Available online at www.sciencedirect.com Surgical Neurology 70 (2008) 182 – 185 www.surgicalneurology-online.com Vasculitis Primary angiitis of the central nervous system mimicking dissemination from brainstem neoplasm: a case report Shinya Nabika, MD a,⁎, Katsuzo Kiya, MD a , Hideki Satoh, MD a , Tatsuya Mizoue, MD a , Hayato Araki, MD a , Jumpei Oshita, MD a , Takashi Nishisaka, MD b , Kaoru Kurisu, MD c , Kazuhiko Sugiyama, MD c Departments of aNeurosurgery, and bPathology, Hiroshima Prefectural Hospital, Minami-Ku, Hiroshima 734-8530, Japan Department of Neurosurgery, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8551, Japan Received 20 February 2007; accepted 3 May 2007 c Abstract Background: Diagnosis of PACNS is very difficult because of the variety of clinical manifestation, especially neurologic and MRI findings. We report the case of a 68-year-old woman with PACNS. Case Description: Her clinical symptoms mimicked malignant brainstem neoplasm disseminated to third and fourth ventricles and cervical spinal cord. Brain biopsy could not be correctly diagnostic. In spite of a trial of high-dose steroids, repeated MRI showed an increasing number of lesions. Two weeks after surgery, she died of respiratory dysfunction. Postmortem examination suggested PACNS, after consideration of histories, laboratory and radiologic findings, and the lack of systemic disease. Conclusion: Although brain biopsy represents the gold standard measure, combination with several other examinations might be necessary to arrive at an early and definitive diagnosis. PACNS should be considered the differential diagnosis of intracranial tumors. © 2008 Elsevier Inc. All rights reserved. Keywords: Autopsy; Magnetic resonance imaging; Primary angiitis of central nervous system 1. Introduction PACNS is a poorly understood inflammatory disorder affecting parenchymal and leptomeningeal vessels [1]. Clinical manifestations are protean and make diagnosis difficult, because of the rarity of this condition and the variety of neurologic and imaging findings [2]. We report a case with poor outcomes after nondiagnostic brain biopsy, in which PACNS mimicked malignant brainstem neoplasm disseminating into the ventricles and the cervical spinal cord. 2. Case report 2.1. History and presentation Abbreviations: AFP, alpha-1 fetoprotein; ANA, antinuclear antibody; CA 19-9, carbohydrate antigen 19-9; CA 125, carbohydrate antigen 125; C-ANCA, cytoplasmic staining pattern of antineutrophil cytoplasmic antibody; CEA, carcinoembryonic antigen; CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; NSE, neuron-specific enolase; PACNS, primary angiitis of the central nervous system; P-ANCA, perinuclear staining pattern of antineutrophil cytoplasmic antibody; PIVKA-2, proteins induced by vitamin K absence or antagonists 2; SCC, squamous cell carcinoma; SLX, sialyl lewis x. ⁎ Corresponding author. Tel.: +81 82 254 1818; fax: +81 82 253 8274. E-mail address: snabika@go4.enjoy.ne.jp (S. Nabika). 0090-3019/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.surneu.2007.05.008 The subject is a 68-year-old woman whose medical history showed no remarkable feature, and had neither taken immunosuppressive drugs nor steroids. The patient had an occasional 1-month history of dizziness and was transferred to our hospital because of syncope. Neurologic examination revealed dysarthria and difficulty in swallowing. MRI indicated a brainstem mass with multifocal small lesions in the third and fourth ventricle, and cervical spinal cord. These were homogeneously enhanced masses with surrounding S. Nabika et al. / Surgical Neurology 70 (2008) 182–185 183 vasogenic edema, as if the medullary lesion were the original neoplasm and had disseminated into ventricles and cervical spinal cord (Fig. 1). Whole-body CT and several serum tumor markers study (AFP, CEA, CA 19-9, SCC, CA125, PIVKA2, NSE, SLX) suggested no evidence of metastatic tumors. Routine chemistries (white blood cell count, 7000 