Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018;31(3 Suppl):1S-95S.
doi: 10.1293/tox.31.1S. Epub 2018 Jul 28.

Nonproliferative and Proliferative Lesions of the Rat and Mouse Endocrine System

Annamaria Brändli-Baiocco  1 , Emmanuelle Balme  2 , Marc Bruder  3 , Sundeep Chandra  4 , Juergen Hellmann  5 , Mark J Hoenerhoff  6 , Takahito Kambara  7 , Christian Landes  1 , Barbara Lenz  1 , Mark Mense  8 , Susanne Rittinghausen  9 , Hiroshi Satoh  10 , Frédéric Schorsch  11 , Frank Seeliger  12 , Takuji Tanaka  13 , Minoru Tsuchitani  14 , Zbigniew Wojcinski  15 , Thomas J Rosol  16
Affiliations
Review

Nonproliferative and Proliferative Lesions of the Rat and Mouse Endocrine System

Annamaria Brändli-Baiocco et al. J Toxicol Pathol. 2018.

Abstract

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is a joint initiative among the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the endocrine organs (pituitary gland, pineal gland, thyroid gland, parathyroid glands, adrenal glands and pancreatic islets) of laboratory rats and mice, with color photomicrographs illustrating examples of the lesions. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. A widely accepted and utilized international harmonization of nomenclature for endocrine lesions in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.

