(Received 11 May, 2000; Review completed, 22 May, 2000; placed online 25 May, 2000)

Summary

Tumoral calcinosis is an uncommon disease that results in single or multiple circumscribed calcium deposits in periarticular connective tissue. When the mineralized focus occurs within the paravertebral soft tissue it can cause spinal cord compression and neurologic deficits. Complete surgical removal of the mass provides long term resolution of clinical signs.

Case Report

A four month old male German shepherd dog was presented to the Neurology Service at the Veterinary Teaching Hospital (VTH) of North Carolina State University because of pelvic limb ataxia. The owners first noticed that the dog lacked coordination of both pelvic limbs about two weeks previously, when he started to stumble and bunny hop. At about the same time they also noted that the dog appeared painful to touch in the interscapular region, and showed other signs that they interpreted as manifestations of pain including intermittent whining and reluctance to rise. These signs became progressively worse. Treatment with buffered aspirin produced a slight improvement, but the dog developed diarrhea, and so the medication was discontinued after a few days. The dog was current on immunizations and was fed a balanced puppy diet. According to the breeder, he was bred from a line of "giant" German shepherd dogs, but there was no history of similar problems amongst other offspring from this line.

General physical examination was unremarkable. On orthopedic examination, mild discomfort was elicited upon abduction of both hips. Abnormalities found on neurological examination included a moderately ataxic pelvic limb gait with conscious proprioceptive deficits and increased patellar reflexes bilaterally. The panniculus reflex was intact. Pain could be elicited by palpation of the thoracic spine in the interscapular region. The lesion was localized to the T3-L3 region of the spinal cord.

A complete blood cell count, biochemistry panel and urinalysis were performed. The blood cell count showed mildly decreased plasma protein and a mild reactive lymphocytosis (5.628x10³, with a normal range of 1 - 5 x10³) suggesting antigenic stimulation, presumably from vaccinations 9 days previously. The biochemistry profile showed normal calcium (10.6 mg/dl, with a normal range of 8.8-10.9 mg/dl), phosphorus (9.1 mg/dl, normal range in dogs younger than 12 months 4.6-10.2 mg/dl)¹ and alkaline phosphatase (103 IU/L, normal range for growing dogs 32-142 IU/L)² for a young dog. Total protein and globulins were decreased, and cholesterol (342 mg/dl, normal range 146-295 mg/dl), potassium (4.9 mmol/L, normal range 3.5-4.7 mmol/L) and creatine kinase (221 IU/L, normal range 28-97 IU/L) were mildly elevated. The slight increases in cholesterol, creatine kinase and potassium were not considered significant. The low globulins were also considered normal for a young dog. Urinalysis was within normal limits.

Further examination was performed under general anesthesia. The dog was premedicated with oxymorphone (Numorphan, Endo Pharmaceuticals Inc., Chadds Ford, PA) and anesthesia was induced with intravenous thiopental (Pentothal, Abbot laboratories, North Chicago, IL) and maintained with a halothane (Halothane U.S.P., Halocarbon laboratories, River Edge, NJ) and oxygen mixture. Cerebrospinal fluid (CSF) was taken from the cerebellomedullary cistern and from a lumbar puncture at L5/6. Survey radiographs of the thoracolumbar spine were performed. A myelogram was then performed by subarachnoid injection of iohexol (Omnipaque 240 mgI/ml, Nycomed Inc., Princeton, NJ) at the L5/6 intervertebral space at a dose of 0.4 ml/kg.