mm3; CRP, negative), collagen screening tests (ANA, β2-microglobulin, P-ANCA, C-ANCA), angiotensin converting enzyme, antiphospholipid antibodies, antibodies to different viruses (herpes simplex virus types 1 and 2, varicella zoster, influenza, parainfluenza, Coxsackie virus, echovirus) and several pathogens (Borrelia, Treponema pallidum) remained within normal range. A CSF study showed an opening pressure of 60 mm H2O and a water-clear CSF containing 50 mg/dL protein, 57 mg/dL glucose, and 4 cells/mm3 (only lymphocytes). Results of cytologic studies, and bacterial and viral cultures were all negative. The patient underwent biopsy of medullo oblongata via a bilateral suboccipital approach. The biopsy material was characterized by reactive gliosis with lymphocytic infiltration. We could not arrive at a definitive diagnosis via brain biopsy. After a nondiagnostic biopsy suggestive of inflammatory disease, a trial of steroids (prednisone, 80 mg/d) was used. However, repeated MRI showed the progressive lesions. Her condition gradually deteriorated due to worsening respiration. She died of respiratory dysfunction 2 weeks after surgery. 2.2. Histopathologic examination A general autopsy revealed multilobulated nodules, devoid of cerebral parenchyma in the medulla oblongata, ventricules, and cervical spinal cord. On cut sections, the nodules were dense, whitish with no hemorrhage. All lesions showed granulomatous form with inflammatory changes, especially perivascular lymphocytic and histiocytic infiltration (Figs. 2 and 3). These processes affected not the large vessels, but the small-sized intracortical arteries. No other lesions were noted in the rest of the autopsy, such as the systemic lymph nodes, lungs, peripheral nerves, or cranial nerves. After considering the patient's history, laboratory and radiologic findings, and absence of systemic diseases, a diagnosis was reached: PACNS. 3. Discussion PACNS can occur mostly when patients are 30 to 50 years old, with men affected slightly more than women. Patients experience confusion (45%), headaches (42%), and focal neurologic sign (16%) as occurs with a stroke [13]. Symptoms progress slowly, over the course of several months. All of these symptoms and signs are nonspecific, and can be mimicked by a variety of other conditions. Fig. 1. MRI reveals a homogeneously intense mass in the medulla oblongata, with multifocal small lesions in the cerebrum, cerebellum and spinal cord. A-C: Gadolinium-enhanced T1-weighted imaging. 184 S. Nabika et al. / Surgical Neurology 70 (2008) 182–185 Fig. 2. Photomicrographs reveal multifocal fibrotic regions of extensive perivascular infliltration by lymphocytes and histiocytes. A: Low-power view at medulla, Masson trichrome, ×200. B: Low-power view at lateral ventricle; Masson trichrome, ×200. C: Low-power view at fornix, Masson trichrome, ×200. The histopathologic feature of PACNS is inflammatory infiltration composed mainly of lymphocytes accompanied by histiocytes and plasma cells, particularly in small leptomeningeal and intracerebral arteries [1,3]. There is a granulomatous or nongranulomatous form that results in multiple lesions of ischemic or hemorrhagic infarctions secondary to vessel wall proliferation with resultant luminal obliteration, thrombotic occlusion, or rupture of necrotic vessel walls. In the present case, multifocal fibrotic regions of extensive perivascular infliltration by lymphocytes and histiocytes were seen. The standard for diagnosis of PACNS is a brain biopsy. However, we could not obtain perivascular lesions by biopsy. The likelihood of a “false-negative” biopsy is unfortunately rather high. Ozawa et al [9] reported that among the 48 patients who underwent cortical biopsy, the first attempts were diagnostic in 31 (65%) patients. Positive cerebral angiographic findings may be useful in making a presumptive diagnosis of PACNS, although angiography produces normal findings in about 50% of pathologically documented cases. In this