Integumentary System

Mammary Gland - Hyperplasia, Atypical

Narrative
Comment:
Atypical hyperplasia is sometimes observed (Figure 1 and Figure 2). This finding can occur in ducts, ductules, alveoli, or even within areas of lobular hyperplasia. It is characterized by lining cells arranged in multiple layers, infoldings, solid nests, or even papillary formations. The affected cells are pleomorphic and often enlarged, with features such as large hyperchromatic nuclei, increased numbers of mitotic figures, and increased cytoplasmic eosinophilia or basophilia. The cells with increased cytoplasmic eosinophilia often contain vacuoles that are suggestive of secretory cells, while the cells with the more basophilic cytoplasm most often do not have vacuoles and are suggestive of ductular epithelium. The alveoli may be normal in shape, or they may be irregular and enlarged. In contrast, proliferating cells of non-atypical hyperplasia lack the cellular atypia, architectural distortion, and other cytological abnormalities seen in atypical hyperplasia. Studies of chemically induced mammary cancer suggest a possible link between atypical ductular hyperplasia and adenocarcinoma (Harvell, et al.).
Recommendations:
Atypical hyperplasia of the mammary gland should be diagnosed and assigned a severity grade whenever present. A site modifier should be included in the diagnosis to indicate the location of the lesion (e.g., ducts or alveoli).
References:

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Abstract: http://www.ncbi.nlm.nih.gov/pubmed/18837892

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Full Text: http://tpx.sagepub.com/content/12/1/26.full.pdf

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Abstract: http://www.sciencedirect.com/science/article/pii/0041008X79900292

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Harvell DME, Strecker TE, Tochacek M, Xie B, Pennington KL, McComb RD, Roy SK, Shull JD. 2000. Rat strain-specific actions of 17β-estradiol in the mammary gland: correlation between estrogen-induced lobuloalveolar hyperplasia and susceptibility to estrogen-induced mammary cancers. Proc Natl Acad Sci U S A 97(6):2779-2784.

Abstract: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC16006

Latendresse JR, Bucci TJ, Olson G, Mellick P, Weis CC, Thorn B, Newbold RR, Delclos KB. 2009. Genistein and ethinyl estradiol dietary exposure in multigenerational and chronic studies induce similar proliferative lesions in mammary gland of male Sprague-Dawley rats. Reprod Toxicol 28(3):342-53.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/19383540

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Abstract: http://www.ncbi.nlm.nih.gov/pubmed/11149571

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Schedin P, Mitrenga T, Kaeck M. 2000. Estrous cycle regulation of mammary epithelial cell proliferation, differentiation, and death in the Sprague-Dawley rat: a model for investigating the role of estrous cycling in mammary carcinogenesis. J Mammary Gland Biol Neoplasia 5(2):211-25.

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Van Zwieten MJ, HogenEsch H, Majka JA, Boorman GA. Nonneoplastic and neoplastic lesions of the mammary gland. In: Mohr U, Dungworth DL, Capen CC (eds.). 1994. Pathobiology of the aging rat, Vol. 2. International Life Sciences Press pp. 459-474.

Harvell DME, Strecker TE, Tochacek M, Xie B, Pennington KL, McComb RD, Roy SK, Shull JD. 2000. Rat strain-specific actions of 17β-estradiol in the mammary gland: correlation between estrogen-induced lobuloalveolar hyperplasia and susceptibility to estrogen-induced mammary cancers. Proc Natl Acad Sci U S A 97(6):2779-2784.

Abstract: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC16006
  • Image of atypical hyperplasia an a female F344/N rat from a chronic study.
    Mammary gland, Alveolus - Atypical Hyperplasia, in a female F344/N rat from a chronic study. There is a focal area of Atypical Hyperplasia (arrow) in the mammary gland.
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Mammary gland, Alveolus - Atypical Hyperplasia, in a female F344/N rat from a chronic study. There is a focal area of Atypical Hyperplasia (arrow) in the mammary gland.
Mammary gland, Alveolus - Atypical Hyperplasia, in a female F344/N rat from a chronic study. There is a focal area of Atypical Hyperplasia (arrow) in the mammary gland.
Mammary gland, Alveolus - Atypical Hyperplasia, in a female F344/N rat from a chronic study (higher magnification of Figure 1). A focal area of Atypical Hyperplasia characterized by pleomorphic lining cells arranged in multiple layers, infoldings, and solid nests in the mammary gland.
Mammary gland, Alveolus - Atypical Hyperplasia, in a female F344/N rat from a chronic study (higher magnification of Figure 1). A focal area of Atypical Hyperplasia characterized by pleomorphic lining cells arranged in multiple layers, infoldings, and solid nests in the mammary gland.

Authors

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

Priyanka Thakur, BVSc, MVSc, PhD, DACVP
Pathologist
Inotiv
Research Triangle Park, NC

Suzanne Fenton, MS, PhD
Director of the Center for Human Health and Environment (CHHE)
Professor Department of Biological Sciences
North Carolina State University
Raleigh, NC

Gabrielle Willson, BVMS, Dip RC Path, FRC Path, MRCVS
Senior Pathologist, Retired
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC

Reviewers

John Latendresse
BSc, DVM, PhD, DACVP
Senior Staff Pathologist and Chief Scientist
Toxicological Pathology Associates, National Center for Toxicological Research
Pine Bluff, Arkansas

Mark Cesta, DVM, PhD, DACVP, FIATP
Staff Scientist/Head, Pathology Evaluation and Peer Review Group
Division of Translational Toxicology, National Institute of Environmental Health Sciences
Research Triangle Park, NC