The cisternal CSF was unremarkable, while the lumbar CSF showed a mild elevation in protein (57.3 mg/dl, normal range up to 45mg/dl). A small focus of amorphous mineralization was evident on plain radiographs lying between the dorsal laminae of the third and fourth thoracic vertebrae (Figure 1).The myelogram showed mild extradural compression of the subarachnoid space at the same site (Figure 2). Based on these findings, the thoracic spine of the dog was imaged using a third generation CT scanner (GE Sytec SRI). Contiguous transverse images were acquired at one millimeter intervals parallel to the vertebral end-plates from mid body of the third through mid body of the fourth thoracic vertebrae. Scanning parameters were 120 kVp, 80mA, with a scan time of five seconds per slice. The mineralized focus noted on the plain radiographs was clearly visible extending from between the dorsal laminae of the third and fourth thoracic vertebrae into the vertebral canal via the left intervertebral foramen (Figure 3).The radiographic findings were consistent with a diagnosis of tumoral calcinosis. Since no abnormalities could be detected on palpation and orthopedic examination of all four limbs, the owner did not want to pursue diagnostic imaging of the limbs to rule out other possible foci of periarticular soft tissue mineralization.

	Click on the image to see a larger view Figure 1. Lateral radiograph of the thoracic spine. Note radiodense focus between the dorsal laminae of the third and fourth thoracic vertebrae (arrow)
	Figure 2. Myelogram of the thoracic spine. The myelogram reveals subtle narrowing of the subarachnoid space between the third and fourth thoracic vertebrae (arrow).
	Figure 3. Transverse CT image of the thoracic spine at the level of theT3-4 intervertebral disc. Note the mineral density material (arrow) extending into the vertebral canal via the left intervertebral foramen.

Two weeks later the dog was presented to the VTH for surgery. On neurologic examination his pelvic limb gait was markedly more dysmetric and paretic and he was still painful on palpation of the thoracolumbar spine in the interscapular region. After premedication with acepromazine maleate (Aceproject, Burns Veterinarian Supply, Rockville Centre, NY) and oxymorphone, general anesthesia was induced as before with thiopental and maintained with halothane and oxygen. Cefazolin (Anacef, Smithkline Beecham Pharmaceuticals, PA) (22 mg/kg) was administered intravenously after induction and at two hour intervals during surgery. The dog was placed in sternal recumbency and the thoracic limbs were crossed to abduct the scapulae from the spine. The cranial thoracic spine was approached as described by Piermattei and Greeley.³ The spinous processes and dorsal laminae of the second, third and fourth thoracic vertebrae were exposed. A round, circumscribed, chalky, white mineralized mass was identified within the flaval ligament on the left side between the dorsal lamina of third and fourth thoracic vertebrae. The mass extended ventrally into the vertebral canal and was not continuous with bony structures. The dorsal spinous process of the third thoracic vertebra was removed with rongeurs. The dorsal lamina of the third thoracic vertebra and the cranial aspect of the dorsal lamina of the fourth thoracic vertebra were then removed with a power drill to expose the mass; the mass was then completely excised. Its approximate size was 1x 0.5x 0.4 cm. Gelfoam (UpJohn, Kalamazoo, MI) was placed over the exposed spinal cord and closure was routine. The mineralized soft tissue mass was submitted for histopathology. Hematoxylin and eosin stained sections revealed changes typical of tumoral calcinosis; there were multifocal areas of mineralization lying within sheets of fibrous tissue and surrounded by marked granulomatous inflammation containing multinucleated giant cells (Figure 4).

The day after surgery the dog could walk with support provided by a sling underneath his abdomen and he was able to urinate on his own. Two weeks after surgery the referring veterinarian evaluated the dog for suture removal and noted a substantial improvement in gait. Three months later, the dog was re-evaluated by the authors at the Veterinary Teaching Hospital and an improvement in his neurologic status was observed although moderate ataxia in the pelvic limbs was still appreciable. A further recheck was performed by the same clinicians 14 months after surgery. At that time, the owners reported that the dog had shown a steady improvement since surgery and could now jump and climb, activities he was unable to perform prior to surgery. On neurologic examination the only abnormality was persistence of mild pelvic limb ataxia especially affecting the left pelvic limb.

