- Email: [email protected]
Surgical treatment of intracranial Erdheim-Chester disease
Journal of Clinical Neuroscience 17 (2010) 1489–1492
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Review
Surgical treatment of intracranial Erdheim-Chester disease Alex Alfieri a,⇑, Roberto Gazzeri b, Marcelo Galarza b, Massimiliano Neroni b a b
Department of Neurological Surgery, Martin-Luther University Halle-Wittenberg, Ernst-Grube Strabe 40, Halle, Germany Department of Neurosurgery, San Giovanni Addolorata Hospital, Rome, Italy
a r t i c l e
i n f o
Article history: Received 12 February 2010 Accepted 28 March 2010
Keywords: Erdheim-Chester disease Histiocytosis Intracranial Erdheim-Chester disease Intracranial tumor
a b s t r a c t We review the clinical presentation, radiological and histological characteristics, and the natural history, of intracranial Erdheim-Chester disease (ECD). ECD is a rare form of non-Langerhans histiocytosis that affects multiple organs. It is clinically characterized by leg pain, exophthalmos and diabetes insipidus (DI). Central nervous system involvement is rare, with only 27 patients reported in the international literature. DI and cerebellar signs represent the most common neurological symptoms. Its treatment is controversial. Intracranial surgical procedures for ECD have been reported in 11 patients with a complete surgical resection performed in six, and an intracerebral biopsy performed in five patients. In seven patients the cranial procedures represented the initial diagnostic method. Surgical resection and radiation therapy have been used in the further management of these cerebral lesions. Ó 2010 Elsevier Ltd. All rights reserved.
1. Erdheim-Chester disease Histiocytoses are a large, heterogeneous group of xanthogranulomatous diseases resulting from proliferation and accumulation of reactive or neoplastic histiocytes. Three classes of histiocytoses have been defined: (i) class I, Langerhans cell disease; (ii) class II, non-Langerhans cell histiocytic disease without features of malignancy; and (iii) class III, malignant histiocytic disorders.1,2 In this context, Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytosis that involves multiple organ systems. Typical systemic features include osteosclerotic lesions in the metaphysis of long tubular bones, exophthalmos, pulmonary and retroperitoneal fibrosis.1–6 Central nervous system involvement is rare, with diabetes insipidus (DI) and cerebellar signs representing the most common neurological symptoms.7–11 Occasionally, intracerebral and dural tumour-like lesions have been reported.12–15 It was first described by Jacob Erdheim and William Chester in 1930.16 However, the term ECD was first coined by Jaffe17 in 1972 and until 1980, a total of 47 patients with ECD had been reported in the medical literature, with 80 patients reported up to 2004.18 The median age of all reported patients is 56 years (range: 7–78 years), with a slight male preponderance (2.7/1).19–21 The clinical manifestations of ECD vary from asymptomatic or minimally symptomatic benign bone lesions to a severe and often fatal multi-systemic disease.22,23 Non-specific symptoms such as weight-loss, fever, weakness, pruritus and cutaneous rush are frequently reported, but the most frequent systemic manifestations are bone lesions secondary to histiocytic infiltrations of long bones. Typically, the diagnosis relies ⇑ Corresponding author. Tel.: +39 345 557 1407; fax: +39 345 557 1412. E-mail address: alex.alfi[email protected] (A. Alfieri). 0967-5868/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2010.03.062
on clinical features in addition to appropriate biopsy findings. Characteristic plain film radiographic findings consist of bilateral and symmetric sclerotic, or in 30% of patients, lytic lesions, predominantly in the lower limbs.4,22,24 Bone CT scans demonstrate typical bilateral and symmetric sclerotic bone lesions along the diaphysis and metaphysis of the femur, tibia, and humerus. Scattered lytic areas may be also present. Skeletal involvement may also affect the skull, spine, and ribs. Abnormal areas may also be detected by increased tracer uptake in radionuclide bone scans. MRI of the bony skeleton reveals diffuse infiltration of the marrow with patchy metaphyseal T2-weighted hyperintense signal using a fat suppression technique