Alimentary System

Stomach, Forestomach, Epithelium - Hyperplasia, Atypical

Narrative
Comment:
Some chemicals cause atypical hyperplasia of the forestomach that is characterized by hyperplasia and disorganization, abnormal keratinization, or the presence of abnormal cells (Figure 1 and Figure 2). The distinction between early squamous cell carcinomas and focal atypical hyperplasia can often be difficult. In atypical hyperplasia there is no invasion beyond the basement membrane, whereas carcinomas have irregular cords or clusters of cells that extend deeper into the submucosa. With hyperplasia, even with marked atypia at the deep aspect of the lesions, there remains some degree of orderly maturation.
Recommendations:
Atypical hyperplasia should be diagnosed and graded whenever present. If there are features of atypia, such as diskeratinization, disorganization, or the presence of atypical cells, then atypical hyperplasia should be diagnosed. If the pathologist feels that two distinct hyperplastic processes are present (e.g., diffuse and atypical), then both should be diagnosed and thoroughly described in the pathology narrative. The modifiers "focal" and "diffuse" should be used whenever possible. Grading should be based on the size, extent of distribution, and thickness of the epithelium. Multifocal lesions are not recorded as "multifocal" but are given a higher severity grade than single
lesions.
References:

Betton GR. 1998. The digestive system I: The gastrointestinal tract and exocrine pancreas. In: Target Organ Pathology (Turton J, Hooson J, eds). Taylor and Francis, London, 29-60.

Abstract: http://www.amazon.com/Target-Organ-Pathology-Basic-Text/dp/0748401571

Betton GR, Salmon GK. 1984. Pathology of the forestomach in rats treated for one year with a new H-2 receptor antagonist, SK&F 93479 trihydrochloride. Scand J Gastroenterol Suppl 101:103-108.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/2888184

Boorman GA, Hong HL, Jameson CW, Yoshitomi K, Maronpot RR. 1986. Regression of methyl bromide-induced forestomach lesions in the rat. Toxicol Appl Pharmacol 86:131-139.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/3764933

Chan PC, Mahler J, Peddada S, Lomnitski L, Nyska A. 2003. Forestomach tumor induction by 2,4-hexadienal in F344N rats and B6C3F1 mice. Arch Toxicol 77:511-520.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/12879212

Frantz JD, Betton GR, Cartwright ME, Crissman JW, Macklin AW, Maronpot RR. 1991. Proliferative lesions of the non-glandular and glandular stomach in rats. GI-3. In Guides for Toxicologic Pathology. STP/ARP/AFIP, Washington, DC, 1-20.

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

Frederick CB, Hazelton GA, Frantz JD. 1990. The histopathological and biochemical response of the stomach of male rats following two weeks of oral dosing with ethyl acrylate. Toxicol Pathol 18:247-256.

Full Text: http://tpx.sagepub.com/content/18/2/247.full.pdf

National Toxicology Program. 2002. NTP TOX-70. Toxicity Studies of p-tert-Butylcatechol (CAS No. 98-29-3) Administered in Feed to F344/N Rats and B6C3F1 Mice. NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/1385

National Toxicology Program. 2007. NTP TR-543. Toxicology and Carcinogenesis Studies of alpha-Methylstyrene (CAS No. 98-83-9) in F344/N rats and B6C3F1 mice (Inhalation Studies). NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/28010

National Toxicology Program. 2010. NTP TR-544. Toxicology and Carcinogenesis Studies of Dibromoacetonitrile (CAS No. 3252-43-5) in F344/N Rats and B6C3F1 Mice (Drinking Water Studies). NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/32617

National Toxicology Program. 2010. NTP TR-558. Toxicology and Carcinogenesis Studies of 3,3’,4,4’-Tetrachloroazobenzene (TCAB) (CAS No. 14047-09-7) in Harlan Sprague Dawley Rats and B6C3F1 Mice (Gavage Studies). NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/33564

Nera EA, Lok E, Iverson F, Ormsby E, Karpinski DF, Clayson DB. 1984. Short term pathological and proliferative effects of butylated hydroxyanisole and other phenolic antioxidants in the forestomach of Fischer 344 rats. Toxicology 32:197-213.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/6474484

Nyska A, Moomaw CR, Lomnitski L, Chan PC. 2001. Glutathione S-transferase pi expression in forestomach carcinogenesis process induced by gavage-administered 2,4-hexadienal in the F344 rat. Arch Toxicol 75:618-624.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/11808924
  • Image of hyperplasia, atypical in the forestomach epithelium from a female F344/N rat in a subchronic study

    Stomach, Forestomach, Epithelium - Hyperplasia, Atypical in a female F344/N rat from a subchronic study. Focal epithelial hyperplasia with large, atypical cells is present.

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Stomach, Forestomach, Epithelium - Hyperplasia, Atypical in a female F344/N rat from a subchronic study. Focal epithelial hyperplasia with large, atypical cells is present.
Stomach, Forestomach, Epithelium - Hyperplasia, Atypical in a female F344/N rat from a subchronic study. Focal epithelial hyperplasia with large, atypical cells is present.
Stomach, Forestomach, Epithelium - Hyperplasia, Atypical in a female F344/N rat from a subchronic study (higher magnification of Figure 1). Focal epithelial hyperplasia with large, atypical cells is present.
Stomach, Forestomach, Epithelium - Hyperplasia, Atypical in a female F344/N rat from a subchronic study (higher magnification of Figure 1). Focal epithelial hyperplasia with large, atypical cells is present.

Authors:

Linda H. Kooistra, DVM, PhD, DACVP
Pathologist
Charles River Laboratories, Inc.
Research Triangle Park, NC

Abraham Nyska, DVM, Diplomate ECVP, Fellow IATP
Expert in Toxicologic Pathology
Visiting Full Professor of Pathology
Sackler School of Medicine, Tel Aviv University Timrat Israel

Reviewers:

Joel R. Leininger, DVM, PhD
Senior Pathologist
MedImmune
Washington, DC

Amy Brix, DVM, PhD, DACVP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC