Proliferative and non-proliferative lesions of the rat and mouse soft tissue, skeletal muscle and mesothelium

Abstract

The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying lesions observed in the soft tissues including skeletal muscle as well as the mesothelium of rats and mice. The standardized nomenclature of lesions presented in this document is also available electronically on the Internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous developmental and aging lesions as well as those induced by exposure to test materials. A widely accepted and utilized international harmonization of nomenclature for lesions in soft tissues, skeletal muscle and mesothelium in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists. (DOI: 10.1293/tox.26.1S; J Toxicol Pathol 2013; 26: 1S-26S).

Keywords: mesotheium; mouse pathology; preclinical safety—assessment/risk management; rat pathology; skeletal muscle; ssoft tissues.

Figure 1.

A) Lesion from the face of a Wistar rats with marked inflammation and abscess formation and development of a fibrous capsule (H&E). The abscess contains much cellular debris including gram positive bacteria seen in B) (Gram stain).

Figure 2.

Other examples of chronic inflammation in connective tissue. In A) there is a dense chronic inflammatory infiltrate composed of mononuclear cells which occurred in response to injected pigment seen here as black fragments. In B) the tissues show no necrosis but contain a sparse scattering of chronic inflammatory cells with a vascular proliferative response (H&E).

Figure 3.

Mesenteric fat from a C67Bl mouse fed a high fat diet. There is a granulomatous inflammatory process in the fat with clusters of macrophages with lipid vacuoles and brown lipofuscin pigment (H&E).

Figure 4.

A) Mesenteric fat from a B6C3F1 mouse showing a large nodule of fat necrosis in which the acellular necrotic fat cells can be seen surrounded by a thin rim of poorly cellular connective tissues (H&E). Image by courtesy of the National Toxicology Program. B) Subcutaneous tissue from a Wistar rat treated with a novel drug that produced fat necrosis. This shows acute damage.

Figure 5.

Muscle showing the stereotypical necrosis and repair response four A) and 10 days B) following a single injection of the local anesthetic lignocaine. Mineralisation of muscle fibers is apparent at 10 days (H&E).

Figure 6.

In A) there is muscle degeneration due to spinal nerve compromise in an aged rat. B) shows section of spinal nerve showing degenerative alterations to nerve fibres (H&E).

Figure 7.

Skeletal muscle from thigh of a Sprague Dawley rat treated for 3 months with a peroxisomal proliferator (WY-14643) showing a degenerative form of myopathy. In A) there focal inflammation associated with muscle fiber necrosis characterised by cytoplasmic eosinophilia and loss of cytoplasmic structure. In B) typical reparative response is seen with numerous central nuclei being visible in fibers that are variable in thickness (H&E). Images by courtesy of the National Toxicology Program.

Figure 8.

Quadriceps muscle from a Wistar rat treated with a novel therapeutic agent drug that produce mild muscle degeneration associated with a chronic inflammatory infiltrate seen in this view (H&E).

Figure 9.

Spontaneous focal muscle fiber necrosis in a 2 year old C57Bl mouse. An intact muscle fiber is seen adjacent to a necrotic fiber with an early cellular response (H&E).

Figure 10.

A) Subcutaneous fibroma from a mouse showing homogenous fibrous structure with overlying epidermis. B) Higher power view of fibroma seen in A) shows paucity of fibroblastic cells (H&E).

Figure 11.

Two examples of rat fibromas. A) poorly cellular tumour with abundant dense eosinophilic bands of collagen (H&E, bar = 100 µm). B) also poorly cellular but with a loose pale-staining myxoid stroma (H&E).

Figure 12.

A) A well differentiated fibrosarcoma from a rat. (H&E, bar = 100 µm). In B) the fairly cellular appearance composed of fine spindle cells exhibiting relatively little nuclear pleomorphism can be seen (H&E).

Figure 13.

Pleomorphic fibrosarcoma induced by implanted foreign bodies in Sprague Dawley rats. A) and B) show the range of histological features of this type of neoplasm: spindle cells, plump cells, multinucleated cells and bizarre cells (H&E).

Figure 14.

Lipoma from a rat. A) Low power view of a round nodule of near normal fat cells partially surrounded by a thin fibrous capsule. B) Higher power view showing cellular detail (H&E).

Figure 15.

Lipoma of angiomatous type from a rat containing numerous thin walled blood vessels (H&E).

Figure 16.

Subcutaneous hibernoma from a B6C3F1 mouse (H&E). Image by courtesy of the National Toxicology Program.

Figure 17.

Higher power view of tumor in Figure 16 showing cellular detail, notably the dense eosinophilic staining cytoplasm (H&E). Image by courtesy of the National Toxicology Program.

Figure 18.

A) and B) low and high power view of hibernoma from the thorax from an aged Wistar rat showing pale staining foamy cytoplasm (H&E).

Figure 19.

Liposarcoma from an aged Wistar rat. A) Shows spindle cells and fat containing cells. B) Higher power view showing atypical fat forming cells (lipoblasts) (H&E).

Figure 20.

Well-differentiated rhabdomysarcoma from a Wistar rat. A) Tumor cells showing good muscle differentiation (H&E). B) Same tumor stained for myoglobin (Immunoperoxidase).

Figure 21.

Rhabdomyosarcoma from a CD1 mouse (H&E). A) Well differentiated tumor cells. B) Shows cross striations confirming muscle differentiation (PTAH).

Figure 22.

A) Well differentiated leiomyosarcoma from a rat showing interwoven bundles of spindle cells with typical oval shaped nuclei of smooth muscle. B) Another example of a leiomyosarcoma but showing clear muscle differentiation (H&E).

Figure 23.

A) Low and B) high power view of mesothelioma of epithelioid type which developed in the pleura of a rat in response to the administration of fine fibers (H&E).

Figure 24.

A) Low and B) high power view of mesothelioma of sarcomatoid type which developed in the pleura of a rat in response to the administration of fine fibers (H&E).