Thyroid Cancer

Thyroid cancer
diagnosis and management

4C1 RI
09-2 78F, 5192444

1.Thyroid cancer, follicular carcinoma,
with multiple lung metastasis and skull
metastasis s/p total thyroidectomy &
parathyroidectomy
2. Obstructive pneumonitis
3. Urinary tract infection with fungus
infection
Neck mass noted for 20+ years , significant
weight loss(8kg loss in 2 months) from 96/2
96/4: admission at
CXR: trachea deviated to left side multiple lung
mass over bilateral lung field
CT: one 6.6x5.2x4.5 cm mass lesion containing
calcification and necrotic component with
treachea and esophagus deviation and multiple
lung masses
Bone scan: left parietal-occipital region of the
skull
Thyroid needle biopsy: follicular carcinoma
07/21 OP: Total thyroidectomy +

parathyroidectomy
Operation Finding
1. Enlarged, hard, irregular, shape;

yellowish, white tumor; 8X7X6cm over Rt
thyroid with invasion to paraspinal muscle.
Parathyroid origin was likely
2. 4X2X2cm Lt thyroid with one 1X1cm
hard tumor inside
Thyroid cancer
1.5% of all cancer

Papillary carcinoma(75-85% of cases)
Follicular carcinoma(10-20%)
Medullary carcinoma(5%)
Anaplastic carcinoma(<5%)
Papillary thyroid carcinoma
Most often in the twenties to forties.

Incidence rinse:
1935 (1.3/100,000 for women and

0.2/100,000 for men)
1991 (5.8/100,000 for women and
2.5/100,000 for men)
Cause:
(1)R/T to children with head and neck benign
disease between 1910 and 1960
(2) increased detection of small papillary cancers

Pathogenesis :
Activation of receptor tyrosine kinases (RET/PTC,
TRK, MET) Produce chimeric proteins with
tyrosine kinase activity
Clinical presentation:
Most: asymptomatic thyroid nodule , discovered by fine
needle aspiration biopsy.

Advanced disease: hoarseness,dysphagia,cough, or
dyspnea
Minority: lung metastasis

Pathologic features: unencapsulated , calcified
psammoma bodies
Good prognosis: micropapillary encapsulated, solid, and
follicular variants
Poor prognosis:with tall cells and diffuse sclerosing variants
Behavioral:
Good prognosis:10 year survival rate:95%
grow slowly,extend to regional lymph node(not necessarily a
bad prognostic sign )

older than 50 years of age : more aggressive local spread,
leading to death in over half of the patients
Distant metastases: uncommon (2 to 3% of patients), lung>bone
Follicular carcinoma
More frequency than papillary cancer in

iodine deficiency area. More frequently
with increasing age
Early hematogenous spread to lung, bone,
brain, and liver (one fifth of patients ).
Lymph node involvement :less than 1%
Anaplastic cancer
Predominantly in persons older than 70

years.
One third arise in preexisting differentiated
cancers
Death : aggressive local invasion :
progressive tracheal obstruction or massive
hemorrhage
Distant metastases :little clinical importance
Medullary carcinoma
malignant tumor of calcitonin-secreting C

cells
Sporadically:80%, sixth and seventh decades

Genetic or familial variants 20%
Genetic :MEN IIa, MEN IIb
Familial form: multicentric in origin and C-cell
hyperplasia precedes
Clinical Manifestations and Diagnosis
Thyroid cancer: 1/20 of thyroid nodule
Rapid, painless growth
Fine-needle aspiration of thyroid nodules

and examination of the obtained material
123I scan: 20% of cold nodules containing
thyroid cancer.
Treatment
Thyroid surgery
Advantage of near-total thyroidectomy :
can be ablated with RAI

can be followed with thyroglobulin levels
Treat for several weeks postoperatively with

liothyronine(T4).,followed by thyroid hormone
withdrawl TSH level increase to>50 IU/L over
3-4 weeks scanning dose of 131I(4-5mCi)
ablative dose of 29 mCi of 131I whole body
scan(6 months after surgery) to identify possible
metastatic disease
Long-term supplementation with levothyroxine
(maintains TSH concentrations at <0.1mU/L)
Whole body scan
rhTSH vs.thyroid hormone withdrawal

