Biomedical subjects

B W Scheithauer

Publications and source records attributed to B W Scheithauer.

At least 91 records · Page 5Linked to original sources

PubMed1999

The blood-brain barrier in primary CNS lymphomas: ultrastructural evidence of endothelial cell death.

The vasculature of 24 primary CNS B-cell lymphomas that were not related to acquired immunodeficiency syndrome was systematically studied by electron microscopy. Seven low-grade astrocytic tumors were included for comparison. Classical electron microscopy features of apoptosis were found in lymphoma cells of 21 of 22 subjects. Capillaries of gliomas and lymphomas showed changes reported previously: variability of endothelial cell (EC)-thickness and number, basal lamina thickness and duplication, and fenestrations. Primary CNS B-cell lymphoma ECs showed two distinctive populations of electron-dense and electron-lucent cells. The electron-dense ECs occurred in 38% of all capillaries, with changes consisting of chromatin condensation in bizarre and contracted nuclei, cytoplasmic shrinkage with markedly increased electron density, and dilatation of the endoplasmic reticulum. We interpreted these changes as indicative of apoptosis. Cell death eventually resulted in complete disintegration of the endothelium with frank discontinuities of the EC component of the blood-tumor barrier in capillaries and postcapillary venules. Another population of ECs had increased cell volume, conspicuous cytoplasmic electron lucency, dispersed organelles, scattered vesicles, and apical stress fibers. We interpreted these changes as indicative of cellular regeneration. Individual apoptotic ECs often lay next to normal or regenerating ECs. Neither type of EC change was observed in gliomas, which also lacked perivascular neoplastic lymphocytic cuffing. We believe that these populations of ECs, which have not been described in other disorders affecting the blood-brain barrier, may be induced by cytokines released from necrotic and/or apoptotic tumor lymphocytes and may explain the unusual imaging characteristics of primary CNS B-cell lymphomas treated with corticosteroids.

Adrenal Cortex Hormones↗

PubMed1999

Immunohistochemical staining for ganglioside GD1b as a diagnostic and prognostic marker for primary human brain tumors.

Immunohistochemical staining intensity for ganglioside GD1b was determined for 108 human neuroectodermal tumors. Most of the tissue elements that immunostained were tumor cells; only a few axons and occasional neurons reacted in some specimens. All pilocytic astrocytomas stained very positively, whereas none of the ependymomas and only 11% of primitive neuroectodermal tumors, 20% of glioblastomas, and 28% of anaplastic astrocytomas showed more than faint staining. A similar association between grade and immunostaining was seen in tumors containing an oligodendrogliomatous component, but reactivity was not as strong as in astrocytic tumors or primitive neuroectodermal tumors. Results of Cox regression showed significant associations between immunostaining intensity and survival for all cases taken together (P = 0.007); for the group consisting of astrocytomas, oligoastrocytomas, and oligodendrogliomas (P = 0.002); and for astrocytomas alone (P = 0.04). Results were also significant using a proportional hazards model controlling for patient age (all cases P = 0.005; astrocytomas only P = 0.02), but not when controlling for tumor grade. Our results indicate that immunohistochemical staining for GD1b is correlated with tumor grade and that it may be of prognostic utility in some primary human brain tumors, especially astrocytomas.

Astrocytoma↗

PubMed1999

Primary melanocytic neoplasms of the central nervous systems.

