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Spontaneous thymoma in a 10-week-old sprague-dawley rat.
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PMID:  22481857     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
Spontaneous thymoma was found in the left lobe of the thymus of a male 10-week-old Sprague-Dawley (SD) rat. Microscopically, the thymic mass showed a sheet of dark area with multiple pale foci. The dark area mainly consisted of densely compacted small lymphoid cells with sporadic large epithelioid cells and mitotic figures. The epithelioid cells and mitotic figures were more frequent than those of the normal thymic cortex in this animal. The multiple pale foci were similar to the normal thymic medulla and occasionally had Hassall's corpuscles; thus, they were regarded as medullary differentiation areas. Furthermore, some perivascular spaces recognized as characteristics of thymoma were present in the center of the mass. Immunohistochemically, the epithelioid cells in the dark area were positive for cytokeratin. Ultrastructurally, desmosomes and tonofilaments were observed in the epithelioid cells. Thus, this tumor was diagnosed as a thymoma. This is a rare case of thymoma occurring spontaneously in young adult SD rat.
Authors:
Hideki Tanaka; Satoshi Suzuki; Fumiko Ninomiya; Kenji Matsubara; Kazuo Hakoi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of toxicologic pathology     Volume:  25     ISSN:  1881-915X     ISO Abbreviation:  J Toxicol Pathol     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-04-06     Completed Date:  2012-08-23     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  9306408     Medline TA:  J Toxicol Pathol     Country:  Japan    
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Languages:  eng     Pagination:  37-40     Citation Subset:  -    
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Journal Information
Journal ID (nlm-ta): J Toxicol Pathol
Journal ID (iso-abbrev): J Toxicol Pathol
Journal ID (publisher-id): TOX
ISSN: 0914-9198
ISSN: 1881-915X
Publisher: Japanese Society of Toxicologic Pathology
Article Information
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©2012 The Japanese Society of Toxicologic Pathology
open-access:
Received Day: 04 Month: 8 Year: 2011
Accepted Day: 20 Month: 9 Year: 2011
Electronic publication date: Month: 4 Year: 2012
Print publication date: Month: 3 Year: 2012
Volume: 25 Issue: 1
First Page: 37 Last Page: 40
ID: 3320155
PubMed Id: 22481857
Publisher Id: 0616
DOI: 10.1293/tox.25.37

Spontaneous Thymoma in a 10-Week-Old Sprague-Dawley Rat
Hideki Tanaka1
Satoshi Suzuki1
Fumiko Ninomiya1
Kenji Matsubara2
Kazuo Hakoi1
1 Toxicology Laboratory, Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., 224-2 Ebisuno, Hiraishi, Kawauchi-cho, Tokushima 771-0194, Japan
2 Evaluation Research Laboratory, Tsukuba Research Center, Taiho Pharmaceutical Co., Ltd., 3 Okubo, Tsukuba, Ibaraki 300-2611, Japan
Correspondence: Mailing address: Hideki Tanaka, Toxicology Laboratory, Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., 224-2 Ebisuno, Hiraishi, Kawauchi-cho, Tokushima 771-0194, Japan
Correspondence: TEL: 81-88-665-5866 FAX: 81-88-665-5692
Correspondence: E-mail: hi-tanaka@taiho.co.jp

Thymomas are commonly observed in aged rats1–3 and are considered to exhibit strain differences in experimental rats. In most cases, thymomas of rodents are age-related and have been scarcely reported in young rats4. Moreover, the rate of occurrence in male Sprague-Dawley rats is described as being in the range of 0.03–0.4% and is recognized as quite rare compared with other strains5,6. Here, we report a case of thymoma that occurred in a 10-week-old SD rat. To our knowledge, this is rare and the youngest case of thymoma in SD rat.

The animal was a 10-week-old male Sprague-Dawley [Crl:CD (SD), Charles River Laboratories Japan, Inc., Hino, Japan] rat used in the vehicle control group of a toxicity study. The animal showed no remarkable changes in clinical signs, body weight, hematology and blood chemistry. In the terminal necropsy at the end of the administration period, a milky white mass approximately 15 × 15 × 7 mm in diameter was found on the left lobe of the thymus. There was no adhesion between the mass and surrounding tissues (Fig. 1). No remarkable findings were observed in other organs and tissues.

