Radiation-Induced Supratentorial Primitive Neuroectodermal Tumor after Treatment for Non-Hodgkin's Lymphoma.

Secondary, radiation-induced, supratentorial primitive neuroectodermal tumors (PNETs) are extremely rare entities which may present in survivors of childhood cancers after central nervous system radiation. These lesions have been described after a number of pediatric cancers and demonstrate unique treatment problems and an accelerated clinical course compared to primary PNETs. We present a case of a sixteen year old male with a history of non-Hodgkin's lymphoma who presented with a radiation-induced PNET, and describe our treatment for this lesion. These secondary, radiation-induced tumors increase in significance as the survival of childhood malignancy increases in West Virginia.

Differences in supratentorial white matter diffusion after radiotherapy--new biomarker of normal brain tissue damage?

INTRODUCTION: Therapy-induced injury to normal brain tissue is a concern in the treatment of all types of brain tumours. The purpose of this study was to investigate if magnetic resonance diffusion tensor imaging (DTI) could serve as a potential biomarker for the assessment of radiation-induced long-term white matter injury. MATERIAL AND METHODS: DTI- and T1-weighted images of the brain were obtained in 19 former radiotherapy patients [nine men and 10 women diagnosed with astrocytoma (4), pituitary adenoma (6), meningioma (8) and craniopharyngioma (1), average age 57.8 (range 35-71) years]. Average time from radiotherapy to DTI scan was 4.6 (range 2.0-7.1) years. NordicICE software (NIC) was used to calculate apparent diffusion coefficient maps (ADC-maps). The co-registration between T1 images and ADC-maps were done using the auto function in NIC. The co-registration between the T1 images and the patient dose plans were done using the auto function in the treatment planning system Eclipse from Varian. Regions of interest were drawn on the T1-weighted images in NIC based on isocurves from Eclipse. Data was analysed by t-test. Estimates are given with 95% CI. RESULTS: A mean ADC difference of 4.6(0.3;8.9)× 10(-5) mm(2)/s, p = 0.03 was found between paired white matter structures with a mean dose difference of 31.4 Gy. Comparing the ADC-values of the areas with highest dose from the paired data (dose > 33 Gy) with normal white matter (dose < 5 Gy) resulted in a mean dose difference of 44.1 Gy and a mean ADC difference of 7.87(3.15;12.60)× 10(-5) mm(2)/s, p = 0.003. Following results were obtained when looking at differences between white matter mean ADC in average dose levels from 5 to 55 Gy in steps of 10 Gy with normal white matter mean ADC: 5 Gy; 1.91(-1.76;5.58)× 10(-5) mm(2)/s, p = 0.29; 15 Gy; 5.81(1.53;10.11)× 10(-5) mm(2)/s, p = 0.01; 25 Gy; 5.80(2.43;9.18)× 10(-5) mm(2)/s, p = 0.002; 35 Gy; 5.93(2.89;8.97)× 10(-5) mm(2)/s, p = 0.0007; 45 Gy; 4.32(-0.24;8.89)× 10(-5) mm(2)/s, p = 0.06; 55 Gy; -4.04(-14.96;6.89)× 10(-5) mm(2)/s, p = 0.39. CONCLUSION: The results indicate that the structural integrity of white matter, assessed by ADC-values based on DTI, undergoes changes after radiation therapy starting as early as total dose levels between 5 and 15 Gy.

[Clinical and CT-scan presentations in tuberous sclerosis complex: report of eight pediatric cases revealed by epilepsy]. / Aspects Cliniques Et Scanographiques De La Sclerose Tubereuse De Bourneville: à propos de huit cas pédiatriques révélés par une épilepsie.

OBJECTIVE: To describe the clinical and CT-scan features of the Tuberous sclerosis complex (TSC) revealed in children by epilepsy. PATIENTS AND METHOD: It was a cross sectional descriptive study carried out in the Yaounde Gyneco-Obstetric and Pediatric Hospital (YGOPH). Eight consecutive patients consulting for epilepsy between January 2005 and December 20010 with clinical and CT-scan diagnosis criteria of TSC were included in this study. RESULTS: There were two girls and six boys (aged 25months to 14years) with drug-resistant epilepsy and characteristics skin lesions of TSC (hypomelanotic macules, angiofibroma of Pringle, shagreen patches). The delay between the onset of epileptic crisis and the diagnosis of TSC varied from 10 months to 6years. One case of renal involvement and another of ophthalmic involvement were found. Cerebral CT-scan was abnormal for each patient with calcified sub-ependymal nodules in 100%, cortical tubers in 5 patients (62.5%) and one suspicion of giant sub-ependymal atrocytoma. CONCLUSION: Features of TSC are ruled by epilepsy, skin lesions, calcified sub-ependymal nodules and cortical tubers. Thus children presenting with epilepsy, should have a careful dermatological examination to search for TSC lesions. Cerebral CT-scan will afterwards seek for characteristic brain lesions.

