1. endocrine
Lect-2

2. TUCOM- department of pathology year 3 endocrine gland lectures 3&4
Pathology of Thyroid
TUCOM- department of pathology
year 3 endocrine gland lectures 3&4

3. Normal Thyroid Gland

4. Thyroid - Normal

5. Normal resting Thyroid

6. Disorders of Thyroid: Hyperthyroidism Hypothyroidism Thyroiditis
Diffuse multinodular Goiter.
Neoplasms – adenoma/carcinoma.
Congenital – Thyroglossal cyst/duct.

7. Goiter It is a diffuse or focal enlargement of the thyroid gland.
Caused by: 1- Colloid goiter. 2- Grave’s disease. 3- Thyroiditis. 4- Tumors.

8. Colloid goiter:
most cases start as diffuse enlargement with nodularity development at later stages.
They represent compensatory hyperplasia of follicular epithelium secondary to decreased thyroid hormone production.

9. Diffuse-Multinodular goitre Pathophysiology
Endemic & sporadic types
Endemic: Cassava – thiocyanate – iodide transport.
Sporadic: rare, females, young and usually of unclear cause. (may be associated mild defect, iodine deficiency and physiological needs).
When there is low T3 and T4 there will be an increase of TRH & TSH that induce secretion of thyroid hs associated with enlargement of thyroid gland by hypertrophy and hyperplasia of follicular epithelium at earlier stages diffuse and by time nodular.

10. Stages Hyperplastic stage & Colloid stage.
Repeated attacks  multinodular due to uneven hyperplasia and accumulation of colloid as a result of tension and stress that lead to rupture of follicles.

11. CLINICALLY:
1- Huge size result in dysphagia, airway obstruction, chocking sensation and stridor. SITE as retrosternal extension causing superior vena cava syndrome with vein enlargement, tachycardia and heart failure.
2- Rarely toxic hyperthyroidism plummer syndrome.
3- Mass effect and misdiagnosed as tumor need US, isotope scanning, FNAC, CT scan and MRI.

12. Morphology:
Grossly: at early stages symmetric and diffusely enlarges the thyroid gland and in late stages there is multiple nodules on cut surfaces. Some nodules show cystic degeneration, hemorrhage, fibrosis, and calcification.
Microscopy show randomly sized colloid filled follicles lined by flattened cells due to pressure of colloid with focal areas of hyperplasia, fibrosis, cystic changes, necrosis & hemorrhage present as hemosiderin laden macrophages.

13. The mass is relatively symmetric and diffusely enlarges the thyroid gland. The patient is from an endemic goiter area (in this case, Cambodia), where more than 10% of the population have goiters due to low-iodine diets (lack of seafood or iodized salt), often combined with diets high in vegetables that block iodine uptake by the thyroid gland ("goitrogens," such as cabbage or cassava).

14. Goitre – Iodine Deficiency

15. Thyroid gland, multinodular goiter - Gross, cut surfaces  The thyroid gland shows multiple nodules on cut surfaces. Some nodules show cystic degeneration, hemorrhage, fibrosis, and calcification.

16. Multinodular Goitre with Papillary Carcinoma

17. Colloid Cysts in MNG

18. Multinodular Goitre

19. Hyperthyroidism
Thyrotoxicosis it is a hypermetabolic state encountered much more often in females caused by High free T3/T4 in the blood.
CAUSES: COMMON:
1- Diffuse toxic hyperplasia (Graves)
2- Toxic multinodular goiter
3- Toxic adenoma.
UNCOMMON CAUSES:
1- Thyroiditis
2- Functioning thyroid carcinoma
3- TSH secreting pituitary adenoma
4- Iatrogenic.
5- Struma ovarii.
6- Choriocarcinoma and hydatidiform mole.

20. Clinical features
Nervousness, palpitations, rapid pulse, fatigability, muscular weakness, weight loss with good appetite, diarrhea, heat intolerance, warm skin, excessive perspiration, emotional liability, menstrual changes, fine tremor of the hand, eye changes and enlargement of the thyroid gland.
Cardiac manifestations: tachycardia, arrhythmias, especially fibrillation or SVT, cause is obscure but more prone to occur in old age group.

21. Graves Disease: Common (2%F)
Females, 20-40y, Autoimmune, associated with other autoimmune diseases.
HLA B8 and DR3.
Triad of clinical features,
Hyperthyroidism
Exopthalmos and retraction of the upper eyelid.
Pretibial myxedema.
Ab to TSH receptor – thyroid stimulating antibody, thyrotropin binding inhibitor immunoglobulin are responsible for hyperfunction.
Thyroid growth immunoglobulin responsible for hyperplasia.
Micro: Diffuse hyperplasia, tall columnar cells, papillary folds
& Scalloped, pale, scanty colloid.

22. Hyperthyroidism Features:

23. Graves exophthalmos - Clinical presentation  Although the patient in our scenario did not have exophthalmos, it may be found in Graves disease, as pictured here. The eyes protrude from the orbit due to increased glycosaminoglycans deposition in the retro-orbital fibrofatty tissue and extraocular muscles, as well as to a marked lymphocytic infiltrate.

