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Postgraduate Education Corner: CHEST IMAGING AND PATHOLOGY FOR CLINICIANS |

Cardiac Tumor and Renal Involvement in a Nonsmoker With Centrilobular Pulmonary Nodules FREE TO VIEW

Huck Chin Chew, MBBS, MMed; Cheah Hooi Ken Lee, MBBS; Foong Koong Cheah, MBBS; Soon Thye Lim, MBBS; Chian Min Loo, MBBS, FCCP
Author and Funding Information

*From the Departments of Respiratory and Critical Care Medicine (Drs. Chew, Lee, and Loo), Diagnostic and Therapeutic Radiology (Dr. Cheah), and Oncology (Dr. Lim), National Cancer Centre, Singapore General Hospital, Singapore.

Correspondence to: Huck Chin Chew, MBBS, MRCS, MMed, MRCP, Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Outram Rd, Singapore 169608; e-mail: chinnjing@pacific.net.sg


The authors have no conflicts of interest to disclose.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).


Chest. 2009;135(4):1102-1106. doi:10.1378/chest.08-0532
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A 57-year-old Chinese man presented with abdominal bloating associated with flatulence and belching over a 4-month period, which was especially worse with the intake of fatty food. He had decreased appetite, with weight loss of approximately 4 kg during the same period.

He denied any fever, chills, nausea, or vomiting. There was no recent change in his bowel habits or caliber of stools. He claimed to have foul-smelling urine, but there was no complaint of dysuria. He had no complaints of cough or dyspnea. There was no history of inhalational exposure.

He had underlying hypertension, non–insulin- dependent diabetes mellitus, hyperlipidemia, and an orbital tumor, for which biopsy was done and reported histologically as having features of resolving fat necrosis. He was a nonsmoker.

On physical examination, vital signs were stable. Bilateral canthal angle lesions were noted. Heart sounds were normal with no detectable murmur, and lungs were clear on auscultation. The abdomen was soft and nontender with no palpable masses. There was no lymphadenopathy.

Full blood count showed an elevated WBC count at 22.85 × 109/L with predominantly neutrophils. Electrolytes were within normal limits. Urinalysis revealed pyuria with urine culture positive for Klebsiella pneumoniae.

The patient was treated with antibiotics for a urinary tract infection. Ultrasound of the kidneys was done to exclude pyelonephritis and revealed a left hydronephrosis. Subsequent CT scans of the abdomen (Fig 1) showed diffuse urothelial thickening of the pelvicalyceal systems and upper ureters bilaterally associated with increased density in the perinephric fat, as well as mural thickening of the lower descending thoracic and abdominal aorta. An incidental pericardial effusion was also noted.

Figure Jump LinkFigure 1 Contrast-enhanced CT scan of sagittal view of kidneys in the nephrogenic phase showing bilateral symmetrical infiltration of the perirenal space (black arrows) encasing both kidneys, giving rise to a “hairy kidney” appearance.Grahic Jump Location

A transthoracic echocardiogram detected a right atrial mass in addition to the pericardial effusion. Further evaluation with non–contrast-enhanced MRI of the heart (Fig 2) confirmed presence of an infiltrating mass involving the right atrium. CT scans of the thorax (Fig 3) revealed multiple centrilobular nodules in both lungs with septal and fissural thickening, as well as patchy ground-glass changes.

Figure Jump LinkFigure 2 T2-weighted MRI of the heart using the half-Fourier, single-shot, spin-echo technique showing an isointense right wall thickening and lumen distortion, giving an atrial pseudomass appearance (white arrow) in addition to a pericardial effusion (black arrow).Grahic Jump Location

Figure Jump LinkFigure 3 Contrast-enhanced CT scans of the thorax in the (top) lung and (bottom) soft-tissue windows, revealing multiple centrilobular nodules (curved arrows) in both lungs with septal (straight black arrows) and fissural thickening (straight white arrows), as well as diffuse patchy ground-glass changes. There was also mural circumferential thickening of the aorta (narrow black arrow on both scans), commonly referred to as coated aorta.Grahic Jump Location

Headache with vomiting developed later, and an MRI of the brain (Fig 4) was performed. This test showed a large mass at the foramen magnum causing compression of the fourth ventricle with obstructive hydrocephalus as well as abnormal stranding of bilateral retroorbital fat.

