Medulloblastoma or cerebellar dysplastic gangliocytoma (Lhermitte-Duclos disease)?

Medulloblastoma or Cerebellar Dysplastic Gangliocytoma (Lhermitte-Duclos Disease)?

cerebellar gangliocytoma on both computed tomography and magnetic resonance imaging of the brain was present in an 18-month-old male. Without a pathologic confirmation it could not be differentiated from a cerebellar dysplastic gangliocytoma diagnosed solely by imaging studies.

Case Report

Dysplastic cerebellar gangliocytoma is a rare benign tumor. Its neuroimaging findings are characterized by an abnormal laminated or folial pattern in the posterior fossa [1]. Some authors proposed that it could be diagnosed by typical neuroimaging findings without a pathologic examination [2]. A medulloblastoma mimicking a dysplastic

This 18-month-old male was well until 2 months before admission. At that time his developmental achievements began gradually to regress so that finally he could no longer walk, stand, crawl, or sit. Clumsiness of hands was evident when he was playing with toys. Although his activity decreased, his appetite, sucking power, and speaking fluency remained the same. There was no fever, and there were no symptoms or signs of upper respiratory tract or gastrointestinal disease. On examination, he was clearly conscious, and vital signs were stable. His anterior fontanel was still open and markedly bulging. The head circumference was 51 cm, which was above the ninety-fifth percentile of the head growth chart of Taiwanese boys of the same age. There was no icteric sclera or sunset eyes. The size and reflex of the pupils were normal. Papilledema was evident bilaterally. Truncal ataxia, mild hypotonia, and dysmetria were noted. The muscle power was symmetrically decreased to grade 4/5. The deep tendon reflexes were normal. There were no cutaneous lesions. The results of a complete blood cell examination, C-reactive protein, and chemistry data were within normal limits. Because of a cerebellar lesion, color Doppler brain sonography via the anterior fontanel disclosed hydrocephalus of the lateral and third ventricles and abnormal echogenicity in the posterior fossa. The pulsatility index and resistance index of anterior cerebral artery were 0.65 and 0.47, respectively. Cranial computed tomography demonstrated a large heterogeneous mass with a laminated pattern in the cerebellum that compressed the fourth ventricle causing hydrocephalus (Fig 1). Magnetic resonance imaging demonstrated that the cerebellar mass was predominantly intermediate in signal intensity on both T1-weighted (TR ⫽ 540, TE ⫽ 14) and T2-weighted (TR ⫽ 4,200, TE ⫽ 99) images, with a laminated or folial configuration. The interspersed stripes were hypointense on T1-weighted images and hyperintense on T2-weighted images. The mass exhibited positive contrast enhancement after intravenous gadolinium administration. All of the findings suggested a dysplastic gangliocytoma (Fig 2). Because of the obstructive hydrocephalus caused by the tumor, a suboccipital craniotomy was undertaken to remove the tumor, and a ventriculoperitoneal shunt was placed later. Grossly, the tumor was ill defined so that it could not be differentiated from the surrounding nerve tissue. The histopathologic study revealed a cellular tumor composed of intranodular and internodular patterns of hyperchromatic cells. The nuclei of internodular cells were more hyperchromatic. The intranodular cells had round nuclei and perinuclear clearings. The tumor cells were undergoing active mitosis. Homer Wright rosettes and subpial aggregates of tumor cells were evident. The reticular stain demonstrated abundant reticulin in the internodular area. The results of immunohistochemical study were negative for glial fibrillary acidic protein, positive for neuron-specific enolase, positive for synaptophysin, and revealed a

From the *Division of Pediatric Neurology; Chang Gung Children’s Hospital; and the †Departments of Pathology and ‡Diagnostic Radiology, Chang Gung Memorial Hospital; Medical College of Chang Gung University, Taoyuan, Taiwan.

Communications should be addressed to: Dr. Wang; Division of Pediatric Neurology; Chang Gung Children’s Hospital; 5-7, Fu-Hsin Street; Kueishan; Taoyuan, 333 Taiwan. Received February 26, 2002; accepted May 22, 2002.

