thyroid malignancy etiology
DESCRIPTION
TRANSCRIPT
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 goitreHurthle cell carcinoma:-
variant of follicular thyroid carcinoma.Abundant oxyphill cellsSpread 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
Contrasting features
Features
Frequency
Age
Female/ male ratio
Relation to radiation
Genetic alterations
Cell of origin
Papillary Carcinoma
60%
all ages
2:1
Maximum
RET gene over expression
Follicular
Follicular Carcinoma
17%
Middle to old age
3:1
Present
RAS mutation
Follicular
Medullary
6%
Middle to old age; Familial
1:1
None
RET mutation
Parafollicular
Anaplastic Carcinoma
13%
Old age
1.5:1
Present
P53 loss
Follicular
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