Diagnosis of Whipple's disease using molecular biology techniques.

The diagnosis of Whipple's disease (WD) is based on the existence of clinical signs and symptoms compatible with the disease and in the presence of PAS-positive diastase-resistant granules in the macrophages of the small intestine. If there is suspicion of the disease but no histological findings or only isolated extraintestinal manifestations, species-specific PCR using different sequences of the T. whippleii genome from different tissue types and biological fluids is recommended.This study reports two cases: the first patient had diarrhea and the disease was suspected after an endoscopic examination of the ileum, while the second patient had multi-systemic manifestations,particularly abdominal, thoracic, and peripheral lymphadenopathies. In both cases, the diagnosis was confirmed using molecular biology techniques to samples from the small intestine or from a retroperineal lymph node, respectively.

Malignant transformation of an intraaxial-supratentorial neurenteric cyst - case report and review of the literature.

Neurenteric cysts are "rare benign mass forming developmental abnormalities" that usually affect young adults. Neurenteric cysts are thought to be derived from primitive endoderm, and form as a result of faulty endodermal-notochordal separation at 3 weeks of embryogenesis. Neurenteric cysts are lined by simple-to-pseudostratified respiratory/gastrointestinal-like epithelium; as such, these lesions closely resemble colloid and Rathke's cleft cysts. Anatomically, neurenteric cysts most frequently arise in an intradural-extraaxial location anterior to the cervical-thoracic spinal cord. Intracranial neurenteric cysts are uncommon but have a tendency to reside in the infratentorial compartment. Malignant transformation of the epithelial component of neurenteric cysts is decidedly rare. Of the 3 reported cases of neurenteric cysts with malignant transformation, all were intracranial (2 infratentorial and 1 supratentorial) and extraaxial. We describe a 58-year-old female with a supratentorial-intraaxial lesion that is consistent with a neurenteric cyst exhibiting malignant transformation into an invasive mucinous papillary cystadenocarcinoma. Areas of direct transition between typical benign neurenteric cyst epithelia and malignant epithelia (i.e., carcinoma in situ), highlighted by an abrupt change in the Ki-67 proliferative index, were identified, and supported the primary nature of this brain neoplasm. Metastatic workup at the time of presentation was unremarkable, and immediately up until being lost to follow-up 38 months after gross total resection, routine follow-up MR imaging had not detected a recurrence. To our knowledge, this would be the first reported case of malignant transformation within a supratentorial-intraaxial neurenteric cyst.

Secondary supratentorial primitive neuroectodermal tumor following treatment of childhood osteosarcoma.

A 16-year-old Caucasian male was diagnosed with a primitive neuroectodermal tumor (PNET) 5 years following the diagnosis of nonmetastatic osteosarcoma of the left proximal humerus. The patient was initially treated with standard chemotherapy and limb salvage resection for osteosarcoma. Nine months after the completion of therapy, he developed lung metastases for which he underwent surgical resection and received additional chemotherapy. Almost 5 years after the osteosarcoma diagnosis, the patient was diagnosed with a supratentorial PNET, which represents the first known case reported in a patient with osteosarcoma.

Poor-risk high-grade gliomas in three survivors of childhood acute lymphoblastic leukaemia--an overview of causative factors and possible therapeutic options.

PURPOSE: Malignant high-grade gliomas are the most common secondary neoplasms in children cured of acute lymphoblastic leukaemia (ALL). Although many predisposing factors exist (including systemic or intrathecal chemotherapy, young age, brain infiltration and genetic predispositions), cranial irradiation appears to be the strongest one. METHODS: Three cases of secondary high-grade gliomas (two multiform glioblastomas, grade IV; one anaplastic astrocytoma, grade III) developed in ALL survivors (F-M, 1:2) 3 to 6.3 years after stopping ALL therapy according to BFM-90 trial. RESULTS: All tumours were supratentorial, contrast-enhancing, space-occupying, highly advanced and aggressive. Possible risk factors and current therapeutic options for paediatric ALL and malignant gliomas are reviewed and discussed. CONCLUSIONS: Prognosis in secondary malignant gliomas in children is poor (overall survival of 5, 10 and 19 months) despite intense therapy. Thus, protocols for paediatric ALL reduce prophylactic cranial irradiation in favour of intrathecal and intravenous high-dose MTX. Nevertheless, ALL survivors must undergo systematic, long-term surveillance for early detection of intracranial neoplasms.

c-Myc and beta-catenin cooperate with loss of p53 to generate multiple members of the primitive neuroectodermal tumor family in mice.

