This toxicologic pathology presentation provided examples of normal, degenerative lesions of the rat and mouse adrenal gland and includes non-neoplastic proliferative lesions as well as common and rare adrenal cortical and medullary cancers.

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Pathology of the Adrenal Gland

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Index of Slides

1. Pathology of the Adrenal Gland R.R. Maronpot maronpot@me.com Photomicrographs courtesy of the National Toxicology Program (http://ntp.niehs.nih.gov)
2. Pathology of the Adrenal Gland • Normal histology & physiology • Hyperplasia – Cortex • Subcapsular • Cortex – Medulla • Neoplasia – Cortex • Subcapsular • Cortex – Medulla
3. Rat Adrenal
4. Mouse Adrenal
5. • Adrenals are 25% heavier in females • No clearly visible zona reticularis in mice Mouse Adrenal Rat Adrenal Zona Reticularis
6. X Zone Female Mouse Adrenal •Unique to mouse •Appears a few days after birth •Fully developed at weaning X-Zone
7. Growth and Involution of the X Zone • In females X zone increases in size with a maximum at about 9 weeks and regresses gradually in virgins and rapidly upon the first pregnancy • In males, X zone disappears at puberty (5 wks) without undergoing vacuolization • Gonadectomy of prepubertal male and female delays involution by several months • Hysterectomy causes the X zone and zona fasiculata to degenerate
8. X-Zone at 9 Weeks Female Mouse Adrenal
9. Fatty valuolation of early involution
10. Nearly complete involution of X-zone
11. Adult Male Mouse Adrenal Normal male mouse does not have an X-zone
12. Lipogenic Pigment in a Swiss Mouse Adrenal Occurs in rats and mice
13. Lipogenic Pigment • Ceroid pigment • In cortical cells at corticomedullary junction • Age-related & occurs due to large amount of lipid in adrenal gland • May be associated with X zone in female mice
14. Deposition of ceroid pigment may be exacerbated by treatment (Female B6C3F1 – tricresylphosphate)
15. B6C3F1 mouse treated with tricresylphosphate
16. Cytoplasmic vacuolization (Multifocal) Can be associated with increased ACTH secretion Female SD High P450
17. Female SD
18. Cortex Cytoplasmic Vacuolation (Diffuse) Harlan SD Male 90-Day study – p-Chloro-A,A,A–trifluoro toluene
19. Cytoplasmic Vacuolization (Diffuse)
20. The vacuoles consist of microvesicular and macrovesicular cytoplasmic fat
21. Discrete foci of fatty change can occur
22. Cortical Cysts Rarely seen B6C3F1 mouse
23. Cystic Degeneration Control female SD Medullary hyperplasia Cystic degeneration
24. Cystic Degeneration Cystic degeneration vs. Focal fatty change
25. Cystic Degeneration with Hemorrhage Male F344 Na chlorate
26. Adrenal Cortical Atrophy PCB118 High dose female SDDecreased thickness of cortical layers
27. Lipogenic pigment also present
28. Cortex necrosis B6C3F1 mouse treated for 90-days with 1-bromopropane (water disinfection biproduct)
29. Vascular Ectasia Thrombus F344
30. Vascular Ectasia Male F344 treated with codeine (Differential Dx = Hemangioma)
31. Chronic inflammation B6C3F1 mouse treated for 90-days with 1-bromopropane (water disinfection biproduct)
32. X-zone involution Mixed inflammatory cell infiltrate plus mineralization Chronic inflammation B6C3F1 mouse treated for 90-days with1bromopropane (water disinfection biproduct)
33. Common in mice 2-14% incidence in past NTP studies Accessory Cortical Nodule
34. Accessory cortical nodule Untreated male B6C3F1 mouse in a 2-year study
