1. Diseases of the endocrine system /diseases of the thyroid gland
Chapter 13
Diseases of the endocrine system /diseases of the thyroid gland
Department of Pathology
Wang Ping

2. Normal structure and function
Histologically, the thyroid is composed of closely packed follicles separated by a rich vascular supply and little intervening stroma
The follicles are lined by cuboidal epthelial cells and contain colloid which compose mainly of thyroglobulin and stored thyroid hormones

3. Histologically, the thyroid is composed of closely packed follicles separated by a rich vascular supply and little intervening stroma
The follicles are lined by cuboidal epthelial cells and contain colloid

4. Normal thyroid seen microscopically consists of follicles lined by an epithelium and filled with colloid.

5. Dispersed between the thyroid follicles are the parafollicular or C cells , which secrete calcitonin
This immunoperoxidase stain with antibody to calcitonin identifies the "C" cells

6. There are three kinds of disease in this part
1. Thyroid goitres
2. Inflammatory thyroid diseases, thyroiditis
3. neoplasmas

7. 1. diffuse nontoxic goiter
Goiter is the most common thyroid disease.
Two kinds of goiter:
endemic goiter
sporadic goiter.

8. Etiology
The basic cause of diffuse nontoxic and multinodular goiter is failure of normal thyroid hormone synthesis
Whether sporadic or endemic, the presence of goiter reflects impaired synthesis of thyroid hormone,
most often caused by dietary iodine deficiency.

9. endemic goiter
Cronic dietary deficiency of iodine
Inland mountainous regions
Goitrogens are responsible for endemic goiter (cabbage and cassava)

10. sporadic goiter
Sporadic goiter may occur anywhere
is due to increased physiologic demand for thyroxine at puberty or pregnancy
Mild deficiency of enzymes involved in thyroid hormone synthesis (less common)

11. Impairment of thyroid hormone synthesis leads to a compensatory
rise in the serum TSH level.
Which in turn causes
hypertrophy and hyperplasia of thyroid follicular cells,
and ultimately,
gross enlargement of the thyroid gland

12. Pathologic changes 1．Diffuse hyperplastic goiter
Initially, diffuse, symmetric enlarement of the gland.
The follicular epithelium may be hyperplastic in the early stages
The follicles are lined by crowded columnar cells which may pile up and form projections.

13. diffuse, symmetric enlarement of the gland

14. The follicles are lined by crowded columnar cells which may pile up and form projections.

15. 2. Diffuse colloid goiter
diffuse, symmetric enlarement of the gland .
>500 g.
The cut surface of the thyroid in such cases is usually brown, and translucent

16. brown, and translucent

17. Moicrocopically,
during periods of involution.
the follicles become distended with colloid, and the lining epithelial cells become flattened or cuboidal.

18. the follicular epithelium may be hyperplastic in the early stages or flattened and cuboidal during periods of involution.

19. the follicles become distended with colloid, and the lining epithelial cells become flattened or cuboidal.

20. 3 Nodular goiter
grossly ,
multilobulated asymmetrically enlarged gland.

21. On the cut surface, irregular nodules containing variable amounts brown gelatinous colloid are present.
Showing part of a massively enlarged gland containing multiple nodules of varying size, some with hemmorhage, cystic degeneration , fibrosis and calcification

22. • Enlarged thyroid with more enlargement on right • Left lobe also shows multiple nodules
asymmetrical

23. • Cut surface of one lobe of thyroid gland showing ill defined nodules
• Cut surface of one lobe of thyroid gland showing ill defined nodules. • Focus of cystic degeneration seen (blue arrow). • Some hemorrhage (red arrow) and some scarring.

