disorders of thyroid

1. PATHOLOGY OF THE THYROID
GLAND
Dr. Kusuma K N

5. DISEASES OF THE THYROID
GLAND
 Congenital diseases
 Inflammation
 Functional abnormality
 Diffuse and Multinodular goiters
 Neoplasia

6. CONGENITAL THYROID DISEASES
 Agenesis /Aplasia
 Hypoplasia
 Accessory or aberrant thyroid glands
 Thyroglossal duct cyst

7. THYROGLOSSAL DUCT CYST
 Children
 Failure of regression
 Squamous or
columnar lining
 Complications:
inflammation, sinus
tracts

9. 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

10. HASHIMOTO THYROIDITIS
 Most common cause of hypothyroidism
 Autoimmune
 45-65 years
 F:M = 10-20:1
 Painless symmetrical enlargement

11. PATHOGENESIS
 Immune systems reacts against a variety of
thyroid antigens.
 circulating autoantibodies against thyroglobulin
and thyroid peroxidase
 Progressive depletion of thyroid epithelial cells
which are gradually replaced by mononuclear
cells → fibrosis

13. HASHIMOTO THYROIDITIS
 Diffuse enlargement
 Firm or rubbery
 Pale, yellow-tan, firm & somewhat nodular cut
surface

14. 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

16.  Risk of developing
 B-cell non-Hodgkin’s lymphoma
 Other concomitant autoimmune diseases
 Endocrine and non-endocrine

17. SUBACUTE THYROIDITIS
 Granulomatous thyroiditis / De Quervain
thyroiditis
 less frequent than Hashimoto disease
 40 and 50
 F: M = 4 : 1
 triggered by a viral infection
 history of an upper respiratory infection just
before the onset of thyroiditis

19. FUNCTIONAL ABNORMALITY
 Hyperfunction- hyperthyroidism
 Thyrotoxicosis : hypermetabolic state caused by
elevated circulating levels of free T3 and T4

22.  Hypofunction- hypothyroidism
↓ in level of hormone → impair development in
infants and slowing of physical and mental
ability in adults
Cretinism
Myxedema

26. GRAVES DISEASE
 Most common cause of endogenous hyperthyroidism
 F:M = 7:1
 3rd to 4th decades
 Characterized by
Hyperthyroidism
ophthalmopathy with exophthalmos
dermopathy (pretibial myxedema)
 Autoimmune disease with genetic susceptibility
associated with HLA-B8 and DR3

27. GRAVES DISEASE….
 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

29. 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

30. GRAVES DISEASE
 Symmetrical
enlargement of thyroid
gland
 C/s: homogenous, soft
and appear meaty
 Hyperplasia and
hypertrophy of follicular
cells

32. 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

33. DIFFUSE NONTOXIC GOITER
 Diffuse non-toxic (simple) goiter
 colloid goiter
 Endemic
 sporadic (dyshormonogenetic)

34. 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

35. 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

36. 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

37.  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

38. MULTINODULAR GOITER
 Asymmetric
enlargement
 Multinodular
 Haemorrhage
 Calcification
 Fibrosis
 Cystic degeneration

39. MULTINODULAR GOITER
 Numerous follicles varying in size
 Recent haemorrhage
 Haemosiderin
 Calcification
 Cystic degeneration
 +/- dominant nodule

41. THYROID NEOPLASMS
I. Primary
 Epithelial
 Malignant Lymphomas
 Mesenchymal tumors
II. Metastatic Tumors

42. 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%)

43. 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

44. FOLLICULAR ADENOMA
 Solitary, Variably sized,
encapsulated, well-
circumscribed with
homogenous gray-white to
red-brown cut-surface
 +/- degenerative changes

46.  Hurthle cell/ oxyphil adenoma

47. FOLLICULAR CARCINOMA
 Second most common form, 10-20%
 Females > Males
 45 - 55 yrs.
 Rare in children
 Solitary nodule, painless, cold on isotopic
scan
 Widely invasive Vs minimaly invasive
 Haematogenous route is preferred mode of
spread

49. FOLLICULAR CARCINOMA
 Solitary round or oval
nodule
 Thick capsule
 Composed of follicles
 Capsular invasion or
vascular invasion

50. 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

52. PAPILLARY CARCINOMA
 Variable size
(microscopic to
several cm)
 Solid or cystic
 Infiltrative or
encapsulated
 Solitary or
multicentric (20%)

53. PAPILLARY CARCINOMA
 Papillae or follicles
 Psammoma bodies
 NUCLEAR
FEATURES***

54. PAPILLARY CARCINOMA
Nuclear Features
Optically clear (ground glass, Orphan Annie)
nuclei
Nuclear pseudoinclusions or nuclear grooves

58. VARIANTS
 Follicular variant
 tall-cell variant
 diffuse sclerosing variant
 papillary microcarcinoma

59. 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

60. 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

61.  Cellular pleomorphism
 +/- multinucleated giant cells
 High mitotic activity
 Necrosis

62. 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

63. 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

64. 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

65.  Histology same for sporadic & familial
 Solid, lobular or insular growth
patterns
 Tumour cells round, polygonal or
spindle-shaped
 Amyloid deposits in many cases

66.  Amyloid deposits stain
orange-red with Congo
Red stain

67. PROGNOSIS OF THYROID
CARCINOMAS
Papillary Best prognosis
Follicular
Medullary
Anaplastic Worst prognosis

68. SECONDARY TUMOURS
 Direct extensions from: larynx, pharynx,
oesophagus etc.
 Metastasis from:
renal cell carcinoma, large intestinal
carcinoma, malignant melanoma, lung
carcinoma, breast carcinoma etc.

69. SOLITARY THYROID NODULE
 Papillary carcinoma
 Follicular carcinoma
 Medullary carcinoma
 Follicular adenoma
 Hyperplastic (dominant) nodule
 Metastatic neoplasms

70. 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