Detection of global hypermethylation in well-differentiated thyroid neoplasms by immunohistochemical (5-methylcytidine) analysis.

PURPOSE: While global hypomethylation of DNA has been found in several malignancies, studies on thyroid tumours have shown controversial results using different techniques. To help resolve this issue, we assessed methylation status using two different techniques in papillary thyroid carcinomas (PTC) and follicular adenomas (FA) and carcinomas (FTC), comparing adjacent non-neoplastic thyroid tissue. METHODS: A series of 15 FA, 18 FTC and 17 PTC were assessed by: (1) measurement of methylation levels of long interspersed nuclear elements (LINE-1) using a combined bisulfite restriction analysis polymerase chain reaction protocol and (2) immunostaining with an anti-5-methylcytidine antibody that detects methylated DNA regardless of the DNA sequence. Immunostaining was scored by image analysis. RESULTS: Methylation levels of LINE-1 in FA, FTC and PTC were not significantly different from adjacent normal tissue. There was no significant difference in methylation levels of LINE-1 between FA, FTC and PTC (p = 0.44). By immunohistochemical staining for methylation, the 5-methylcytidine score was significantly higher in tumours than in normal tissue counterparts, for FA (p < 0.001), FTC (p = 0.04) and PTC (p = 0.02). PTC showed the highest 5-methylcytidine expression amongst all tumours which was significantly different from FTC (p = 0.015), but not FA (p = 0.09). There was no correlation in methylation level between LINE-1 and 5-methylcytidine scores for each group and overall. CONCLUSIONS: Well-differentiated thyroid neoplasms (FA, FTC and PTC) were not found by two independent methods to undergo global hypomethylation as part of an oncogenic sequence from normal tissue to carcinoma. Instead, hypermethylation was detected in all types of tumours, implying that this epigenetic event may contribute to oncogenic development of thyroid neoplasms (both benign and malignant).

Fatal Balamuthia amebic encephalitis in a healthy child: a case report with review of survival cases.

Balamuthia mandrillaris is one of the 4 amebas in fresh water and soil that cause diseases in humans. Granulomatous amebic encephalitis (GAE), caused by B. mandrillaris, is a rare but life-threatening condition. A 4-year-old, previously healthy, Thai girl presented with progressive headache and ataxia for over a month. Neuroimaging studies showed an infiltrative mass at the right cerebellar hemisphere mimicking a malignant cerebellar tumor. The pathological finding after total mass removal revealed severe necrotizing inflammation, with presence of scattered amebic trophozoites. Cerebrospinal fluid (CSF) obtained from lumbar puncture showed evidence of non-specific inflammation without identifiable organisms. A combination of pentamidine, sulfasalazine, fluconazole, and clarithromycin had been initiated promptly before PCR confirmed the diagnosis of Balamuthia amebic encephalitis (BAE). The patient showed initial improvement after the surgery and combined medical treatment, but gradually deteriorated and died of multiple organ failure within 46 days upon admission despite early diagnosis and treatment. In addition to the case, 10 survivors of BAE reported in the PubMed database were briefly reviewed in an attempt to identify the possible factors leading to survival of the patients diagnosed with this rare disease.

Primary intracranial peripheral primitive neuroectodermal tumor/Ewing's sarcoma presenting with acute intracerebral hemorrhage.

OBJECTIVE: To report two cases of intracerebral hemorrhage due to primary intracranial peripheral primitive neuroectodermal tumor (pPNET)/Ewing's sarcoma (ES) and review of related literatures. MATERIAL: Two cases of 17-year-old patients presented with acute increased intracranial pressure one of which also had left hemiparesis. METHOD: On neuroimaging studies, the first patient had an intraparenchymal hematoma with a size of 4 cm at the right fronto-parietal junction adjacent to tumor infiltrating the superior sagittal sinus. The second patient had a large left temporal tumor with intraventricular hemorrhage. Both patients underwent craniotomy with complete removal of tumor and hematoma. RESULTS: Pathological examination in both cases revealed numerous small round tumor cells with stippled chromatin pattern and scanty cytoplasm. Tumor cells strongly expressed CD99. Vimentin immunoreactivity was observed. The final diagnosis of pPNET/ES was rendered. There was no evidence of extracranial disease in both cases. Both patients were doing well without evidence of recurrent disease at 12 and 24-month follow-up respectively. CONCLUSIONS: Peripheral primitive neuroectodermal tumor (pPNET)/Ewing's sarcoma (ES) is a malignant small round cell tumor, commonly arising in soft tissue of the trunk and lower extremity. Those occurring in the intracranium are rare, and most patients present with progressively increased intracranial pressure and/or cranial nerve deficit. The occurrence of intracerebral hemorrhage due to primary intracranial pPNET/ES is exceedingly rare. The role of adjuvant therapy in this condition is yet to be investigated.