Kuo-Shin Chen, MD*, Po-Cheng Hung, MD*, Huei-Shyong Wang, MD*, Shih-Ming Jung, MD†, and Shu-Hang Ng, MD‡ Dysplastic cerebellar gangliocytoma is a rare benign tumor associated with specific neuroimaging findings of abnormal laminated or folial pattern in the posterior fossa. Some authors thus proposed that it could be diagnosed by neuroimaging studies alone. We encountered a patient with medulloblastoma in which the neuroimaging findings mimicked those of dysplastic gangliocytoma. In patients with a posterior fossa tumor suggestive of a dysplastic gangliocytoma on neuroimaging studies, a pathologic confirmation is necessary. © 2002 by Elsevier Science Inc. All rights reserved. Chen K-S, Hung P-C, Wang H-S, Jung S-M, Ng S-H. Medulloblastoma or cerebellar dysplastic gangliocytoma (Lhermitte-Duclos disease)? Pediatr Neurol 2002;27: 404-406.

Introduction

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© 2002 by Elsevier Science Inc. All rights reserved. PII S0887-8994(02)00455-1 ● 0887-8994/02/$—see front matter

Figure 1. Brain CT without intravenous contrast medium enhancement demonstrates a heterogeneous cerebellar tumor of laminated pattern with noncommunicating hydrocephalus in the 18-month-old male.

proliferation index of 20%. The above results were compatible with a diagnosis of medulloblastoma, instead of dysplastic gangliocytoma. A postoperative spinal magnetic resonance imaging study revealed no evidence of cerebrospinal fluid seeding. The patient then received two courses of chemotherapy (cis-platin and VP-16) and another operation for the residual tumor. At 6 months after the second surgery the patient could walk with support. Further chemotherapy is scheduled.

Discussion Approximately one half of posterior fossa tumors in children are intracranial neoplasms. The most common posterior fossa tumors are medulloblastomas, cerebellar astrocytomas, brainstem gliomas, and ependymomas [1]. Although the clinical presentations of different posterior fossa tumors are similar, the treatment may vary. For medulloblastoma the treatment begins with the attempt of total gross resection, followed by radiotherapy. In children less than 3 years of age with a large tumor size, postoperative chemotherapy may improve the outcome. On the contrary, total excision of a grade I cerebellar astrocytoma may cure the patient. A definite diagnosis is important in the management of a posterior fossa tumor. Dysplastic cerebellar gangliocytoma, or Lhermitte-Duclos disease (named after the first clinicians to report it in 1920), is an unusual hamartomatous lesion that causes progressive mass effects in the posterior fossa and is often associated with cerebellar dysfunction, noncommunicating hydrocephalus, and intracranial hypertension [3,4]. It is not a true neoplasm but an abnormality of cell migration or a hamartoma, although there was one report of a dysplastic gangliocytoma that unusually transformed into a malignant astrocytoma [5]. The pathology of dysplastic gangliocytoma was caused by profusion of dysplastic cortical neurons, hypertrophic change of the granule cell layer, and

Figure 2. The magnetic resonance appearance of the medulloblastoma in an 18-month-old male. (A) T1-weighted magnetic resonance image (TR ⫽ 540, TE ⫽ 14) reveals an intermediate signal intensity cerebellar mass with a folial pattern, interspersing with hypointense stripes. The fourth ventricle is compressed. (B) T2-weighted magnetic resonance image (TR ⫽ 4,200, TE ⫽ 99) demonstrates the folial-pattern mass interspersed with hyperintense stripes.

hypermyelination of the molecular layer of the cerebellum. Loss of Purkinje cells and thinning of the medullary hemisphere were also presented. From 1969 to 1997, fewer than 150 cases of dysplastic gangliocytoma were reported [2]. The ages of the patients reported in these studies ranged from infancy to 74 years of age. Dysplastic gangliocytoma is currently thought to be a new phacomatosis because of its coexistence with Cowden’s disease [6]. Cowden’s disease, which is also termed multiple hamartoma-neoplasia syndrome, is an autosomal-dominant hereditary disorder characterized by mucocutaneous lesions, including facial papules, gingival papillomas, and acral keratoses [6]. Other systemic hamartomas are frequently present, and there are high incidences of breast, thyroid, genitourinary, and endometrial cancers [6]. The initial presentation of dysplastic cerebellar gangliocytoma, similar to other posterior fossa tumors, include

