Endocrine System

Adrenal Gland - Accessory Adrenocortical Nodule

Narrative
Comment:
Accessory adrenocortical nodules (Figure 1, Figure 2, Figure 3, Figure 4, Figure 5, and Figure 6) are fairly common in rats and mice. Also known by many other terms (e.g., ectopic adrenal tissue, accessory cortical tissue, hamartoma, accessory adrenal gland, supernumary adrenal, and adrenocortical rest), accessory adrenocortical nodules are minor developmental anomalies arising from partly or completely detached rests of the coelomic epithelial primordia from which the adrenal cortex is derived. They are most frequently located in contact with the capsule at one pole of the adrenal gland (Figure 1, Figure 2, Figure 3, and Figure 4) but can occur completely separated from the adrenal gland in the retroperitoneal fat (Figure 5 and Figure 6), attached to the kidney capsule, or anywhere in the peritoneal cavity. In and of themselves, accessory adrenocortical nodules are almost always innocuous incidental findings without clinical or toxicologic relevance. However, they can develop the same degenerative, hyperplastic, and even neoplastic changes as the adrenal cortex proper.

Most nodules are spherical to ovoid structures surrounded by a usually delicate fibrous capsule and composed of well-differentiated zonae glomerulosa-type and fasciculata-type cells (Figure 1 and Figure 2), sometimes admixed and sometimes arranged in typical layers. Some adrenocortical accessory tissue consists of less densely packed nests of more primitive-appearing cortical cells (Figure 3 and Figure 4). The typical surrounding fibrous capsule distinguishes accessory adrenocortical nodules from focal cortical hyperplasia and from extracapsular protrusions of cortical tissue. Accessory nodules must also be distinguished from cortical adenomas and carcinomas, which exhibit cellular pleomorphism and atypia and loss of cortical layering but are not commonly encapsulated.
Recommendations:
Adrenal gland - Accessory adrenocortical nodule should be diagnosed whenever present, but a severity grade is not necessary. If a nodule is located in the periadrenal fat (separated from the adrenal gland), the tissue should be listed as periadrenal fat. If a nodule is associated with another organ (e.g., kidney), ectopic tissue of that organ is a more appropriate diagnosis (e.g., Kidney - Ectopic tissue, Adrenal gland).
References:

Dunn TB. 1970. Normal and pathologic anatomy of the adrenal gland of the mouse, including neoplasms. J Natl Cancer Inst 44:1323-1389.

Abstract: http://jnci.oxfordjournals.org/content/44/6/1323.abstract

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

McInnes EF. 2011. Wistar and Sprague Dawley rats. In: Background Lesions in Laboratory Animals: A Color Atlas (McInnes EF, ed). Saunders Elsevier, Amsterdam, 16-36.

Abstract: http://www.sciencedirect.com/science/book/9780702035197

Parker GA, Valerio MG. 1983. Accessory adrenocortical tissue, rat. In: Monographs on the Pathology of Laboratory Animals: Endocrine System (Jones TC, Mohr U, Hunt RD, eds). Springer, Berlin, 16-17.

Abstract: http://www.springer.com/medicine/pathology/book/978-3-642-64649-2

National Toxicology Program. 2007. NTP TR-535. Toxicology and Carcinogenesis Studies of 4- Methylimidazole (CAS No. 822-36-6) in F344/N Rats and B6C3F1 Mice (Feed Studies). NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/13651

National Toxicology Program. 2010. NTP TR-560. Toxicology and Carcinogenesis Studies of Androstenedione (CAS No. 63-05-8) in F344/N Rats and B6C3F1 Mice (Gavage Studies). NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/33555

National Toxicology Program. 2013. NTP TR-578. Toxicology and Carcinogenesis Studies of Gingko biloba Extract in F344/N Rats and B6C3F1 Mice (Gavage Studies). NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/37193

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

Sass B. 1983. Accessory adrenocortical tissue, mouse. In: Monographs on the Pathology of Laboratory Animals: Endocrine System (Jones TC, Mohr U, Hunt RD, eds). Springer, Berlin, 12-15.

Abstract: http://www.springer.com/medicine/pathology/book/978-3-642-64649-2

Taylor I. 2011. Mouse. In: Background Lesions in Laboratory Animals: A Color Atlas (McInnes EF, ed). Saunders Elsevier, Amsterdam, 45-72.

Abstract: http://www.sciencedirect.com/science/book/9780702035197
  • Image of accessory adrenocortical nodule in the adrenal gland from a male F344/N rat in a chronic study

    Adrenal gland - Accessory adrenocortical nodule in a male F344/N rat from a chronic study. There is a nodule of adrenal cortical cells on the extracapsular surface (arrow).

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Adrenal gland - Accessory adrenocortical nodule in a male F344/N rat from a chronic study. There is a nodule of adrenal cortical cells on the extracapsular surface (arrow).
Adrenal gland - Accessory adrenocortical nodule in a male F344/N rat from a chronic study. There is a nodule of adrenal cortical cells on the extracapsular surface (arrow).
Adrenal gland - Accessory adrenocortical nodule in a male F344/N rat from a chronic study (higher magnification of Figure 1). The cells of this accessory adrenocortical nodule (asterisk) at the extracapsular surface are well-differentiated zona fasciculata cells and are surrounded by a delicate fibrous capsule (arrow).
Adrenal gland - Accessory adrenocortical nodule in a male F344/N rat from a chronic study (higher magnification of Figure 1). The cells of this accessory adrenocortical nodule (asterisk) at the extracapsular surface are well-differentiated zona fasciculata cells and are surrounded by a delicate fibrous capsule (arrow).
Adrenal gland - Accessory adrenocortical nodule in a male F344/N rat from a chronic study. Accessory cortical tissue within the capsule is composed of nests of cortical cells (arrow).
Adrenal gland - Accessory adrenocortical nodule in a male F344/N rat from a chronic study. Accessory cortical tissue within the capsule is composed of nests of cortical cells (arrow).
Adrenal gland - Accessory adrenocortical nodule in a male F344/N rat from a chronic study (higher magnification of Figure 3). The cortical cells comprising this accessory cortical tissue in the capsule have a more primitive appearance (arrow).
Adrenal gland - Accessory adrenocortical nodule in a male F344/N rat from a chronic study (higher magnification of Figure 3). The cortical cells comprising this accessory cortical tissue in the capsule have a more primitive appearance (arrow).
Periadrenal fat - Accessory adrenocortical nodule in a male B6C3F1/N mouse from a chronic study. An accessory cortical nodule (arrow) is present in the periadrenal (retroperitoneal) fat.
Periadrenal fat - Accessory adrenocortical nodule in a male B6C3F1/N mouse from a chronic study. An accessory cortical nodule (arrow) is present in the periadrenal (retroperitoneal) fat.
Periadrenal fat - Accessory adrenocortical nodule in a male B6C3F1/N mouse from a chronic study (higher magnification of Figure 5). Accessory cortical nodule (arrow) is composed of well-differentiated adrenal cortical cells surrounded by a thin fibrous capsule in the periadrenal (retroperitoneal) fat.
Periadrenal fat - Accessory adrenocortical nodule in a male B6C3F1/N mouse from a chronic study (higher magnification of Figure 5). Accessory cortical nodule (arrow) is composed of well-differentiated adrenal cortical cells surrounded by a thin fibrous capsule in the periadrenal (retroperitoneal) fat.

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