This is a well known entity to neuropathologists who deal with many obscure pathological entities that may simulate a brain neoplasm. Classically, it presents as a solitary contrast enhancing mass lesion within the brain, that by radiographic examination, simulates a neoplasm. Even on frozen sections, performed by the pathologist, the diagnosis may be treacherous, with many sections resembling a neoplasm or infectious process. Only with the aid of specialized stains can a diagnosis be confidently made.
Epidemiology Disease Associations Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/Immunohistochemistry/Electron Microscopy Differential Diagnosis Prognosis and Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE Rare AGE RANGE-MEDIAN All ages SEX (M:F) Both
DISEASE ASSOCIATIONS CHARACTERIZATION MULTIPLE SCLEROSIS
Multiple sclerosis mimicking primary brain tumor.
Hunter SB, Ballinger WE Jr, Rubin JJ.
Arch Pathol Lab Med 1987 May;111(5):464-8 Abstract quote
Surgical biopsy specimens of multiple sclerosis plaques have been only infrequently reported, and the scanty descriptions of these specimens have generally emphasized the inflammatory nature of the lesion.
We present surgical specimens from four patients with multiple sclerosis on whom biopsies were performed because of clinical features mimicking brain tumor. Both general pathologists and neuropathologists involved with these cases experienced difficulty in arriving at the correct diagnosis. In all four cases, the lesions were remarkably uniform in microscopic appearance, consisting of monotonous sheets of gemistocytic astroglia interspersed by numerous foamy macrophages.
In sections stained with hematoxylin-eosin, the most helpful diagnostic features were the even distribution of the foamy macrophages and the absence of associated necrosis. In each case, the diagnosis was confirmed with special stains that disclosed total destruction of myelin sheaths with relative preservation of axons. Significant inflammatory infiltration was present in only one of five biopsy specimens.
CHARACTERIZATION RADIOLOGIC White matter crescent sign where the open portion of the partial rings abuts agains the cortical gray matter and the area of enhancement sweeps through the white matter in a crescent-like pattern
Open-ring imaging sign: highly specific for atypical brain demyelination.
Masdeu JC, Quinto C, Olivera C, Tenner M, Leslie D, Visintainer P.
Departments of Neurology, New York Medical College (St. Vincent's Hospital and Westchester Medical Center), Valhalla, NY , USA.
Neurology 2000 Apr 11;54(7):1427-33 Abstract quote
OBJECTIVE: To test the specificity for demyelination of a new neuroimaging sign: contrast enhancement shaped as an open ring or a crescent circumscribed to the white matter.
BACKGROUND: Brain demyelination can cause ring enhancement mimicking neoplasm or infection on CT or MRI.
METHODS: A MEDLINE search of pathology-proved demyelination yielded 32 illustrated cases of ring-enhancing lesions published between 1981 and 1995. Controls consisted of the same number of published images of neoplasms and infections, pathology proved, and matched by year of publication, and age and gender of the patient. Two neuroradiologists read the images twice independently 1 year apart.
RESULTS: Interrater agreement was good (kappa = 0.64 and 0.66 for either reading). Test-retest reliability was high (kappa = 0.75 and 0.74 for either rater). The open-ring sign clearly distinguished demyelinating lesions from neoplasms and infections. For demyelination versus neoplasm or infection, the specificity of the reading by the first neuroradiologist was 93.8 (95% CI, 86 to 98), and that of the second was 84.4 (95% CI, 74 to 92). The likelihood ratio of demyelination versus neoplasm averaged 5.2, and versus infection, 17.2. That is, if the lesions had the same incidence in the population, in the presence of an open-ring sign demyelination would be five times more likely than neoplasm and 17 times more likely than infection. However, given the much higher incidence of neoplasms and infections, these lesions are still frequently responsible for open-ring enhancement.
CONCLUSIONS: The open-ring sign is often present in large, contrast-enhancing demyelinating lesions and helps to differentiate them from neoplasms and infections.
Large focal tumor-like demyelinating lesions of the brain: intermediate entity between multiple sclerosis and acute disseminated encephalomyelitis? A study of 31 patients.