Figure Jump LinkFigure 4 Postconstrast T1-weighted MRI of the brain in the coronal plane showing a large irregular and heterogeneously enhanced mass (arrow) at the foramen magnum, causing compression of the fourth ventricle with obstructive hydrocephalus.Grahic Jump Location

The findings of subsequent tests, including a myeloma screen, an autoimmune screen, a bone marrow trephine, a biopsy followed by flow cytometry, and a skeletal survey, were unremarkable. CT scan-guided biopsy of the right perinephric tissue and kidney revealed a fibroinflammatory infiltrate, which stained positively for CD68 and negatively for CD1a and S100 (Fig 6). Biopsy samples were taken from the canthal angle masses (Fig 5).

Figure Jump LinkFigure 5 Biopsy specimen from canthal xanthogranulomas showing touton-type multinucleated giant cells (black arrow). There was proliferation of large histiocytes with round-to-oval nuclei and moderate-to-abundant cytoplasm and surrounding fibrosis. Accompanying the histiocytic proliferation was infiltration of small lymphocytes and plasma cells (Diff-Quick stain [Siemens Healthcare Diagnostics; Deerfield, IL]; original ×600).Grahic Jump Location

Figure Jump LinkFigure 6 Biopsy of the perinephric mass showing infiltration of foamy lipid-laden histiocytes with round-to-oval nuclei and eosinophilic cytoplasm. Accompanying the histiocytic proliferation was variable infiltration of small lymphocytes and plasma cells (Papanicolaou stain, original ×600).Grahic Jump Location
What is the diagnosis?
What is the typical histologic appearance?

Diagnosis: Erdheim-Chester disease

Histologic appearance (Fig 5) showed dermal aggregates of foamy histiocytes with occasional touton-type multinucleated giant cells. An associated mild lymphoplasmacytic infiltration was present.

Erdheim-Chester disease is a rare non–Langerhans-cell histiocytosis of unknown etiology that usually affects middle-aged adults with no sex predilection. It was first described in 1930 by Chester1 in two patients with a distinctive lipoidosis, characterized by the proliferation of lipid-containing foamy histiocytes involving long bones, without visceral involvement. In 1972, Jaffe2 reported a third patient and coined the term Erdheim-Chester because the features of this condition appeared to constitute a distinctive pathological entity.

The clinical spectrum of this disease shows broad variation even though only < 100 cases have been published to date. These range from asymptomatic tissue infiltration to minimally symptomatic bone lesions and finally severe multisystem involvement.3 Long bone involvement is almost universal in Erdheim-Chester disease, which accounts for bone pain as the most common presenting symptom of this condition.37 Extraskeletal manifestations have been noted in more than half of the case reports, including constitutional symptoms such as fever, weight loss, and weakness. The most common sites of soft-tissue involvement are the retroperitoneum, pituitary, orbits, kidneys, lungs, and heart.8 The diagnosis of this disease relies on both pathologic as well as radiologic correlation, but exact criteria for diagnosis are still not well defined. Bone involvement is not required to establish diagnosis of this condition but enhances clinical suspicion for Erdheim-Chester disease.

Erdheim-Chester disease differs from pulmonary Langerhans-cell histiocytosis in its age distribution and immunohistochemical and radiologic characteristics (Table 1). Pulmonary Langerhans-cell histiocytosis typically affects young adults (usually smokers), while the average age of presentation for Erdheim-Chester disease is 53 years. Langerhans-cell histiocytes stain positively for CD1a and S-100, and negatively for CD68, and have Birbeck granules viewable by electron microscopy, which are not found in Erdheim-Chester disease. The histiocytes in Erdheim-Chester disease stain negatively for CD1a and S-100, and positively for CD68. Upon histologic staining, Touton multinucleated giant cells that are characteristically found in xanthogranulomas may be identified.8,9 The bony lesions in Erdheim-Chester disease are symmetrical, sclerotic, and involve the metadiaphyses of long bones, whereas those of Langerhans-cell histiocytosis are lytic and involve the axial skeleton.47

Table Graphic Jump Location
Table 1 Differences Between Erdheim-Chester Disease and Pulmonary Langerhans-Cell Histiocytosis

This patient presented with abdominal bloating and weight loss. Interestingly, he lacked the most common presenting symptom of bone pain. The absence of bone findings in our skeletal survey is a striking feature, although a rare occurrence, given that the most unique aspect of Erdheim-Chester disease is its effect on the long tubular bones, which manifests radiologically as bilateral symmetrical sclerotic lesions in the metadiaphyses. Several diagnoses of Erdheim-Chester disease have, in fact, been made based on this pathognomonic pattern of bone involvement, although a few cases of osteolytic lesions have been reported.

