Metastatic Calcification Research Articles

Radiological Features of Soft Tissue Calcification: A Pictorial Essay

Calcification of soft tissue may represent a nonspecific local response or be a manifestation of underlying disease. The diagnosis and principle of treatment varies depending on the characteristics of the calcified lesions. Soft tissue calcification is classified by mechanism into 3 types: metastatic calcifications, calcinosis, and dystrophic calcifications. However, classification according to the site and shape of calcification may be more helpful for a clinical diagnosis. The purpose of this pictorial essay is to classify soft tissue calcifications according to their location: vessel, periarticular, joint capsule, tendon, bursa, cartilage, ligament, and in tumors, as well as to document the characteristic radiological findings and causes of calcifications.

Hypercalcemia and metastatic calcification in a neonate with subcutaneous fat necrosis

We report a 30-day-old baby with subcutaneous fat necrosis and symptomatic hypercalcemia, who developed metastatic calcification in the subcutaneous tissue, kidneys, pericardium and brain. The baby also had anemia, hypertriglyceridemia and hypercholesterolemia. He was managed with intravenous saline, furosemide, oral steroids and bisphosphonates and improved with treatment.

Nephrogenic systemic fibrosis associated with stromal and vascular calcification, report of two cases

Nephrogenic systemic fibrosis (NSF) is a systemic fibrosing disorder characterized by the development of large indurated plaques on the skin, primarily in patients with end-stage renal disease (ESRD). Skin biopsy reveals an increased frequency of CD34(+) and Factor XIIa+ cells. Microscopic calcification has been reported in the skin biopsies of rare cases of NSF. The etiology and significance of this calcification is not clear. We present two cases of typical NSF, for which marked stromal and vascular calcification was identified on skin biopsy. In both cases, the calcification was within typical NSF lesions and was intimately associated with aggregates of CD34(+), Factor XIIIa+ spindle and stellate cells. This particular pattern of calcification strongly argues against either nonspecific dystrophic calcification or coincidental metastatic calcification. These findings suggest that calcification may be intrinsic to the pathophysiology of NSF, at least in a subset of NSF patients. In addition, the vascular calcification involving small arteries and arterioles in these two cases morphologically resembled calciphylaxis, which is another poorly understood complication of ESRD. This resemblance raises the possibility that NSF may predispose to or develop in the vicinity of indolent lesions of early-stage calciphylaxis. We propose that skin biopsies performed as part of a diagnostic workup for suspected NSF should preferably include the deep dermis and subcutis, in order to assess possible vascular calcification.

Metastatic pulmonary calcification in a patient with long dialysis vintage.

A 53-year-old man with end-stage kidney disease on haemodialysis thrice weekly for 32 years due to purpura nephritis presented with exertional dyspnoea and fever. Chest radiograph revealed nodular shadows in the periphery of lung areas, especially bilateral upper lung areas (Fig- ure ​ure1),1), and computed tomography of the chest revealed high dense foci of a ground-glass appearance in bilateral upper lung areas (Figure ​(Figure2A).2A). At first, he was suspected to have infectious pneumonitis, because of opportunistic condition due to long-lasting steroid use and immunosuppressive therapy for recurrent episodes of purpura. However, the symmetrical and upper lung distribution of the lesions raised the possibility of metastatic pulmonary calcification (MPC). A Technetium 99 methylene diphosphonate (Tc-99m-MDP) bone scan was then performed and an increased uptake in the upper lobe lesions (Figure ​(Figure2B)2B) confirmed the diagnosis of MPC. Indeed, respiratory function tests noted a restrictive pattern. Fig. 1 Chest radiograph showing nodular shadows in the bilateral upper lung. Fig. 2 (A) Computed tomography showing diffuse ground-glass opacities in the bilateral upper lung. (B) 99mTc-MDP bone scan showing prominent uptake of the bilateral upper lung. The review of the medical history revealed that he had undergone a total parathyroidectomy for secondary hyperparathyroidism 17 years ago and, subsequently, developed adynamic bone disease. For hypocalcaemia, he had been taking large doses of calcium carbonate and alfacalcidol for a long term. His recent intact parathyroid hormone level was 15 pg/ml, serum calcium 9.0 mg/dl, serum phosphate 2.2 mg/dl, and calcium phosphate product 19.8 mg2/dl2. Doses of calcium carbonate and vitamin D were reduced to a minimum to maintain normocalcaemia. MPC was found to be common (60–80%) by bone scan or autopsy among dialysis patients and can cause restrictive lung disease, however, rarely manifests overt symptoms and is often overlooked. Pathogenesis of MPC still remains to be determined but is suspected to be associated with bone and mineral disorders as in other ectopic calcification. Therefore, reduction of calcium-containing medication, vitamin D or its analogues is a mainstay for the management of MPC. Conflict of interest statement. None declared.

