Noriko Aida

Possible linkage between specific histological structures and aberrant reactivation of the Wnt pathway in adamantinomatous craniopharyngioma

This study concerns the significance of nuclear/cytoplasmic expression of beta‐catenin and mutation of the beta‐catenin gene in craniopharyngiomas. Fourteen adamantinomatous type and one squamous papillary type craniopharyngiomas were studied. Histologically, 13 of 14 adamantinomatous type craniopharyngiomas showed typical features, ie mixtures of ‘palisading cells’, ‘stellate cells’, and ‘ghost cells’. In addition, ‘whorl‐like arrays’ of epithelial cells were frequently observed in the areas of stellate cells. On immunohistochemistry, all typical adamantinomatous type craniopharyngiomas showed nuclear/cytoplasmic expression of beta‐catenin predominantly in cohesive cells within the whorl‐like arrays and in cells transitional towards ghost cells, where immunoreactivity for Ki‐67 was almost absent. The cohesive cells in the whorl‐like arrays also demonstrated loss of cytokeratin isoform expression. Using direct sequencing of amplified nucleic acids, nine of the 13 typical adamantinomatous type craniopharyngiomas with nuclear beta‐catenin accumulation showed heterozygous one‐base substitution mutation of the beta‐catenin gene. The other unusual adamantinomatous type and squamous papillary type craniopharyngiomas showed no obvious nuclear/cytoplasmic beta‐catenin immunoreactivity and no mutation of the beta‐catenin gene, suggesting molecular heterogeneity. These findings suggest that the pathogenesis of typical adamantinomatous type craniopharyngioma is associated with abnormalities of Wnt signalling that act as a morphogenetic signal towards whorl‐like arrays and ghost cells rather than as simple proliferation stimuli. Copyright

Natural Course of Neuroblastoma Detected by Mass Screening: A 5-Year Prospective Study at a Single Institution

PURPOSE To describe various favorable courses of neuroblastoma (NBL) detected by mass screening and to present our observation program as a temporary treatment option, to be used until a final decision is made regarding the mass screening program for 6-month-old infants. PATIENTS AND METHODS Between October 1993 and November 1999, 26 of 51 patients with NBL detected by mass screening were enrolled in our observation program. The criteria for observation included urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels less than 50 microg/mg creatinine, smaller tumor size (< 5.0 cm), preoperative status, and granted informed consent. Patients were divided into four groups according to changes in urinary VMA and HVA values and tumor size. Patients who no longer fulfilled criteria underwent surgery. RESULTS The observation period ranged from 4 to 73 months. Urinary VMA and HVA levels decreased in 19 of 26 patients, often by age 16 months. Eighteen patients had regressing tumors, and in 10 of these cases, the tumor was undetectable or barely detectable by imaging techniques. Four patients younger than 12 months had increased tumor marker levels and tumor volume, histologically reflecting neuroblastic proliferation. The remaining three patients, all older than 18 months, had varied tumor marker levels but increased tumor volume, histologically reflecting an increase in Schwann cells. No upgrading of tumor stage or unfavorable biologic factor was noted in any patient. CONCLUSION None of our patients showed evidence of transition from favorable to unfavorable prognosis, a finding that points to a reduction in the significance of screening as a public health measure. Until results of ongoing screening trials involving older patients have been evaluated, the observation program can be used as a temporary measure to avoid, with little risk, unnecessary surgical intervention.

Large intracranial vessel occlusive vasculopathy after radiation therapy in children: Clinical features and usefulness of magnetic resonance imaging

PURPOSE To assess the relationship between large intracranial vessel occlusive vasculopathy (vasculopathy) and radiation therapy, and to clarify the clinical efficacy of magnetic resonance (MR) imaging in the diagnosis and screening of the vasculopathy. METHODS AND MATERIALS We retrospectively evaluated the medical records and serial MR images for 32 pediatric patients, in whom radiation therapy had been given to fields including the circle of Willis and major cerebral arteries. All children had periodically undergone follow-up neurologic assessment and MR imaging examinations at Kanagawa Childrens Medical Center for more than one year after radiation therapy (range 1.3-14 years). Patients who had not remained free of tumor progression up to the time of final evaluation were excluded. RESULTS Vasculopathy developed in 6 of 32 patients 2-13 years after radiation therapy. Three of them presented with transient ischemic attacks (TIA) and the other three showed infarctions without preceding TIA. Steno-occlusive changes of major cerebral arteries were identified by MR imaging in all six patients, but not obtained in the remaining 26 patients. In the patients with TIA, MR imaging demonstrated steno-occlusive changes at the time of TIA, before irreversible infarction. They have been doing well subsequent to encephaloduroarteriosynangiosis. In the three patients who presented infarction without preceding TIA, MR imaging did not demonstrate the vascular change before the onset of infarction, and two of them developed neurologic deficits. The mean exposure dose for the circle of Willis and major cerebral arteries in these six patients was significantly higher than that in the remaining 26 patients without this sequela (61 Gy vs. 50 Gy, p < 0.05). The mean age at radiation therapy of the six patients was lower, but the difference was not significant. CONCLUSION The incidence of vasculopathy after radiation therapy has a considerable correlation with radiation dose and age at radiation therapy. MR examination is useful for the diagnostic evaluation of vasculopathy, and it is also effective in screening for vasculopathy in patients with TIA, and may be helpful in the prevention of neurologic sequela.

