Urinary System

Renal Tubule - Atypical Tubule Hyperplasia

Narrative
Comment:
Atypical tubule hyperplasia (ATH) may occur spontaneously, in association with chronic progressive nephropathy, or as a result of chemical administration. ATH usually arises from the proximal convoluted tubule, but a distal tubule or collecting duct origin is possible. It is considered a putative preneoplastic lesion that is part of the continuum leading to neoplasia (Figure 1, Figure 2, and Figure 3).

ATH is characterized by an increased number of epithelial cells within the confines of a single tubule, as opposed to an adenoma, in which the proliferating cells are no longer within the confines of a single tubule. The proliferative lining epithelium in ATH is greater than two or three cell layers. Hyperplastic cells appear enlarged with a slightly basophilic “glassy” cytoplasmic sheen. Variable degrees of cytoplasmic and nuclear pleomorphism may be present. Evidence of lesion expansion is identified by fibroblast flattening and margination around the lesion. Neovascularization noted in renal tubule adenomas is not apparent in ATH.

ATH should not be confused with tubule hyperplasia, which is often observed in foci of advanced chronic progressive nephropathy (see Kidney - Nephropathy, Chronic Progressive ) and characterized as a tubule lined by a single layer of increased numbers of epithelial cells. This form of tubule hyperplasia is rarely induced by chemical administration and is considered to represent a form of regeneration.
Recommendations:
Since atypical tubule hyperplasia is presumed to be a preneoplastic lesion, it should be diagnosed and given a severity grade whenever present.
Related Links:
Kidney - Nephropathy, Chronic Progressive
Kidney - Renal Tubule - Hyperplasia, Amphophilic-Vacuolar
Kidney - Renal Tubule - Hyperplasia, Oncocytic
References:

Frazier KS, Seely JC, Hard GC, Betton G, Burnett R, Nakatsuji S, Nishikawa A, Durchfeld-Meyer B, Bube A. 2012. Proliferative and non-proliferative lesions in the rat and mouse urinary system. Toxicol Pathol 40:14S-86S.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/22637735

Greaves P. 2012. Histopathology of Preclinical Toxicity Studies, 4th ed. Elsevier, Amsterdam, 569-571.

Abstract: http://www.sciencedirect.com/science/book/9780444538567

Hard GC, Seely JC. 2005. Recommendations for the interpretation of renal tubule proliferative lesions occurring in rat kidneys with advanced chronic progressive nephropathy (CPN). Toxicol Pathol 33:641-649.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/16207638

Hard GC, Seely JC. 2006. Histological investigation of diagnostically challenging tubule profiles in advanced chronic progressive nephropathy (CPN) in the Fischer 344 rat. Toxicol Pathol 34:941-948.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/17178694
  • Image of renal tubule epithelium atypical tubule hyperplasia in the kidney from a male F344/N rat in a chronic study

    Kidney, Renal tubule - Atypical tubule hyperplasia in a male F344/N rat from a chronic study. Atypical tubule hyperplasia is confined to one tubule and is characterized by an increase in cellularity and cell size, cytoplasmic basophilia, nuclear enlargement, and circumferential expansion.

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Kidney, Renal tubule - Atypical tubule hyperplasia in a male F344/N rat from a chronic study. Atypical tubule hyperplasia is confined to one tubule and is characterized by an increase in cellularity and cell size, cytoplasmic basophilia, nuclear enlargement, and circumferential expansion.
Kidney, Renal tubule - Atypical tubule hyperplasia in a male F344/N rat from a chronic study. Atypical tubule hyperplasia is confined to one tubule and is characterized by an increase in cellularity and cell size, cytoplasmic basophilia, nuclear enlargement, and circumferential expansion.
Kidney, Renal tubule - Atypical tubule hyperplasia in a male F344/N rat from a chronic study. This larger focus of tubule hyperplasia contains three cross sections of presumably the same tubule.
Kidney, Renal tubule - Atypical tubule hyperplasia in a male F344/N rat from a chronic study. This larger focus of tubule hyperplasia contains three cross sections of presumably the same tubule.
Kidney, Renal tubule - Atypical tubule hyperplasia in a female F344/N rat from a chronic study. Early proliferation of epithelial cells indicates atypical tubule hyperplasia.
Kidney, Renal tubule - Atypical tubule hyperplasia in a female F344/N rat from a chronic study. Early proliferation of epithelial cells indicates atypical tubule hyperplasia.

Authors 

John Curtis Seely, DVM, DACVP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC

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

Reviewers

Kendall S. Frazier, DVM, PhD, DACVP, DABT
Director, Cellular and Molecular Pathology, Safety Assessment
GlaxoSmithKline
King of Prussia, PA

Gordon C. Hard, BSc, BVSc, PhD, DSc, FRCPath, FRCVS, FAToxSci, DACVP
Expert Consultant
Tairua, New Zealand

Susan A. Elmore, MS, DVM, DACVP, DABT, FIATP
Staff Scientist, NTP Pathologist
NTP Pathology Group
National Toxicology Program
National Institute of Environmental Health Sciences
Research Triangle Park, NC