Chen et al: Medulloblastoma or Dysplastic Gangliocytoma? 405

elevated intracranial pressure, impaired hearing, vomiting, intermittent headache, and unsteady gait [7,8]. Dietlein et al. [9] reported on an infant with a dysplastic gangliocytoma, which was diagnosed by ultrasonography and confirmed by magnetic resonance imaging. The brain ultrasound of our patient did not demonstrate the abnormal laminated pattern, perhaps because of the poor far-field resolution of the posterior fossa from the anterior fontanel in a male after early infancy. The diminished pulsatility index and resistance index of anterior cerebral artery on Doppler examination was suggestive of intracranial hypertension. The demonstration of obstructive hydrocephalus with abnormal echogenicity in the posterior fossa suggested that a further neuroimaging study, either computed tomography or magnetic resonance imaging, be performed. Magnetic resonance imaging is the modality of choice to demonstrate the striated pattern of dysplastic gangliocytoma because many artifacts may occur in the posterior fossa on computed tomography [10,11]. The uniqueness of these neuroimaging features suggested to some authors that an obligatory biopsy is unnecessary in asymptomatic patients [2]. The typical neuroimaging pictures of a dysplastic gangliocytoma are a result of the indolent growth of the cerebellar cortex, causing enlargement of the cerebellar folia and loss of secondary folding. These morphologic features produce a characteristic pattern on computed tomography scans and magnetic resonance imaging, which affords an opportunity for a preoperative diagnosis [2]. The computed tomography and sonographic studies usually demonstrate hydrocephalus caused by a cerebellar mass, which consists of isodensities, hypodensities, and abnormal laminated patterns of the cortical architecture. The typical findings of dysplastic gangliocytoma on magnetic resonance images are low-signal intensity on T1weighted and high-signal intensity on T2-weighted images. The neuroimaging findings of medulloblastoma vary in patients, but contrast-enhanced magnetic resonance imaging reveals an increased T2-weighted mass in the midline of the cerebellum in combination with hydrocephalus. Most dysplastic gangliocytomas are not enhanced after contrast medium injection. On the basis of a comparison of the magnetic resonance imaging features with histologic findings in patients with dysplastic gangliocytoma, Meltzer et al. [12] concluded that most other cerebellar masses destroy the folial pattern and reveal enhancement. The nonenhancing cerebellar hemisphere mass with the characteristic striated magnetic resonance appearance (thickened cerebellar folia) in a patient with dysplastic gangliocytoma is distinctive and should suggest the diagnosis. However, dysplastic gangliocytoma demonstrating enhancement on computed tomography or magnetic resonance imaging has been reported by Kulkantrakorn et al. [2] in one of their six patients with this condition. The mass may or may not be accompanied by

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adjacent occipital thinning, hydrocephalus, and calcification. Kulkantrakorn et al. also proposed that in the immature cerebellum of the infant and neonate the signal characteristics might not be well defined. One patient who was 1 year of age did not demonstrate the laminated appearance observed in adults [2]. In summary, the finding of a typical picture of laminated or folial pattern without contrast enhancement in a patient older than 1 year of age may highly suggest a diagnosis of dysplastic gangliocytoma. However, in patients less than 1 year of age, this characteristic pattern may be absent. Also, the presence of enhancement, although not favoring the diagnosis of a dysplastic gangliocytoma, may not exclude the possibility of it. We report a patient with medulloblastoma that mimicked dysplastic gangliocytoma by manifesting a characteristic foliated pattern on magnetic resonance imaging. The presence of contrast enhancement was the only clue that did not favor a diagnosis of dysplastic gangliocytoma. In this condition the importance of surgical confirmation cannot be overemphasized.

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