April 2022

C-M01 (NP)

Signalment (JPC #1532051): 465-day-old female Balb/c mouse

HISTORY: None

HISTOPATHOLOGIC DESCRIPTION: Heart: Multifocally and extensively within the myocardium and the subepicardial and subendocardial 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 foci 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

GENERAL DISCUSSION:

DCC is asymptomatic and usually an incidental finding in inbred strains of mice including Balb/c, C3H, DBA
Locations:
- Epicardial (right ventricle) in Balb/c
- Deep myocardial (both ventricles and IV septum) in C3H (also axial skeletal muscles)
- Epicardial and/or myocardial in DBA/2
In C3H and C3Hf strains, multiparous females are more often and more severely affected; 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; selenium/vitamin E deficient diets; and concomitant disease
Usually incidental and appears to be dystrophic (no elevation of serum calcium)

PATHOGENESIS:

Pathogenesis is not entirely understood

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 nuclear pyknosis, and rupture of the sarcolemma
Mineralization progresses until the fiber becomes densely calcified; fibrosis around affected fibers is common
Focal mineralization in muscles of the tongue and axial skeleton, cornea, and aorta sometimes surrounded by lymphocytic or granulomatous inflammation

DIFFERENTIAL DIAGNOSES:

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 (renal secondary hyperparathyroidism in dogs), vitamin D toxicosis from cholecalciferol rodenticides, dietary ration imbalances, or ingestion of vitamin D analogue-containing plants (Solanum spp., Cestrum diurnum, Trisetum flavescens)

COMPARATIVE PATHOLOGY:

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, vitamin D, 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

REFERENCES:

Anderson KM, Lewandowski A, Dennis PM. Suspected hypervitaminosis D in a red-rumped agouti (Dasyprocta leporina) receiving a commercial rodent diet. J Zoo Wildl Med. 2018; 49(1):196-200.
Barthold SW, Griffey SM, Percy DH . Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016: 93-94, 242.
Cole GC, Naylor AD, Hurst E, et al. Hypervitaminosis D in a giant anteater (Myrmecophaga tridactyla) and a large hairy armadillo (Chaetophractus villosus) receiving a commercial insectivore diet. J Zoo Wildl Med. 2020; 51(1):245-248.
Craig LE, Dittmer KE, Thompson KG. Bones and joints. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6^th ed. St. Louis, MO: Elsevier; 2016:89.
Han S, Garner MM.Soft Tissue Mineralization in Captive 2-Toed Sloths. Vet Pathol. 2016 May;53(3):659-65.
Holcombe H, Parry, N et al. Hypervitaminosis D and metastatic calcification in a colony of inbred strain 13 Guinea pigs, Cavia porcellus. Vet Pathol. 2015; 52:741-751.
Odriozola ER, Rodriguez AM, Micheloud JF, et. al. Enzootic calcinosis in horses grazing Solanum glaucophyllum in Argentina. J Vet Diagn Invest. 2018;30(2):286-289.
Robinson WF, Robinson NA. Cardiovascular system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6^th ed. 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.