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Thyroid Malignancy
Aetiology

-Mohammed Shujauddin
Introduction
• Thureoeides (Ancient Greek), meaning ‘Sheild
Shaped’.
• Anterior aspect of neck.
• Two lobes connected by isthmus.
• Endocrine gland.
• Regulates BMR, stimulates somatic and psychic
growth, calcium metabolism.
Embryology
• Floor of primitive pharynx, caudal to tuberculum
impar. (Marked by foramen caecum of tongue)
• Median endodermal thyroid diverticulum
• Downward growth, bifurcates and forms lobes.
Anatomy
• Weight: About 25g (Larger in Females).
• Lies against C5, C6, C7 and T1 vertebrae.
• Lobes: Middle of thyroid cartilage to IV or V tracheal
ring.
• Isthmus: II – IV tracheal ring.
• Dimensions (cm): Lobe – 5 × 2.5 × 2.5
Isthmus – 1.2 × 1.2
Capsules of Thyroid
• True capsule: condensed peripheral connective
tissue of the gland.

• False capsule: derived from pretracheal layer of
deep cervical fascia. (Ligament of Berry)
Relation to surrounding structures
Blood supply
• Arterial supply:
– Superior thyroid artery (ECA)
– Inferior thyroid artery (thyrocervical trunk, SCA)
– Thyroidea ima artery (Brachiocephalic trunk or AOA)
– Accessory thyroid arteries.

• Venous drainage:
– Superior thyroid vein – IJV
– Middle thyroid vein – IJV
– Inferior thyroid vein – left bracheocephalic vein
– Fourth thyroid vein of Kocher – IJV.
Histology
Two types of secretory cells.
• Follicular cells:
– Columnar in active phase, cuboidal in resting phase.
– Secrete T3, T4.
– Follicles contain colloid in lumen

• Parafollicular cells (C cells):
– Fewer, lie in between follicles.
– Secrete thyrocalcitonin
Classification (Dunhill)
• Differentiated – 80%
– Papillary carcinoma (60%)
– Follicular carcinoma (17%)
– Paillofollicular carcinoma
– Hurthle cell carcinoma

• Undifferentiated – (20%)
– Anaplastic carcinoma (13%)

• Medullary carcinoma (6%)
• Malignant Lymphoma - (4%)
• Secondaries in thyroid (rare)
Etiology
• Radiation : Proloned exposure to high dose of external
radiation or radioiodine. Children and young adults.
(papillary carcinoma)
• Iodine excess and TSH
– Papillary thyroid carcinoma:•
•
•
•

External radiation or radioactive iodine therapy
Iodine sufficient areas.
Common in children and females.
RET overexpression (chr 10)
– 20% cases
– Tyrosine kinase receptor targeted by tumor promoting factors

• NTRK1 rearrangement
• Elevated TSH , Hormone dependent tumor.
• Hushimotos thyroiditis
– Follicular thyroid carcinoma:- agressive
• Common in females
• Iodine-deficient areas
• 50% cases with RAS oncogene mutation
• Gene translocation:- PAX- 8 and PPARγ-1
• De novo or Pre-existing Multinodular goitre
Hurthle cell carcinoma:variant of follicular thyroid carcinoma.
Abundant oxyphill cells
Spread more commonly to regional lymph nodes.
Vascular or capsular invasion.

– Medullary thyroid carcinoma:
• Origin:- parafollicular C-cells.
• Site:- Superolaterally in the thyroid lobes.
• RET gene mutation, familial and sporadic
• Associated with MEN II syndrome and pheochromocytoma with
hypertention. MCT associated with MEN II B with pheochromocytoma
(Sipple’s disease) is most aggressive.
• Not TSH dependant and does not take up radioactive iodine.
– Anaplastic thyroid carcinoma:- very aggressive
• Common in women 7th to 8th decade of life.
• Undifferentiated.
• Origin- dedifferentiation of differentiated PTC or FTC, or
Inactivating point mutation in p53 gene.