Magnetic Resonance Imaging Regional T1 Abnormalities at Term Accurately Predict Motor Outcome in Preterm Infants

OBJECTIVE. The aim of this study was to assess whether periventricular leukomalacia findings are sufficiently sensitive for predicting the severity of motor prognosis by conventional MRI in the near term. METHODS. Preterm infants with T1 hyperintensity or cysts in the periventricular regions on term MRI were selected, and their gross motor functions were evaluated at the age of 3 to 5 years. Sixty-two infants had findings of T1 hyperintensity or cysts, and except for infants with these findings, none were diagnosed later as periventricular leukomalacia. RESULTS. All 37 patients with cerebral palsy had periventricular lesions with T1 hyperintensity or cysts in the corona radiata above the posterior limb of the internal capsule on coronal sections. Small T1 hyperintensity lesions were seen on coronal slices and were often difficult to detect on axial slices. All of the 17 infants with T1 hyperintensity findings sparing the corona radiata above the posterior limb of the internal capsule showed normal motor development, irrespective of findings of ventriculomegaly. There was a tendency for the presence of widespread lesions in corona radiata above the posterior limb of the internal capsule to be correlated with the severity of motor handicap. CONCLUSIONS. Lesions in the corona radiata above the posterior limb of the internal capsule on a coronal view by term MRI were useful for predicting motor prognosis in preterm infants with periventricular leukomalacia.

Syndromes Associated with Vascular Tumors and Malformations: A Pictorial Review

Use of the International Society for the Study of Vascular Anomalies (ISSVA) classification system has been strongly recommended in recent years because of the need for separate therapeutic measures for patients with vascular tumors and malformations. In the ISSVA classification system, vascular tumors, which are neoplastic, are distinguished from vascular malformations, which are caused by vascular structural anomalies and are not neoplastic, on the basis of the presence or absence of neoplastic proliferation of vascular endothelial cells. It is important that radiologists be familiar with the development, diagnosis, and treatment of vascular tumors and malformations, especially the imaging features of low- and high-flow vascular malformations. Some vascular tumors and malformations develop in isolation, whereas others develop within the phenotype of a syndrome. Syndromes that are associated with vascular tumors include PHACE syndrome. Syndromes that are associated with vascular malformations include Sturge-Weber, Klippel-Trénaunay, Proteus, blue rubber bleb nevus, Maffucci, and Gorham-Stout syndromes, all of which demonstrate low flow, and Rendu-Osler-Weber, Cobb, Wyburn-Mason, and Parkes Weber syndromes, all of which demonstrate high flow. Because imaging findings may help identify such syndromes as systemic, it is important that radiologists familiarize themselves with these conditions.

Congenital absence of the portal vein: clinical and radiologic findings.

Congenital absence of the portal vein (CAPV) is a rare anomaly in which the intestinal and splenic venous drainage bypasses the liver and drains into the systemic veins through various venous shunts. In patients with CAPV, the portosystemic shunting causes disruption of the enterohepatic circulation and leads to various clinical manifestations. CAPV can be diagnosed without invasive techniques. This article illustrates the clinical and radiologic findings (including ultrasound, CT, and MRI) of CAPV.

NUT midline carcinoma: report of 2 cases suggestive of pulmonary origin.

