Pathology of the Thyroid Gland it includes disease spectrums like 1.Congenital diseases 2.Inflammation 3.Functional abnormality 4.Diffuse and Multinodular goiters 5.Neoplasia

1. Pathology of the Thyroid Gland

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:
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

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 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

45. Thank you