Keywords: C cells; adrenal; chief cells; cortical cells; diagnostic pathology; follicular cells; hypophysis; islets; islets of Langerhans; medullary cells; nomenclature; pancreas; parathyroid; pineal; pinealocytes; pituicytes; pituitary; thyroid.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Rat pituitary gland. Aberrant craniopharyngeal structures between the pars intermedia and pars nervosa and within the pars intermedia (arrow). Adjacent cyst of Rathke’s cleft (C).
Figure 2.
Figure 2.
Rat pituitary gland. Aberrant craniopharyngeal structures with salivary gland-like differentiation and associated cyst of Rathke’s cleft (left).
Figure 3.
Figure 3.
Rat pituitary gland. Angiectasis of capillaries in the pars distalis.
Figure 4.
Figure 4.
Rat pituitary gland. Atrophy of the pars distalis (top and right) with fibrosis and hemosiderophages. The pars intermedia and nervosa (lower and left) are normal.
Figure 5.
Figure 5.
Rat pituitary gland. Atrophy of the pars distalis (upper right) with fibrosis, hemosiderophages, and mild angiectasis. The pars intermedia (lower left) is normal.
Figure 6.
Figure 6.
Rat pituitary gland. Cyst in the pars distalis.
Figure 7.
Figure 7.
Rat pituitary gland. Cyst in the pars distalis lined by endocrine and folliculostellate cells.
Figure 8.
Figure 8.
Rat pituitary gland. Cyst of Rathke’s pouch, multiloculated.
Figure 9.
Figure 9.
Rat pituitary gland. Cyst of Rathke’s pouch. The lining epithelial cells are cuboidal or flattened. The cuboidal epithelial cells have luminal cilia.
Figure 10.
Figure 10.
Rat pituitary gland. Gliosis, pars nervosa. Increased numbers of glial cells in the pars nervosa. The pars intermedia is on the lower right.
Figure 11.
Figure 11.
>Rat pituitary gland. Hemorrhage into Rathke’s pouch. Angiectasis in the pars distalis (lower left and right). Note the normal follicle present in the pars intermedia (upper left) formed by protein secretion from folliculostellate cells.
Figure 12.
Figure 12.
Rat pituitary gland. Hypertrophy of chromophobic endocrine cells in the pars distalis.
Figure 13.
Figure 13.
Mouse pituitary gland. Hypertrophy of TSH cells with few cytoplasmic vacuoles in the pars distalis. Immunohistochemistry for TSH.
Figure 14.
Figure 14.
Mouse pituitary gland. Pseudocyst formation in the pars distalis.
Figure 15.
Figure 15.
Rat pituitary gland. Vacuolation of hypertrophied endocrine cells in the pars distalis.
Figure 16.
Figure 16.
Rat pituitary gland. Hyperplasia, focal, pars distalis.
Figure 17.
Figure 17.
Rat pituitary gland. Hyperplasia, focal, pars distalis.
Figure 18.
Figure 18.
Mouse pituitary gland. Hyperplasia, diffuse, pars intermedia.
Figure 19.
Figure 19.
Rat pituitary gland. Hyperplasia, focal, pars intermedia.
Figure 20.
Figure 20.
Rat pituitary gland. Adenoma, pars distalis.
Figure 21.
Figure 21.
Rat pituitary gland. Adenoma, pars distalis.
Figure 22.
Figure 22.
Rat pituitary gland. Adenoma, pars intermedia (arrows).
Figure 23.
Figure 23.
Rat pituitary gland. Adenoma, pars intermedia (arrows). The pars intermedia and adenoma stain positive using ACTH immunohistochemistry (brown cytoplasmic staining). The adenoma is less positively stained.
Figure 24.
Figure 24.
Rat pituitary gland. Adenoma, pars intermedia. The adenoma cells are enlarged.
Figure 25.
Figure 25.
Rat pituitary gland. Ganglioneuroma, pars distalis with hemosiderin pigment and a cyst of Rathke’s pouch.
Figure 26.
Figure 26.
Rat pituitary gland. Ganglioneuroma, pars distalis. Note the large ganglion cells.
Figure 27.
Figure 27.
Rat pituitary gland. Pituicytoma, pars nervosa.
Figure 28.
Figure 28.
Rat pituitary gland. Pituicytoma, pars nervosa.
Figure 29.
Figure 29.
Rat pituitary gland. Pituicytoma, pars nervosa. Positive immunohistochemical staining for glial fibrillary acidic protein (GFAP), brown intracytoplasmic staining.
Figure 30.
Figure 30.
Rat pituitary gland. Carcinoma, pars distalis with invasion into the sphenoid bone.
Figure 31.
Figure 31.
Rat pituitary gland. Carcinoma, pars distalis with invasion into the neurophil of the brain.
Figure 32.
Figure 32.
Rat pituitary gland. Craniopharyngioma with compression of the pars distalis.
Figure 33.
Figure 33.
Rat pineal gland. Fibrosis.
Figure 34.
Figure 34.
Rat pineal gland. Infiltrate, inflammatory cell.
Figure 35.
Figure 35.
Rat pineal gland. Mineralization.
Figure 36.
Figure 36.
Rat pineal gland. Striated muscle fibers.
Figure 37.
Figure 37.
Rat pineal gland. Striated muscle fibers. Positive immunohistochemical staining for desmin (brown cytoplasmic staining).
Figure 38.
Figure 38.
Rat pineal gland. Vacuolation.
Figure 39.
Figure 39.
Rat pineal gland. Pinealoma, benign.
Figure 40.
Figure 40.
Rat pineal gland. Pinealoma, benign.