In this study, we report 2 pediatric cases of nuclear protein of the testis (NUT) midline carcinoma (NMC) suggestive of pulmonary origin: case 1 was a 14-year-old Japanese boy and case 2 was a 7-year-old Japanese girl. Initial symptoms of both cases were prolonged cough and chest pain, and the case 2 patient also complained of lumbago and lumbar mass due to bone metastases. Imaging studies revealed that pulmonary tumors from both patients were located at the hilar region of the lower lobe. Biopsies of the tumors showed undifferentiated carcinoma in case 1 and combined undifferentiated and squamous cell carcinoma in case 2. Despite intensive treatment with chemotherapy and radiation, progression of neither tumor was controlled, and both patients died of the tumors at 1 year (case 1) and 4 months (case 2) after onset of disease. Both tumors were diffusely positive for p63 and NUT expression and were partially positive for various cytokeratins. Reverse transcription polymerase chain reaction analysis and subsequent direct sequencing revealed that the bromodomain-containing protein 4-NUT chimeric gene was present in tumor tissue of both patients, leading to a diagnosis of NMC. The tumor cells of case 1 were also positive for thyroid transcription factor-1 expression, but those of case 2 were negative. Histologic examination of the surgically removed lung tumor of case 1 indicated that the origin of the tumor was basal cells of the bronchiolar epithelia.

Susceptibility-Weighted Imaging Findings of Cortical Laminar Necrosis in Pediatric Patients

BACKGROUND AND PURPOSE: MR susceptibility-weighted imaging (SWI) is a highly sensitive technique for detection of hemorrhage, but its utility in the evaluation of children with laminar necrosis is not yet known. We assessed whether cortical laminar necrosis in pediatric patients contains hemorrhage on SWI. MATERIALS AND METHODS: “Cortical laminar necrosis” was defined as a hyperintense cortical lesion on T1-weighted imaging in the subacute or chronic phase of brain damage in some foci involving the cerebral cortex and white matter such as hypoxic-ischemic incidents and encephalopathy. Medical records, CT, and MR images were retrospectively analyzed. Fifteen patients (7 boys, 8 girls; age range, 0–13 years) were included. The areas of signal-intensity loss on SWI that were considered to be hemorrhage were correlated with the laminar necrosis. CT was assessed to correlate with the presence of calcification at the location of the signal-intensity loss on SWI. To assess appearance or signal-intensity changes of hemorrhage in the laminar necrosis, follow-up SWI was performed. RESULTS: The causes of laminar necrosis included infarction in 4 patients, ischemic changes from Moyamoya disease in 2, meningoencephalitis in 2, hypoxic-ischemic encephalopathy in 2, shaken baby syndrome in 1, encephalopathy from severe infection in 1, status epilepticus in 1, citrullinemia in 1, and brain injury with posterior reversible encephalopathy syndrome in 1. T1-weighted imaging showed focal laminar necrosis in 8, multifocal laminar necrosis in 2, and diffuse laminar necrosis in 5. SWI findings correlated with laminar necrosis included the following: no hemorrhage in 13 patients (80.0%), dotted hemorrhage in 2 (13.3%), and laminar hemorrhage in 1 (6.7%). Follow-up SWI performed in 6 patients showed no additional hemorrhage. CONCLUSION: Most areas of cortical laminar necrosis in pediatric patients showed no hemorrhage on SWI.

MRI findings of dysplasia epiphysealis hemimelica

We report a boy with dysplasia epiphysealis hemimelica of the knee, particularly emphasizing MRI findings. When he was 14 months of age, plain radiography exhibiting juxta-articular soft tissue mass with small, punctate, calcified foci did not warrant the definitive diagnosis, while MRI clearly demonstrated osteocartilaginous overgrowth of the femoral epiphysis. The epiphyseal mass mostly showed the same signal intensity as normal cartilage but contained low signal spots corresponding to calcified foci. The cartilaginous cap was depicted as a mottled area of high intensity on a T2-weighted image. When the patient was 4 years of age, this ossified mass was resected surgically and pathologically identified as osteochondroma incorporated into the epiphysis.

A cloverleaf skull syndrome probably of Beare-Stevenson type associated with Chiari malformation

A case of cloverleaf skull (CLS) syndrome with Chiari malformation was reported. The patient developed congenital hydrocephalus, upper airway obstruction and breath holding spells. Ventriculo-peritoneal shunt improved the hydrocephalus, but the patient progressively developed apneic episodes in spite of intubation. Brain magnetic resonance imaging (MRI) disclosed severe Chiari malformation. Laminectomy of the cervical vertebrae and craniectomy at the occipital bone were performed to relieve the brain stem compression. Postoperatively, the respiratory symptoms improved slightly, but 8 weeks later the patient suddenly died. Literature survey revealed that this is the second case report of CLS associated with Chiari malformation. It was assumed that the respiratory problems in our patient are ascribable to the Chiari malformation as well as the upper airway obstruction. The patient here reported seems to be a case of Beare-Stevenson cutis gyrata syndrome, in view of an association of multiple characteristic dysmorphic features, in addition to CLS.