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

Fossey, Stacey L.; Vahle, John L.; Long, Philip H.; Schelling, Scott H.; Ernst, Heinrich; Boyce, Rogely; Jolette, Jacquelin; Bolon, Brad; Bendele, Alison M.; Rinke, Matthias; Healy, Laura; High, Wanda; Roth, Daniel; Boyle, Michael; Leininger, Joel R.

doi:10.1293/tox.29.3s-2

Cited by 40 publications

(39 citation statements)

References 173 publications

(167 reference statements)

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“…The discussion among audience members mainly focused on what term should be used to describe the changes in the dentin: dentin dysplasia or dentin matrix alteration. As per the INHAND skeletal tissues guidance (Fossey et al 2016), dentin matrix alteration is characterized as abnormal dentin (dentin tubules arranged in disorderly fashion) with trapped cells or cellular inclusions. Dentin matrix alteration is considered a secondary response to odontoblast degeneration.…”

Section: White Rat Toothmentioning

confidence: 99%

Proceedings of the 2018 National Toxicology Program Satellite Symposium

et al. 2018

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The 2018 annual National Toxicology Program Satellite Symposium, entitled “Pathology Potpourri,” was held in Indianapolis, Indiana at the Society of Toxicologic Pathology’s 37th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers’ talks along with select images that were used by the audience for voting and discussion. Various lesions and other topics covered during the symposium included seminiferous tubule dysgenesis in rats, ameloblast and odontoblast degeneration/necrosis in an SD rat, intestinal leiomyositis in a beagle dog, gallbladder mucinous hyperplasia, focus of hepatocellular alteration and bile duct alteration in otters, renal tubule cytoplasmic vacuolation with basophilic granules in mice treated with antisense oligonucleotide therapy, a uterine choriocarcinoma in a rhesus macaque and rete ovarii proliferative ovarian lesions in various aged rat strains. One particularly provocative lesion was a malignant neoplastic proliferation in the renal pelvic region of a cynomolgus macaque from a 21-day study. Additional challenging lesions included thyroid proliferative lesions in Zebrafish and gross findings in fish larvae during routine chemical screening. The Rabbit and Minipig International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Groups also presented a series of challenging lesions.

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Section: White Rat Toothmentioning

confidence: 99%

Proceedings of the 2018 National Toxicology Program Satellite Symposium

et al. 2018

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“…Decreased physeal thickness (as noted with some bisphosphonates) has been less commonly encountered in toxicologic studies than thickened or dysplastic physes but can occur with drug treatment, particularly in rodents. Like physeal dysplasia, it is noted most commonly in the femur and tibia and may be related to chronic inanition or from drugs that persistently affect chondrocyte differentiation such as doxorubicin or FGF21 inhibitors (Fossey et al 2016).…”

Section: Examples Of Drug-induced Physeal Injury and Their Morphologymentioning

confidence: 99%

Drug-induced Physeal Abnormalities in Preclinical Toxicity Studies

Frazier

2017

Toxicol Pathol

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Most toxic physeal changes are characterized microscopically by altered chondrocyte development, proliferation, or maturation in the growth plate and eventually result in disordered appositional bone growth. Many therapeutic drugs directly or indirectly target proteins involved in chondrocytic differentiation and maturation pathways, so toxic physeal injury has become increasingly common in preclinical toxicologic pathology. While physeal dysplasia has been associated with several different drug classes including bisphosphonates, vascular endothelial growth factor receptor inhibitors, fibroblast growth factor receptor inhibitors, transforming growth factor beta receptor inhibitors, and vascular targeting agents, physeal changes often share similar morphologic features including thickening and disorganization of the hypertrophic layer, increased numbers of hypertrophic chondrocytes, altered mineralization of endochondral ossification, and/or increased thickness of subphyseal bone. Knowledge of genetic and nutritional diseases affecting bone growth has been important in helping to determine which specific target drugs may be affecting that could result in toxic physeal lesions. A pathophysiologic mechanism for most physeal toxicants has been determined in detail using a variety of investigative techniques. However, due to the signaling cross talk and the tight regulation required for chondrocyte maturation in the physis, several growth factor pathways are likely to be affected simultaneously with pharmacologic disruption of physeal homeostasis and inhibition of one factor necessary for chondrocyte function often affects others.

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“…The audience opinion was largely that the finding was increased bone, trabeculae and cortex (91%) with trabecular hypertrophy, osteosclerosis, osteopetrosis, hyperostosis, and “other” each receiving ≤3% of the votes. The most popular choice, increased bone, was also considered the preferred terminology according to the INHAND manuscript (Fossey et al 2016). …”

Section: Introductionmentioning

confidence: 99%

“…Other options included within normal limits, growth plate closed, physeal atrophy, physeal dystrophy, and “other” with each receiving ≤ 4% of the votes. The most popular choice, decreased physeal thickness, was considered the preferred terminology according to the INHAND manuscript (Fossey et al 2016). …”

Section: Introductionmentioning

confidence: 99%

“…Fossey's take home message was that descriptive nomenclature is recommended for histopathologic diagnoses in nonclinical toxicity studies. INHAND nomenclature for bone, joint, and tooth has been published (Fossey et al 2016) and this terminology can also be found on the Society of Toxicologic Pathology website (www.toxpath.org) and goRENI website (www.goreni.org). …”

Section: Introductionmentioning

confidence: 99%

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Proceedings of the 2017 National Toxicology Program Satellite Symposium

Elmore

Aeffner

Bangari³

et al. 2017

Toxicol Pathol

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The 2017 annual National Toxicology Program Satellite Symposium, entitled “Pathology Potpourri,” was held in Montreal, Quebec, Canada, at the Society of Toxicologic Pathology's (STP) 36th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers' talks, along with select images that were used by the audience for voting and discussion. Various lesions and other topics covered during the symposium included renal papillary degeneration in perinatally-exposed animals; an atriocaval mesothelioma; an unusual presentation of an alveolar bronchiolar carcinoma; a paraganglioma of the Organ of Zuckerkandl, also called an extra adrenal pheochromocytoma; the use of human muscle samples to illustrate the challenges of manual scoring of fluorescent staining; intertubular spermatocytic seminomas; medical device pathology assessment and discussion of the approval process; collagen induced arthritis; incisor denticles; ameloblast degeneration and poorly mineralized enamel matrix; connective tissue paragangliomas; microcystin LR toxicity; perivascular mast cells in the forebrain thalamus unrelated to treatment; and two cases that provided a review of the International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) bone nomenclature and recommended application of the terminology in routine nonclinical toxicity studies.

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

Cited by 40 publications

References 173 publications

Proceedings of the 2018 National Toxicology Program Satellite Symposium

Proceedings of the 2018 National Toxicology Program Satellite Symposium

Drug-induced Physeal Abnormalities in Preclinical Toxicity Studies

Proceedings of the 2017 National Toxicology Program Satellite Symposium

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