24. Graves Disease: e.g. Of orbitopathy before and after
Decompression surgery.

25. Graves’ Thyroiditis:

26. (Graves disease) - Gross  This thyroid gland is symmetrically moderately enlarged and would show beefy red parenchyma on cut sections.

27. Graves Disease

28. The hyperfunctioning follicular epithelium is tall columnar, representing cellular hypertrophy. Papillary infoldings into the follicular lumens result from epithelial proliferation and overcrowding, representing hyperplasia. Peripheral scalloping of the colloid within follicular lumens represents active pinocytosis by the hyperfunctioning epithelium.

29. Hypothyroidism Cretinism / Myxedema – Low T3/T4, High TSH Causes:
Hashimoto’s thyroiditis - autoimmune
Iodine deficiency
Drugs – PAS, iodides, lithium
Developmental – Atrophy, hypoplasia Pituitary disorders
Radiation/Surgery

30. Hypothyroidism Cretinism (child) Myxedema (adult)
Impaired CNS & bone growth
Mental retardation
Short stature
Coarse facial features
Protruding tongue
Umbilical hernia
Myxedema (adult)
Slow physical and mental activity
Cold intolerance
Over weight
Low cardiac output
Constipation and decreased sweating
Cool pale thick skin

31. Hypothyroidism Myxedema Features:

32. Myxedema: showing periorbital bags under eyes
Note loss of lateral eyebrow; Anne’s sign

33. Thyroid Atrophy

34. Thyroiditis Some are ill defined as interstitial th.
Some are rare as palpation th. And suppurative (always blood borne).
Reidel’s fibrous thyroiditis of unknown etiology manifested as atrophy and hypothyroidism with fibrous adhesions.
Common types are: 1- Hashimoto’s thyroiditis, 2- subacute lymphocytic thyroiditis and 3- subacute granulomatous.

35. Hashimoto Thyroiditis
Common non endemic goitre.
females more common 45-65y.
Autoimmune disease with genetic basis HLA-DR5, DR3.
( defect in thyroid specific suppressor T cells lead to emergence of T helper cells against specific thyroid antigens which cooperate with B cells lead to formation of auto-antibodies as Ab to thyroid peroxidases formerly known as antimicrosomal Abs & Anti- thyroglobulin antibody)
Initial hyperthyroidism and in long standing cases hypothyroidism.
High risk of B cell lymphoma.
Grossly: Firm diffuse goitre.
Microscopy: Follicle atrophy with lymphocytic infiltration.
Hürthle cells – eosinophilic cells.
Fibrosis & destruction of follicular tissue.

36. Hashimoto’s Thyroiditis:

37. Hashimoto’s Disease

38. Hashimoto’s Disease

39. Anti-thyroglobulin Antibody

40. Anti- microsomal Autoantibody

41. Granulomatous Thyroiditis:
Subacute or DeQuervain thyroiditis.
Less common, Females, years
Pain, fever, fatigue, myalgia.
Post viral syndrome.
Genetic association - HLA B35
Patchy microabscess, granulomas with giant cells.
Hyperthyroidism.
Heals with normal thyroid function.

42. DeQuervain's Disease - SAGT

43. Subacute lymphocytic thyroiditis
Foci of lymphocytic infiltration with mild fibrosis.
Obscure origin but may be an autoimmune in origin.

44. Thyroid Cancer Classification
Epithelial cell tumors:
Differentiated
Papillary (75- 80%)
Follicular (10-20%)
Undifferentiated
Anaplastic (3-5%)
Parafollicular (C- cell) tumors
Medullary ( 5% )
Lymphoma (1-2%)
Others

45. Neoplasms of Thyroid Adenoma – Follicular adenoma - hot
Papillary Carcinoma – 75-80%
Follicular carcinoma %
Medullary carcinoma – 5%
Anaplastic carcinoma - <5%

46. Neoplasms of Thyroid Usually solitary, benign.
Good prognosis - <1% cancer mort.
May be functional – hot nodule.
Malignancy - Infiltration – fixation, hoarseness, recurrent laryngeal nerve damage.

47. Clinical Presentation
Thyroid nodule (most common)
Cervical lymph node(s)
Local compressive symptoms
Distant metastasis
Thyroid dysfunction

48. Thyroid Nodules Prevalence : Physical Exam 4-7% Ultrasound 30%
Autopsy 50%
Incidence increases with age

49. Thyroid Nodules (Cont’d)
Most thyroid nodules are BENIGN
A thyroid nodule has 5-12% malignancy rate
History of radiation increases the chance of malignancy to 30-50%

50. Thyroid Nodules Evaluation
History
Physical Examination
Laboratory Evaluation
- TSH and FNAC
Imaging Studies
NOT VERY HELPFUL

51. Thyroid Nodules Evaluation
HISTORY
Age < 20 or > 50
Head or neck irradiation
Family history
Male sex
Recent growth
Pressure symptoms