Department of Pathology and Oncology, University of Kansas School of Medicine, Kansas City.
Ann Neurol 1993 Jan;33(1):18-27 Abstract quote
Thirty-one patients with large, focal cerebral demyelinating lesions are reported. Twenty-four patients had solitary lesions and 7 had multiple foci, the latter apparently of identical age. The lesions presented clinically and radiologically as brain tumors (gliomas or metastases) or as multiple cysts. Six patients were older than 57 years (2 in their 70s) at the onset of their symptoms.
The demyelinating nature of the lesions was established through biopsy in each patient and all improved significantly after corticosteroid therapy. Three patients developed additional lesions during the follow-up periods ranging from 9 months to 12 years consistent with the course of multiple sclerosis. Twenty-eight patients did not develop additional lesions. These included 6 patients with multiple lesions at the onset. In 1 of the patients, the first symptoms developed 10 days after receiving vaccination against influenza. Two patients had concomitant malignancy (chronic monomyelogenous leukemia and retroperitoneal seminoma respectively) and 1 patient developed immunoblastic sarcoma in the opposite hemisphere after biopsy diagnosis and steroid treatment of her demyelinating lesion. Tumor-like masses of demyelination may occupy an intermediate position between multiple sclerosis and postinfectious/postvaccination encephalitis.
The clinical course (history of vaccination in one instance, acute onset, good response to corticosteroids, no clinical or radiological evidence of new lesions in the great majority of patients) favored postinfectious/postvaccination encephalitis. Lesion size however greatly exceeded that of the small foci of perivenous demyelination seen in typical postinfectious/postvaccination encephalitis and tended to present as space-occupying masses.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
Acute focal demyelinating disease simulating brain tumors: histopathologic guidelines for an accurate diagnosis.
Sugita Y, Terasaki M, Shigemori M, Sakata K, Morimatsu M.
Department of Pathology, Kurume University School of Medicine, Kurume-shi, Fukuoka-ken, Japan.
Neuropathology 2001 Mar;21(1):25-31 Abstract quote
The object of the present study was to determine the histopathological guidelines for accurate diagnosis of cases of acute focal demyelinating disease that simulates brain tumors. The surgical pathology of three such cases is assessed.
Histopathological keys to the diagnosis of such cases are as follows. First, a pattern of sheets of atypical gemistocytic astrocytes in the white matter that show well-formed processes and that are adequately distanced from each other argues against a diagnosis of neoplasm. Second, uniform distribution of foamy macrophages aligned along axons, with occasional focal collections surrounding blood vessels and in the absence of any associated coagulative necrosis argues against the presence of a tumor. Third, perivascular chronic inflammatory infiltration, especially a mixture of lymphocytes and macrophages, favors the diagnosis of demyelination plaque. In such cases the lymphocytes will be predominantly T cells. Fourth, pleomorphic astrocytic proliferation with a lack of vascular endothelial proliferation should raise the suspicion that the lesion may not be a brain tumor.
These diagnostic keys should be followed when diagnosing cases that are suspected to be demyelination processes rather than brain tumors. The presence of demyelination plaque should then be confirmed by imaging modalities such as staining with myelin-and axon-specific stains.
CHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE
Erana-Rojas IE, Barboza-Quintana A, Ayala AG, Fuller GN.
Department of Pathology, Hospital San Jose-Tec de Monterrey, Monterrey, Nuevo Leon, Mexico; and the Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX.
Ann Diagn Pathol 2002 Oct;6(5):265-71 Abstract quote
Demyelinating disease presenting as a solitary contrast-enhancing mass poses a diagnostic challenge for both radiologists and surgical pathologists.
We report the cases of two female patients, aged 23 and 37 years, who exhibited the clinical and radiologic features of a space-occupying mass strongly suggestive of neoplasia. In both patients, magnetic resonance imaging showed a ring-enhancing parietal lesion. Intraoperative frozen sections in both patients displayed histologic features strongly suggestive of a glial neoplasm, including marked hypercellularity, a prominent astrocytic component, and easily identifiable mitotic figures. However, permanent sections showed additional and helpful histologic findings that included Creutzfeldt astrocytes and granular mitoses.
