Voxel-based morphometric magnetic resonance imaging postprocessing in non-lesional pediatric epilepsy patients using pediatric normal databases.

BACKGROUND AND PURPOSE: Pre-surgical evaluation of pediatric patients with drug-resistant focal epilepsy and negative (non-lesional) magnetic resonance imaging (MRI) is particularly challenging. Focal cortical dysplasia (FCD), a frequent pathological substrate in such setting, may be subtle on MRI and evade detection. The aim of this study was to use voxel-based MRI postprocessing to improve the detection of subtle FCD in pediatric surgical candidates. METHODS: A consecutive cohort of pediatric patients undergoing pre-surgical evaluation with a negative MRI by visual analysis was included. MRI postprocessing was performed using a voxel-based morphometric analysis program (MAP) on T1-weighted volumetric MRI, with comparison to an age-specific normal pediatric database. The pertinence of MAP-positive areas was confirmed by surgical outcome and pathology. RESULTS: A total of 78 patients were included. Forty-four patients (56%) had positive MAP regions. Complete resection of the MAP-positive regions was positively associated with seizure-free outcome compared with the no/partial resection group (P < 0.001). Patients with no/partial resection of the MAP-positive regions had worse seizure outcomes than the MAP-negative group (P = 0.002). The MAP-positive rate was 100%, 77%, 63% and 40% in the 3-5, 5-10, 10-15 and 15-21 year age groups, respectively. MAP-positive rates were 45% in patients with temporal resection and 63% in patients with extratemporal resection. Complete resection of the MAP-positive regions was positively associated with seizure-free outcome in the extratemporal group (P = 0.001) but not in the temporal group (P = 0.070). CONCLUSION: Our data suggest the importance of using MRI postprocessing in the pre-surgical evaluation process of pediatric epilepsy patients with apparently normal MRI.

Hamartia in hippocampal sclerosis-associated mesial temporal lobe epilepsy.

Hamartia are small collections of rounded glioneuronal cells that are thought to be due to aberrant cell migration. Their presence has been recognized in association with mesial temporal lobe epilepsy; their prevalence among cases of hippocampal sclerosis (HS) and any potential association with patient demographics and outcomes is unknown. This study examines hamartia in a series of 292 patients with pathologically confirmed HS. Medical records were reviewed for pertinent patient clinical information (follow-up mean 5years). Hamartia were identified in 96 cases (33%) and were seen primarily in the amygdala (n=88) and less commonly in the hippocampus (n=10) and temporal lobe (n=4). A statistically significant relationship was found between the presence of hamartia and male gender, younger age of seizure onset, and history of childhood febrile seizures and developmental delay. It is unclear if these associations represent a real association or are a result of the underlying pathologies related to chronic epilepsy. At follow-up, there were no significant differences between patients who had hamartia and those who lacked this finding. Hamartia were observed in all subtypes of HS and there was a significant difference found in subtype distribution as well as proportion of cases between subtypes, but no association with any specific subtype overall. The presence of hamartia was not associated with the coexistence of focal cortical dysplasia or any specific histologic pattern of dysplasia. Hamartia are a common concomitant finding in HS and indicates evidence of aberrant cell migration in the hippocampal and parahippocampal regions in these patients.

Effects of dual pathology on cognitive outcome following left anterior temporal lobectomy for treatment of epilepsy.

The objective of this retrospective study was to determine if dual pathology [DUAL - focal cortical dysplasia (FCD) and mesial temporal sclerosis (MTS)] in patients with left temporal lobe epilepsy is associated with greater risk for cognitive decline following temporal lobectomy than single pathology (MTS only). Sixty-three adults (Mage=36.5years, female: 52.4%) who underwent left anterior temporal lobectomy for treatment of epilepsy (MTS=28; DUAL=35) completed preoperative and postoperative neuropsychological evaluations. The base rate of dual pathology was 55.5%. Repeated measures ANOVAs yielded significant 2-way interactions (group×time) on most measures of language and memory with generally moderate effect sizes. Specifically, patients with MTS only demonstrated postoperative declines, while those with dual pathology remained unchanged or improved. Results suggest that dual pathology may be associated with better cognitive outcome following epilepsy surgery than MTS alone, possibly reflecting limited functionality of the resected tissue or intrahemispheric reorganization of function in the context of a developmental lesion.