The thymus with mass and other organs were fixed in 10% neutral-buffered formalin, embedded in paraffin, sectioned and stained with hematoxylin and eosin (HE) staining. Immunohistochemical staining was performed on sections from the thymus using antibodies against cytokeratin (34βE12; Dako, Denmark, dilution 1:50), CD3 (1F4; Serotec, UK, dilution 1:20), CD79α (HM57; Dako, Denmark, dilution 1:50) and Ki-67 (MIB-5; Dako, Denmark, dilution 1:100). Antigen retrieval was performed using an autoclave with citrate buffer (pH 6.0), and the HRP-conjugated polymer method (Histofine® Simple Stain MAX-PO(M) Nichirei, Tokyo, Japan) was applied to detect positive signals. For transmission electron microscopic examinations, 10% phosphate-buffered formalin fixed mass was postfixed in 1% osmium, routinely processed into epoxy resin-embedded. Ultrathin sections stained with uranyl acetate and lead citrate were examined using a JEM-1200EX electron microscope (JEOL, Tokyo, Japan).

Microscopically, the mass surrounded by a fibrous capsule occupied the left lobe of the thymus and was clearly separated from the right lobe. Thymic lobular structures disappeared inside the mass and were replaced by dark and pale area resembling the normal thymic tissue (Fig. 2). The dark area was composed of a mixture of densely compacted small lymphoid cells and sporadic large epithelioid cells, the proportions of which varied within the dark area (Fig. 3b,c). The nuclei of epithelioid cells were round to polygonal with prominent nucleoli and vesicular chromatin. Mitotic figures were more frequently observed in dark area of the tumor than in the cortex of the normal thymus. The pale foci of the tumor, which was thought to be a medullary differentiation, included Hassall’s corpuscles (Fig. 3d). Some perivascular spaces recognized as characteristics of thymoma were present in the center of the tumor (Fig. 3e). Microscopic examination of other organs and tissues showed no significant changes. The results of immunohistochemistry of the tumor and normal parts of the thymus are summarized in Table 1. Cytokeratin-positive cells were prominent in the dark area of the tumor compared with the normal thymic cortex (Fig. 4a). The cytoplasm of positive cells showed a meshwork-like structure (Fig. 4b). CD3-positive T-cells were more frequently observed in the pale foci than the dark area of the tumor, and a few CD79α-positive B-cells were observed in the pale foci only. Ki-67-positive cells were mainly located in the dark area and were sparse in the pale foci. These labeling patterns of the tumor except for the positive index of cytokeratin were similar to the corresponding area in the normal thymic tissue (Table 1). Ultrastructurally, desmosomes and bundles of tonofilaments were observed in the epithelioid cells, but the dense-core secretory granules were not confirmed (Fig. 5). Based on histopathological, immunohistochemical and electron microscopic findings, this tumor was diagnosed as a benign thymoma. Thymic lymphoma was ruled out as a differential diagnosis because of the presence of cytokeratin-positive epithelioid cells and lack of atypical lymphocytes.

The cellular components of thymomas are considered to vary from an epithelial cell type to lymphoid cell type3,7. Thymoma in rodents was previously categorized into three histological types by its predominant cellular population, that are epithelial cell type, lymphoid cell type and mixed cell type8. The present case was mainly composed of lymphoid cells with slightly increased numbers of epithelioid cells compared with the normal cellularity in the thymic cortex. Therefore, it was considered to be a lymphoid cell type. In addition, the present case was characterized by the predominant lymphocytes, medulla differentiation and perivascular space resembling a B1/B2 type thymoma, which is its counterpart in humans9.

Thymomas commonly grow slowly in an expansive fashion and are recognized accidentally in aged rats10. Actually, thymomas have been reported to occur in W/Nhg rats7 from around 12 months of age and in Wistar (Cpb:WU) rats3 from after 104 weeks of age. Furthermore, the occurrence of thymoma in SD-derived rats (Tif:RAI) under 400 days old is quite rare11. Moreover, the occurrence of thymoma in the Sprague-Dawley strain5,6 is recognized as being quite rare compared with certain inbred strains of rats such as the W/Nhg and BUF/Mna strains7,12, which have a higher incidence. Therefore, the present case was quite rare and the youngest case of spontaneous thymoma occurring in SD rat.