Click on the image to see a larger view Figure 4. Histologic section of the surgically resected tissue mass (hematoxylin and eosin stain X 180). The lesion consists of lakes of mineral deposits (large arrow) surrounded by zones of granulomatous inflammation, often containing multinucleate giant cells (arrow head) and other zones of thick fibrous tissue (small arrow).

Literature Review and Discussion

Calcinosis circumscripta or tumoral calcinosis is a syndrome of ectopic mineralization characterized by deposition of calcium salts (calcium phosphate crystals, including hydroxyapatite crystals) in soft tissues.⁴ It has been reported in many species.^5-18 Other synonyms that have been used to indicate this condition include calcium gout, lipocalcinosis, apocrine cystine calcinosis, tumoral lipocalcinosis, granulomatosis and hip stone.⁴ The term tumoral calcinosis has generally been used to indicate calcium deposits in periarticular connective tissue, while the term calcinosis circumscripta is generally used when the ectopic mineralization takes place in the subcutis. However, there is a tendency to use these terms interchangeably.^4,14

The deposition of calcium and phosphorus salts in soft tissues has been classified according to the underlying etiology into three categories: metastatic, dystrophic or idiopathic.¹⁹ Metastatic mineralization is secondary to derangement in calcium and/or phosphorus homeostasis. The calcification is generally widespread and involves normal tissues. Dystrophic calcification occurs in the presence of normal metabolism in tissue that has been damaged or devitalized by some pathological process such as trauma, inflammation, parasitic infestation, infection, connective tissue disease or neoplasia. When the ectopic mineralization occurs in normal soft tissues with no abnormality of calcium and phosphorus homeostasis it is defined as idiopathic.¹⁹

In humans, tumoral calcinosis is most frequently metastatic, occurring secondary to metabolic disorders such as renal disease.¹⁹ As a general rule it is necessary to treat the underlying disorder to resolve the lesions, surgical resection alone is unsuccessful.¹⁹ There are many reports of dystrophic tumoral calcinosis in people secondary to trauma, but idiopathic tumoral calcinosis appears to be less common.^{20, 21} Complete surgical excision of dystrophic or idiopathic calcifications is usually curative. It is interesting to note the existence of a familial disease known as primary hyperphosphatemic tumoral calcinosis in which the lesions are classified as metastatic.¹⁹ This disease is characterized by elevated levels of serum phosphate and serum vitamin D, elevated renal tubular resorption of phosphate, and normal serum calcium. The lesions are usually multiple and frequently recur after complete surgical removal.¹⁹

In small animals, all three forms of tumoral calcinosis have been described, but unlike humans, the idiopathic and dystrophic forms occur more frequently than the metastatic form. Metastatic tumoral calcinosis has been reported in dogs and cats with renal failure.^22-29 Mineralization of the foot pads is the most common presenting lesion, but there have been reports of widespread visceral mineralization²³ and mineralization of the vasculature.²⁷ It is not known why metastatic tumoral calcinosis due to chronic renal failure affects the footpads primarily in small animals, but it has been suggested that the repetitive trauma of walking and running may be the predisposing factor. In all dogs reported, the renal disease was lethal and no treatment was attempted to resolve the ectopic mineralization. The lesions in one cat with renal hyperparathyroidism recurred after surgical removal but responded to dietary phosphorus restriction.²⁸