Arteriovenous malformation of the brain mimicking primary central nervous system vasculitis.

In the diagnosis of primary central nervous system (CNS) vasculitis, it is crucial to rule out clinical, angiographic, and pathological mimics. We report a case of arteriovenous malformation (AVM) mimicking primary CNS vasculitis. A young male presented with intracerebral haemorrhage and no other clinical, laboratory, or angiographic features suggesting vasculitis. Cerebral biopsy showed perivascular inflammation and slight infiltration of the muscular layer of cerebral vessels by chronic inflammatory cells close to the haemorrhagic areas. These findings led to a diagnosis of CNS vasculitis. The patient was initially treated with corticosteroids, but 10 months after the discovery and surgical repair of the AVM, the patient is not receiving any immunosuppressant and has not developed any features of cerebral or systemic vasculitis.

In situ expression of interleukin-4 (IL-4) receptors in human brain tumors and cytotoxicity of a recombinant IL-4 cytotoxin in primary glioblastoma cell cultures.

We have reported that human malignant glioma cell lines express high levels of plasma membrane interleukin-4 receptors (IL-4R). We have also reported that biopsy/surgical samples or primary explant cell cultures from brain tumors express mRNA and protein for the IL-4Ralpha chain, a primary IL-4-binding protein. However, whether IL-4R are expressed in brain tumors in situ has not been resolved. In addition, expression of IL-4R on the cell surface of various normal brain tissues is not known. We examined the expression of IL-4R by using a monoclonal antibody to the IL-4Ralpha chain (also known as IL-4R beta) in surgical/biopsy samples of brain tumor tissues by immunohistochemistry. Our data indicate that 15 of 18 glioblastoma multiforme (GBMs) tumors obtained from two different institutions and 12 other brain tumor samples are moderately to intensely positive for IL-4Ralpha. In contrast, although IL-4Ralpha mRNA was expressed, no IL-4R protein was detectable in two adult and one pediatric brain tissue specimens. In addition, a commercially available human neural tissue grid containing fixed tissues from various areas of brain showed no positive staining for the IL-4Ralpha chain. IL-4Ralpha expression was also demonstrated on astrocytoma grades I, II, and III. Because IL-4 cytotoxin comprised of a circularly permutated IL-4 and a mutated form of Pseudomonas exotoxin [IL4(38-37)-PE38KDEL] is cytotoxic to IL-4R-expressing cells, we tested whether primary GBM explant cell cultures are sensitive to IL-4 cytotoxin. Our data indicate that 13 of 15 GBM cell cultures were 25-74 times more sensitive to IL-4 cytotoxin compared with normal human astrocytes or the NT2 neuronal cell line. These observations indicate that human brain tumors in situ overexpress IL-4R compared with normal brain tissues, thus confirming our previous conclusions that IL-4R in brain tumors may serve as an attractive target for anticancer therapy.

Re-review of MRI with post-processing in nonlesional patients in whom epilepsy surgery has failed.

Management of MRI-negative patients with intractable focal epilepsy after failed surgery is particularly challenging. In this study, we aim to investigate whether MRI post-processing could identify relevant targets for the re-evaluation of MRI-negative patients who failed the initial resective surgery. We examined a consecutive series of 56 MRI-negative patients who underwent resective surgery and had recurring seizures at 1-year follow-up. T1-weighted volumetric sequence from the pre-surgical MRI was used for voxel-based MRI post-processing which was implemented in a morphometric analysis program (MAP). MAP was positive in 15 of the 56 patients included in this study. In 5 patients, the MAP+ regions were fully resected. In 10 patients, the MAP+ regions were not or partially resected: two out of the 10 patients had a second surgery including the unresected MAP+ region, and both became seizure-free; the remaining 8 patients did not undergo further surgery, but the unresected MAP+ regions were concordant with more than one noninvasive modality in 7. In the 8 patients who had unresected MAP+ regions and intracranial-EEG before the previous surgery, the unresected MAP+ regions were concordant with ictal onset in 6. Our data suggest that scrutiny of the presurgical MRI guided by MRI post-processing may reveal relevant targets for reoperation in nonlesional epilepsies. MAP findings, when concordant with the patient's other noninvasive data, should be considered when planning invasive evaluation/reoperation for this most challenging group of patients.

