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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