rhTSH: stimulate 131I uptake without symptoms of
hypothyroidism. Recommened for pts predicted
to be at low risk of recurrence
thyroid hormone withdrawal: for pts with likely
residual disease.T4 switch to T3(rapidly cleared
hormone)
Tg measurements after rhTSH administration or
when TSH level risen after thyroid hormone
withdrawal.
Follow up
whole-body scan is negative and Tg level are low

repeat scan perform one year laterstill negative
management with suppressive therapy and
measurements of Tg every 6 to 12 months
Scan negative, Tg-positive(>5 to 10 ng/mL)
radioiodine treatment.
Lung metastasis:CXR,131I scan,spiral CT
Bone metastasis:bone scintigraphy , CT , MRI
Epidemiology of incurable DTC
85% of patients with DTC :disease-free

after initial treatment
1015% : recurrent disease
5%: distant metastases
Distant metastases :lungs (50%), bones
(25%), lungs and bones (20%) ,10-yearsurvival rates ranging from 25% to 42%
Local and regional recurrences
Small lymph-node metastases: 131I

treatment , but abnormalities can still
persist after two to three coursessurgery
Recurrent disease in the thyroid bed or in

other soft tissue, or aerodigestive tract
staging with endoscopies and various
imaging modalities
Disease limited to the neck :extensive

surgery and external-beam radiotherapy
patients older than 40 years , poorlydifferentiated tumors, no radioiodine uptake,
large tumor burden, rapid progressive disease,
soft tissue involvement, and high [18F]FDG
uptake : develop distant metastases after
treatment .
Treatment of patients with

persistent or recurrent disease
Indications
Abnormal clinical findings

Abnormal imaging findings
Increasing trend in serum thyroglobulin
concentration
Staging
Neck ultrasonography, whole body scintigraphy with

a large activity of radioiodine
Conventional imaging: neck and chest CT, bone
MRI, [18F]FDG PET
Fine-needle biopsy or surgical biopsy in case of
unusual presentation
Treatment methods
Surgery (when feasible)

Radioiodine treatment in presence of
radioiodine uptake in tumor foci
Other local treatments (dependent on location
and extent of disease): external radiation
beam treatment, embolisation,
radiofrequency, cement injection
New treatment methods, eg, molecularly
targeted treatments,
Selection of patients with

metastases for treatment
Candidates for radioiodine treatment
Younger age
Well differentiated tumour
High radioiodine uptake
Small metastases
Location in lungs
Stable or slow progressive disease
Low uptake of fluorodeoxyglucose
Repeated radioiodine treatment (response rate: 85%,
with 96% of complete responses seen with a
cumulative activity <600 mCi)
Candidates for other treatment modalities
Older age
Poorly differentiated tumor
No or low radioiodine uptake
Large metastases
Location in bones
Rapidly progressive disease
High uptake of fluorodeoxyglucose
Patients with initial uptake but poor or no response to
radioiodine treatment and patients with no initial
uptake of radioiodine, especially when disease is
progressive
Radioiodine treatment for lung metastases :

45% of patients with radioiodine uptake
and no substantial sequellae.
Large bone metastases : surgery and
radiotherapy , but remission is rarely
achieved.
local procedures such as embolisation,

radiofrequency or cement injection, and
treatment with biphosphonates can delay
tumor progression and palliate symptoms
High initial [18F]FDG uptake : indicate

progressive disease and resistance to
radioiodine treatment can help to select
patients who should be treated either with
radioiodine or with other modalities
Complete remission after treatment: only a
third of patients with metastases
Cytotoxic chemotherapy
and biotherapy
absence of evidence of benefits

