Pathology of the Thyroid Gland

Lt.col. R.Targon PhD medicine, professor assistant

Diseases of the Thyroid Gland

Congenital diseases Inflammation Functional abnormality Diffuse and Multinodular goiters Neoplasia

Anatomy

Intimate anatomical relationships TG and recurrent laryngeal nerve

TG and superior laryngeal nerve TG and parathyroid glands

Embriology

Originates from foramen ceacum at the base of the tongue and descends into the neck, anterior to the hyoid bone, in front of the trachea. The tract left behind ( thyreoglossal tract) may persist and form a cyst (thyreoglossal cyst) The cyst may form a cutaneous fistula (thyreoglossal fistula)

Evaluation of Patients with Thyroid Disease

Tests of Thyroid Function
Serum TSH Total T4 and Total T3 Free T4 and Free T3 Thyroid Antibodies Serum Thyroglobulin

Evaluation of Patients with Thyroid Disease

Thyroid Imaging
Radionuclide Imaging (iodine-123 (123I) and iodine-131 (131I)) Ultrasound CT/MRI Scan

Cases of midline swelling

Thyroid (patient with multinodular goitre)

Cases of midline swelling

Thyreoglossal cyst

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

Inflammation
Thyroiditis
Acute illness with pain
Infectious
Acute (Suppurative) Chronic

Subacute or granulomatous (De Quervains)

Little inflammation with dysfunction

Subacute lymphocytic thyroiditis Fibrous (Riedel) thyroiditis

Autoimmune
Hashimoto (lymphocytic) thyroiditis

HASHIMOTO THYROIDITIS
Most common cause of hypothyroidism Autoimmune, non-Mendelian inheritance 45-65 years, F:M = 10-20:1 Painless symmetrical enlargement (minimally or moderately enlarged firm gland) 20% of patients present with hypothyroidism, and 5% present with hyperthyroidism (hashitoxicosis). Risk of developing
B-cell non-Hodgkins lymphoma Other concomitant autoimmune diseases
Endocrine and non-endocrine

Hashimoto Thyroiditis Pathogenesis

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

Riedel's Thyroiditis
Riedel's struma or invasive fibrous thyroiditis
predominates in women between the ages of 30 and 60 years replacement of all or part of the thyroid parenchyma by fibrous tissue, which also invades into adjacent tissues "woody" thyroid gland with fixation to surrounding tissues associated with other focal sclerosing syndromes, including mediastinal, retroperitoneal, periorbital, and retro-orbital fibrosis, and sclerosing cholangitis, suggesting that it may in fact be a primary fibrotic disorder.

Functional Abnormality
Hyperfunction
in level of hormone toxic effects
Due to:
Diffuse hyperplasia Hyperfunctioning multinodular goiter Hyperfunctioning adenoma Subacute lymphocytic 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 Autoimmune disease with genetic susceptibility associated with HLA-B8 and DR3 Female:Male = 5:1 Peak incidence between the ages 40 and 60 years Characterized by hyperthyroidism, symptoms of increased adrenergic stimulation include palpitations, nervousness, fatigue, emotional lability, hyperkinesis, and tremors Diffuse enlargement with audible bruit Ophthalmopathy with exophthalmos: Wide,staring gaze (fixed look) Lid lag, (von Graefe's sign) Spasm of the upper eyelid revealing the sclera above the corneoscleral limbus (Dalrymple's sign)

Dermopathy (Pretibial myxedema) Gynecomastia

levels of free T4 & T3 and levels of TSH in blood uptake of radioactive iodine

Graves Disease

Ophthalmopathy with exophthalmos

Graves Disease

Ophthalmopathy with exophthalmos

Graves Disease

Dermopathy (Pretibial myxedema)

Graves Disease
Autoimmune disease with breakdown of helper-T-cell tolerance

Excessive production of TWO thyroid autoantibodies: 1) Thyroid-stimulating antibody (TSAb) & 2) 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

Latin gutteria, struma 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

Multinodular Goiter
Numerous follicles varying in size Recent haemorrhage Haemosiderin Calcification Cystic degeneration +/- dominant nodule

Multinodular Goiter

Multinodular Goiter

Toxic Multinodular Goiter

Toxic multinodular goiters usually occur in individuals older than 50 years of age Symptoms and signs of hyperthyroidism are similar to Graves' disease Extrathyroidal manifestations are absent

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, wellcircumscribed with homogenous graywhite to red-brown cut-surface +/- degenerative changes

Plummer's Disease (Toxic Adenoma)

Hyperthyroidism from a single hyperfunctioning nodule Physical examination usually reveals a solitary thyroid nodule without palpable thyroid tissue on the contralateral side RAI scanning shows a "hot" nodule with suppression of the rest of the thyroid gland. Rarely malignant

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 Carcinoma Prognosis

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 spindleshaped Amyloid deposits in many cases

Medullary Thyroid Carcinoma (MTC)

Amyloid deposits stain orange-red with Congo Red stain

Prognosis of Thyroid Carcinomas

Papillary Follicular Medullary Best prognosis

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