JPC SYSTEMIC PATHOLOGY
Signalment (JPC# 1532051): 465-day-old female Balb/c mouse
HISTOPATHOLOGIC DESCRIPTION: Heart: Multifocally and extensively within the myocardium and the subepicardial right ventricular wall, cardiac myocytes are swollen and vacuolated with loss of sarcoplasmic detail (degeneration), or hypereosinophilic, shrunken and fragmented with pyknotic or karyolytic nuclei (necrosis). Separating, surrounding, and replacing degenerate and necrotic cardiac myofibers, there is abundant basophilic granular material (mineral) and increased collagen (fibrosis) with moderate numbers of hypertrophied fibroblasts. There are scattered lymphocytes and plasma cells within the areas of mineralization and multiple areas of osseous metaplasia. Occasionally, adjacent cardiomyocytes have large vesiculate nuclei.
Thymus: Essentially normal tissue.
MORPHOLOGIC DIAGNOSIS: Heart, myocardium: Mineralization, degeneration, and necrosis, multifocal, moderate, with fibrosis, Balb/c mouse, rodent.
CONDITION: Dystrophic cardiac calcinosis (DCC)
CONDITION SYNONYM: Dystrophic mineralization
- DCC is asymptomatic and usually an incidental finding in inbred strains of mice including Balb/c, C3H, DBA, CBA, CHI, CCF1, and KK/HIJ
- Epicardial (right ventricle) in Balb/c
- Deep myocardial in C3H
- Epicardial and/or myocardial in DBA/2
- In C3H and C3Hf strains, multiparous females are more often and more severely affected than males or virgin females; fatalities can occur in lactating or pregnant females; There is no gender variation in Balb/c and DBA mice
- Other sites of mineralization include aorta, testes, tongue, muscle, cornea, kidney, stomach, small intestine, and ovary
- Lesions are evident at 3 weeks of age, but increase in severity with age
- Incidence and severity increase with exogenous corticosteroids or ACTH, high fat, low protein diets, and selenium/vitamin E deficient diets, and concomitant disease
- Usually incidental and appears to be dystrophic (no elevation of serum calcium)
- Pathogenesis is not entirely understood
- In KK/HIJ mice, polymporphism in ABCC6 efflux transporter protein within liver and kidneys is suggested as pathogenesis
TYPICAL CLINICAL FINDINGS:
- Usually none
- Occasional sudden death
TYPICAL GROSS FINDINGS:
- Cardiomegaly with subepicardial atrial and ventricular mineralization; chalky white streaks
- Occasional mineralization in tongue, lungs, and diaphragm
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Early myocardial degeneration: Myofiber swelling and vacuolation, karyolysis or pyknosis, and rupture of the sarcolemma
- Mineralization progresses until the fiber becomes densely calcified; fibrosis around affected fibers is common
- 50% of DBA/2NCrj mice also have calcification of smooth muscle and the elastic lamina of the aorta, beginning as early as 3 weeks of age
- Focal mineralization in muscles of the tongue and axial skeleton, cornea, and aorta sometimes surrounded by lymphocytic or granulomatous inflammation
- Metastatic mineralization – a different pathogenesis than dystrophic mineralization, but tissue appearance can be similar
- Occurs secondary to hypercalcemia and/or hyperphosphatemia
- These may develop due to renal insufficiency (pseudohyperparathyroidism in dogs), vitamin D toxicosis from cholecalciferol rodenticides, dietary ration imbalances or ingestion of vitamin D analogue-containing plants (Solanum, Cestrum diurnum, Trisetum flavescens)
- 2-toed sloths: May develop soft tissue mineralization in aorta, arteries, as well as myocardium and other tissues; pathogenesis unclear – may be metastatic mineralization secondary to renal issues or nutritional causes
- Rabbits and Guinea pigs: Metastatic mineralization can develop secondary to renal disease or dietary imbalances of magnesium, calcium and/or phosphorus
- Guinea pig: Multifocal myocardial degeneration, fibrosis and mineralization are uncommonly observed; the exact cause is unclear
- Rats: Mineralization has also been documented in the myocardium of rats and may be associated with cardiomyopathy, although the precise cause / pathogenesis is not well defined
- Berndt A, et al. Phenotypic characterization of the KK/HIJ inbred mouse strain. Vet Pathol. 2014;51(4): 846-857.
- Craig LE, Dittmer KE, Thompson KG. Bones and joints. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th St. Louis, MO: Elsevier; 2016:89.
- Han S, Garner MM. Soft tissue mineralization in captive 2-toed sloths. Vet Pathol. 2016;53(3)659-665.
- Percy DH, Barthold SW. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016: 93-94, 242.
- Robinson WF, Robinson NA. Cardiovascular system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th St. Louis, MO: Elsevier; 2016: 30, 60-61.
- Rothenburger JL, Himsworth CG, Treuting PM, Leighton FA. Survey of cardiovascular pathology in wild urban Rattus norvegicus and Rattus rattus. Vet Pathol. 2015;52(1):201-208.