and decreased signal on T1-weighted and T2-weighted sequences.25,26 Dermatological manifestations include xanthelasma, periorbital xanthomata and pruritic rash. In 25% of patients there is involvement of the retroperitoneal space with renal dysfunction, hydronephrosis and retroperitoneal fibrosis secondary to a xanthogranulomatous infiltration (Fig. 1). Involvement of the aortic adventitia with fibrous encasement of the major vessels has also been reported.16 Lung involvement is fairly uncommon but, when present, contributes to morbidity and mortality. Lung involvement usually shows a diffuse interstitial infiltrate with an upper lung predominance, and scattered reticular or centrilobular opacities with pleural thickening and effusion. Typically, the clinical course is characterized by a progressive course with dyspnea and respiratory failure.24 2. Central nervous system involvement The central nervous system (CNS) involvement is variable in ECD. Sometimes neurological symptoms are secondary to a diffuse hypothalamic and orbital involvement of the disease. In these
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Fig. 1. Axial T2-weighted abdominal MRI showing retroperitoneal fibrosis involving the perirenal and para-aortic regions with right hydronephrosis, enlarged renal calices and left kidney atrophy.
instances a neurogenic DI can be related to a hypothalamic lesion detectable on MRI not associated with other causes. Orbital involvement has been reported in 23 patients, with infiltration of the retro-orbital tissues, which may lead typically to painless bilateral exophthalmos, double vision, and ocular motility impairment.27,28 Although DI has been associated with orbital involvement, suggesting an extension of the process from the orbit along the optic nerves and the chiasm to the hypothalamic/pituitary region, evidence on cerebral MRI of pathological lesions in the pituitary or hypothalamus regions is rare. However, DI has been reported in 34% of patients with ECD. Frequently, DI precedes the clinical diagnosis of ECD by 10 or more years, perhaps because MRI seldom detects early abnormalities such as thickening of the pituitary stalk.13,18,24 Although uncommon, extrapituitary neurological involvement has also been reported infrequently in ECD. The second most common neurological signs in ECD are cerebellar symptoms with ataxia and gait disturbances.7,29 Nevertheless, the multifocal character of ECD involvement can also produce a wide variety of symptoms and signs, possibly leading to a misdiagnosis of multiple sclerosis with diffuse, multiple, or infiltrative MRI signal abnormalities.4,14 Spinal neural involvement has also been reported with extra-axial and extradural spinal masses.22,30 The most usual features, mainly in intracranial ECD, are dural granulomas in the brainstem or cerebellum with encasement of major vessels, including vertebral and basilar arteries.4,15,31,32 So far only, 27 patients with intracranial lesions have been documented in ECD (Supplementary Table 1). 3. Neuroradiology Intracranial ECD lesions typically appear hypodense on unenhanced CT scans and have homogeneous contrast-enhancement on post-contrast scans. MRI is more sensitive than CT scans in detecting ECD lesions, revealing even small intracerebral and extracerebral lesions. In most patients who have ECD with DI there is no abnormality of the hypothalamic/pituitary region. Nevertheless, a loss of the posterior pituitary-hyperintensity on T1weighted MRI with infundibular thickening has been described.33 A characteristic MRI feature is the prolonged retention of the lesions, even after several days, of gadolinium. This may be due to the abnormal histiocyte content in the intracranial masses. Kujat et al.4 reported prolonged lesion enhancement 14 days after gadolinium administration. In the patient reported by Martinez,33 a persistent enhancement was documented in an extra-axial cervico-medullary brainstem lesion after 23 days. The typical MRI signal of the intracranial lesions is a bright hyperintensity on
Fig. 2. (a) Sagittal and (b) coronal T1-weighted postcontrast brain MRI showing a homogeneous infra- and supra-tentorial tumor with a dural tail sign at the level of the torcular with encasement of the posterior aspect of the superior sagittal sinus, the straight sinus and transverse sinuses.