– Malignant Lymphoma
• NHL type
• Occurs in pre-existing Hushimoto’s thyroiditis
Features

Papillary
Carcinoma

Follicular
Carcinoma

Medullary

Anaplastic
Carcinoma

Frequency

60%

17%

6%

13%

Age

all ages

Middle to old
age

Middle to old
age; Familial

Old age

Female/
male ratio

2:1

3:1

1:1

1.5:1

Relation
to
radiation

Maximum

Present

None

Present

Genetic
alterations

RET gene
over
expression

RAS mutation

RET mutation

P53 loss

Cell of
origin

Follicular

Follicular

Parafollicular

Follicular

Contrasting features
Thyroid malignancy etiology

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Thyroid malignancy etiology

  • 2. Introduction • Thureoeides (Ancient Greek), meaning ‘Sheild Shaped’. • Anterior aspect of neck. • Two lobes connected by isthmus. • Endocrine gland. • Regulates BMR, stimulates somatic and psychic growth, calcium metabolism.
  • 3. Embryology • Floor of primitive pharynx, caudal to tuberculum impar. (Marked by foramen caecum of tongue) • Median endodermal thyroid diverticulum • Downward growth, bifurcates and forms lobes.
  • 4.
  • 5.
  • 6. Anatomy • Weight: About 25g (Larger in Females). • Lies against C5, C6, C7 and T1 vertebrae. • Lobes: Middle of thyroid cartilage to IV or V tracheal ring. • Isthmus: II – IV tracheal ring. • Dimensions (cm): Lobe – 5 × 2.5 × 2.5 Isthmus – 1.2 × 1.2
  • 7. Capsules of Thyroid • True capsule: condensed peripheral connective tissue of the gland. • False capsule: derived from pretracheal layer of deep cervical fascia. (Ligament of Berry)
  • 9. Blood supply • Arterial supply: – Superior thyroid artery (ECA) – Inferior thyroid artery (thyrocervical trunk, SCA) – Thyroidea ima artery (Brachiocephalic trunk or AOA) – Accessory thyroid arteries. • Venous drainage: – Superior thyroid vein – IJV – Middle thyroid vein – IJV – Inferior thyroid vein – left bracheocephalic vein – Fourth thyroid vein of Kocher – IJV.
  • 10.
  • 11. Histology Two types of secretory cells. • Follicular cells: – Columnar in active phase, cuboidal in resting phase. – Secrete T3, T4. – Follicles contain colloid in lumen • Parafollicular cells (C cells): – Fewer, lie in between follicles. – Secrete thyrocalcitonin
  • 12. Classification (Dunhill) • Differentiated – 80% – Papillary carcinoma (60%) – Follicular carcinoma (17%) – Paillofollicular carcinoma – Hurthle cell carcinoma • Undifferentiated – (20%) – Anaplastic carcinoma (13%) • Medullary carcinoma (6%) • Malignant Lymphoma - (4%) • Secondaries in thyroid (rare)
  • 13. Etiology • Radiation : Proloned exposure to high dose of external radiation or radioiodine. Children and young adults. (papillary carcinoma) • Iodine excess and TSH – Papillary thyroid carcinoma:• • • • External radiation or radioactive iodine therapy Iodine sufficient areas. Common in children and females. RET overexpression (chr 10) – 20% cases – Tyrosine kinase receptor targeted by tumor promoting factors • NTRK1 rearrangement • Elevated TSH , Hormone dependent tumor. • Hushimotos thyroiditis
  • 14. – Follicular thyroid carcinoma:- agressive • Common in females • Iodine-deficient areas • 50% cases with RAS oncogene mutation • Gene translocation:- PAX- 8 and PPARγ-1 • De novo or Pre-existing Multinodular goitre Hurthle cell carcinoma:variant of follicular thyroid carcinoma. Abundant oxyphill cells Spread more commonly to regional lymph nodes. Vascular or capsular invasion. – Medullary thyroid carcinoma: • Origin:- parafollicular C-cells. • Site:- Superolaterally in the thyroid lobes. • RET gene mutation, familial and sporadic • Associated with MEN II syndrome and pheochromocytoma with hypertention. MCT associated with MEN II B with pheochromocytoma (Sipple’s disease) is most aggressive. • Not TSH dependant and does not take up radioactive iodine.
  • 15. – Anaplastic thyroid carcinoma:- very aggressive • Common in women 7th to 8th decade of life. • Undifferentiated. • Origin- dedifferentiation of differentiated PTC or FTC, or Inactivating point mutation in p53 gene. – Malignant Lymphoma • NHL type • Occurs in pre-existing Hushimoto’s thyroiditis
  • 16. Features Papillary Carcinoma Follicular Carcinoma Medullary Anaplastic Carcinoma Frequency 60% 17% 6% 13% Age all ages Middle to old age Middle to old age; Familial Old age Female/ male ratio 2:1 3:1 1:1 1.5:1 Relation to radiation Maximum Present None Present Genetic alterations RET gene over expression RAS mutation RET mutation P53 loss Cell of origin Follicular Follicular Parafollicular Follicular Contrasting features