Rapidly progressive metastatic pulmonary calcification: evolution of changes on CT

Metastatic pulmonary calcification occurs in association with several disease processes and has a highly variable prognosis. In certain patients, it may prove fatal, and therefore prompt recognition of radiological signs is helpful for optimising patient management. We describe the progressive changes seen on CT in a 59-year-old man who had undergone renal transplant and subsequently developed metastatic pulmonary calcification. The merits of the different imaging techniques available and possible treatment options are reviewed.

Metastatic Pulmonary Calcification in a Patient with Chronic Renal Failure

Metastatic pulmonary calcification characterized by diffuse calcium deposition in the lungs is known to occur in patients with chronic renal failure. We present a case of a 47-year-old man with chronic renal failure presented with dyspnea, high-resolution computed tomography of the chest revealed multiple, centrilobular, calcified nodules and patchy areas of ground-glass opacity throughout both lungs, consistent with metastatic pulmonary calcification. Calcification was also seen in the bronchi and trachea.

Bilateral Elongated Styloid Process in an End-stage Renal Disease Patient with Peritoneal Dialysis: Is there Any Role for Ectopic Calcification?

A 26-year-old man who had end-stage renal disease (ESRD) due to primary glomerulonephritis presented for a routine dental examination. He had peritoneal dialysis (PD) as renal replacement therapy for 2 years. He had smoking one to two packs of cigarettes a day for five years and did not drink alcohol. On clinical examination, the maxillary left canine tooth was absent. The left first molar tooth’s clinical crown was fully carious, but its roots were in the jaw. In the mandibular jaw, the right first molar tooth and the left first molar tooth were carious. A panoramic radiography (PR) was taken as a screening film after the examination. Radiographic imaging showed that the left canine tooth was impacted, and the left first molar tooth’s roots were in the maxillary jaw. In the mandibular jaw, the left third molar tooth was also impacted and the right first molar tooth was carious, but the roots were in the jaw. Bilateral styloid process elongations (SPEs) were also detected (right: 47 mm, left: 58 mm) in the PR of the patient (Figure 1). He had any complaints regarding SPE or Eagle’s syndrome. Figure 1. Bileteral styloid process elongation in an end-stage renal disease patient with peritoneal dialysis on a panoramic radiography. The styloid process (SP) is a cylindrical, long cartilaginous bone located on the temporal bone. There are many vessels such as carotid arteries and nerves adjacent to the SP.1,2 The normal length of the SP is approximately 20–30 mm.3–8 The length of SP and/or stylohyoid ligament, which are longer than 30 mm were considered to be SPE.3,5,7–10 SPE resulted in facial and neck pain is known as Eagle’s syndrome.5,6,10,11 More uncommonly, symptoms such as dysphagia, tinnitus, and otalgia may occur in patients with this syndrome. The symptoms and signs with this syndrome are due to the anatomic relationship between the SP and its surrounding structures.1,12 Therefore, it may also cause stroke due to the compression of carotid arteries.3,13 The exact cause of the elongated SP due to calcified and ossified bone and the ligament is not clear. It was suggested that local chronic irritations, surgical trauma, endocrine disorders in female at menopause, persistence of mesenchymal elements, growth of the osseous tissue and mechanical stress or trauma during development of SP could result in calcified hyperplasia of the SP.3,10,14,15 Extraskeletal (ectopic) calcification or ossification may have a role for the elongation of the SP. Ectopic calcification (EC) in nonosseous soft tissue may be due to three mechanisms: metastatic calcification due to disorders causing abnormal serum Ca and P levels, dystrophic calcification due to mineral deposition into metabolically impaired or dead tissue despite normal serum levels of Ca and P, and ectopic ossification. The patients with ESRD have risks for EC due to disorders (renal failure, dialysis, secondary hyperparathyroidism) causing metastatic calcification.16 In the present report, a detailed differential diagnosis was done for the disorders causing dystrophic calcification (scleroderma, dermatomyositis, systemic lupus erythematosis, trauma-induced etc.), ectopic ossification (post surgery, burns, neurologic injury, myositis ossificans etc.) and also, any diseases causing metastatic calcification. Except renal failure, disease causing metastatic calcification such as sarcoidosis, tumoral calcinosis, primary hyperparathyroidism, milk alkali syndrome etc. were investigated for this patient and any disease was detected.16 As a result, SPE found as incidental findings on PRs may be important clinically in not only patients with ESRD, but also normal population. Instead of many hypotheses and studies, the exact etiology of elongated SP and the role of ectopic calcification are unknown. Abnormality in Ca and P metabolism (EC) is very common in patients with ESRD. According to our knowledge, this is the first case study showing SPE associated with ESRD in a patient. In conclusion, this report suggests that EC or the abnormality in Ca and P metabolism may have a role in the elongation of SP. However, further studies and large samples are needed to clarify the etiology of this disorder, and the role of EC.

