Pathology of the Thyroid Gland

Pathology of the Thyroid Gland Prof. Dipak Shah Department of Pathology UWI, 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 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 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: 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  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 redbrown 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 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 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 Follicular Medullary Anaplastic Worst prognosis Best 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