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Soft tissue calcifications: a pictorial essay

Soft-tissue calcifications are extremely common. Because the imaging findings are nonspecific, soft-tissue calcifications are often problematic for radiologists, sometimes prompting unnecessary interventions. In addition, the nomenclature is quite confusing. Classically, soft-tissue calcifications are divided into four categories, by mechanism of formation-dystrophic, iatrogenic, metastatic, and idiopathic-depending on the clinical and biochemical correlation. However, it is also possible to classify such calcifications by compartment, and that classification can be quite useful in the radiological diagnostic assessment. In this article, we illustrate the main causes of soft-tissue calcifications, organizing them according to their anatomical and pathophysiological aspects, thus narrowing the differential diagnosis.


INTRODUCTION
On imaging examinations, soft-tissue calcifications are findings that are as common as they are nonspecific, ranging from a nonspecific local reaction (in response to a traumatic insult) to the manifestation of a systemic condition (1,2) . In addition to this lack of specificity and the long list of differential diagnoses, the nomenclature is confusing and not very intuitive (3,4) .
Classically, these calcifications are divided into four categories, depending on the mechanism of formation as well as the clinical and biochemical correlation (5) : dystrophic, metastatic, idiopathic, and iatrogenic. However, it is also possible to classify such calcifications by compartment (subcutaneous, neurovascular, fascial, muscle, and periarticular), and that classification can be quite useful in the radiological diagnostic assessment (1,2) .
In this article, we illustrate the main causes of softtissue calcifications in a practical and didactic manner. We believe that this knowledge will help narrow the differential diagnosis of such calcifications.
formations, from which phleboliths can arise. Vascular calcifications have a characteristic shape, being either tubular or arranged in parallel lines (1,2,6) .

Subcutaneous compartment
Subcutaneous calcifications are associated with diseases of various origins. Preeminent among those diseases are conditions with inflammatory and traumatic causes, such as connective tissue diseases, injection-site granulomas, and panniculitis ossificans, which is a form of heterotopic ossification involving the subcutaneous tissue, usually resulting from local trauma (1) .

Fascial compartment
Calcifications of the fascial compartment are associated with dermatomyositis and polymyositis, diseases that are characterized by muscle inflammation, with or without cutaneous/subcutaneous involvement, a clinical feature that differentiates them from other conditions. During the chronic phase of these diseases, after episodes of myositis, calcifications develop in necrotic areas of the fascial planes. The calcifications are typically long and linear (leaf-like), following the outline of the fascial compartment (1) , as depicted in Figure 3.

Muscle compartment
Calcifications in the muscle compartment result from infectious, traumatic, or congenital insults (1) . Preeminent among the infectious causes are granulomatous and parasitic infections, particularly cysticercosis ( Figure 4). Chief among the traumatic causes is myositis ossificans ( Figure 5), a type of heterotopic ossification that develops after a trauma (burns are a classic cause). In individuals with myositis ossificans, the initial X-ray findings (small calcifications) appear two to six weeks after the trauma (6) .
Although it is called myositis, there is no inflammatory process (1,6) . Other traumatic causes of muscle calcifications include calcified muscle hematomas ( Figure 6) and calcific myonecrosis (4) . The congenital causes include fibrodysplasia ossificans progressiva (Figure 7), a rare autosomal dominant disorder that is extremely debilitating,   R characterized by diffuse, progressive heterotopic ossification and equally progressive impairment of mobility (7) .