Treatment of severe metastatic calcification in hemodialysis patients

Soft tissue and vascular calcifications are commonly present in uremic patients secondary to disturbances in calcium and phosphate balance and secondary to hyperparathyroidism. We report a uremic patient who developed uncontrolled hyperparathyroidism rapidly within 6 months after commencing hemodialysis (HD) therapy, with clinical presentations of tumoral calcinosis, calciphylaxis, and myocardial calcifications. After treatment with a low-calcium dialysate, non-calcium-containing phosphate binders, and parathyroidectomy, a dramatic resolution of soft tissue calcification was achieved. However, there was relatively little change in the vascular and other visceral calcifications over the 3-month observation period. This case highlights an unusual and rapid development of tertiary hyperparathyroidism, the importance of tight calcium/phosphate control in uremic patients, the potential hazards of a high calcium concentration dialysate, and the dangers of the overzealous use of active vitamin D therapy in HD patients with uncontrolled hyperparathyroidism.

Massive and rapid left ventricular calcification.

A 21-year-old woman was diagnosed with Hodgkin’s lymphoma (stage IV-B) in 2001 and underwent chemotherapy and then three stem cell transplantations [auto-peripheral blood stem cell transplantation (PBSCT) in 2002, allo-bone marrow transplantation from her mother in 2002 and alloPBSCT from her sister in 2003]. From 2004, her serum creatinine began to rise and, in March 2005, she reached end-stage renal failure. From 28 February 2005, she started to experience severe and rapid calcification localized to left ventricle and died in June 2005. Secondary hyperparathyroidism was present (the PTH value on 13 April 2005 was 502 pg/ml: the normal range was 10–60 pg/ml); however, the product of serum calcium and phosphate was always<65 (mg/dl)2, or 5.25 (mmol/l)2. Metastatic calcification of various organs including myocardium has been reported with HTLV-1 infection [1], but in our case, HTLV-1 was negative. The cytology of the pericardial effusion did not show any lymphoma cells; therefore, metastatic lymphoma would be the least likely cause. Myocardial calcification has been reported after orthotopic

A Model on the Induction of Adverse Vascular Long-Term Effects of NSAIDs

The causes of increased rates of myocardial infarctions and strokes by application of non-steroidal anti-inflammatory agents (NSAIDs) are unclear. Here we present a biochemical model that the long-term vascular effects of NSAIDs can be consequences of their antiproliferative cellular mechanism. The analysis of the model suggests that the intramitochondrial uncoupling of oxidative phosphorylation induced by NSAIDs increases, through a reduced activity of ATP-dependent ionic pumps, the intra-cellular calcium x phosphate product with a consecutively increased formation and export of various calcium phosphate compounds. The latter cause, by chemical replication mechanisms of arterial hydroxyapatite deposits, a metatstatic calcifying vascular process. This sclerogenic vascular mineralization corresponds to an early arteriosclerotic development resembling the Mönckeberg's media calcification. The mechanism shows direct analogies to the accelerated and metastatic calcification of coronary arteries seen in chronic kidney disease and dialysis. This appears an extra-cellular time-lapse version of the protracted cell model. The induction of this degenerative mechanism may explain the increased number of adverse cardiovascular, renovascular and cerebrovascular effects of NSAIDs as they are observed in long-term therapies.