Anti-sense oligonucleotide of p21(waf1/cip1) prevents interleukin 4-mediated elevation of p27(kip1) in low grade astrocytoma cells.

Elevation of the cyclin-dependent kinase (cdk) inhibitor, p27(kip1) is necessary for Interleukin (IL)-4-mediated growth arrest of human low grade astrocytoma (RTLGA) cells and occurs at 24 h of treatment. Pathways involved in IL4 alteration of p27(kip1) are unknown, however. Here we investigated whether other cdk inhibitors contributed to the actions of IL-4 on RTLGA cells. By 12 h of IL-4 treatment, both cdk4 and cdk2 kinase activities against the retinoblastoma protein (pRb) were reduced and nuclear entry of pRb was prohibited. Twelve-hour cdk complexes contained elevated p21(waf1/cip1) but not p27(kip1), p15(ink4B) or p16(ink4A). IL-4 increased p21(waf1/cip1) but not p27(kip1) mRNA levels, and stimulated luciferase activity of a p21(waf1/cip1) promoter-luciferase reporter. In p53-mutant WITG3 cells, IL-4 did not alter p21(waf1/cip1) mRNA and promoter-luciferase activity or p27(kipl) protein, suggesting a need for functional p53. STAT6 phosphorylation by IL-4, however, occurred in both p53-mutant WITG3 and p53-functional RTLGA cells. Pre-treatment of RTLGA with anti-sense but not missense p21(waf1/cip1) oligonucleotide prior to IL-4: (a) restored cdk activities; (b) reduced cdk4-associated p21(waf1/cip1) levels; (c) prevented p27(kipl) elevation; and (d) reversed growth arrest. These results are the first to suggest that p21(waf1/cip1) is essential for IL-4-mediated elevation of p27(kip) and growth arrest of astrocytoma cells.

Cortical architectural abnormalities and MIB1 immunoreactivity in gangliogliomas: a study of 60 patients with intracranial tumors.

Gangliogliomas are generally low grade neoplasms composed of mixtures of neoplastic glial and neuronal elements whose origin and exact nature are still controversial. We studied a series of 60 intracranial gangliogliomas looking for coexistent cortical architectural abnormalities (cortical dysplasia, microdysgenesis) and to determine if tumor behavior correlates with MIB1 (marker of cellular proliferation) labeling. The patients included 34 males and 26 females who ranged in age from 6 months to 55 years (mean 20 years). Thirty-eight tumors (63%) were located in the temporal lobe and 6 (10%) in the frontal lobe. Fifty-four patients (90%) presented with seizures (most with intractable epilepsy) and the duration of seizures ranged from 1 to 38 years (mean 14 years). In all cases, the predominant glioma component resembled a low grade fibrillary astrocytoma. In 14 tumors (23%), an oligodendroglial component was present. In one case, the glial component resembled an anaplastic astrocytoma. The tumors were characterized variously by perivascular chronic inflammation (N = 45, 75%), vascular proliferation (N = 36, 60%), granular bodies (N = 54, 90%), binucleated neurons (N = 36, 60%), calcification (N = 28, 47%), and cystic degeneration (N = 26, 43%). Meningeal involvement by tumor was observed in five (8%) cases. In 38 patients, sufficient tissue was resected to evaluate for the presence of concomitant cortical architectural abnormalities. Cortical architectural abnormalities were identified near to but clearly separate from the tumor in 19 (50%) patients. Only four patients including the anaplastic tumor died with tumor progression. MIB1 indices (positive tumor cells/1,000 tumor cells counted) in 54 cases ranged from 0 to 10.2 (mean 1.1 +/- 1.0).(ABSTRACT TRUNCATED AT 250 WORDS)

Epilepsy surgery in the setting of periventricular leukomalacia and focal cortical dysplasia.