Idiopathic and dystrophic tumoral calcinosis occur most commonly in young, large breed dogs with an apparently higher incidence in the German shepherd dog.^{15, 23, 24, 30} The lesions are generally solitary and occur in specific anatomical locations such as the lateral metatarsus and digits, the elbow, the shoulder, the spine, the hip, the tongue and the foot pads.^{15, 23, 24} In some cases, tumoral calcinosis has been reported in association with Medroxyprogesterone injections,^{31, 32} polydioxanone suture material,³³ and previous surgical procedures^{34, 35} and the ectopic mineralization can be classed as dystrophic. For cases in which there was no obvious underlying cause, several theories have been proposed in order to explain the etiology of calcium salt deposition in the soft tissues. Some authors noted that most lesions occurred in the deep dermis at the level of apocrine gland sites and hypothesized that the ectopic calcification was dystrophic, arising from abnormal apocrine sweat gland secretion.^{23, 36} They proposed that mechanical pressure could induce cystic dilation and hyperplasia of the apocrine glands whose secretion became abnormal, representing an ion-binding matrix for mineralization. As the lesions occurred mainly in young dogs of large breeds and in sites of mechanical pressure, trauma was considered responsible for the cystic apocrine changes^{23, 36} and the higher incidence in German shepherd dogs suggested a hereditary apocrine vulnerability. Further studies failed to prove a relationship between the lesions and the apocrine sweat glands changes, and this theory could not explain the lesions in the tongue and deep along the spinal column.¹⁵ Other authors proposed that trauma alone could be the triggering cause of the mineralization process in tumoral calcinosis.^{14, 24} Their hypothesis was supported by the fact that the majority of lesions occurred in young, active large breed dogs over pressure points and sites exposed to trauma. However, in only a limited number of cases there was a true history of local trauma preceding the development of lesions. In addition, if every day "wear and tear" is sufficient to cause soft tissue damage and dystrophic mineralization, tumoral calcinosis should be a much more common disease¹⁵ and the lesions should recur following surgical resection.³⁴

As tumoral calcinosis has been reported in siblings and most frequently in German shepherd dogs, an underlying genetic defect is suspected to play a role. Some authors have suggested that tumoral calcinosis in German shepherd dogs could be caused by a familial syndrome similar to the human primary hyperphosphatemic tumoral calcinosis,^{4, 37-39} but such defects of mineral homeostasis have never been identified in these dogs.^{15, 34} In addition primary hyperphosphatemic tumoral calcinosis in humans generally causes multiple lesions that recur after surgical removal, whereas in German shepherd dogs the lesion is typically solitary and does not recur after complete surgical excision.

Several cases of paravertebral tumoral calcinosis similar to the case presented in this paper have been reported and are summarized in Table 1. In the majority of these dogs, the mineralized lesion was localized within the cervical spine. The focus of mineralization occurred most frequently between the dorsal aspects of the first and the second cervical vertebrae causing spinal cord compression. In all cases in which the mass was surgically removed the dogs made a complete recovery with no recurrence. Three dogs with C1-C2 spinal cord compression⁴⁶ have not been included in the table as in those cases the histological findings were not typical of tumoral calcinosis. However, these dogs appeared to suffer from a very similar syndrome as all were young, (three to five months old) large breed dogs (Bernese mountain dog, St Bernard and Rottweiler). It was suggested that their lesions could be a variant of calcinosis circumscripta and that the condition was developmental and derived from aberrant mesodermal tissue. Interestingly, myxomatous connective tissue was found in several lesions classified as tumoral calcinosis by other authors.^{24, 30, 37, 46} In two studies it was theorized that these rudimentary cells of mesenchymal origin could stimulate a foreign body reaction leading to soft tissue mineralization.^{24, 30} The remaining two studies proposed a congenital or hereditary malformation.^{37, 46} Both theories are credible as these paraspinal lesions are always diagnosed within the first year of life.

The German shepherd dog presented in our report had no evidence of metabolic disease and no history of trauma. The absence of a previous trauma was supported by the fact that at surgery no gross abnormalities were detected in the tissues surrounding the lesion. As in other dogs, surgical resection resulted in a cure. We conclude that if no underlying disease is identified when a diagnosis of paraspinal tumoral calcinosis is made, complete surgical resection of the lesion is likely to produce a cure. In contrast, if there is an underlying disease causing abnormalities of calcium/phosphorus metabolism, previous experience in both veterinary and human medicine suggests that the underlying metabolic problem should be addressed and surgical resection alone is inappropriate.

Table 1. Cases of paraspinal tumoral calcinosis reported in dogs

*GSD: German Shepherd dog; BMD: Bernese mountain dog
** Age at time of diagnosis.

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