Fig. 3. Lateral cerebral angiography of the patient in Fig. 2 showing a thrombosis of the transverse sinuses, the straight sinus and the posterior superior sagittal sinus, with a narrowed anterior superior sagittal sinus; anomalous anastomotic venous circuits are also present.
T2-weighted sequences.34,35 In several studies, disease progression from a focal to a diffuse pachymeningitis has been recorded with MRI. Sometimes, the ECD presented on MRI as a homogenous contrast-enhancing lesion with a dural-tail mimicking a meningioma (Fig. 2), while some reports included localization at the falx.4,10,36–39 Intracranial angiography may show anomalous anastomotic venous circles and no hypervascular tumour stain, with thrombosis of the sinuses (Fig. 3). 4. Pathology A combination of clinical and radiological features in addition to appropriate biopsy and histopathological analysis provide the
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medical treatment is with corticosteroids. Radiotherapy has been used to treat ECD lesions, but the rationale is based on its use in similar diseases such as Langerhans cell histiocytosis. Vincristine, vinblastine and cyclosporine chemotherapies have shown no manifest results.29,45 Although the initial clinical course of the disease may be asymptomatic or slowly progressive for years, most patients deteriorate rapidly. Overall prognosis depends on the severity of the disease, with an average survival of 32 months after the initial diagnosis24 and respiratory distress and heart failure as the main causes of death.37 6. Conclusions Intracranial ECD is a rare xanthogranulomatous syndrome of unknown aetiology with protean systemic manifestations. Typical systemic features include osteosclerotic lesions in the metaphyses of long tubular bones, exophthalmos, and pulmonary and retroperitoneal fibrosis, whereas CNS involvement is rare, with DI and cerebellar signs as the most common neurological symptoms. Intracranial biopsy procedures or surgical resection of these lesions should be performed as an initial diagnostic method only when diagnosis of the systemic disease is not possible. In a patient with one circumscribed intracranial lesion and neurological symptoms, a surgical resection may be indicated. Fig. 4. Photomicrographs of a mixed, chronic inflammatory infiltrate consisting of lymphocytes and foamy histiocytes, including some giant and multi-nucleated histiocytes. A Touton-like multi-nucleated giant cell is readily identified (black arrow) (hematoxylin and eosin stain, original magnification 400).
Appendix A. Supplementary material
definitive diagnosis. The most frequent biopsy sites are sclerotic bone areas and retro-orbital masses. A cerebral biopsy is consequently performed rarely. Histologically ECD is characterized by foamy lipid-laden infiltrating histiocytes with small, bland nuclei and lack of nuclear grooves.27 Characteristic scattered multi-nuclear Touton-type giant cells, fibrosis and a scant amount of inflammatory infiltrate with a minimal number of lymphocytes and eosinophils are present (Fig. 4). Histiocytes show immunoreactivity to CD68 and none to S-100 and CD1a. Electron microscopy may identify a histiocytic subtype, with non-Langerhans cell histiocytes indicative of rare distinctive Birbeck granules in the Langerhans cells.
References
5. Clinical management The optimal treatment of intracranial ECD is uncertain because there are only case reports on the natural history of the disease. Surgical resection is reasonable in patients with circumscribed intracranial lesions and neurological signs or symptoms. To our knowledge there are 11 reports of intracranial surgery for ECD13–15,27,31,36–38,40–42 with surgical total resection reported in six patients and cerebral biopsy in the other patients. An intracranial procedure was the first step to establish diagnosis in seven patients, even though these patients had already presented with ECD involvement in multiple extracranial systems. The diagnosis of ECD after resection of a meningioma-like lesion has been described in only one patient. Intracranial involvement is normally suspected on the basis of neurological signs, and thus diagnosed by radiological investigations. The histological proof of the ECD diagnosis generally occurs after biopsy of organs other than the brain. Reported adjuvant treatment for intracranial xanthogranulomas in ECD has resulted in temporary relief of symptoms only. Therapies described in ECD include corticosteroids, chemotherapy,29 radiotherapy43 and immunotherapy.30,44 The most common
Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.jocn.2010.03.062.
