Proliferative Bone Lesions in Rats Given Anticancer Compounds

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is an initiative of the Societies of Toxicological 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 microscopic lesions observed in the skeletal tissues and teeth of laboratory rats and mice, with color photomicrographs illustrating examples of many common lesions. The standardized nomenclature presented in this document is also available on the internet (http://www.goreni.org/). Sources of material were databases from government, academic and industrial laboratories throughout the world.

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“…Courtney et al (1991), Felix et al (1996), Hartke (1996), Li et al (2009), Qi et al (1995), Stromberg and Vogtsberger (1983)…”

Section: Bonementioning

confidence: 99%

Nonproliferative and Proliferative Lesions of the Rat and Mouse Skeletal Tissues (Bones, Joints, and Teeth)

Fossey

Vahle

Long³

et al. 2016

J Toxicol Pathol

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“…and has been observed in rats administered chemicals or anticancer drugs (NTP, 1986;Courtney et al, 1991) (Figure 20). In their report, Courtney et al (1991) characterized the lesion as an accelerated proliferation of trabecular bone and foci or bands of proliferating spindle-cells (with or without osteoid formation) that encroached on the center of the marrow cavity. When the lesion occurred, the remaining bone marrow appeared either normo-to hypo-cellular.…”

Section: Fibro-osseous Lesion and Fibrous Osteodystrophymentioning

confidence: 99%

Histopathology of Bone Marrow

Travlos

2006

Toxicol Pathol

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As a major hematopoietic and lymphoid organ, morphological evaluation of the bone marrow is an important component of toxicity or safety assessment studies. While definitive characterization of bone marrow lesions often requires cytological aspirates or smears, assessment of histological bone marrow sections provides information regarding tissue architecture and hematopoietic status that is relevant for the detection of direct or indirect responses to chemical exposure. A variety of lesions have been observed in bone marrow. For example, lesions involving disturbances in growth, degenerative changes, inflammatory changes and neoplasia have been described. Lesions identified in hematoxylin and eosin-stained sections typically represent changes in the hematopoietic cell lineage and/or stromal cells since definitive identification of lymphoid cells is difficult except in cases of lymphoma. This review provides a descriptive and pictorial representation of a wide range of bone marrow lesions. Since large animal-to-animal variation may exist and there can be collection site- and age-related differences, it is imperative that the pathologist reviews all potential treatment-related findings against appropriate concurrent controls.

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“…Observed in a Variety of Species Administered Pharmacologic Compounds or Having Altered Cytokine Expression New bone deposition (endosteal proliferation, osteosclerosis) has been observed among rats administered a variety of chemically and pharmacologically distinct small molecule antineoplastic compounds (Courtney et al 1991;Norbury and Allen 1981). Findings are variably described as woven bone with myelostromal proliferation or osteopetrosis.…”

Section: Bone And/or Stromal Changes Have Beenmentioning

confidence: 99%

Bone Marrow Findings Secondary to Antineoplastic Compounds: Hematopoietic, Bone, and Cytokine Cross Talk

et al. 2017

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New medullary bone formation has been observed in rats administered a variety of antineoplastic compounds. Similar effects reported in rats administered granulocyte colony-stimulating factor (G-CSF) were attributed to exaggerated pharmacology of G-CSF as a cytokine and growth factor, resulting in stromal proliferation in addition to the intended hematopoietic effects. Similar phenomena of marrow stromal change are reported among other species in association with various growth factors. Case study summaries of test item-related histopathologic changes in bone marrow, reflecting trabecular and/or endosteal new bone formation, are presented. In each of these cases, it was concluded that the new medullary bone and stromal proliferation did not reflect a primary target-related toxicity; rather, the mesenchymal changes were attributed to nonspecific, secondary effects of cytokines elaborated in response to primary cytotoxic effects on hematopoietic cells with subsequent impact on circulating blood cells. The common features associated with marrow stromal changes in the case studies, as well as with a variety of pharmacologic compounds across several species described in the literature, are hematologic effects and/or changes in growth factor levels and cytokine expression.

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Proliferative Bone Lesions in Rats Given Anticancer Compounds

Cited by 13 publications

References 9 publications

Nonproliferative and Proliferative Lesions of the Rat and Mouse Skeletal Tissues (Bones, Joints, and Teeth)

Nonproliferative and Proliferative Lesions of the Rat and Mouse Skeletal Tissues (Bones, Joints, and Teeth)

Histopathology of Bone Marrow

Bone Marrow Findings Secondary to Antineoplastic Compounds: Hematopoietic, Bone, and Cytokine Cross Talk

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