Phagocytic astrocytes and neurons in old encephalomalacia.

Cytoplasmic accumulation of hemosiderin was observed within astrocytes and neurons as well as in other phagocytes associated with old encephalomalacia. The first patient was 3 years old when she died with malnutrition and superimposed infection. A cortical infarct had been caused by an old thrombus in a small artery. The second case was a 9-year-old girl who had old encephalomalacia in the pineal region after extirpation of a pineoloma. The third patient was a 22-year-old man who had a cortical infarct from an embolus associated with chronic rheumatic endocarditis. Granules of hemosiderin had accumulated within the perikaryon of many astrocytes and other phagocytes in all cases, and in a few neurons in the second instance. Review of the literature reveals that cytoplasmic accumulation of particulate matter has been described infrequently with regard to neuroepithelial derivatives. Our findings indicate that astrocytes and neurons as well as derivations of mesenchyme may act as phagocytes of old blood.

Melanosis of the choroid plexua.

A unique case of melanosis of the choroid plexus in a 74-year-old man who died of hypertensive cardiovascular disease is described. The cerebral lesion did not cause symptoms. The proposed pathogenesis is the conversion of choroidal epithelial lipofuscin into melanin. Our findings also may explain the origin of a previously reported primary malignant melanoma of the choroid plexus and of black cortical adenomas of the adrenal gland.

Combined congenital vascular anomalies and neuroepithelial (colloid) cysts.

We present two unique cases of intracranial congenital lesions of different origins. A 29-year-old woman had an angioma of the choroid plexus of the third ventricle and paraventricular region; a small neuroepithelia cyst was also included in the lesion. This case is the first known description of a choroidal angioma in the third ventricle. The other patient, a 39-year-old woman, had a ruptured saccular aneurysm at the junction of the anterior communicating and left anterior cerebral arteries, a cerebellar hemangioma, and a small neuroepithelial cyst with numerous papillary infoldings in the pineal region. The presence of choroid plexus in this cyst is further evidence of a developmental malformation. Review of the literature disclosed that vascular malformations and neuroepithelial cysts are occasionally associated with other congenital anomalies. The findings support the congenitally derived nature of these lesions.

Combined neuroepithelial (colloid) cyst and xanthogranuloma (xanthoma) in the third ventricle.

A case is reported of a combined neuroepithelial cyst and xanthogranuloma of the choroid plexus in the third ventricle of a 22-year-old woman. It is suggested that proliferated neuroepithelial cells lining the cyst enter the fibrous wall through the disrupted basal lamina, and then become xanthomatous cells. Disintegration of these foamy epithelial cells releases lipids and other materials into the cyst wall, provoking a response of macrophages and multinucleated giant cells of foreign-body type. A xanthogranuloma is then formed. The origin of "colloid" cysts is from neuroepithelium; these cysts arise from both ependyma and choroid plexus. Those cysts arising in or near the floor of the third ventricle may originate in stomodeal epithelium, but a distinction cannot be made from neuroepithelial cysts by presently available methods.

Multiple neuroepithelial (colloid) cysts: association with other congenital anomalies.

A 4-year-old boy had three neuroepithelial cysts, one in the third ventricle and two in the supratentorial subarachnoid space, and also had stenosis of the cerebral aqueduct, obstructive internal hydrocephalus, frontoethmoidal meningoencephalocele, and right microphthalmia. The occurence of these combined lesions supports the congenitially derived nature of the cysts. The cysts originated from neuroepithelium including ectopic ependyma-lined structures. The exception may be those cysts arising in or near the floor of the third ventricle; these cysts could be derived from the cleft of Rathke's pouch, an endodermal derivative. Folding of the neuroepithelium in contact with mesenchyma or neuroglial tissue is proposed as the mode of formation of most "colloid" cysts. Review of the literature as well as our experience indicates that neuroepithelial cysts are widely distributed throughout the central nervous system.

Ganglioglioma of the optic chiasm: case report and review of the literature.