Primary melanocytic neoplasms of the central nervous system (CNS) consist of a spectrum ranging from well-differentiated melanocytoma to its overtly malignant counterpart, melanoma. Diagnostically difficult intermediate lesions lie between these extremes. Clinicopathologic features of 33 cases were studied to define histologic appearances, diagnostic criteria, and the clinical behavior of lesions along this spectrum. Seventeen cases were well-differentiated, solitary leptomeningeal tumors classified as melanocytomas. They contained variably pigmented melanocytic cells arranged in tight nests, sheets, or fascicles. Mitotic rates ranged from zero to one per 10 high-power fields (HPFs), with most having zero per 10 HPFs. All tumors were immunoreactive for HMB-45 and S-100 protein and negative for epithelial membrane antigen. MIB-1 staining was low (<1-2%). Nuclei were regular, often with small, eosinophilic nucleoli. These lesions arose predominantly in the spinal canal (65%) in patients ranging in age from 17 to 73 years. None recurred after surgical resection. In contrast to these benign lesions, there were 13 cases with histologic and cytologic features consistent with those of malignant melanoma. These cases contained larger, cytologically atypical, pigmented tumor cells growing in loose nests or sheets, often with CNS invasion or necrosis. Some contained bizarre, pleomorphic nuclei; others were densely cellular and mitotically active, but less pleomorphic. Mitotic rates (mean, 5.7 per 10 HPFs) and MIB-1 labeling indices (mean, 8.1%) were higher than those of melanocytomas. Melanomas occurred at spinal (38%), posterior fossa (38%), and supratentorial (23%) levels in patients ranging in age from 15 to 71 years. After resection, 8 of 13 lesions recurred, with four being fatal (mean survival, 14 months). Of five totally resected melanomas, four did not recur (mean follow-up, 26 months). Three intermediate-grade melanocytic tumors could not be classified as melanocytoma or melanoma. All showed sheetlike growth patterns, microscopic CNS invasion, and occasional mitoses. MIB-1 staining ranged from 1% to 4%. One tumor recurred after 17 months; one patient was lost to follow-up after 5 months; and the third died after surgery. Although melanocytic tumors represent a spectrum of lesions, certain histopathologic features are helpful in predicting biologic behavior.

Adolescent↗

PubMed1999

Cellular proliferation in pilocytic and diffuse astrocytomas.

Using quantitative image analysis, we evaluated the MIB-1 labeling index (LI) in a large population of pilocytic (n = 131) and diffuse astrocytomas (n = 140), explored its significance as a prognostic predictor of survival, and compared it to other commonly accepted predictors, including grade and its histologic determinants, atypia, mitoses, endothelial proliferation, and necrosis. Diffuse astrocytomas were graded according to the St Anne-Mayo scheme and included 45 grade 2, 50 grade 3, and 45 grade 4 astrocytomas. In pilocytic astrocytomas, mean, median, and range of MIB-1 LIs were 1.1, 0.9, and 0-3.9%, respectively. In diffuse astrocytomas, these values were 2.3, 2, and 0-7.6% in grade 2; 6, 4.4, and 0.1-25.7% in grade 3; 9.1, 6, and 0.3-36% in grade 4. There was a significant difference in the distribution of MIB-1 LIs between pilocytic and diffuse grade 2 astrocytomas (p < 0.001), between grade 2 and grade 3 (p < 0.001), and between tumors of grade 3 and 4 (p = 0.014). Among pilocytic astrocytomas there was no association between survival and MIB-1 LI or any histologic parameter. In diffuse astrocytomas, MIB-1 LI was significantly correlated with grade as well as with mitotic activity (<0.001) and survival. While in diffuse astrocytomas of all grades, necrosis was the strongest factor associated with survival, in tumors of grades 2 and 3 the MIB-1 LI preceded other histologic parameters and, on multivariate analysis, remained the only feature predictive of survival. Grade 3 astrocytomas with a single "solitary" mitosis had a significantly lower MIB-I LI than did grade 3 tumors with >1 mitosis and, compared to the latter, had a significantly longer survival (p = 0.013), one not significantly different from patients with grade 2 astrocytomas. These findings suggest that the cutoff point between grade 2 and 3 in the St. Anne-Mayo scheme may not be optimal and may need to be revised.

Adolescent↗

PubMed1999

Glycolipid markers of astrocytomas and oligodendrogliomas.