1. Dion E, Graef C, Haroche J, et al. Imaging of thoracoabdominal involvement in Erdheim Chester disease. AJR Am J Roentgenol 2004;183:1253–60. 2. Fortman BJ, Beall DP. Erdheim Chester disease of the retroperitoneum: a rare cause of ureteral obstruction. AJR Am J Roentgenol 2001;176:1330–1. 3. Kim EE, Romero JA. Erdheim Chester disease demonstrated by bone radiograph and scans. Clin Imaging 1997;21:328–31. 4. Kujat C, Junk B, Hermes M, et al. Cerebral manifestations of Erdheim Chester disease. Radiologe 1991;31:307–9 (In German). 5. Rozas Reyes P, Senaris Gonzalez A, Gonzalez Rodriguez CM. Orbit xanthogranulomatosis. Erdheim Chester disease. Arch Soc Esp Oftalmol 2004;79:515–8 (In Spanish). 6. Simpson FG, Robinson PJ, Hardy GJ, et al. Erdheim Chester disease associated with retroperitoneal xanthogranuloma. Br J Radiol 1979;52:232–5. 7. Bohlega S, Alwatban J, Tulbah A, et al. Cerebral manifestation of Erdheim Chester disease: clinical and radiologic findings. Neurology 1997;49:1702–5. 8. Evidente VG, Adler CH, Giannini C, et al. Erdheim Chester disease with extensive intraaxial brain stem lesions presenting as a progressive cerebellar syndrome. Mov Disord 1998;13:576–81. 9. Fukazawa T, Tsukishima E, Sasaki H, et al. Erdheim Chester disease and slowly progressive cerebellar dysfunction. J Neurol Neurosurg Psychiatry 1995;58: 238–40. 10. Tien RD, Brasch RC, Jackson DE, et al. Cerebral Erdheim Chester disease: persistent enhancement with Gd-DTPA on MR images. Radiology 1989;172: 791–2. 11. Weidauer S, von Stuckrad-Barre S, Dettmann E, et al. Cerebral Erdheim Chester disease: case report and review of the literature. Neuroradiology 2003;45: 241–5. 12. 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;56:1207–16. 13. Oweity T, Scheithauer BW, Ching HS, et al. Multiple system Erdheim Chester disease with massive hypothalamic-sellar involvement and hypopituitarism. J Neurosurg 2002;96:344–51. 14. Smith ME, Katz DA, Harris JO. Systemic histiocytosis presenting as multiple sclerosis. Ann Neurol 1993;33:549–54. 15. Tashjian V, Doppenberg EM, Lyders E, et al. Diagnosis of Erdheim Chester disease by using computerized tomography-guided stereotactic biopsy of a caudate lesion. Case report. J Neurosurg 2004;101:521–7. 16. Chester W. Über lipoidgranulomatose. Virchows Arch A Pathol Anat Histopathol 1930;279:561–602. 17. Jaffe HL. Metabolic degenerative and inflammatory diseases of bone and joints. Philadelphia: Lea and Febiger; 1972.