We report an infant who had successful epilepsy surgery for intractable infantile spasms in the setting of bilateral periventricular leukomalacia and remote germinal matrix hemorrhage. Although MRI gave evidence of a diffuse cerebral insult and EEG showed hypsarrhythmia, focal epileptogenicity was suggested by previous partial seizures with onset over the right temporoparietal-occipital region and PET hypometabolism in that same area. Right temporoparietal and lateral occipital resection at 15 months resulted in seizure freedom and dramatic developmental progress at 1-year follow-up. Histopathologic examination of resected tissue showed cortical dysplasia, possibly due to the same insult that also resulted in the bilateral periventricular leukomalacia. From an etiologic perspective, this is one of very few reported cases strongly implicating acquired focal cortical dysplasia in response to a prenatal insult. From a clinical perspective, the case illustrates that the spectrum of potential surgical candidacy in infants may be broader than usually suspected.

Seizure outcome after surgery for epilepsy due to malformation of cortical development.

PURPOSE: To explore seizure outcome after surgery for focal epilepsy due to malformation of cortical development (MCD), with focus on the role of MRI. METHODS: Thirty-five patients who had surgery for intractable focal epilepsy due to MCD identified by preoperative MRI and confirmed by histopathologic analysis of resected tissue were studied. Patients were aged 3 months to 47 years (median, 14 years) at the time of surgery. Duration of follow-up was 1 to 7.9 (mean, 3.4) years. RESULTS: At latest follow-up, 17 patients (49%) had Engel Class I outcome with no seizures or auras only; eight patients (23%) had Class II outcome, with rare disabling seizures; seven patients (20%) had worthwhile improvement; and three patients (9%) had no improvement. Seizure-free outcome tended to be more frequent among patients who had complete resection of unilateral MCD (excluding hemimegalencephaly) based on postoperative MRI (7/12; 58%), compared with patients with unilateral MCD who had incomplete resection (3/11; 27%), but the difference was not significant. The frequency of seizure-free outcome did not differ significantly between children (8/14; 57%), adolescents (7/15; 47%) or adults (2/6; 33%); between patients who had daily (12/24; 50%), weekly (4/9; 44%), or monthly (1/2; 50%) seizures preoperatively; between patients who had temporal (2/6; 33%) or extratemporal or multilobar resections (14/28; 50%); or between patients who were (9/16; 56%) or were not (8/19; 42%) studied with subdural electrodes. Results for all analyses were similar when analyzed at latest available follow-up or at 1 year after surgery. CONCLUSIONS: Surgery can offer seizure-free outcome for approximately one half of carefully selected patients with intractable focal epilepsy due to MCD. Complete resection of the MRI-apparent lesion may improve the likelihood for favorable outcome. MRI evidence of hemimegalencephaly or bilateral MCD suggests a low likelihood for postoperative freedom from seizures.

Local control and overall survival in atypical meningioma: a retrospective study.

