Different pattern of expression of nestin in the non-specific form of dysembryoplastic neuroepithelial tumors compared to the simple and complex forms

Dysembryoplastic neuroepithelial tumors (DNTs) are benign glial-neuronal neoplasms with characteristic cliniopathologic features. Three histologic forms of DNTs have been described (simple, complex, and non-specific). The developmental origin of the tumors remains controversial. To determine the developmental origin and nature of the histologic forms of DNTs, immunohistochemical studies of nestin, TrkA, TrkB, p75, and NeuN were conducted in 40 cases of DNTs, including 11, 9, and 20 simple, complex, and non-specific forms, respectively. Nestin positivity of oligodendroglia-like cells (OLCs) was present in 50 and 27.3% of simple and complex forms, respectively. In the non-specific form of DNT, 94.7% of the cases were positive for nestin. Most DNTs exhibited diffuse, strong staining for TrkA and TrkB, irrespective of the histologic subtypes. Both p75 and NeuN positivity were found in about one-half of the simple, complex, and non-specific forms, respectively. Our study suggests that OLCs are a heterogeneous population of cells, and higher expression of nestin in the non-specific form of DNTs compared to the simple or complex forms suggests that the non-specific form has an earlier developmental origin than the simple or complex forms.     

Accuracy of distinguishing between dysembryoplastic neuroepithelial tumors and other epileptogenic brain neoplasms with [11C]methionine PET

Background

Dysembryoplastic neuroepithelial tumors (DNTs) represent a prevalent cause of epileptogenic brain tumors, the natural evolution of which is much more benign than that of most gliomas. Previous studies have suggested that [¹¹C]methionine positron emission tomography (MET-PET) could help to distinguish DNTs from other epileptogenic brain tumors, and hence optimize the management of patients. Here, we reassessed the diagnostic accuracy of MET-PET for the differentiation between DNT and other epileptogenic brain neoplasms in a larger population.

Methods

We conducted a retrospective study of 77 patients with focal epilepsy related to a nonrapidly progressing brain tumor on MRI who underwent MET-PET, including 52 with a definite histopathology. MET-PET data were assessed by a structured visual analysis that distinguished normal, moderately abnormal, and markedly abnormal tumor methionine uptake and by semiquantitative ratio measurements.

Results

Pathology showed 21 DNTs (40%), 10 gangliogliomas (19%), 19 low-grade gliomas (37%), and 2 high-grade gliomas (4%). MET-PET visual findings significantly differed among the various tumor types (P < .001), as confirmed by semiquantitative analyses (P < .001 for all calculated ratios), regardless of gadolinium enhancement on MRI. All gliomas and gangliogliomas were associated with moderately or markedly increased tumor methionine uptake, whereas 9/21 DNTs had normal methionine uptake. Receiver operating characteristics analysis of the semiquantitative ratios showed an optimal cutoff threshold that distinguished DNTs from other tumor types with 90% specificity and 89% sensitivity.

Conclusions

Normal MET-PET findings in patients with an epileptogenic nonrapidly progressing brain tumor are highly suggestive of DNT, whereas a markedly increased tumor methionine uptake makes this diagnosis unlikely.     

Vascular abnormalities in surgical specimens obtained from the resected focus of intractable epilepsy

The histopathological features, particularly hypervascularity, were examined in specimens resected from 21 patients, 15 with intractable epilepsy accompanying cortical dysplasia or dysembryoplastic neuroepithelial tumor (DNT), and 6 with benign brain tumors, such as ganglioglioma and low-grade glioma. Hypervascularity was found in resected specimens from 15 of the 21 patients (71.4%) and in 10 of the 12 patients (83.3%) who had double pathology. Counting of numbers of vessels by CD31 immunohistochemistry revealed that hypervascularity was prominent, especially in cases of vascular malformation or cortical dysplasia. However, almost all cases were negative for vascular endothelial growth factor (VEGF) staining, except for some cases of benign brain tumors. Moreover, all cases showed low or no proliferative potential in MIB-1 immunohistochemistry. These results suggest that the etiology of hypervascularity in the dysplastic lesions is one of a variety of cerebral malformations, as is the case with abnormal maturation and differentiation in neuroglial elements.     

The impact of technical adjuncts in the surgical management of cerebral hemispheric low-grade gliomas of childhood

Pediatric brain tumors occur within a frequency of 24 to 27 cases/year within a cohort of 1 million children. Nearly 25% of these lesions will involve the cerebral hemisphere, with the low-grade glioma representing the most common group of tumors in this location. Pilocytic and fibrillary astrocytomas are the most frequently encountered glioma, although other variants, such as the ganglioglioma, pleomorphic xanthoastrocytoma, astroblastoma, ependymoma, and oligodendroglioma, must also be considered in the differential diagnosis. The etiology of these tumors remains obscure, although may be linked to therapeutic radiotherapy, previous history of hematopoietic malignancy, and maternal exposure to nitrosamine-laden foods. An associated link to a phakomatosis, e.g., neurofibromatosis, tuberous sclerosis, has also been documented to exist with astrocytomas, in particular. The goals of surgery include a complete removal, in most circumstances, with an attempt to alleviate an associated seizure disorder when intractable. This is possible in nearly every type of hemispheric glioma with the aid of intraoperative navigational systems, i.e., frameless stereotaxy, neurophsyiological based stimulation mapping, and electrocorticography. In the setting where a complete removal is possible, no further therapy is warranted. For those lesions that are incompletely resected, conservative management with routine diagnostic imaging follow-up is appropriate. Reoperation is necessary if recurrence is documented and radiotherapy is utilized for those lesions that are incompletely resected following recurrence.     