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18. Alper MG, Zimmerman LE, Piana FG. Orbital manifestations of Erdheim Chester disease. Trans Am Ophthalmol Soc 1983;81:64–85. 19. Globerman H, Burstein S, Girardina PJ, et al. Xanthogranulomatous histiocytosis in a child presenting with short stature. Am J Pediatr Hematol Oncol 1991;13:42–6. 20. Resnick D, Greenway G, Genant H, et al. Erdheim Chester disease. Radiology 1982;142:289–95. 21. Lantz B, Lange TA, Heiner J, et al. Erdheim Chester disease. A report of three cases. J Bone Joint Surg Am 1989;71:456–64. 22. Caparros-Lefebvre D, Pruvo JP, Remy M, et al. Neuroradiologic aspects of Chester-Erdheim disease. AJNR Am J Neuroradiol 1995;16:735–40. 23. Pautas E, Cherin P, Pelletier S, et al. Cerebral Erdheim Chester disease: report of two cases with progressive cerebellar syndrome with dentate abnormalities on magnetic resonance imaging. J Neurol Neurosurg Psychiatry 1998;65:597–9. 24. Veyssier-Belot C, Cacoub P, Caparros-Lefebvre D, et al. Erdheim Chester disease. Clinical and radiologic characteristics of 59 cases. Medicine (Baltimore) 1996;75:157–69. 25. 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. 26. Gottlieb R, Chen A. MR findings of Erdheim Chester disease. J Comput Assist Tomogr 2002;26:257–61. 27. Wright RA, Hermann RC, Parisi JE. Neurological manifestations of Erdheim Chester disease. J Neurol Neurosurg Psychiatry 1999;66:72–5. 28. De Abreu MR, Chung CB, Biswal S, et al. Erdheim Chester disease: MR imaging, anatomic, and histopathologic correlation of orbital involvement. AJNR Am J Neuroradiol 2004;25:627–30. 29. Miller RL, Sheeler LR, Bauer TW, et al. Erdheim Chester disease. Case report and review of the literature. Am J Med 1986;80:1230–6. 30. Babu RP, Lansen TA, Chadburn A, et al. Erdheim Chester disease of the central nervous system. Report of two cases. J Neurosurg 1997;86: 888–92.
31. Boulos AS, Deshaies EM, Qian J, et al. Preoperative stent placement for intradural vertebral artery stenosis from a rare xanthogranuloma. Case report. J Neurosurg 2004;101:864–8. 32. Mascalchi M, Nencini P, Nistri M, et al. Failure of radiation therapy for brain involvement in Erdheim Chester disease. J Neurooncol 2002;59:169–72. 33. Martinez R. Erdheim Chester disease: MR of intraaxial and extraaxial brain stem lesions. AJNR Am J Neuroradiol 1995;16:1787–90. 34. Murray D, Marshall M, England E. Erdheim Chester disease. Clin Radiol 2001;56:481–4. 35. Shimada S, Ono K, Hashizume Y, et al. Intracranial lesion of Erdheim Chester disease. Hum Pathol 2007;38:950–1. 36. Rushing EJ, Bouffard JP, Neal CJ, et al. Erdheim Chester disease mimicking a primary brain tumor. Case report. J Neurosurg 2004;100:1115–8. 37. Gazzeri R, Galarza M, Amoroso R, et al. Neurological picture. Torcular Erdheim Chester disease. J Neurol Neurosurg Psychiatry 2006;77:1078. 38. Sandrock D, Merino MJ, Scheffknecht BH, et al. Scintigraphic findings and follow up in Erdheim Chester disease. Eur J Nucl Med 1990;16:55–60. 39. Johnson MD, Aulino JP, Jagasia M, et al. Erdheim Chester disease mimicking multiple meningiomas syndrome. AJNR Am J Neuroradiol 2004;25:134–7. 40. Miyachi S, Kobayashi T, Takahashi T. An intracranial mass lesion in systemic xanthogranulomatosis: case report. Neurosurgery 1990;27:822–6. 41. Stojkovic T, de Seze J, Maurage CA, et al. Atypical form of non-Langerhans histiocytosis with disseminated brain and leptomeningeal lesions. J Neurol Neurosurg Psychiatry 2000;69:675–8. 42. Reithmeier T, Trost HA, Wolf S, et al. Xanthogranuloma of the Erdheim Chester type within the sellar region: case report. Clin Neuropathol 2002;21:24–8. 43. Tien R, Kucharczyk J, Newton TH, et al. MR of diabetes insipidus in a patient with Erdheim Chester disease: case report. AJNR Am J Neuroradiol 1990;11: 1267–70. 44. Esmaeli B, Ahmadi A, Tang R, et al. Interferon therapy for orbital infiltration secondary to Erdheim Chester disease. Am J Ophthalmol 2001;132:945–7. 45. Poehling GG, Adair DM, Haupt HA. Erdheim Chester disease. A case report. Clin Orthop Relat Res 1984;185:241–4.
