this presentation is about pathogenesis of thyroid carcinoma... hope it is more useful for the guys... who need it

1. A Final Year Part 2 Student

2.  Thyroid is the most common Endocrine malignancy
 Annual incidence is 1 to 10 per 100,000 persons
 Highest incidence → Northern America
 Can occur at any age group
a. Peak incidence after age of 30
b. Aggressiveness increases with age
 Female to male ratio is 3 : 1
 Mortality → 2-3%

3.  Hormones like oestrogen and prolactin have an
important role in modulating the immune system
 Interaction between fluctuating female hormones
(during pregnancy , puberty and perimenopause) and
immune system puts into risk
 Oestrogen has the ability to enhance the
inflammatory process of immune system. This means
oestrogen could contribute to attack on their own
thyroid gland

4. Benign Malignant
Para follicular cells Lymphoid cellsFollicular cells
UNDIFFERENTIATE
D
FOLLICULAR
MEDULLAR
Y
LYMPHOMA
ANAPLASTI
C
FOLLICULAR
PAPILLARY
HURTHLE
CELL
PRIMARY
DIFFERENTIATED
THYROID NEOPLASM
SECONDARY
Dunhill’s
Classification

5. Papillary carcinoma – 60-70%
Follicular carcinoma – 10-20%
Anaplastic carcinoma – 10%
Medullary carcinoma – 5%
Malignant lymphoma – 5%
OTHERS
FOLLICULAR
PAPILLARY

7. PTEN
gene

9. ADENOMA THYROID
 Benign lesion derived from follicular epithelium
 Usually single well encapsulated
 Completely enveloped by thin fibrous capsule
 Different from surrounding gland
Closely packed follicles trabeculae or solid sheets
No capsular or vascular invasion.

10. PAPILLARY CARCINOMA OF
THYROID
Accounts for 80% of all thyroid malignancies
Most common thyroid cancer in ____________
Sex -
Age -
Spread -
Most common site of metastasis –
Gene implicated is RET ,TRK1 , RAS , BRAF

11. PAPILLARY
CARCINOMA
Occult
<1cm
Intra thyroidal Extra Thyroidal

12.  This association is much stronger for thyroid cancer than for other
malignancies and the radiation is the only environmental risk factor for
thyroid malignancy.
 High risk people are children , who are exposed to greater radiation.
 This association with radiation is much stronger for papillary than for
follicular cancer.
Ionizing radiation Genetic mutations Malignant transformation

13. Gross features Solitary ,Hard firm and whitish
Well circumscribed & Encapsulated
On cut section Hemorrhagic calcification
Necrosis and cyst formation
Visible papillae may seen

14. Papillary projections

Branching papillae of
cuboidal epithelial cells
Orphan Annie eye nuclei
 Nuclei contain dispersed
chromatin which imparts optically
clear or empty appearance
giving rise to Ground glass
appearance or orphan Annie eye
nuclei
HISTOLOGY FINDINGS

15. Intra nuclear inclusions or
grooves
 Abundant cytoplasm with
crowded nuclei
Psammoma bodies
 Microscopic , calcified
deposits representing the
clumps of sloughed cells
Diagnosis is based on these nuclear characters even in the absence of papillary
structures

16.  Multiple foci in same lobe (due to lymphatic spread in rich intra thyroidal
lymphatic plexus )
 Sometimes in opposite lobe.
 Multi focality is associated with increased risk of cervical nodal
metastasis
 Rarely invade trachea oesophagus and RLN
 Prognosis is better with >95% , 10year survival rate
Rarely persistent thyro-glossal duct can become cancerous
and present as papillary carcinoma of thyroid

17. MICRO-CARCINOMA (OCCULT
CARCINOMA )
 Papillary carcinoma <1cm in
diameter
 Presented with Enlarged
lymph nodes in jugular chain
or pulmonary metastasis with
no abnormality of thyroid
 Excellent prognosis

