Endocrine System

Adrenal Gland, Cortex - Degeneration, Cystic

Narrative
Comment:
Cystic degeneration of the adrenal cortex (Figure 1, Figure 2, Figure 3, Figure 4, and Figure 5) occurs in many strains of rats but has apparently not been reported in mice. Incidences vary with rat strain, with some strains (e.g., Sprague-Dawley, Wistar) exhibiting much higher incidences than others (e.g., F344). In all rat strains, cystic degeneration is much more common in females than in males. It is usually a spontaneous, age-related change, though treatment-related increased incidences have been reported after administration of certain chemicals.

Early stages of cystic degeneration are characterized by small, noncompressive foci of widened cortical sinusoids and dilated blood vessels in the zona fasciculata; cortical cells in the intervening cords can be vacuolated or slightly flattened. As the lesion progresses, affected areas enlarge and can compress adjacent parenchyma (Figure 3 and Figure 4). The sinusoidal and vascular ectasia progressively becomes more extensive, resulting in large, often confluent, cyst-like cavitations (Figure 1, Figure 2, Figure 3, Figure 4, and Figure 5) that are filled with proteinaceous fluid, red blood cells, and/or fibrinous thrombi but lack the epithelial lining characteristic of true cysts. Clusters of vacuolated or swollen cortical cells can be scattered among the dilated spaces. Areas of cystic degeneration can also be features of large cortical hyperplastic or hypertrophic foci or of cortical neoplasms; however, in cystic degeneration the number of cells is decreased compared with normal cortex.
Recommendations:
Cystic degeneration of the adrenal cortex should be diagnosed and assigned a severity grade. Areas of cystic degeneration occurring in foci of hyperplasia or hypertrophy or in cortical neoplasms should not be diagnosed separately but should be described in the pathology narrative. If cystic degeneration is seen in both adrenal glands, the modifier "bilateral" should be added to the diagnosis (lesions are assumed to be unilateral unless otherwise indicated).
References:

Brix AE, Nyska A, Haseman JK, Sells DM, Jokinen MO, Walker NJ. 2005. Incidences of selected lesions in control female Harlan Sprague-Dawley rats from two-year studies performed by the National Toxicology Program. Toxicol Pathol 33:477-483.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/16036865

Dohm G, Hohbach C, Mäusle E, Scherr O, Ueberberg H. 1981. Peliosis of the female adrenal cortex of aging rats. Virchows Arch B (Cell Pathol) 36:195-206.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/6116334

Elmore SA, Berridge BR, Boyle MC, Cora MC, Hoenerhoff MJ, Kooistra L, Laast VA, Morrison JP, Rao D, Rinke M, Yoshizawa K. 2013. Proceedings of the 2012 National Toxicology Program Satellite Symposium. Toxicol Pathol 41:151-180.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/23262640

Frith CH, Botts S, Jokinen MP, Eighmy JJ, Hailey JR, Morgan SJ, Chandra M. 2000. Non-proliferative lesions of the endocrine system in rats, E-1. In: Guides for Toxicologic Pathology. STP/ARP/AFIP, Washington, DC.

Full Text: https://www.toxpath.org/docs/SSNDC/EndocrineNonprolifRat.pdf

Hamlin MH, Banas DA. 1990. Adrenal gland. In: Pathology of the Fischer Rat: Reference and Atlas (Boorman GA, Eustis SL, Elwell MR, Montgomery CA, MacKenzie WF, eds). Academic Press, San Diego, 501-518.

Abstract: https://www.ncbi.nlm.nih.gov/nlmcatalog/9002563

Imazawa T, Nishikawa A, Todate A, Furukawa F, Onodera H, Mitsumori K, Hirose M, Hayashi Y. 2000. Dual effects of prolonged ACTH stimulation on 4-hydroxyaminoquinoline 1-oxide-induced adrenocortical lesions in rats. Toxicol Pathol 28:535-539.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/10930039

McMartin DL, Sahota PS, Gunson DE, Han Hsu H, Spaet RH. 1992. Neoplasms and related proliferative lesions in control Sprague-Dawley rats from carcinogenicity studies. Historical data and diagnostic considerations. Toxicol Pathol 20:212-225.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/1475582

National Toxicology Program. 2006. NTP TR-525. Toxicology and Carcinogenesis Studies of 2,3,4,7,8-Pentachlorodibenzofuran (PeCDF) (CAS No. 57117-31-4) in Female Harlan Sprague-Dawley Rats (Gavage Studies). NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/9304

National Toxicology Program. 2010. NTP TR-559. Toxicology and Carcinogenesis Studies of 2,3',4,4',5-Pentachlorobiphenyl (PCB 118) (CAS No. 31508-00-6) in Female Harlan Sprague-Dawley Rats (Gavage Studies). NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/33539

Nyska A, Maronpot RR. 1990. Adrenal gland. In: Pathology of the Mouse: Reference and Atlas (Maronpot RR, Boorman GA, Gaul BW, eds). Cache River Press, Vienna, IL, 509-536.