The radiographic findings of the CT scans of the abdomen were initially thought to resemble idiopathic retroperitoneal fibrosis, also known as Ormond disease. However, there are distinguishing radiographic features between the two conditions. In Ormond disease, fibrosis involves the anterior and lateral aspects of the aorta, typically sparing the posterior. There is rarely involvement of the perirenal space. In contrast, the findings from the CT abdomen scan of our patient revealed a circumferential periaortic infiltration, “coated aorta,” and bilateral infiltration of the perirenal fat giving rise to a “hairy kidney” appearance, features which are more compatible with Erdheim-Chester disease.10,11

Pulmonary involvement in this disease is characterized in high-resolution CT scans by interstitial infiltrates, smooth interlobular septal thickening, fissural thickening, and centrilobular ground glass opacities.1114 Our patient had fissural thickening and centrilobular ground-glass opacities, although alone these findings are not truly diagnostic of Erdheim-Chester disease. Differential diagnosis of centrilobular nodules and ground glass opacities include respiratory bronchiolitis-associated interstitial lung disease, lymphoid interstitial pneumonia, and hypersensitivity pneumonitis.

Cardiac involvement in Erdheim-Chester disease most commonly manifests as a pericardial effusion or pericardial thickening.11,15 Myocardial involvement is rare and appears as a left atrial thickening or a mass in the right atrium, as in the case of our patient.11,16

Neurologic manifestations in Erdheim-Chester disease vary tremendously. The most frequently observed symptom is central diabetes insipidus, secondary to infiltration of the pituitary or hypothalamus, followed by cerebellar symptoms with ataxia.17 Focal or multifocal neurologic signs due to parenchymal infiltration or compression by dural masses have been reported.18 Our patient presented with symptoms suggestive of raised intracranial pressure, and MRI of the brain later confirmed the presence of an intracranial mass causing obstructive hydrocephalus. The patient declined surgery or a shunt procedure and was started on an initial course of high-dose corticosteroids. Despite all of our efforts, our patient subsequently died a few weeks later as a result of his disease.

The prognosis for Erdheim-Chester disease depends on the extent of extraskeletal manifestations. Respiratory distress, extensive pulmonary fibrosis, and cardiac failure are the most common causes of death. To date, various attempts at treatment on empirical grounds with steroids, radiotherapy, and chemotherapy in varying combinations have shown limited improvement or stabilization of disease.3,19

This was a rare case of Erdheim-Chester disease in a patient with extensive multisystem involvement with the absence of skeletal findings. Diagnosis of this condition is often delayed or missed due to the absence of skeletal complaints and a wide variety of symptoms. Radiographic evidence of the disease frequently precedes clinical symptoms. Clinical suspicion of this condition should be considered in patients presenting with bone pain and sclerotic lesions involving long bones as well as evidence of other soft-tissue involvement in various organs and can be verified using a combination of clinicoradiologic as well as histopathologic correlation. The disease is relentlessly progressive despite treatment, and overall prognosis remains poor.

Chester W. Uber Lipoidgranulomatose. Virchows Arch Pathol Anat. 1930;279:561-602. [CrossRef]
 
Jaffe HL.Jaffe HL. Gaucher's disease and certain other inborn metabolic disorders: lipid (cholesterol) granulomatosis. Metabolic, degenerative, and inflammatory diseases of bones and joints. 1972; Philadelphia, PA Lea and Febiger:535-541
 
Veyssier-Belot C, Cacoub P, Capparros-Lefebvre D, et al. Erdheim-Chester disease: clinical and radiologic characteristics of 59 cases. Medicine (Baltimore). 1996;75:157-169. [PubMed]
 
Bancroft LW, Berquist TH. Erdheim Chester disease: radiographic findings in five patients. Skeletal Radiol. 1998;27:127-132. [PubMed]
 
Franzius C, Schiuk J, Bremer C, et al. Determination of extent and activity with radionuclide imaging in Erdheim-Chester disease. Clin Nucl Med. 1999;24:252-255. [PubMed]
 
Breuil V, Brocq O, Pellegrino C, et al. Erdheim-Chester disease: typical radiological bone features for a rare xanthogranulomatosis. Ann Rheum Dis. 2002;61:199-200. [PubMed]
 
Dion E, Graef C, Miquel A, et al. Bone involvement in Erdheim-Chester disease: imaging findings including periostitis and partial epiphyseal involvement. Radiology. 2006;238:632-639. [PubMed]
 