Subsequent immunostaining showed that the hypercellularity was principally caused by macrophage infiltration (HAM-56 and CD68) and an associated reactive astrocytosis (glial fibrillary acidic protein). Additional confirmatory tests included special stains for myelin (Luxol-fast-blue), which demonstrated focal, sharply marginated loss of myelin, and for axons (silver stain for axons and neurofilament protein immunohistochemistry), which showed relative preservation of axons in areas of myelin loss. Together, the special stains confirmed the demyelinating nature of the lesions.
The keys to avoiding misdiagnosing a demyelinating pseudotumor as a diffuse glioma include a general awareness of this potential pitfall, including the radiologic appearance of demyelinating pseudotumors as contrast-enhancing solitary masses that mimic tumor; knowledge of the characteristic histologic features, including Creutzfeldt astrocytes and granular mitoses; and a high index of suspicion for macrophage infiltration combined with a willingness to use appropriate confirmatory immunohistochemical studies in suspicious or uncertain cases. This approach will minimize the chance of misdiagnosis and subsequent use of inappropriate and deleterious therapies.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES GENERAL
Demyelinating disease versus tumor in surgical neuropathology. Clues to a correct pathological diagnosis.
Zagzag D, Miller DC, Kleinman GM, Abati A, Donnenfeld H, Budzilovich GN.
Department of Pathology, New York University Medical Center, NY 10016.
Am J Surg Pathol 1993 Jun;17(6):537-45 Abstract quote
Clinical presentations as well as radiological and histopathological findings in biopsies from patients with multiple sclerosis (MS) or other demyelinating disorders of the central nervous system are sometimes misleading, resulting in an erroneous diagnosis of brain or spinal cord tumor.
We report 17 patients who presented with symptoms mimicking those of brain (14 cases) or spinal cord (three cases) tumors. Computerized tomography or magnetic resonance imaging studies or both were interpreted as consistent with a tumor in each case. All patients underwent surgery, and all 17 pathological specimens were eventually diagnosed as showing demyelinating disease, usually consistent with MS. In each case we examined a variety of histological features and immunohistochemical studies and addressed their relative importance in considering the diagnosis of MS. All cases showed perivascular lymphocytic inflammation with variable amounts of macrophage infiltration, necrosis, and edema. The hypercellularity of the lesions and the presence of atypical reactive astrocytes with mitotic figures were the disturbing features that might have led to the erroneous diagnosis of an astrocytic neoplasm.
Immunohistochemistry for astrocytic (glial fibrillary acidic protein) and macrophage (HAM-56) markers are helpful in evaluating biopsies. Our results emphasize the need to perform special stains (i.e., for myelin and axons) that demonstrate myelin loss and relative preservation of axons and allow a correct diagnosis.
Deep white matter infarction: correlation of MR imaging and histopathologic findings.
Marshall VG, Bradley WG Jr, Marshall CE, Bhoopat T, Rhodes RH.
MR Imaging Laboratory, Hunington Medical Research Institutes, Pasadena, CA 91105.
Radiology 1988 May;167(2):517-22 Abstract quote
Focal and confluent areas of periventricular hyperintensity have been reported on magnetic resonance (MR) images in 30% of patients over 60 years of age. In order to better understand the pathologic basis of these lesions, the authors studied 14 formalin-fixed brains with MR imaging.
Multiple focal areas of hyperintensity were identified in the periventricular white matter in three of the 14 brains studied (21%). Subsequent gross and microscopic pathologic examination of both hyperintense and normal-intensity areas was performed on 87 tissue sections. The larger lesions were characterized centrally by necrosis, axonal loss, and demyelination and therefore represent true infarcts.
Reactive astrocytes oriented along the degenerated axons were identified at distances of up to several centimeters from the central infarct. This is called isomorphic gliosis and is associated with increased intensity on T2-weighted images that increases the apparent size of the central lesion.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS Related to underlying pathology causing demyelination
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
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