Metastatic Pulmonary Calcification Research Articles

Warfarin-Induced Pulmonary Metastatic Calcification and Calciphylaxis in a Patient With End-stage Renal Disease

Patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) suffer from a number of metabolic derangements. Ectopic deposition of calcium in the skin, soft tissues, blood vessels, and viscera is a potentially devastating consequence of disorders of calcium and phosphorus homeostasis. We report the case of a patient with ESRD and secondary hyperparathyroidism receiving HD who developed metastatic pulmonary calcification and calciphylaxis following initiation of warfarin therapy after mechanical valve replacement. Because not all patients with ESRD receiving HD develop ectopic calcification, there appears to be a complex cascade of metabolic interactions that predispose patients to this process. Warfarin is a vitamin K antagonist with inhibitory effects not only on proteins of the coagulation cascade, but also on other important protein systems. Its role in ectopic calcium deposition has been the subject of theories and has been reported in the literature, but no link with metastatic pulmonary calcification has been made. Patients receiving HD have an increased incidence of conditions that require chronic anticoagulation with warfarin, such as VTE, atrial fibrillation, and valvular heart disease requiring valve replacement surgery. Bioprosthetic valves should be considered in these patients because of the potential risk of metastatic calcification when warfarin is used in the setting of mechanical valve replacement.

Metastatic Pulmonary Calcification

A chest radiograph of a 47-year-old woman with a dry cough and mild exertional dyspnea showed poorly defined bilateral nodular opacities in the superior lung fields (Panel A). The patient had undergone renal transplantation at 23 years of age for an unspecified glomerulonephritis. She had no history of exposure to tobacco or occupational aerosols. An axial computed tomographic scan of the chest showed centrilobular ground-glass nodules and heterogeneous attenuation, features that were suggestive of calcium deposition (Panel B). Results of serum tests revealed increased serum creatinine (285 μmol per liter [3.2 mg per deciliter]), a normal calcium level (2.3 mmol . . .

Detection of pulmonary calcification in haemodialised patients by whole-body scintigraphy and the impact of the calcification to parameters of spirometry

The early diagnosis of metastatic pulmonary calcification is beneficial, as some patients may develop restrictive changes in respiratory function or in some cases lethal acute respiratory distress. The aim of the study was to evaluate whether scanning with ⁹⁹(m)Tc DPD might be useful in early diagnosis of pulmonary calcification in setting of chronic renal failure and hemodialysis and if presence of pulmonary calcification is associated with an abnormality in respiratory parameters. Forty-two patients with end-stage renal disease, who were treated by regular haemodialysis, were investigated. Twenty five (59.5%) out of forty two patients had increased lung uptake of ⁹⁹(m)Tc DPD at whole body scintigraphy-grade 2 group. These patients were on dialysis 149±26 months compared with 57±16 months in 17 patients with a normal lung uptake of ⁹⁹(m)Tc DPD at whole body scintigraphy- grade 1 group (p<0.01). In grade 2 group 22 patients (88%) had significantly lower (p<0.01) parameters of spirometry (FEF25-75, FEF75 FEF50, FEF25) compared to predicted values while in grade 1 group the parameters were significantly lower in only six patients (35.3%). There was statistically insignificant difference between these two groups regarding parathyroid hormone level (p>0.05). These observations confirm previous findings that scintigraphy with ⁹⁹(m)Tc DPD may be efficious in early diagnosis of pulmonary calcification in hemodialised patients as well as the fact that spirometry is useful in patients with confirmed pulmonary calcifications.

Pulmonary Metastatic Calcification in a Leukemic Patient

Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children and accounts for 80% to 85% of cases. Hypercalcemia-associated pulmonary calcification has been observed in ALL, but overall it is a rare condition. Hereby, we wanted to report a case of pulmonary metastatic calcification in a 4-year-old girl with diagnosis of ALL in our center, who died 1 year after diagnosis of leukemia. Pulmonary infiltrates were seen 2 months after diagnosis of leukemia, which was proved to be the flecks of calcium in alveolar spaces after open-lung biopsy performed 4 months after diagnosis of ALL, but elevated serum calcium was detected late in the course of the disease (7 mo after lung biopsy), this late occurrence of hypercalcemia is not reported yet.