Neutral glycolipids and gangliosides were analyzed in 149 astrocytomas (A), 46 oligodendrogliomas (O), and 21 oligoastrocytomas (OA) to determine if specific glycolipids correlate with histologic diagnosis and grade. Positivity for asialoGM1 (GA1) and negativity for paragloboside by immuno-TLC correlated with histological diagnosis of O and OA, whereas the reverse pattern correlated with A. High levels (over 5 microg hexose per mg dry weight) of CMH generally correlated with an O component, but the association was not as strong as for either GA1 presence or paragloboside absence. Pilocytic astrocytomas and pleomorphic xanthoastrocytomas had high proportions (> 15%) of globoside, low ratios (< 0.5) of GD1a: GD1b, and identifiable ceramide trihexoside (CTH). Three gangliosides of the 1b pathway were progressively lost with increasing grade of A, but a similar correlation with grade was not seen in O or OA. A high proportion of cases expressing sialosylparagloboside (3'LM1; 6'LM1) were grade 4 A. Glycolipids are synthesized by glycosyltransferases that add specific sugars to the nascent oligosaccharide. Correlation of specific glycolipids with histological diagnoses and grades indicate that these tumor types express specific patterns of glycosyltransferases, several of which have been cloned. It is possible that critical genes coding for these enzymes are deleted, overexpressed, or mutated in certain tumor types and grades, thus leading to the patterns of glycolipids that we found to be associated with these tumors.

Adolescent↗

PubMed1999

Aggressive enterogenous cyst with extensive craniospinal spread: case report.

OBJECTIVE AND IMPORTANCE: Considered benign and malformative in nature, enterogenous cysts are predominantly spinal lesions. Although recurrences have been reported, especially in the rare intracranial examples, craniospinal dissemination has never been described. CLINICAL PRESENTATION: We report a 63-year-old woman who presented 16 years previously with a histologically typical enterogenous cyst of the cerebellum. Fourteen years after its incomplete excision, numerous supratentorial, infratentorial, and spinal subarachnoid cysts were detected. A histological examination revealed multiple enterogenous cysts without evidence of malignancy. Ki-67 (MIB-1) proliferative indices were less than 1% in all except one specimen, wherein it was 4%; immunohistochemistry demonstrated rare p53 protein overexpression. INTERVENTION: During the last 2 years, four subtotal resections of spinal enterogenous cysts have been performed for progressive paraplegia, pain, paresthesia, and bladder dysfunction. Considering the multiple recurrences and progressive neurological deficits, craniospinal radiation therapy was given. CONCLUSION: To our knowledge, this is the first report of widespread craniospinal dissemination associated with the incomplete resection of an enterogenous cyst. Although a rare complication, it emphasizes the advantages of early, aggressive surgery.

Bone Diseases↗

PubMed1999

Leptin and leptin receptor expression in normal and neoplastic human pituitary: evidence of a regulatory role for leptin on pituitary cell proliferation.

Leptin is a circulating hormone secreted by adipose and a few other tissues. The leptin receptor consists of a single transmembrane-spanning polypeptide that is present as a long physiologically important form as well as in several short isoforms. Recent studies have suggested that the anterior pituitary may have a role in the regulatory effects of leptin in animal models. To test this possibility in human pituitaries, we examined the expression of leptin and OB-R in normal and neoplastic pituitaries, and the possible functions of leptin in the pituitary were also analyzed. Leptin was present in 20-25% of anterior pituitary cells and was expressed in most normal anterior pituitary cells, including ACTH (70% of ACTH cells), GH (21%), FSH (33%), LH (29%), TSH (32%), and folliculo-stellate cells (64%), but was colocalized with very few PRL cells (3%), as detected by double labeling immunohistochemistry with two different antileptin antibodies. In addition, leptin expression was detected by RT-PCR in some pituitary tumors, including ACTH (three of four), GH (one of four), null cells (two of four), and gonadotroph (one of four) tumors as well as in normal pituitary. Immunohistochemical staining showed greater immunoreactivity for leptin in normal pituitaries compared to adenomas. Treatment of an immortalized cultured anterior pituitary cell line, HP75, with leptin stimulated pancreastatin secretion in vitro. Leptin also inhibited cell growth in the human HP75 and in the rat pituitary GH3 cell lines. Both long (OB-Rb) and common (OB-Ra) forms of the leptin receptor messenger ribonucleic acid and leptin receptor protein were expressed in normal and neoplastic anterior pituitary cells. These findings show for the first time that leptin is expressed by most human anterior pituitary cell types and that there is decreased leptin protein immunoreactivity in pituitary adenomas compared to that in normal pituitary tissues. We also show that OB-Rb is widely expressed by normal and neoplastic anterior pituitary cells, implicating an autocrine/paracrine loop in the production and regulation of leptin in the pituitary.