PURPOSE: To evaluate local control and overall survival after primary surgery for patients with atypical meningiomas. METHODS AND MATERIALS: From the Department of Pathology database, we identified 491 cases of meningioma treated at the Cleveland Clinic Foundation from 1979 through 1995. Thirty-three were diagnosed with atypical meningioma. Eleven of the excluded patients had incomplete records, were lost to follow-up, or received treatment elsewhere. Of the 22 evaluable patients, 15 underwent gross total resection (GTR), 4 had a subtotal resection (STR), and 3 had a resection of unknown extent. Eight patients received radiation therapy (2 after initial resection and 6 after at least one recurrence). The median radiation dose was 5,400 cGy (range 3,500-5,940). The median age at presentation was 55.5 years, the male:female ratio was 14:8, and 19/22 patients had a Karnofsky performance score (KPS) > or =80. The independent variables analyzed for overall survival and local control were gender, KPS (> or =80 vs. < 80), extent of surgery (GTR vs. STR or unknown extent of surgery), and postoperative radiation therapy. RESULTS: Median survival was 10.6 years, with a median follow-up of 5.5 years (range 1.5-14.8). Eight of the 22 patients had local recurrence, including 2/15 with GTR, 3/4 with STR, and all 3 patients who underwent resection of unknown extent. At 10 years, patients with GTR had a higher local control rate than those who had either a STR or a resection of unknown extent (87% vs. 17%; p = 0.02). The 5- and 10-year overall survival rates for the entire group were 91% and 76%, respectively. Patients who had GTR had 5- and 10-year overall survival of 87% and 87%, respectively. Patients with STR or resection of unknown extent had 5- and 10-year overall survival rates of 100% and 75%, respectively. CONCLUSION: In patients with atypical meningiomas, gross total resection is associated with a lower recurrence rate than in subtotal resection.

Primary pulmonary malignant meningioma.

Fewer than 20 cases of primary pulmonary meningioma have been reported. Most of these cases have been histologically and clinically benign. We report an unusual case of primary pulmonary malignant meningioma with atypical histologic features and malignant behavior. A computed tomography scan of the head did not show evidence of tumor. The right upper lobe mass was resected and showed features of an atypical meningioma with loss of architectural pattern, mild nuclear pleomorphism, increased mitotic counts (up to 15 mitotic figures per 10 high power fields), and focally prominent nucleoli. Focally, cells with rhabdoid features were identified. The tumor's immunohistochemical and ultrastructural profiles were consistent with a meningioma. The tumor stained negative for estrogen and focally positive for progesterone receptors and had a MIB-1 labeling index (marker of cell proliferation) of 9.2%. Approximately 5 months after the initial resection, the patient experienced a tumor recurrence with multiple lymph node metastases, spread to the middle and lower lobes of the right lung, and metastasis to the diaphragm. Rarely, primary pulmonary meningiomas may present as high-grade malignant lesions.

Epithelioid smooth-muscle tumors of the uterus: a clinicopathologic study of 18 patients.

Epithelioid smooth-muscle tumors of the uterus are uncommon neoplasms for which prognostic factors have not been well established. A retrospective follow-up study of 18 uterine epithelioid smooth-muscle tumors was performed. Patients ranged in age from 27 to 83 years (mean, 45 years) and were separated into three groups based on the nuclear grade of the epithelioid tumor cells. Two tumors had grade 1 nuclei; both were examples of intravenous leiomyomatosis. They had highest mitosis counts of 1 and 3 mitotic figures (MF)/10 high-power fields (HPF), no tumor cell necrosis was found, and both patients were alive with no evidence of disease at 64 and 5 months' follow-up. Ten tumors had grade 2 nuclei. All had highest mitosis counts of 0 to 3 MF/10 HPF, except one (5 MF/10 HPF). Tumor cell necrosis was absent in nine and only one had an infiltrative border. Tumor size ranged from 1.5 to 14 cm. Two tumors contained pleomorphic ("symplastic") multinucleated giant cells similar to those seen in bizarre leiomyomas. All nine patients with follow-up were alive with no evidence of disease 5 to 203 months postoperatively (median, 74 months). One patient had also received adjuvant radiation therapy. Six tumors had grade 3 nuclei. Highest mitosis counts of 4 to 9 MF/10 HPF were found in five; one had 1 MF/10 HPF. Maximum tumor size ranged from 4.5 to 13 cm. Two had tumor cell necrosis, and two had an infiltrative border. Two of these patients died of tumor 11 and 132 months postoperatively. The former had widespread metastases at initial surgery (stage IVb); the latter patient (stage I) developed the first of seven tumor recurrences 3 years postoperatively. Both patients had also received adjuvant chemotherapy. Of the remaining four patients, two were alive with no evidence of disease at 48 and 83 months, one was alive (tumor status unknown) at 28 months, and one was lost to follow-up. Based on our findings and those in the literature, we conclude that uterine smooth-muscle tumors with a predominance of epithelioid cells are extremely uncommon and metastasize infrequently. No single histologic feature is predictive of metastatic potential. Clinically malignant tumors (i.e., epithelioid leiomyosarcomas) typically have the combination of significant nuclear atypia (either grade 2 or grade 3 nuclei) and some mitotic activity (usually at least 3 to 4 MF/10 HPF); most also have tumor cell necrosis.