24. This diffusely enlarged thyroid gland is somewhat nodular
This diffusely enlarged thyroid gland is somewhat nodular. This patient was euthyroid

26. Microscopic appearance includes：
1. follicular epithelial hypertrophy and hyperplasia
2. colloid-rich follicles lined by flattened epithelium and regressive changes
3. ill defined nodules fibrosis.
4. hemorrhage, cystic degeneration, calcification

27. The red arrow points to an area of scarring
The red arrow points to an area of scarring. The blue arrow points to a large and the yellow to a small follicle

28. The follicular cells have round to oval nuclei with small visible nucleoli.
The follicle cell cytoplasm is scant

29. ill defined nodules fibrosis

30. Clinical features It occurs mainly in inland mountainous regions
Patients present with painless diffuse enlargement of the thyroid.
As the disease progress, the thyroid becomes larger and more nodular.
The risk of development of carcinoma in multinodular goiter is small.
Compression symptoms are present.

31. Diffuse toxic goiter (Graves’ Disease)
hyperthyroidism
Etiology
An autoimmune disease characterized by the presence in serum of autoantibodies of IgG class directed against the TSH receptor in the thyoid cell.

32. The combination of the antibody with the receptor leads to stimulation of the cell to produce thyroid hormone

33. Pathologic changes Grossly
The thyroid gland is diffusely and symmetrically enlarged and the surface is usually smooth and soft,
cut surface is red tan.
Slight lobulation but no large cyst formed.

34. • Diffusely enlarged red tan thyroid gland
• Diffusely enlarged red tan thyroid gland. • Slight lobulation but no large cyst formed.

35. Microscopically
thyroid follicular epithelia cells are increased in size and number.
The follicles are closely packed and lined by tall columnar epithelium which is frequently thrown into papillary infoldings.
colloid is scanty and its periphery is scalloped because of rapid thyroglobulin proteolysis.

36. lymphocytic infiltration of the interstitium is common, and lymphoid follicles with germinal centers may be present.
Vascular proliferation, congestion.

37. A diffusely enlarged thyroid gland associated with hyperthyroidism is known as Grave's disease. At low power here, note the prominent infoldings of the hyperplastic epithelium.

38. colloid is scanty and its periphery is scalloped
At high power, the tall columnar thyroid epithelium with Grave's disease lines the hyperplastic infoldings into the colloid.

39. lymphocytic infiltration of the interstitium is common, and lymphoid follicles with germinal centers may be present.

40. colloid is scanty and its periphery is scalloped

41. Clinical features
Females is four times more commonly than males.
it has its highest incidence in 15-40y age group

42. 1. The thyroid gland is diffusely enlarged and appear as a mass in the neck.
2. hyperthyroidism
3. Eye changes are present in most patients with Grave’s disease. These include exophthalmos, a staring gaze due to decreased blinking and impaired eye muscle function.
4. Laboratory evidence of hyperthyroidism-most reliably elevation of free thyroxine T4 index-is prsent.
5. myxedema

43. Inflammatory thyroid diseases
1 Subacute thyroiditis
Also called granulomatous thyroiditis
Etiology
A viral origin is considerd most likely
Autoimmunity has also been suggested a possible mechanism but considered an unlikely one

44. pathologic changes Grossly ,
The gland is unilaterally or bilaterally enlarged, firm, and often adherent to surrounding structures.

45. Microscopically,
extensive destruction and fibrosis of thyroid follicles with aggregates of macrophages and giant cells around fragment of colloid.
Inflammation with a giant cell granulomatous reaction engulfing leaked colloid
Degeneration of follicles with inflammatory cell infiltration
Fibrous scarring

46. Degeneration of follicles with inflammatory cell infiltration
Inflammation with a giant cell granulomatous reaction engulfing leaked colloid
destruction and fibrosis of thyroid follicles with aggregates of macrophages and giant cells around fragment of colloid

47. Clinical features
A viral origin is considered most likely.
Autoinmmunity has also been suggested as a possible mehcanism
It afffect both sex and all ages, f>m
There is actue onset of painful enlargement of the thyroid.
Often associated with fever, malaise and muscle aches
Most patients are euthyroid but in a few cases there is transient hyperthyroidism,
The disease is self-limted with recovery occurring within 3 months

48. Chronic thyroiditis
Chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis )
Affects middle-age (>40y) females 10 times more frequently than males.
an autoimmune response against the thyroid.