Animals↗

PubMed1999

Clinicopathological characteristics of atypical teratoid/rhabdoid tumor.

The clinicopathological features of atypical teratoid/rhabdoid tumor, a new entity among malignant pediatric brain tumors, and the differential diagnosis from primitive neuroectodermal tumor (PNET)/medulloblastoma, and germ cell tumor are described. Histologically, atypical teratoid/rhabdoid tumor is defined as a polymorphous neoplasm often featuring rhabdoid, PNET, epithelial, and mesenchymal components. Atypical teratoid/rhabdoid tumors usually include PNET components and occur mainly in the posterior fossa, so mimic medulloblastoma. Atypical teratoid/rhabdoid tumor is characterized by the cytogenetic finding of monosomy 22 rather than i(17q). The tumor is similarly mistaken for PNET at supratentorial sites. Germ cell tumors also enter into the differential diagnosis due to their histological immunophenotypic diversity, particularly features indicative of epithelial and mesenchymal differentiation. Nonetheless, the remarkable spectrum of tissues that typify teratoma is absent in atypical teratoid/rhabdoid tumor. The same is true of germ cell marker in tumor tissues and serum. The prognosis of atypical teratoid/rhabdoid tumor is far less favorable than that of PNET/medulloblastoma of malignant or germ cell tumor. Meta-analysis of 133 cases, including 15 new and 118 reported cases, confirm that atypical teratoid/rhabdoid tumor is as a clinicopathological entity and emphasizes the necessity for distinguishing this unique tumor from other pediatric central nervous system neoplasms.

Adolescent↗

PubMed1999

Development of postoperative fibromatosis after resection of an intraspinal meningioma. Case report.

The authors report the case of an adult female patient who developed a paraspinous thoracic fibromatosis (desmoid tumor) after undergoing resection of an intraspinal thoracic meningioma that was complicated by postoperative wound infection. To the best of the authors' knowledge, this is the first report of such a tumor occurring after resection of a spinal meningioma. Awareness of the development of postoperative fibromatosis and recognition of its association with wound sepsis is important. Although rare, this distinctive lesion should be considered in the differential diagnosis of the apparent rapid regrowth of otherwise indolent lesions including meningioma.

Female↗

PubMed1999

Hemangioma of spinal nerve root.

