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Case of the season
Case of the S e a s o n Joseph W. Sam
A
53-YEAR-OLD white woman with a history of end-stage liver failure due to cryptogenic cirrhosis presented to our institution for an orthotopic liver transplant. The operation was extremely difficult secondary to fibrinous peritonitis and the patient's severe coagulopathy, which necessitated the transfusion of 105 units of packed red blood cells and a comparable amount of fresh, frozen plasma and platelets. Furthermore, the postoperative course was complicated by a peritoneal hematoma requiring surgical evacuation, several episodes of bacterial sepsis, which responded well to antibiotics, and Candida peritonitis and sepsis, which was treated with a 6-week course of amphotericin. Ultimately, the patient recovered and chest radiographs taken 8 weeks after the original surgery showed no active disease. Two weeks later, the patient developed a patchy opacity in her left upper lobe (Fig 1) that was believed to represent a developing pneumonia; however, sputum cultures remained negative. Over the next 2 weeks, the area of opacification persisted and became more nodular
Fig 1. Chest radiograph demonstrates a left upper lobe infiltrate.
in character; however, the patient demonstrated no pulmonary symptoms and was eventually discharged 2 months later, with close follow-up and a repeat chest radiograph scheduled for 1 month later. The follow-up chest radiograph showed worsening of the left upper lobe nodular opacity (Fig 2), which was now believed to represent a smoldering fungal pneumonia. The patient was admitted for bronchoscopic biopsy. Bronchial brushings and washings were negative, as was a transbronchial biopsy. Two days later, the patient, who remained asymptomatic, underwent a diagnostic procedure.
From the Hospital of the University of Pennsylvania, Philadelphia, PA. Address reprint requests to Joseph W. Sam, MD, PhD, Department of Radiology, University of Pennsylvania Medical Center, 3400 Spruce St, Philadelphia, PA 19104. Copyright © 1999 by W.B. Saunders Company 0037-198X/99/3404-0003510. 00/0
Fig 2.
Seminars in Roentgenology, Vol XXXIV, No 4 (October), 1999: pp 253-255
Chest radiograph shows worsening of the infiltrate.
253
254
JOSEPH W, SAM
DIAGNOSIS
Metastatic Pulmonary Calcification Following Orthotopic Liver Transplant The patient underwent an open lung biopsy of the lingula, which revealed alveolar septal calcifications with mild chronic inflammation. The patient remained asymptomatic and was discharged with follow-up chest radiographs (Fig 3), now 9 years later, still displaying the focal metastatic calcifications.
Metastatic Pulmonary Calcification Metastatic calcification, also known as pulmonary calcinosis, refers to deposition of calcium on the elastic tissue of otherwise normal alveolar septa, arteries, veins, bronchioles, and bronchi in the presence of an elevated serum calcium phosphate product. It is to be distinguished from dystrophic pulmonary calcification in which there is deposition of calcium in damaged lung tissue in the setting of normal serum calcium levels. Although metastatic pulmonary calcification is usually related to renal failure, hyperparathyroidism, osseous neoplasms, or hypervitaminosis D, the extent of calcification correlates poorly with the serum calcium-phosphate product, length of dialysis, or parathormone levels. 1-6 Metastatic pulmonary calcification has also been described in patients following orthotopic liver transplants, as in the present case, with an incidence that varies in the literature from 5% to 25%. 7-1° Libson et al7 have suggested that this group of patients is predisposed to pulmonary calcification due to the large amount of blood products these patients receive during the course of their operations. In their theory,7 the citrate contained in packed red blood cells and fresh frozen plasma chelates calcium, causing secondary hyperparathyroidism, and ultimately an elevated serum calcium phosphate product. Accordingly, the extensive blood and blood woduct transfusions received by the patient described in this article would appear to support this contention. Most patients with metastatic pulmonary calcifications are asymptomatic and have normal chest radiographs; the calcinosis is usually discovered incidentally at autopsy. 1 When visible on chest radiographs, the calcifications have a highly variable appearance but usually manifest as diffuse,
A
Fig 3.