Rapid onset metastatic pulmonary calcifications in end‐stage renal disease

AbstractMetastatic calcification occurs in patients on long‐term dialysis. Electrolyte imbalances in these individuals can result in calcium deposition into otherwise normal tissues. In this article, we present the unusual case of a patient who progressed to end‐stage renal disease soon after a liver transplant and developed extensive pulmonary metastatic calcifications within a few months of starting dialysis. A 56‐year‐old female underwent an orthotopic liver transplant for end‐stage liver disease secondary to hepatitis C; her immunosuppression included tacrolimus and prednisone. She developed acute kidney injury in the immediate post‐operative period, which progressed to end‐stage renal disease. Her serum calcium and phosphorus levels were within normal limits. Within a few months, a CT scan of her chest showed progressive development of metastatic pulmonary calcification. A CT‐guided right lung biopsy showed extensive calcification in the alveolar and blood vessel walls with fibroblastic plugs in the alveolar spaces. To our knowledge, this is the first report of metastatic pulmonary calcification developing rapidly after initiation of hemodialysis. Immunosuppressive therapy may have played a role in the development of metastatic calcification.

Pulmonary Calciphylaxis and Metastatic Calcification With Acute Respiratory Failure in Multiple Myeloma

Pulmonary Calciphylaxis and Metastatic Calcification With Acute Respiratory Failure in Multiple Myeloma

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.

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.

Bronchoscopic and Electron Microscopic Findings in a Dialysis Patient with Metastatic Pulmonary Calcification

Bronchoscopic and Electron Microscopic Findings in a Dialysis Patient with Metastatic Pulmonary Calcification

Progressive Pulmonary Calcification after Successful Renal Transplantation

In 2005, a 46-year-old woman consulted our department for an evaluation of a chest radiographic abnormality. She had undergone a successful living renal transplantation in 1999 after being treated by dialysis for four years. A chest computed tomographic scan revealed progressive bilateral fluffy, poorly defined small nodules and the bronchoscopic study revealed a unique linear and nodular lesion pattern. Based on the findings of these modalities, we confirmed the diagnosis of metaplastic pulmonary calcification. This is the first report of these bronchoscopic findings and submucosal calcification in a case of metastatic pulmonary calcification.

Pleural Effusion in Long-Term Hemodialysis Patients

As a consequence of the expanded use of long-term hemodialysis and extended life spans, complications of chronic renal failure are encountered with an increased frequency among uremic patients. Such patients may develop many thoracic and extrathoracic problems—most frequently uremic pleuritis and pericarditis, uremic pneumonia, infection, and metastatic pulmonary calcification. We retrospectively analyzed the medical records of 257 patients who had received long-term hemodialysis between 1990 and 2006 to better understand the incidence, causes, and clinical features of pleural effusions in this population. The incidence of pleural effusion in hospitalized patients receiving long-term hemodialysis was 20.2% ( n = 52; mean age, 55.83 ± 16.56 years; male-to-female ratio, approximately 3:2). Pleural effusion resulted from hypervolemia in 61.5% and was bilateral in 68.8% of patients. Unilateral effusion was present in 25 of 52 (48%) patients. The most frequent causes of unilateral effusion were hypervolemia ( n = 9) and parapneumonic effusion ( n = 5). Thoracenteses were performed in 14 of the 52 patients in the study group. Of thoracenteses performed, 64.3% of the patients had transudative pleural effusion and 35.7% had exudative effusion. Transudative pleural effusion resulted from hypervolemia in 66.7% and heart failure in 22.2%. Of the patients with transudative effusion, 85.7% were bilateral. The most frequent cause of exudative pleural effusion was uremic pleuritis, which occurred in 40% of the patients. The most common symptom was dyspnea, which occurred in 53.8% of patients. In conclusion, pleural effusions are common in patients receiving chronic hemodialysis. Thoracentesis may be performed in patients with unilateral pleural effusion. Since hypervolemia was the most common cause of pleural effusion, this complication should not be considered an obstacle in renal transplant recipients.

Acute Adult Leukemia (ATL) Successfully Treated with Full Matched Sibling Bone Marrow Transplantation and Haplo-Identical (3 Locus Mis-Matched) Peripheral Stem Cell Transplantation.