OBJECT: Hemangiomas of the spinal nerve roots are rare. Only 12 cases have been reported in the literature, all since 1965. These lesions occurred in adults, primarily in males, and were located in the cauda equina. Of the 12 lesions, eight were cavernous hemangiomas. The authors report here the clinicopathological features of 10 cases of hemangioma of the spinal nerve root, nine of which were of the capillary type. METHODS: The group included six men and four women who ranged in age from 40 to 62 years. The majority of patients presented with pain and weakness. One patient also experienced worsening of pain during menses. In all cases, gadolinium-enhanced magnetic resonance imaging or computerized tomography myelography demonstrated a discrete intraspinal extramedullary mass. Administration of contrast agent resulted in uniform, intense enhancement. A gross-total resection was achieved in all but one case; in most cases, it was necessary to sacrifice the parent nerve root. Preoperative symptoms and signs improved in nine cases. On histological examination, all but one tumor, a spindle-cell hemangioendothelioma, were shown to be ordinary capillary hemangiomas. Two lesions exhibited a cavernous component, and five showed a partly solid growth pattern resembling juvenile capillary hemangioma. In all cases, the relationship with the nerve root was histologically confirmed. The tumor-nerve relation varied. The intact nerve was displaced by the epineurial mass in three cases. The fascicles appeared separated in six cases, and individual nerve fibers were seen throughout one lesion with endoneurial involvement. CONCLUSION: . Hemangiomas of spinal nerve roots pose a challenging diagnostic problem. Knowledge of their existence is relevant in that they may mimic tumors and are amenable to surgical treatment.

Adult↗

PubMed1999

Tumor suppressor gene alterations in malignant gliomas: histopathological associations and prognostic evaluation.

We have examined a series of 135 gliomas for alterations of the p53, CDKN2A (p16) and PTEN tumor suppressor genes (TSGs) in order to evaluate the incidence of their inactivation as a function of tumor malignancy and cellular differentiation, and to examine potential associations with patient outcome. The composition of this series, classified using WHO criteria, is as follows: 27 grade 2 tumors (11 astrocytomas, 12 oligoastrocytomas, 4 oligodendrogliomas), 42 grade 3 tumors (22 astrocytomas, 16 oligoastrocytomas, 4 oligodendrogliomas), and 66 grade 4 tumors (63 astrocytomas and 3 oligoastrocytomas). Similar frequencies of p53 mutation were observed among grade 2 (37.0%), and grade 3 tumors (38.1%), as well as between astrocytomas and mixed tumors. CDKN2A and PTEN mutations were clearly associated with increasing tumor malignancy (occurring in 0% of grade 2 tumors, 14.3% and 4.8% respectively of grade 3 tumors, and 27.3% and 30.3% respectively of grade 4 tumors) and were observed at substantially higher rates among astrocytomas. For the tumor suppressor genes examined, there was no relationship between the occurrence of any two TSG inactivation events. With regard to outcome, the p53 genetic status showed no significant relationship with patient survival. The CDKN2 and PTEN alterations were negative prognostic indicators of survival when evaluated in all 135 gliomas, but failed to predict outcome when evaluated in either of the high grade (3 or 4) tumor groups.

Adolescent↗

PubMed1999

Meningioma metastatic to the lung.

Meningiomas constitute 15% to 18% of all primary intracranial and intraspinal tumors. Distant extracranial metastases are reported to occur in fewer than 1 in 1000 cases. Of 1992 primary intracranial meningiomas seen at Mayo Clinic Rochester from 1972 through 1994, we identified 3 (0.15%) with documented extracranial metastasis. A review of the literature suggests that previous craniotomy, venous sinus invasion, local recurrences, histological malignancy, and papillary morphology may be risk factors for systemic spread, as demonstrated in our cases. Although rare, metastatic meningioma should be considered in the differential diagnosis of abnormal findings on chest radiography in patients with known or suspected intracranial meningioma.

Adolescent↗

PubMed1998

The results of radiotherapy for ependymomas: the Mayo Clinic experience.

