Reproductive System, Male

Prostate, Epithelium - Hyperplasia

Narrative
Comment:
Hyperplasia is characterized by an increased number of epithelial acinar lining cells that typically project into the acinar lumen. Hyperplasia typically affects one to three contiguous acini, and the lining cells may almost completely fill the acinar lumen but do not compress contiguous acini. The hyperplastic cells range from cuboidal to tall columnar and in the rat usually have a granular eosinophilic cytoplasm. There may be a multilocular appearance when there are multiple isolated areas of secretion (Figure 3image opens in a pop-up window and Figure 4image opens in a pop-up window). As the hyperplastic cells pile up, some undergo degeneration and necrosis or apoptosis (arrow, Figure 2image opens in a pop-up window). Subcutaneous administration of the α-androgenic agonist phenylephrine in rats induces prostatic hyperplasia characterized by piling up of epithelial cells, with papillary and cribriform patterns and budding out. Spontaneous age-dependent overgrowth of cells, consistent with hyperplasia, in the dorsal and ventral lobes of prostate in old brown Norway rats has been reported. Prostatic hyperplasia is seen in aging animals and can involve any lobe. Distinction from prostatic adenoma is based largely on compression of contiguous acini by an expanding and relatively discrete epithelial proliferation filling acini. By way of contrast, the prostatic hyperplasia seen in the TRAMP mouse consists of piling up of hyperbasophilic cells (arrows, Figure 5image opens in a pop-up window). In the TRAMP mouse these are considered prostatic intraepithelial neoplasia lesions by some investigators.
Recommendations:
The distribution of hyperplasia should be recorded, along with the severity of this lesion. The affected lobe(s) should be identified if possible and indicated in the tissue identification (e.g., prostate, ventral lobe, epithelium hyperplasia, mild). If paired lobes are affected, the diagnosis should be qualified as bilateral and the severity score determined by the more severely affected lobe. Any potentially treatment-related increase in hyperplasia should be documented in the pathology narrative and correlated with related changes in other reproductive and endocrine tissues.
References:

Banerjee PP, Banerjee S, Lai JM, Strandberg JD, Zirkin BR, Brown TR. 1998. Age-dependent and lobe-specific spontaneous hyperplasia in the brown Norway rat prostate. Biol Reprod 59:1163-1170.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/9780323

Boorman GA, Elwell MR, Mitsumori K. 1990. Male accessory sex glands, penis, and scrotum. In: Pathology of the Fischer Rat: Reference and Atlas (Boorman GA, Eustis SL, Elwell MR, Montgomery CA, MacKenzie WF, eds). Academic Press, San Diego, 419-428.

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

Bosland MC. 1992. Lesions in the male accessory glands and penis. In: Pathobiology of the Aging Rat, Vol 1 (Mohr U, Dungworth DL, Capen CC, eds). ILSI Press, Washington, DC, 443-467.

Abstract: http://catalog.hathitrust.org/Record/008994685

Creasy D, Bube A, de Rijk E, Kandori H, Kuwahara M, Masson R, Nolte T, Reams R, Regan K, Rehm S, Rogerson P, Whitney K. 2012. Proliferative and nonproliferative lesions of the rat and mouse male reproductive system. Toxicol Pathol 40:40S-121S.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/22949412

Golomb E, Kruglikova A, Dvir D, Parnes N, Abramovici A. 1998. Induction of atypical prostatic hyperplasia in rats by sympathomimetic stimulation. Prostate 34:214-221.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/9492850

Gordon LR, Majka JA, Boorman GA. 1996. Spontaneous nonneoplastic and neoplastic lesions and experimentally induced neoplasms of the testes and accessory sex glands. In: Pathobiology of the Aging Mouse, Vol 1 (Mohr U, Dungworth DL, Capen CC, Carlton WW, Sundberg JP, Ward JM, eds). ILSI Press, Washington, DC, 421-441.

Abstract: http://catalog.hathitrust.org/Record/008994685

Greaves P. 2007. Male genital tract. In: Histopathology of Preclinical Toxicity Studies: Interpretation and Relevance in Drug Safety Evaluation. 3rd ed. Academic Press, San Diego, 661-716.

Abstract: http://www.sciencedirect.com/science/book/9780444527714

Reznik G, Hamlin MH II, Ward JM, Stinson SF. 1981. Prostatic hyperplasia and neoplasia in aging F344 rats. Prostate 2:261-268.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/6170967

Suwa T, Nyska A, Peckham JC, Hailey JR, Mahler JF, Haseman JK, Maronpot RR. 2001. A retrospective analysis of background lesions and tissue accountability for male accessory sex organs in Fischer-344 rats. Toxicol Pathol 29(4):467-478.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/11560252

Suwa T, Nyska A, Haseman JK, Mahler JF, Maronpot RR. 2002. Spontaneous lesions in control B6C3F1 mice and recommended sectioning of male accessory sex organs. Toxicol Pathol 30(2):228-234.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/11950166

Tam NN, Nyska A, Maronpot RR, Kissling G, Lomnitski L, Suttie A, Bakshi S, Bergman M, Grossman S, Ho SM. 2006. Differential attenuation of oxidative/nitrosative injuries in early prostatic neoplastic lesions in TRAMP mice by dietary antioxidants. Prostate 66:57-69.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/16114064
  • Image of epithelial hyperplasia in the prostate from a male F344/N rat in a chronic study

    Prostate, Epithelium - Hyperplasia. Epithelial hyperplasia of the prostate in a male F344/N rat from a chronic study.

Enlarge Image
Enlarge All Images
Prostate, Epithelium - Hyperplasia. Epithelial hyperplasia of the prostate in a male F344/N rat from a chronic study.
Prostate, Epithelium - Hyperplasia. Higher magnification of Figure 1. Proliferative epithelial cells have formed a thickened lining of the affected acini, and there is evidence of associated apoptosis (arrows) in a male F344/N rat from a chronic study.
Prostate, Epithelium - Hyperplasia. Proliferative epithelial cells fill an acinus with multilocular areas of secretion in a male F344/N rat from a chronic study.
Prostate, Epithelium - Hyperplasia. Higher magnification of Figure 3. Epithelial hyperplasia of the prostate in a male F344/N rat from a chronic study.
Prostate, Epithelium - Hyperplasia. Arrows indicate multiple areas of hyperplasia from a male TRAMP mouse in a 1-month study.

Authors:

Dianne M. Creasy, PhD, Dip RCPath, FRCPath
Dianne Creasy Consulting LLC
Pipersville, PA

Robert R. Maronpot, DVM, MS, MPH, DACVP, DABT, FIATP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC

Dipak K. Giri, DVM, PHD, DACVP
Toxicologic Pathologist
Integrated Laboratory Systems, Inc.
Research Triangle Park, NC
 

Reviewers:

Mark F. Cesta, DVM, PhD, DACVP
Staff Scientist, NTP Pathologist
Cellular and Molecular Pathology Branch
Division of the National Toxicology Program
National Institute of Environmental Health Sciences
Research Triangle Park, NC
 

David E. Malarkey DVM, PhD, DACVP, FIATP
Head, National Toxicology Program Pathology Group
Cellular and Molecular Pathology Branch
Division of the National Toxicology Program
National Institute of Environmental Health Sciences
Research Triangle Park, NC