case, we could not perform angiography after surgery because of acute deterioration. MRI was also a distraction in achieving correct diagnosis in the present case. The most common features are multiple bilateral asymmetric supratentorial ischemic lesions, involving gray and white matter [4,7,10]. Less commonly, it presents as brainstem lesions or simulates primary brain tumor [5,8,11,12]. Interestingly, in the present case, lesions were confined only to the ventricles and spinal cord, suggesting dissemination of malignant neoplasm. S. Nabika et al. / Surgical Neurology 70 (2008) 182–185 185 Fig. 3. Photomicrographs reveal perivascular lesions infiltrated by lymphocytes and histiocytes. A: Hematoxylin and eosin, ×300. B: α-Smooth muscle actin, ×300. C: CD68, ×300. The prognosis for patients with PACNS is significantly better than it was 2 or 3 decades ago because of imaging techniques and the effectiveness of cyclophosphamide and prednisone [1]. Correct diagnosis is critical, because prognosis is poor if patients are left untreated or are treated incorrectly [6]. For an early and definitive diagnosis, PACNS should be considered the differential diagnosis of intracranial tumors. References [1] Abdulrahman AA, William JP. Prognosis of patients with suspected primary CNS angiitis and negative brain biopsy. Neurology 2003;61:831-3. [2] Antonia C, Roberto DB, Isabella P, et al. Primary Angiitis of the central nervous system: a misinterpreted clinical onset of CNS vasculitis. Eur Neurol 2005;53:40-2. [3] Athear A, Jonathan DT, Blaivas M, et al. Brain biopsy in primary angiitis of the central nervous system. Neurology 1999;53:858-60. [4] Campi A, Benndorf G, Filippi M, et al. Primary angiitis of the central nervous system: serial MRI of brain and spinal cord. Neuroradiology 2001;43:599-607. [5] Johnson M, Maciunas R, Dutt P, et al. Granulomatous angiitis masquerading as a mass lesion: magnetic resonance imaging and stereotactic biopsy findings in a patient with occult Hodgkin's disease. Surg Neurol 1989;31:49-53. [6] Koo EH, Massey EW. Granulomatous angiitis of the central nervous system: protean manifestation and response to treatment. J Neurol Neurosurg Psychiatry 1988;51:1126-33. [7] Moore PM. Diagnosis and management of isolated angiitis of central nervous system. Neurology 1989;39:167-73. [8] Neeraj JP, Soheil N, Steven GI. Lymphocytic vasculitis mimicking aggressive multifocal cerebral neoplasm: MR imaging and MR spectroscopic appearance. AJNR Am J Neuroradiol 2005;26:642-5. [9] Ozawa T, Sasaki O, Sorimachi T, et al. Primary angiitis of the central nervous system: report of two cases and review of the literature. Neurosurgery 1995;36:173-9. [10] Shoemaker EL, Lin ZS, Rae-Grant AD, et al. Primary angiitis of the central nervous system: unusual MR appearance. AJNR Am J Neuroradiol 1994;15:331-4. [11] Valavanis A, Friede R, Schubiger O, et al. Cerebral granulomatous angiitis simulating brain tumor. J Comput Assist Tomogr 1979;3:536-8. [12] Vollmer TL, Guarnaccia J, Harrington W, et al. Idiopathic granulomatous angiitis of the central nervous system: diagnostic challenges. Arch Neurol 1993;50:925-30. [13] Younger DS, Hays AP, Brust JC, et al. Granulomatous angiitis of the brain. An inflammatory reaction of diverse etiology. Arch Neurol 1988;45:514-8. Commentary The authors report an intriguing case of PACNS that presented as an enhancing mass in the brainstem that mimicked a neoplasm that later disseminated. Although a brain biopsy was attempted, the results were not diagnostic. Serologies and other blood tests are not useful in diagnosing PACNS. The CSF was not diagnostic of sarcoid or multiple sclerosis. The diagnosis of PACNS during life can be especially difficult as illustrated by this case. Aggressive immunosuppression may yield remissions in some cases, although immunosuppression was not beneficial in this specific case. Daniel B. Hier, MD MBA Neurology and Rehabilitation University of Illinois at Chicago Chicago, IL 60612, USA