Pseudomyxoma peritonei. A clinicopathologic study of 19 cases with emphasis on site of origin and nature of associated ovarian tumors.

Nineteen patients (10 men, 9 women) with pseudomyxoma peritonei were studied to determine the site of origin of the disease and the nature of associated ovarian tumors. A primary appendiceal mucinous neoplasm was found in 16 of the 17 patients with an evaluable appendix. One woman's appendix had intramural and serosal mucinous deposits without neoplastic epithelial cells. The appendiceal tumors were classified as mucin-producing adenoma ("mucinous cystadenoma") in 13 patients (seven women, six men), intramucosal adenocarcinoma associated with mucin-producing adenoma in one man, and invasive adenocarcinoma associated with mucin-producing adenoma in one man and one woman. Five of the nine women had cystic mucinous ovarian neoplasms; each also had an appendiceal mucinous neoplasm (adenoma in four, invasive adenocarcinoma with adenoma in one). The ovarian neoplasms had histologic features resembling a borderline (low malignant potential) mucinous tumor in four and a mucinous cystadenoma in one; all five ovarian tumors also had features of pseudomyxoma ovarii. Mucinous implants were also on the ovarian surface of the contralateral ovary in four of the five women with ovarian tumors and in the other four women without ovarian tumors. The intraperitoneal mucus deposits contained neoplastic mucinous epithelial cells in 16 patients (eight men, eight women) and were acellular in three (two women, one man). Of 17 patients with more than 6 months of follow-up, 12 (seven women, five men) were alive after postoperative intervals of 7 to 147 months, including three with known residual disease. Five (three men, two women) died of disease 16 to 60 months after initial operation, including two patients with appendiceal carcinoma. Acellular intraperitoneal mucus appeared to be a favorable prognostic feature. We conclude that (a) the appendix is the primary site of origin of pseudomyxoma in the vast majority of cases in both men and women, and (b) the associated mucinous ovarian tumors are most likely secondary neoplasms resulting from incorporation of implanted mucus and neoplastic mucinous epithelial cells of the pseudomyxoma peritonei.

Vulvar vestibulitis. A histopathologic study of 36 cases, including human papillomavirus in situ hybridization analysis.

Vulvar vestibulitis is a recently described clinical condition of unknown etiology. Human papillomavirus (HPV) infection has been implicated as a causal pathogen by some investigators. Because reports on this entity are few, we studied the pathologic features of vestibulectomy specimens from 36 women with a clinical diagnosis of vulvar vestibulitis. The patients' ages ranged from 19 to 53 years (mean, 31 years). Bilateral excisions were performed in 34 patients and a unilateral excision in two. Minor vestibular glands or ducts were identified in 28 patients (78%). Chronic inflammation was present in all specimens. The inflammatory infiltrate consisted predominantly of T lymphocytes and plasma cells with smaller numbers of B lymphocytes. Lymphoid follicles were present in four patients, ulcers in two. The predominant site of inflammation was the squamous mucosa, especially the lamina propria, where the degree of inflammation was graded as mild in 11 patients, moderate in 21 patients, and severe in four patients. To a lesser degree, the inflammation also typically involved the periglandular/periductal connective tissue of the minor vestibular glands, where it was graded as mild in 25 patients and moderate in three patients. Foci of squamous metaplasia were observed in 27 of 28 patients with demonstrable vestibular ducts or glands. Nodular hyperplasia of a vestibular gland (so-called "adenoma") occurred in one patient. In six selected cases, fungi were not identified on silver stains. Morphologic findings of HPV infection, such as koilocytotic atypia or squamous dysplasia, were absent. In-situ hybridization studies for HPV types 6, 11, 16, 18, 31 and 35 were negative in all 36 cases. We conclude that (a) vestibulectomy specimens from patients with a clinical diagnosis of vulvar vestibulitis typically show a chronic inflammatory cell infiltrate that predominantly involves the mucosal lamina propria and periglandular/periductal connective tissue and (b) a pathogenetic role for HPV types 6, 11, 16, 18, 31 and 35 is not substantiated.

