Neoplastic and Non-neoplastic Rodent Thyroid Lesions and Their Relevance

1. Neoplastic and Non-neoplastic Rodent Thyroid Lesions and Their Relevance Bob Maronpot RTP Rodent Pathology Course - 2014

2. Acknowledgment The majority of the photomicrographs in this presentation were provided courtesy of the National Toxicology Program Archives

3. http://ntp.niehs.nih.gov/nnl/

4. Toxicologic Pathology Vol 22 (2): 179-186, 1994 Haschek and Rousseaux’s Handbook of Toxicologic Pathology, 3rd Edition (2013)

5. Hypothalamus Pit TRH Thyroid TSH Blood T3 T4 T3/T4 Negative feedback Liver Elimination T4T3 TSH Basics of Thyroid Hormone Physiology Figure courtesy of Doug Wolf

6. Rat-Human Species Differences

7. Effects of Xenobiotics on the Thyroid Toxicologic Pathology Vol 22 (2): 179-186, 1994

8. Effects of Xenobiotics on the Thyroid Toxicologic Pathology Vol 22 (2): 179-186, 1994

9. Nomenclature • Thyroid – changes affecting the thyroid in general (e.g., inflammation) • Follicles – changes restricted to the follicles (e.g., secretory depletion) • Follicular epithelium - effect is specific to the follicular epithelium (e.g., hypertrophy) • C-Cells – changes specifically affecting the C- cells (e.g., hyperplasia)

10. Thyroid Lesions Non-Proliferative • Cysts • Enlarged/dilated follicles • Secretory depletion/colloid depletion • Colloid alteration • Degeneration • Inflammation • Mineralization • Hypertrophy Proliferative • Follicular epithelium – Hyperplasia • Generalized • Cystic – Adenoma – Adenocarcinoma • C-cells – Hyperplasia • Diffuse • Focal – Adenoma – Carcinoma

11. Parathyroid Lesions Non-Proliferative • Cysts • Syncytial giant cells/cytomegaly • Angiectasis Proliferative • Hyperplasia • Adenoma • Carcinoma

13. Rat Thyroid - Normal

17. Mouse Thyroid - Normal

19. Mouse Thyroid - Normal

20. Rat versus Mouse

21. Rat Thyroid - Mineral

22. Embryonal Cyst

23. Embryonal Cyst

24. Embryonal Cyst

25. Embryonal Cyst

26. Ectopic Thymus

28. Enlarged Follicles F344

29. Follicular Degeneration

30. Follicular Degeneration B6C3F1 Control Female

33. Pigment Vehicle control. Male F344

34. Pigment High dose methoxypsoralen male F344

35. Pigment 1 of 3

36. Pigment 2 of 3

37. Pigment 3 of 3Subchronic trinitrofluorenone study in F344 rats

38. Follicular Cell Hypertrophy

39. Concurrent Control

41. Follicular Cell Hypertrophy 1 of 3 Female SD Rat

42. Follicular Cell Hypertrophy 2 of 3

43. Follicular Cell Hypertrophy 3 of 3

44. Follicular Cell Hypertrophy Subchronic study. SD Rat

45. Hypertrophy Subchronic study. F344 Rat

46. Hypertrophy Harlan SD Rat.

47. Hypertrophy & Hyperplasia 1 of 4Subchronic study. F344 Rat

48. Hypertrophy & Hyperplasia 2 of 4

51. Hypertrophy

52. Hypertrophy

53. Secretory Depletion Subchronic study. F344 Rat

54. Secretory Depletion 1 of 2Subchronic study. F344 Rat

55. Secretory Depletion 2 of 2Subchronic study. F344 Rat

56. Secretory Depletion Chronic study. F344 Rat

57. Lymphoid Infiltrate, Secretory Depletion and Hypertrophy 1 of 2Subchronic study. FVB/N Mouse.

58. Lymphoid Infiltrate, Secretory Depletion and Hypertrophy 2 of 2

59. Lymphoid Infiltrate, Secretory Depletion and Hypertrophy 1 of 2Female SD Rat

60. Lymphoid Infiltrate, Secretory Depletion, Pigment, and Hypertrophy 2 of 2

61. Periarteritis 1 of 2B6C3F1 Mouse

62. Periarteritis 2 of 2

64. Follicular Cell Proliferative Lesions • Hyperplasia – Follicular cell hyperplasia • Diffuse • Focal (simple papillary infoldings) – Cystic hyperplasia – Minimal compression • Adenoma – Circumscribed, compressive – Growth pattern – complex papillary or follicular – Cells well differentiated and hyperchromatic • Carcinoma – Capsular invasion – Infiltrative, disorganized, varied growth pattern – Cellular pleomorphism and atypia – Varying sized follicles – Scirrhous reaction