Figure 41.
Figure 41.
Rat pineal gland. Pinealoma, benign.
Figure 42.
Figure 42.
Rat pineal gland. Pinealoma, benign. Positive immunohistochemical staining for synaptophysin.
Figure 43.
Figure 43.
Rat pineal gland. Pinealoma, benign. Positive immunohistochemical staining for neuron-specific enolase.
Figure 44.
Figure 44.
Rat pineal gland. Pinealoma, malignant.
Figure 45.
Figure 45.
Rat pineal gland. Pinealoma, malignant.
Figure 46.
Figure 46.
Rat pineal gland. Pinealoma, malignant with pseudorosettes.
Figure 47.
Figure 47.
Mouse thyroid gland. Amyloid.
Figure 48.
Figure 48.
Rat thyroid gland. Colloid alteration.
Figure 49.
Figure 49.
Mouse thyroid gland. Cystic follicle.
Figure 55.
Figure 55.
Rat thyroid gland. Persistent thyroglossal duct.
Figure 50.
Figure 50.
Rat thyroid gland. Follicular cell hypertrophy.
Figure 51.
Figure 51.
Rat thyroid gland. Follicular dilatation, diffuse.
Figure 52.
Figure 52.
Mouse thyroid gland. Infiltrate, inflammatory cell.
Figure 53.
Figure 53.
Rat thyroid gland. Inflammation, mononuclear.
Figure 54.
Figure 54.
Rat thyroid gland. Mineralization of the colloid.
Figure 56.
Figure 56.
Rat thyroid gland. Pigment in the thyroid follicular cells and colloid.
Figure 57.
Figure 57.
Rat thyroid gland. Thyroid dysplasia and ectopic thymus.
Figure 58.
Figure 58.
Rat thyroid gland. Thyroid dysplasia.
Figure 59.
Figure 59.
Rat thyroid gland. Ultimobranchial cyst.
Figure 60.
Figure 60.
Rat thyroid gland. Hyperplasia, follicular cell, focal with papillary projections into the colloid.
Figure 61.
Figure 61.
Mouse thyroid gland. Hyperplasia, follicular cell, focal with piling up of follicular cells.
Figure 62.
Figure 62.
Mouse thyroid glands. Hyperplasia, follicular cell, diffuse.
Figure 63.
Figure 63.
Mouse thyroid gland. Hyperplasia, follicular cell, diffuse.
Figure 64.
Figure 64.
Rat thyroid gland. Adenoma, follicular cell, papillary and cystic.
Figure 65.
Figure 65.
Rat thyroid gland. Adenoma, follicular cell, papillary and cystic.
Figure 66.
Figure 66.
Mouse thyroid gland. Adenoma, follicular cell, papillary.
Figure 67.
Figure 67.
Mouse thyroid gland. Adenoma, follicular cell, cystic.
Figure 68.
Figure 68.
Rat thyroid gland. Carcinoma, follicular cell.
Figure 69.
Figure 69.
Rat thyroid gland. Carcinoma, follicular cell with cellular atypia and tissue invasion.
Figure 70.
Figure 70.
Rat thyroid gland. Carcinoma, follicular cell with invasion into a blood vessel.
Figure 71.
Figure 71.
Rat thyroid gland. C-cell hyperplasia, focal (adjacent to the parathyroid gland that is at the top of the image).
Figure 72.
Figure 72.
Rat thyroid gland. C-cell hyperplasia, diffuse.
Figure 73.
Figure 73.
Rat thyroid gland. C-cell hyperplasia, diffuse.
Figure 74.
Figure 74.
Rat thyroid gland. C-cell hyperplasia, focal and diffuse, calcitonin immunohistochemistry.
Figure 75.
Figure 75.
Rat thyroid gland. C-cell adenoma.
Figure 76.
Figure 76.
Rat thyroid gland. C-cell adenoma.
Figure 77.
Figure 77.
Rat thyroid gland. C-cell adenoma, calcitonin immunohistochemistry.
Figure 78.
Figure 78.
Rat thyroid gland. C-cell carcinoma.
Figure 79.
Figure 79.
Rat thyroid gland. C-cell carcinoma, capsular invasion.
Figure 80.
Figure 80.
Rat lung. C-cell carcinoma, metastasis.
Figure 81.
Figure 81.
Mouse parathyroid gland. Angiectasis.
Figure 82.
Figure 82.
Mouse parathyroid gland. Cyst.
Figure 83.
Figure 83.
Rat parathyroid gland. Fibrosis.
Figure 84.
Figure 84.
Rat parathyroid gland. Multinucleate giant cell (arrow).
Figure 85.
Figure 85.
Rat parathyroid gland. Hyperplasia, diffuse.
Figure 86.
Figure 86.
Rat parathyroid gland. Hyperplasia, multifocal.
Figure 87.
Figure 87.
Rat parathyroid gland. Hyperplasia, focal, water clear cell type.
Figure 88.
Figure 88.
Rat parathyroid gland. Adenoma.
Figure 89.
Figure 89.
Rat parathyroid gland. Carcinoma.
Figure 90.
Figure 90.
Mouse adrenal gland. Amyloidosis at the corticomedullary junction.
Figure 91.
Figure 91.
Rat adrenal cortex. Angiectasis.
Figure 92.
Figure 92.
Rat adrenal cortex. Atrophy with pigment in the zona reticularis.
Figure 93.
Figure 93.
Mouse adrenal cortex. Cyst lined by simple cuboidal to columnar epithelium.
Figure 94.
Figure 94.
Rat adrenal cortex. Degeneration, cystic.
Figure 95.
Figure 95.
Mouse adrenal gland. Ectopic tissue, containing only cortex at top of the image.
Figure 96.
Figure 96.
Rat adrenal gland. Fibrosis in the zona reticularis with pigment.
Figure 97.
Figure 97.
Rat adrenal cortex. Extramedullary hematopoiesis.
Figure 98.
Figure 98.
Rat adrenal cortex. Hemorrhage.
Figure 99.
Figure 99.
Rat adrenal cortex. Normal control (compare to Figure 100 for hypertrophy, diffuse).
Figure 100.
Figure 100.
Rat adrenal cortex. Hypertrophy, cortical, diffuse (compare to Figure 99, control).