Doxorubicin :response rates :0% to 22% ,
lasting only a few months
Dendritic cell immunotherapy might be
effective but no studies on DTC.
Molecularly targeted treatments
Two main theoretical approaches:
inhibition of tumor growth by inhibiting cell

signaling and angiogenesis
induction of redifferentiation of thyroid tumor
tissue.
Targets in cell signalling and

angiogenesis
Papillary carcinomas :
80% :mutations of genes of mitogen-activated

protein kinase (MAPK) pathway.
530%: RET/PTC rearrangements
10%: RAS mutations
40%: BRAF mutations
Follicular carcinomas:
2035% : RAS mutations

30% :PAX8/PPAR rearrangements
Targets in cell signalling and

angiogenesis
Only a few relations between gene

mutations and prognosis
BRAF mutations :more aggressive and less

differentiated papillary tumors, and this is
consistent with the inhibition of thyroidtumor cell growth induced by the blockade of
BRAF kinase.
Angiogenesis
Thyroid cancer cells :Overexpression of

tyrosine kinase receptors :fibroblast growth
factor, epidermal growth factor (EGF),
hepatocyte growth factor (c-Met),VEGF,
insulin, and insulin-growth factor 1
Antivascular treatment blocks the growth
of differentiated thyroid carcinoma in
experimental models.
Interference with signal

transduction pathways
AMG 706, BAY 43-9006, ZD 64-74, and

AG-013736, in DTC is being studied in
phase II trials
effect :inhibition of the MAPK pathway
and of angiogenesis and others.
BAY 43-9006 also inhibits BRAF kinase
Restoring radioiodine uptake
Retinoic acid analogues : increase the

expression of the natrium iodide symporter
increase radioidodine uptake ,but in only
a few patients.
Other drugs
Anti-EGF receptor (EGFR) antibodies and

small molecules targeting the kinase
activity of the EGFR : successfully tested
for inhibition of tumour growth in thyroidcancer cell lines.
COX-2 inhibitor :Cyclooxygenase-2 :
overexpressed in thyroid cancer that
promotes tumour progression
Combination treatment
The use of antiangiogenic drugs can

enhance the efficacy of radiotherapy,
radioiodine treatment, or chemotherapy.
MAPK and the PI3K pathways blockers.

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Thyroid cancer

diagnosis and management

09-2 78F, 5192444

07/21 OP: Total thyroidectomy +

1. Enlarged, hard, irregular, shape;

1.5% of all cancer

Papillary thyroid carcinoma

Most often in the twenties to forties.

1935 (1.3/100,000 for women and

Papillary thyroid carcinoma

needle aspiration biopsy.

Papillary thyroid carcinoma

bad prognostic sign )

More frequency than papillary cancer in

Predominantly in persons older than 70

Distant metastases :little clinical importance

malignant tumor of calcitonin-secreting C

Sporadically:80%, sixth and seventh decades

Clinical Manifestations and Diagnosis

Thyroid cancer: 1/20 of thyroid nodule

Rapid, painless growth

Fine-needle aspiration of thyroid nodules

can be ablated with RAI

Treat for several weeks postoperatively with

Whole body scan

rhTSH vs.thyroid hormone withdrawal

whole-body scan is negative and Tg level are low

Epidemiology of incurable DTC

85% of patients with DTC :disease-free

Local and regional recurrences

Small lymph-node metastases: 131I

Recurrent disease in the thyroid bed or in

Disease limited to the neck :extensive

Treatment of patients with

Abnormal clinical findings

Neck ultrasonography, whole body scintigraphy with

Surgery (when feasible)

Selection of patients with

Candidates for radioiodine treatment

Candidates for other treatment modalities

Radioiodine treatment for lung metastases :

local procedures such as embolisation,

High initial [18F]FDG uptake : indicate

absence of evidence of benefits

Molecularly targeted treatments

Two main theoretical approaches:

inhibition of tumor growth by inhibiting cell

Targets in cell signalling and

80% :mutations of genes of mitogen-activated

2035% : RAS mutations

Targets in cell signalling and

Only a few relations between gene

BRAF mutations :more aggressive and less

Thyroid cancer cells :Overexpression of

Interference with signal

AMG 706, BAY 43-9006, ZD 64-74, and

Restoring radioiodine uptake

Retinoic acid analogues : increase the