PURPOSE: This analysis was performed to examine the outcome of patients with histologically confirmed ependymomas of the brain or spinal cord who received postoperative radiotherapy. METHODS AND MATERIALS: Eighty patients with histologically confirmed ependymomas were evaluated retrospectively. All were treated with various combinations of surgery, radiotherapy (RT), and chemotherapy. Follow-up ranged from 5 to 30 years (median 10.4 years). RESULTS: The 5- and 10-year survival rates for the entire study group were 79% and 73%, respectively. Patients with low-grade (1 and 2 of 4) tumors had a 5-year survival rate of 87% as compared to 27% for those with high-grade (3 and 4 of 4) tumors (p < 0.0001). Patients with tumors of the spine had a 5-year survival rate of 97% as compared to 68% for those with infratentorial tumors, and 62% for those with supratentorial tumors (p = 0.03). Patients with myxopapillary ependymomas of the spine had a 5-year survival rate of 100% as compared with 76% for patients with other histological subtypes of ependymoma (p = 0.02). Multivariate analysis revealed that the survival rate was independently associated with tumor grade (p = 0.0007) and histological subtype (p = 0.02). Twenty-eight patients (35%) experienced local failure and 10 patients (13%) developed leptomeningeal seeding. The 5-year leptomeningeal failure rate was 10% in patients with low-grade tumors as compared to 41% for patients with high grade tumors (p = 0.01). CONCLUSION: Patients with low-grade tumors, especially those with myxopapillary subtypes, have high 5-year survival rates when treated with post-operative radiotherapy. High grade ependymomas are associated with a much poorer outcome. New forms of therapy are required to improve the outcome of patients with high-grade ependymomas.

Adolescent↗

PubMed1998

Malignant tumors of the kidney, brain, and soft tissues in children and young adults with the tuberous sclerosis complex.

BACKGROUND: The tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by seizures, mental retardation, and benign tumors of the brain, heart, skin, and kidney. Malignant tumors also can occur in patients with tuberous sclerosis, particularly in the kidney, although they occur less frequently than benign tumors. The types of malignancy that occur in TSC have not been characterized fully. METHODS: Clinical and pathologic features of 8 malignant tumors from 6 TSC patients ranging in age from 22 months to 21 years are reviewed. Six tumors were renal, one was from the inguinal region, and one was from the brain. The tumors were analyzed for loss of heterozygosity (LOH) in the chromosomal regions of the TSC1, TSC2, and VHL genes. RESULTS: Three patients (ages 7, 8, and 20 years) had renal cell carcinomas (RCCs). Two of these patients had multifocal RCCs. All three patients with RCC also had prominent multifocal dysplasia of renal cyst epithelium. Two patients (ages 20 and 21 years) had malignant angiomyolipomas (1 renal and 1 inguinal). One patient (age 22 months) had a Grade 4 giant cell astrocytoma (glioblastoma multiforme). LOH in the region of the TSC2 gene was found, either in the malignant tumor or in benign tumors, in all five patients whose DNA could be analyzed. CONCLUSIONS: Children with TSC, as well as adults with the disease, are at risk for developing malignant tumors. Two types of renal malignancy occur in TSC: RCC, which appears to arise from dysplastic renal cyst epithelial cells, and malignant angiomyolipoma. Tumors cytologically similar to malignant angiomyolipomas also may occur at extrarenal sites. LOH analyses suggest that the majority of patients with TSC who develop malignant tumors have germline TSC2, rather than TSC1, gene mutations.

Adult↗

PubMed1998

Malignant peripheral nerve sheath tumor: analysis of treatment outcome.