The authors would like to thank Mr. Shigenori Katayama and Ms. Tamiko Watanabe for skillful technical assistance.


References
1. Kuper CF,Beems RB,Bruijntjes JP,Schuurman HJ,Vos JG. Thymoma. In: Pathology of the Aging Rat volume 1, U Mohr, DL Dungworth and CC Capen (eds). ILSI Press, Washington, D.C. 39–41. Year: 1992
2. Altman PL. Pathology of laboratory mice and rats. Pergamon Infoline INC. Virginia. 295–298. Year: 1985
3. Kuper CF,Beems RB,Hollanders VMH. Spontaneous pathology of the tymus in aging Wistar (Cpb:WU) rat. Vet Pathol.23: 270–277Year: 19863727313
4. Son W-C,Gopinath C. Early occurrence of spontaneous tumors in CD-1 mice and Sprague-Dawley rats. Toxicol Pathol.32: 371–374Year: 200415307208
5. McMartin DN,Sahota PS,Gunson DE,Hsu HH,Spaet RH. Neolasms and related proliferative lesions in control Sprague-Dawley rats from carcinogenicity studies. Historical data and diagnostic consideration. Toxicol Pathol.20: 212–225Year: 19921475582
6. Maeda H,Omori M,Miyajima H. Comparison of historical control data between Crj:CD(SD)IGS and Crj:CD(SD) rats. CD(SD)IGS Study Group. Yokohama. 105–118. Year: 1999
7. Murray AB,Schaffer E,Nussel M,Luz A. Incidence, morphology, and ultrastructure of spontaneous thymoma–the most common neoplasm in W/Nhg rats. J Natl Cancer Inst.75: 369–379Year: 19853860689
8. Greaves P. Hematopoietic and lymphatic systems In: Histopathology of Preclinical Toxicity Studies, Interpretation and Relevance in Drug Safety Evaluation. Elsevier, Amsterdam. 87–156. Year: 2000
9. Hasserjian RP,Strobel P,Marx A. Pathology of thymic tumors. Semin Thorac Cardiovasc Surg.17: 2–11Year: 200516104355
10. Kuper CF,Beems RB. Thymoma, epithelial, rat. In: Hemopoietic System, Monographs on Pathology of Laboratory Animals. TC Jones, JM Ward, U Mohr, and RD Hunt (eds). Springer-Verlag, Berlin. 280–286. Year: 1990
11. Naylor DC,Krinke GJ,Ruefenacht HJ. Primary tumors of the thymus in the rat. J Comp Path.99: 187–203Year: 19882846660
12. Yamada S,Masuko K,Ito M,Nagayo T. Spontaneous thymoma in Buffalo rats. Gann.64: 287–291Year: 19734730596

Figures

[Figure ID: fig_001]
Fig. 1. 

Gross appearance of the thymic mass. The mass is observed on the left thymus.



[Figure ID: fig_002]
Fig. 2. 

The mass consists of a dark area with multiple pale foci without thymic lobular patterns. HE. Bar=1000 μm.



[Figure ID: fig_003]
Fig. 3. 

Higher magnification of Fig. 2. a: The normal thymic cortex of this animal. HE. Bar=10 μm. b, c: The dark area in the tumor. Mitotic figures are observed more frequently in the dark area, and the ratio of epithelioid cells is slightly or remarkably higher than in the normal thymic cortex. HE. Bar=10 μm. d: A Hassall’s corpuscle (Inset) is found in the pale focus. HE. Bar=40 μm. e: Some perivascular spaces in the center of the tumor. HE. Bar=20 μm.



[Figure ID: fig_004]
Fig. 4. 

Immunohistochemistry for cytokeratin. a: Cytokeratin-positive cells are prominent in the tumor compared with the normal thymic cortex. Bar=1000 μm. b: Higher magnification of Fig. 4a. The cytoplasm of positive cells show a meshwork-like structure. Bar=10 μm.



[Figure ID: fig_005]
Fig. 5. 

Electron micrograph of the epithelioid cells. Desmosomes are found between the epithelioid cells, and bundles of tonofilaments are also observed in the cytoplasm. Bar=500 nm.



Tables
[TableWrap ID: tbl_001] Table 1.  Results of Immunohistochemistry


Article Categories:
  • Case Report

Keywords: thymoma, thymus, rat, medullary differentiation, perivascular space.

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