Pathology of the Thyroid Gland

Prof. Dipak ShahDepartment of PathologyUWI, Mona

Diseases of the Thyroid Gland

• Congenital diseases• Inflammation• Functional abnormality• Diffuse and Multinodular goiters• Neoplasia

Inflammation

Thyroiditis Acute illness with pain

• Infectious Acute Chronic

• Subacute or granulomatous (De Quervain’s)

Little inflammation with dysfunction• Subacute lymphocytic thyroiditis• Fibrous (Riedel) thyroiditis

Autoimmune• Hashimoto thyroiditis

HASHIMOTO THYROIDITIS

• Most common cause of hypothyroidism• Autoimmune, non-Mendelian inheritance• 45-65 years, F:M = 10-20:1• Painless symmetrical enlargement• Risk of developing

B-cell non-Hodgkin’s lymphoma Other concomitant autoimmune diseases

• Endocrine and non-endocrine

Hashimoto ThyroiditisPathogenesis

• Immune systems reacts against a variety of thyroid antigens

• Progressive depletion of thyroid epithelial cells which are gradually replaced by mononuclear cells → fibrosis

• Immune mechanisms may includes: CD8+ cytotoxic T cell-mediated cell death Cytokine-mediated cell death Binding of antithyroid antibodies → antibody

dependent cell-mediated cytotoxicity

Hashimoto Thyroiditis

• Diffuse enlargement• Firm or rubbery• Pale, yellow-tan, firm

& somewhat nodular cut surface

Hashimoto Thyroiditis

• Massive lymphoplasmcytic infiltration with lymphoid follicles formation

• Destruction of thyroid follicles

• Remaining follicles are small and many are lined by Hurthle cells

• Increased interstitial connective tissue

Functional Abnormality

• Hyperfunction ↑ in level of hormone toxic effects→

• Due to: Diffuse hyperplasia Hyperfunctioning multinodular goiter Hyperfunctioning adenoma Subacute lymphocytic (painless) thyroiditis

Functional Abnormality

• Hypofunction ↓ in level of hormone impair development in infants →

and slowing of physical and mental ability in adults• Due to:

Postablation Surgery Radiation

Autoimmune thyroiditis Drugs Dyshormonogenetic

Graves Disease

• Most common cause of endogenous hyperthyroidism• Characterized by hyperthyroidism, ophthalmopathy with

exophthalmos and dermopathy (pretibial myxedema)• Autoimmune disease with genetic susceptibility associated with HLA-

B8 and DR3• Female:Male = 7:1• 3rd to 4th decades• Diffuse enlargement with audible bruit• Wide,staring gaze,lid lag,exophthalmos,pretibial myxedema• ↑ levels of free T4 & T3 and levels of TSH in blood↓• ↑ uptake of radioactive iodine

Graves’ Disease

Autoimmune disease with breakdown of helper-T-cell tolerance

Excessive production of TWO thyroid autoantibodies: 5) Thyroid-stimulating antibody (TSAb) &

6) Growth-stimulating antibody (GSAb)

Antibodies bind to the TSH receptor of the follicular cell

Stimulation of the cell resulting in:Increased levels of thyroid hormones &

Hyperplasia of the thyroid gland

Hyperthyroidism and Thyroid gland enlargement

Graves Disease

• Symmetrical enlargement of thyroid gland

• Cut-surface is homogenous, soft and appear meaty

• Hyperplasia and hypertrophy of follicular cells

Diffuse & Multinodular goiters

Reflects impaired synthesis of thyroid hormone most often caused by iodine deficiency

Impairment leads to compensatory in TSH ↑levels hypertrophy and hyperplasia of →follicular cells gross enlargement of gland→

Euthyroid metabolic state Degree of enlargement is proportional to level

and duration

Diffuse nontoxic goiter

Diffuse non-toxic (simple) goiter • colloid goiter• Endemic • sporadic (dyshormonogenetic)

Endemic Goiter

• Low iodine content in drinking water & food (Himalayas, Alps, Andes, areas far from the sea)

• Prevalence decreasing due to prophylactic iodination of salt

• Iodine deficiency causes decreased hormone levels & consequent elevation in TSH

Sporadic Goiter

• Commonest type of goiter• Euthyroid, but may be hypo- or hyper-• Mostly idiopathic, but RARELY, may be

caused by: Drugs used in Rx of hyperthyroidism Goitrogens e.g. cauliflower, cabbage, cassava Suboptimal iodine intake Hereditary enzymatic defects

Multinodular goiter

• Recurrent episodes of hyperplasia and involution leads to irregular enlargement

• All long standing diffuse endemic and sporadic goiter may eventually convert to multinodular goiter

• Causes most extreme enlargement and may be mistaken for neoplasm

• May arise due to variable response of follicular cells to external stimuli such as trophic hormones

• With uneven follicular hyperplasia, generation of new follicles and uneven accumulation of colloid rupture of →follicle and vessels hemorrhage, scarring & calcification →

nodularity→

Multinodular Goiter

• Asymmetric enlargement

• Multinodular• Haemorrhage• Calcification• Fibrosis• Cystic degeneration

Multinodular Goiter

• Numerous follicles varying in size

• Recent haemorrhage• Haemosiderin • Calcification• Cystic degeneration• +/- dominant nodule