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Review
Surgical treatment of intracranial Erdheim-Chester disease Alex Alfieri a,⇑, Roberto Gazzeri b, Marcelo Galarza b, Massimiliano Neroni b a b
Department of Neurological Surgery, Martin-Luther University Halle-Wittenberg, Ernst-Grube Strabe 40, Halle, Germany Department of Neurosurgery, San Giovanni Addolorata Hospital, Rome, Italy
a r t i c l e
i n f o
Article history: Received 12 February 2010 Accepted 28 March 2010
Keywords: Erdheim-Chester disease Histiocytosis Intracranial Erdheim-Chester disease Intracranial tumor
a b s t r a c t We review the clinical presentation, radiological and histological characteristics, and the natural history, of intracranial Erdheim-Chester disease (ECD). ECD is a rare form of non-Langerhans histiocytosis that affects multiple organs. It is clinically characterized by leg pain, exophthalmos and diabetes insipidus (DI). Central nervous system involvement is rare, with only 27 patients reported in the international literature. DI and cerebellar signs represent the most common neurological symptoms. Its treatment is controversial. Intracranial surgical procedures for ECD have been reported in 11 patients with a complete surgical resection performed in six, and an intracerebral biopsy performed in five patients. In seven patients the cranial procedures represented the initial diagnostic method. Surgical resection and radiation therapy have been used in the further management of these cerebral lesions. Ó 2010 Elsevier Ltd. All rights reserved.
1. Erdheim-Chester disease Histiocytoses are a large, heterogeneous group of xanthogranulomatous diseases resulting from proliferation and accumulation of reactive or neoplastic histiocytes. Three classes of histiocytoses have been defined: (i) class I, Langerhans cell disease; (ii) class II, non-Langerhans cell histiocytic disease without features of malignancy; and (iii) class III, malignant histiocytic disorders.1,2 In this context, Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytosis that involves multiple organ systems. Typical systemic features include osteosclerotic lesions in the metaphysis of long tubular bones, exophthalmos, pulmonary and retroperitoneal fibrosis.1–6 Central nervous system involvement is rare, with diabetes insipidus (DI) and cerebellar signs representing the most common neurological symptoms.7–11 Occasionally, intracerebral and dural tumour-like lesions have been reported.12–15 It was first described by Jacob Erdheim and William Chester in 1930.16 However, the term ECD was first coined by Jaffe17 in 1972 and until 1980, a total of 47 patients with ECD had been reported in the medical literature, with 80 patients reported up to 2004.18 The median age of all reported patients is 56 years (range: 7–78 years), with a slight male preponderance (2.7/1).19–21 The clinical manifestations of ECD vary from asymptomatic or minimally symptomatic benign bone lesions to a severe and often fatal multi-systemic disease.22,23 Non-specific symptoms such as weight-loss, fever, weakness, pruritus and cutaneous rush are frequently reported, but the most frequent systemic manifestations are bone lesions secondary to histiocytic infiltrations of long bones. Typically, the diagnosis relies ⇑ Corresponding author. Tel.: +39 345 557 1407; fax: +39 345 557 1412. E-mail address: alex.alfi[email protected] (A. Alfieri). 0967-5868/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2010.03.062
on clinical features in addition to appropriate biopsy findings. Characteristic plain film radiographic findings consist of bilateral and symmetric sclerotic, or in 30% of patients, lytic lesions, predominantly in the lower limbs.4,22,24 Bone CT scans demonstrate typical bilateral and symmetric sclerotic bone lesions along the diaphysis and metaphysis of the femur, tibia, and humerus. Scattered lytic areas may be also present. Skeletal involvement may also affect the skull, spine, and ribs. Abnormal areas may also be detected by increased tracer uptake in radionuclide bone scans. MRI of the bony skeleton reveals diffuse infiltration of the marrow with patchy metaphyseal T2-weighted hyperintense signal using a fat suppression technique and decreased signal on T1-weighted and T2-weighted sequences.25,26 Dermatological manifestations include xanthelasma, periorbital xanthomata and pruritic rash. In 25% of patients there is involvement of the retroperitoneal space with renal dysfunction, hydronephrosis and retroperitoneal fibrosis secondary to a xanthogranulomatous infiltration (Fig. 1). Involvement of the aortic adventitia with fibrous encasement of the major vessels has also been reported.16 Lung involvement is fairly uncommon but, when present, contributes to morbidity and mortality. Lung involvement usually shows a diffuse interstitial infiltrate with an upper lung predominance, and scattered reticular or centrilobular opacities with pleural thickening and effusion. Typically, the clinical course is characterized by a progressive course with dyspnea and respiratory failure.24 2. Central nervous system involvement The central nervous system (CNS) involvement is variable in ECD. Sometimes neurological symptoms are secondary to a diffuse hypothalamic and orbital involvement of the disease. In these
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Fig. 1. Axial T2-weighted abdominal MRI showing retroperitoneal fibrosis involving the perirenal and para-aortic regions with right hydronephrosis, enlarged renal calices and left kidney atrophy.