Abstract: http://www.cacheriverpress.com/books/pathmouse.htm

Tucker MJ. 1997. Diseases of the Wistar rat. In: The Endocrine System. Taylor & Francis, London: 183-215.

Abstract: http://www.crcpress.com/product/isbn/9780748405213
  • Image of degeneration, cystic in the adrenal gland cortex from a female Sprague-Dawley rat in a chronic study

    Adrenal gland, Cortex - Degeneration, Cystic in a female Sprague-Dawley rat from a chronic study (higher magnification of Figure 1). Cystic degeneration is characterized by dilated spaces filled with proteinaceous fluid and/or blood and scattered vacuolated cortical cells.

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Adrenal gland, Cortex - Degeneration, Cystic in a female Sprague-Dawley rat from a chronic study. The cortex is distended by dilated spaces filled with proteinaceous fluid and/or blood (CD).
Adrenal gland, Cortex - Degeneration, Cystic in a female Sprague-Dawley rat from a chronic study. The cortex is distended by dilated spaces filled with proteinaceous fluid and/or blood (CD).
Adrenal gland, Cortex - Degeneration, Cystic in a female Sprague-Dawley rat from a chronic study (higher magnification of Figure 1). Cystic degeneration is characterized by dilated spaces filled with proteinaceous fluid and/or blood and scattered vacuolated cortical cells.
Adrenal gland, Cortex - Degeneration, Cystic in a female Sprague-Dawley rat from a chronic study (higher magnification of Figure 1). Cystic degeneration is characterized by dilated spaces filled with proteinaceous fluid and/or blood and scattered vacuolated cortical cells.
Adrenal gland, Cortex - Degeneration, Cystic in a female Sprague-Dawley rat from a chronic study (higher magnification of Figure 1). Cavitated spaces (C) delineated by attenuated cortical cells (arrow) are filled with proteinaceous fluid.
Adrenal gland, Cortex - Degeneration, Cystic in a female Sprague-Dawley rat from a chronic study (higher magnification of Figure 1). Cavitated spaces (C) delineated by attenuated cortical cells (arrow) are filled with proteinaceous fluid.
Adrenal gland, Cortex - Degeneration, Cystic in a female Sprague-Dawley rat from a chronic study. Multiple irregular cavitations (asterisk) formed by loss of cortical cells expand and distort the cortex (C) and compress the adjacent medulla (M).
Adrenal gland, Cortex - Degeneration, Cystic in a female Sprague-Dawley rat from a chronic study. Multiple irregular cavitations (asterisk) formed by loss of cortical cells expand and distort the cortex (C) and compress the adjacent medulla (M).
Adrenal gland, Cortex - Degeneration, Cystic in a female Sprague-Dawley rat from a chronic study (higher magnification of Figure 4). Multiple irregular cavitations (asterisk) formed by loss of cortical cells contain proteinaceous fluid.
Adrenal gland, Cortex - Degeneration, Cystic in a female Sprague-Dawley rat from a chronic study (higher magnification of Figure 4). Multiple irregular cavitations (asterisk) formed by loss of cortical cells contain proteinaceous fluid.

Authors

Mark J. Hoenerhoff, DVM, PhD, DACVP
Associate Professor
Veterinary Pathologist, In Vivo Animal Core
Unit for Laboratory Animal Medicine
University of Michigan
Ann Arbor, MI

Georgette D. Hill, D.V.M., Ph.D.
Toxicologic Pathologist/Assistant Pathology Program Manager
Comparative Molecular Pathology Division
Integrated Laboratory Systems, Inc.
Research Triangle Park, NC

Margarita M. Gruebbel, DVM, PhD, DACVP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC

Reviewers

Thomas J. Rosol, DVM, PhD, DACVP
Professor of Veterinary Biosciences
Senior Advisor, Life Sciences, Technology Commercialization and Knowledge Transfer
The Ohio State University
Columbus, OH

Gordon Flake, MD
Staff Scientist
NTP Pathologist
Cellular and Molecular Pathology Branch
National Institute of Environmental Health Sciences
Research Triangle Park, NC