Primitive neuroectodermal tumors (PNETs) are a family of primary malignant brain tumors that include medulloblastomas. Although genetic models of a subset of medulloblastomas are documented over the past decade, the molecular basis of other subclasses of PNET remains unclear. As elevated c-Myc expression, activation of Wnt/beta-catenin signaling and dysfunction of p53 are seen in human PNETs, we investigated what role these abnormalities have in the formation of PNETs. Incorporating these abnormalities, we generated supratentorial PNET (sPNET) in mice using somatic cell gene transfer. We show that sPNETs arise from GFAP-expressing cells by forced c-Myc expression combined with p53 inactivation. beta-catenin activation promotes tumor progression and induces divergent differentiation. These c-Myc+beta-catenin-induced PNETs are histologically similar to large cell/anaplastic medulloblastomas and can occur in both cerebrum and cerebellum. Furthermore, we have obtained one PNET with marked epithelial differentiation having histological resemblance to choroid plexus carcinoma in this series. Our results in mice suggest that sPNET with varied differentiation and large cell/anaplastic medulloblastomas may be two tumor groups with similar genetic foundations. These data provide insights into the biology and classification of human PNETs and suggest that multiple tumor types or variants can be generated from a fixed set of genetic abnormalities.

Delayed occurrence of intracranial supratentorial chondroma following compound depressed skull fracture.

We describe an exceptional case of a frontal convexity chondroma arising at the site of a compound depressed skull fracture operated on 12 years earlier. We conclude that intracranial chondroma should be included in the differential diagnosis of a calcified mass for the patients who had had a compound, depressed skull fracture along the suture line, especially in cases of dural laceration by the fragmented bone.

[Supratentorial cavernomas: clinical picture, diagnosis, treatment]. / Supratentorial'nye kavernomy: klinicheskaia kartina, diagnostika, lechenie.

The study was undertaken to examine the clinical picture, diagnosis, morphology and substantiate management policy for patients with supratentorial cavernomas. Examination was made in 160 patients with this abnormality, 87 of them were operated on. The histological structure of cavernomas was shown to be heterogeneous. Different types of their clinical course are analyzed and the optimum diagnostic criteria of the diseases substantiated. Removal of supratentorial cavernomas is the method of choice, which eliminates a risk for rehemorrhage and positively affects the course of the convulsive syndrome. Exceptions are the cavernomas that are located in the functionally important brain regions difficult to reach. In these cases, the indication for surgery may be severe rehemorrhage or drug-untreated frequent seizures. Removal of cavernomas does not rule out a long-term use of anticonvulsants. They may be discontinued only on the basis of clinical and electroencephalographic control.

The natural history of hemangioblastomas of the central nervous system in patients with von Hippel-Lindau disease.

OBJECT: The goals of this study were to define the natural history and growth pattern of hemangioblastomas of the central nervous system (CNS) that are associated with von Hippel-Lindau (VHL) disease and to correlate features of hemangioblastomas that are associated with the development of symptoms and the need for treatment. METHODS: The authors reviewed serial magnetic resonance images and clinical histories of 160 consecutive patients with VHL disease who harbored CNS hemangioblastomas and serially measured the volumes of tumors and associated cysts Six hundred fifty-five hemangioblastomas were identified in the cerebellum (250 tumors), brainstem (64 tumors, all of which were located in the posterior medulla oblongata), spinal cord (331 tumors, 96% of which were located in the posterior half of spinal cord), and the supratentorial brain (10 tumors). The symptoms were related to a mass effect. A serial increase in hemangioblastoma size was observed in cerebellar, brainstem, and spinal cord tumors as patients progressed from being asymptomatic to symptomatic and requiring surgery (p < 0.0001). Twenty-one (72%) of 29 symptom-producing cerebellar tumors had an associated cyst, whereas only 28 (13%) of 221 nonsymptomatic cerebellar tumors had tumor-associated cysts (p < 0.0001). Nine (75%) of 12 symptomatic brainstem tumors had associated cysts, compared with only four (8%) of 52 nonsymptomatic brainstem lesions (p < 0.0001). By the time the symptoms appeared and surgery was required, the cyst was larger than the causative tumor; cerebellar and brainstem cysts measured 34 and 19 times the size of their associated tumors at surgery, respectively. Ninety-five percent of symptom-producing spinal hemangioblastomas were associated with syringomyelia. The clinical circumstance was dynamic. Among the 88 patients who had undergone serial imaging for 6 months or longer (median 32 months), 164 (44%) of 373 hemangioblastomas and 37 (67%) of 55 tumor-associated cysts enlarged. No tumors or cysts spontaneously diminished in size. Symptomatic cerebellar and brainstem tumors grew at rates six and nine times greater, respectively, than asymptomatic tumors in the same regions. Cysts enlarged seven (cerebellum) and 15 (brainstem) times faster than the hemangioblastomas causing them. Hemangioblastomas frequently demonstrated a pattern of growth in which they would enlarge for a period of time (growth phase) and then stabilize in a period of arrested growth (quiescent phase). Of 69 patients with documented tumor growth, 18 (26%) harbored tumors with at least two growth phases. Of 160 patients with hemangioblastomas, 34 patients (median follow up 51 months) were found to have 115 new hemangioblastomas and 15 patients new tumor-associated cysts. CONCLUSION: In this study the authors define the natural history of CNS hemangioblastomas associated with VHL disease. Not only were cysts commonly associated with cerebellar, brainstem, and spinal hemangioblastomas, the pace of enlargement was much faster for cysts than for hemangioblastomas. By the time symptoms appeared, the majority of mass effect-producing symptoms derived from the cyst, rather than from the tumor causing the cyst. These tumors often have multiple periods of tumor growth separated by periods of arrested growth, and many untreated tumors may remain the same size for several years. These characteristics must be considered when determining the optimal timing of screening for individual patients and for evaluating the timing and results of treatment.