We report a case of a hypothalamic chiasmatic ganglioglioma in a 21-year-old woman who presented with hyperprolactinemia and developed visual field defects. This circumscribed cystic lesion with an enhancing mural nodule was radiologically indistinguishable from a pilocytic astrocytoma. Although rare, gangliogliomas should be included in the differential diagnosis of lesions occurring in this area of the brain.

Regional distribution of rabies viral antigen in central nervous system of human encephalitic and paralytic rabies.

We studied the distribution of rabies viral antigen in the brain and spinal cord of 7 patients with rabies by immunohistochemical techniques. Four patients presented with encephalitis, the remaining 3 had paralysis. Neither the rabies viral antigen distribution nor inflammation paralleled clinical presentations. Patients who had survival times of 7 days or less (4/7) had a greater amount of antigen-positive neurons in brainstem and spinal cord regardless of the clinical type. Neuroglial cells were also found to contain rabies antigen. Our findings suggest that virus localization may not account for the difference in clinical manifestations.

Solitary primary lymphoma of the cerebellopontine angle: case report.

A 27-year-old woman had a solitary primary B-cell lymphoma that involved the right cerebellopontine angle. The tumor invaded the ipsilateral acoustic nerve and produced profound sensory neural hearing loss. Surgical resection was promptly followed by radiotherapy and a concluding brief chemotherapy treatment. The patient survived 34 months after the initial onset of the disease or 22 months after the combined treatments. Only six lymphomas affecting the cerebellopontine angle, three primary and three secondary, have been recorded. The combination of surgical treatment and radiotherapy appeared to offer encouraging results for primary lymphomas. The differential diagnosis of lymphoma of the cerebellopontine angle includes common acoustic neurilemoma, meningioma, epidermoid tumor, and other rare neoplasms involving this region that required pathological verification to distinguish them.

Extramedullary subdural meningioma after trauma.

A 61-year-old man had an extramedullary subdural meningioma occurring close to the site of an old vertebral traumatic fracture and spinal cord injury. The tumor was discovered 3 years after the spinal trauma. This finding supports the existence of a causal relationship between trauma and subsequent tumor development. A review of the literature disclosed only one other case of intraspinal meningioma after the traumatic fracture of the spine with spinal cord compression.

Genetic heterogeneity and progression in different areas within high-grade diffuse astrocytoma.

The primary objective of this study was to determine loss of heterozygosity (LOH) in various portions of 9 high-grade diffuse astrocytomas, 8 glioblastomas and 1 anaplastic astrocytoma. LOH was observed on chromosomes 9, 10, 17 and 19 in 8, 3, 4 and 2 cases, respectively. Genetic heterogeneity and a multistep process were identified in 4 glioblastomas explaining the diverse morphological characteristics, a common feature of diffuse astrocytomas. In 2, 2, 3 and 1 cases, the allele losses were found within part of grade IV astrocytomas but not grades II or II/III, on chromosomes 9, 10, 17 and 19, respectively. In one of these, while genetic heterogeneity was observed on chromosome 17 between the area of grade II and grade IV, 9pLOH was found within both areas and occurred on the same allele. The other 5 cases did not demonstrate genetic heterogeneity and the LOH was on the same allele, irrespective of grade, suggesting clonal origin. In conclusion, at the molecular level, the diverse morphological features of astrocytoma develops by a multistep mechanism of genetic alterations from one cell via low-grade and more malignant tumors towards glioblastoma.

Neurilemmoma of the oculomotor nerve.

A case is presented of neurilemmoma of the left oculomotor nerve occurring in a 64-year-old hypertensive woman. The incipient tumour produced ptosis, limited inwards rotation of the eyeball, and persistent pupillary dilatation on the left side. The mechanism of this process is discussed, having regard to the interruption of the fibres innervating these structures by the tumour, and considering the mode of occurrence of the ocular and pupillary impairments. The patient also had generalized athero-sclerosis and fusiform aneurysm of the terminal part of the left internal carotid artery. The symptoms of headache, seizure, coma, and temporary right hemiparesis were considered as manifestations of hypertensive encephalopathy unrelated to the tumour.

Neoplasm of mixed mesenchymal and neuroepithelial origin of the optic nerve.

A case is reported of a 19-year-old male having right proptosis for 4 years because of a mixed meningioma and astrocytoma of the ipsilateral optic nerve. The sheath of this nerve is analogous to the leptomeninges, and neuroglial cells constitute the stroma of the nerve. Both meningioma and astrocytoma therefore can arise primarily in the optic nerve, and they may be combined in the same mass, forming a neoplasm of mixed mesenchymal and neuroepithelial origin.

