx of thyroiditis
8.Hoarseness
9.Cervical lymphadenopathy
17. Papillary carcinoma
- Slow growing ,60% multicentric .
- M:F--- 1:3 .
- Common 20-30 yrs old.
- Painless lump in the thyroid gland with enlarged
lymph gland.
- 80-90% of postradiation ca of the thyroid.
- Spread by lymphatics (50% have +ve node at
diagnosis) ,with good prognosis ,the presence of
nodes does not affect prognosis.
- Type of surgery __Lobectomy with
isthmusectomy .
18. • If the tumor is >3 cm ,male >40 , female
>50 , distant metastasis or angioinvasion
then _____ Total thyroidectomy is
indicated because of poor prognosis.
• 85% 10 yr survival.
19. • Occult carcinoma:
- Papillary carcinoma may present as an
enlarged lymph node in Jugular chain with no
palpable abnormality of the thyroid .The
primary tumour may be about few millimeter
in size & termed occult.
-The term occult is now applied to all papillary
carcinoma < 1.5 cm
- These tumor have an excellent prognosis.
20. Papillary thyroid carcinoma
Pathogenesis:
1. Activation of tyrosine kinase receptors by
rearrangement or gene amplification
• Results in a chimeric gene
• Occurs either by radiation or sporadic
2. Point mutations in BRAF gene
• 10X increased risk of thyroid cancer in relatives of
thyroid cancer patients: suggests a genetic link
21. PTC
Presentation:
• Solitary nodule most common
• Pathology: typically unencapsulated; may
be cystic
Papillae: 1 or 2 layers of tumor surrounding
fibrovascular core
Follicles and colloid are typically absent
22. PTC
• Psommoma bodies: scarred remnants of
tumor papillae that have infarcted
• Present in half of papillary thyroid
carcinomas
23. Histology of papillary thyroid carcinoma
showing
typical papillary projections and empty
(Orphan Annie-eyed) nuclei
24. PTC
Growth and behavior: minor to major
• Microcarcinoma: occult papillary
carcinoma, with tumor <1cm
• Found in up to 50% of glands at autopsy
(rarer in children)
• Incidental finding of no clinical importance
25. PTC
• Other end of spectrum: aggressive metastasis
through interthyroidal lymphatic channels to
form multifocal tumors
• Involves regional lymph nodes
• At diagnosis: clinically detectable nodes more
common in children (50%) than adults
• 2-10% distant mets at dx: 2/3 pulmonary, 1/4
skeletal; also brain, kidneys, liver, adrenals
26. PTC
Prognosis
• Most patients do not die of their disease
• 80-95% 10 year survival rates
• Patients between 20-45: best long term survival
• Patients older than 45 with lymph node
recurrences are most likely to die from PTC
27. PTC
• Prognosis is poorer in patients with large
tumors: one large series showed cancer
related mortality of 6%/2-3.9cm, 16%/4-
6.9cm and 50%7 cm and above
• Several variants have a worse prognosis:
tall cell variant=1% of PTC; more aggressive
and invasive
29. Schlumberger, M. J. N Engl J Med 1998;338:297-306
Survival Rate among 1701 Patients with Papillary or Follicular Carcinoma and No Distant
Metastases at the Time of Diagnosis
30. Follicular carcinoma
• Unifocal , more aggressive.
• M:F___1:3
• 30_40 yrs old.
• Common presentation __ lump in the neck.
• If tumor spread beyond the thyroid__ pt may
complain of breathlessness , chest pain , pain
or swelling in the bone.
31. • Capsular & vascular invasion are prominent
feature.
• Blood-borne metastases.
• Metastasis to lung &bone
• Total thyroidectomy is indicated .
• 40% 10 yr survival.
32. Follicular thyroid carcinoma
• Characterized by follicular differentiation and
encapsulation
• Invasion of the capsule and blood vessels is the
main determinant between adenomas and
carcinoma
• 2 main forms: minimally invasive and widely
invasive
• Multicentricity and lymph node involvement are
less frequent than in PTC
37. FTC
• Minimally invasive FTC behaves more like
PTC
• Widely invasive behaves more like
anaplastic thyroid carcinoma
• Hurthle Cell variant:more aggressive
• FTC is more likely than PTC to be
nonresponsive to I 131.
38. Anaplastic carcinoma
• Very aggressive tumor.
• It is the worst variety of thyroid tumor due its rapid
spread.
• Local infiltration is an early feature.
• The common complaint is a swelling in the neck
rather than lump ( because the tumor is diffuse &
infiltrating)
• A dull aching neck pain is quit common.
• Hoarseness or change in voice quality is a diagnostic
symptom because it implies infiltration of recurrent
laryngeal nerve.
39. • Many of these aggressive lesion present in an
advanced stage with tracheal obstruction
&required urgent tracheal decompression.
• Spread by lymphatic & blood stream.
• Chemotherapy & radiation may improve 5 %.