PA and lateral chest radiographs several years later.
bilateral, most commonly interstitial, but occasionally air-space, opacities that are commonly misdiagnosed as pulmonary edema or pneumonia. 1 Some authors have noted an upper lobe predominance that is believed to be related to the increased ventilation:perfusion ratio in these lung zones, causing a relatively alkaline environment that favors the deposition of calcium salts. 6,11"14Incidentally, a similar argument relating increased pH to
CASE OF THE SEASON
255
calcium deposition has been made to explain the frequent involvement of the stomach, heart, and kidney by metastatic calcification. 1 Again, the present case is in accord with this theory, as the calcification was present in the nondependent lingula in this patient who was primarily supine during her complicated 3-month recovery period. Although the diagnosis of metastatic pulmonary calcification is often difficult to make, it is an
important one in that small subset of patients who are symptomatic from the restrictive respiratory dysfunction that sometimes develops, and also, as in the current example, to avoid unnecessary invasive diagnostic procedures. In cases where the findings on plain films are subtle or equivocal, studies have shown that dual-energy radiography, 6 computed tomography, 13,1s,16and radionuclide studies 11,17may be of use.
REFERENCES 1. Dail DH, Hammar SP (eds): Pulmonary Pathology (ed 2). New York, NY, Springer-Verlag, 1994, pp 728-730 2. Neff M, Yalcin S, Bupta S, et at: Extensive metastatic calcification of the lung in an azotemic patient. Am J Med 56:103-109, 1974 3. Kuzela DC, Huffer WE, Conger JD, et al: Soft tissue calcification in chronic dialysis patients. Am J Pathol 86:403424, 1977 4. Kaltreider HB, Banm GL, Bogaty G, et at: So-called "metastatic" calcifications of the lung. Am J Med 46:188-196, 1969 5. Conger JD, Hammond WS, Alfrey AC, et al: Pulmonary calcification in chronic dialysis patients. Ann Intern Med 83:330-336, 1975 6. Sanders C, Frank MS, Rostand SG, et at: Metastatic calcification of the heart and lungs in end-stage renal disease: Detection and quantification by dual energy chest radiography. AJR Am J Roentgenol 149:881-887, 1987 7. Libson E, Wechsler RJ, Steiner RM: Pulmonary calcinosis following orthotopic liver transplantation. J Thorac Imaging 8:305-308, 1993 8. Winter EM, Pollard AJ, Chapman S, et al: Case report: Pulmonary calcification after liver transplantation in children. Br J Radio168:923-925, 1995 9. Costello P, Williams CR, Jenkins RW, et al: The incidence and implications of chest radiographic abnormalities following
orthotopic liver transplantation. J Can Assoc Radiol 38:90-95, 1987 10. Munoz SJ, Magelborg SB, Green PJ, et al: Ectopic soft tissue calcium deposition following liver transplantation. Hepatology 8:476-483, 1988 11. Mootz JR, Sagel SS, Roberts TH: Roentgenographic manifestations of pulmonary calcifications: A rare cause of respiratory failure in chronic renal failure. Radiology 107:55-60, 1973 12. Jost RG, Sagel SS: Metastatic calcification in the lung apex. AJR Am J Roentgenol 133:1188-1190, 1979 13. Kuhlman JE, Ren H, Hutchins GM, et al: Fulminant pulmonary calcifications complicating renal transplantation: CT demonstration. Radiology 173:459-460, 1989 14. van der Bij W, Gouw ASH, Meinesz AF, et al: Consolidation of both upper lobes. Chest 100:1685-1686, 1991 15. Hartman TE, Mtfller NL, Primack SL, et al: Metastatic pulmonary calcification in patients with hypercalcemia: Findings on chest radiographs and CT scans. AJR Am J Roentgenol 162:799-802, 1994 16. Greenberg S, Suster B: Metastatic pulmonary calcification: Appearance on high resolution CT. J Comput Assist Tomogr 18:497-499, 1994 17. Brodeur FJ Jr, Kazerooni EA: Metastatic pulmonary calcification mimicking air space disease: Technetium-99mMDP SPECT imaging. Chest 106:620-622, 1994
A
53-YEAR-OLD white woman with a history of end-stage liver failure due to cryptogenic cirrhosis presented to our institution for an orthotopic liver transplant. The operation was extremely difficult secondary to fibrinous peritonitis and the patient's severe coagulopathy, which necessitated the transfusion of 105 units of packed red blood cells and a comparable amount of fresh, frozen plasma and platelets. Furthermore, the postoperative course was complicated by a peritoneal hematoma requiring surgical evacuation, several episodes of bacterial sepsis, which responded well to antibiotics, and Candida peritonitis and sepsis, which was treated with a 6-week course of amphotericin. Ultimately, the patient recovered and chest radiographs taken 8 weeks after the original surgery showed no active disease. Two weeks later, the patient developed a patchy opacity in her left upper lobe (Fig 1) that was believed to represent a developing pneumonia; however, sputum cultures remained negative. Over the next 2 weeks, the area of opacification persisted and became more nodular
Fig 1. Chest radiograph demonstrates a left upper lobe infiltrate.