Unilateral proptosis as a clinical presentation in primary angiosarcoma of skull.

A case is reported of unilateral proptosis of the left eyeball as a unique clinical presentation of primary angiosarcoma of the skull involving the sphenoid and frontal bones and roof of the orbit on the left side of a 32-year-old man. The intraosseous, extradural non-encapsulated, and friable tumour contained cytoplasmic factor VIII-related antigen. After complete removal of the tumour the patient has been well for 10 months of the follow-up period. This case brings the total number of reported primary angiosarcomas of the cranium to nine. All patients were male and most of them were young. The average age was 24 years. The frontal bone seems to be the site of predilection for cranial angiosarcomas. Surgical extirpation, radiation, or combined surgical removal and radiation have been used for treating angiosarcoma of the skull with variable results. It is suggested that angiosarcoma of the skull has a worse prognosis than angiosarcoma of bones other than the cranium because the patient may die of secondary neoplastic involvement of the brain.

Primary intraorbital extraocular primitive neuroectodermal (neuroepithelial) tumour.

A case is reported of primary primitive neuroectodermal (neuroepithelial) tumour occurring in the right orbit of a 52-year-old man. The intraorbital extraocular location is unique for this kind of neoplasm. The malignant tumour was differentiated into primitive neuroepithelial, ependymal, and oligodendroglial cells. The neuroglia was identified by localisation of cytoplasmic glial fibrillary acidic protein. It is suggested that this primary intraorbital, extraocular, primitive neuroectodermal tumour with neuroglial differentiation is akin to the primitive neuroectodermal tumours of the neuraxis, including the cerebellar medulloblastomas, and to some peripheral nerve tumours known as malignant neuroepitheliomas, malignant ependymomas, and neuroblastomas. The ectomesenchymal remnant of the neural crest or ectopic neuroepithelium or both may have been the origin of the present tumour. Differentiation of the neuroectodermal component of the neural crest or heterotopic neuroepithelium or both would create a primitive neuroectodermal tumour with diverse neuroglial elements.

Cerebellar neoplasm of mixed mesenchymal and neuroepithelial origin. Case report.

A 3 1/2-year-old boy had a neoplasm of mixed mesenchymal and neuroepithelial origin in the cerebellar vermis. The tumor was composed of rhabdomyosarcoma and medulloblastoma. There was additional differentiation within the neuroepithelium, including neoplastic neurons, neuroblasts, astroglia, oligodendroglia, ependymal cells as well as foci of glioblastomatous transformation. It is suggested that this combined tumor arose from the neural crest or combined neural crest and neural tube. The rhabdomyosarcoma could have arisen from the mesenchymal portion of the neural crest, and the medulloblastoma from the neuroectodermal part of the neural crest or from the neural tube itself. The two tumor types formed a neoplasm of mixed mesenchymal and neuroepithelial origin.

Solitary primary intracranial extracerebral glioma. Case report.

A case is presented of a solitary primary extracerebral mixed glioma occurring in the right suprasellar and parasellar region of a 49-year-old woman who had bilateral temporal hemianopsia for 3 months. At craniotomy, the well demarcated outline and extracerebral location of the tumor suggested that it was a meningioma. However, its gliomatous nature was confirmed by identification of glial fibrillary acidic protein (GFAP) in the tumor cells. Review of nine reported solitary primary intracranial extracerebral gliomas, including the present case, revealed that they tended to occur in the third to fifth decades of life, in patients with an average age of 42 1/2 years, and without sexual predilection. All were supratentorial with a tendency to be situated in the vicinity of the Sylvian fissure. Only the glioma in the present case was at the cranial base. They were diagnosed as three astrocytomas, two glioblastomas, two oligodendrogliomas, one astroblastoma, and one mixed glioma. A suggestion is made that all these gliomas arose primarily from heterotopic neuroglia in the leptomeninges.

A combined neurilemmoma and angioma of the parasellar region. Case report.

A combined neurilemmoma and angioma of the parasellar region is presented that clinically simulated a pituitary tumor. The lesion produced increased intracranial pressure and subarachnoid hemorrhage (SAH). This neoplasm is believed to have originated from the leptomeninges or the perivascular neural elements, or both. The angiomatous network within the tumor could have been the source of the SAH.