instances a neurogenic DI can be related to a hypothalamic lesion detectable on MRI not associated with other causes. Orbital involvement has been reported in 23 patients, with infiltration of the retro-orbital tissues, which may lead typically to painless bilateral exophthalmos, double vision, and ocular motility impairment.27,28 Although DI has been associated with orbital involvement, suggesting an extension of the process from the orbit along the optic nerves and the chiasm to the hypothalamic/pituitary region, evidence on cerebral MRI of pathological lesions in the pituitary or hypothalamus regions is rare. However, DI has been reported in 34% of patients with ECD. Frequently, DI precedes the clinical diagnosis of ECD by 10 or more years, perhaps because MRI seldom detects early abnormalities such as thickening of the pituitary stalk.13,18,24 Although uncommon, extrapituitary neurological involvement has also been reported infrequently in ECD. The second most common neurological signs in ECD are cerebellar symptoms with ataxia and gait disturbances.7,29 Nevertheless, the multifocal character of ECD involvement can also produce a wide variety of symptoms and signs, possibly leading to a misdiagnosis of multiple sclerosis with diffuse, multiple, or infiltrative MRI signal abnormalities.4,14 Spinal neural involvement has also been reported with extra-axial and extradural spinal masses.22,30 The most usual features, mainly in intracranial ECD, are dural granulomas in the brainstem or cerebellum with encasement of major vessels, including vertebral and basilar arteries.4,15,31,32 So far only, 27 patients with intracranial lesions have been documented in ECD (Supplementary Table 1). 3. Neuroradiology Intracranial ECD lesions typically appear hypodense on unenhanced CT scans and have homogeneous contrast-enhancement on post-contrast scans. MRI is more sensitive than CT scans in detecting ECD lesions, revealing even small intracerebral and extracerebral lesions. In most patients who have ECD with DI there is no abnormality of the hypothalamic/pituitary region. Nevertheless, a loss of the posterior pituitary-hyperintensity on T1weighted MRI with infundibular thickening has been described.33 A characteristic MRI feature is the prolonged retention of the lesions, even after several days, of gadolinium. This may be due to the abnormal histiocyte content in the intracranial masses. Kujat et al.4 reported prolonged lesion enhancement 14 days after gadolinium administration. In the patient reported by Martinez,33 a persistent enhancement was documented in an extra-axial cervico-medullary brainstem lesion after 23 days. The typical MRI signal of the intracranial lesions is a bright hyperintensity on
Fig. 2. (a) Sagittal and (b) coronal T1-weighted postcontrast brain MRI showing a homogeneous infra- and supra-tentorial tumor with a dural tail sign at the level of the torcular with encasement of the posterior aspect of the superior sagittal sinus, the straight sinus and transverse sinuses.
Fig. 3. Lateral cerebral angiography of the patient in Fig. 2 showing a thrombosis of the transverse sinuses, the straight sinus and the posterior superior sagittal sinus, with a narrowed anterior superior sagittal sinus; anomalous anastomotic venous circuits are also present.