in character; however, the patient demonstrated no pulmonary symptoms and was eventually discharged 2 months later, with close follow-up and a repeat chest radiograph scheduled for 1 month later. The follow-up chest radiograph showed worsening of the left upper lobe nodular opacity (Fig 2), which was now believed to represent a smoldering fungal pneumonia. The patient was admitted for bronchoscopic biopsy. Bronchial brushings and washings were negative, as was a transbronchial biopsy. Two days later, the patient, who remained asymptomatic, underwent a diagnostic procedure.
From the Hospital of the University of Pennsylvania, Philadelphia, PA. Address reprint requests to Joseph W. Sam, MD, PhD, Department of Radiology, University of Pennsylvania Medical Center, 3400 Spruce St, Philadelphia, PA 19104. Copyright © 1999 by W.B. Saunders Company 0037-198X/99/3404-0003510. 00/0
Fig 2.
Seminars in Roentgenology, Vol XXXIV, No 4 (October), 1999: pp 253-255
Chest radiograph shows worsening of the infiltrate.
253
254
JOSEPH W, SAM
DIAGNOSIS
Metastatic Pulmonary Calcification Following Orthotopic Liver Transplant The patient underwent an open lung biopsy of the lingula, which revealed alveolar septal calcifications with mild chronic inflammation. The patient remained asymptomatic and was discharged with follow-up chest radiographs (Fig 3), now 9 years later, still displaying the focal metastatic calcifications.
Metastatic Pulmonary Calcification Metastatic calcification, also known as pulmonary calcinosis, refers to deposition of calcium on the elastic tissue of otherwise normal alveolar septa, arteries, veins, bronchioles, and bronchi in the presence of an elevated serum calcium phosphate product. It is to be distinguished from dystrophic pulmonary calcification in which there is deposition of calcium in damaged lung tissue in the setting of normal serum calcium levels. Although metastatic pulmonary calcification is usually related to renal failure, hyperparathyroidism, osseous neoplasms, or hypervitaminosis D, the extent of calcification correlates poorly with the serum calcium-phosphate product, length of dialysis, or parathormone levels. 1-6 Metastatic pulmonary calcification has also been described in patients following orthotopic liver transplants, as in the present case, with an incidence that varies in the literature from 5% to 25%. 7-1° Libson et al7 have suggested that this group of patients is predisposed to pulmonary calcification due to the large amount of blood products these patients receive during the course of their operations. In their theory,7 the citrate contained in packed red blood cells and fresh frozen plasma chelates calcium, causing secondary hyperparathyroidism, and ultimately an elevated serum calcium phosphate product. Accordingly, the extensive blood and blood woduct transfusions received by the patient described in this article would appear to support this contention. Most patients with metastatic pulmonary calcifications are asymptomatic and have normal chest radiographs; the calcinosis is usually discovered incidentally at autopsy. 1 When visible on chest radiographs, the calcifications have a highly variable appearance but usually manifest as diffuse,
A
Fig 3.