Figure 101.
Figure 101.
Rat adrenal cortex. Hypertrophy, cortical, focal.
Figure 102.
Figure 102.
Rat adrenal cortex. Infiltrate, mononuclear.
Figure 103.
Figure 103.
Mouse adrenal cortex. Inflammation, mixed.
Figure 104.
Figure 104.
Mouse adrenal cortex. Inflammation, suppurative.
Figure 105.
Figure 105.
Mouse adrenal cortex. Inflammation, suppurative with secondary peritonitis.
Figure 106.
Figure 106.
Rat adrenal cortex. Mineralization.
Figure 107.
Figure 107.
Mouse adrenal cortex. Necrosis, zona fasiculata and reticularis.
Figure 108.
Figure 108.
Rat adrenal cortex. Necrosis, zona fasiculata.
Figure 109.
Figure 109.
Rat adrenal cortex. Osseous metaplasia.
Figure 110.
Figure 110.
Mouse adrenal gland. Pigmentation, X-zone.
Figure 111.
Figure 111.
Mouse adrenal cortex. Thrombosis.
Figure 112.
Figure 112.
Rat adrenal cortex. Vacuolation, cortical, increased, diffuse.
Figure 113.
Figure 113.
Rat adrenal cortex. Vacuolation, cortical, increased, focal.
Figure 114.
Figure 114.
Rat adrenal cortex. Vacuolation, cortical, decreased, focal.
Figure 115.
Figure 115.
Mouse adrenal cortex. X-zone persistence.
Figure 116.
Figure 116.
Rat adrenal cortex. Hyperplasia, cortical, focal, large cells.
Figure 117.
Figure 117.
Rat adrenal cortex. Hyperplasia, cortical, focal, small cells.
Figure 118.
Figure 118.
Rat adrenal cortex. Adenoma, cortical.
Figure 119.
Figure 119.
Rat adrenal cortex. Adenoma, cortical.
Figure 120.
Figure 120.
Rat adrenal cortex. Carcinoma, cortical with invasion into surrounding adipose tissue.
Figure 121.
Figure 121.
Rat adrenal cortex. Carcinoma, cortical.
Figure 122.
Figure 122.
Rat lung. Adrenal carcinoma, cortical, intravascular metastasis.
Figure 123.
Figure 123.
Mouse adrenal cortex. Hyperplasia, subcapsular cell.
Figure 124.
Figure 124.
Mouse adrenal cortex. Adenoma, subcapsular cell, type B.
Figure 125.
Figure 125.
Mouse adrenal cortex. Adenoma, subcapsular cell, type B.
Figure 126.
Figure 126.
Mouse adrenal cortex. Adenoma, subcapsular cell, type A.
Figure 127.
Figure 127.
Mouse adrenal cortex. Carcinoma, subcapsular cell, mixed type A & B.
Figure 128.
Figure 128.
Rat adrenal medulla. Hyperplasia, medullary, focal.
Figure 129.
Figure 129.
Rat adrenal medulla. Hyperplasia, medullary, focal.
Figure 130.
Figure 130.
Rat adrenal medulla. Hyperplasia, medullary, focal.
Figure 131.
Figure 131.
Rat adrenal medulla. Pheochromocytoma, benign.
Figure 132.
Figure 132.
Rat adrenal medulla. Pheochromocytoma, benign.
Figure 133.
Figure 133.
Rat adrenal medulla. Pheochromocytoma, malignant with extracapsular invasion.
Figure 134.
Figure 134.
Rat adrenal medulla. Pheochromocytoma, malignant.
Figure 135.
Figure 135.
Rat adrenal medulla. Pheochromocytoma, malignant with immunohistochemistry for synaptophysin.
Figure 136.
Figure 136.
Rat adrenal medulla. Pheochromocytoma, complex, benign.
Figure 137.
Figure 137.
Rat adrenal medulla. Ganglioneuroma, benign.
Figure 138.
Figure 138.
Rat adrenal medulla. Neuroblastoma.
Figure 139.
Figure 139.
Rat adrenal medulla. Neuroblastoma with pseudorosettes.
Figure 140.
Figure 140.
Rat adrenal cortex. Myelolipoma.
Figure 141.
Figure 141.
Mouse endocrine pancreas. Amyloid, islet.
Figure 142.
Figure 142.
Rat endocrine pancreas. Angiectasis, islet.
Figure 143.
Figure 143.
Rat endocrine pancreas. Atrophy, islet, β cells. The atrophic β cells in the central region of the islet have eosinophilic cytoplasm and the islets are irregular in shape and shrunken. Apoptosis is present in the surrounding exocrine pancreas.
Figure 144.
Figure 144.
Rat endocrine pancreas. Atrophy, islet, α cells. The atrophic α cells at the islet periphery have a reduced amount of cytoplasm and nuclear condensation.
Figure 145.
Figure 145.
Rat endocrine pancreas. Fibrosis, islet, Sirius red stain.
Figure 146.
Figure 146.
Rat endocrine pancreas. Inflammation, islet, mononuclear with fibrosis and pigment.
Figure 147.
Figure 147.
Rat endocrine pancreas. Metaplasia, hepatocyte.
Figure 148.
Figure 148.
Rat endocrine pancreas. Necrosis, islet.
Figure 149.
Figure 149.
Rat endocrine pancreas. Pigment, islet.
Figure 150.
Figure 150.
Rat endocrine pancreas. Vacuolation, islet.
Figure 151.
Figure 151.
Rat endocrine pancreas. Hyperplasia, islet.
Figure 152.
Figure 152.
Rat endocrine pancreas. Adenoma, islet.
Figure 153.
Figure 153.
Rat endocrine pancreas. Adenoma, islet with a fibrous capsule.
Figure 154.
Figure 154.
Rat endocrine pancreas. Adenoma, islet-acinar.
Figure 155.
Figure 155.
Rat endocrine pancreas. Adenoma, islet-acinar.
Figure 156.
Figure 156.
Rat endocrine pancreas. Carcinoma, islet.
Figure 157.
Figure 157.
Rat endocrine pancreas. Carcinoma, islet.
See this image and copyright information in PMC