Sheu SY, Wenzel RR, Kersting C, et al. Erdheim-Chester disease: case report with multisystemic manifestations including testes, thyroid, and lymph nodes, and a review of literature. J Clin Pathol. 2004;57:1225-1228. [PubMed]
 
Kenn W, Eck M, Allolio B, et al. Erdheim-Chester disease: evidence of a disease entity different from Langerhans cell histiocytosis? Three cases with detailed radiological and immunohistochemical analysis. Hum Path. 2000;31:734-739. [PubMed]
 
Serratice J, Granel B, De Roux C, et al. “Coated aorta”: a new sign of Erdheim-Chester disease. J Rheumatol. 2000;27:1550-1553. [PubMed]
 
Dion E, Graef C, Haroche J, et al. Imaging of thoracoabdominal involvement in Erdheim-Chester disease. AJR Am J Roentgenol. 2004;183:1253-1260. [PubMed]
 
Remy-Jardin M, Remy J, Gosselin B, et al. Pulmonary involvement in Erdheim-Chester disease: high-resolution CT findings. Eur Radiol. 1993;3:389-392
 
Egan AJ, Boardman LA, Tazelaar HD, et al. Erdheim-Chester disease: clinical, radiologic, and histopathologic findings in five patients with interstitial lung disease. Am J Surg Pathol. 1999;23:17-26. [PubMed]
 
Wittenberg KH, Swensen SJ, Myers JL. Pulmonary involvement with Erdheim-Chester disease: radiographic and CT findings. AJR Am J Roentgenol. 2000;174:1327-1331. [PubMed]
 
Gupta A, Kelly B, McGuigan JE. Erdheim-Chester disease with prominent pericardial involvement: clinical, radiologic, and histologic findings. Am J Med Sci. 2002;324:96-100. [PubMed]
 
Ammann P, Bosch B, Buchholz S, et al. Cardiac tumor due to Erdheim-Chester disease. Am J Med. 2001;111:672-673. [PubMed]
 
Wright RA, Hermann RC, Parisi JE. Neurological manifestations of Erdheim-Chester disease. J Neurol Neurosurg Psychiatry. 1999;66:72-75. [PubMed]
 
Adle-Biassette H, Chetritt J, Bergemer-Fouquet AM, et al. Pathology of the central nervous system in Chester-Erdheim disease: report of three cases. J Neuropathol Exp Neurol. 1997;56:1207-1216. [PubMed]
 
Bourke SC, Nicholson AG, Gibson GJ. Erdheim-Chester disease: pulmonary infiltration responding to cyclophosphamide and prednisolone. Thorax. 2003;58:1004-1005. [PubMed]
 

Figures

Figure Jump LinkFigure 1 Contrast-enhanced CT scan of sagittal view of kidneys in the nephrogenic phase showing bilateral symmetrical infiltration of the perirenal space (black arrows) encasing both kidneys, giving rise to a “hairy kidney” appearance.Grahic Jump Location
Figure Jump LinkFigure 2 T2-weighted MRI of the heart using the half-Fourier, single-shot, spin-echo technique showing an isointense right wall thickening and lumen distortion, giving an atrial pseudomass appearance (white arrow) in addition to a pericardial effusion (black arrow).Grahic Jump Location
Figure Jump LinkFigure 3 Contrast-enhanced CT scans of the thorax in the (top) lung and (bottom) soft-tissue windows, revealing multiple centrilobular nodules (curved arrows) in both lungs with septal (straight black arrows) and fissural thickening (straight white arrows), as well as diffuse patchy ground-glass changes. There was also mural circumferential thickening of the aorta (narrow black arrow on both scans), commonly referred to as coated aorta.Grahic Jump Location
Figure Jump LinkFigure 4 Postconstrast T1-weighted MRI of the brain in the coronal plane showing a large irregular and heterogeneously enhanced mass (arrow) at the foramen magnum, causing compression of the fourth ventricle with obstructive hydrocephalus.Grahic Jump Location
Figure Jump LinkFigure 5 Biopsy specimen from canthal xanthogranulomas showing touton-type multinucleated giant cells (black arrow). There was proliferation of large histiocytes with round-to-oval nuclei and moderate-to-abundant cytoplasm and surrounding fibrosis. Accompanying the histiocytic proliferation was infiltration of small lymphocytes and plasma cells (Diff-Quick stain [Siemens Healthcare Diagnostics; Deerfield, IL]; original ×600).Grahic Jump Location
Figure Jump LinkFigure 6 Biopsy of the perinephric mass showing infiltration of foamy lipid-laden histiocytes with round-to-oval nuclei and eosinophilic cytoplasm. Accompanying the histiocytic proliferation was variable infiltration of small lymphocytes and plasma cells (Papanicolaou stain, original ×600).Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 Differences Between Erdheim-Chester Disease and Pulmonary Langerhans-Cell Histiocytosis

