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Thymus - Atrophy

Image of atrophy in the thymus from a male Harlan Sprague-Dawley rat in a subchronic study
Thymus - Normal in a male Harlan Sprague-Dawley rat from a subchronic study. The ratio of cortex to medulla is approximately 2:1 (1:1:1, two cortices to medulla).
Figure 1 of 10
Image of atrophy in the thymus from a male Harlan Sprague-Dawley rat in a subchronic study
Thymus - Normal in a male Harlan Sprague-Dawley rat from a subchronic study (higher magnification of Figure 1). The lymphocytes are more numerous in the cortex than in the medulla.
Figure 2 of 10
Image of atrophy in the thymus from a female F344/Ntac rat in a subchronic study
Thymus - Atrophy in a treated female F344/NTac rat from a subchronic study. The cortex, showing minimal atrophy, is thinner and more irregular compared with normal (Figure 1).
Figure 3 of 10
Image of atrophy in the thymus from a female F344/Ntac rat in a subchronic study
Thymus - Atrophy in a treated female F344/NTac rat from a subchronic study (higher magnification of Figure 3). The cortex, showing minimal atrophy, is thinner and more irregular compared with normal (Figure 2).
Figure 4 of 10
Image of atrophy in the thymus from a female Harlan Sprague-Dawley rat in a chronic study
Thymus - Atrophy in a treated female Harlan Sprague-Dawley rat from a chronic study. With mild atrophy, the cortex becomes progressively thinner and the cortical-medullary junction becomes less distinct.
Figure 5 of 10
Image of atrophy in the thymus from a female Harlan Sprague-Dawley rat in a chronic study
Thymus - Atrophy in a treated female Harlan Sprague-Dawley rat from a chronic study (higher magnification of Figure 5). The cortex is thinner, and the cortical-medullary junction is less distinct compared with Figure 4.
Figure 6 of 10
Image of atrophy in the thymus from a female Harlan Sprague-Dawley rat in a chronic study
Thymus - Atrophy in a treated female Harlan Sprague Dawley from a chronic study. With moderate atrophy, delineation of the cortex and medulla is multifocally indistinct.
Figure 7 of 10
Image of atrophy in the thymus from a female Harlan Sprague-Dawley rat in a chronic study
Thymus - Atrophy in a treated female Harlan Sprague Dawley from a chronic study (higher magnification of Figure 7). With moderate atrophy, delineation of the cortex and medulla is multifocally indistinct.
Figure 8 of 10
Image of atrophy in the thymus from a female Harlan Sprague-Dawley rat in a chronic study
Thymus - Atrophy in a treated female Harlan Sprague-Dawley from a chronic study. With marked atrophy, the lack of distinction between the cortex and medulla due to lymphocyte depletion gives the thymus a more uniform appearance.
Figure 9 of 10
Image of atrophy in the thymus from a female Harlan Sprague-Dawley rat in a chronic study
Thymus - Atrophy in a treated female Harlan Sprague-Dawley from a chronic study (higher magnification of Figure 9). With marked atrophy, the distinction between the thymic cortex and medulla is no longer visible due to lymphocyte depletion.
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comment:

Atrophy is characterized by reduced thymus size and weight secondary to thymic lymphocyte depletion. A normal thymus typically has similarly sized lobules, a closely apposed capsule, a densely cellular cortex compared with the medulla, a distinct corticomedullary (CM) junction, and a cortex to medulla ratio of ~1:1:1 (two cortices to the medulla) ( Figure 1image opens in a pop-up window and Figure 2image opens in a pop-up window ). With minimal atrophy ( Figure 3image opens in a pop-up window and Figure 4image opens in a pop-up window ), the cortex may become thinner and irregular, with progressive loss of the CM demarcation as the lesion becomes mild ( Figure 5image opens in a pop-up window , Figure 6image opens in a pop-up window ) and moderate ( Figure 7image opens in a pop-up window and Figure 8image opens in a pop-up window ). As the lesion becomes marked ( Figure 9image opens in a pop-up window and Figure 10image opens in a pop-up window ), cellularity of the cortex and medulla is decreased, and the CM junction may no longer be apparent. The medulla may appear larger than the cortex, and the cellular appearance of thymic compartments may appear reversed, with a pale eosinophilic cortex due to reduced cellularity and a darkly basophilic medulla due to increased cellularity. Thymic atrophy may be influenced by nutrition, adrenocortical hyperactivity, and changes in hormone levels (e.g., sex or growth hormones). Thymic atrophy must be differentiated from thymic involution. Age-related involution is a gradual, nonreversible change, likely associated with sex steroid circulation. In addition to decreased cortical cellularity, normal involution may include blurring of the CM junction, adipocyte infiltration of the capsule and parenchyma, increased prominence and/or hyperplasia of medullary epithelial cells, and formation of follicular-like B-cell aggregates in the medulla. Atrophy that is unrelated to age is generally caused by toxic insult and is potentially reversible with removal of the inciting agent.

recommendation:

When present, atrophy of the thymus should be diagnosed and graded. If atrophy involves only one lobe or is localized, this should be discussed in the pathology narrative. Induced atrophy must be differentiated from normal involution of the thymus. An animal with potential treatment-related thymic atrophy should be compared with age- and sex-matched concurrent controls. Age of the animal and a clear dose-response relationship will help differentiate between thymic atrophy and normal involution.

references:

Elmore SA. 2006. Enhanced histopathology of the thymus. Toxicol Pathol 34:656-665.
Full Text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1800589/

National Toxicology Program. 2006. NTP TR-521. Toxicology and Carcinogenesis Studies of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) (CAS No. 1746-01-6) in Female Harlan Sprague-Dawley Rats (Gavage Studies). NTP, Research Triangle Park, NC.
Abstract: http://ntp.niehs.nih.gov/go/9303

National Toxicology Program. 2007. Toxicology Studies of Sodium Bromate (CAS No. 7789-38-0) in Genetically Modified (FVB Tg.AC Hemizygous) Mice (Dermal and Drinking Water Studies) and Carcinogenicity Studies of Sodium Bromate in Genetically Modified [B6.129-Trp53tm1Brd (N5) Haploinsufficient] Mice (Drinking Water Studies). NTP, Research Triangle Park, NC.
Abstract: http://www.ncbi.nlm.nih.gov/pubmed/18784759

National Toxicology Program. 2010. NTP TR-557. Toxicology and Carcinogenesis Studies of β-Myrcene (CAS No. 123-35-3) in F344/N Rats and B6C3F1 MICE (Gavage Studies). NTP, Research Triangle Park, NC.
Abstract: http://ntp.niehs.nih.gov/go/33584

National Toxicology Program. 2010. NTP TR-558. Toxicology and Carcinogenesis Studies of 3,3’,4,4’-Tetrachloroazobenzene (TCAB) [CAS No. 14047-09-7] in Sprague-Dawley Rats and B6C3F1 Mice (Gavage Studies). NTP, Research Triangle Park, NC.
Abstract: http://ntp.niehs.nih.gov/go/33564

Pearse G. 2006. Histopathology of the thymus. Toxicol Pathol 34:515-547.
Full Text: http://tpx.sagepub.com/content/34/5/515.long

Stefanski SA, Elwell MR, Stromberg PC. 1990. Spleen, lymph nodes, and thymus. In: Pathology of the Fischer Rat: Reference and Atlas (Boorman GA, Eustis SL, Elwell MR, Montgomery CA, MacKenzie WF, eds). Academic Press, San Diego, 369-394.

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.

NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.