18. FOLLICULAR CARCINOMA OF
THYROID Accounts for 10% of all thyroid malignancies
 __ Most common thyroid cancer
 Occurs in -
 Sex -
 Age -
 Spread -
 Most common site of metastasis -
 More aggressive and dangerous.
 Mortality is twice that of papillary carcinoma
 GENE implicated in PTEN , RAS , P53 , PAX8 / PPAR1

19. Gross features • Tumour is solitary
• encapsulated demarcated lesions are
present
• Large lesions may penetrate beyond
capsule and infilterate into neck
On cut section • Grey to pink nodules ,
• Transculant ( due to large colloid follicles )
• Degenerated changes like central fibrosis,
foci of calcification

20.  Histologically , follicles are crowded with uniform
cells containing colloid
 Malignancy is defined by presence of capsular
and vascular invasion

21. Characteristics Papillary carcinoma Follicular carcinoma
Aetiology Sporadic / IR-Radiation Endemic goitre
Incidence 60-70% 10-20%
Age 20-30 years 40-50 years
Diagnosis Thyroid swelling with
lymph node metastasis
Thyroid swelling with
bony metastasis
Microscopy Orphan annie eye
nuclei
Psammoma bodies
Angio invasion
Capsular invasion
Spread Lymphatic Blood
Treatment of metastasis Functional neck
dissection
Radioiodine 131iodine

22. HURTHLE CELL CARCINOMA
 It accounts 3% of all thyroid malignancies.
 It is a subtype of follicular carcinoma
 Spread → metastasise to local nodes and
distant sites
 Higher mortality rate

23.  Tumour contains sheets of eosinophilic cells with mitochondria which are
derived from oxyphilic cells of thyroid gland.
 The characteristic feature is distinct granular acidophilic cytoplasm.
 Characterised by vascular and capsular invasion

24. ANAPLASTIC CARCINOMA
It accounts 1% of all thyroid malignancies
Sex →
Age →
Spread →
Site of metastasis →
Highly Aggressive and Uniformly lethal
Gene implicated is BRAF

25. Gross features
Large solid tumour with necrosis
& Haemorrhage that invades
surrounding structures.
Microscopy findings
Composed of highly anaplastic cells includes
 pleomorphic giant cells → osteoclast like
 Spindle cells → sarcomatous appearance
 Mixed spindle and giant cells

26. MEDULLARY CARCINOMA
It accounts for about 5% of all thyroid malignancies.
It arises from Para follicular cells and c cells
Age -
Sex -
Spread -
Most common site of metastasis –
It secretes calcitonin , CEA , Histamine , Seratotine

27. Sporadic ( 80 % )
 Originate in one lobe
 Unilateral
 Seen in 60 years
 RET proto oncogene mutation
Familial ( 20 % )
 Multicentric
 Bilateral
 Seen in young age
 Associated with c cell
hyperplasia and RET proto
oncogene mutation

28. Presence of amyloid ( altered calcitonin ) is diagnostic histologic finding
Gross features  Tumour tissue is firm pale gray
 Larger lesions often contains area of necrosis and
haemorrhage extends through the capsule of thyroid
Microscopy  Tumour composed of sheets of infilterating neoplastic
cells separated by the collagen and amyloid
 Marked heterogenicity is seen
 Cells → polygonal or spindle shape
P
A
T
H
O
L
O
G
Y

29. LYMPHOMA
Most common is non Hodgkin's B cell lymphoma
It accounts 5% of all thyroid malignancy
Sex →
Age →
Usually develops in patient with pre existing chronic
lymphocytic thyroiditis

30. METASTATIC TUMOURS OF
THYROID
Usually Rare
Found in Autopsy
Most common site is
Other sites are colon kidney
melanoma
If detected pre-mortem → mc site is
Ca Breast > Ca Lung
RCC > Ca Breast > Ca Lung

31. Familial Adenomatous polyposis PTC
.