35. Pathology of the Adrenal Gland • Normal histology & physiology • Hyperplasia – Cortex • Subcapsular • Cortex – Medulla • Neoplasia – Cortex • Subcapsular • Cortex – Medulla
36. Subcapsular Hyperplasia B6C3F1 mouse treated for 90-days with Na bromate (water disinfection biproduct)
37. Subcapsular Hyperplasia • Common, age-related in mouse adrenals – 60 to 90% incidence; first seen at about 4 months • Type A spindle cells, Type B polygonal cells, or mixed population of Type A and Type B • Scattered aggregates (usually Type A cells) • Focal nodules (usually Type B cells)
38. Type A spindle cells Type B polygonal cells
39. Type A spindle cells Type B polygonal cells
40. Subcapsular hyperplasia (Type B cells) Vehicle male B6B3F1 mouse in a chronic study
41. Cortical Hyperplasia Female SD Dioxin-related study
42. Cortical hyperplasia – focal increased number of basophilic cells
43. Cortical Hypertrophy (Treated Female SD) Cellular enlargement; may be associated with hyperplasia but not in this example.
44. Cortical Hypertrophy (Vehicle male B6C3F1)
45. Medullary Hyperplasia Vehicle female SD
46. Pathology of the Adrenal Gland • Normal histology & physiology • Hyperplasia – Cortex • Subcapsular • Cortex – Medulla • Neoplasia – Cortex • Subcapsular • Cortex – Medulla
47. NTP Historical Control Data Adrenal Tumors (Incidences > 1 %)
48. Subcapsular Adenoma High dose female B6C3F1 Subcapsular hyperplasia also present
49. Well circumscribed nodule of poorly differentiated cells
50. Subcapsular Adenoma A more typical example consisting of mostly Type B cells Treated male B6C3F1
51. Subcapsular Adenoma A more typical example consisting of mostly Type B cells Treated male B6C3F1
52. Subcapsular hyperplasia (Type B cells) Vehicle male B6B3F1 mouse in a chronic study
53. Subcapsular Carcinoma High dose female B6C3F1 N-methylolacrylamide study
54. Consistently of predominantly Type A spindle cells Subcapsular Carcinoma
55. Cortical Adenoma Low dose male B6C3F1
56. Cortical Adenoma Low dose male B6C3F1
57. Cortical Adenoma Low dose F344 male
58. Cortical Carcinoma Treated F344 rat
59. Cortical Carcinoma
60. Benign Pheochromocytoma in a Mouse
61. Epinephrine Chromagranin Catecholamine (tyrosine hydroxylase) Phenylethanolamine-N-methyltransferase
62. Benign Pheochromocytoma Treated male F344 Male F344
63. Pheochromocytoma • Benign pheochromocytoma • Malignant pheochromocytoma – Penetrates capsule or blood vessels – Extreme pleomorphism • Complex pheochromocytoma – Contains neural elements
64. Malignant Pheochromocytoma Low dose male F344 Penetrates capsule
65. Malignant Pheochromocytoma Low dose male F344 Penetrates capsule
66. Malignant Pheochromocytoma Cellular pleomorphism
67. F344 Rat from Chronic Urea Study
68. Complex Pheochromocytoma • Adrenal medullary sympathoblasts can develop into: – Pheochromocytes, neuroblasts, ganglion cells, Schwann cells, neurofibrils • Neural component less than 80% • If neural component is 80% or greater, diagnosed as neural tumor: – Neuroblastoma, ganglioneuroma, paraganglioma, Schwannoma
69. Complex Pheochromocytoma Treated male B6C3F1
70. Complex Pheochromocytoma High dose male F344 in water disinfection byproduct study
71. Neurofibrils Ganglion cells
72. Neuroblastoma Low dose F344 male
73. Neuroblastoma
74. Neuroblastoma 156 Week-old Male B6C3F1 – Lifetime study
75. Ganglioneuroma High dose male F344
76. Pathology of the Adrenal Gland • Normal histology & physiology • Hyperplasia – Cortex • Subcapsular • Cortex – Medulla • Neoplasia – Cortex • Subcapsular • Cortex – Medulla
77. Thank you for your attention