References

Chester W. Uber Lipoidgranulomatose. Virchows Arch Pathol Anat. 1930;279:561-602. [CrossRef]
 
Jaffe HL.Jaffe HL. Gaucher's disease and certain other inborn metabolic disorders: lipid (cholesterol) granulomatosis. Metabolic, degenerative, and inflammatory diseases of bones and joints. 1972; Philadelphia, PA Lea and Febiger:535-541
 
Veyssier-Belot C, Cacoub P, Capparros-Lefebvre D, et al. Erdheim-Chester disease: clinical and radiologic characteristics of 59 cases. Medicine (Baltimore). 1996;75:157-169. [PubMed]
 
Bancroft LW, Berquist TH. Erdheim Chester disease: radiographic findings in five patients. Skeletal Radiol. 1998;27:127-132. [PubMed]
 
Franzius C, Schiuk J, Bremer C, et al. Determination of extent and activity with radionuclide imaging in Erdheim-Chester disease. Clin Nucl Med. 1999;24:252-255. [PubMed]
 
Breuil V, Brocq O, Pellegrino C, et al. Erdheim-Chester disease: typical radiological bone features for a rare xanthogranulomatosis. Ann Rheum Dis. 2002;61:199-200. [PubMed]
 
Dion E, Graef C, Miquel A, et al. Bone involvement in Erdheim-Chester disease: imaging findings including periostitis and partial epiphyseal involvement. Radiology. 2006;238:632-639. [PubMed]
 
Sheu SY, Wenzel RR, Kersting C, et al. Erdheim-Chester disease: case report with multisystemic manifestations including testes, thyroid, and lymph nodes, and a review of literature. J Clin Pathol. 2004;57:1225-1228. [PubMed]
 
Kenn W, Eck M, Allolio B, et al. Erdheim-Chester disease: evidence of a disease entity different from Langerhans cell histiocytosis? Three cases with detailed radiological and immunohistochemical analysis. Hum Path. 2000;31:734-739. [PubMed]
 
Serratice J, Granel B, De Roux C, et al. “Coated aorta”: a new sign of Erdheim-Chester disease. J Rheumatol. 2000;27:1550-1553. [PubMed]
 
Dion E, Graef C, Haroche J, et al. Imaging of thoracoabdominal involvement in Erdheim-Chester disease. AJR Am J Roentgenol. 2004;183:1253-1260. [PubMed]
 
Remy-Jardin M, Remy J, Gosselin B, et al. Pulmonary involvement in Erdheim-Chester disease: high-resolution CT findings. Eur Radiol. 1993;3:389-392
 
Egan AJ, Boardman LA, Tazelaar HD, et al. Erdheim-Chester disease: clinical, radiologic, and histopathologic findings in five patients with interstitial lung disease. Am J Surg Pathol. 1999;23:17-26. [PubMed]
 
Wittenberg KH, Swensen SJ, Myers JL. Pulmonary involvement with Erdheim-Chester disease: radiographic and CT findings. AJR Am J Roentgenol. 2000;174:1327-1331. [PubMed]
 
Gupta A, Kelly B, McGuigan JE. Erdheim-Chester disease with prominent pericardial involvement: clinical, radiologic, and histologic findings. Am J Med Sci. 2002;324:96-100. [PubMed]
 
Ammann P, Bosch B, Buchholz S, et al. Cardiac tumor due to Erdheim-Chester disease. Am J Med. 2001;111:672-673. [PubMed]
 
Wright RA, Hermann RC, Parisi JE. Neurological manifestations of Erdheim-Chester disease. J Neurol Neurosurg Psychiatry. 1999;66:72-75. [PubMed]
 
Adle-Biassette H, Chetritt J, Bergemer-Fouquet AM, et al. Pathology of the central nervous system in Chester-Erdheim disease: report of three cases. J Neuropathol Exp Neurol. 1997;56:1207-1216. [PubMed]
 
Bourke SC, Nicholson AG, Gibson GJ. Erdheim-Chester disease: pulmonary infiltration responding to cyclophosphamide and prednisolone. Thorax. 2003;58:1004-1005. [PubMed]
 
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