Meningeal myofibroblastoma.

Myofibroblastoma is a recently described benign mesenchymal tumor. Only one case has been reported previously in the CNS. We report a second case of myofibroblastoma arising in the meninges in a 70-year-old woman who presented with visual changes. The histologic appearance was characterized by alternating areas of spindled and rounded cells separated by collagen and amianthoid fibers. Immunostaining demonstrated strong vimentin and focal smooth-muscle actin positivity; staining for epithelial membrane antigen, cytokeratin, S-100, desmin, myosin, glial fibrillary acidic protein, and factor VIII-related antigen was negative. Ultrastructurally, the myofibroblasts had features of both smooth-muscle cells and fibroblasts. Differentiating the benign myofibroblastoma from more aggressive meningeal sarcomas and meningeal meningiomas is important. The tumor most likely arises from myofibroblasts that probably reside in the meninges.

Histopathologic findings in 107 uterine leiomyomas treated with leuprolide acetate compared with 126 controls.

The reported histopathologic findings in leiomyomas treated with leuprolide acetate (LA) differ. We examined 233 myomectomy specimens, including 107 myomas from 30 patients (mean age, 34.7 +/- 4.6 years) treated with LA. Their histopathologic findings were compared with those from a control group of 126 myomas from 30 untreated patients (mean age 32.7 +/- 5.3 years). The LA-treated leiomyomas had myxoid change (n = 2; 1.9%), total necrosis (n=4; 3.7%), focal necrosis (n = 5; 4.7%), calcifications (n = 5; 4.7%), hemorrhage (n = 8, 7.5%), vascular changes (n = 12; 11.2%), hydropic degeneration (n = 22; 20.5%), and hyalinization (n = 61; 57.0%). None of these changes differed significantly from the untreated controls. None of the LA-treated leiomyomas had nuclear atypia, whereas nuclear atypia occurred in four (3.2%) of the untreated leiomyomas; this difference was also not significant. Mitotic figures were present in 8.4% of the LA-treated myomas and 8.5% of untreated controls. The number of mitotic figures per 10 high-power fields was slightly higher in the untreated myomas, but the difference was not statistically significant (range, 0-3 for treated, 0-5 for controls). The degree of cellularity did not differ between the two groups. In conclusion, (a) LA-treated myomas do not significantly differ from untreated myomas with respect to nuclear atypia, calcification, total coagulative necrosis, focal coagulative necrosis, hemorrhage, vascular changes, myxoid change, hydropic degeneration, hyalinization, mitotic activity, or cellularity; and (b) the mechanism leading to a reduction in the size of myomas treated with LA is not apparent from routine histologic examination.

Gliofibroma: a distinct entity or a subtype of desmoplastic astrocytoma?

Gliofibromas are rarely encountered astrocytic neoplasms characterized by an admixture of astrocytic and fibroblastic cell components. The exact nature of these rare tumors are still a matter of considerable debate. This article reports a case of gliofibroma occurring in a 3-month-old boy. The astrocytic component of the tumor stained diffusely positive for glial fibrillary acidic protein (GFAP) and S-100 protein. Prominent reticulin staining was observed within the fibroblastic component of the tumor. The MIB1 labeling index (positive number of tumor cells divided by total tumor cells counted X 100) was low (0.9), supporting the general slow growth of these tumors. Immunohistochemical staining with antibody against p53 protein was negative. Gliofibromas seem to be a low-grade variant of an astrocytoma that shares many features with other desmoplastic astrocytic neoplasms (desmoplastic infantile astrocytoma, desmoplastic infantile ganglioglioma) including a generally favorable prognosis.