PURPOSE: To analyze the results of therapy for malignant peripheral nerve sheath tumor (MPNST) and to identify prognostic factors of survival, and of local and distant control of disease. METHODS AND MATERIALS: From 1975 through 1993, 134 MPNSTs were diagnosed and treated at our institution. Tumor sites included extremities in 36 (27%) cases and non-extremities in 98 (73%). Median follow-up for survivors was 53 months (range: 7-280). There were 14 tumors of histologic grade I disease (10%), 43 of grade II disease (32%), 43 of grade III disease (32%), and 32 of grade IV (24%). Seventy-three patients (54%) underwent radiation therapy (RT) as part of their initial treatment of the primary tumor, including 14 (10%) who had brachytherapy and 16 (12%) who had intraoperative electron irradiation (IOERT) as part of their radiation course. RESULTS: The 5- and 10-year survival rates were 52% and 34%, respectively. Local and distant failure rates at 5 years were both 49%. On univariate analysis, prognostic factors significantly related to survival (log-rank: p < 0.05) included tumor size, location of disease, history of neurofibromatosis type 1 (NF-1), history of prior irradiation, surgical margin status, use of IOERT or brachytherapy, disease stage, histologic grade and tumor subtype, as well as mitotic rate and the presence or absence of necrosis. On multivariate analysis, only history of prior irradiation (p = 0.023), and surgical margin status (p = 0.0044) remained significant. For local control of disease, univariate analysis showed location of disease, surgical margin status, history of NF-1, history of prior irradiation, mitotic rate, radiation dose > or = 60 Gy, and use of IOERT or brachytherapy to be significant prognostic factors. On multivariate analysis, only surgical margin status (p = 0.0024), RT dose (p = 0.021), and use of IOERT or brachytherapy (p = 0.016) remained significant. For distant control of disease, significant prognostic factors on univariate analysis included tumor size, stage, tumor grade, mitotic rate, presence or absence of necrosis, and histologic subtype. On multivariate analysis, tumor size (p = 0.0065), grade (p = 0.036), and histologic subtype (p = 0.001) remained significant. Patients with perineurial MPNSTs had a much lower rate of distant metastasis and a better overall survival as compared with other histologic subtypes. CONCLUSION: Management of patients with MPNST involves a multi-modality approach. The goal of surgery is complete resection with negative margins. Adjuvant irradiation to doses > or = 60 Gy and the inclusion of IOERT or brachytherapy are associated with improved local control of disease.

Adolescent↗

PubMed1998

The prognostic significance of MIB-1, p53, and DNA flow cytometry in completely resected primary meningiomas.

BACKGROUND: Despite the availability of clinical and pathologic parameters of prognosis, the behavior of an individual meningioma may be difficult to predict. In a recent review of gross totally resected (GTR) meningiomas, the authors found strong associations between microscopic brain invasion, increased mitotic rate (> or = 4/10 high-power fields), the presence of at least 3 of 4 morphologic variables (sheeting, hypercellularity, macronucleoli, and small cells), and decreased recurrence free survival (RFS). In this study, they assessed the prognostic value of three ancillary techniques: DNA flow cytometry, MIB-1 labeling, and p53 protein expression. METHODS: The authors evaluated primary GTR meningiomas from 425 patients with DNA flow cytometry, immunostaining for MIB-1, and determination of p53 protein expression. The patients were followed until death or for a median of 8.9 years. RESULTS: An MIB-1 labeling index (LI) of > or = 4.2%, identified in 8% of cases, was strongly associated with decreased RFS in univariate analysis (P=0.0001). Fourteen percent contained aneuploid cell populations, and 48% exhibited a p53 LI of >10%. Neither variable was associated with decreased RFS. Further analysis revealed a close association between MIB-1 LI and mitotic index, the latter being the parameter of greatest significance in multivariate analysis. CONCLUSIONS: MIB-1 LI is a useful adjunct to routine histologic evaluation of meningiomas and appears to be of greatest value in the evaluation of tumors exhibiting borderline atypia. In contrast, our data suggest that, regarding patients with primary GTR meningiomas, neither flow cytometry nor p53 immunohistochemistry provides useful prognostic information.

Adolescent↗

PubMed1998

Management of recurrent meningeal hemangiopericytoma.

