Signalment:  

3-year-old, female, rhesus macaque, Macaca mulattaThis animal was born at the Yerkes National Primate Research Center in June 2003. The animal had two incidents of trauma to the hands and feet that resulted in amputation of digits between December 2003 and March 2004. The digit wounds from both episodes healed after routine surgery and treatment with antibiotics and anti-inflammatory drugs, and the animal was returned to her social group. Swelling of both hands, due to subcutaneous deposition of a white material, was reported in March 2006, and the animal was suspected to have calcinosis. The calcified material was debulked surgically and the animal replaced in her group. In October 2006, the white chalky material had returned and the swelling had progressed. Serum ionized calcium level was within normal limits at 1.35 in October 2006. Due to the severity of the condition affecting both hands the animal was humanely sacrificed.

Gross Description:  

The animal weighed 5.3 kilograms at necropsy. Digits from both the hands and feet had been previously amputated and were replaced by multiple, blunt, subcutaneous nodules. On sectioning, these foci contained subcutaneous deposition of a white gritty material. Occasionally, liquefied white material exuded from these nodules.

Histopathologic Description:

The deep dermis and subcutis are expanded by extensive multifocal deposition of a basophilic granular material (mineral) which often disrupts and replaces the normal dermal architecture (Fig. 2-1). The mineral is surrounded by dense aggregates of multinucleate giant cells and macrophages which are occasionally further surrounded by mature fibrous connective tissue. Rare aggregates of degenerate and viable neutrophils are also observed in the dermis. Von Kossa stain revealed localized deposits of calcium salts in the skin and subcutis. Special stains for bacteria and fungi were negative for any infectious agent in these lesions.

Morphologic Diagnosis:  

Skin, Calcinosis cutis circumscripta

Lab Results:  

Normal phosphate, calcium and serum ionized calcium levels. No significant pathogen isolated from the skin lesions. 

Condition:  

Calcinosis circumscripta

Contributor Comment:  

Calcinosis cutis is a rare disorder characterized by deposition of hydroxyapatite crystals or amorphous calcium phosphate in the skin. Depending on the pathophysiologic mechanism, calcinosis can be classified as dystrophic, metastatic or idiopathic.(6) Dystrophic calcinosis is characterized by normal calcium and phosphate serum levels in the presence of tissue damage. The internal organs are not affected. Metastatic calcification occurs in undamaged tissues and is associated with elevated serum phosphate or calcium levels or both.(1) Renal failure, paraneoplastic hypercalcemia, hypervitaminosis D and hyperparathyroidism may develop metastatic deposits of calcium in organs like lung, stomach, kidney, and vasculature.(4) Idiopathic calcification occurs in the absence of evident tissue or metabolic abnormalities.(6)

Dystrophic calcification occurs because of local tissue injuries or abnormalities like alterations in collagen, elastin, or subcutaneous fat, which may precipitate calcification even with normal serum levels of calcium and phosphate.(3) Dystrophic calcification has been divided into calcinosis cutis universalis, which has widespread deposits of calcium, and calcinosis cutis circumscripta, which has only a few localized deposits.(6) Apocrine gland cysts, follicular cysts and skin tumors have been associated with calcinosis cutis circumscripta. Hyperadrenocorticism and diabetes mellitus have been associated with calcinosis cutis universalis.(7)

The gross and histological appearance of the calcified masses in the hands and feet in this case were compatible with a diagnosis of dystrophic mineralization, specifically calcinosis cutis circumscripta. Events potentially leading to these lesions in this macaque included the trauma to digits in hands and feet. Metastatic calcinosis was excluded from the diagnosis due to the presence of normal phosphate, calcium and serum ionized calcium levels. No evidence of mineralization in multiple organs was found on radiographs, grossly at necropsy or histologically. A retrospective analysis done at the Yerkes Primate Center showed 11 cases of calcinosis cutis. Previous trauma was reported at the calcinosis site in digits, tails and in the inguinal area of these animals. In literature, calcinosis cutis circumscripta has been reported in four rhesus macaques without any history of trauma and in a marmoset with a history of trauma.(5)

JPC Diagnosis:  

Haired skin: Granulomas, calcareous, multifocal to coalescing (calcinosis circumscripta)

Conference Comment:  

The different types of calcification and the pathogenesis of these lesions were discussed. Pathologic calcification occurs when calcium salts and small amounts of other trace mineral salts form within tissues. In dystrophic mineralization, such as in this monkey, the end result is the formation of crystal phosphate mineral apatite. There are two phases to the mineralization process dubbed initiation and propagation, and both can occur inside and outside the cell. Dystrophic mineralization can either be a signpost for an area of previous disease or it may cause significant organ dysfunction as seen in valvular disease secondary to calcification.(2)

Hypercalcemia can worsen a nidus of dystrophic calcification. In domestic species there are numerous causes of hypercalcemia. The mnemonic HARD IONS may be useful to remember some common causes of hypercalcemia in domestic animals. This is by no means an all inclusive list. 

H	Hyperparathyroidism
A	Addisons (Hypoadrenocorticism), Acidosis
R	Renal failure (horses and familial renal disease in Lhasa Apsos)
D	Vitamin D toxicity (rodenticides, hypervitaminosis D, and vitamin D glycoside-containing plants)
I	Immobilization
O	Osteolytic lesions
N	Neoplasia (Apocrine gland tumors, carcinomas in bone, lymphoma, multiple myeloma)
S	Spurious (granulomatous disease, hyperproteinemia, and hemoconcentration)

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References:

1. Ferguson DC, Hoenig M: Endocrine system. In: Duncan & Prasses Veterinary Laboratory Medicine, Clinical Pathology, 4th ed., pp. 270-303. Blackwell Publishing, Ames, IA, 2003
2. Kumar V, Abbas AK, Fausto N: Robbins and Cotran Pathologic Basis of Disease, 7th ed., pp 40-42. Elsevier Saunders, Philadelphia, PA 2005
3. Larralde M, Giachetti A, C+�-�ceres MR, Rodr+�-�guez M, Casas J: Calcinosis cutis following trauma. Pediatric Dermatology 22:227229, 2005
4. Poesen N, Heidb+�-+chel M, Van der Oord JJ, Morren M: Chronic renal failure and skin calcifications. Dermatology 190:321323, 1995
5. Wachtman LM, Pistorio AL, Eliades S, Mankowski JL: Calcinosis circumscripta in a common marmoset (Callithrix jacchus jacchus). JAALAS 45:54-57, 2006
6. Walsh JS, Fairely JA: Cutaneous mineralization and ossification. In: Dermatology in General Medicine, eds. Eisen AZ, Wolf K, Freedberg IM, Austen KF, 6th ed., pp. 14901496. McGraw-Hill, New York, 2003
7. Wilkinson AC, Harris LD, Saviolakis GA, Martin DG: Cushing's syndrome with concurrent diabetes mellitus in a rhesus monkey. Contemporary Topics in Laboratory Animal Science 38:62-66, 1999

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