References

    1. Abe M, Hayashi S, Usuda K, Hagio S, Furukawa S, and Nakae D. Carcinogen-induced thyroid proliferative lesions in Wistar Hannover GALAS rats with thyroid dysplasia. J Toxicol Pathol. 25: 11–17. 2012. - PMC - PubMed
    1. Ackermann MR. Cellular and tissue responses to injury. In: Pathologic Basis of Veterinary Disease. Zachary, JF and McGavin, MD (eds). 5th ed. Elsevier, St. Louis, MO. pp. 51–57, 2012.
    1. Adeghate E, Hameed RS, Ponery AS, Tariq S, Sheen RS, Shaffiullah M, and Donáth T. Streptozotocin causes pancreatic beta cell failure via early and sustained biochemical and cellular alterations. Exp Clin Endocrinol Diabetes. 118: 699–707. 2010. - PubMed
    1. Aguzzi A, Wagner EF, Williams RL, and Courtneidge SA. Sympathetic hyperplasia and neuroblastomas in transgenic mice expressing polyoma middle T antigen. New Biol. 2: 533–543. 1990. - PubMed
    1. Aigelsreiter A, Janig E, Stumptner C, Fuchsbichler A, Zatloukal K, and Denk H. How a cell deals with abnormal proteins. Pathogenetic mechanisms in protein aggregation diseases. Pathobiology. 74: 145–158. 2007. - PubMed

LinkOut - more resources