[Back ground] HTLV-1 known as the 1st recognized human retrovirus infection described 1979 is endemic to some regions of the world, especially southwest Japan, Caribbean and others. Acute ATL type among the HTLV-1 associated leukemia/lymphoma has the poorest prognosis after various chemotherapies that are easily mutated chemo-resistantly. We hereby present 2 acute ATL cases receiving stem cell transplantation. [Case 1] The patient was a 21 years-old female. Induction therapy like ALL setting and then CHOP 14 for acute ATL induced to CR. The patient had HTLV-1 negative full matched 31 years-old brother. We performed bone marrow transplantation at day 90 from the beginning of initial chemotherapy. Typical conditioning regimens and immunotherapies consisted of CY (60mg/kg×3) +TBI (12Gy) and tacrolimus+steroid respectively. The engraftment was day 14 with no aGVHD of grade 2 to 4 observed till day 100. HTLV-1 viral load by RT -PCR was not detected at day 40 after BMT although HTLV-1 antibody and Western blotting analysis were still positive. [Case 2] The patient was a 32 years-old male. He was admitted our emergency room due to hypercalcemia (Ca 26.5mg/dl).CHOP and other chemotherapies were performed for a critical life saving situation. However, the control of his hypercalcemia was difficult even under intensive chemotherapy with steroid, elcatonin and bisphosphonates. His metastatic pulmonary calcification and arthralgia due to hypercalcemia were progressive on bone scintigram and CAT scan. The Japan Marrow Donor Program failed to provide an adequate donor. We decided to initiate peripheral stem cell transplantation (PBSCT) from his haplo-identical (3 locus mis-matched) HTLV-1 positive 68 years-old mother with informed consent from the patient and his family, as there was no life expectancy from usual chemotherapeutic treatment only. We performed PBSCT at day 90. The conditioning regimen and immunotherapy consisted of fludarabine phosphate (25mg×5) +L-PAM (240mg) +TBI (4Gy) and tacrolimus +steroid +short term MTX from the beginning of initial chemotherapy. At day 16 from PBSCT, Hypercalcemia and metastatic calcification as well as leukemic status improved dramatically. Engraftment and complete chimera were observed on day 11 and day 26 respectively with no aGVHD till day100. Although immunotherapy induced CMV infection was severe, the infection improved by using ganciclovir and foscarnet.[Results] The former case showed positive for results the successful eradication of HTLV-1. The latter case is still positive for HTLV-1 on PCR. However, this case showed CR in acute ATL with neither hypercalcemia nor its related complications.[Conclusion] In our limited studies, the modality for stem cell transplantation in acute ATL to cure or control leukemic cells in young patients has strong potential, even in a haplo-identical setting.

Metastatic pulmonary calcification in a dialysis patient: Case report and a review

A 19-year-old male presented with chest pain and dyspnea. He was anephric following nephrectomy for focal segmental glomerulosclerosis, had a subsequent failed transplant, and had been dialysis dependent for 3 years. Workup revealed hyperparathyroidism and an abnormal chest X-ray and computed tomography scan, significant for massive extra-skeletal pulmonary calcification. A markedly abnormal Technitium99 methylene diphosphonate (Tc99m-MDP) bone scan confirmed the clinical suspicion of metastatic pulmonary calcification. Metastatic pulmonary calcification (MPC) is common, occurring in 60% to 80% of dialysis patients on autopsy and bone scan series. It may lead to impaired oxygenation and restrictive lung disease. Typically, the calcium crystal is whitlockite rather than hydroxyapatite, which occurs in vascular calcification. Four major predisposing factors may contribute to MPC in dialysis patients. First, chronic acidosis leaches calcium from bone. Second, intermittent alkalosis favors deposition of calcium salts. Third, hyperparathyroidism tends to cause bone resorption and intracellular hypercalcemia. Finally, low glomerular filtration rate can cause hyperphosphatemia and an elevated calcium-phosphorus product. There may be other factors. Some authors suggest that the incidence of MPC in recent years may be lower due to improved dialysis techniques. The diagnosis is confirmed by biopsy, but can be suspected by typical findings on a Tc99m-MDP bone scan. Therapy is limited to ensuring adequate dialysis, correcting calcium-phosphorus product, and hyperparathyroidism; discontinuing vitamin D analogues may help. Conflicting reports show that transplantation may either improve or worsen the situation. MPC should be considered in dialysis patients who have characteristic abnormal chest radiography and/or pulmonary symptoms.