Periarticular compartment
Periarticular calcifications occur in intra-or extraarticular components that have previously been involved in inflammatory or degenerative processes. Extra-articular calcifications occur when in tendons, bursae, and ligaments (Figure 8), typically after surgery/trauma or as a result of hydroxyapatite crystal deposition.
As shown in Figure 9, calcific tendinopathy and calcific bursitis (hydroxyapatite deposition in degenerated tendons or bursae) are quite common in the general population, usually affecting the shoulder (the tendon of the supraspinatus muscle) in the fifth decade of life (2,8) . In addition to their deposition in the tendons, the hydroxyapatite crystals can accumulate in the joints (crystal arthropathy), causing synovitis and articular damage. The most commonly affected site is the shoulder, causing what is known as Milwaukee shoulder syndrome (1) , as depicted in Figure 10.
Intra-articular calcifications are calcifications of articular cartilage (chondrocalcinosis). The most common cause of such calcifications is arthropathy resulting from the deposition of calcium pyrophosphate dihydrate (CPPD) in hyaline cartilage and fibrocartilage, including the meniscus, acetabular labrum, and intervertebral discs (3,6) , as illustrated in Figure 11. The term chondrocalcinosis denotes the radiological or histological identification of calcifications in cartilage, which can occur in metastatic calcifications; therefore, it should not be used as a synonym for CPPD deposition disease. Another term that is often used incorrectly to refer to CPPD deposition disease is pseudogout, which actually refers to a gout-like clinical syndrome and not to the radiological finding (3) . The origin of CPPD arthropathy is most probably degenerative, resulting from an abnormality in the local metabolism of the synovial fluid and articular cartilage (2) . It is quite common in the elderly and is usually asymptomatic (3) .
The shape and distribution of intra-articular calcifications facilitate their differential diagnosis. Calcifications resulting from hydroxyapatite deposition (calcific tendinopathy and calcific bursitis) are nodular or cotton ball-like, mainly affecting extra-articular tissue (8) , whereas  Figure 10. Hydroxyapatite-induced arthropathy in Milwaukee shoulder syndrome. Frontal X-ray of the chest showing the right shoulder with joint surface deformity, joint space reduction, and superior displacement of the humeral head with loss of the subacromial space (probably associated with a rotator cuff tear). Periarticular calcifications and intra-articular loose bodies can also be seen. R those resulting from CPPD deposition tend to be smaller and more linear, with a stratified appearance (2) .
Another cause of intra-articular calcification is synovial osteochondromatosis, a rare entity caused by chondroid metaplasia of the synovial tissue with proliferation of osteocartilaginous bodies within the synovium. These bodies typically have a chondroid mineralization pattern and can be completely calcified or have a typical calcified halo (1,4,9) , as depicted in Figure 12.
Various other benign and malignant tumors of bone or soft tissue produce periarticular (intra-and extra-articular) calcifications, including a wide range of differential diagnoses (1,6) , the review of which is beyond the scope of this article.

METASTATIC (METABOLIC) CALCIFICATIONS
Metastatic (metabolic) calcifications are generalized calcifications that occur in normal tissue and are typically caused by the deposition of calcium salts resulting from a systemic metabolic disorder that leads to an elevation of the calcium-phosphate product to above the 60-70 range (2,4) .
The most common cause of metastatic calcifications is end-stage renal disease, which is also the main cause of massive periarticular calcifications. When that is the case,  R the metabolic disorder results from renal dysfunction, showing a correlation with the duration of the disease and possibly occurring even in the absence of hyperparathyroidism (4,9) . Metastatic calcifications consist of periarticular lobulated calcified masses that are usually multicystic and contain fluid-calcium levels (Figure 13), which is known as the sedimentation sign (1,4,10) . Other causes of metastatic calcifications with disorders of calcium and phosphate metabolism include primary hyperparathyroidism, milk-alkali syndrome, and hypervitaminosis D.
Other ionic imbalances, secondary to mechanisms such as skeletal demineralization, massive bone destruction, and increased intestinal absorption, can also cause metastatic calcifications. Gout, which results from hyperuricemia, is one such cause (Figure 14). When calcifications are present in gout, they are usually accompanied by tophi, with or without other bone findings, such as erosion (2,4,6) .

IDIOPATHIC CALCIFICATIONS
Idiopathic calcifications occur in tumoral calcinosis, a rare familial disease caused by abnormal regulation of phosphate metabolism. This disease is characterized by the appearance, around the second decade of life, of periarticular calcified masses, which, in imaging tests, are indistinguishable from metastatic calcifications caused by a disorder of calcium and phosphorus metabolism, and are typically distributed on the extensor surfaces (bursal sur-faces) of large joints (Figure 15). They are often asymptomatic and can progress slowly. Two forms of idiopathic tumoral calcinosis have been identified (2,4) . Although both are caused by specific genetic mutations, phosphate levels

A B
L are increased in one (the familial form) and normal in the other (the sporadic form). Although metastatic calcifications are often referred to as "secondary tumoral calcinosis", the term "tumoral calcinosis" should be used strictly in reference to the familial form of the disease (4) .

CALCINOSIS CIRCUMSCRIPTA AND CALCINOSIS UNIVERSALIS
Calcinosis circumscripta and calcinosis universalis are well-established terms, used in order to refer to cutaneous and subcutaneous calcifications that occur in the absence of an underlying metabolic disorder and are typically associated with connective tissue diseases.
In calcinosis circumscripta, calcium deposition occurs in a localized way, in the form of densely calcified, homogeneous nodules around the fingertips, especially the thumbs and index fingers (2) . Patients develop papules, plaques, and subcutaneous nodules that can ulcerate and discharge a whitish material (1,4) . The condition is usually associated with scleroderma (5) , as illustrated in Figure 16.
In calcinosis universalis, there are bands or sheet-like calcifications in subcutaneous, muscle, and fascial tissues with a diffuse, symmetrical distribution. It is usually seen in connective tissue diseases, primarily dermatomyositis and polymyositis (4) , as shown in Figure 17.

CONCLUSION
Soft-tissue calcifications are extremely common findings in imaging tests and are often a source of confusion   for radiologists, sometimes prompting unnecessary interventions. A thorough and systematic evaluation of these lesions, in conjunction with the analysis of clinical and biochemical data, can help narrow the differential diagnosis.