Consolidation With Diffuse or Focal High Attenuation

This pictorial essay aims to present various lesions that could present as consolidations with diffuse of focal high attenuation on computed tomography, helping to make the diagnosis more confident and specific. The radiologic literature has limited information about such findings and the role of computed tomography in the differential diagnosis. The following diseases are presented: metastatic pulmonary calcification, pulmonary alveolar microlithiasis, amiodarone lung, talcosis, iodinated oil embolism, tuberculosis, silicoproteinosis, and amyloidosis. In conclusion, air-space consolidations can be seen in a wide variety of diseases affecting the lungs. The identification of the different patterns of consolidation with focal high attenuation narrows the differential diagnosis. We present a diagnostic approach based on appearance and distribution of these lesions.

Metastatic calcification involving the true vocal cord

Metastatic calcification (MC) commonly results secondary to phosphorus and calcium dysregulation in end-stage renal disease (ESRD). Only once before has MC been reported to involve a true vocal cord. A 35-year-old man with ESRD and secondary hyperparathyroidism was evaluated for hoarseness. Three years ago, he underwent a total parathyroidectomy with parathyroid autograft to the forearm. Simultaneously, he had a left lobe thyroidectomy that displayed a papillary thyroid carcinoma. Since that time, he continued to have hyperphosphatemia and hypocalcemia. Laryngoscopy displayed a small papillomatous lesion on the right true vocal cord. He underwent excision of the vocal cord lesion; histologic examination demonstrated benign squamous epithelium with extensive submucosal calcification. In patients with ESRD with secondary dysregulation of serum phosphorus to calcium level balance, MC may involve variable anatomical locations, including the true vocal cords. Regarding histologic findings, pathologists must consider malignancies associated with calcification, mimicking a benign process.

Extensive pelvic calcification in association with ovarian serous cystadenofibroma

We describe the first reported case of extensive calcification seen in association with serous cystadenofibroma of the ovary, illustrating that calcification in the female genital tract may be extensive in nature, presenting in a fashion that is not entirely typical of dystrophic or metastatic calcification. This case demonstrates that extensive calcification within the pelvis should be interpreted with caution, as it may not represent disseminated malignancy.

Unusual Metastatic Soft Tissue Calcification in a Hemodialysis Patient

Unusual Metastatic Soft Tissue Calcification in a Hemodialysis Patient

Bone Scan Findings in Metastatic Calcification From Calciphylaxis

A 51-year-old woman on peritoneal dialysis for chronic renal failure secondary to diabetic and nonsteroidal anti-inflammatory drug nephropathy was referred for a Tc-99m MDP bone scan to assess firm subcutaneous plaques in the sacral and gluteal regions. This showed extensive superficial tracer localization in the subcutaneous tissues as well as visceral tracer activity in the myocardium, lungs, stomach, and kidneys. These findings were typical for calciphylaxis (calcific uremic arteriolopathy), a form of metastatic calcification encountered in patients with chronic renal failure that is characterized by subcutaneous soft tissue calcification, painful ulcerations, high morbidity, and mortality. Treatment with sodium thiosulfate resulted in dramatic scintigraphic improvement.

Breast cancer screening in women with chronic kidney disease: the unrecognized effects of metastatic soft-tissue calcification

Patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD) are known to develop metastatic soft-tissue calcification, secondary to hyperparathyroidism, in tissues including the breast. Such calcifications in women could pose a problem for interpretation of mammograms, since they are thought to mimic malignant lesions and interfere with differentiation of benign from malignant disease. Investigation of this issue is important to provide high-quality, accurate breast care to women with CKD or ESRD, but little evidence is so far available. In a systematic review of the literature on the types and patterns of breast calcifications, we found only three studies that examined metastatic soft-tissue calcifications of the breast. The studies did, however, confirm that women with CKD or ESRD have a higher frequency of breast calcification than women with normal kidney function. The two older studies reported that these breast calcifications are not associated with malignancy, but the later study reported a raised rate of suspicious breast calcification among women with ESRD receiving hemodialysis, leading to an increased biopsy referral rate. In this Review we discuss the strengths and limitations of the available data and whether mammography is recommended in women with CKD or ESRD.