Myofibroblasts in the stroma of metastatic pulmonary calcification in a patient with chronic renal failure

We present a case of metastatic pulmonary calcification. Histologically, deposition of hematoxyphilic materials was seen along the alveolar and vessel walls. Fibrous tissues were also seen within the alveolar lumens, resulting in intra-alveolar fibrous pneumonia. Immunohistochemically, CD34-positive perivascular adventitial fibroblasts were seen in normal alveolar septa, whereas no myofibroblasts were observed. In contrast, perivascular adventitial fibroblasts were absent in the alveolar septa of the lesion of metastatic calcification, whereas many myofibroblasts were present in the fibrous tissue within alveolar lumens. No positive cells for TGF-(beta1) were observed in the lesion of metastatic calcification, but positive cells for PDGF-BB were focally seen in adveolar epithelial cells. Finally, many myofibroblasts appear in the alveolar lumens of metastatic pulmonary calcification, and we suggest that these myofibroblasts may be derived from CD34-positive perivascular adventitial fibroblasts and PDGF-BB may be involved in the pathogenesis of surrounding fibrosis.

Fulminant Pulmonary Calciphylaxis and Metastatic Calcification Causing Acute Respiratory Failure in a Uremic Patient

Calciphylaxis is a rare and life-threatening disorder characterized by small-vessel mural calcification with intimal proliferation, fibrosis, and thrombosis, resulting in tissue ischemic necrosis. Although it has been viewed as a systemic disease involving mainly the dermis, subcutaneous fat, or muscle, calciphylaxis of other organs rarely is reported. We describe the case of a 25-year-old uremic woman who rapidly developed massive pulmonary calcification that led to acute respiratory failure after the initiation of hemodialysis therapy. Chest radiography and high-resolution computed tomography showed typical pulmonary calcification. Pulmonary calciphylaxis and metastatic calcification were confirmed further by lung tissue biopsy. No skin or muscle calciphylaxis was discovered. Despite multiple factors precipitating pulmonary calciphylaxis in this patient, we speculate that hemodialysis was the main culprit in accelerating the development of fulminant pulmonary calciphylaxis and metastatic calcification. Alteration in the local environment from an acid to an alkaline condition and a relatively high dialysate calcium level in the presence of systemic hyperphosphatemia are believed to have facilitated the deposition of calcification. This case highlights the importance of "visceral calciphylaxis" and early identification of its causes.

Imaging of diffuse metastatic and dystrophic pulmonary calcification in children after haematopoietic stem cell transplantation

The authors describe three cases of diffuse pulmonary calcification; two metastatic in children with acute transitory renal failure and the other dystrophic in a child with leukaemia. All three patients underwent haematopoietic stem cell transplantation (HSCT). Chest radiographs disclosed diffuse calcification within the lungs. The distribution of this calcification was bilateral but asymmetric. Diagnosis was made in two cases by high resolution computed tomography (HRCT) and in one case by HRCT and bone scan. Radiological characteristics, scintigraphic features, pathological mechanism and clinical outcome of such pulmonary calcification are discussed.

Metastatic Pulmonary Calcification in Renal Failure Mimicking Pulmonary Embolism on Lung Scan

Metastatic pulmonary calcification (MPC) characterized by diffuse calcium deposition in the lungs is known to occur in patients with chronic renal failure. However, MPC with pulmonary artery calcification is uncommon and has only been detected in a few patients with severe disorders. A 48-year-old man with chronic renal failure had cough and progressive dyspnea. Ventilation-perfusion (V/Q) lung scans showed multiple large-sized mismatched V/Q defects in the left middle and lower zones of lungs, which was consistent with a high probability of pulmonary embolism (PE). The findings of pulmonary scintigraphy resulted from MPC with pulmonary artery calcification, revealed by simultaneous technetium-99m MDP scintigraphy, low-dose computed tomography, and high-resolution computed tomography (HRCT) of the chest.

Unusual Manifestations of Metastatic Pulmonary Calcification

The aim of this report is to describe the high-resolution CT and pathologic findings of 3 patients with unusual manifestations of metastatic pulmonary calcification. These include a case that presented with extensive dense consolidation, a case of metastatic calcification that improved spontaneously, and a case of metastatic calcification in a patient with no demonstrable biochemical abnormality or underlying disease. We conclude that metastatic calcification may present with dense bilateral consolidation, may improve spontaneously, and may rarely present in patients with no apparent underlying biochemical abnormality.