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 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

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 II. Metastatic 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 ~ 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 = 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 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

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 patients in 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