52. Thyroid Nodules Evaluation
PHYSICAL EXAMINATION
Hard non tender nodule
Nodule of different consistency within MNG
Fixed nodule
Cervical lymphadenopathy
Immobile vocal cord

53. Thyroid Nodules Ultrasonography
Generally has a minor role in the evaluation of thyroid nodules
Palpable nodules do not need ultrasound
Small non-palpable nodules (<1cm) are generally unimportant even if malignant
Cystic nodules can be malignant

54. Ultrasound Scan Solid nodule:

55. Thyroid Nodules FNA
The most important test in the evaluation of a thyroid nodule
Has an overall sensitivity of 83-98% and specificity of %
Complications are very rare and usually minor

56. Thyroid Nodules Radionucleotide Scans
Most thyroid nodules are cold (95%)
Most cold nodules are benign (80-85%)
Hot nodules are usually functioning and can be detected by TSH (suppressed)
Warm nodules can be malignant

58. Radioactive iodine
is concentrated from the blood by thyroid follicular cells, allowing correlation of anatomic features with thyroid function. Decay of radioactive iodine is detected as dark spots on the scan. A normal thyroid gland shows diffuse moderate iodine uptake in the right and left lobes and isthmus. Graves disease is characterized by diffuse increased uptake. Multinodular goiter most often shows patchy, irregular uptake with some nodules hyperfunctional compared to normal (dark, or "warm," on scan) and other nodules hypofunctional (pale, or "cold"). The focal rounded defect lacking uptake (cold nodule) is characteristic of thyroid neoplasms and cysts. A focal rounded area of increased uptake that suppresses the remaining thyroid gland (hot nodule, not pictured) is most often a hyperfunctional follicular adenoma or goiter nodule.

59. Technetium Scan
Normal
Hot nodules
Cold nodule

60. Thyroid Nodules Evaluation (Summary)
Most thyroid nodules are benign
TSH determines the thyroid functional status
Thyroid scanning and U/S are generally not helpful
FNA is the most useful diagnostic procedure

61. Adenoma Follicular common, rarely Papillary
Compact follicles (large in MNG)
Solitary, rarely Functional or hot.
Centre may show necrosis/hem.
Well capsulated.
Compressed normal gland.

62. Follicular Adenoma

63. Follicular Adenoma

64. Solitary Adenoma

65. Follicular Adenoma

66. Thyroid Carcinoma Uncommon – child – elderly.
Common - Papillary adenocarcinoma.
Associated with radiation exposure, especially during the first 2 decades.

67. Thyroid Carcinoma Type Age Spread Prognosis Papillary Young <45y
Lymph
Excellent
Follicular
Middle age
B.V.
Good
Anaplastic
elderly
Local
Poor
Medullary
Elderly
familial
All
variable

68. Papillary Carcinoma Most common cancer – 75-80%
Idiopathic, Radiation, Gardner & Cowden syndromes.
Papillary folds, Psammoma bodies, Orphan-Anne nucleus.
98% 10 year survival when localized.

69. This is a lobectomy specimen of thyroid gland showing normal parenchyma, within which is a 2-cm, white, slightly irregular, expansile tumor. No grossly discernible papillae are present on the cut surface. The neoplasm is not encapsulated, but is well demarcated from adjacent, beefy-red thyroid parenchyma, and it appears to distend and distort the capsule of the thyroid gland without penetrating through it.

70. Papillary Carcinoma

71. Papillary Carcinoma

72. Papillary Carcinoma

73. The papillae shown here are covered by cuboidal epithelium that has nuclei that are characteristic of papillary thyroid carcinoma: large, crowded, and overlapping nuclei with vesicular chromatin, small nucleoli, infrequent mitotic figures and loss of polarity. Chromatin clearing (ground-glass "Orphan Annie" nuclei) and irregular nuclear contours with grooves and cytoplasmic pseudoinclusions are hallmark features of papillary thyroid carcinoma. Shared features between histopathology and cytology of papillary thyroid carcinoma are nuclear enlargement, intranuclear inclusions, nuclear grooves, small nucleoli, and nuclear overlapping. Unlike tissue sections, cytologic smears of papillary thyroid carcinoma show finely granular chromatin (inset). Normal follicular cells are roughly the same size as a mature lymphocyte nucleus or a red blood cell. Note that the inset shows nuclear detail, but the cytoplasm of the tumor cells is pale.

74. Medullary Carcinoma

75. Amyloid in Medullary Carcinoma – Polarized microscopy

76. Anaplastic Carcinoma

77. Conclusions: Hyperthyroidism Thyrotoxicosis:
Graves, thyrotoxicosis, LATS.
Hypermetabolism, high T3/T4, low TSH
Thyrotoxicosis:
Antithyroglobulin, anti microsomal
Hypometabolism, Low T3/T4, high TSH.
Multinodular goitre – low iodine.
Neoplasms
Follicular adenoma – capsulated, single.
Carcinoma: Papillary follicular, medullary, anaplastic.