Epidemiology of seizures in children with brain tumors

Summary We examined potential clinical and pathologic correlates of seizures among the 3,291 children in the Childhood Brain Tumor Consortium database. Fourteen percent had seizures prior to their hospitalization for a brain tumor. Among children who had a supratentorial tumor, seizures occurred in 22% of those less than 14 years of age. The prevalence of seizures increased to 68% of older teenagers. Among children with an infratentorial tumor, the prevalence of seizures was relatively constant at 6% over all age groups. The onset of seizures began more than one year prior to surgical tumor removal in over half of the children aged five or more with supratentorial tumors, significantly longer than for those of the same age with infratentorial tumors. Almost all children (98.9%) with an infratentorial tumor and seizures had at least one other symptom and more than three-fourths of them had at least three. Eighty-nine percent of children with a supratentorial tumor and seizures had at least one other symptom and more than one-half had at least three symptoms. Regardless of whether the tumor was above or below the tentorium, confusion or stupor and coma were more common in children with seizures than in children without seizures. Among children with supratentorial tumors, symptoms of a declining academic performance or an abnormality of personality, speech, walking, or sensation were significantly more frequent in children with seizures, while visual symptoms (other than visual loss or diplopia) and nausea or vomiting were less frequent. Among children with supratentorial tumors, those who had seizures were more likely to have paralysis of an arm, hand, or face, confusion or stupor, or coma and less likely to exhibit irritability, papilledema, optic atrophy, decreased visual acuity, pupillary abnormalities, or abducens paresis. Among children with infratentorial tumors, those with seizures were significantly less likely to have truncal ataxia, but more likely to experience confusion.     

Long‐term surgical outcomes of temporal lobe epilepsy associated with low‐grade brain tumors

BACKGROUND:

Tumor‐related temporal lobe epilepsy (TLE) has a high likelihood of medical intractability and requires surgical treatment. The aims of this study were to analyze the long‐term surgical outcomes of and to present appropriate surgical strategies for tumor‐related TLE.

METHODS:

The clinical data of 87 consecutive patients diagnosed with tumor‐related TLE were analyzed. The median age at surgery was 22 years. Sixteen patients had a tumor confined to the amygdala or the parahippocampal gyrus, and 10 of them received a tailored lesionectomy without hippocampectomy. The surgical outcome was evaluated based on 3 aspects: seizure control, tumor control, and discontinuation of antiepileptic drugs (AEDs).

RESULTS:

The actuarial seizure and tumor control rates at the fifth year postoperatively were 79% and 90%, respectively. Seizure control was highly correlated with tumor control. The following factors were found to be significantly associated with poor seizure control: duration of epilepsy >10 years, presence of a remote focus on surface electroencephalography, and incomplete tumor removal. The actuarial AED maintenance rates were 47% at the second year and 11% at the fifth year. The median time to AED discontinuation was 22 months. A younger age at surgery was found to be significantly associated with an increased chance of AED discontinuation. Tailored resection focusing on the tumor resulted in a favorable outcome, even for tumors confined to the amygdala or the parahippocampal gyrus.

CONCLUSIONS:

Surgical treatment of tumor‐related TLE resulted in long‐term seizure control in the majority of patients. Maximal tumor removal can be recommended for tumor‐related TLE. Cancer 2009. © 2009 American Cancer Society.     

Double minutes in human carcinoma cell lines, with special reference to breast tumors.

Small DNA-containing particles called double minutes (dm) were observed in metaphases during a survey of human tumor cell lines. Detection of dm in uncultured malignant effusions, in a series of 14 breast carcinoma cell lines, and in a cervical carcinoma cell line, and a literature survey indicated that dm may be more common among human malignant cells than previously suspected. Some of the human breast carcinoma cell lines showed a high incidence of dm, which permitted a series of cytochemical studies. The dm stained identically with euchromatic regions of human chromosomes. Unlike typical chromsomes, dm contained neither C-bands nor Cd bands indicative of paracentromeric heterochromatin and centromeres, respectively. The dm were observed to cluster at the ends of chromosomes, and individual dm adhered to chromosomes. This clustering behavior allows dm to pass through cell division in the absence of centromeric regions. These results should alert tumor cytogeneticists to the possibility that their material may contain a low incidence of undetected dm.     