BACKGROUND: Meningeal hemangiopericytoma is an uncommon neoplasm with a high propensity for recurrence. The purpose of this study was to analyze the efficacy of different treatment options in patients with recurrent disease. METHODS: The records of all patients with recurrent meningeal hemangiopericytoma treated at the study institution between 1976 and 1996 were reviewed. RESULTS: Thirty-four consecutive patients were studied. The mainstay of treatment was brain surgery in 21 patients (62%); the median time to recurrence from surgery was 12 months. Ten patients (29%) had 20 recurrent central nervous system (CNS) lesions treated by stereotactic radiosurgery. Of these, 3 previously nonirradiated patients (all with lesion size < 25 mm) achieved a complete response, which persisted at a median of 3 years. In 14 lesions (70%) a partial response (PR) occurred with a median duration of 12 months, whereas 3 lesions (15%) remained stable. Two patients with inoperable CNS lesions received external beam radiation therapy and both had PRs lasting 14 and 24 months, respectively. Nine patients (26%) received radiation therapy for metastatic disease. Of these, seven patients remained stable with good symptomatic relief, and two patients experienced tumor progression. Chemotherapy with doxorubicin-containing regimens was administered in 7 patients (21%); there was only 1 PR that lasted 8 months. The median survival from first recurrence was 4.6 years. CONCLUSIONS: Surgical management is important for the successful treatment of patients with recurrent meningeal hemangiopericytoma. Radiosurgery plays a definite role in the treatment of smaller recurrent CNS lesions. Radiation therapy is helpful in the management of inoperable tumors. More effective chemotherapeutic agents are needed.

Adult↗

PubMed1998

Amyloidomas of the nervous system: a monoclonal B-cell disorder with monotypic amyloid light chain lambda amyloid production.

BACKGROUND: Amyloidomas or localized tumor-like amyloid deposits rarely affect the nervous system. To the authors' knowledge, no comprehensive studies on central and peripheral nervous system amyloidomas have been published. The amyloid subtype of amyloidomas of the nervous system only recently was characterized and almost invariably was found to be of amyloid light chain (AL) lambda type. The nature of the plasma cell population responsible for AL amyloid production has not been investigated further. METHODS: The current analysis included the clinical findings, neuroimaging characteristics, and pathology of seven amyloidomas (four cerebral and three involving peripheral nerves). All were subjected to histochemical staining (Congo red, thioflavine S) and to immunohistochemical study using primary antibodies detecting serum amyloid component P, serum amyloid protein A (SAA), transthyretin, beta2 microglobulin (beta2m), and free immunoglobulin (Ig) light chain. For the detection of mRNA of light chain Ig, fluorescein-conjugated kappa and lambda mRNA oligonucleotide probes were used. For the assessment of B-cell clonality, polymerase chain reaction (PCR) was applied on extracted DNA from two cases using VH FRIII and JH primers. Two cases were assessed ultrastructurally. RESULTS: All amyloidomas were organ restricted and unrelated to systemic amyloidosis. The clinical symptoms of the cerebral lesions were nonspecific, whereas neurologic deficits were noted in the distribution of the involved peripheral nerves. Cerebral deposits, either solitary or multiple, were associated spatially with the choroid plexus and secondarily extended into white matter. All peripheral nerve amyloidomas involved the gasserian ganglion of the trigeminal nerve. Imaging by computed tomography and magnetic resonance imaging scans revealed hyperdense and contrast-enhancing mass lesions unassociated with significant edema. Immunohistochemically, the amyloid was present in the interstitium and within the walls of the intralesional vessels, was invariably of AL lambda subtype, and was negative for free Ig kappa light chains, SAA, transthyretin, and beta2m. Plasma cells along the perivascular sheaths and occasionally squeezed between amyloid masses showed no cytologic atypia. In situ hybridization for Ig light chain mRNA reflected a massive preponderance of lambda-producing cells. PCR revealed monoclonal rearrangement of the heavy chain Ig gene. CONCLUSIONS: The results of the current study provide strong support for the concept that amyloidomas of the nervous system are neoplasms of an AL lambda-producing B-cell clone capable of terminal differentiation. Nevertheless, all seven patients lacked clinical evidence of an aggressive or systemic lymphoplasmacytic neoplasm. Unlike plasmacytomas, the relatively indolent course of most nervous system amyloidomas is reminiscent of the similarly indolent biologic behavior of extranodal, low grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type.

Adult↗