• Mean survival 2-4 months.( poor prognosis)
40. Anaplastic thyroid carcinoma
• Undifferentiated tumor of thyroid follicular
epithelium
• Very aggressive, with a disease specific mortality
approaching 100%
• 2/1,000,000 annual incidence
• Typical patient is older than differentiated
carcinoma, mean age 65
• <10% under 50
• 60-70% women
41. ATC
• 20% of ATC: history of differentiated
thyroid carcinoma, most papillary
• 10% of Hurthle cell carcinoma: has
anaplastic tumor within
• Up to 1/2 of ATC: history of multinodular
goiter
42. ATC
• Presentation:
• Nearly all present with a thyroid mass
• Regional or distant spread is present 90% of the
time at dx
• Lungs, bones, brain most common mets
• Rapidly enlarging tumor; often causes
compression symptoms like dyspnea, dysphagia,
hoarseness
• Constitutional symptoms like fatigue, anorexia,
wt loss
43. ATC
• 50% have palpable nodes at dx
• Dx: made by FNA, then CT neck and mediastinum,
CXR
• Prognostic factors: tumor size
<6 cm=25% 2 yr survival
>6cm=3-15% 2 yr survival
Others: older age, male sex, dyspnea at
presentation
• No effective treatment for advanced or metastatic
ATC: uniformly fatal, with median survival 3-7 mo
44. Treatment of differentiated
thyroid carcinoma
• Surgery: goal is to remove all tumor tissue
from neck
• Total or near total thyroidectomy because
of risk of multicentricity
• Removal of local nodes in PTC, only
palpable nodes in FTC because of lower
rate of lymph node involvement
45. Treatment
• I 131: given post op: destroys any remaining
normal thyroid tissue, and may destroy occult
microcarcinomas
• Increases sensitivity of subsequent 1 131 total
body scans
• 4-6 wks after surgery a total body scan off thyroid
replacement with low dose 1 131; if any uptake, a
treatment dose is given (2 mCi vs. 30-100 mCi)
• Radiation: only if surgical excision is impossible
and tissue doesn’t take up I 131
46. Followup
Goals of followup:
• Maintain adequate thyroxine treatment
• Detect persistent or recurrent cancer
• Recurrences usually occur early but may
occur later so follow up for life
47. • Thyroxine treatment goals: initial serum
thyrotropin level 0.1 or less, serum free T3
normal
• Check U/S of thyroid area and nodal areas
• Serum thyroglobulin levels: TG produced by
follicular cells-should not be detectable after total
ablation; presence signifies persistent or
recurrent disease
• 80% of patients with TG >40 have detectable foci
or I 131 uptake
48. • I 131 scanning: needs to be done after
withdrawal of thyroxine tx, with TSH >30
needed
• Scanning is done 3 days after I 131 given
• Low risk patients with no I 131 uptake after
1 year: TSH maintained at low but
detectable level (0.1-0.5)
49. • Local or regional mets: occur in 5-20%
• Excision/I 131 tx/ Radiation tx if no I 131
uptake
• Distant mets: If I 131 uptake, high dose I
131 given + RT
50. Complications of treatment:
• I 131: nausea, sialadenitis common but mild and
short duration
• Genetic defects: can’t be given to pregnant
women
• Increased risk of miscarriage in pregnancies
within 1 year of tx
• Overall relative risk of a second type of cancer
only if high cumulative dose of I 131 and/or
radiation
51. Medullary carcinoma
• Aggressive tumors.
• It is a neoplasm of parafollicular ( c ) cell.
• C-cell calcitonin producing tumor.
• High level of serum calcitonin >0.08 ng/ml
• Sporadic form is unifocal with worse
prognosis , familial form is multifocal with
a better prognosis.
• Involvement of lymph node occurs in
50_60%.
52. • May occur in combination with adrenal
phaeochromocytoma &
hyperparathyroidism in syndrome known
as multiple endocrine neoplasia type IIa
(MEN IIa)
-Blood-born metastases are common.
-Treatment__ Total thyroidectomy with
resection of involved lymph node.
53. Medullary thyroid cancer
• Much less common than epithelial thyroid
cancers
• Involves abnormalities of parafollicular C-
cells
• Most cases are sporadic
54. Hyperplasia of parafollicular C
cells in a child from a
family with medullary cancer
Histology of medullary carcinoma
showing characteristic
‘cell balls’ and amyloid
55. MTC
• MEN 2 A: autosomal dominant disorder
characterized by MTC, pheochromocytoma, and
primary parathyroid hyperplasia
• MEN 2 B: same inheritance; MTC +
pheochromocytoma. Occurs at a younger age;
more aggressive.
• Familial MTC: like MEN 2 A but no other
associated abnormalities
56. Total thyroidectomy specimen from a young girl undergoing
surgery following genetic screening, showing a small medullary
cancer in the right lobe.
57. MTC
• Female to male ratio=1:1
• MEN 2 A and familiar MTC: peak in index
cases in 3rd decade
• MEN 2 B: children and teens most common
age of presentation.
• Basal serum calcitonin: usually correlates
with tumor mass and is almost always high
with palpable tumor
58. MTC
• MTC in MEN 2 B: more aggressive
• Early onset
• Surgery often not curative
• Death from MTC: 50% of MEN 2 B,
10 % MEN 2 A
59. Lymphoma
• Usually affect female( may have hx of
hashimoto’s)
• There is a rapid enlargement.
• Compressive symptoms are common.
• Sensitive for chemotherapy & radiotherapy
• Surgery for diagnosis & compressive
symptom
• Good prognosis if there is no involvement
of cervical LN.