Intracavernous sinus ectopic adrenocorticotropin-secreting tumours causing therapeutic failure in transsphenoidal surgery for Cushing's disease.

BACKGROUND: The major cause of surgical failure in the treatment of Cushing's disease lies in unsuccessful identification of adenomas. In the present study, we investigated the pathogenesis of negative exploration in transsphenoidal surgery for Cushing's disease by analyzing neuro-imaging studies, endocrinological examination and selective venous sampling. METHODS: Thirty patients with ACTH-dependent Cushing's syndrome that met the endocrinological criteria for Cushing's disease were treated by transsphenoidal microsurgery. Depending on positive or negative identification of adenomas during the surgery, selective adenomectomy, partial hypophysectomy or subtotal hypophysectomy was performed. FINDINGS: All nine patients who underwent selective adenomectomy showed endocrinological remission and did not need any hormone replacement therapy. Of the 12 patients who underwent partial hypophysectomy, 11 showed normalization of hypercortisolism but seven needed permanent replacement of hydrocortisone. Four patients underwent subtotal hypophysectomy because no adenoma could be identified in spite of detailed exploration, and three of them showed remission but with permanent requirements of hydrocortisone and other pituitary hormones. Five patients, whose hypercortisolism persisted after initial surgery, underwent total hypophysectomy as secondary transsphenoidal surgery, and only one of them showed endocrinological remission. Of the six patients with surgical failure, four were thought to be rare cases in whom the ACTH-secreting tumours may have occurred ectopically in the cavernous sinus without direct contact with the pituitary gland. Endocrinologically, these four patients showed a low or no response to corticotropin releasing hormone (CRH) stimulation, and for three of them, radiation therapy to the sellar region including the cavernous sinus was effective for persistent hypercortisolemia. INTERPRETATION: Recognition of an ectopic intracavernous sinus ACTH-secreting tumour as a pathological entity for Cushing's disease may not only enhance the diagnostic accuracy but also be important for determining the optimal surgical mode for persistent Cushing's disease.

Radiation therapy and malignant degeneration of benign supratentorial gangliogliomas.

OBJECTIVE: Gangliogliomas are indolent tumors comprised of neoplastic glial and neuronal cells. Benign lesions tend to be associated with long survival unless the tumor degenerates to a histologically malignant form. This study reviews four cases of histologically proven benign ganglioglioma that later demonstrated malignant features within the glial component of the tumor. Features common to each case are analyzed, and similar cases from the literature are reviewed. METHODS: The records of 42 supratentorial gangliogliomas operated on at our institution since 1985 were reviewed. Special attention was paid to histological characteristics, use of adjuvant radiotherapy, time to tumor recurrence, and histology of the recurrent tumor. RESULTS: Of the 42 cases of gangliogliomas, 29 were initially histologically benign. Of these 29, 14 received postoperative radiation therapy and 14 did not; it was unclear whether one patient received adjuvant radiotherapy, and this patient was excluded from further analysis. Four benign gangliogliomas exhibited malignant degeneration of the glial component. These four all occurred in patients who had undergone postoperative irradiation. The time to identified histological change within recurrent tumors averaged 65 months (range, 22-144 mo). CONCLUSION: All of the benign gangliogliomas undergoing malignant change had postoperative radiation therapy as a common feature. This represents a potential correlation that requires further study.

[Late growth of supratentorial meningioma after radiotherapy of cerebellar tumor]. / Odlegly wzrost oponiaka nadnamiotowego po radioterapii guza mózdzku.

The authors report a case of supratentorial meningioma of the brain developing after radiotherapy for cerebellar astrocytoma. On the basis of a survey of the literature and own speculations the authors try to demonstrate a cause-and-effect relationship between radiotherapy and meningioma development.