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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

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Pathology of the Thyroid Gland


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    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