Immune System

Spleen - Fibrosis

Narrative

Comment:

Fibrosis is characterized by increased deposition of collagenous stroma in the spleen. Fibrosis can occur as a reparative process following injury (trauma or toxicity), inflammation, infarction, or neoplasia. It may be limited to the capsule or occur as a focal or diffuse lesion in the parenchyma and/or subcapsular region. Parenchymal fibrosis can extend into the marginal zone and surround or infiltrate the periarteriolar lymphatic sheaths (Figure 1, arrow); when marked, lymphoid tissue is often atrophied (Figure 2, arrow). Capsular fibrosis is more common and typically occurs as a localized lesion (Figure 3 and Figure 4, arrows), although it can occur concurrently with parenchymal fibrosis. Hemorrhage and/or pigments such as hemosiderin and ceroid/lipofuscin may be present within regions of capsular and/or parenchyma fibrosis (Figure 2). Sinusoids of the red pulp may be narrowed and contain few erythrocytes. Blood vessels may become ectatic (angiectasis). Extensive fibrosis may result in a collapsed or contracted spleen (Figure 1). Mesothelial hyperplasia or hypertrophy may accompany capsular fibrosis (Figure 4). Fibrosis is an uncommon background lesion in the B6C3F1 mouse, but it has been identified in untreated rats. Chemically induced fibrosis may lead to sarcoma formation.

Recommendations:

Whenever present, fibrosis of the spleen should be diagnosed and assigned a severity grade. A site modifier (i.e., parenchyma or capsule) should be included in the diagnosis to indicate the location of the fibrosis. Splenic fibrosis that is considered to be secondary to neoplasia or inflammation in the spleen should not be diagnosed separately unless warranted by severity, but should be described in the pathology narrative.

References:

Goodman DG, Ward JM, Reichardt WD. 1984. Splenic fibrosis and sarcomas in F344 rats fed diets containing aniline hydrochloride, p-chloroaniline, azobenzene, o-toluidine hydrochloride, 4,4'-sulfonyldianiline, or D&C red no. 9. J Natl Cancer Inst 73:265-273.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/6588231

National Toxicology Program. 2000. NTP TR-484. Toxicology and Carcinogenesis Studies of 2-Butoxyethanol (CAS No. 111-76-2) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/9770

National Toxicology Program. 2008. NTP TR-540. Toxicology and Carcinogenesis Studies of Methylene Blue Trihydrate (CAS No. 7220-79-3) in F344/N Rats and B6C3F1 Mice (Gavage Studies). NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/32989

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.

Suttie AW. 2006. Histopathology of the spleen. Toxicol Pathol 34:466-503.

Full Text: http://tpx.sagepub.com/content/34/5/466.full.pdf

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.

All Images

Spleen, Parenchyma - Fibrosis in a male F344/N rat from a chronic study. The splenic red pulp is contracted by fibrous connective tissue (arrow).

Spleen, Parenchyma - Fibrosis in a male F344/N rat from a chronic study (higher magnification of Figure 1). The splenic white pulp is atrophied (arrow), and there is pigment within the surrounding fibrous connective tissue.

Spleen, Capsule - Fibrosis in a male F344/N rat from a chronic study. The splenic capsule is expanded by fibrous connective tissue (arrow).

Spleen, Capsule - Fibrosis in a male F344/N rat from a chronic study (higher magnification of Figure 3). The fibrotic splenic capsule is lined by hypertrophied mesothelial cells (arrow).

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