Neoplasms occurring in aged Fischer rats, with special reference to testicular, uterine, and thyroid tumors

Inbred Fischer rats were set aside as nonbreeders specifically to obtain tumors of endocrine organs and endocrine-responsive tissues that might be used in studies of hormone responsivity. The average age at death or autopsy was 675 days for 102 females, and 725 days for 92 males. The tumor data are recorded for those animals that were autopsied (91%). Sixty-eight percent of the males developed testicular interstitial (Leydig) cell tumors and in three fourths these were bilateral. One half of the 20 tumors transplanted into isologous hosts grew to a palpable size. In all instances where growth occurred it was more rapid in castrate than in intact male recipients. At least four of these transplanted tumors produced androgen. Twenty-one percent of the females had macroscopically evident uterine polypoid tumors that were endometrial in origin. Nine of these were transplanted into isologous hosts; 4 grew as sarcomas and 5 maintained their original benign, polyp-like microscopic appearance. Three of these latter tumors grew more rapidly in intact females than in intact males or castrate hosts of either sex. Nine of the aged rats developed grossly evident tumors of the thyroid that morphologically were typical type-gamma nodules. A papillary adenocarcinoma was found in the contralateral lobe of the thyroid of 1 of these rats. Only 1 type-gamma nodule was transplanted, and after 1 year it has grown to approximately 1 cm in diameter in 1 of the 2 untreated male recipients. The incidence of breast, adrenal medullary, and pituitary tumors, as well as of other miscellaneous tumors, was not notably different from that reported by several investigators observing aged rats of different genetic background.     

General concepts of alpha-fetoprotein (AFP)-secreting tumors, with special reference to the histogenesis

Recently, in addition to yolk sac tumors (YST) and hepatocellular carcinomas, many AFP-secreting tumors have been reported. A comparative morphological study of YST to the human yolk sac has revealed tumor cells mimicking the behavior of the human yolk sac endodermal cells (HYSEC). Another investigation suggests that an embryonal carcinoma (adult type), a gastric adenocarcinoma, or an ovarian adenocarcinoma, each showing no histologic features specific for YST, have a selective differentiation to HYSEC which can secrete an increased serum AFP. These tumors might well be called endodermal cell tumors. The histogenesis of AFP-secreting tumors can be attributed to the endodermal origin (or retrodifferentiation to the HYSEC).     

A rat glioma model,CNS-1, with invasive characteristics similar to those of human gliomas: A comparison to 9L gliosarcoma

Summary A glioma cell line, CNS-1, was developed in the inbred Lewis rat to obtain a histocompatible astrocytoma cell line with infiltrative and growth patterns that more closely simulate those observed in human gliomas. Rats were given weekly intravenous injections for a six month period with N-nitroso-N-methylurea to produce neoplasm in the central nervous system. Intracranial tumor was isolated, enzymatically and mechanically digested, and placed into culture. The tumor cell line injected subcutaneously on the flanks of Lewis rats grew extensivelyin situ as cohesive tumor masses but did not metastasize. Intracranially, CNS-1 demonstrated single cell infiltration of paranchyma and leptomeningeal, perivascular, and periventricular spread with expansion of the tumor within choroid plexus stroma. CNS-1 cells titrated in right frontal brain of Lewis rats at 10⁵, 5×10⁵, 10⁵, 5×10⁴ cells per group had mean survival times ranging from 20.5 to 30.2 days. CNS-1 was immunoreactive for glial fibrillary acidic protein, S100 protein, vimentin, neural cell adhesion molecule, retinoic acid receptor , intercellular adhesion molecule, and neuron specific enolase. The CNS-1 cells commonly had one or more trisomies of chromosomes 11, 13 or 18; losses, possibly random, of chromosomes (3, 5, 19, 30, X or Y) were noticed, and a marker chromosome made up of approximately 3 chromosomes was usual. Comparisons of CNS-1 to 9L gliosarcoma tumor were made. The glial CNS-1 tumor model provides an excellent system in which to investigate a variety of immunological therapeutic modalities. It spreads within brain in a less cohesive mass than 9L and is accepted without rejection in non-central nervous system sites by Lewis rats.     

Malignant sex-cord stromal tumor of the testis: report of a case with special reference to its unusual intracytoplasmic substructures.

A case of malignant sex-cord stromal tumor (gonadal stromal tumor) in the left testis of a 42-year-old man with no sign of hormonal abnormality is reported. Histologically, a large portion of the tumor was composed of solid nests of round cells with a moderate amount of eosinophilic cytoplasm, but some areas contained small spaces somewhat resembling Call-Exner bodies and/or the follicular structures of granulosa cell tumors. In general, however, the tumor cells did not show a clear-cut differentiation into either Sertoli cells or granulosa cells. The tumor, because of its high mitotic rate, lymphatic, venous and capsular invasion, and metastasis to the para-aortic lymph nodes, was considered to be malignant. We simply designated this tumor, therefore, as a malignant sex-cord stromal tumor. An ultrastructural study revealed unique intracytoplasmic bodies composed of multiple stacks of tubular structures which superficially mimicked annulate lamellae. No lipid droplets, Reinke's crystalloids or Charcot-B?ttcher filaments were seen. The rarity of the tumor and the presence of unusual substructures prompted us to report the case.