49. It is an autoimmune inflammatory disorder of the thyroid
The most likely mechanism of thyroid cell destruction is a cytotoxic T-cell-mediated hypersensitivity reaction

50. Grossly
In the early stages , the thyroid is enlarged duffusely
The gland is firm and rubbery, with a coarsely nodular appearrance
As the disease progress, the gland become smaller
The end result is a markedly atrophic, fibrosed thyroid

51. Microscopically
1. There is evidence of destruction of the thyroid follices associated with severe lymohocytic infiltration of the gland (thyroid follicles are atrophic.)
mononuclear inflammatory infiltrate, Large lymphoid follicular with germinal centers are commonly present

52. Residual thyroid follicular epithelial cells are enlarged and have abundant pink cytoplasm know as Hurthle cells
Progressive fibrosis occurs

53. Marked lymphocytic infiltration and loss of thyroid follicles.
Residual thyroid follicular epithelial cells are enlarged and have abundant cytoplasm

54. (Riedel’s thyroiditis)
Fibrous thyroiditis
(Riedel’s thyroiditis)
It is a rare chronic disorder occurring in older patients, with women affected more frequently than men

55. The gland is usually mildly enlarged and replaced wholly or in part by hard, grayish-white fibrous tissue
(woody or ligneous thyroiditis) , which extends beyond the capsule.

56. Microscopically,
there is atrophy of thyroid follicles with replacement by dense, scar-like collagen.
Scattered lymphocytes and plasma cells are present

57. Clinical features
Both clinically and at surgery, it resembes a malignant neoplasm of thyroid
Painless rock-hard enlargement of thyroid
The fibrosis may constrict the trachea, producing dyspnea and stridor, the esophagus, causing dysphagia
In most case, the disorder causes slowly incrasing fibrosis of the neck structurs.

58. Thyroid neoplasms thyroid adenoma
Is the commonest neoplasm of the thyroid , accounting for about 30% of all cases of solitary thyroid nodules.
It may occure at any age, female are affected four times as frequently as males

59. Morphology
1、solitary nodule (Thyroid adenoma presents as a solitary, firm gray or red nodular, hemorrage, fibrosis, calcification, and cystic degeneration maybe present)
2、Showing a well-encapsulated (Follicular adenoma are srrounded by a complete fibrous capsule of varying thickness well-formed capsule)
3、 There is difference between inside and outside.
4、Compression of the adjacent gland. (The nomal thyroid parenchyma arround the adenoma is compressed)

60. hemorrage, fibrosis, calcification, and cystic degeneration
solitary, firm gray or red nodular
solitary nodule
well-encapsulated

61. Here is a surgical excision of a small mass from the thyroid gland that has been cut in half. The mass is well-circumscribed. Grossly it felt firm.
This is a follicular adenoma.

62. Here is another follicular neoplasm (a follicular adenoma histologically) that is surrounded by a thin white capsule. It is sometimes difficult to tell a well-differentiated follicular carcinoma from a follicular adenoma.

63. difference between inside and outside
Compression of the adjacent gland
• The red arrow is located within the adenoma. • Although composed of follicular cells, little colloid is seen. • The blue arrow points to the capsule of the adenoma, a few strands of connective tissue. • The yellow arrow points to colloid within a large normal follicle

64. 1、 Simple adenoma 
2、 Fetal adenoma
3、 Colloid adenoma
4、 Embryonal adenoma
5、 Follicular adenoma
6、 Hurthle cells adenoma :
cells with abundant pink granular cytoplasm

65. Simple adenoma

66. Macrofollicular structures
Colloid adenoma

67. Microfollicular structures
Fetal adenoma

68. Rudimentary follicular structures
Embryonal adenoma

69. Thyroid carcinoma
It is derived from the follicular epithelia or calcitonin-secreting parafollicular cells (C cells) of the thyroid．