Amyloid myopathy: clinicopathologic study of 16 cases.

Amyloid deposition in skeletal muscle is a well-recognized but rare occurrence. Sixteen such cases seen in a 17-year period (1979 to 1996) out of a total of 3,937 muscle biopsy specimens (0.004%) form this study group. Either Congo red or sulfated alcian blue stains were routinely performed in each biopsy to screen for amyloid. Patients in this study (eight men, eight women) ranged in age from 42 to 90 years (mean, 61 years) at initial presentation. The most common symptoms at presentation included weakness/fatigue (n = 10), autonomic symptoms (n = 8), and weight loss/decreased appetite (n = 7). Five patients had a concomitant malignancy (myeloma, n = 3; malignant carcinoid tumor, n = 1; melanoma, n = 1). Two patients had known hereditary forms of amyloidosis. Five patients had amyloid diagnosed on another organ biopsy (excluding peripheral nerve). Histologically, amyloid was deposited in the interstitium or perivascular region in 14 muscles and endomysial region in seven muscles. All cases were confirmed with Congo red staining (apple green birefringence) or by electron microscopic identification of fibrillary amyloid material. Scattered angular atrophic esterase-positive muscle myofibers indicative of acute denervation atrophy were seen in 14 muscles. Eight muscles showed small group atrophy, and seven showed myofiber type grouping. Scattered regenerating muscle fibers were seen in nine cases, degenerating myofibers in six, and foci of chronic endomysial and perivascular inflammation in two. Four muscles showed type II muscle fiber atrophy. A concomitant sural nerve biopsy specimen was evaluated in seven patients; all seven contained amyloid, confirmed either by Congo red staining or electron microscopic examination. In two nerves, there was a mild loss of myelinated axons; four had a moderate loss, and one, severe loss. Six of seven nerves showed predominantly axonopathic changes. In conclusion, (1) the prevalence rate of amyloid myopathy in muscle biopsy specimens was low (in this series, 0.004%); (2) only a minority of patients had multiple myeloma, and most presented with muscle weakness/fatigue or autonomic symptoms; (3) most of the muscles showed neurogenic features histologically; (4) all concomitant sural nerve biopsy specimens contained amyloid, and most showed a predominance of axonopathic changes.

Bcl-2 and Bcl-X expression in gangliogliomas.

Bcl-2 and bcl-xL are proteins known to inhibit cell death (apoptosis). Expression of these proteins in gangliogliomas has not been extensively examined. This study retrospectively evaluates bcl-2 and bcl-x immunostaining in paraffin-embedded materials in gangliogliomas. Twenty-nine gangliogliomas in 17 males and 12 females, age 2.5 to 47 years (mean, 20.7 years), were studied. Nineteen tumors were situated primarily in the temporal lobe. All but three patients presented with seizures ranging from 3 months to 28 years' duration (mean, 11.1 years) before surgery. All tumors histologically were comprised of an atypical neuronal component and a glioma component, which most frequently resembled a low-grade astrocytoma. Cortical dysplasia was observed adjacent to eight tumors. MIB-1 (marker of cell proliferation) labeling indices (percentage of positively staining tumor cell nuclei) ranged from 0 to 7.7 (mean, 0.8). bcl-2 staining was observed in 25 tumors (86%); neuronal staining was present in 24 cases (83%), and glial cell staining in 21 tumors (72%). Bcl-xL staining was only observed in eight gangliogliomas (28%); in all eight tumors (28%), neuronal staining was seen, and focal glial cell staining was present in two cases (7%). Four tumors (14%) did not stain with either bcl-2 or bcl-xL. There appeared to be no relationship between MIB-1 immunostaining and staining with bcl-2 or bcl-xL. bcl-2 expression by immunohistochemistry was observed more frequently than bcl-xL in gangliogliomas. Expression of these proteins may reflect abnormalities of apoptosis, which could play a role in the survival of cells that may be involved in the development of gangliogliomas.