T2-weighted sequences.34,35 In several studies, disease progression from a focal to a diffuse pachymeningitis has been recorded with MRI. Sometimes, the ECD presented on MRI as a homogenous contrast-enhancing lesion with a dural-tail mimicking a meningioma (Fig. 2), while some reports included localization at the falx.4,10,36–39 Intracranial angiography may show anomalous anastomotic venous circles and no hypervascular tumour stain, with thrombosis of the sinuses (Fig. 3). 4. Pathology A combination of clinical and radiological features in addition to appropriate biopsy and histopathological analysis provide the
A. Alfieri et al. / Journal of Clinical Neuroscience 17 (2010) 1489–1492
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medical treatment is with corticosteroids. Radiotherapy has been used to treat ECD lesions, but the rationale is based on its use in similar diseases such as Langerhans cell histiocytosis. Vincristine, vinblastine and cyclosporine chemotherapies have shown no manifest results.29,45 Although the initial clinical course of the disease may be asymptomatic or slowly progressive for years, most patients deteriorate rapidly. Overall prognosis depends on the severity of the disease, with an average survival of 32 months after the initial diagnosis24 and respiratory distress and heart failure as the main causes of death.37 6. Conclusions Intracranial ECD is a rare xanthogranulomatous syndrome of unknown aetiology with protean systemic manifestations. Typical systemic features include osteosclerotic lesions in the metaphyses of long tubular bones, exophthalmos, and pulmonary and retroperitoneal fibrosis, whereas CNS involvement is rare, with DI and cerebellar signs as the most common neurological symptoms. Intracranial biopsy procedures or surgical resection of these lesions should be performed as an initial diagnostic method only when diagnosis of the systemic disease is not possible. In a patient with one circumscribed intracranial lesion and neurological symptoms, a surgical resection may be indicated. Fig. 4. Photomicrographs of a mixed, chronic inflammatory infiltrate consisting of lymphocytes and foamy histiocytes, including some giant and multi-nucleated histiocytes. A Touton-like multi-nucleated giant cell is readily identified (black arrow) (hematoxylin and eosin stain, original magnification 400).
Appendix A. Supplementary material
definitive diagnosis. The most frequent biopsy sites are sclerotic bone areas and retro-orbital masses. A cerebral biopsy is consequently performed rarely. Histologically ECD is characterized by foamy lipid-laden infiltrating histiocytes with small, bland nuclei and lack of nuclear grooves.27 Characteristic scattered multi-nuclear Touton-type giant cells, fibrosis and a scant amount of inflammatory infiltrate with a minimal number of lymphocytes and eosinophils are present (Fig. 4). Histiocytes show immunoreactivity to CD68 and none to S-100 and CD1a. Electron microscopy may identify a histiocytic subtype, with non-Langerhans cell histiocytes indicative of rare distinctive Birbeck granules in the Langerhans cells.
References
5. Clinical management The optimal treatment of intracranial ECD is uncertain because there are only case reports on the natural history of the disease. Surgical resection is reasonable in patients with circumscribed intracranial lesions and neurological signs or symptoms. To our knowledge there are 11 reports of intracranial surgery for ECD13–15,27,31,36–38,40–42 with surgical total resection reported in six patients and cerebral biopsy in the other patients. An intracranial procedure was the first step to establish diagnosis in seven patients, even though these patients had already presented with ECD involvement in multiple extracranial systems. The diagnosis of ECD after resection of a meningioma-like lesion has been described in only one patient. Intracranial involvement is normally suspected on the basis of neurological signs, and thus diagnosed by radiological investigations. The histological proof of the ECD diagnosis generally occurs after biopsy of organs other than the brain. Reported adjuvant treatment for intracranial xanthogranulomas in ECD has resulted in temporary relief of symptoms only. Therapies described in ECD include corticosteroids, chemotherapy,29 radiotherapy43 and immunotherapy.30,44 The most common
Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.jocn.2010.03.062.
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