70. 1. Papillary carcinoma most common type，60%
females three times more than males,
younger age range 15-35y are predominantly affected，
grow very slow，the prognosis of papillary Ca is good ,
even when metastases are present, patients survive for long periods after surgical excision of thyroid and metastatic tumor

71. Lymphatic spread can be found at an early stage.
Blood stream dissemination is rare in papillary carcinoma

72. grossly
papillary car. may present as solitary or multifocal lesions within the thyroid.
range from microscopic lesions to large masses over 10cm in diameters.
There are usually infiltrative lesions , but small number appear as circumscribed nodules on the cut surface,
they may appear granular and sometimes contain grossly discernible papillary foci.

73. Sectioning through a lobe of excised thyroid gland reveals papillary carcinoma.
granular and sometimes contain grossly discernible papillary foci.

74. Microscopically：
1）arrangement of cells in papillary structures; clear nuclei, optically clear appearence
2）prominent nuclear grooves
3）intranuclear inclusions caused by cytoplasmic invaginations into nucleus
4) Psammoma body
<1cm microcarcinoma

75. This is the microscopic appearance of a papillary carcinoma of the thyroid. The fronds of tissue have thin fibrovascular cores. The fronds have an oval papillary pattern.

76. The blue arrow points to a papillary structure. •
The center is fibrovascular; the cells covering it are epithelial. The red arrow shows a similar papillary structure in cross section.

77. This closeup shows that the cells range from low columnar to columnar
This closeup shows that the cells range from low columnar to columnar. The red arrow shows a cell with an Orphan Annie eye nucleus.

78. 2．follicular carcinoma
Comprise 20% of thyroid carcinoma
Females are affected more commonly than males
The disease is more common in middle age the prognosis is not very good
Spread is usually to bones and lungs via the blood stream at an early stage

79. Grossly
Follicular carcinoma may be indistinguishable from adenoma (encapsulated follicular car.) , or it may form a large infiltrative mass.
a hard grayish-white infiltrative mass.

80. minimally invasive follicular carcinoma of the thyroid

81. Microscopically：
varying size follicles lined by thyroid cells
The diagnosis of carcinoma depends on the presence of invasion of the capsule or vascular structure

83. 3．Medullary carcinoma
It is derived from the calcitonin-secreting parafollicular cells (C cells) of the thyroid. belong to APUD tumor,

84. Grossly,
medullary Car. forms a hard, grayish-white infiltrative mass.

85. Microscopically,
it is composed of small spindle-shaped and polygonal cells arranged in nests, cords, and sheets.
The stroma contains amyloid in most cases
IHC：The cells stain positively for calcitonin by the immunoperoxidase staining

86. At the center and to the right is a medullary carcinoma of thyroid
At the center and to the right is a medullary carcinoma of thyroid. At the far right is pink hyaline material with the appearance of amyloid. These neoplasms are derived from the thyroid "C" cells and, therefore, have neuroendocrine features such as secretion of calcitonin.

87. Medullary Carcinoma of Thyroid
small spindle-shaped and polygonal cells arranged in nests, cords, and sheets.
The stroma contains amyloid

89. Have a slow but progressive growth pattern
The stroma contains amyloid
Have a slow but progressive growth pattern
Local invasion of neck is common, both lymphatic and bloodstream metastasis occurs

90. Thyrocalcitonin markers in Medullary Carcinoma of the thyroid
Thyrocalcitonin markers in Medullary Carcinoma of the thyroid. Immunoperoxidase stain

91. 4. undifferentiated carcinoma
grossly：
Anaplastic carcinoma appears as a massive infiltrative lesion. It is hard , and grayish-white and frequently shows areas of necrosis and hemorrhage.
Microscopically:
it is composed of highly malignant-appearing spindle or giant cells.

92. Rare, aggressive, rapidly growing neoplasm that disseminate extensively.
Death usurally occurs whin a year after diagnosis
and is mainly due to local invasion of neck structures

93. it is composed of highly malignant-appearing spindle or giant cells.

94. thank you for you attention