Pathology of the Thyroid Gland

1. Pathology of the Thyroid Gland Prof. Dipak Shah Department of Pathology UWI, Mona

2. Diseases of the Thyroid Gland • Congenital diseases • Inflammation • Functional abnormality • Diffuse and Multinodular goiters • Neoplasia

3. 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

4. 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

5. 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

6. Hashimoto Thyroiditis • Diffuse enlargement • Firm or rubbery • Pale, yellow-tan, firm & somewhat nodular cut surface

7. 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

8. Functional Abnormality • Hyperfunction •  in level of hormone → toxic effects • Due to: • Diffuse hyperplasia • Hyperfunctioning multinodular goiter • Hyperfunctioning adenoma • Subacute lymphocytic (painless) thyroiditis

9. 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

10. 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

11. Graves’ Disease Autoimmune disease with breakdown of helper-T-cell tolerance Excessive production of TWO thyroid autoantibodies: • Thyroid-stimulating antibody (TSAb) & • 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

12. Graves Disease • Symmetrical enlargement of thyroid gland • Cut-surface is homogenous, soft and appear meaty • Hyperplasia and hypertrophy of follicular cells

13. 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

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

15. 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

16. 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

17. 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

18. Multinodular Goiter • Asymmetric enlargement • Multinodular • Haemorrhage • Calcification • Fibrosis • Cystic degeneration

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

20. Thyroid Neoplasms I. Primary Tumours • Epithelial • Malignant Lymphomas • Mesenchymal tumours II. Metastatic Tumours

21. 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%)

22. 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

23. Follicular Adenoma • Solitary, Variably sized, encapsulated, well-circumscribed with homogenous gray-white to red-brown cut-surface • +/- degenerative changes

24. 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

25. Follicular Carcinoma • Solitary round or oval nodule • Thick capsule • Composed of follicles • Capsular invasion or vascular invasion within our outside capsular wall

26. 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

27. Papillary Carcinoma • Variable size (microscopic to several cm) • Solid or cystic • Infiltrative or encapsulated • Solitary or multicentric (20%)

28. Papillary Carcinoma • Papillae or follicles • Psammoma bodies • NUCLEAR FEATURES***

29. Papillary Carcinoma Nuclear Features • Optically clear (ground glass, Orphan Annie) nuclei • Nuclear pseudoinclusions or nuclear grooves

30. 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

31. 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

32. 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

33. Anaplastic Carcinoma • Cellular pleomorphism • +/- multinucleated giant cells • High mitotic activity • Necrosis

34. 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

35. 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

36. 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

37. Medullary Thyroid Carcinoma (MTC) Associated with MEN IIA • Younger patients in twenties • Multicentric and bilateral • Slow growing Associated with MEN IIB • Even younger patientsin teens • Aggressive with early metastasis • Poor prognosis

38. 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

39. Medullary Thyroid Carcinoma (MTC) • Amyloid deposits stain orange-red with Congo Red stain

40. Prognosis of Thyroid Carcinomas Papillary Best prognosis Follicular Medullary Anaplastic Worst prognosis

41. Secondary Tumours • Direct extensions from: larynx, pharynx, oesophagus etc. • Metastasis from: renal cell carcinoma, large intestinal carcinoma, malignant melanoma, lung carcinoma, breast carcinoma etc.

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

43. Congenital Thyroid Diseases • Agenesis /Aplasia • Hypoplasia • Accessory or aberrant thyroid glands • Thyroglossal duct cyst

44. Thyroglossal Duct Cyst • Children • Failure of regression • Neck, medial • Squamous or columnar lining • Complications: inflammation, sinus tracts