Endocrine System

Adrenal Gland, Cortex - Cellular Atypia

Narrative
Comment:
Atypia of adrenocortical cells (Figure 1, Figure 2, and Figure 3) is an uncommon finding in rats and mice. It is characterized by hypertrophic cortical cells that, in addition to expanded cytoplasmic volume, also have nuclei with pleomorphism, hyperchromasia, irregular shape, and other atypical features. There may be a few cells within a region of cortical hypertrophy that have irregular nuclei, but the diagnosis of cellular atypia in the adrenal cortex is reserved for those lesions in which a large proportion of the cells are atypical. The pathologist must use his or her judgment in deciding whether the number of atypical cells is large enough to warrant a diagnosis of cellular atypia. Atypical cells can also be found in foci of cortical hyperplasia.

Foci of atypical adrenocortical cells must be differentiated from adrenocortical adenomas. Adenomas typically cause compression of adjacent tissue, and there is loss of the normal radial arrangement of the cords; these features are not present in foci of cellular atypia.
Recommendations:
Adrenal gland, Cortex - Cellular atypia should be diagnosed and assigned a severity grade. The diagnosis should be used in cases where a large proportion of the cells in a hypertrophic focus also have nuclei that exhibit features of atypia as described above. In such cases, only the diagnosis of "Cellular atypia" (and not "Hypertrophy") should be recorded. When the number of atypical cells in a focus of hypertrophy does not warrant a diagnosis of atypia (the pathologist must use his or her judgment to determine if this is the case), then hypertrophy should be diagnosed and the few scattered atypical cells described in the narrative. In cases where atypical cells occur in a significant number of cells in an area of cortical hyperplasia, the diagnosis should be "Hyperplasia, Atypical" (see Adrenal Gland - Hyperplasia ). If cellular atypia is seen in both adrenal glands, the modifier "bilateral" should be added to the diagnosis (lesions are assumed to be unilateral unless otherwise indicated).
Related Links:
Adrenal Gland - Hyperplasia
References:

National Toxicology Program. 1992. NTP TR-388. Toxicology and Carcinogenesis Studies of Ethylene Thiourea (CAS No. 96-45-7) in F344/N Rats and B6C3F1 Mice (Feed Studies). NTP, Research Triangle, Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/12227

National Toxicology Program. 1993. NTP TR-404. Toxicology and Carcinogenesis Studies of 5,5-Diphenylhydantoin (Phenytoin) (CAS No. 57-41-0) in F344/N Rats and B6C3F1 Mice (Feed Studies). NTP, Research Triangle, Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/7688

National Toxicology Program. 2001. NTP TR-479. Toxicology and Carcinogenesis Studies of Coconut Oil Acid Diethanolamine Condensate (CAS No. 68603-42-9) in F344/N Rats and B6C3F1 Mice (Dermal Studies). NTP, Research Triangle, Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/9760
  • Image of cellular atypia in the adrenal gland cortex from a female F344/N rat in a chronic study

    Adrenal gland, Cortex - Cellular atypia in a female F344/N rat from a chronic study. There is a focal area in the inner cortex (arrows) with scattered cells with enlarged, pleomorphic, irregular nuclei.

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Adrenal gland, Cortex - Cellular atypia in a female F344/N rat from a chronic study. There is a focal area in the inner cortex (arrows) with scattered cells with enlarged, pleomorphic, irregular nuclei.
Adrenal gland, Cortex - Cellular atypia in a female F344/N rat from a chronic study. There is a focal area in the inner cortex (arrows) with scattered cells with enlarged, pleomorphic, irregular nuclei.
Adrenal gland, Cortex - Cellular atypia in a female F344/N rat from a chronic study (higher magnification of Figure 1). Enlarged cortical cells (arrows) have large, pleomorphic, irregular nuclei.
Adrenal gland, Cortex - Cellular atypia in a female F344/N rat from a chronic study (higher magnification of Figure 1). Enlarged cortical cells (arrows) have large, pleomorphic, irregular nuclei.
Adrenal gland, Cortex - Cellular atypia in a male F344/N rat from a chronic study. There is a focus of enlarged cells with large, pleomorphic nuclei (arrows).
Adrenal gland, Cortex - Cellular atypia in a male F344/N rat from a chronic study. There is a focus of enlarged cells with large, pleomorphic nuclei (arrows).

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