Immune System

Thymus - Atypical Hyperplasia, Lymphocyte

Narrative

Comment:

Atypical hyperplasia of the thymic lymphocytes has been described in chemically treated B6C3F1 and p53-deficient mice. This lesion also occurs in other mouse strains that develop thymic lymphomas and possibly in rats with chemically induced thymic lymphomas. It may be unilateral or bilateral; when unilateral, the unaffected lobe is typically larger than the abnormal lobe (Figure 1, arrow), and atrophy of the other lobe may occur. This lesion is characterized by depletion of small lymphocytes and a diffuse change with loss of the normal thymic corticomedullary junction. Normal thymic architecture is replaced by a sheet of large, atypical lymphocytes, including lymphoblasts and fewer, admixed small lymphocytes (Figure 2); these cells do not extend beyond the capsule of the thymus. Atypical hyperplasia of the thymic lymphocytes is regarded as a proliferative change that may progress to lymphoma, although it may occur without progression. This putative preneoplastic lesion can be differentiated from lymphoma by the heterogeneous population of lymphocytes, mitotic rate, and lack of capsular invasion.

Recommendations:

Whenever present, atypical hyperplasia of the thymic lymphocytes should be diagnosed and assigned a severity grade. It should be noted in the pathology narrative whether the lesion is present in one or both thymic lobes.

References:

Dunnick JK, Hardisty JF, Herbert RA, Seely JC, Furedi-Machacek EM, Foley JF, Lacks GD, Stasiewicz S, French JE. 1997. Phenolphthalein induces thymic lymphomas accompanied by loss of the p53 wild type allele in heterozygous p53-deficient (+/-) mice. Toxicol Pathol 25:533-540.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/9437796

National Toxicology Program. 2007. NTP GMM-12. Toxicology and Carcinogenesis Study of Phenolphthalein (CAS No. 77-09-8) in Genetically Modified Haploinsufficient p16Ink4a/p19Arf Mice (Feed Study). NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/28495

Pearse G. 2006. Histopathology of the thymus. Toxicol Pathol 34:515-547.

Full Text: http://tpx.sagepub.com/content/34/5/515.long

Ward JM, Mann PC, Morishima H, Frith CH. 1999. Thymus, spleen, and lymph nodes. In: Pathology of the Mouse (Maronpot RR, ed). Cache River Press, Vienna, IL, 333-360.

Ward JM, Tadesse-Heath L, Perkins SN, Chattopadhyay SK, Hursting SD, Morse HC 3rd. 1999. Splenic marginal zone B-cell and thymic T-cell lymphomas in p53-deficient mice. Lab Invest 79:3-14.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/9952106

All Images

Thymus - Atypical hyperplasia, Lymphocyte in a female p53+/- (C57Bl/6) mouse from a subchronic study. When atypical lymphocyte hyperplasia is unilateral, the affected lobe (arrow) is typically smaller than the unaffected lobe.

Thymus - Atypical hyperplasia, Lymphocyte in a female p53+/- (C57Bl/6) mouse from a subchronic study (higher magnification of Figure 1). Normal thymic architecture is replaced by a sheet of large, atypical lymphocytes, including lymphoblasts and fewer, admixed small lymphocytes.

Authors and Reviewers

Authors

Kristen Hobbie, DVM, PhD
Principal Pathologist
Huntingdon Life Sciences
Peterborough, UK

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

Holly M. Kolenda-Roberts, DVM, PhD, DACVP
Veterinary Pathologist
SNBL USA
Everett, WA

Reviewers

Jerrold M. Ward, DVM, PhD, DACVP, FIATP
Veterinary Pathologist
Global VetPathology
Montgomery Village, MD

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