PA and lateral chest radiographs several years later.
bilateral, most commonly interstitial, but occasionally air-space, opacities that are commonly misdiagnosed as pulmonary edema or pneumonia. 1 Some authors have noted an upper lobe predominance that is believed to be related to the increased ventilation:perfusion ratio in these lung zones, causing a relatively alkaline environment that favors the deposition of calcium salts. 6,11"14Incidentally, a similar argument relating increased pH to
CASE OF THE SEASON
255
calcium deposition has been made to explain the frequent involvement of the stomach, heart, and kidney by metastatic calcification. 1 Again, the present case is in accord with this theory, as the calcification was present in the nondependent lingula in this patient who was primarily supine during her complicated 3-month recovery period. Although the diagnosis of metastatic pulmonary calcification is often difficult to make, it is an
important one in that small subset of patients who are symptomatic from the restrictive respiratory dysfunction that sometimes develops, and also, as in the current example, to avoid unnecessary invasive diagnostic procedures. In cases where the findings on plain films are subtle or equivocal, studies have shown that dual-energy radiography, 6 computed tomography, 13,1s,16and radionuclide studies 11,17may be of use.
REFERENCES 1. Dail DH, Hammar SP (eds): Pulmonary Pathology (ed 2). New York, NY, Springer-Verlag, 1994, pp 728-730 2. Neff M, Yalcin S, Bupta S, et at: Extensive metastatic calcification of the lung in an azotemic patient. Am J Med 56:103-109, 1974 3. Kuzela DC, Huffer WE, Conger JD, et al: Soft tissue calcification in chronic dialysis patients. Am J Pathol 86:403424, 1977 4. Kaltreider HB, Banm GL, Bogaty G, et at: So-called "metastatic" calcifications of the lung. Am J Med 46:188-196, 1969 5. Conger JD, Hammond WS, Alfrey AC, et al: Pulmonary calcification in chronic dialysis patients. Ann Intern Med 83:330-336, 1975 6. Sanders C, Frank MS, Rostand SG, et at: Metastatic calcification of the heart and lungs in end-stage renal disease: Detection and quantification by dual energy chest radiography. AJR Am J Roentgenol 149:881-887, 1987 7. Libson E, Wechsler RJ, Steiner RM: Pulmonary calcinosis following orthotopic liver transplantation. J Thorac Imaging 8:305-308, 1993 8. Winter EM, Pollard AJ, Chapman S, et al: Case report: Pulmonary calcification after liver transplantation in children. Br J Radio168:923-925, 1995 9. Costello P, Williams CR, Jenkins RW, et al: The incidence and implications of chest radiographic abnormalities following
orthotopic liver transplantation. J Can Assoc Radiol 38:90-95, 1987 10. Munoz SJ, Magelborg SB, Green PJ, et al: Ectopic soft tissue calcium deposition following liver transplantation. Hepatology 8:476-483, 1988 11. Mootz JR, Sagel SS, Roberts TH: Roentgenographic manifestations of pulmonary calcifications: A rare cause of respiratory failure in chronic renal failure. Radiology 107:55-60, 1973 12. Jost RG, Sagel SS: Metastatic calcification in the lung apex. AJR Am J Roentgenol 133:1188-1190, 1979 13. Kuhlman JE, Ren H, Hutchins GM, et al: Fulminant pulmonary calcifications complicating renal transplantation: CT demonstration. Radiology 173:459-460, 1989 14. van der Bij W, Gouw ASH, Meinesz AF, et al: Consolidation of both upper lobes. Chest 100:1685-1686, 1991 15. Hartman TE, Mtfller NL, Primack SL, et al: Metastatic pulmonary calcification in patients with hypercalcemia: Findings on chest radiographs and CT scans. AJR Am J Roentgenol 162:799-802, 1994 16. Greenberg S, Suster B: Metastatic pulmonary calcification: Appearance on high resolution CT. J Comput Assist Tomogr 18:497-499, 1994 17. Brodeur FJ Jr, Kazerooni EA: Metastatic pulmonary calcification mimicking air space disease: Technetium-99mMDP SPECT imaging. Chest 106:620-622, 1994