Thyroid Neoplasms

I. Primary Tumours• Epithelial• Malignant Lymphomas• Mesenchymal tumours

II. Metastatic Tumours

Epithelial Thyroid Neoplasms

• Tumours of follicular cells Benign (adenomas)

• Follicular adenoma

Malignant (carcinomas)• Follicular carcinoma (10-20%)• Papillary carcinoma (75-85%)• Undifferentiated (anaplastic) carcinoma (<5%)

• Tumours of C-cells Medullary thyroid carcinoma (MTC - 5%)

Follicular Adenoma

• Benign, encapsulated tumor showing evidence of follicular differentiation

• Common• Predominantly young to middle women • Presents as solitary thyroid nodule• Painless nodular mass, cold on isotopic scan

Follicular Adenoma

• Solitary, Variably sized, encapsulated, well-circumscribed with homogenous gray-white to red-brown cut-surface

• +/- degenerative changes

Follicular Carcinoma

• Second most common form, 10-20%• Females > Males, average age ~ 45 - 55 yr• Rare in children• Solitary nodule, painless, cold on isotopic scan• Widely invasive Vs minimaly invasive• 50% 10 yr survival Vs 90%10 yr survival• Haematogenous route is preferred mode of spread

Follicular Carcinoma

• Solitary round or oval nodule

• Thick capsule• Composed of follicles• Capsular invasion or

vascular invasion within our outside capsular wall

Papillary Carcinoma

• Commonest thyroid malignancy, 75-85%• Female:Male = 2.5:1• Mean age at onset = 20 - 40 yr• May affect children• Prior head & neck radiation exposure• Indolent, slow-growing painless mass cold on

isotopic scan• Cervical lymphadenopathy may be presenting

feature

Papillary Carcinoma

• Variable size (microscopic to several cm)

• Solid or cystic• Infiltrative or

encapsulated• Solitary or

multicentric (20%)

Papillary Carcinoma

• Papillae or follicles• Psammoma bodies

• NUCLEAR FEATURES***

Papillary Carcinoma

Nuclear Features Optically clear (ground

glass, Orphan Annie) nuclei

Nuclear pseudoinclusions or nuclear grooves

Papillary CarcinomaPrognosis

Excellent but following factors play important role: Age and sex Size Multicentricity Extra-thyroid extension Distant metastasis Total encapsulation, pushing margin of growth

& cystic change

Anaplastic Carcinoma

• Rare; < 5% of thyroid carcinomas• Highly malignant and generally fatal < 1yr.

• Elderly ≈ 65 yrs; females slightly > males• Rapidly enlarging bulky neck mass• Dysphagia, dyspnoea, hoarseness

Anaplastic Carcinoma

• Large, firm, necrotic mass• Frequently replaces entire thyroid gland• Extends into adjacent soft tissue, trachea

and oesophagus• Highly anaplastic cell on histology with:

Giant, spindle,small or mix cell population

• Foci of papillary or follicular differentiation

Anaplastic Carcinoma

• Cellular pleomorphism

• +/- multinucleated giant cells

• High mitotic activity• Necrosis

Medullary Thyroid Carcinoma (MTC)

• Malignant tumour of thyroid C cells producing cacitonin

• 5 % of all thyroid malignancies• Sporadic (80%)• Rest in the setting of MEN IIA or B or as

familial without associated MEN syndrome

Medullary Thyroid Carcinoma (MTC)

Sporadic MTC Middle-aged adults Female:male = 1.3:1 Unilateral involvement of gland +/- cervical lymph node metastases Indolent course with 60-70% 5-yr survival after

thyroidectomy

Multiple Endocrine Neoplasia Types IIA & IIB

• Germ-line mutation in Ret protooncogene on chromosome 10q11.2

• MEN IIA: MTC, phaeochromocytoma, parathyroid adenoma or hyperplasia

• MEN IIB: MTC, phaeochromocytoma, mucosal ganglioneuromas, Marfanoid habitus, other skeletal abnormalities

Medullary Thyroid Carcinoma (MTC)

Associated with MEN IIA Younger patients in twenties Multicentric and bilateral Slow growing

Associated with MEN IIB Even younger patients in teens Aggressive with early metastasis Poor prognosis

Medullary Thyroid Carcinoma (MTC)

• Histology same for sporadic & familial

• Solid, lobular or insular growth patterns

• Tumour cells round, polygonal or spindle-shaped

• Amyloid deposits in many cases

Medullary Thyroid Carcinoma (MTC)

• Amyloid deposits stain orange-red with Congo Red stain

Prognosis of Thyroid Carcinomas

Papillary Best prognosis

Follicular

Medullary

Anaplastic Worst prognosis

Secondary Tumours

• Direct extensions from: larynx, pharynx, oesophagus etc.

• Metastasis from: renal cell carcinoma, large intestinal carcinoma, malignant melanoma, lung carcinoma, breast carcinoma etc.

Solitary thyroid nodule

• Papillary carcinoma• Follicular carcinoma• Medullary carcinoma• Follicular adenoma• Hyperplastic (dominant) nodule• Metastatic neoplasms• FINE NEEDLE ASPIRATION CYTOLOGY

Congenital Thyroid Diseases

• Agenesis /Aplasia• Hypoplasia• Accessory or aberrant thyroid glands• Thyroglossal duct cyst

Thyroglossal Duct Cyst

• Children• Failure of regression• Neck, medial• Squamous or columnar lining• Complications: inflammation, sinus tracts