Massive Soft Tissue Calcifications and Cinacalcet

A 37-yr-old man on long-term hemodialysis developed a relapse of secondary hyperparathyroidism after subtotal parathyroidectomy. Dialysis treatment adjustment and conventional medical therapies, involving noncalcium phosphate binders and active vitamin D sterols, proved ineffective. Painful and rapidly increasing tumor-like masses appeared over the second finger and the back of his right hand. Laboratory studies showed persistent serum levels of intact PTH of more than 1500 pg/ml and calcium-phosphate product of more than 100 mg/dl [recommended levels in dialysis patients, 150–300 pg/ml (16.5–33 pmol/liter) and 55 mg/dl, respectively] (1). A radiograph of the right hand revealed massive soft tissue swelling and calcifications (Fig. 1). Due to the patient’s disinclination for further surgical treatment, we decided to administer cinacalcet (2, 3), a calcimimetic agent, at doses of 30–60 mg/d, achieving a significant suppression of intact PTH (350 pg/ml) and calcium-phosphate product (60 mg/dl). After correction of the calcium-phosphate product, oral calcitriol and calcium acetate were administered. Six months later, a radiographic control showed the disappearance of the calcifications (Fig. 2). Massive soft tissue calcification is a feature of severe renal hyperparathyroidism and is due to chronic elevation of calciumphosphate product, resulting in the precipitation of calcium phosphate. The calcified masses should not be misdiagnosed as tumors and surgically excised, because they will recur unless the biochemical abnormalities are corrected (4). High serum calcium and phosphate levels may also cause disseminated calcification in the skin, joints, viscera, and arteries (calciphylaxis) resulting in painful ischemic necrosis of skin and gangrene, cardiac arrhythmias, and pulmonary failure. Uncontrolled hyperphosphatemia and progressive metastatic calcifications have always been indications for surgical parathyroidectomy (5). When conventional therapies have been exhausted, cinacalcet represents an exceptional therapeutic opportunity particularly for patients exposed to technical difficulties linked to a neck re-operation (3).

Metastatic calcification as a result of extensive bone metastases in a paediatric patient with Parameningeal Embryonal Rhabdomyosarcoma

We present a case of Parameningeal Embryonal Rhabdomyosarcoma with the primary lesion arising in the middle and inner ear, with associated diffuse skeletal metastases and metastatic calcifications.

Les calcifications métastatiques de l’hyperparathyroïdie identifiées par scintigraphie osseuse au MDP-Tc99m dans le cadre du carcinome parathyroïdien : à propos d’un cas

The authors report a case of gastric, renal, pulmonary, and myocardial uptake of MDP-Tc99m in a patient with parathyroid carcinoma. Parathyroid carcinoma is a rare cause of primary hyperparathyroidism which becomes complicated during its evolution by metastatic calcifications. Metastatic calcifications are frequently located in lungs and heart. If an adequate treatment is not undertaken, these calcifications progress and evolve into severe respiratory and cardiac complications. In our patient, quasi-complete disappearance of metastatic calcifications on the follow-up bone scintigraphy, performed four weeks after surgical cure of parathyroidal tumour, indicates the great interest of this examination in early identification of metastatic calcifications and monitoring of their disappearance after treatment.

Myocardial calcification: observation in a infant death with congenital heart malformation

Calcification of the myocardium occurs by one or two mechanisms: metastatic or dystrophic. Metastatic calcification usually involves a disturbance in calcium-phosphate metabolism with result in the deposition of calcium. Dystrophic calcification occurs in myocardial hemorrhage, fibrosis, or necrosis, myocarditis. Common etiologies of dystrophic calcification include myocardial infarction and ventricular aneurysms. Authors present a case of 2-month-old-child with heart malformation and unexpected death in progressive involution. Histopathological examination of myocard evidenced disseminates fibrosis, and myocardial calcifications. The etiology of myocardial calcification is not classifiable.