65. Diffuse Hyperplasia 1 of 2F344 Rat Chronic Study

66. Diffuse Hyperplasia 2 of 2

67. Focal Hyperplasia B6C3F1 Mouse Sodium Chlorate Study

68. Follicular Cell Hyperplasia 1 of 2B6C3F1 Mouse

69. Follicular Cell Hyperplasia 2 of 2

70. Hyperplasia vs. Adenoma 1 of 2B6C3F1 Mouse. Original dx = Adenoma

71. Hyperplasia vs. Adenoma 2 of 2

72. Hyperplasia vs. Adenoma 1 of 2B6C3F1 Mouse Original dx = Hyperplasia

73. Hyperplasia vs. Adenoma 2 of 2

74. Follicular Cell Adenoma F344 Rat

75. Cystic Follicular Cell Adenoma

76. Follicular Cell Adenoma F344 Rat

77. Follicular Cell Adenoma 1 of 4 F344 Rat

78. Follicular Cell Adenoma 2 of 4

81. Follicular Cell Adenoma 1 of 3SD Female Rat

84. Follicular Cell Carcinoma 1 of 2Wistar Han Rat

85. Follicular Cell Carcinoma 2 of 2

86. Follicular Cell Carcinoma B6C3F1 Mouse

87. Follicular Cell Carcinoma F344 Rat

88. Follicular Cell Carcinoma

89. Follicular Cell Carcinoma 1 of 2 F344 Rat

90. Follicular Cell Carcinoma 2 of 2

91. Macrofollicular Carcinoma

92. Squamous Cell Carcinoma 1 of 2F344 Rat

93. Squamous Cell Carcinoma 2 of 2

94. Follicular Cell Proliferative Lesions • Hyperplasia – Follicular cell hyperplasia • Diffuse • Focal (simple papillary infoldings) – Cystic hyperplasia – Minimal compression • Adenoma – Circumscribed, compressive – Growth pattern – complex papillary or follicular – Cells well differentiated and hyperchromatic • Carcinoma – Capsular invasion – Infiltrative, disorganized, varied growth pattern – Cellular pleomorphism and atypia – Varying sized follicles – Scirrhous reaction

95. C-Cell Proliferative Lesions • Hyperplasia – Diffuse, focal, both – Maximum diameter less than 5 average colloid-filled follicles • Adenoma – Maximum diameter greater than 5 average colloid-filled follicles – Discrete, circumscribed – May compress adjacent follicles • Carcinoma – Infiltrative, local & capsular invasion – Pleomorphism & atypia may be present

96. C-Cell Hyperplasia, Diffuse 1 of 2

97. C-Cell Hyperplasia, Diffuse 2 of 2

98. C-Cell Hyperplasia, Focal 1 of 2

99. C-Cell Hyperplasia, Focal 2 of 2

100. C –Cell Hyperplasia Female SD Rat

101. Hyperplasia vs Adenoma 1 of 2F344 Rat

102. 2 of 2Original dx = Adenoma

103. C-Cell Adenoma

104. C-cell Adenoma

105. C-Cell Carcinoma 1 of 3F344 Rat

106. C-Cell Carcinoma 2 of 3

111. C-Cell Proliferative Lesions • Hyperplasia – Diffuse, focal, both – Maximum diameter less than 5 average colloid-filled follicles • Adenoma – Maximum diameter greater than 5 average colloid-filled follicles – Discrete, circumscribed – May compress adjacent follicles • Carcinoma – Infiltrative, local & capsular invasion – Pleomorphism & atypia may be present

112. If I have more time…..

114. Normal Parathyroid

115. Cyst, NOS

116. Embryonal Cyst 1 of 2

118. Ectopic Thymus & Embryonal Cyst 1 of 2

120. Angiectasis 1 of 2

121. Angiectasis 2 of 2

122. Cytomegaly

123. Syncytial Giant Cells

124. Parathyroid Fibrosis Downloaded from NTP Non-Neoplastic Lesion Atlas 1 of 2

125. Parathyroid Fibrosis Downloaded from NTP Non-Neoplastic Lesion Atlas 2 of 2

126. Ectopic Thymus

128. Parathyroid Hyperplasia, Diffuse 1 of 3

129. Parathyroid Hyperplasia, Diffuse 2 of 3

130. Parathyroid Hyperplasia 3 of 3

131. Parathyroid Hyperplasia

134. Parathyroid Adenoma 1 of 2

140. Parathyroid Carcinoma 1 of 2

141. Parathyroid Carcinoma 2 of 2

142. Thank you for your attention

Neoplastic and Non-neoplastic Rodent Thyroid Lesions and Their Relevance

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